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11,800 | 16,856,051 | School-based secondary prevention programmes to reduce aggressive behaviour appear to produce improvements in behaviour greater than would have been expected by chance .
Benefits can be achieved in both primary and secondary school age groups and in both mixed sex groups and boys-only groups . | BACKGROUND Early aggressive behaviour is a risk factor for later violence and criminal behaviour .
Despite over 20 years of violence prevention interventions being delivered in the school setting , questions remain regarding the effectiveness of different interventions for children exhibiting aggressive behaviour .
OBJECTIVES To examine the effect of school based violence prevention programmes for children identified as aggressive or at risk of being aggressive . | This study examined the effectiveness of the universal component of the Fast Track prevention model : the PATHS ( Promoting Alternative THinking Strategies ) curriculum and teacher consultation . This r and omized clinical trial involved 198 intervention and 180 comparison classrooms from neighborhoods with greater than average crime in 4 U.S. locations . In the intervention schools , Grade 1 teachers delivered a 57-lesson social competence intervention focused on self-control , emotional awareness , peer relations , and problem solving . Findings indicated significant effects on peer ratings of aggression and hyperactive-disruptive behavior and observer ratings of classroom atmosphere . Quality of implementation predicted variation in assessment s of classroom functioning . The results are discussed in terms of both the efficacy of universal , school-based prevention models and the need to examine comprehensive , multiyear programs The influence of cognitive self-instructional training on the impulsive-aggressive behavior of 16 third- grade boys was examined . Children were equated by ranks on the frequency of their aggressive and motor behavior in the classroom and r and omly assigned to the cognitive self-instruction or an attention-control group . The instruction condition employed a training procedure which required the child to talk to himself , initially overtly and then covertly , to increase self-control . Posttreatment classroom observations and teachers ' ratings showed that the instruction group exhibited fewer deviant behaviors compared to controls although the differences were non-significant . Daring a staged problematic situation the instruction condition showed somewhat fewer deviant responses than controls and the number of prosocial responses differed only slightly . However , there was a significant difference between groups in the frequency of waiting and verbal aggressive behaviors . Results suggest that the instruction group may have used covert speech for controlling deviant responses to frustration rather than generating prosocial approach behavior This study tested the hypothesis that both aggressive and withdrawn children would benefit from participating in brief daily learning sessions with peers having similar behavioral problems . In particular the study looked for gains in self-concept and in the children 's behavioral difficulties . Sixty children from a Buffalo public school were r and omly placed into three groups : tutors , tutees , and control subjects . After r and om assignments were made , I met with the tutors for two training sessions in which they learned how to correct and reinforce their students in an easygoing , nonhostile manner . Tutors were given freedom to manipulate content material s of each session and were allowed to meet with their tutees as often as they wanted . After the five weeks of peer tutoring , almost all children who actively participated in the program showed higher gains than the control subjects . They had higher self-concepts and made greater behavioral improvements . In addition they demonstrated a renewed interest in school and in the learning process . A significant correlation was found between gain scores and the number of times of participation in the peer-tutoring sessions . Teachers and administrators were in favor of continuing the project with some modification . They felt that the sessions should be more structured and more under a teacher 's control A multiyear , multi context aggression prevention intervention was provided during the early or late elementary school years in an inner-city and an urban poor community . Sixteen schools were r and omly assigned to 1 of 4 conditions : ( a ) no-treatment control , ( b ) general enhancement classroom program , ( c ) general enhancement plus small-group peer-skills training , or ( d ) general enhancement plus small-group peer-skills training plus family intervention . This article reports on results for the high-risk sub sample of 1,500 children . Results from hierarchical linear modeling indicate that comprehensive interventions , if provided in early grade s , can be effective for children in schools in setting s with re sources adequate to support learning and development , but some unintended effects can occur in schools in the most distressed communities when delivered too late in development Annual screenings of preschool children at kindergarten registration identified 158 children having high levels of aggressive , hyperactive , impulsive , and inattentive behavior . These " disruptive " children were r and omly assigned to four treatment conditions lasting the kindergarten school year : no treatment , parent training only , full-day treatment classroom only , and the combination of parent training with the classroom treatment . Results showed that parent training produced no significant treatment effects , probably owing largely to poor attendance . The classroom treatment produced improvement in multiple domains : parent ratings of adaptive behavior , teacher ratings of attention , aggression , self-control , and social skills , as well as direct observations of externalizing behavior in the classroom . Neither treatment improved academic achievement skills or parent ratings of home behavior problems , nor were effects evident on any lab measures of attention , impulse control , or mother-child interactions . It is concluded that when parent training is offered at school registration to parents of disruptive children identified through a brief school registration screening , it may not be a useful approach to treating the home and community behavioral problems of such children . The kindergarten classroom intervention was far more effective in reducing the perceived behavioral problems and impaired social skills of these children . Even so , most treatment effects were specific to the school environment and did not affect achievement skills . These findings must be viewed as tentative until follow-up evaluations can be done to determine the long-term outcomes of these interventions First through fourth grade rs from 22 suburban elementary schools were screened for cross- setting disruptive behavior as eligibility criteria for participation in a longitudinal secondary prevention study aim ed at reducing the risk for serious externalizing behavioral disorders . Three hundred nine subjects participated in either a multicomponent competence enhancement intervention ( MCEI ) or an information/attention control ( IAC ) condition over a 2-year period . Following baseline measurements , initial intervention effects were assessed at the end of intervention Year 1 , at the beginning of intervention Year 2 ( fall of the next school year ) , and at the end of intervention Year 2 . Multi source assessment s were not supportive of the efficacy of the MCEI over the IAC condition . Children in both groups rated themselves as improved over time in terms of increased adaptive skills and decreased school problems and internalizing symptoms . Teacher and parent ratings of externalizing behavior did not yield evidence of positive change , but teachers noted improved problem solving and observers noted a decrease in behavioral interference in both groups over time , possibly as a result of maturation OBJECTIVE To compare the effectiveness of the Violence Prevention Curriculum for Adolescents to the Conflict Resolution : A Curriculum for Youth Providers among middle school students . METHODS A sample ( N = 225 ) of adolescents ( males = 48 % ) representing 20 % of the student population in two middle schools were administered a pretest question naire . Of these students , 89 % were African-American , 10 % were white , and 1 % were Native-American and lived in public housing ( 40 % ) or in neighborhoods adjacent to public housing ( 60 % ) . Each school was r and omly assigned to one of the curricula . Each curriculum was administered during 10 50-min sessions held twice a week over 5 weeks . One week later , 209 students who completed the 10 sessions were tested with the same question naire . The data were analyzed with a repeated- measures analysis of variance . RESULTS Students who received either curriculum reported significant decreases in their self-reported use of violence in hypothetical conflict situations , frequency of use of violence in the previous 30 days , and frequency of physical fights in the previous 30 days . The conflict resolution curriculum was more effective in reducing the frequency of fights result ing in an injury requiring medical treatment in the previous 30 days . CONCLUSIONS Both curricula were successful in reducing three indicators of violence . However , the conflict resolution approach was more successful in reducing the frequency of more severe physical fights requiring medical treatment . The latter finding is of particular importance , because that physical fighting is the form of violence behavior in which young adolescents most often engage An attributional intervention was design ed to reduce aggressive males ' tendency to attribute hostile intentions to peers following ambiguously caused peer provocations . African-American elementary school boys ( N = 101 ) , aggressive and nonaggressive , were r and omly assigned to the attributional intervention , an attention training program , or a no-treatment control group . Data were collected on subjects ' attributions about hypothetical and laboratory simulations of peer provocation , disciplinary referrals to the school office , and teacher ratings of aggressive behavior . Aggressive subjects in the attributional intervention were less likely to presume hostile intent by peers in hypothetical and laboratory simulations of ambiguous provocation . They were also less likely to endorse hostile retaliation on judgment measures and to engage in verbally hostile behaviors in the laboratory task . Further , intervention subjects were rated as less aggressive by their teachers following the treatment . Both the benefits of attributional change and its limitations in the African-American population are discussed From a school population of normal children third through fifth grade s ) , thirty children initially identified as “ angry”were r and omly assigned to either an affective imagery training group , an attention group , or a control group . The treatment group received three sessions of affective imagery in which they focused on physiological changes and on their thoughts associated with prior emotional experiences . Teachers recorded pre- , post- , and short term follow-up aggressive behaviors for all thirty children . Cognitive perceptions and attributions were recorded at the same three occasions on the Affect Question naire . Results suggested that , as a result of affective imagery training , angry children 's perceptions and cognitions shifted from “ angry ” towards “ sad , ” and there was a concomitant decrease in observed aggressive classroom behavior Fast Track is a multisite , multicomponent preventive intervention for young children at high risk for long-term antisocial behavior . Based on a comprehensive developmental model , intervention included a universal-level classroom program plus social skills training , academic tutoring , parent training , and home visiting to improve competencies and reduce problems in a high-risk group of children selected in kindergarten . At the end of Grade 1 , there were moderate positive effects on children 's social , emotional , and academic skills ; peer interactions and social status ; and conduct problems and special-education use . Parents reported less physical discipline and greater parenting satisfaction/ease of parenting and engaged in more appropriate/consistent discipline , warmth/positive involvement , and involvement with the school . Evidence of differential intervention effects across child gender , race , site , and cohort was minimal This paper describes a preventive intervention trial called EARLY ALLIANCE which is aim ed at reducing risk for three adverse outcomes in childhood and adolescence : conduct problems , substance abuse , and school failure . The structure of the prevention trial is unique because two linked design s are being implemented concurrently . The primary design focuses on children at elevated risk for adverse outcomes , and compares a targeted , multi context ual preventive intervention with family , classroom , peer relational , and academic components to a universal , schoolwide preventive intervention that emphasizes peaceful conflict management and serves as a " usual care " control condition . The secondary design focuses on children at lower risk for adverse outcomes and compares a universally administered classroom program to the control condition . The paper describes the theoretical foundation for EARLY ALLIANCE , the goals of the prevention trial , the rationale for design choices , and the methods employed The Montréal Longitudinal Study of Disruptive Boys , an experimental study , was design ed to underst and boys who were considered disruptive in kindergarten . One part of the study involved assessing effects of a preventive treatment program carried out during the boys ' early years in primary school . This paper reports on the outcome of the r and omized treatment experiment 3 years after treatments ended . Disruptive boys were r and omly allocated to a treated group and two nontreated groups . Treatment consisted of parent training and training of boys for social skills , fantasy play and television viewing . Results suggest that the treatment program had some positive effects . Some of the improvements were not evident immediately after treatment ended The purpose s of this study were to examine the type of response to different situations displayed by children with or without conduct disorders and to assess the efficacy of the social skills training program herein proposed for modifying styles of interpersonal relationship in children . The sample included 315 children , 8 to 12 years of age . Those exhibiting conduct problems were 164 boys , and those having no conduct problems were 151 boys . All participants shared a low socioeconomic and cultural status and attended schools located in poor districts of Mendoza City in Argentina . Analysis showed that the groups trained in social skills improved in social interaction by reducing disruptive behaviors , whereas the groups without social skills training showed no behavioral changes . These data were confirmed by the teachers ' assessment s. These results suggest social skills training seems an efficient therapeutic approach to the attenuation of behavior disorders of boys V and alism is a major problem facing educators and taxpayers alike . The present investigation analyzed how v and alism costs and student disruption were related to the implementation of a training and consultation package design ed to increase the reinforcing ambience of the school . A positive environment , it was posited , would displace previous events that may have set the occasion for v and alism , with cues to promote productive school performance . Eighteen elementary and junior high schools were involved over a 3-year period . Using a delayed treatment control design , treatment was delivered following either 4 or 13 months of baseline . During treatment , teams of school personnel attended training workshops in behavioral strategies for reducing v and alism and disruption by students in school . Each team also met regularly on its campus to plan and implement programs on a schoolwide basis . To demonstrate that reinforcing procedures were actually implemented and accompanied by change in student performance , these variables were periodically probed throughout the study . Project staff also provided consultation . V and alism costs decreased significantly ( p less than .05 ) more in treatment than control schools , with an average reduction of 78.5 % for all project schools . Rates of praise delivered by project teachers and other r and omly selected teachers in the school increased significantly ( p less than .05 ) , and rates of off-task behavior by students decreased significantly ( p less than .05 ) following treatment . The staff development model used in this study appeared to be both feasible and economical Thirty-two boys who were rejected by their peers in Grade s 1 - 3 were identified on the basis of negative sociometric nominations and negative social behavior . They were r and omly assigned to one of four treatment conditions : ( a ) instructions to promote positive social behavior , ( b ) prohibitions to reduce negative social behavior , ( c ) a combination of instructions and prohibitions , or ( d ) no treatment . Interventions were applied during 10 half-hour school play sessions . Behavioral observations and peer and teacher ratings were collected prior to treatment , immediately after treatment , and at a follow-up assessment 6 weeks after treatment . Additional peer and teacher ratings were collected at a I-year follow-up . Prohibitions combined with a response cost for negative behaviors result ed in immediate and stable declines in negative behavior and led to temporary increases in positive responses received from peers . Instructions and the reinforcement of specific social skills promoted sustained positive peer interactions 6 weeks after treatment . Only the combination of instructions and prohibitions led to improved sociometric ratings from nontarget treatment partners Abstract The effects of four school-based interventions design ed to decrease children 's aggression and promote prosocial behavior were assessed . One hundred and four aggressive boys , ages 8–13 , from ‘ Behavior Disorder ’ classrooms , were assigned to one of four training conditions : cognitive ( self-control ) training , behavioral ( prosocial skills ) training , combined cognitive-behavioral training , or attention/play training . School psychologists trained the boys in small groups for 10 1-h sessions . It was hypothesized that training in both cognitive and behavioral competencies would lead to the most behavioral improvement . Results indicated that , according to teacher report , those children receiving the cognitive-behavioral and attention/play interventions improved significantly more than those exposed to cognitive and behavioral training by decreasing their aggression and increasing their prosocial behavior immediately following the intervention . At 6-month follow-up , only those children exposed to the attention/play intervention remained significantly improved This study evaluates the effects of an indicated preventive intervention and a universal preventive intervention . Children were identified as being at risk on the basis of 4th- grade teachers ' ratings of children 's aggressive and disruptive behaviors , and interventions were delivered during the 5th- and 6th- grade years . Children were r and omly assigned to the Coping Power intervention , the universal intervention , the combined Coping Power plus universal intervention , or a control condition . The Coping Power program included child and parent components . Results indicated that all 3 intervention cells produced relatively lower rates of substance use at postintervention than did the control cell . The interventions also produced effects on 3 of the 4 predictor variable domains : children 's social competence and self-regulation and parents ' parenting skills BACKGROUND Violence among adolescents may have serious developmental , physical , and mental health consequences for the affected individuals . In this study , we assessed the prevalence of violent behaviour and its correlates among 15 - 16 year old schoolchildren in Icel and . METHODS In 1997 , a cross-sectional survey was conducted among a r and om half of all Icel and ic schoolchildren aged 15 - 16 years . The overall response rate was 91 % ( N = 3872 ) . In the present study , socio-demographic background , social support , negative life events , psychological distress , and substance use were considered in relation to violent behaviour using logistic regression techniques . RESULTS The majority of the respondents reported having committed violence within the last year . Boys were more likely to use violence than girls ( odds ratio [ OR ] = 5.6 ; 95 % CI : 4.7 , 6.6 ) . Respondents who had experienced > /=4 negative life events in the past year were more likely to use violence than respondents with no negative life events ( OR = 3.0 ; 95 % CI : 2.2 , 4.2 ) . Smokers were more likely than non-smokers to use violence ( OR = 1.7 ; 95 % CI : 1.2 , 2.2 ) , and adolescents who had used alcohol > 20x in their lifetime were more than twice as likely to commit violence compared with those who had never used alcohol ( OR = 2.5 ; 95 % CI : 1.8 , 3.4 ) . CONCLUSION Rates of violent behaviour among Icel and ic schoolchildren were high . Gender , parental support , life stress , anger/aggression , and substance use were all significantly related to the perpetration of violent acts |
11,801 | 30,702,632 | Conclusions : This systematic review will present the existing evidence for the efficacy and safety of SPGL for treating patients with AD . | Background : Previous studies have reported that spore powder of Ganoderma lucidum ( SPGL ) may be effective for the treatment of Alzheimer 's disease ( AD ) .
However , its efficacy is still inconclusive .
Thus , this systematic review will aim to assess its efficacy and safety for AD . | Background Alzheimer ’s disease ( AD ) is the most common cause of dementia . However , none of medical treatment can stop or reverse the underlying neurodegenerative of AD at present . Acupuncture has attracted more and more attention in recent years due to its efficacy and very few side effects . Lately , a systematic review has thought that the evidence on the effectiveness of acupuncture in improving the cognitive function of AD patients was not powerful enough . Therefore , the aim of this study is to explore the efficacy and safety of acupuncture in patients with mild to moderate AD . Methods This was a r and omized , controlled , parallel-group , exploratory study with 4-week baseline ( T0 ) , 12-week treatment phase ( T1 ) and 12-week follow-up period ( T2 ) . Patients with mild to moderate AD meeting the included criteria were r and omly allocated into either acupuncture or donepezil hydrochloride groups . The acupuncture group(AG ) was given acupuncture treatment three times per week and the donepezil hydrochloride group(DG ) group was administered donepezil hydrochloride once daily ( 5 mg/day for the first 4 weeks and 10 mg/day thereafter ) . Primary efficacy was measured using Alzheimer ’s disease Assessment Scale-Cognitive ( ADAS-cog ) and Clinician ’s Interview-Based Impression of Change-Plus ( CIBIC-Plus ) . The second outcomes were measured with 23-Item Alzheimer ’s disease Cooperative Study Activities of Daily Living Scales ( ADAS-ADL23 ) and Neuropsychiatric Index ( NPI ) . Results Of 87 participants enrolled in the study , 79 patients finished their treatment and follow-up processes . The ADAS-cog scores for AG group showed obvious decreases at T2 and ∆(T2-T0)when compared with DG group , and significant between-group differences were detected ( all p < 0.05 ) . The mean CIBIC-Plus values for the AG group at T1 and T2 were much lower than that for the DG group , and there were significant differences between the two groups ( 푃<0.05 ) . There were no significant between-group differences in the scores of ADAS-ADL23 and NPI during the study period . Treatment discontinuations due to adverse events were 0 ( 0 % ) and 4 ( 9.09 % ) for the AG and DG groups , respectively . Conclusions Acupuncture is safe , well tolerated and effective in improving the cognitive function , global clinical status of AD.Trial Registration ChiCTR-IOR-17010465 ( Retroactively registered on 18 JAN 2017 ) Background Alzheimer ’s disease is a progressive neurodegenerative disease . Although some of the current treatments offer some symptomatic relief , this disease can not be cured at present . Electroacupuncture may be effective for Alzheimer ’s disease for cognitive function , but the evidence for its effectiveness is still limited . The aim of this study is to evaluate the add-on effect of electroacupuncture to donepezil for improving the cognitive function of Alzheimer ’s disease . Methods / design A total of 334 participants with Alzheimer ’s disease will be r and omly assigned to either an electroacupuncture combined with donepezil group or a donepezil group with a ratio of 1:1 . Participants in the electroacupuncture combined with donepezil group will receive electroacupuncture in addition to donepezil for 12 weeks and will keep taking donepezil for the following 24 weeks . Participants in the control group will take donepezil only . The primary outcome is the change from baseline in the total score of the Alzheimer ’s Disease Assessment Scale-cognition at week 12 . A follow-up will be conducted 24 weeks after the treatment . Discussion We expect to verify the hypothesis that acupuncture in addition to donepezil is better than donepezil in improving the cognitive function of patients with Alzheimer ’s disease . This trial has a limitation that participant blinding is impossible . Trial registration Clinical Trials.gov : ID : NCT02305836 . Registered on 13 November 2014 BACKGROUND / OBJECTIVE Balance problems are common in older adults with Alzheimer 's disease ( AD ) . The objective was to study the effects of a Wii-Fit interactive video-game-led physical exercise program to a walking program on measures of balance in older adults with mild AD . METHODS A prospect i ve r and omized controlled parallel-group trial ( Wii-Fit versus walking ) was conducted in thirty community-dwelling older adults ( 73±6.2 years ) with mild AD . Home-based exercises were performed under caregiver supervision for 8 weeks . Primary ( Berg Balance Scale , BBS ) and secondary outcomes ( fear of falls and quality of life ) were measured at baseline , 8 weeks ( end of intervention ) , and 16 weeks ( 8-weeks post-intervention ) . RESULTS At 8 weeks , there was a significantly greater improvement ( average inter-group difference [ 95 % CI ] ) in the Wii-Fit group compared to the walking group in BBS ( 4.8 [ 3.3 - 6.2 ] , p < 0.001 ) , after adjusting for baseline . This improvement was sustained at 16 weeks ( 3.5 [ 2.0 - 5.0 ] , p < 0.001 ) . Analyses of the secondary outcome measures indicated that there was a significantly greater improvement in the Wii-Fit group compared to walking group in Activity-specific Balance Confidence scale ( 6.5 [ 3.6 - 9.4 ] , p < 0.001 ) and Falls Efficacy Scale ( -4.8 [ -7.6 to -2.0 ] , p = 0.002 ) at 8 weeks . However , this effect was not sustained at 16 weeks . Quality of life improved in both groups at 8 weeks ; however , there were no inter-group differences ( p = 0.445 ) . CONCLUSION Home-based , caregiver-supervised Wii-Fit exercises improve balance and may reduce fear of falling in community-dwelling older adults with mild AD Background : This study explored the feasible efficacy and safety of the Spore Powder of Ganoderma Lucidum ( SPGL ) for treating patients with Alzheimer disease ( AD ) . Methods : Forty-two eligible patients with AD were recruited . These patients were r and omly allocated to an intervention group and a control group equally . The patients in the intervention group underwent SPGL , whereas the subjects in the control received placebo . All patients were treated for a total of 6 weeks . The primary outcome was measured by Alzheimer 's disease Assessment Scale-Cognitive ( ADAS-cog ) . The secondary outcomes were measured by the World Health Organization Quality of Life question naire ( WHOQOL-BREF ) and Neuropsychiatric Index ( NPI ) . The adverse events were also recorded during the treatment period . Results : At the end of the treatment , GLSP did not show more encouraging outcomes in symptoms improvement , measured by the ADAS-cog ( P = .31 ) , and NPI ( P = .79 ) ; and quality of life enhancement , measured by the WHOQOL-BREF ( physical , P = .62 ; psychological , P = .69 ; social relationships , P = .75 ; environment , P = .82 ; overall quality of life , P = .74 ) , compared with the control group . In addition , all adverse events were mild , and no significant differences were found between 2 groups . Conclusion : The results of this study did not find the promising efficacy of SPGL for the treatment of AD after 6-week treatment . It may be because of the relative short-term of intervention . Future clinical trials with larger sample size and longer treatment period are urgently needed BACKGROUND Alzheimer 's disease is characterized by the deposition of amyloid‐beta ( Aβ ) plaques in the brain . Aβ is produced from the sequential cleavage of amyloid precursor protein by β‐site amyloid precursor protein – cleaving enzyme 1 ( BACE‐1 ) followed by γ‐secretase . Verubecestat is an oral BACE‐1 inhibitor that reduces the Aβ level in the cerebrospinal fluid of patients with Alzheimer 's disease . METHODS We conducted a r and omized , double‐blind , placebo‐controlled , 78‐week trial to evaluate verubecestat at doses of 12 mg and 40 mg per day , as compared with placebo , in patients who had a clinical diagnosis of mild‐to‐moderate Alzheimer 's disease . The co primary outcomes were the change from baseline to week 78 in the score on the cognitive subscale of the Alzheimer 's Disease Assessment Scale ( ADAS‐cog ; scores range from 0 to 70 , with higher scores indicating worse dementia ) and in the score on the Alzheimer 's Disease Cooperative Study Activities of Daily Living Inventory scale ( ADCS‐ADL ; scores range from 0 to 78 , with lower scores indicating worse function ) . RESULTS A total of 1958 patients underwent r and omization ; 653 were r and omly assigned to receive verubecestat at a dose of 12 mg per day ( the 12‐mg group ) , 652 to receive verubecestat at a dose of 40 mg per day ( the 40‐mg group ) , and 653 to receive matching placebo . The trial was terminated early for futility 50 months after onset , which was within 5 months before its scheduled completion , and after enrollment of the planned 1958 patients was complete . The estimated mean change from baseline to week 78 in the ADAS‐cog score was 7.9 in the 12‐mg group , 8.0 in the 40‐mg group , and 7.7 in the placebo group ( P=0.63 for the comparison between the 12‐mg group and the placebo group and P=0.46 for the comparison between the 40‐mg group and the placebo group ) . The estimated mean change from baseline to week 78 in the ADCS‐ADL score was ‐8.4 in the 12‐mg group , ‐8.2 in the 40‐mg group , and ‐8.9 in the placebo group ( P=0.49 for the comparison between the 12‐mg group and the placebo group and P=0.32 for the comparison between the 40‐mg group and the placebo group ) . Adverse events , including rash , falls and injuries , sleep disturbance , suicidal ideation , weight loss , and hair‐color change , were more common in the verubecestat groups than in the placebo group . CONCLUSIONS Verubecestat did not reduce cognitive or functional decline in patients with mild‐to‐moderate Alzheimer 's disease and was associated with treatment‐related adverse events . ( Funded by Merck ; Clinical Trials.gov number , NCT01739348 . Objectives To explore the cost-effectiveness of a supervised moderate-to-high intensity aerobic exercise programme in people diagnosed with Alzheimer ’s disease ( AD ) and estimate incremental cost-effectiveness ratios ( ICER ) using participant-reported and proxy-reported measures of health-related quality of life ( HRQoL ) Design A cost-effectiveness analysis of economic and HRQoL data from a r and omised trial delivered over 16 weeks . Setting Memory clinics in Denmark . Participants 200 individuals with mild AD aged 50–90 years gave informed consent to participate in the study . Participants were r and omised to control or intervention group . Interventions Control group received treatment as usual . The intervention group performed 1 hour of supervised moderate-to-high intensity aerobic exercise three times weekly for 16 weeks . Primary and secondary outcomes measures Different physical , functional and health measures were obtained at inclusion ( baseline ) and 4 and 16 weeks after . HRQoL ( EuroQol-5 Dimensions-5 Levels/EQ-Visual Analogue Scale ) was reported by the participants and the primary caregivers as proxy respondents . Differences in HRQOL as reported by the participant and caregiver were explored as were different values of caregiver time with respite from care tasks . Results The intervention cost was estimated at € 608 and € 496 per participant , with and without transport cost , respectively . Participants and caregivers in the intervention group reported a small , positive non-significant improvement in EQ-5D-5L and EQ-VAS after 16 weeks . The ICER was estimated at € 72 000/ quality -adjusted life year using participant-reported outcomes and € 87000 using caregiver-reported outcomes . Conclusions The findings suggest that the exercise intervention is unlikely to be cost-effective within the commonly applied threshold values . The cost of the intervention might be offset by potential savings from reduction in use of health and social care . Trial registration number https:// clinical trials.gov/ct2/show/NCT01681602 BACKGROUND Alzheimer 's disease is characterized by amyloid‐beta ( Aβ ) plaques and neurofibrillary tangles . The humanized monoclonal antibody solanezumab was design ed to increase the clearance from the brain of soluble Aβ , peptides that may lead to toxic effects in the synapses and precede the deposition of fibrillary amyloid . METHODS We conducted a double‐blind , placebo‐controlled , phase 3 trial involving patients with mild dementia due to Alzheimer 's disease , defined as a Mini – Mental State Examination ( MMSE ) score of 20 to 26 ( on a scale from 0 to 30 , with higher scores indicating better cognition ) and with amyloid deposition shown by means of florbetapir positron‐emission tomography or Aβ1‐42 measurements in cerebrospinal fluid . Patients were r and omly assigned to receive solanezumab at a dose of 400 mg or placebo intravenously every 4 weeks for 76 weeks . The primary outcome was the change from baseline to week 80 in the score on the 14‐item cognitive subscale of the Alzheimer 's Disease Assessment Scale ( ADAS‐cog14 ; scores range from 0 to 90 , with higher scores indicating greater cognitive impairment ) . RESULTS A total of 2129 patients were enrolled , of whom 1057 were assigned to receive solanezumab and 1072 to receive placebo . The mean change from baseline in the ADAS‐cog14 score was 6.65 in the solanezumab group and 7.44 in the placebo group , with no significant between‐group difference at week 80 ( difference , ‐0.80 ; 95 % confidence interval , ‐1.73 to 0.14 ; P=0.10 ) . As a result of the failure to reach significance with regard to the primary outcome in the prespecified hierarchical analysis , the secondary outcomes were considered to be descriptive and are reported without significance testing . The change from baseline in the MMSE score was ‐3.17 in the solanezumab group and ‐3.66 in the placebo group . Adverse cerebral edema or effusion lesions that were observed on magnetic resonance imaging after r and omization occurred in 1 patient in the solanezumab group and in 2 in the placebo group . CONCLUSIONS Solanezumab at a dose of 400 mg administered every 4 weeks in patients with mild Alzheimer 's disease did not significantly affect cognitive decline . ( Funded by Eli Lilly ; EXPEDITION3 Clinical Trials.gov number , NCT01900665 . |
11,802 | 29,031,822 | There was a diversity of removal rate and reasons in the studies over the world .
High frequent VLP removal did not contribute to better clinical outcomes | BACKGROUND Indication of volar locking plate ( VLP ) removal after bony healing of distal radius fracture ( DRF ) is controversial .
Studies with various range of removal rate were reported .
The purpose of this systematic review was to investigate the frequency and the reasons of hardware removal over the world .
We hypothesized that more frequent VLP removal contribute to better clinical outcomes . | BACKGROUND Outcome measurement following surgery is increasingly the focus of attention in current health-care debates because of the rising costs of medical care and the large variety of operative options . The purpose of the present study was to correlate quality of life after volar locked plate fixation of unstable intra-articular distal radial fractures with functional and radiographic results as well as with quality -of-life data from population norms . METHODS Fifty-four consecutive patients with intra-articular distal radial fractures and a mean age of sixty-three years were managed with a volar locked plate system . Range of motion , grip strength , and radiographs were assessed at a mean of six years postoperatively . The wrist-scoring systems of Gartl and and Werley and Castaing were adopted for the assessment of objective outcomes . The Disabilities of the Arm , Shoulder and H and and Short Form-36 question naires were completed as subjective outcome measures , and the results were compared with United States and Austrian population norms . RESULTS Functional improvement continued for two years postoperatively . At the time of the latest follow-up , > 90 % of all patients had achieved good or excellent results according to the scoring systems of Gartl and and Werley and Castaing . The results of the Short Form-36 question naire were similar to the United States and Austrian population norms . The mean Disabilities of the Arm , Shoulder and H and score was 5 points at two years , and it increased to 13 points at six years . The twenty patients with radiocarpal arthritis had significantly poorer results in the physical component summary measure of the Short Form-36 question naire ( p = 0.012 ) . CONCLUSIONS The results of the present single-center study show that , following distal radial fracture fixation , wrist arthritis may affect the patient 's subjective well-being , as documented with the Short Form-36 , without influencing the functional outcome . Well- design ed longitudinal clinical trials are needed to confirm the findings of the present investigation in terms of quality of life after surgical treatment of intra-articular distal radial fractures Different methods exist to treat distal radius fractures . A prospect i ve r and omized study was conducted to establish whether palmar plate fixation with locking screws gave better results than percutaneous K-wire fixation in patients over 50 years of age . Only fractures with dorsal displacement after a simple fall were included in the study . Twenty wrists were treated with K-wires and 20 with a plate . Radiological parameters were measured on preoperative radiographs and at five weeks postoperatively . Clinical results and DASH scores were determined at three months postoperatively and at more than one year . No significant difference in radial inclination , palmar tilt , clinical outcome and DASH score was found between plating and K-wires , but the mean difference in ulnar variance between pre- and postoperative radiographs was significantly better with plates . It can be concluded that plates were superior to K-wires in restoring ulnar variance , but functional outcome was similar with both techniques INTRODUCTION Malunion following open reduction and internal fixation of distal radius fracture threatens wrist function . Fixed-angle palmar plates provide rigid fixation that is stable over time ; however , the pronator quadratus sectioning required by the anterior approach entails a risk of pronation strength loss and of distal radioulnar joint destabilization . The present study assessed recovery of grip , pronation and supination strength following such internal fixation . PATIENTS AND METHOD A prospect i ve study included 26 distal radial fractures with dorsal displacement , osteosynthesized using a fixed-angle palmar plate , in 25 patients ( mean age : 47.5 years ; range : 17 - 72 years ) . Assessment concerned the classical parameters , plus grip and pronosupination strength recovery . RESULTS At a mean 14 months follow-up ( range : 6 - 30 months ) , patients had recovered 91 % grip strength , 88 % pronation strength and 85 % supination strength with respect to the healthy side . Complications comprised three cases of malunion , two of reflex sympathetic dystrophy syndrome , and four of post-traumatic carpal tunnel syndrome . DISCUSSION A study of the literature found 75 - 95 % grip strength recovery following osteo synthesis using fixed-angle plates . Few studies , however , have focused on pronosupination strength , and none reported its evolution following osteo synthesis . CONCLUSION The present study found no drawbacks associated with a technique which usually involves sectioning the pronator quadratus . Except in case of malunion or joint stiffness , fixed-angle palmar plate osteo synthesis was followed by recovery of grip and pronosupination strength . LEVEL OF EVIDENCE Level IV : prospect i ve non-r and omized , non-comparative observational study PURPOSE To compare minimally invasive intramedullary nails ( IMN ) and volar locking plates ( VLP ) for the treatment of unstable distal radius fractures by evaluating postoperative subjective , radiographic , and functional outcomes . The hypothesis was that IMN patients would have less pain and required less pain medication in the early postoperative period and returned to work earlier than VLP patients . METHODS Sixty patients with closed , displaced , unstable , extra-articular , metaphyseal fractures of the distal radius were r and omized to receive a VLP or an IMN for internal fixation . Functional outcomes ( Quick Disabilities of the Arm , Shoulder , and H and , Michigan H and Question naire ) , radiographic measurements ( ulnar variance , radial height , inclination , and volar tilt ) , and range of motion were assessed until final follow-up at 2 years after surgery . Narcotic pain medication use was documented for 5 weeks following surgery . RESULTS There were 2 groups of 30 patients with IMN ( mean age , 55 ± 14 y ) or VLP ( mean age , 55 ± 16 y ) with similar demographics and comorbidities . Patients with IMN regained extension earlier but had similar range of motion to patients with VLP at final follow-up . There was similar improvement in Michigan H and Question naire , Quick Disabilities of the Arm , Shoulder , and H and , and strength between groups . Five weeks after surgery , fewer IMN patients required narcotic pain medication ( 13 % ) than VLP patients ( 33 % ) . Radiographic outcomes were similar at final follow-up . There were 3 failures with IMN versus 1 failure with VLP . All 10 employed patients with IMN returned to previous work compared with 10 of the 12 employed patients with VLP . Time to return to work was similar for both groups . CONCLUSIONS In a cohort of similar patients , IMN and VLP provided comparable improvement in functional and radiographic outcomes . Patients with IMN required less narcotic pain medication after surgery than VLP patients . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic II ABSTRACT The purpose of this study was to determine whether volar locking plate fixation for distal radius fracture benefits the fragility fracture population as much as it benefits the non-fragility fracture population . This matched case-control study was conducted based on a multi-center clinical prospect i ve cohort . A comparison of treatment outcomes after volar locking plate fixation was made between females 55 years of age and older ( fragility fracture population ) and males less than 75 years of age ( non-fragility fracture population ) by evaluating clinical , radiological , and subjective outcomes using H and 20 , a vali date d patient-rated disability instrument . A total of 170 patients were enrolled in this study . The two cohorts were matched in terms of AO fracture type . The fragility fracture population group and the non-fragility fracture population group each consisted of 50 patients . All objective measurements including wrist range of motion and radiological evaluations , but excluding grip strength , were not significantly different between the two groups . However , the H and 20 at 18 months after surgery was worse in the fragility fracture population group than in the non-fragility fracture population group . Carpal tunnel syndrome was the most frequently encountered complication in the fragility fracture population group , with one case ( 2 % ) in the non-fragility fracture population group and six cases ( 12 % ) in the fragility fracture population group , but the difference was not significant . In conclusion , there was a significant deficit in the improvement in disability despite favorable radiological and functional outcomes in fragility fracture population patients . Therefore , the fragility fracture population , especially middle-aged or older women , needs to be informed about prolonged disability and the higher risk of upper extremity disorders prior to surgery Objectives : The purpose of this study was to compare the postoperative radiologic and clinical outcomes of conventional plate osteo synthesis ( C ) with minimally invasive plate osteo synthesis ( M ) using a transverse skin incision without cutting the pronator quadratus muscle for distal radius fractures . Design : Retrospective consecutive cohort with prospect i ve data collection . Setting : One community teaching hospital . Surgical treatment was performed by a single surgeon . Patients : Sixty-six patients ( C group , 36 ; M group , 30 ) underwent open reduction and internal fixation of dorsally displaced distal radius fractures with the volar locking plating system from June 2006 to August 2008 . Their mean age was 63.5 years and the mean follow-up period was 22.7 months . Main Outcome Measures : Radiologic parameters ( volar tilt , radial inclination , ulnar variance ) , range of motion , grip strength , and Disability of the Arm , Shoulder , and H and score were evaluated at each examination . The visual analog scale of wrist pain and evaluations of cosmetic problems were assessed at the final follow-up . Results : The groups did not differ significantly in all main outcomes . In the M group , the mean values of the Disability of the Arm , Shoulder , and H and score at 2 weeks postoperatively ( P = 0.06 ) and visual analog scale ( P = 0.07 ) were lower and the mean value of the patient 's satisfaction score of cosmetic problems ( P = 0.08 ) was higher than those in the C group , but no statistically significant differences were apparent in these values . Conclusion : No significant differences were found between the minimally invasive plate osteo synthesis and conventional plating for distal radius fractures based on the data from postoperative radiologic and clinical outcomes Background Current surgical approaches to the distal radius include dorsal and palmar plate fixation . While palmar plates have gained widespread popularity , few reports have provided data on long term clinical outcomes in comparison . This paper reports the result of a r and omised clinical study comparing dorsal Pi plates and palmar , angle-stable plates for treatment of comminuted , intraarticular fractures of the distal radius over the course of twelve months . Methods 42 patients with unilateral , intraarticular fractures of the distal radius were included and r and omised to 2 groups , 22 were treated with a palmar plate , 20 received a dorsal Pi-plate . Results were evaluated after 6 weeks , 3 , 6 and 12 months postoperatively focussing on functional recovery as well as radiological results . Results The palmar plate group demonstrated significantly better results regarding range of motion and grip strength over the course of 12 months . While a comparable increase in function was observed in both groups , the better results from the early postoperative period in the palmar plate group prevailed over the whole course . Radiological results showed a significantly increased palmar tilt and carpal sag in dorsal plates , with other radiological parameters being comparable . Pain levels were decreased in dorsal plates after hardware removal and failed to show significant differences after 12 months . However , complications such as tendon ruptures were more frequent in the dorsal plate group . Conclusions Functional advantage of palmar plates gained within the first 6 weeks prevails over the course of a year . Both groups demonstrate further gradual increase of function after 6 months , although dorsal plates did not catch up completely . Improved early postoperative function seems to be the cornerstone for the best possible results . Patients with dorsal plates benefit from hardware removal more than palmar plates in terms of reduction of pain levels . The advantage of palmar plates is a faster functional recovery with lower complication rates . This is especially important in the elderly population . Radiological results did not show a superiority of palmar plates over dorsal plates Introduction : Distal radius fracture ( DRF ) is a common injury and various treatment modalities including open reduction and internal fixation ( ORIF ) with volar locking plate are available . More recently , a non-invasive external fixator has been used . Aims : To prospect ively compare the use of a non-invasive external fixator with early dynamisation for DRF against ORIF with volar locking plate control group . Methods : Consecutive patients with closed DRF were included in a prospect i ve case-controlled study . Patients were assigned to non-invasive external fixator or ORIF . Minimum follow-up was two years . Follow-up was at weeks 2 , 4 , 6 , 8 , 12 , 26 and at one and two-year post-operatively . The outcome measures included demographic details , injury mechanism , AO fracture type , risk factors , body mass index ( BMI ) , ulnar styloid fracture and dorsal comminution , radiographs , grip strength and DASH score . Results : Consecutive 50 patients were treated either with non-invasive external fixator ( 25/50 ) or with ORIF ( 25/50 ) and the mean age of the two groups was 53 years ( SD 17.1 ) and 49 years ( SD 19.5 ) , respectively . Demographics were matched in two groups . In the non-invasive external fixator group , there were 10 AO Type-A , 5 Type-B and 10 Type-C fractures . The ORIF group included 8 Type-A , 6 Type-B and 11 Type-C fractures . The mean DASH score at three-months and one-year post-injury in non-invasive fixator group was 12.2 ( SD 3.1 ) and 3.5 ( SD 0.7 ) , respectively , significantly greater than those of ORIF group 14.5 ( SD 5.6 ) and 11.2 ( SD 4.4 ) , respectively ( p < 0.05 ) . Conclusion : DRF treated with non-invasive external fixator can give functional results superior to ORIF at three-months and the trend is maintained at one and two-year post-operatively We performed a prospect i ve , r and omised trial to evaluate the outcome after surgery of displaced , unstable fractures of the distal radius . A total of 280 consecutive patients were enrolled in a prospect i ve data base and 88 identified who met the inclusion criteria for surgery . They were r and omised to receive either bridging external fixation with supplementary Kirschner-wire fixation or volar-locked plating with screws . Both groups were similar in terms of age , gender , h and dominance , fracture pattern , socio-economic status and medical co-morbidities . Although the patients treated by volar plating had a statistically significant early improvement in the range of movement of the wrist , this advantage diminished with time and in absolute terms the difference in range of movement was clinical ly unimportant . Radiologically , there were no clinical ly significant differences in the reductions , although more patients with AO/OTA ( Orthopaedic Trauma Association ) type C fractures were allocated to the external fixation group . The function at one year was similar in the two groups . No clear advantage could be demonstrated with either treatment but fewer re-operations were required in the external fixation group PURPOSE To evaluate the radiographic , objective ( range of motion and grip strength ) , and subjective outcomes of variable-angle volar locking plate ( VAVLP ) fixation for unstable distal radius fractures . METHODS Over a 12-month period , we prospect ively evaluated 39 consecutive distal radius fractures treated operatively with VAVLPs . Surgical exposure , fracture reduction , plate application , and postoperative rehabilitation were uniformly performed . Clinical outcome and radiographic measures , with a minimum follow-up of 12 months , were obtained . RESULTS Final follow-up data were available in 37 patients ( 26 females and 11 males ) with average age of 57 years ( range , 16 - 89 y ) . The average follow-up time was 14 months ( range , 12 - 22 mo ) . At final evaluation , average volar tilt was 3 ° , average radial inclination was 21 ° , average radial height was 12 mm , and average ulnar variance was -0.2 mm . There was no statistical difference between first postoperative and 1-year follow-up radiographs for any of the measured variables , although there were 4 cases of loss of volar tilt . Average Disabilities of the Arm , Shoulder , and H and score was 6 and average visual analog scale pain score was 0.3 . Mean grip strength at 1 year was 96 % of the contralateral side . There was 1 case of variable-angle locking screw loosening and 1 case of extensor tenosynovitis requiring hardware removal . There were no tendon ruptures . CONCLUSIONS The VAVLP fixation restored and maintained acceptable reduction in all patients in this series with a complication rate comparable to st and ard volar fixed-angle locking plates . Treatment of unstable distal radius fractures with a VAVLP result ed in excellent clinical outcomes at 1-year follow-up . However , use of the VAVLP risks soft tissue irritation , hardware failure , and loss of fracture reduction . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic IV Background and purpose Promising results have been reported after volar locked plating of unstable dorsally displaced distal radius fractures . We investigated whether volar locked plating results in better patient-perceived , objective functional and radiographic outcomes compared to the less invasive external fixation . Patients and methods 63 patients under 70 years of age , with an unstable extra-articular or non-comminuted intra-articular dorsally displaced distal radius fracture , were r and omized to volar locked plating ( n = 33 ) or bridging external fixation . Patient-perceived outcome was assessed with the Disability of the Arm , Shoulder , and H and ( DASH ) question naire and the Patient-Rated Wrist Evaluation ( PRWE ) question naire . Results At 3 and 6 months , the volar plate group had better DASH and PRWE scores but at 12 months the scores were similar . Objective function , measured as grip strength and range of movement , was superior in the volar plate group but the differences diminished and were small at 12 months . Axial length and volar tilt were retained slightly better in the volar plate group . Interpretation Volar plate fixation is more advantageous than external fixation , in the early rehabilitation period BACKGROUND Despite the recent trend toward the internal fixation of distal radial fractures in older patients , the currently available literature lacks adequate r and omized trials examining whether open reduction and internal fixation ( ORIF ) with a volar locking plate is superior to nonoperative ( cast ) treatment . The purpose of the present r and omized clinical trial was to compare the outcomes of two methods that were used for the treatment of displaced and unstable distal radial fractures in patients sixty-five years of age or older : ( 1 ) ORIF with use of a volar locking plate and ( 2 ) closed reduction and plaster immobilization ( casting ) . METHODS A prospect i ve r and omized study was performed . Seventy-three patients with a displaced and unstable distal radial fracture were r and omized to ORIF with a volar locking plate ( n = 36 ) or closed reduction and cast immobilization ( n = 37 ) . The outcome was measured on the basis of the Patient-Rated Wrist Evaluation ( PRWE ) score ; the Disabilities of the Arm , Shoulder and H and ( DASH ) score ; the pain level ; the range of wrist motion ; the rate of complications ; and radiographic measurements including dorsal radial tilt , radial inclination , and ulnar variance . RESULTS There were no significant differences between the groups in terms of the range of motion or the level of pain during the entire follow-up period ( p > 0.05 ) . Patients in the operative treatment group had lower DASH and PRWE scores , indicating better wrist function , in the early postoperative time period ( p < 0.05 ) , but there were no significant differences between the groups at six and twelve months . Grip strength was significantly better at all times in the operative treatment group ( p < 0.05 ) . Dorsal radial tilt , radial inclination , and radial shortening were significantly better in the operative treatment group than in the nonoperative treatment group at the time of the latest follow-up ( p < 0.05 ) . The number of complications was significantly higher in the operative treatment group ( thirteen compared with five , p < 0.05 ) . CONCLUSIONS At the twelve-month follow-up examination , the range of motion , the level of pain , and the PRWE and DASH scores were not different between the operative and nonoperative treatment groups . Patients in the operative treatment group had better grip strength through the entire time period . Achieving anatomical reconstruction did not convey any improvement in terms of the range of motion or the ability to perform daily living activities in our cohorts Background With an incidence of about 2–4 per 1,000 residents per year , the distal radial fracture is the most common fracture in the human skeleton . The introduction of fixed-angle plate systems for extension fractures at the radius was evaluated in a prospect i ve study performed at our hospital after selection and acquisition of a new system . The focus of our interest was whether a secondary loss of reduction can be avoided by this plating system . Methods We review ed 80 patients treated for unstable distal radius fractures using a volar fixed-angle plate . Postoperative management included immediate finger motion , early functional use of the h and , a wrist splint used for 4 weeks and physiotherapy . St and ard radiographic and clinical fracture parameters after 12 months ( range 12–14 months ) were measured and final functional results where assessed . Results Bone healing had occurred in all patients at the time of follow-up after 1 year . On X-rays taken at the time of follow-up 60 patients ( 75 % ) had no radial shortening , 20 patients ( 25 % ) had a mean radial shortening of only 1.8 mm ( range 1–3 mm ) compared to the contralateral side . The radial tilt was on average 22 ° ( range 14 ° –36 ° ) ; the volar tilt was on average 6 ° ( range 0 ° –18 ° ) . Comparing the first postoperative X-rays with those taken at final evaluation showed no measureable loss of reduction in the volar or radial tilt . Castaing ’s score , which includes the radiographic results , yielded a perfect outcome in 30 cases , a good outcome in 49 cases and an adequate outcome in one case . The range of motion was on average reduced by 21 % during extension/flexion , by 11 % during radial/ulnardeviation and by 7 % in pronation and supination compared to the contralateral side . Grip strength was 65 % that of the contralateral side . The mean DASH score was 25 points . Conclusion Fixed-angle plate osteo synthesis at the distal radius signifies a significant improvement in the treatment of distal radial fractures in terms of restoration of the shape and function of the wrist . The technically simple palmar access , with a low rate of complications , allows exact anatomical reduction of the fracture . The multidirectional fixed-angle system we used provides solid support for the joint surface even in osteoporotic bone and allows simple subchondral placement of screws with sustained retention of the outcome of reduction . Secondary correction loss can be avoided by this procedure . Early mobilisation can be achieved and is recommended PURPOSE To determine whether volar locking plates ( VLP ) are superior to external fixation ( EF ) with adjuvant pins in unstable distal radius fractures after 5 years of follow-up . METHODS We r and omized 111 unstable distal radius fractures to treatment with either a VLP or EF using adjuvant pins . The patients ' mean age was 54 years ( range , 20 - 84 y ) . Twenty patients were lost to follow-up . At 5 years , 91 patients ( 82 % ) were assessed using the visual analog scale ( VAS ) pain score , Mayo wrist score , Quick Disabilities of the Arm , Shoulder and H and ( QuickDASH ) question naire , range of motion , and radiological evaluation . The QuickDASH score at 5 years was the primary outcome measure . RESULTS The QuickDASH score was not statistically significantly different between the groups ( VLP 10 vs EF 13 ) at 5 years . Patients with VLP had statistically significant better supination ( 85 ° vs 81 ° ) , better radial deviation ( 18 ° vs 16 ° ) , and less radial shortening ( 1 mm vs 2 mm ) . For AO/OTA type C2 fractures , the VLP had statistically significant better supination ( 84 ° vs 78 ° ) , flexion ( 64 ° vs 56 ° ) , grip strength ( 34 kg vs 28 kg ) , Mayo wrist score ( 92 vs 76 ) , and less ulnar shortening ( 1 mm vs 3 mm ) . The QuickDASH score in the C2 subset analysis showed a difference of 10 ( VLP 8 vs EF 18 ) , but this was not statistically significant . In the VLP group , 11 patients ( 21 % ) had their plates removed owing to surgically related complications . In the EF group , 5 patients had proximal radial scar correction surgery owing to skin contracture . CONCLUSIONS The findings were satisfactory for both groups at 5 years . The VLP provided statistically significantly better results for several clinical outcomes in the C2 subset analysis . However , 21 % of the VLPs were removed because of surgical complications . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic BACKGROUND The aim of this study was to compare the outcomes of displaced distal radial fractures treated with a volar locking plate with the results of such fractures treated with a conventional method of closed reduction and percutaneous wire fixation with supplemental bridging external fixation when required . Our aim was to ascertain whether the use of a volar locking plate improves functional outcomes . METHODS A single-center , pragmatic , r and omized controlled trial was conducted in a tertiary care institution . One hundred and thirty patients ( eighteen to seventy-three years of age ) who had a displaced distal radial fracture were r and omized to treatment with either a volar locking plate ( n = 66 ) or a conventional percutaneous fixation method ( n = 64 ) . Outcome assessment s were conducted at six weeks , twelve weeks , and one year . Outcomes were measured on the basis of scores on the Patient Evaluation Measure ( PEM ) and QuickDASH question naire ( a shortened version of the Disabilities of the Arm , Shoulder and H and , or DASH , Outcome Measure ) , EuroQol-5D ( EQ-5D ) scores , wrist range of motion , grip strength , and radiographic parameters . RESULTS The rate of follow-up at one year was 95 % . Patients in the volar locking-plate group had significantly better PEM and QuickDASH scores and range of motion at six weeks compared with patients in the conventional-treatment group , but there were no significant differences between the two groups at twelve weeks or one year . Grip strength was better in the plate group at all time points . The volar locking plate was better at restoring palmar tilt and radial height . Significantly more patients in the plate group were driving at the end of six weeks , but this did not translate to a significant difference between groups in terms of those returning to work by that time . CONCLUSIONS Use of a volar locking plate result ed in a faster early recovery of function compared with use of conventional methods . However , no functional advantage was demonstrated at or beyond twelve weeks . Use of the volar locking plate result ed in better anatomical reduction and grip strength , but there was no significant difference in function between the groups at twelve weeks or one year . The earlier recovery of function may be of advantage to some patients . LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence The purpose of this prospect i ve , r and omized and blinded study was to compare the clinical outcomes of distal radial fractures treated with either an intramedullary nail or a volar locking plate . Sixty two patients were enrolled in the study and r and omized to treatment with a MICRONAILTM ( Group 1 , 31 patients ) or an adaptive plate ( Group 2 , 31 patients ) . Fracture types included were unstable extra-articular metaphyseal distal radial fractures and simple or multifragmentary sagittal articular distal radial fractures ( AO classification types A2 , A3 , B1.1 and B1.2 ) . All patients were evaluated at 6 weeks , 3 months and 12 months after surgery . Outcome measures included st and ard radiographic parameters , active wrist range of motion , the disabilities of the arm , shoulder and h and ( DASH ) and Mayo wrist scores . We concluded that treatment of this subset of distal radius fractures with minimally invasive intramedullary nailing gives better clinical outcomes at 6 weeks after surgery than treatment with a volar locking plate . By 3 and 12 months following surgery , there are no significant differences in outcome between the two treatment methods . Disadvantages of the MICRONAIL ™ fixation system include risk of injury to the superficial branch of the radial nerve and a narrower spectrum of indications than volar locking plates PURPOSE To prospect ively determine the results of treatment of distal radius fractures with a volar locking plate system with no bone graft and early mobilization . METHODS Internal fixation and early mobilization of dorsally displaced , unstable fractures of the distal radius using a volar locking plate system without bone grafting was investigated in a prospect i ve series of 49 fractures in 49 consecutive patients . All patients were allowed to move the wrist joint immediately after surgery . Physical examination at 5 weeks , 3 months , 6 months , and 1 year after the operation were performed . Radiographic parameters on preoperative , postoperative , and 1-year postoperative radiographs were compared . At 1-year review , the final clinical functions were evaluated with the Gartl and and Werley functional scoring system , a modified Green and O'Brien system , and the Disabilities of the Arm , Shoulder , and H and question naire . RESULTS The average radiographic results at 1 year were 9 degrees of volar tilt ; 22 degrees of radial inclination ; 1 mm of ulnar variance , and 0 mm of articular incongruity . At 1-year review , an excellent or good result was found according to the system of Gartl and and Werley and a modified Green and O'Brien system with scores of 100 % and 98 % , respectively . The Disabilities of the Arm , Shoulder , and H and score averaged 6 , indicating a high degree of patient satisfaction . There were no cases of infection , complex regional pain syndrome , tendon rupture , tendon irritation , nerve injury , or implant failure . CONCLUSIONS The volar locking plate fixation without bone grafting and early mobilization is a safe and effective treatment for dorsally displaced , unstable fractures of the distal radius PURPOSE Locking plates are thought to have many advantages such as a decreased incidence of loss of reduction secondary to screw toggling and improved bone healing due to an increased periosteal blood supply . We hypothesized that locking plates will also provide increased stiffness and increased load to failure when they are applied dorsally to stabilize dorsally comminuted distal radius fractures . This study compared the stiffness and strength of dorsally applied locking and st and ard ( nonlocking ) T-plates applied to a dorsally comminuted distal radius fracture model . METHODS Sixteen pairs of embalmed cadaveric human radii were potted , and a st and ard wedge osteotomy was performed simulating a dorsally comminuted distal radius fracture . The radii were r and omized into 2 groups , so that 8 pairs received a 3.5-mm dorsal locking T-plate over the osteotomy on the right radius and 8 pairs received the same on the left radius . A dorsal 3.5-mm st and ard T-plate was placed over the osteotomy on the contralateral radius in each group . An axial load was used to test the strength and stiffness of each construct . Paired t tests were then used to compare the strength and stiffness of the locking plate with those of the st and ard plate . RESULTS A significant difference was found in both the stiffness and the strength between the locking and st and ard nonlocking plates . The locking T-plate was 33 % stiffer than the st and ard T-plate . The locking T-plate had a 91 % increase in the load to failure . Failure for both locking and st and ard T-plates occurred via volar cortex bone fracture . CONCLUSIONS Locking T-plates increased both the stiffness and strength of dorsally comminuted distal radius fractures compared with st and ard nonlocking T-plates by a statistically significant margin Our purpose s were to report the radiographic outcomes and complications of patients with Colles ' fracture treated with the Nakashima locking volar plate system ( variable angled distal screw locking mechanism ) prospect ively and to report the results of objective clinical variables such as grip strength and range of motion of the wrist prospect ively at up to one year . This study consisted of eight men and 32 women for analysis of radiographic parameters ( volar tilt , radial inclination and radial length ) and complications . Radiographic parameters were measured pre-operatively , immediately post-operatively and at final follow-up visit . The average age at operation was 60.3 years old . Among them , we selected 25 cases ( 6 men and 19 women ) whom we followed up at six weeks , three months , six months and one year post-operatively . The average age at operation in this group was 62 years old . We measured objective clinical variables ( grip strength , forearm rotation , wrist extension/flexion ) at each visit . Except for volar tilt , radiographic parameters revealed no significant changes between immediately post-operative radiographs and radiographs at final follow-up visit . Complications included loss of reduction in two cases . Objective clinical variables other than pronation measurement showed significant increase at each visit up to one year post-operatively . Satisfactory clinical and radiographic results were obtained by using this system . The variable angled distal fragment plating system appears to be a reliable construct for rigid fixation of Colles ' fractures ; however , technical errors can occur , as with other fixation systems . We demonstrated that the follow-up of Colles ' fracture treated by our volar locking plate less than one year post-operative may be insufficient PURPOSE To identify risk factors for tendon attrition after volar locking plate fixation of distal radius fractures . METHODS We prospect ively assessed attrition of the flexor pollicis longus tendon at volar plate removal in 127 h and s in 126 patients . We also evaluated preoperative lateral wrist radiographs , sonographs , and crepitus with flexor pollicis longus tendon motion and compared the demographic and radiographic characteristics of patients with and without tendon attrition . Multivariate logistic regression analysis was employed to identify the factors independently associated with tendon attrition . RESULTS We found 12 cases of tendon attrition ( 10 % ) and 1 that presented with tendon rupture in our cohort . Crepitus was recognized in 14 patients ( 11 % ) : 6 cases ( 50 % ) were among the 12 h and s in 12 patients with tendon attrition whereas 8 ( 7 % ) were detected in the remaining 114 h and s in 113 patients . Logistic regression examination revealed that audible crepitus and volar placement of the plate in lateral radiographs were independent predictors of tendon attrition . CONCLUSIONS Crepitus and volar placement of hardware in lateral radiographs were independent risk factors for flexor tendon attrition after volar plating for distal radius fracture . These results may facilitate surgical decisions regarding early plate removal to prevent possible tendon rupture . TYPE OF STUDY /LEVEL OF EVIDENCE Diagnostic II BACKGROUND To evaluate functional , radiologic , and subjective outcome after volar locking plate osteo synthesis ( VLPO ) for unstable distal radius fractures ( DRF ) . METHODS In this study , patients treated with VLPO for isolated DRF between March 2005 and December 2007 were prospect ively evaluated . Patients with multiple injuries or those unavailable for follow-up were excluded from further evaluation . Range of motion , grip strength , and the subjective Patient-Rated Wrist Evaluation score were monitored for 6 weeks , 3 months , 6 months , and finally 1 year after surgery . The uninjured contralateral wrist served as control . The radiologic outcome after 1 year was scored using the Lidstrom score . RESULTS In total , 245 patients were included in the study with a mean age of 62 years ± 18 years . At the final follow-up , 1 year after surgery , 228 patients ( 93 % ) could be controlled . Range of motion significantly increased during follow-up . One year after surgery , mean flexion was 64 ° ± 15 ° , and mean extension reached 64 ° ± 15 ° corresponding with > 90 % of the uninjured contralateral wrist function . Grip strength increased from 14 kg ± 8 kg ( 54 % ) 6 weeks after surgery to 25 kg ± 11 kg ( 91 % ) at the final follow-up . Patient-Rated Wrist Evaluation score result ed in mean 8 points ± 16 points after 1 year . Lidstrom score reached a mean of 1.3 points ± 0.6 points , demonstrating a good initial fracture reduction and stable fixation . A complication rate of 15 % could be seen in our series , among secondary fracture displacement in two patients ( 1 % ) . CONCLUSIONS VLPO for the treatment of unstable DRF is a reliable technique with excellent subjective , objective , and radiologic outcome PURPOSE To determine whether volar locking plates are superior to external fixation with adjuvant pins in the treatment of unstable distal radius fractures . METHODS A total of 111 unstable distal radius fractures were r and omized to treatment with external fixation ( EF ) using adjuvant pins or with a volar locking plate ( VLP ) . The mean age of the patients was 54 years ( range , 20 - 84 y ) . Seven patients were lost to follow-up . At 1 year , 104 patients were assessed with a visual analog scale pain score , Mayo wrist score , Quick-Disabilities of the Arm , Shoulder , and H and ( QuickDASH ) , range of motion , and radiological evaluation . The QuickDASH score at 52 weeks was the primary outcome measure . RESULTS The operative time in the EF group was 77 minutes , compared with 88 minutes in the VLP group . At 52 weeks , patients with VLPs had a higher Mayo wrist score ( 90 vs. 85 ) , better supination ( 89 ° vs. 85 ° ) , and less radial shortening ( + 1.4 mm vs. + 2.2 mm ) . There were more patients with pain over the ulnar styloid in the EF group ( 16 vs 6 patients ) . For AO type C2/C3 , the patients with VLPs had better supination ( 90 ° vs. 76 ° ) and less ulnar shortening ( + 1.1 mm vs. + 2.8 mm ) . The complication rate was 30 % in the EF group , compared with 29 % in the VLP group . Eight ( 15 % ) plates were removed due to complications . The QuickDASH score was not significantly different between the groups . CONCLUSIONS Although we did not find a significant difference between the groups for the QuickDASH score , we believe that our results support the use of VLPs for the treatment of unstable distal radius fractures . A serious concern is that some patients will have to have their plates removed ; therefore , improving the surgical technique is important . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic BACKGROUND Intramedullary techniques for stabilization of displaced distal radius fractures are now available . Purported benefits include limited soft tissue dissection while affording sufficient stability to allow early wrist motion . The primary null hypothesis of this r and omized trial is that there is no significant difference with respect to functional outcome , pain and disability between patients treated with either 2.4-mm volar locking plate fixation or intramedullary nail fixation of unstable dorsally displaced extra-articular fractures of the distal radius . METHODS We conducted a single-centre , parallel-group trial , with unrestricted r and omization . Patients with dorsally displaced extra-articular distal radius fractures were r and omized to receive volar locking plate ( n=72 ) fixation or intramedullary nailing ( n=80 ) . The outcome was measured on the basis of the Gartl and and Werley and Castaing score ; the pain level ; the range of wrist motion ; the rate of complications ; and radiographic measurements including volar tilt and ulnar variance . Clinical and radiographic assessment was performed at 8 weeks , 6 months , 1 year and 2 years after the operation . RESULTS There were no significant differences between groups in terms of range of motion , grip strength or the level of pain during the entire follow-up period ( p>0.05 ) . There was no significant difference between treatment groups with respect to volar tilt or ulnar variance ( p>0.05 ) . There was no significant difference in the complication rate between groups ( p>0.05 ) . CONCLUSIONS The present study supports the view that intramedullary nail fixation and volar plate fixation for the treatment of displaced extra-articular distal radius fractures have equivalent radiographic and functional outcomes . LEVEL OF EVIDENCE Level I therapeutic study PURPOSE To compare surgical outcomes of volar locking plates ( VP ) and external fixation ( EF ) ( with or without intra-focal fixation ) for AO-type C2 and C3 fractures of the distal radius . METHODS From an initial group of 92 patients with AO-type C2 and C3 distal radius fractures who were enrolled in a prospect i ve , r and omized study comparing volar plate fixation with external fixation ( with or without intra-focal fixation ) , 74 patients were studied . The research ers evaluated functional assessment s ( wrist range of motion , grip strength , and Michigan H and Question naire ) at each patient visit and measured radiographic assessment ( radial inclination , volar tilt , ulnar variance , and articular congruity ) at 12 months . RESULTS The grip strength of the VP group was significantly greater than that of the EF group at 3 and 6 months . The range of motion was significantly greater in the VP group than in the EF group at 3 months . There were no significant differences in the range of motion and grip strength between the 2 groups at 12 months . The Michigan H and Question naire score was higher in the VP group than in the EF group at 3 months but was same at 12 months . There was no significant difference between groups with respect to volar tilt or radial inclination . The VP group showed superior radiologic outcomes in terms of the ulnar variance . One patient in the VP group and 3 in the EF group had an intra-articular stepoff deformity greater than 2 mm . This difference did not reach statistical significance . CONCLUSIONS These results for functional recovery after distal radius surgery offer insight into treatment decisions and interpretations of treatment outcomes for patients with comminuted intra-articular distal radius fractures |
11,803 | 29,171,076 | Weight stigma was positively associated with obesity , diabetes risk , cortisol level , oxidative stress level , C-reactive protein level , eating disturbances , depression , anxiety , body image dissatisfaction and negatively associated with self-esteem among overweight and obese adults .
Weight stigma is associated with adverse physiological and psychological outcomes . | AIM To summarize the associations between weight stigma and physiological and psychological health for individuals who are overweight or obese .
BACKGROUND Weight stigma can be defined as individuals experiencing verbal or physical abuse secondary to being overweight or obese .
Weight stigma has negative consequences for both physiological and psychological health . | Background Few studies have explored the relationship between weight bias and weight loss treatment outcomes . Purpose This investigation examined the relationship between implicit and explicit weight bias and ( a ) program attrition , ( b ) weight loss , ( c ) self-monitoring adherence , ( d ) daily exercise levels and overall caloric expenditure , ( e ) daily caloric intake , and ( f ) daily caloric deficit among overweight/obese treatment-seeking adults . Methods Forty-six overweight/obese adults ( body mass index ≥ 27 kg/m2 ) participating in an 18-week , stepped-care , behavioral weight loss program completed implicit and explicit measures of weight bias . Participants were instructed to self-monitor and electronically report daily energy intake , exercise , and energy expenditure . Results Greater weight bias was associated with inconsistent self-monitoring , greater caloric intake , lower energy expenditure and exercise , creation of a smaller caloric deficit , higher program attrition , as well as less weight loss during the self-help phase of the stepped-care treatment . Conclusions Weight bias may interfere with overweight/obese treatment-seeking adults ' ability to achieve optimal health An implicit association test ( IAT ) measures differential association of 2 target concepts with an attribute . The 2 concepts appear in a 2-choice task ( 2-choice task ( e.g. , flower vs. insect names ) , and the attribute in a 2nd task ( e.g. , pleasant vs. unpleasant words for an evaluation attribute ) . When instructions oblige highly associated categories ( e.g. , flower + pleasant ) to share a response key , performance is faster than when less associated categories ( e.g. , insect & pleasant ) share a key . This performance difference implicitly measures differential association of the 2 concepts with the attribute . In 3 experiments , the IAT was sensitive to ( a ) near-universal evaluative differences ( e.g. , flower vs. insect ) , ( b ) expected individual differences in evaluative associations ( Japanese + pleasant vs. Korean + pleasant for Japanese vs. Korean subjects ) , and ( c ) consciously disavowed evaluative differences ( Black + pleasant vs. White + pleasant for self-described unprejudiced White subjects ) |
11,804 | 32,281,936 | The interventions showed the highest effects on satisfaction with information , adherence to treatment instructions and to medication usage , clinical outcomes , and knowledge .
Conclusions This review demonstrates that educating patients with timely medical information through their smartphones or tablets improves their levels of knowledge , medication or treatment adherence , satisfaction , and clinical outcomes , as well as having a positive effect on health care economics .
These effects are most pronounced in interventions with a short duration ( ie , less than a month ) and with a high frequency of messages to patients ( ie , once per week or more ) . | Background Patient education is a crucial element within health care .
It is a known predictor for increased engagement in shared decision making , improved medication and treatment adherence , higher levels of satisfaction , and even better treatment outcomes .
Unfortunately , often patients only remember a very limited amount of medical information .
An important reason is that most patients are simply not capable of processing large amounts of new medical information in a short time .
Apps for smartphones and tablets have the potential to actively educate patients by providing them with timely information through the use of push notifications .
Objective The objective of this systematic review is to provide an overview of the effects of using smartphone and tablet apps to educate patients with timely education .
Within this review , we focused on patients that receive their care in a hospital setting .
We assessed the effects of the interventions on outcomes , such as patients ’ knowledge about their illness and treatment , adherence to treatment instructions and to medication usage , and satisfaction with the care they received . | Background Despite the increasing breast cancer incidence and mortality rates , Korean American immigrant women have one of the lowest rates of breast cancer screening across racial groups in the United States . Mobile health ( mHealth ) , defined as the delivery of health care information or services through mobile communication devices , has been utilized to successfully improve a variety of health outcomes . Objective This study adapted the principles of mHealth to advance breast cancer prevention efforts among Korean American immigrant women , an underserved community . Methods Using a r and omized controlled trial design , 120 Korean American women aged 40 to 77 years were recruited and r and omly assigned to either the mMammogram intervention group ( n=60 ) to receive culturally and personally tailored multilevel and multimedia messages through a mobile phone app along with health navigator services or the usual care control group ( n=60 ) to receive a printed brochure . Outcome measures included knowledge , attitudes , and beliefs about breast cancer screening , readiness for mammography , and mammogram receipt . The feasibility and acceptability of the mMammogram intervention was also assessed . Results The intervention group showed significantly greater change on scores of knowledge of breast cancer and screening guidelines ( P=.01 ) . The intervention group also showed significantly greater readiness for mammography use after the intervention compared with the control group . A significantly higher proportion of women who received the mMammogram intervention ( 75 % , 45/60 ) completed mammograms by the 6-month follow-up compared with the control group ( 30 % , 18/60 ; P<.001 ) . In addition , the intervention group rated satisfaction with the intervention ( P=.003 ) , effectiveness of the intervention ( P<.001 ) , and increase of knowledge on breast cancer and screenings ( P=.001 ) significantly higher than the control group . Conclusions A mobile phone app – based intervention combined with health navigator service was a feasible , acceptable , and effective intervention mechanism to promote breast cancer screening in Korean American immigrant women . A flexible , easily tailored approach that relies on recent technological advancements can reach underserved and hard-to-recruit population s that bear disproportionate cancer burdens . Trial Registration Clinical trials.gov NCT01972048 ; https:// clinical trials.gov/show/NCT01972048 ( Archived by WebCite at https:// clinical trials.gov/archive/NCT01972048/2013_10_29 The progressive nature of Parkinson ’s disease , its complex treatment regimens and the high rates of comorbid conditions make self-management and treatment adherence a challenge . Clinicians have limited face-to-face consultation time with Parkinson ’s disease patients , making it difficult to comprehensively address non-adherence . Here we share the results from a multi-centre ( seven centres ) r and omised controlled trial conducted in Engl and and Scotl and to assess the impact of using a smartphone-based Parkinson ’s tracker app to promote patient self-management , enhance treatment adherence and quality of clinical consultation . Eligible Parkinson ’s disease patients were r and omised using a 1:1 ratio according to a computer-generated r and om sequence , stratified by centre and using blocks of variable size , to intervention Parkinson ’s Tracker App or control ( Treatment as Usual ) . Primary outcome was the self-reported score of adherence to treatment ( Morisky medication adherence scale −8 ) at 16 weeks . Secondary outcomes were Quality of Life ( Parkinson ’s disease question naire −39 ) , quality of consultation for Parkinson ’s disease patients ( Patient-centred question naire for Parkinson ’s disease ) , impact on non-motor symptoms ( Non-motor symptoms question naire ) , depression and anxiety ( Hospital anxiety and depression scale ) and beliefs about medication ( Beliefs about Medication Question naire ) at 16 weeks . Primary and secondary endpoints were analysed using a generalised linear model with treatment as the fixed effect and baseline measurement as the covariate . 158 patients completed the study ( Parkinson ’s tracker app = 68 and TAU = 90 ) . At 16 weeks Parkinson ’s tracker app significantly improved adherence , compared to treatment as usual ( mean difference : 0.39 , 95%CI 0.04–0.74 ; p = 0.0304 ) with no confounding effects of gender , number of comorbidities and age . Among secondary outcomes , Parkinson ’s tracker app significantly improved patients ’ perception of quality of consultation ( 0.15 , 95 % CI 0.03 to 0.27 ; p = 0.0110 ) . The change in non-motor symptoms was −0.82 ( 95 % CI −1.75 to 0.10 ; p = 0.0822 ) . 72 % of participants in the Parkinson ’s tracker app group continued to use and engage with the application throughout the 16-week trial period . The Parkinson ’s tracker app can be an effective and novel way of enhancing self-reported medication adherence and quality of clinical consultation by supporting self-management in Parkinson ’s disease in patients owning smartphones . Further work is recommended to determine whether the benefits of the intervention are maintained beyond the 16 week study period . Digital healthcare : App helps patients stick to planA smartphone-based application improves treatment adherence of patients with Parkinson ’s disease ( PD ) . Rashmi Lakshminarayana , from uMotif Ltd , and research ers from the UK and The Netherl and s describe the results of a 16 week trial of a Parkinson ’s tracker app ( PTA ) that r and omised 215 patients from seven different health centres . Patients using the app reported significantly better adherence to their medication plan compared with control patients who continued their treatment as usual . Interestingly , using the PTA also improved the patients ’ perception of the quality of their clinical care , possibly as a result of feeling more involved and in control of their care . These findings suggest that by sending medication reminders and tracking symptoms , the app can help patients with Parkinson ’s self-manage their increasingly complex treatment regimen as the disease progresses Background : Little is known about the benefits of social networks in the management of patients . Objective : The aim of this study was to compare the effects of self-management ( SM ) education using telephone follow-up and mobile phone-based social networking on SM behaviors among patients with hypertension . Methods : This r and omized clinical trial was conducted with 100 patients . They were r and omly allocated to four groups : ( i ) control , ( ii ) SM training without follow-up , ( iii ) telephone follow-up and ( iv ) smartphone-based social networking follow-up . The hypertension SM behavior question naire was used for data collection before and six weeks after the study . Results : Those patients who underwent SM education training ( with and without follow-up ) had statistically significant differences from those in the control group in terms of SM behaviors ( p < .001 ) . There was no statistically significant difference between different types of follow-up . Conclusion : SM education using telephone follow-up and /or smartphone-based social networking follow-up influenced SM behaviors among patients with hypertension Background Many preventable behaviors contribute to adolescent mortality and morbidity . Non-adherence to preventive measures represents a challenge and has been associated with worse health outcomes in this population . The widespread use of electronic communication technologies by adolescents , particularly the use of text messaging ( short message service , SMS ) and mobile phones , presents new opportunities to intervene on risk and preventive risk behavior , but little is known about their efficacy . Objective This study aim ed to systematic ally evaluate evidence for the efficacy of text messaging and mobile phone app interventions to improve adherence to preventive behavior among adolescents and describe intervention approaches to inform intervention development . Methods This review covers literature published between 1995 and 2015 . Search es included PubMed , Embase , CENTRAL , PsycINFO , CINAHL , INSPEC , Web of Science , Google Scholar , and additional data bases . The search strategy sought articles on text messaging and mobile phone apps combined with adherence or compliance , and adolescents and youth . An additional h and search of related themes in the Journal of Medical Internet Research was also conducted . Two review ers independently screened titles and abstract s , assessed full-text articles , and extracted data from articles that met inclusion criteria . Included studies reflect original research —experimental or preexperimental design s with text messaging or mobile phone app interventions —targeting adherence to preventive behavior among adolescents ( 12 - 24 years old ) . The preferred reporting items of systematic review s and meta-analyses ( PRISMA ) guidelines were followed for reporting results , and findings were critically appraised against the Oxford Centre for Evidence -based Medicine criteria . Results Of 1454 records , 19 met inclusion criteria , including text messaging ( n=15 ) and mobile phone apps ( n=4 ) . Studies targeted clinic attendance , contraceptive use , oral health , physical activity and weight management , sun protection , human papillomavirus ( HPV ) vaccination , smoking cessation , and sexual health . Most studies were performed in the United States ( 47 % , 9/19 ) , included younger adolescents ( 63 % , 12/19 ) , and had sample size < 100 ( 63 % , 12/19 ) . Although most studies were r and omized controlled trials ( RCTs ; 58 % , 11/19 ) , only 5 followed an intent-to-treat analysis . Only 6 of 19 studies ( 32 % ) incorporated a theoretical framework in their design . Most studies reported good feasibility with high acceptability and satisfaction . About half of the included studies ( 42 % , 8/19 ) demonstrated significant improvement in preventive behavior with moderate st and ardized mean differences . As early efforts in this field to establish feasibility and initial efficacy , most studies were low to moderate in quality . Studies varied in sample size and methods of preventive behavior adherence or outcome assessment , which prohibited performing a meta- analysis . Conclusions Despite the promising feasibility and acceptability of text messaging and mobile phone apps in improving preventive behavior among adolescents , overall findings were modest in terms of efficacy . Further research evaluating the efficacy , effectiveness , and cost-effectiveness of these intervention approaches in promoting preventive behavior among adolescents is needed Purpose The purpose of this prospect i ve r and omized-controlled trial ( RCT ) was to evaluate if an app-based feedback-controlled active muscle training programme can be used to improve the outcome in the immediate postoperative period after total knee arthroplasty ( TKA ) . Methods Sixty patients , with a median age of 65.9 years ( range 45–84 ) , awaiting primary TKA were r and omized into a control and training group . Both groups followed an identical postoperative protocol . In addition , the training group postoperatively performed an app-based feedback-controlled active muscle training programme multiple times daily . Outcome measures were active and passive range of motion ( ROM ) , pain at rest and in motion , knee extension strength , the timed “ Up and Go ” , 10-m Walk Test , 30-s Chair St and Test , Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , Knee Society Score ( KSS ) , and clinical data . Results The training group performed an average of 18.4 training sessions , which led to significantly higher ROM , less pain at rest and in motion , higher strength , and significantly higher functional scores . More training correlated with a better outcome . Conclusions The use of an app-based feedback-controlled active muscle training programme can improve the clinical outcome after TKA , especially ROM and reduce pain . Clinical ly relevant is that the training programme could be considered an alternative to continuous passive motion after total knee arthroplasty . Level of evidence II Background Modern health care focuses on shared decision making ( SDM ) because of its positive effects on patient satisfaction , therapy compliance , and outcomes . Patients ’ knowledge about their illness and available treatment options , gained through medical education , is one of the key drivers for SDM . Current patient education relies heavily on medical consultation and is known to be ineffective . Objective This study aim ed to determine whether providing patients with information in a subdivided , categorized , and interactive manner via an educational app for smartphone or tablet might increase the knowledge of their illness . Methods A surgeon-blinded r and omized controlled trial was conducted with 213 patients who were referred to 1 of the 6 Dutch hospitals by their general practitioner owing to knee complaints that were indicative of knee osteoarthritis . An interactive app that , in addition to st and ard care , actively sends informative and pertinent content to patients about their illness on a daily basis by means of push notifications in the week before their consultation . The primary outcome was the level of perceived and actual knowledge that patients had about their knee complaints and the relevant treatment options after the intervention . Results In total , 122 patients were enrolled in the control group and 91 in the intervention group . After the intervention , the level of actual knowledge ( measured on a 0 - 36 scale ) was 52 % higher in the app group ( 26.4 vs 17.4 , P<.001 ) . Moreover , within the app group , the level of perceived knowledge ( measured on a 0 - 25 scale ) increased by 22 % during the week within the app group ( from 13.5 to 16.5 , P<.001 ) , compared with no gain in the control group . Conclusions Actively offering patients information in a subdivided ( per day ) , categorized ( per theme ) , and interactive ( video and quiz questions ) manner significantly increases the level of perceived knowledge and demonstrates a higher level of actual knowledge , compared with st and ard care educational practice s. Trial Registration International St and ard R and omized Controlled Trial Number IS RCT N98629372 ; http://www.is rct n.com/IS RCT N98629372 ( Archived by WebCite at http://www.webcitation.org/73F5trZbb BACKGROUND AND AIM Getting ready for a colonoscopy is difficult and involves many steps . Information given to patients is very important for adherence to treatment . We created a novel smart phone application ( SPA ) aim ed to increase bowel preparation quality and patient satisfaction . METHODS We carried out a prospect i ve , endoscopist-blinded , r and omized , controlled trial . We enrolled 260 outpatient ( 58 % female , age range 21 - 75 years ) owners of a smartphone . Patients were allocated to two different protocol s : instructions provided by SPA ( SPA group ; n = 108 ) or written instructions with visual aids ( control group ; n = 152 ) . All procedures were carried out in the afternoon and patients received the same purgative regimen ( 2 L polyethylene glycol ( PEG ) solution plus ascorbic acid ) , in a full-dose same-day regimen . The study was design ed to detect an improvement in quality of bowel preparation using the Harefield Cleansing Scale ( HCS ) scale . Effect of protocol on patient satisfaction was assessed with a specific question naire at the time of colonoscopy . RESULTS Proportion of patients who obtained successful bowel preparation for colonoscopy ( HCS A or B ) was significantly higher in the SPA group than in the control group ( 100 % vs 96.1 % , respectively ; P = 0.037 ) . Mean global HCS scores were similar in both groups . Patient-reported tolerability and overall experience with the prescribed bowel preparation were significantly higher for the SPA group than for the control group . CONCLUSION Successful cleansing and patient acceptability with the use of SPA were superior to written instructions in out patients su bmi tted for colonoscopy using 2 L PEG solution plus ascorbic acid OBJECTIVES : Adherence with diet and prescribed purgative is essential for proper cleansing with low‐volume bowel preparations . The aim of this work was to assess the effect of a customized mobile application ( App ) on adherence and quality of bowel preparation . METHODS : One hundred and sixty ( 160 ) eligible patients scheduled for elective colonoscopy were r and omly assigned to paper ( control ) or App‐based instructions . The preparation consisted of low‐fiber diet for 2 days , clear fluids for one day and split‐dose sodium picosulfate/magnesium citrate ( SPS ) . Before colonoscopy , information was collected regarding adherence with , and utility of the provided instructions . The colonoscopists , blinded to assignment , grade d bowel preparation using the Aronchick , Ottawa , and Chicago preparation scales . The primary endpoint was adherence with instructions . Quality of preparation was a secondary endpoint . RESULTS : No difference in overall adherence or bowel cleanliness was observed between the study arms . Adherence was reported in 82.4 % of App vs. 73.4 % of controls ( P=0.40 ) . An adequate bowel preparation on the Aronchick scale was noted in 77.2 vs. 82.5 % , respectively ( P=0.68 ) . Mean scores on the Ottawa and Chicago scales were also similar . Gender , age , time of colonoscopy , and BMI did not influence preparation or adherence . Compliance with the clear fluid diet component was noted in 94 % of patients with BMI < 30 vs. 77 % with BMI ≥30 ( P<0.01 ) . SPS was well tolerated by 81.9 % of patients . The App was user‐friendly and received higher overall rating in this respect than paper instructions ( P<0.01 ) . CONCLUSIONS : SPS is well tolerated and effective for bowel cleansing regardless of instruction method . Customized smartphone applications are effective , well‐accepted and could replace st and ard paper instructions for bowel preparation . Clinical Trials.gov : AIMS To evaluate the effect of a mobile app treatment for stress urinary incontinence ( SUI ) in women . METHODS R and omized controlled trial , conducted 2013 - 2014 in Sweden . Community-dwelling adult women with ≥1 SUI episode/week recruited through our website and r and omized to app treatment ( n = 62 ) or control group ( postponed treatment , n = 61 ) . One participant from each group was lost to follow-up . Intervention was the mobile app Tät ® with a treatment program focused on pelvic floor muscle training ( PFMT ) , and information about SUI and lifestyle factors . Primary outcomes , 3 months after r and omization : symptom severity ( International Consultation on Incontinence Modular Question naire Urinary Incontinence Short Form [ ICIQ-UI SF ] ) ; and condition-specific quality of life ( ICIQ Lower Urinary Tract Symptoms Quality of Life [ ICIQ-LUTSqol ] ) . RESULTS One hundred and twenty-three women were included ( mean age 44.7 ) , with moderate/severe SUI ( 97.5 % , 120/123 ) , mean ICIQ-UI SF score 11.1 ( SD 2.8 ) and mean ICIQ-LUTSqol score 34.4 ( SD 6.1 ) at baseline . At follow-up , the app group reported improvements in symptom severity ( mean ICIQ-UI SF score reduction : 3.9 , 95 % confidence interval 3.0 - 4.7 ) and condition-specific quality of life ( mean ICIQ-LUTSqol score reduction : 4.8 , 3.4 - 6.2 ) and the groups were significantly different ( mean ICIQ-UI SF score difference : -3.2 , -4.3to -2.1 ; mean ICIQ-LUTSqol score difference : -4.6 , -7.8 to -1.4 ) . In the app group , 98.4 % ( 60/61 ) performed PFMT at follow-up , and 41.0 % ( 25/61 ) performed it daily . CONCLUSIONS The mobile app treatment was effective for women with SUI and yielded clinical ly relevant improvements . This app may increase access to first-line treatment and adherence to PFMT BACKGROUND Patients with myocardial infa rct ion ( MI ) seldom reach recommended targets for secondary prevention . This study evaluated a smartphone application ( " app " ) aim ed at improving treatment adherence and cardiovascular lifestyle in MI patients . DESIGN Multicenter , r and omized trial . METHODS A total of 174 ticagrelor-treated MI patients were r and omized to either an interactive patient support tool ( active group ) or a simplified tool ( control group ) in addition to usual post-MI care . Primary end point was a composite nonadherence score measuring patient-registered ticagrelor adherence , defined as a combination of adherence failure events ( 2 missed doses registered in 7-day cycles ) and treatment gaps ( 4 consecutive missed doses ) . Secondary end points included change in cardiovascular risk factors , quality of life ( European Quality of Life-5 Dimensions ) , and patient device satisfaction ( System Usability Scale ) . RESULTS Patient mean age was 58 years , 81 % were men , and 21 % were current smokers . At 6 months , greater patient-registered drug adherence was achieved in the active vs the control group ( nonadherence score : 16.6 vs 22.8 [ P = .025 ] ) . Numerically , the active group was associated with higher degree of smoking cessation , increased physical activity , and change in quality of life ; however , this did not reach statistical significance . Patient satisfaction was significantly higher in the active vs the control group ( system usability score : 87.3 vs 78.1 [ P = .001 ] ) . CONCLUSIONS In MI patients , use of an interactive patient support tool improved patient self-reported drug adherence and may be associated with a trend toward improved cardiovascular lifestyle changes and quality of life . Use of a disease-specific interactive patient support tool may be an appreciated , simple , and promising complement to st and ard secondary prevention Background eHealth interventions appear and change so quickly that they challenge the way we conduct research . By the time a r and omized trial of a new intervention is published , technological improvements and clinical discoveries may make the intervention date d and unappealing . This and the spate of health-related apps and websites may lead consumers , patients , and caregivers to use interventions that lack evidence of efficacy . Objective This paper aims to offer strategies for increasing the speed and usefulness of eHealth research . Methods The paper describes two types of strategies based on the authors ’ own research and the research literature : those that improve the efficiency of eHealth research , and those that improve its quality . Results Efficiency strategies include : ( 1 ) think small : conduct small studies that can target discrete but significant questions and thereby speed knowledge acquisition ; ( 2 ) use efficient design s : use such methods as fractional-factorial and quasi-experimental design s and surrogate endpoints , and experimentally modify and evaluate interventions and delivery systems already in use ; ( 3 ) study universals : focus on timeless behavioral , psychological , and cognitive principles and systems ; ( 4 ) anticipate the next big thing : listen to voices outside normal practice and connect different perspectives for new insights ; ( 5 ) improve information delivery systems : research ers should apply their communications expertise to enhance inter- research er communication , which could synergistically accelerate progress and capitalize upon the availability of “ big data ” ; and ( 6 ) develop models , including mediators and moderators : valid models are remarkably generative , and tests of moderation and mediation should eluci date boundary conditions of effects and treatment mechanisms . Quality strategies include : ( 1 ) continuous quality improvement : research ers need to borrow engineering practice s such as the continuous enhancement of interventions to incorporate clinical and technological progress ; ( 2 ) help consumers identify quality : consumers , clinicians , and others all need to easily identify quality , suggesting the need to efficiently and publicly index intervention quality ; ( 3 ) reduce the costs of care : concern with health care costs can drive intervention adoption and use and lead to novel intervention effects ( eg , reduced falls in the elderly ) ; and ( 4 ) deeply underst and users : a rigorous evaluation of the consumer ’s needs is a key starting point for intervention development . Conclusions The challenges of distinguishing and distributing scientifically vali date d interventions are formidable . The strategies described are meant to spur discussion and further thinking , which are important , given the potential of eHealth interventions to help patients and families Background Digital health interventions ( DHI ) have been shown to improve intermediates of cardiovascular health , but their impact on cardiovascular ( CV ) outcomes has not been fully explored . The aim of this study was to determine whether DHI administered during cardiac rehabilitation ( CR ) would reduce CV‐related emergency department ( ED ) visits and rehospitalizations in patients after percutaneous coronary intervention ( PCI ) for acute coronary syndrome ( ACS ) . Methods We r and omized patients undergoing CR following ACS and PCI to st and ard CR ( n = 40 ) or CR + DHI ( n = 40 ) for 3 months with 3 patients withdrawing from CR prior to initiation in the treatment arm and 6 in the control group . The DHI incorporated an online and smartphone‐based CR platform asking the patients to report of dietary and exercise habits throughout CR as well as educational information toward patients ' healthy lifestyles . We obtained data regarding ED visits and rehospitalizations at 180 days , as well as other metrics of secondary CV prevention at baseline and 90 days . Results Baseline demographics were similar between the groups . The DHI + CR group had improved weight loss compared to the control group ( −5.1 ± 6.5 kg vs. −0.8 ± 3.8 kg , respectively , P = .02 ) . Those in the DHI + CR group also showed a non‐significant reduction in CV‐related rehospitalizations plus ED visits compared to the control group at 180 days ( 8.1 % vs 26.6 % ; RR 0.30 , 95 % CI 0.08‐1.10 , P = .054 ) . Conclusions The current study demonstrated that complementary DHI significantly improves weight loss , and might offer a method to reduce CV‐related ED visits plus rehospitalizations in patients after ACS undergoing CR . The study suggests a role for DHI as an adjunct to CR to improve secondary prevention of CV disease . Trial registration This trial is registered at clinical trials.gov ( NCT01883050 ) BACKGROUND & AIMS Bowel preparation is closely linked to the quality of colonoscopy . We investigated whether delivery of instructions via a social media app increases the quality of colonoscopy by improving adequacy of bowel preparation . METHODS We performed a prospect i ve study at 3 endoscopic centers in China of 770 colonoscopy out patients ( 18 - 80 years old ) with convenient access to Wechat ( a widely used mobile social media app ) from May through November 2014 . Patients were r and omly assigned to groups that received st and ard education along with delivery of interactive information via Wechat ( n = 387 ) or st and ard education ( controls , n = 383 ) . The primary outcome was proportion of patients with adequate bowel preparation ( Ottawa score < 6 ) . Secondary outcomes included rates of adenoma detection and cecal intubation , cecal intubation time , rates of incomplete compliance with instructions , and patient willingness to repeat bowel preparation . RESULTS Demographic features were comparable between the groups . A higher proportion of patients in the group that received social media instruction had adequate bowel preparation than the control group ( 82.2 % vs 69.5 % , P < .001 ) . Among patients with successful colonoscopies , the group that received social media instruction had lower mean total and segmental Ottawa scores ( P < .05 ) . A higher proportion of patients receiving social media instruction also had cecal intubation ( 97.2 % vs 93.2 % in controls , P = .014 ) and were found to have adenomas ( 18.6 % vs 12.0 % in controls , P = .012 ) . CONCLUSIONS Instruction via a mobile social media app , in conjunction with regular instruction , increases subjective measures of adequacy of bowel preparation . Use of the app significantly increased the proportion of patients with successful cecal intubation and in whom adenomas were detected , indicating increased quality of colonoscopy . Clinical Trials.gov number : NCT02140827 BACKGROUND Mobile Health technology for the management of patients with atrial fibrillation is unknown . METHODS The simple mobile AF ( mAF ) App was design ed to incorporate clinical decision-support tools ( CHA2DS2-VASc [ Congestive heart failure , Hypertension , Age ≥75 years , Diabetes Mellitus , Prior Stroke or TIA , Vascular disease , Age 65 - 74 years , Sex category ] , HAS-BLED [ Hypertension , Abnormal renal/liver function , Stroke , Bleeding history or predisposition , Labile INR , Elderly , Drugs/alcohol concomitantly ] , SAMe-TT2R2 [ Sex , Age < 60 years , Medical history , Treatment , Tobacco use , Race ] scores ) , educational material s , and patient involvement strategies with self-care protocol s and structured follow-up . Patients with atrial fibrillation were r and omized into 2 groups ( mAF App vs usual care ) in a cluster r and omized design pilot study . Patients ' knowledge , quality of life , drug adherence , and anticoagulation satisfaction were evaluated at baseline , 1 month , and 3 months . Usability , feasibility , and acceptability of the mAF App were assessed at 1 month . RESULTS A total of 113 patients were r and omized to mAF App intervention ( mean age , 67.4 years ; 57.5 % were male ; mean follow-up , 69 days ) , and 96 patients were r and omized to usual care ( mean age , 70.9 years ; 55.2 % were male ; mean follow-up , 95 days ) . More than 90 % of patients reported that the mAF App was easy , user-friendly , helpful , and associated with significant improvements in knowledge compared with the usual care arm ( P values for trend < .05 ) . Drug adherence and anticoagulant satisfaction were significantly better with the mAF App versus usual care ( all P < .05 ) . Quality of life scores were significantly increased in the mAF App arm versus usual care , with anxiety and depression reduced ( all P < .05 ) . CONCLUSIONS The pilot mAFA Trial is the first prospect i ve r and omized trial of Mobile Health technology in patients with atrial fibrillation , demonstrating that the mAF App , integrating clinical decision support , education , and patient-involvement strategies , significantly improved knowledge , drug adherence , quality of life , and anticoagulation satisfaction BACKGROUND Instructing and guiding patients after surgery is essential for successful recovery . However , the time that health-care professionals can spend with their patients postoperatively has been reduced because of efficiency-driven , shortened hospital stays . We evaluated the effect of a personalised e-health-care programme on return to normal activities after surgery . METHODS A multicentre , single-blind , r and omised controlled trial was done at seven teaching hospitals in the Netherl and s. Patients aged 18 - 75 years who were scheduled for laparoscopic cholecystectomy , inguinal hernia surgery , or laparoscopic adnexal surgery for a benign indication were recruited . An independent research er r and omly allocated participants to either the intervention or control group using computer-based r and omisation lists , with stratification by sex , type of surgery , and hospital . Participants in the intervention group had access to a perioperative , personalised , e-health-care programme , which managed recovery expectations and provided postoperative guidance tailored to the patient . The control group received usual care and access to a placebo website containing st and ard general recovery advice . Participants were unaware of the study hypothesis and were asked to complete question naires at five timepoints during the 6-month period after surgery . The primary outcome was time between surgery and return to normal activities , measured using personalised patient-reported outcome measures . Intention-to-treat and per- protocol analyses were done . This trial is registered in the Netherl and s National Trial Register , number NTR4699 . FINDINGS Between Aug 24 , 2015 , and Aug 12 , 2016 , 344 participants were enrolled and r and omly allocated to either the intervention ( n=173 ) or control ( n=171 ) group . 14 participants ( 4 % ) were lost to follow-up , with 330 participants included in the primary outcome analysis . Median time until return to normal activities was 21 days ( 95 % CI 17 - 25 ) in the intervention group and 26 days ( 20 - 32 ) in the control group ( hazard ratio 1·38 , 95 % CI 1·09 - 1·73 ; p=0·007 ) . Complications did not differ between groups . INTERPRETATION A personalised e-health intervention after abdominal surgery speeds up the return to normal activities compared with usual care . Implementation of this e-health programme is recommended in patients undergoing intermediate- grade abdominal , gynaecological , or general surgical procedures . FUNDING ZonMw Background / Aim We aim ed to evaluate the efficacy of sending educational video clips via smartphone mobile messenger ( SMM ) on enhancing bowel preparation before colonoscopy . Methods This was a prospect i ve , endoscopist-blinded , r and omized controlled study . Patients in the SMM group received two video clips sent via SMM that explained the diet and regimen for bowel preparation , whereas those in the control group did not receive any video clips . We compared the quality of bowel preparation between the two groups , which was assessed by an endoscopist using the Ottawa scale . Results Between August and November 2014 , 140 patients in the SMM group and 141 patients in the control group underwent colonoscopic examination . The total Ottawa score of the SMM group was significantly lower than that of the control group ( 5.47±1.74 vs. 5.97±1.78 , p=0.018 ) . These results were particularly prominent in the younger age group ; the total Ottawa score of patents in the SMM group aged < 40 years was significantly lower than that of patients in the control group aged < 40 years ( 5.10±1.55 vs. 6.22±2.33 , p=0.034 ) . Conclusions We demonstrated that sending educational video clips via SMM could result in better bowel preparation , especially in the younger age group Objective Adequate bowel preparation is essential for a successful colonoscopy ; clinical studies suggest reinforced education can improve the preparation process . However , there have been no trials to compare WeChat directions ( the most widely used social media app in China ) with those of the short message service ( SMS ) . This study was aim ed to assess the effect of WeChat and SMS on the bowel preparation quality . Participants and methods This was a single-center , prospect i ve , endoscopically blinded , r and omized , controlled study . Patients in reinforced education groups received additional reminder messages by WeChat and SMS 2 days before colonoscopy . The primary outcome was bowel preparation quality evaluated by the Boston bowel preparation scale ( BBPS ) score and the rate of adequacy ( BBPS score ≥6 ) . Secondary outcomes included polyp detection rate , adenoma detection rate , and mean total adenomas detected . Patient tolerance level and subjective feelings were also evaluated . Results The total BBPS score and the percentage of adequacy were significantly higher in the reinforced education groups compared with the control ( WeChat vs. control , P<0.001 ; SMS vs. control , P<0.001 ) . Moreover , statistically significant differences between the two interventions were found in the total BBPS score but not in the rate of adequacy ( P=0.007 and 0.561 , respectively ) . The detection of adenomas , using multiplicity detection rate , advanced adenoma detection rate , and mean total adenomas detected , was much higher in the intervention groups ( P=0.039 , 0.037 , and 0.019 , respectively ) . Conclusion WeChat was superior to SMS for bowel preparation , although both of them may help improving the detection of adenomas Background Increased adherence with enhanced recovery pathways ( ERP ) is associated with improved outcomes . However , adherence to postoperative elements that rely on patient participation remains suboptimal . Mobile device apps may improve delivery of health education material and have the potential to foster behavior change and improve patient compliance . The objective of this study was to estimate the extent to which a novel mobile device app affects adherence to an ERP for colorectal surgery in comparison to st and ard written education . Methods This was a superiority , parallel-group , assessor-blind , sham-controlled r and omized trial involving 97 patients undergoing colorectal resection . Participants were r and omly assigned with a 1:1 ratio into one of two groups : ( 1 ) iPad including a novel mobile device app for postoperative education and self- assessment of recovery , or ( 2 ) iPad without the app . The primary outcome measure was mean adherence ( % ) to a bundle of five postoperative ERP elements requiring patient participation : mobilization , gastrointestinal motility stimulation , breathing exercises , and consumption of oral liquids and nutritional drinks . Results In the intervention group , app usage was high ( 94 % completed surveys on POD0 , 82 % on POD1 , 72 % on POD2 ) . Mean overall adherence to the bundle on the two first postoperative days was similar between groups : 59 % ( 95 % CI 52–66 % ) in the intervention group and 62 % ( 95 % CI 56–68 % ) in the control group [ Adjusted mean difference 2.4 % ( 95 % CI − 5 to 10 % ) p = 0.53 ] . Conclusions In this r and omized trial , access to a mobile health application did not improve adherence to a well-established enhanced recovery pathway in colorectal surgery patients , when compared to st and ard written patient education . Future research should evaluate the impact of applications integrating novel behavioral change techniques , particularly in context s where adherence is low Background Primary health professionals are well positioned to support the delivery of patient self-management in an evidence -based , structured capacity . A need exists to better underst and the active components required for effective self-management support , how these might be delivered within primary care , and the training and system changes that would subsequently be needed . Objectives ( 1 ) To examine self-management support interventions in primary care on health outcomes for a wide range of diseases compared to usual st and ard of care ; and ( 2 ) To identify the effective strategies that facilitate positive clinical and humanistic outcomes in this setting . Method A systematic review of r and omized controlled trials evaluating self-management support interventions was conducted following the Cochrane h and book & PRISMA guidelines . Published literature was systematic ally search ed from inception to June 2019 in PubMed , Scopus and Web of Science . Eligible studies assessed the effectiveness of individualized interventions with follow-up , delivered face-to-face to adult patients with any condition in primary care , compared with usual st and ard of care . Matrices were developed that mapped the evidence and components for each intervention . The method ological quality of included studies were appraised . Results 6,510 records were retrieved . 58 studies were included in the final qualitative synthesis . Findings reveal a structured patient-provider exchange is required in primary care ( including a one-on-one patient-provider consultation , ongoing follow up and provision of self-help material s ) . Interventions should be tailored to patient needs and may include combinations of strategies to improve a patient ’s disease or treatment knowledge ; independent monitoring of symptoms , encouraging self-treatment through a personalized action plan in response worsening symptoms or exacerbations , psychological coping and stress management strategies , and enhancing responsibility in medication adherence and lifestyle choices . Follow-up may include tailored feedback , monitoring of progress with respect to patient set healthcare goals , or honing problem-solving and decision-making skills . Theoretical models provided a strong base for effective SMS interventions . Positive outcomes for effective SMS included improvements in clinical indicators , health-related quality of life , self-efficacy ( confidence to self-manage ) , disease knowledge or control . An SMS model has been developed which sets the foundation for the design and evaluation of practical strategies for the construct of self-management support interventions in primary healthcare practice . Conclusions These findings provide primary care professionals with evidence -based strategies and structure to deliver SMS in practice . For this collaborative partnership approach to be more widely applied , future research should build on these findings for optimal SMS service design and upskilling healthcare providers to effectively support patients in this collaborative process Abstract The number of elective day-case surgeries has considerably increased in recent years , especially in China . Few studies have investigated the ability of mobile applications to assist recovery for patients having undergone day-surgery ; however , these studies have indicated that the use of mobile applications is cost-efficient and has a positive effect on recovery after surgery . This study aim ed to evaluate the utility and efficacy of using the 317-nursing mobile application program ( 317NAPP ) for monitoring home recovery following day-surgery involving high ligation of the hernial sac in pediatric patients . Prospect i ve clinical study involving 2 parallel groups . Patients were r and omly divided into the “ intervention 317NAPP group ” ( n = 64 ) and the control group ( n = 63 ) . Patients were followed-up using the 317NAPP in the intervention group and via telephonic consultations in the control group . All patients were enrolled after being provided sufficient guidance with respect to discharge and health education . The health index , including the physiological function , ability to perform daily activities , and the injury response , was evaluated before and 24 hours after surgery . The time duration of each follow-up session was also evaluated in both groups . The preoperative ( T1 ) health index scores were significantly higher than the postoperative ( T0 ) ones in both groups ( P = .00 ) . The quality of recovery ( T1–T0 ) of the intervention group ( 10.75 ± 5.28 ) was better than that of the control group ( 11.78 ± 5.16 ) , but the differences were not significant ( P = .27 ) . In the intervention group , the follow-up time duration was significantly lower in comparison to that in the control group ( P = .00 ) . This study demonstrated that 317NAPP had a positive effect on recovery following day-surgery , and the time- duration for follow-up was shorter than that performed using telephonic consultation . Monitoring recovery using 317NAPP was safe , efficient , inexpensive , and relatively easy ; therefore , it may help improve the recovery of patients having undergone day-surgery Background Patients who undergo primary Total Knee Replacement surgery ( TKR ) are often discharged within 1 - 3 days after surgery . With this relatively short length of hospital stay , a patient ’s self-management is a crucial factor in optimizing the outcome of their treatment . In the case of TKR , self-management primarily involves adequate pain management , followed by physiotherapy exercises and daily self-care activities . Patients are educated on all these topics by hospital staff upon discharge from the hospital but often struggle to comprehend this information due to its quantity , complexity , and the passive mode of communication used to convey it . Objective This study primarily aims to determine whether actively educating TKR patients with timely , day-to-day postoperative care information through an app could lead to a decrease in their level of pain compared to those who only receive st and ard information about their recovery through the app . In addition , physical functioning , quality of life , ability to perform physiotherapy exercises and daily self-care activities , satisfaction with information , perceived involvement by the hospital , and health care consumption were also assessed . Methods A multicenter r and omized controlled trial was performed in five Dutch hospitals . In total , 213 patients who had undergone elective , primary , unilateral TKR participated . All patients had access to an app for their smartphone and tablet to guide them after discharge . The intervention group could unlock day-to-day information by entering a personal code . The control group only received weekly , basic information . Primary ( level of pain ) and secondary outcomes ( physical functioning , quality of life , ability to perform physiotherapy exercises and activities of daily self-care , satisfaction with information , perceived involvement by the hospital , and health care consumption ) were measured using self-reported online question naires . All outcomes were measured weekly in the four weeks after discharge , except for physical functioning and quality of life , which were measured at baseline and at four weeks after discharge . Data was analyzed using Student t tests , chi-square tests , and linear mixed models for repeated measures . Results In total , 114 patients were enrolled in the intervention group ( IG ) and 99 in the control group ( CG ) . Four weeks after discharge , patients in the IG performed significantly better than patients in the CG on all dimensions of pain : pain at rest ( mean 3.45 vs mean 4.59 ; P=.001 ) , pain during activity ( mean 3.99 vs mean 5.08 ; P<.001 ) and pain at night ( mean 4.18 vs mean 5.21 ; P=.003 ) . Additionally , significant differences were demonstrated in favor of the intervention group for all secondary outcomes . Conclusions In the four weeks following TKR , the active and day-to-day education of patients via the app significantly decreased their level of pain and improved their physical functioning , quality of life , ability to perform physiotherapy exercises and activities of daily self-care , satisfaction with information , perceived involvement by the hospital , and health care consumption compared to st and ard patient education . Given the rising number of TKR patients and the increased emphasis on self-management , we suggest using an app with timely postoperative care education as a st and ard part of care . Trial Registration Netherl and s Trial Register NTR7182 ; BACKGROUND Adolescents with asthma are at risk of poor outcomes and are traditionally difficult to reach . OBJECTIVE To examine adolescents ' use of and asthma outcomes associated with smartphone- vs paper-based asthma action plans ( AAPs ) . METHODS We conducted a 6-month r and omized clinical trial with adolescents ( 12 - 17 years old ) with persistent asthma . Participants used their respective smartphone or paper AAPs for medication instructions and peak flow or asthma symptoms logging . AAP use was measured electronically for smartphone users and via mail-in diaries for the paper group . Changes in Asthma Control Test ( ACT ) and self-efficacy scores were examined . RESULTS Thirty-four adolescents participated in this study ( median age , 15.4 years ) . Participants were mostly African American ( 62 % ) with state-issued insurance ( 71 % ) . Adolescents in the smartphone group accessed the AAP a median of 12.17 times per week or 4.36 days per week but only recorded medications or symptoms and peak flow data in the electronic diary a median of 10 days per month during the 6-month period . Participants in the paper group recorded data a median of 23.5 days per month on their paper diaries . Overall , there were no changes in ACT and self-efficacy scores between groups . Adolescents with uncontrolled asthma ( baseline ACT score ≤19 ) had an improvement in ACT for the smartphone group ( before , 11 ; after , 20 ) ( [ P = .04 ) compared with no change in the paper group ( before , 17 ; after , 17 ) ( P = .64 ) . Adolescent satisfaction with the application was high , with 100 % stating they would recommend the smartphone AAP to a friend . CONCLUSION Adolescents were frequent and highly satisfied users of the smartphone AAP with a subset of participants with uncontrolled asthma demonstrating possible clinical benefit . Findings suggest a need for larger-scale studies to determine the effectiveness of smartphone-based AAPs among high-risk patients with asthma . TRIAL REGISTRATION clinical trials.gov Identifier : NCT02091869 |
11,805 | 23,506,796 | Meta- analysis supported dexmedetomidine sedation , multicomponent interventions and antipsychotics were useful in preventing postoperative delirium | Introduction The ideal measures to prevent postoperative delirium remain unestablished .
We conducted this systematic review and meta- analysis to clarify the significance of potential interventions . | BACKGROUND Postoperative delirium and cognitive decline are common in elderly surgical patients after non-cardiac surgery . Despite this prevalence and clinical importance , no specific aetiological factor has been identified for postoperative delirium and cognitive decline . In experimental setting in a rat model , nitrous oxide ( N(2)O ) produces neurotoxic effect at high concentrations and in an age-dependent manner . Whether this neurotoxic response may be observed clinical ly has not been previously determined . We hypothesized that in the elderly patients undergoing non-cardiac surgery , exposure to N(2)O result ed in an increased incidence of postoperative delirium than would be expected for patients not receiving N(2)O. METHODS Patients who were > or=65 yr of age , undergoing non-cardiac surgery and requiring general anaesthesia were r and omized to receive an inhalational agent and either N(2)O with oxygen or oxygen alone . A structured interview was conducted before operation and for the first two postoperative days to determine the presence of delirium using the Confusion Assessment Method . RESULTS A total of 228 patients were studied with a mean ( range ) age of 73.9 ( 65 - 95 ) yr . After operation , 43.8 % of patients developed delirium . By multivariate logistic regression , age [ odds ratio ( OR ) 1.07 ; 95 % confidence interval ( CI ) 1.02 - 1.26 ] , dependence on performing one or more independent activities of daily living ( OR 1.54 ; 95 % CI 1.01 - 2.35 ) , use of patient-controlled analgesia for postoperative pain control ( OR 3.75 ; 95 % CI 1.27 - 11.01 ) and postoperative use of benzodiazepine ( OR 2.29 ; 95 % CI 1.21 - 4.36 ) were independently associated with an increased risk for postoperative delirium . In contrast , the use of N(2)O had no association with postoperative delirium . CONCLUSIONS Exposure to N(2)O result ed in an equal incidence of postoperative delirium when compared with no exposure to OBJECTIVES To determine whether donepezil hydrochloride can reduce the prevalence and severity of delirium in older adults undergoing hip fracture repair . DESIGN Pilot double-masked r and omized placebo-controlled trial . SETTING Large academic medical center . PARTICIPANTS Sixteen individuals aged 70 and older with hip fracture . INTERVENTION Donepezil 5 mg or placebo was r and omly allocated and initiated within 24 hours of surgery , preoperatively or postoperatively . Daily treatment was continued for 30 days or until side effects or the clinical situation required termination . MEASUREMENTS All outcomes were ascertained masked to treatment status . Information on drug tolerability and safety was obtained from the participant , nurse , and medical record . Delirium presence and severity were measured during daily hospital interviews and at 2 , 4 , and 6 weeks after surgery after a st and ardized assessment using the Confusion Assessment Method ( CAM ) and the Memorial Delirium Assessment Scale ( MDAS ) . RESULTS Participants in the donepezil and placebo arms had similar baseline characteristics . Participants in the donepezil arm experienced significantly more side effects . In longitudinal models , there were no significant differences between the donepezil and placebo arms with regard to delirium presence over time ( odds ratio = 0.9 , 95 % confidence interval ( CI ) = 0.4 - 2.3 ) or delirium severity over time ( effect size = -0.2 on 30-point MDAS scale , 95%CI = -1.5 - 1.2 ) . CONCLUSION Participants r and omized to donepezil had no significant improvement in delirium presence or severity but experienced more side effects . Overall , sufficient evidence was not found from this pilot study to warrant a definitive Phase III trial Background Hip fractures are common among frail elderly persons and often have serious consequences on function , mobility and mortality . Traditional treatment of these patients is performed in orthopedic departments without additional geriatric assessment . However , studies have shown that interdisciplinary geriatric treatment may be beneficial compared to traditional treatment . The aim of the present study is to investigate whether treatment of these patients in a Department of Geriatrics ( DG ) during the entire hospital stay gives additional benefits as compared to conventional treatment in a Department of Orthopaedic Surgery ( DOS ) . Findings A new clinical pathway for in-hospital treatment of hip fracture patients was developed . In this pathway patients were treated pre- and postoperatively in DG . Comprehensive geriatric assessment was performed as an interdisciplinary , multidimensional , systematic assessment of all patients focusing on each patient ’s capabilities and limitations as recommended in guidelines and systematic review s. Identification and treatment of co-morbidities , pain relief , hydration , oxygenation , nutrition , elimination , prevention and management of delirium , assessment of falls and osteoporosis were emphasized . Discharge planning started as early as possible . Initiation of rehabilitation with focus on early mobilisation and development of individual plans was initiated in hospital and continued after discharge from hospital . Fracture specific treatment was based upon st and ard treatment for the hospital , expert opinions and a review of the literature . Conclusion A new treatment program for old hip fracture patients was developed , introduced and run in the DG , the potential benefits of which being compared with traditional care of hip fracture patients in the DOS in a r and omised clinical trial Background and objectives : Postoperative confusion and delirium is a common complication in the elderly with a poorly understood pathophysiology . The aim of this study was to examine whether the type of anaesthesia ( general or regional ) plays a role in the development of cognitive impairment in elderly patients during the immediate postoperative period . Methods : Forty‐seven patients > 60 yr of age and undergoing major surgery were r and omly allocated to receive either regional or general anaesthesia . The mental status of the patients was assessed preoperatively and during the first three postoperative days with the Mini Mental State Examination . The incidence of delirium was also examined during the same period with the use of DSM III criteria . Results : Overall , during the first three postoperative days , the mean Mini Mental State Examination score decreased significantly ( P < 0.001 ) . However , this decline was very significant only in patients assigned to receive general anaesthesia ( P < 0.001 ) compared to regional anaesthesia . Nine patients developed delirium but the type of anaesthesia did not affect its incidence . The only important factor for the development of delirium was pre‐existing cardiovascular disease irrespective of anaesthesia type ( P < 0.025 ) . Conclusions : Elderly patients subjected to general anaesthesia displayed more frequent cognitive impairment during the immediate postoperative period in comparison to those who received a regional technique OBJECTIVE To determine whether limiting intraoperative sedation depth during spinal anesthesia for hip fracture repair in elderly patients can decrease the prevalence of postoperative delirium . PATIENTS AND METHODS We performed a double-blind , r and omized controlled trial at an academic medical center of elderly patients ( > or=65 years ) without preoperative delirium or severe dementia who underwent hip fracture repair under spinal anesthesia with propofol sedation . Sedation depth was titrated using processed electroencephalography with the bispectral index ( BIS ) , and patients were r and omized to receive either deep ( BIS , approximately 50 ) or light ( BIS , > or=80 ) sedation . Postoperative delirium was assessed as defined by Diagnostic and Statistical Manual of Mental Disorders ( Third Edition Revised ) criteria using the Confusion Assessment Method beginning at any time from the second day after surgery . RESULTS From April 2 , 2005 , through October 30 , 2008 , a total of 114 patients were r and omized . The prevalence of postoperative delirium was significantly lower in the light sedation group ( 11/57 [ 19 % ] vs 23/57 [ 40 % ] in the deep sedation group ; P=.02 ) , indicating that 1 incident of delirium will be prevented for every 4.7 patients treated with light sedation . The mean + /- SD number of days of delirium during hospitalization was lower in the light sedation group than in the deep sedation group ( 0.5+/-1.5 days vs 1.4+/-4.0 days ; P=.01 ) . CONCLUSION The use of light propofol sedation decreased the prevalence of postoperative delirium by 50 % compared with deep sedation . Limiting depth of sedation during spinal anesthesia is a simple , safe , and cost-effective intervention for preventing postoperative delirium in elderly patients that could be widely and readily adopted Introduction We hypothesized that delirium symptoms may respond differently to antipsychotic therapy . The purpose of this paper was to retrospectively compare duration and time to first resolution of individual delirium symptoms from the data base of a r and omized , double-blind , placebo-controlled study comparing quetiapine ( Q ) or placebo ( P ) , both with haloperidol rescue , for critically ill patients with delirium . Methods Data for 10 delirium symptoms from the eight-domain , intensive care delirium screening checklist ( ICDSC ) previously collected every 12 hours were extracted for 29 study patients . Data between the Q and P groups were compared using a cut-off P- value of ≤0.10 for this exploratory study . Results Baseline ICDSC scores ( 5 ( 4 to 7 ) ( Q ) vs 5 ( 4 to 6 ) ) ( median , interquartile range ( IQR ) ) and % of patients with each ICDSC symptom were similar in the two groups ( all P > 0.10 ) . Among patients with the delirium symptom at baseline , use of Q may lead to a shorter time ( days ) to first resolution of symptom fluctuation ( 4 ( Q ) vs. 14 , P = 0.004 ) , inattention ( 3 vs. 8 , P = .10 ) and disorientation ( 2 vs. 10 , P = 0.10 ) but a longer time to first resolution of agitation ( 3 vs. 1 , P = 0.04 ) and hyperactivity ( 5 vs. 1 , P = 0.07 ) . Among all patients , Q-treated patients tended to spend a smaller percent of time with inattention ( 47 ( 0 to 67 ) vs. 78 ( 43 to 100 ) , P = 0.025 ) , hallucinations ( 0 ( 0 to 17 ) vs. 28 ( 0 to 43 ) , P = 0.10 ) and symptom fluctuation ( 47 ( 19 to 67 ) vs. 89 ( 33 to 00 ) , P = 0.04 ] and there was a trend for Q-treated patients to spend a greater percent of time at an appropriate level of consciousness ( 26 % ( 13 to 63 % ) vs. 14 % ( 0 to 33 % ) , P = 0.17 ] . Conclusions Our exploratory analysis suggests that quetiapine may resolve several intensive care unit ( ICU ) delirium symptoms faster than the placebo . Individual symptom resolution appears to differ in association with the pharmacologic intervention ( that is , P vs Q , both with as needed haloperidol ) . Future studies evaluating antipsychotics in ICU patients with delirium should measure duration and resolution of individual delirium symptoms and their relation to long-term outcomes BACKGROUND People with cognitive impairment and dementia have a poor outcome after a hip fracture surgery , about 30 - 50 % of all those who sustain a hip fracture have dementia . Therefore the aim was to investigate whether a multidisciplinary postoperative intervention program could reduce postoperative complications and improve functional recovery among people with dementia . METHODS A r and omized controlled trial with subgroup analyses among patients with dementia . Sixty-four patients with femoral neck fracture , aged ≥70 years at Umeå University Hospital , Sweden . The intervention consisted of staff education , individualized care planning and rehabilitation , active prevention , detection and treatment of postoperative complications , especially delirium . The staff worked in teams to apply comprehensive geriatric assessment , management and rehabilitation , including a follow-up at 4 months postoperatively . The control group followed conventional postoperative routines . RESULTS There were fewer postoperative complications in the intervention group such as urinary tract infections , p=0.001 ; nutritional problems , p=0.025 ; postoperative delirium , p=0.002 ; falls , p=0.006 . At 4 months a larger proportion in the intervention group had regained their previous independent indoor walking ability performance , p=0.005 . At 12 months a larger proportion in the intervention group had regained the activities of daily living ( ADL ) performance level they had before the fracture , p=0.027 . CONCLUSION This study demonstrates that patients with dementia who suffer a hip fracture can benefit from multidisciplinary geriatric assessment and rehabilitation and should not be excluded from rehabilitation programs Background Approximately 40 % of hospitalized older adults have cognitive impairment ( CI ) and are more prone to hospital-acquired complications . The Institute of Medicine suggests using health information technology to improve the overall safety and quality of the health care system . Objective Evaluate the efficacy of a clinical decision support system ( CDSS ) to improve the quality of care for hospitalized older adults with CI . Design A r and omized controlled clinical trial . Setting A public hospital in Indianapolis . Population A total of 998 hospitalized older adults were screened for CI , and 424 patients ( 225 intervention , 199 control ) with CI were enrolled in the trial with a mean age of 74.8 , 59 % African Americans , and 68 % female . InterventionA CDSS alerts the physicians of the presence of CI , recommends early referral into a geriatric consult , and suggests discontinuation of the use of Foley catheterization , physical restraints , and anticholinergic drugs . Measurements Orders of a geriatric consult and discontinuation orders of Foley catheterization , physical restraints , or anticholinergic drugs . Results Using intent-to-treat analyses , there were no differences between the intervention and the control groups in geriatric consult orders ( 56 % vs 49 % , P = 0.21 ) ; discontinuation orders for Foley catheterization ( 61.7 % vs 64.6 % , P = 0.86 ) ; physical restraints ( 4.8 % vs 0 % , P = 0.86 ) , or anticholinergic drugs ( 48.9 % vs 31.2 % , P = 0.11 ) . Conclusion A simple screening program for CI followed by a CDSS did not change physician prescribing behaviors or improve the process of care for hospitalized older adults with CI Background Recent studies have indicated that unmanaged pain , both acute and chronic , can affect mental status and might precipitate delirium , especially in elderly patients with hip fractures . The aim of this study was to assess the effectiveness of fascia iliaca compartment block ( FICB ) for prevention of perioperative delirium in hip surgery patients who were at intermediate or high risk for this complication . Material s and methods On admission , all included patients were divided into three groups according to low , intermediate or high risk for perioperative delirium . Eligible patients ( those classified as at intermediate or high risk for developing delirium ) were sequentially r and omly assigned to study treatment ( FICB prophylaxis or placebo ) according to a computer-generated r and omization code . The primary outcome was perioperative delirium . Diagnosis of the syndrome was defined using the Diagnostic and Statistical Manual of Mental Disorders , 4th edition ( DSM-IV ) and Confusion Assessment Method ( CAM ) criteria . Secondary outcome variables were severity of delirium and delirium duration . Results Delirium occurred in 33 ( 15.94 % ) out of 207 patients r and omized to FICB prophylaxis or the placebo group . Incidence of delirium in the FICB prophylaxis group was 10.78 % ( 11/102 ) , significantly different from the incidence ( 23.8 % , 25/105 ) in the placebo group [ relative risk 0.45 , 95 % confidence interval ( CI ) 0.23–0.87 ] . Nine of 17 patients with high risk for delirium and included in the FICB prophylaxis group developed delirium , whereas 10 of 16 high-risk patients included in the placebo group became delirious ( relative risk 0.84 , CI 0.47–1.52 ) . Two of 85 patients with intermediate risk for delirium and included in the FICB prophylaxis group developed delirium , whereas 15 of 89 intermediate-risk patients included in the placebo group became delirious ( relative risk 0.13 , CI 0.03–0.53 ) . Severity of delirium according to the highest value of the DRSR-98 during an episode with delirium in patients in the FICB prophylaxis group was on average 14.34 , versus 18.61 in the placebo group ( mean difference 4.27 , 95 % CI 1.8–5.64 , P < 0.001 ) . Mean duration of delirium in the FICB prophylaxis group was significantly shorter than in the placebo group ( FICB 5.22 days versus placebo 10.97 days , 95 % CI 3.87–7.62 , P < 0.001 ) . Conclusion No significant difference was found among high-risk patients between FICB prophylaxis and placebo groups in terms of delirium incidence . However , FICB prophylaxis significantly prevented delirium occurrence in intermediate-risk patients . Thus FICB prophylaxis could be beneficial , particularly for intermediate-risk patients Objective : To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol . Design : Prospect i ve , r and omized , double-blind , placebo-controlled study . Setting : Three academic medical centers . Patients : Thirty-six adult intensive care unit patients with delirium ( Intensive Care Delirium Screening Checklist score ≥4 ) , tolerating enteral nutrition , and without a complicating neurologic condition . Interventions : Patients were r and omized to receive quetiapine 50 mg every 12 hrs or placebo . Quetiapine was increased every 24 hrs ( 50 to 100 to 150 to 200 mg every 12 hrs ) if more than one dose of haloperidol was given in the previous 24 hrs . Study drug was continued until the intensive care unit team discontinued it because of delirium resolution , therapy ≥10 days , or intensive care unit discharge . Measurements and Main Results : Baseline characteristics were similar between the quetiapine ( n = 18 ) and placebo ( n = 18 ) groups . Quetiapine was associated with a shorter time to first resolution of delirium [ 1.0 ( interquartile range [ IQR ] , 0.5–3.0 ) vs. 4.5 days ( IQR , 2.0–7.0 ; p = .001 ) ] , a reduced duration of delirium [ 36 ( IQR , 12–87 ) vs. 120 hrs ( IQR , 60–195 ; p = .006 ) ] , and less agitation ( Sedation-Agitation Scale score ≥5 ) [ 6 ( IQR , 0–38 ) vs. 36 hrs ( IQR , 11–66 ; p = .02 ) ] . Whereas mortality ( 11 % quetiapine vs. 17 % ) and intensive care unit length of stay ( 16 quetiapine vs. 16 days ) were similar , subjects treated with quetiapine were more likely to be discharged home or to rehabilitation ( 89 % quetiapine vs. 56 % ; p = .06 ) . Subjects treated with quetiapine required fewer days of as-needed haloperidol [ 3 [ ( IQR , 2–4 ) ] vs. 4 days ( IQR , 3–8 ; p = .05 ) ] . Whereas the incidence of QTc prolongation and extrapyramidal symptoms was similar between groups , more somnolence was observed with quetiapine ( 22 % vs. 11 % ; p = .66 ) . Conclusions : Quetiapine added to as-needed haloperidol results in faster delirium resolution , less agitation , and a greater rate of transfer to home or rehabilitation . Future studies should evaluate the effect of quetiapine on mortality , re source utilization , post-intensive care unit cognition , and dependency after discharge in a broader group of patients Background : The aim of this r and omized , parallel-arm trial was to study the effect of treating subsyndromal delirium with risperidone on the incidence of clinical delirium in elderly patients who underwent on-pump cardiac surgery . Methods : One hundred one patients aged 65 yr or older who experienced subsyndromal delirium after on-pump cardiac surgery were r and omized using a computer-generated list to receive 0.5 mg risperidone ( n = 51 ) or placebo ( n = 50 ) every 12 h by mouth . Patients were assessed at 8 h by a blinded observer using the Intensive Care Delirium Screening Checklist , and those scoring more than 3 were evaluated by a blinded psychiatrist to confirm delirium . Patients in either group who experienced delirium were treated according to the same algorithm . Initially , risperidone was administered and if symptoms were not controlled , haloperidol was administered . The primary outcome was the proportion of patients who experienced delirium in either group . Results : Seven ( 13.7 % ) patients in the risperidone group experienced delirium versus 17 ( 34 % ) in the placebo group ( P = 0.031 ) Competing-risks regression analysis showed that failure to treat subsyndromal delirium with risperidone was an independent risk factor for delirium ( subhazard ratio , 3.83 ; 95 % CI , 1.63–8.98 ; P = 0.002 ) . Two ( 3.9 % ) patients in the risperidone group experienced extrapyramidal manifestations versus one ( 2 % ) in the placebo group ( P = 1.0 ) . Conclusion : Administration of risperidone to elderly patients who experienced subsyndromal delirium after on-pump cardiac surgery was associated with significantly lower incidence of delirium . Larger studies are required to determine whether early administration of risperidone during the subsyndromal phase of delirium would influence the clinical course of such patients BACKGROUND Delirium is a serious postoperative condition for which few pharmacologic prevention trials have been conducted . OBJECTIVE The authors tested the efficacy of perioperative olanzapine administration to prevent postoperative delirium in elderly patients after joint-replacement surgery . METHOD The authors conducted a r and omized , double-blind , placebo-controlled , prophylaxis trial at an orthopedic teaching hospital , enrolling 495 elderly patients age ≥65 years , who were undergoing elective knee- or hip-replacement surgery ; 400 patients received either 5 mg of orally-disintegrating olanzapine or placebo just before and after surgery . The primary efficacy outcome was the incidence of ( DSM-III-R ) delirium . RESULTS The incidence of delirium was significantly lower in the olanzapine group than in the placebo group ; this held true for both knee- and hip-replacement surgery . However , delirium lasted longer and was more severe in the olanzapine group . Advanced age , a high level of medical comorbidity , an abnormal albumin level , and having knee-replacement surgery were independent risk factors for postoperative delirium ( Clinical trials.gov Identifier : NCT000699946 ) . CONCLUSION Administration of 10 mg of oral olanzapine perioperatively , versus placebo , was associated with a significantly lower incidence of delirium . These findings suggest that olanzapine prophylaxis of postoperative delirium may be an effective strategy HYPOTHESIS Increased knowledge about motor subtypes of delirium may aid clinicians in the management of postoperative geriatric patients . DESIGN Prospect i ve cohort study defining preoperative risk factors , outcomes , and adverse events related to motor subtypes of postoperative delirium . SETTING Referral medical center . PATIENTS Persons 50 years and older with planned postoperative intensive care unit ( ICU ) admission following an elective operation were recruited . MAIN OUTCOME MEASURES Before surgery , a st and ardized frailty assessment was performed . After surgery , delirium and its motor subtypes were measured using the vali date d tools of the Confusion Assessment Method -ICU and the Richmond Agitation-Sedation Scale . Statistical analysis included the univariate t and χ(2 ) tests and analysis of variance with post hoc analysis . RESULTS Delirium occurred in 43.0 % ( 74 of 172 ) of patients , representing 67.6 % ( 50 of 74 ) hypoactive , 31.1 % ( 23 of 74 ) mixed , and 1.4 % ( 1 of 74 ) hyperactive motor subtypes . Compared with those having mixed delirium , patients having hypoactive delirium were older ( mean [ SD ] age , 71 [ 9 ] vs 65 [ 9 ] years ) and more anemic ( mean [ SD ] hematocrit , 36 % [ 8 % ] vs 41 % [ 6 % ] ) ( P = .002 for both ) . Patients with hypoactive delirium had higher 6-month mortality ( 32.0 % [ 16 of 50 ] vs 8.7 % [ 2 of 23 ] , P = .04 ) . Delirium-related adverse events occurred in 24.3 % ( 18 of 74 ) of patients with delirium ; inadvertent tube or line removals occurred more frequently in the mixed group ( P = .006 ) , and sacral skin breakdown was more common in the hypoactive group ( P = .002 ) . CONCLUSIONS Motor subtypes of delirium alert clinicians to differing prognosis and adverse event profiles in postoperative geriatric patients . Hypoactive delirium is the most common motor subtype and is associated with worse prognosis ( 6-month mortality , 1 in 3 patients ) . Knowledge of differing adverse event profiles can modify clinicians ' management of older patients with postoperative delirium Background Hip fractures mainly affect older people . It is associated with high morbidity and mortality , and in particular a high frequency of delirium . Incident delirium following hip fracture is associated with an increased risk of dementia in the following months , but it is still not firmly established whether this is an association or a causal relationship . Orthogeriatric units vary with respect to content and timing of the intervention . One main effect of orthogeriatric care may be the prevention of delirium , especially if preoperative and postoperative care are provided . Thus , the aim of Oslo Orthogeriatric Trial , is to assess whether combined preoperative and postoperative orthogeriatric care can reduce the incidence of delirium and improve cognition following hip fracture . Methods / design Inclusion and r and omisation will take place in the Emergency Department , as soon as possible after admission . All patients with proximal femur fractures are eligible , irrespective of age , pre-fracture function and accommodation , except if the fracture is caused by a high energy trauma or the patient is terminally ill . The intervention is pre- and post-operative orthogeriatric care delivered on a dedicated acute geriatric ward . The primary outcome measure is a composite endpoint combining the Clinical Dementia Rating Scale ( CDR ) and the 10 word memory task at four months after surgery . Secondary outcomes comprise incident delirium , length of stay , cognition , mobility , place of residence , activities of daily living and mortality , measured at 4 and 12 months after surgery . We have included 332 patients in the period 17th September 2009 to 5th January 2012 . Discussion Our choice of outcome measures and our emphasis of orthogeriatric care in the preoperative as well as the postoperative phase will enable us to provide new knowledge on the impact of orthogeriatric care on cognition . Trials registration Clinical Trials.gov The purpose of this r and omized controlled study was to determine the effects of music listening on acute confusion that is common in older adults after hip or knee surgery . A control group demonstrated greater decreases in cognition on the first postoperative day compared to a music-listening group ( F = 8.448 , p = .009 ) . In the 3-day postoperative period , the cognitive status of the control group improved ; on the third postoperative day , there was no significant difference between the two groups ( F = 3.52 , p = .075 ) . The music-listening group had higher scores on the NEECHAM Acute Confusion Scale across the 3-day postoperative period ( F = 7.28 , p = .014 ) OBJECTIVES Delirium ( or acute confusional state ) affects 35 % to 65 % of patients after hip-fracture repair , and has been independently associated with poor functional recovery . We performed a r and omized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture . DESIGN Prospect i ve , r and omized , blinded . SETTING Inpatient academic tertiary medical center . PARTICIPANTS 126 consenting patients 65 and older ( mean age 79 + /- 8 years , 79 % women ) admitted emergently for surgical repair of hip fracture . MEASUREMENTS Detailed assessment through interviews with patients and design ated proxies and review of medical records was performed at enrollment to ascertain prefracture status . Subjects were then r and omized to proactive geriatrics consultation , which began preoperatively or within 24 hours of surgery , or " usual care . " A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol . To ascertain study outcomes , all subjects underwent daily , blinded interviews for the duration of their hospitalization , including the Mini-Mental State Examination ( MMSE ) , the Delirium Symptom Interview ( DSI ) , and the Memorial Delirium Assessment Scale ( MDAS ) . Delirium was diagnosed using the Confusion Assessment Method ( CAM ) algorithm . RESULTS The 62 patients r and omized to geriatrics consultation were not significantly different ( P>.1 ) from the 64 usual-care patients in terms of age , gender , prefracture dementia , comorbidity , type of hip fracture , or type of surgical repair . Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively . A mean of 10 recommendations were made throughout the duration of the hospitalization , with 77 % adherence by the orthopedics team . Delirium occurred in 20 /62 ( 32 % ) intervention patients , versus 32 / 64 ( 50 % ) usual-care patients ( P = .04 ) , representing a relative risk of 0.64 ( 95 % confidence interval ( CI ) = 0.37 - 0.98 ) for the consultation group . One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group . There was an even greater reduction in cases of severe delirium , occurring in 7/ 60 ( 12 % ) of intervention patients and 18 / 62 ( 29 % ) of usual-care patients , with a relative risk of 0.40 ( 95 % CI = 0.18 - 0.89 ) . Despite this reduction in delirium , length of stay did not significantly differ between intervention and usual-care groups ( median + /- interquartile range = 5 + /- 2 days in both groups ) , likely because protocol s and pathways predetermined length of stay . In subgroup analyses , geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living ( ADL ) functional impairment . CONCLUSIONS Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair . Geriatrics consultation reduced delirium by over one-third , and reduced severe delirium by over one-half . Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients Background Postoperative delirium is common in the elderly and is associated with a significant increase in mortality , complications , length of hospital stay and admission in long care facility . Although several interventions have proved their effectiveness to prevent it , the Cochrane advises an assessment of multifaceted intervention using rigorous methodology based on r and omized study design . Our purpose is to present the methodology and expected results of the CONFUCIUS trial , which aims to measure the impact of a multifaceted program on the prevention of postoperative delirium in elderly . Method / Design Study design is a stepped wedge cluster r and omized trial within 3 surgical wards of three French university hospitals . All patients aged 75 and older , and admitted for scheduled surgery will be included . The multifaceted program will be conducted by mobile geriatric team , including geriatric preoperative consultation , training of the surgical staff and implementation of the Hospital Elder Life Program , and morbidity and mortality conference related to delirium cases . The primary outcome is based on postoperative delirium rate within 7 days after surgery . This program is planned to be implemented along four successive time periods within all the surgical wards . Each one will be affected successively to the control arm and to the intervention arm of the trial and the order of program introduction within each surgical ward will be r and omly assigned . Based on a 20 % reduction of postoperative delirium rate ( ICC = 0.25 , α = 0.05 , β = 0.1 ) , three hundred sixty patients will be included i.e. thirty patients per service and per time period . Endpoints comparison between intervention and control arms of the trial will be performed by considering the cluster and time effects . Discussion Better prevention of delirium is expected from the multifaceted program , including a decrease of postoperative delirium , and its consequences ( mortality , morbidity , postoperative complications and length of hospital stay ) among elderly patients . This study should allow better diagnosis of delirium and strengthen the collaboration between surgical and mobile geriatric teams . Should the program have a substantial impact on the prevention of postoperative delirium in elderly , it could be extended to other facilities . Trial registration Clinical Trials.gov : Background Patient-controlled analgesia ( PCA ) with intravenous morphine and patient-controlled epidural analgesia ( PCEA ) , using an opioid either alone or in combination with a local anesthetic , are two major advances in the management of pain after major surgery . However , these techniques have been evaluated poorly in elderly people . This prospect i ve , r and omized study compared the effectiveness on postoperative pain and safety of PCEA and PCA after major abdominal surgery in the elderly patient . Methods Seventy patients older than 70 yr of age and undergoing major abdominal surgery were assigned r and omly to receive either combined epidural analgesia and general anesthesia followed by postoperative PCEA , using a mixture of 0.125 % bupivacaine and sufentanil ( PCEA group ) , or general anesthesia followed by PCA with intravenous morphine ( PCA group ) . Pain intensity was tested three times daily using a visual analog scale . Postoperative evaluation included mental status , cardiorespiratory and gastrointestinal functions , and patient satisfaction scores . Results Pain relief was better at rest ( P = 0.001 ) and after coughing ( P = 0.002 ) in the PCEA group during the 5 postoperative days . Satisfaction scores were better in the PCEA group . Although incidence of delirium was comparable in the PCA and PCEA groups ( 24%vs . 26 % , respectively ) , mental status was improved on the fourth and fifth postoperative days in the PCEA group . The PCEA group recovered bowel function more quickly than did the PCA group . Cardiopulmonary complications were similar in the two groups . Conclusion After major abdominal surgery in the elderly patient , patient-controlled analgesia , regardless of the route ( epidural or parenteral ) , is effective . The epidural route using local anesthetics and an opioid provides better pain relief and improves mental status and bowel activity Objective To compare the safety and estimate the response profile of olanzapine , a second-generation antipsychotic , to haloperidol in the treatment of delirium in the critical care setting . Design Prospect i ve r and omized trial Setting Tertiary care university affiliated critical care unit . Patients All admissions to a medical and surgical intensive care unit with a diagnosis of delirium . Interventions Patients were r and omized to receive either enteral olanzapine or haloperidol . Measurements Patient ’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium . Main results Delirium Index decreased over time in both groups , as did the administered dose of benzodiazepines . Clinical improvement was similar in both treatment arms . No side effects were noted in the olanzapine group , whereas the use of haloperidol was associated with extrapyramidal side effects . Conclusions Olanzapine is a safe alternative to haloperidol in delirious critical care patients , and may be of particular interest in patients in whom haloperidol is contraindicated OBJECTIVES To study the effectiveness of haloperidol prophylaxis on incidence , severity , and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Large medical school-affiliated general hospital in Alkmaar , The Netherl and s. PARTICIPANTS A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium . INTERVENTION Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively . Proactive geriatric consultation was provided for all r and omized patients . MEASUREMENTS The primary outcome was the incidence of postoperative delirium ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , and Confusion Assessment Method criteria ) . Secondary outcomes were the severity of delirium ( Delirium Rating Scale , revised version-98 ( DRS-R-98 ) ) , the duration of delirium , and the length of hospital stay . RESULTS The overall incidence of postoperative delirium was 15.8 % . The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1 % and 16.5 % , respectively ( relative risk=0.91 , 95 % confidence interval (CI)=0.6 - 1.3 ) ; the mean highest DRS-R-98 score+/-st and ard deviation was 14.4+/-3.4 and 18.4+/-4.3 , respectively ( mean difference 4.0 , 95 % CI=2.0 - 5.8 ; P<.001 ) ; delirium duration was 5.4 versus 11.8 days , respectively ( mean difference 6.4 days , 95 % CI=4.0 - 8.0 ; P<.001 ) ; and the mean number of days in the hospital was 17.1+/-11.1 and 22.6+/-16.7 , respectively ( mean difference 5.5 days , 95 % CI=1.4 - 2.3 ; P<.001 ) . No haloperidol-related side effects were noted . CONCLUSION Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium . It did have a positive effect on the severity and duration of delirium . Moreover , haloperidol reduced the number of days patients stayed in the hospital , and the therapy was well tolerated Objective : To compare the incidence of delirium in postoperative cardiac surgical patients treated with either cimetidine or ranitidine . Method : Cardiac surgery patients were r and omized to receive either cimetidine or ranitidine postoperatively . Each patient underwent three Mini-Mental Status Examinations ( MMSE ) and the medical record was review ed for pertinent past medical history , laboratory data , and evidence of delirium on three occasions : one day preoperatively ( before H-2 blocker was given ) , in the early postoperative period ( while receiving the H-2 blocker ) ; usually two days postoperatively on the day of hospital discharge ( several days after the H-2 blocker had been discontinued ) . Results : Overall , both groups in the early postoperative period showed a significant decrease in the MMSE score ( 27.11 ± 4.44 to 25.38 ± 2.87 , mean ± SD ; t = 5.16 , p < .0005 ) , which resolved by the time of hospital discharge . There was no significant difference between cimetidine and ranitidine . Both age and preoperative MMSE score were strongly associated with the development of delirium . Conclusions : We found no significant difference between cimetidine 's versus ranitidine 's effect upon cognitive functioning in the postoperative cardiac surgical patient . This was true even when controlling for age and length of stay BACKGROUND In this prospect i ve , r and omized , double-blind , placebo-controlled study , we investigated the effect of pregabalin on oxycodone consumption , postoperative confusion , and pain in elderly cardiac surgery patients . METHODS Seventy patients , aged ≥75 yr , were r and omized to receive either 150 mg of pregabalin before operation and 75 mg of pregabalin twice daily for 5 postoperative days or placebo . Pain intensity was measured with the Verbal Rating Scale ( VRS ) . When pain intensity was ≥2 on the VRS , patients received oxycodone either i.v . ( 0.05 mg kg(-1 ) ) or orally ( 0.10 - 0.15 mg kg(-1 ) ) . Postoperative confusion was measured with the Confusion Assessment Method for the intensive care unit ( CAM-ICU ) . Postoperative pain was assessed by a telephone interview 1 and 3 months after operation . RESULTS Cumulative consumption of parenteral oxycodone during 16 h after extubation was reduced by 44 % and total oxycodone consumption from extubation to the end of the fifth postoperative day was reduced by 48 % in the pregabalin group . Time to extubation was 138 min shorter and CAM-ICU scores were significantly lower on the first postoperative day in the placebo group , although there was no significant difference with respect to the Mini-Mental State Examination or the Richmond Agitation Sedation Score . The incidence of pain during movement was significantly lower in the pregabalin group at 3 months postoperative . CONCLUSIONS The administration of pregabalin reduced postoperative opioid consumption after cardiac surgery reduced the incidence of confusion on the first postoperative day and increased time to extubation when compared with placebo . Three months after operation , patients in the pregabalin group experienced less pain during movement BACKGROUND Data are sparse on the incidence of postoperative cognitive , cardiac , and renal complications after deliberate hypotensive anesthesia in elderly patients . METHODS This r and omized , controlled clinical trial included 235 older adults with comorbid medical illnesses undergoing elective primary total hip replacement with epidural anesthesia . The patients were r and omly assigned to one of two levels of intraoperative mean arterial blood pressure management : either to a markedly hypotensive mean arterial blood pressure range of 45 - 55 mmHg or to a less hypotensive range of 55 - 70 mmHg . Cognitive outcome was assessed by within-patient change on 10 neuropsychologic tests assessing memory , psychomotor , and language skills from before surgery to 1 week and 4 months after surgery . Prospect i ve st and ardized surveillance was performed for cardiovascular and renal outcomes , delirium , thromboembolism , and blood loss and replacement . RESULTS The two groups were similar at baseline in terms of age ( mean , 72 yr ) , sex ( 50 % women ) , comorbid conditions , and cognitive function . After operation , no significant differences in the incidence of early or long-term cognitive dysfunction were observed between the two blood pressure management groups . There were no significant differences in the rates of other adverse consequences , including cardiac , renal , and thromboembolic complications . In addition , no differences occurred in the duration of surgery , intraoperative estimated blood loss , or transfusion rates . CONCLUSIONS Elderly patients can safely receive controlled hypotensive epidural anesthesia with this protocol . There was no evidence of greater risks , or early benefits , with the use of the more markedly hypotensive range Background : Post‐operative mental dysfunction may be an important problem in elderly patients . This study was design ed to compare the effects of propofol and sevoflurane anesthesia on recovery characteristics and the incidence of post‐operative delirium ( POD ) in long‐ duration laparoscopic surgery for elderly patients Background and aims : Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs . We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures . Methods : One hundred and ninety-nine patients , aged 70 years and over ( mean age±SD , 82±6 , 74 % women ) , were r and omly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward . The intervention consisted of staff education focusing on the assessment , prevention and treatment of delirium and associated complications . The staff worked as a team , applying comprehensive geriatric assessment , management and rehabilitation . Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale , and delirium was diagnosed according to DSM-IV criteria . Results : The number of days of postoperative delirium among intervention patients was fewer ( 5.0±7.1 days vs 10.2±13.3 days , p=0.009 ) compared with controls . A lower proportion of intervention patients were delirious postoperatively than controls ( 56/102 , 54.9 % vs 73/97 , 75.3 % , p=0.003 ) . Eighteen percent in the intervention ward and 52 % of controls were delirious after the seventh postoperative day ( p<0.001 ) . Intervention patients suffered from fewer complications , such as decubitus ulcers , urinary tract infections , nutritional complications , sleeping problems and falls , than controls . Total postoperative hospitalization was shorter in the intervention ward ( 28.0±17.9 days vs 38.0±40.6 days , p=0.028 ) . Conclusions : Patients with postoperative delirium can be successfully treated , result ing in fewer days of delirium , fewer other complications , and shorter length of hospitalization OBJECTIVE To develop and vali date a clinical prediction rule for postoperative delirium using data available to clinicians preoperatively . DESIGN Prospect i ve cohort study . SETTING General surgery , orthopedic surgery , and gynecology services at Brigham and Women 's Hospital , Boston , Mass. PATIENTS Consenting patients older than 50 years admitted for major elective noncardiac surgery between November 1 , 1990 , and March 15 , 1992 ( N = 1341 ) . MEASUREMENTS All patients underwent preoperative evaluations , including a medical history , physical examination , laboratory tests , and assessment s of physical and cognitive function using the Specific Activity Scale and the Telephone Interview for Cognitive Status . Postoperative delirium was diagnosed using the Confusion Assessment Method or using data from the medical record and the hospital 's nursing intensity index . Patients were followed up for the duration of hospitalization to determine major complication rates , length of stay , and discharge disposition . RESULTS Postoperative delirium occurred in 117 ( 9 % ) of the 1341 patients studied . Independent correlates included age 70 years or older ; self-reported alcohol abuse ; poor cognitive status ; poor functional status ; markedly abnormal preoperative serum sodium , potassium , or glucose level ; noncardiac thoracic surgery ; and aortic aneurysm surgery . Using these seven preoperative factors , a simple predictive rule was developed . In an independent population , the rule stratified patients into groups with low ( 2 % ) , medium ( 8 % , 13 % ) , and high ( 50 % ) rates of postoperative delirium . Patients who developed delirium had higher rates of major complications , longer lengths of stay , and higher rates of discharge to long-term care or rehabilitative facilities . CONCLUSIONS Using data available preoperatively , clinicians can stratify patients into risk groups for the development of delirium . Since delirium is associated with a variety of adverse outcomes , patients with substantial risk for this complication could be c and i date s for interventions to reduce the incidence of postoperative delirium and potentially improve overall surgical outcomes BACKGROUND Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances . OBJECTIVE The authors investigated the effects of postoperative sedation on the development of delirium in patients undergoing cardiac-valve procedures . METHODS Patients underwent elective cardiac surgery with a st and ardized intraoperative anesthesia protocol , followed by r and om assignment to one of three postoperative sedation protocol s : dexmedetomidine , propofol , or midazolam . RESULTS The incidence of delirium for patients receiving dexmedetomidine was 3 % , for those receiving propofol was 50 % , and for patients receiving midazolam , 50 % . Patients who developed postoperative delirium experienced significantly longer intensive-care stays and longer total hospitalization . CONCLUSION The findings of this open-label , r and omized clinical investigation suggest that postoperative sedation with dexmedetomidine was associated with significantly lower rates of postoperative delirium and lower care costs OBJECTIVES To prospect ively develop and vali date a predictive model for delirium based on precipitating factors during hospitalization , and to examine the interrelationship of precipitating factors and baseline vulnerability . DESIGN Two prospect i ve cohort studies , in t and em . SETTING General medical wards , university teaching hospital . PATIENTS For the development cohort , 196 patients aged 70 years and older with no delirium at baseline , and for the validation cohort , 312 comparable patients . MAIN OUTCOME MEASURE New-onset delirium by hospital day 9 , defined by the Confusion Assessment Method diagnostic criteria . RESULTS Delirium developed in 35 patients ( 18 % ) in the development cohort . Five independent precipitating factors for delirium were identified ; use of physical restraints ( adjusted relative risk [ RR ] , 4.4 ; 95 % confidence interval [ CI ] , 2.5 to 7.9 ) , malnutrition ( RR , 4.0 ; 95 % CI , 2.2 to 7.4 ) , more than three medications added ( RR , 2.9 ; 95 % CI , 1.6 to 5.4 ) , use of bladder catheter ( RR , 2.4 ; 95 % CI , 1.2 to 4.7 ) , and any iatrogenic event ( RR , 1.9 ; 95 % CI , 1.1 to 3.2 ) . Each precipitating factor preceded the onset of delirium by more than 24 hours . A risk stratification system was developed by adding 1 point for each factor present . Rates of delirium for low-risk ( 0 points ) , intermediate-risk ( 1 to 2 points ) , and high-risk groups ( > or equal to 3 points ) were 3 % , 20 % , and 59 % , respectively ( P < .001 ) . The corresponding rates in the validation cohort , in which 47 patients ( 15 % ) developed delirium , were 4 % , 20 % , and 35 % , respectively ( P < .001 ) . When precipitating and baseline factors were analyzed in cross-stratified format , delirium rates increased progressively from low-risk to high-risk groups in all directions ( double-gradient phenomenon ) . The contributions of baseline and precipitating factors were documented to be independent and statistically significant . CONCLUSIONS A simple predictive model based on the presence of five precipitating factors can be used to identify elderly medical patients at high risk for delirium . Precipitating and baseline vulnerability factors are highly interrelated and contribute to delirium in independent substantive , and cumulative ways Background : Commonly used sedatives/analgesics can increase the risk of postoperative complications , including delirium . This double-blinded study assessed the neurobehavioral , hemodynamic , and sedative characteristics of dexmedetomidine compared with morphine-based regimen after cardiac surgery at equivalent levels of sedation and analgesia . Methods : A total of 306 patients at least 60 yr old were r and omized to receive dexmedetomidine ( 0.1–0.7 & mgr;g · kg−1 · h−1 ) or morphine ( 10 - 70 & mgr;g · kg−1 · h−1 ) with open-label propofol titrated to a target Motor Activity Assessment Scale of 2–4 . Primary outcome was the prevalence of delirium measured daily via Confusion Assessment Method for intensive care . Secondary outcomes included ventilation time , additional sedation/analgesia , and hemodynamic and adverse effects . Results : Of all sedation assessment s , 75.2 % of dexmedetomidine and 79.6 % ( P = 0.516 ) of morphine treatment were in the target range . Delirium incidence was comparable between dexmedetomidine 13 ( 8.6 % ) and morphine 22 ( 15.0 % ) ( relative risk 0.571 , 95 % confidence interval [ CI ] 0.256–1.099 , P = 0.088 ) , however , dexmedetomidine-managed patients spent 3 fewer days ( 2 [ 1–7 ] versus 5 [ 2–12 ] ) in delirium ( 95 % CI 1.09–6.67 , P = 0.0317 ) . The incidence of delirium was significantly less in a small subgroup requiring intraaortic balloon pump and treated with dexmedetomidine ( 3 of 20 [ 15 % ] versus 9 of 25 [ 36 % ] ) ( relative risk 0.416 , 95 % CI 0.152–0.637 , P = 0.001 ) . Dexmedetomidine-treated patients were more likely to be extubated earlier ( relative risk 1.27 , 95 % CI 1.01–1.60 , P = 0.040 , log-rank P = 0.036 ) , experienced less systolic hypotension ( 23 % versus 38.1 % , P = 0.006 ) , required less norepinephrine ( P < 0.001 ) , but had more bradycardia ( 16.45 % versus 6.12 % , P = 0.006 ) than morphine treatment . Conclusion : Dexmedetomidine reduced the duration but not the incidence of delirium after cardiac surgery with effective analgesia/sedation , less hypotension , less vasopressor requirement , and more bradycardia versus morphine regimen OBJECTIVE To compare the effect of post-operative analgesia using epidural versus intravenous infusions on the incidence of delirium after bilateral knee replacement surgery in elderly patients . Additional risk factors and impact on post-operative recovery were also assessed . DESIGN Prospect i ve r and omized controlled trial . SETTING Urban referral hospital specializing in elective orthopedic surgery . PATIENTS 60 consecutive patients undergoing bilateral knee replacement surgery with epidural anesthesia were approached ; 51 patients were eligible and consented . The mean age was 68 , 55 % were women , and there was a high prevalence of comorbid medical disease . No patient was demented pre-operatively . INTERVENTION R and om allocation to either continuous epidural infusion of bupivacaine and fentanyl or continuous intravenous infusion of fentanyl . Infusions were initiated at the first complaint of pain and continued through the 36- to 48-hour stay in the recovery room . MAIN OUTCOME MEASURE Acute post-operative delirium defined using an algorithm based on DSM III criteria . RESULTS The overall incidence of acute delirium was 41 % , with no difference between types of post-operative analgesia . Predictors of delirium were age , gender , and pre-operative alcohol use . All cases resolved within 1 week , and length of stay and achievement of physical therapy goals were the same for delirious and non-delirious patients . CONCLUSIONS There is a high incidence of post-operative delirium in elderly non-demented patients following bilateral knee replacement , regardless of whether post-operative analgesia is administered by the epidural or intravenous route OBJECTIVE To compare the effect of epidural vs general anesthesia on the incidence of long-term cognitive dysfunction after total knee replacement surgery in older adults . DESIGN R and omized controlled clinical trial . SETTING Orthopedic specialty academic hospital . PATIENTS A total of 262 patients undergoing elective primary total knee replacement with a median age of 69 years ; 70 % women . INTERVENTION R and om assignment to either epidural or general anesthesia . MAIN OUTCOME MEASURES A thorough neuropsychological assessment was performed preoperatively and repeated at 1 week and 6 months postoperatively . Cognitive outcome was assessed by within-patient change on 10 tests of memory , psychomotor , and language skills . Prospect i ve st and ardized surveillance for cardiovascular complications was performed to allow simultaneous assessment of anesthetic effects on cognitive and cardiovascular outcomes . RESULTS The two groups were similar at baseline in terms of age , sex , comorbidity , and cognitive function . There were no significant differences between the epidural and general anesthesia groups in within-subject change from baseline on any of the 10 cognitive test results at either 1 week or 6 months . Overall , 5 % of patients showed a long-term clinical ly significant deterioration in cognitive function . There was no difference between the anesthesia groups in the incidence of major cardiovascular complications ( 3 % overall ) . CONCLUSIONS The type of anesthesia , general or epidural , does not affect the magnitude or pattern of postoperative cognitive dysfunction or the incidence of major cardiovascular complications in older adults undergoing elective total knee replacement . This is the largest trial of the effects of general vs regional anesthesia on cerebral function reported to date , with more than 99 % power to detect a clinical ly significant difference on any of the neuropsychological tests This r and omised , double-blinded , placebo-controlled study was primarily aim ed to evaluate the potential of risperidone to prevent postoperative delirium following cardiac surgery with cardiopulmonary bypass and the secondary objective was to explore clinical factors associated with postoperative delirium . One-hundred- and -twenty-six adult patients undergoing elective cardiac surgery with cardiopulmonary bypass were r and omly assigned to receive either 1 mg of risperidone or placebo sublingually when they regained consciousness . Delirium and other outcomes were assessed . The confusion assessment method for intensive care unit was used to assess postoperative delirium . The incidence of postoperative delirium in the risperidone group was lower than the placebo group ( 11.1 % vs. 31.7 % respectively , P=0.009 , relative risk=0.35 , 95 % confidence interval [CI]=0.16 - 0.77 ) . Other postoperative outcomes were not statistically different between the groups . In exploring the factors associated with delirium , univariate analysis showed many factors were associated with postoperative delirium . However multiple logistic regression analysis showed a lapse of 70 minutes from the time of opening eyes to following comm and s and postoperative respiratory failure were independent risk factors ( P=0.003 , odds ratio [OR]=4.57 , 95 % CI=1.66 - 12.59 and P=0.038 , OR=13.78 , 95 % CI=1.15 - 165.18 respectively ) . A single dose of risperidone administered soon after cardiac surgery with cardiopulmonary bypass reduces the incidence of postoperative delirium . Multiple factors tended to be associated with postoperative delirium , but only the time from opening eyes to following comm and s and postoperative respiratory failure were independent risk factors in this study Abstract Purpose . Postoperative delirium ( POD ) is known to be one of the most critical complications of major operative procedures in elderly patients . Since disorders of the sleep-wake cycle have been reported to be one of the key factors in POD , we attempted to clarify the effectiveness of improving sleep-wake cycle disorders with medication after surgery to prevent POD , by conducting a prospect i ve r and omized study of 42 elderly patients who underwent resection of either gastric or colon cancer through an open laparotomy . Methods . The delirium-free protocol ( DFP ) group was given an intramuscular injection of diazepam at 20:00 h each night , as well as a continuous intravenous infusion of flunitrazepam and pethidine administered over 8 h , for the first three nights postoperatively . Two patients were excluded because of failure to complete the DFP . Results . The incidence of POD was 7/20 ( 35.0 % ) in the non-DFP group and 1/20 ( 5.0 % ) in the DFP group , this difference being significant ( P = 0.023 ) . Morning lethargy produced by the DFP was observed in 40 % of the DFP group ; however , no other side effects were seen . Conclusions . These findings indicate that DFP treatment is effective for controlling POD in elderly patients after general surgery and does not appear to be associated with severe complications or side effects . To our knowledge , this is the first report proposing artificial control of the sleep-awake rhythm by medication as a means of preventing POD in elderly patients Objective : Cardiac surgery is frequently followed by postoperative delirium , which is associated with increased 1-year mortality , late cognitive deficits , and higher costs . Currently , there are no recommendations for pharmacologic prevention of postoperative delirium . Impaired cholinergic transmission is believed to play an important role in the development of delirium . We tested the hypothesis that prophylactic short-term administration of oral rivastigmine , a cholinesterase inhibitor , reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery . Design : Double-blind , r and omized , placebo-controlled trial . Setting : One Swiss University Hospital . Patients : One hundred twenty patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass . Intervention : Patients were r and omly assigned to receive either placebo or 3 doses of 1.5 mg of oral rivastigmine per day starting the evening before surgery and continuing until the evening of the sixth postoperative day . Measurements and Main Results : The primary predefined outcome was delirium diagnosed with the Confusion Assessment Method within 6 days postoperatively . Secondary outcome measures were the results of daily Mini-Mental State Examinations and clock drawing tests , and the use of a rescue treatment consisting of haloperidol and /or lorazepam in patients with delirium . Delirium developed in 17 of 57 ( 30 % ) and 18 of 56 ( 32 % ) patients in the placebo and rivastigmine groups , respectively ( p = 0.8 ) . There was no treatment effect on the time course of Mini-Mental State Examinations and clock drawing tests ( p = 0.4 and p = 0.8 , respectively ) . There was no significant difference in the number of patients receiving haloperidol ( 18 of 57 and 17 of 56 , p = 0.9 ) or lorazepam ( 38 of 57 and 35 of 56 , p = 0.6 ) in the placebo and rivastigmine groups , respectively . Conclusion : This negative or , because of method ologic issues , possibly failed trial does not support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in elderly patients undergoing elective cardiac surgery with cardiopulmonary bypass OBJECTIVE To determine if ketamine attenuates postoperative delirium concomitant with an anti-inflammatory effect in patients undergoing cardiac surgery using cardiopulmonary bypass . DESIGN A prospect i ve r and omized study . SETTING A Veterans Affairs medical center . PARTICIPANTS Cardiac surgical patients . INTERVENTIONS Patients at least 55 years of age r and omly received placebo ( 0.9 % saline , n = 29 ) or an intravenous bolus of ketamine ( 0.5 mg/kg intravenously , n = 29 ) during anesthetic induction in the presence of fentanyl and etomi date . MEASUREMENTS AND MAIN RESULTS Delirium was assessed by using the Intensive Care Delirium Screening Checklist before and after surgery . Serum C-reactive protein concentrations were determined before and 1 day after surgery . The incidence of postoperative delirium was lower ( p = 0.01 , Fisher exact test ) in patients receiving ketamine ( 3 % ) compared with placebo ( 31 % ) . Postoperative C-reactive protein concentration was also lower ( p < 0.05 ) in the ketamine-treated patients compared with the placebo-treated patients . The odds of developing postoperative delirium were greater for patients receiving placebo compared with ketamine treatment ( odds ratio = 12.6 ; 95 % confidence interval , 1.5 - 107.5 ; logistic regression ) . CONCLUSIONS After cardiac surgery using cardiopulmonary bypass , ketamine attenuates postoperative delirium concomitant with an anti-inflammatory effect Bright light therapy is a method of maintaining or restoring the natural circadian rhythm by assisting daytime awakening using bright lights . Postoperative delirium is one of the potential complications encountered by patients receiving postoperative care in the intensive care unit ( ICU ) , but there have been no studies on the use of light for the prevention of postoperative delirium . The objective of this study was to examine whether the circadian rhythms of patients after surgery for oesophageal cancer can be adjusted and whether the postoperative delirium crisis rate can be reduced by bright light therapy . The subjects were 11 patients operated on for oesophageal cancer in Osaka University Hospital . After informed consent was obtained , they were divided into a study group and a control group by a r and om sampling method . After removal of the endotracheal tube , the study group was exposed to light . The light intensity was about 5000lx immediately before the eyes , and the distance from the light source was about 100 cm . The control group was placed in a natural lighting environment after extubation . In both groups , the rhythms of physical activities and autonomic activities were monitored after surgery , and delirium was evaluated . A significant difference was observed in the delirium score between the study group and control group on the morning of day 3 of bright light therapy by the Mann-Whitney U-test ( P=0.014 ) . The study group could begin ambulation about 2 days earlier than the control group . Bright light therapy may reduce the rate of postoperative delirium and make early ambulation possible . However , our study involved a very small sample size . We want to increase the sample in the future after having review ed clinical application methods Delirium and transient neurologic dysfunctions ( TND ) often complicate the postoperative course after surgery for acute type-A aortic dissection ( AAD ) . We evaluated the role of clonidine on neurological outcome and respiratory function in 30 consecutive patients undergoing surgery for AAD . Patients were prospect ively r and omized to receive either clonidine ( 0.5 microg/kg bolus , followed by continuous infusion at 1 - 2 microg/kg/h ) or placebo ( NaCl 0.9 % ) in on starting and throughout the weaning period from the mechanical ventilation . Incidence of delirium and TND , Delirium Detection Score ( DDS ) , weaning parameters [ respiratory rate to tidal volume ratio - f/VT ; pressure-frequency product ( PFP ) ; partial pressure of arterial oxygen to fractional inspired oxygen concentration ( PaO(2)/FiO(2 ) ) ; partial pressure of carbon dioxide ( PaCO(2 ) ) ] , weaning duration and intensive care unit ( ICU ) length of stay were recorded . The two groups were similar for preoperative and operative variables and also for the incidence of postoperative complications . DDS was lower in the clonidine group ( P<0.001 ) . Patients weaned with clonidine showed lower f/VT and PFP , higher PaO(2)/FiO(2 ) and PaCO(2 ) , lower DDS , weaning period and the related ICU length of stay ( P<0.001 ) . This was further confirmed in patients developing delirium/TND . Intravenous clonidine after surgery for AAD reduces the severity of delirium , improves the respiratory function , shortens the weaning duration and the ICU length of stay OBJECTIVE Delirium is a frequent complication of major surgery in older persons . The authors evaluated the possible benefit of donepezil versus placebo in the prevention and treatment of postoperative delirium in an older population without dementia undergoing elective total joint-replacement surgery . METHODS A sample of 80 patients participated in this r and omized , double-blind , placebo-controlled trial of donepezil . Each participant was evaluated before surgery and then received donepezil or placebo for 14 days before surgery and 14 days afterward . Postoperative delirium was assessed with the Delirium Symptom Interview , Confusion Assessment Method , daily medical record , nurse-observation review s , and DSM-IV diagnostic criteria for delirium . Subsyndromal delirium was also assessed for each participant . RESULTS Delirium , diagnosed by DSM-IV criteria , was found on at least 1 postoperative day in 18.8 % of subjects , but there were no significant differences between the donepezil and placebo groups . When delirium was present , it lasted only 1 day , and there was no difference between the groups . Subsyndromal delirium was found on at least 1 postoperative day for 68.8 % of subjects , and , when this occurred , lasted 2 days or less , on average . There was no difference between the groups in the occurrence or duration of subsyndromal delirium . There was no difference between the groups in disposition to home or to another facility . CONCLUSIONS This pilot study was unable to demonstrate a benefit for donepezil in preventing or treating delirium in a relatively young and cognitively-intact group of elderly patients undergoing elective orthopedic surgery . Furthermore , postoperative delirium was not a major problem in this population Delirium , defined as an acute disorder of attention and cognition , occurs in 14 % to 56 % of elderly , hospitalized patients [ 1 - 16 ] and may be the most frequent complication of hospitalization in this population [ 6 ] . Delirium is associated with increased rates of morbidity , mortality , and nursing home placement and with longer , costlier hospitalizations [ 17 - 29 ] . Effective prevention requires the identification of risk factors for delirium . Seven prospect i ve studies have systematic ally examined risk factors for delirium in elderly , hospitalized patients [ 9 , 12 - 14 , 16 , 30 , 31 ] . The risk factors generally identified included age , dementia , severe illness , metabolic and electrolyte imbalance , the use of psychoactive medications , and infections . However , most studies failed to distinguish prevalent cases of delirium at admission from incident cases occurring during hospitalization , a necessary step to define risk factors that truly precede the onset of delirium . In addition , only one of the previous studies [ 16 ] used a st and ardized , vali date d instrument to identify delirium . Finally , no study proposed a predictive model for delirium that was vali date d in an independent sample . Previous studies focused on identifying precipitating factors for delirium ( hospitalization-related factors such as medications , procedures , and intercurrent infections ) or have simultaneously examined precipitating and predisposing conditions [ 9 , 12 - 14 , 16 , 30 , 31 ] . Although identifying these precipitating factors is undoubtedly important , an essential , prerequisite step is elucidation of baseline ( or host ) characteristics that indicate a particular vulnerability to delirium . The focus of our study was to better define host or baseline vulnerability factors that would assist clinicians in identifying , at admission , those patients with a high risk for developing delirium during hospitalization . Our objectives were to estimate the incidence of delirium in an elderly hospitalized cohort using a st and ardized , vali date d instrument ; to identify admission characteristics associated with the new occurrence of delirium ; and to develop and vali date a predictive model for the occurrence of delirium in the hospital based on the characteristics present at admission . Methods Patients The potential study patients were consecutive weekday admissions from the emergency service to six general medicine floors at Yale-New Haven Hospital from June 1988 through March 1989 . Eligibility criteria , which were met by 135 patients , included age of 70 years or more ; no evidence of delirium at admission by clinical evaluation ; and no history of severe dementia reported by the admitting attending physician or nurse or documented in the medical record . The latter criterion was selected to exclude patients with severe underlying dementia ; patients with mild-to-moderate cognitive impairment were still eligible for the study . Exclusion criteria included an inability to undergo interviewing for such reasons as terminal illness , violent behavior , or intubation ( n = 14 ) ; brief hospitalization ( < 48 hours ) ( n = 5 ) ; language barrier ( n = 2 ) ; refusal by the patient , family , or physician ( n = 3 ) ; and other reasons ( n = 4 ) . Of the 135 eligible patients , 107 ( 79 % ) were enrolled in the study . Clinical Evaluation Trained clinician- research ers carried out daily structured interviews with the patients and their primary nurses from entry until hospital discharge . The baseline patient interview , completed within 48 hours of admission , was design ed to gather demographic information ; to discover whether the patient had a history of confusion ; and to determine the patient 's pre-illness social activity level , activities of daily living [ 32 ] , instrumental activities of daily living [ 33 ] , and social network and supports [ 34 ] . The interview also included the Mini-Mental State Examination [ 35 ] , the Geriatric Depression Scale [ 36 ] , st and ard vision ( Jaeger- and Snellen-type tests ) and hearing tests ( Welch-Allyn audioscope ) , and questions design ed to screen for hearing loss [ 37 , 38 ] . Baseline information obtained from the nurses included an overall rating of illness severity [ 39 ] . Early in the hospital admission , family members or caregivers underwent a structured interview that included a modified Blessed Dementia Rating Scale [ 40 , 41 ] and an estimation of the duration of any cognitive impairment . Thereafter , the clinician- research ers interviewed the patients and their nurses daily and review ed medical records to detect any new cases of delirium . The discharge assessment included determination of discharge location . Medical records were review ed for admission medical diagnoses ( inclusive list based on review of all admission notes ) , medications , and laboratory data . Informed consent was obtained from the patient or , for those with significant cognitive impairment , from the closest relative . The study was approved by the institutional review board of Yale University School of Medicine . Identification of Delirium Suspected cases of delirium were identified during the daily patient and nurse interviews . The Confusion Assessment Method [ 42 ] question naire , a previously vali date d instrument with a sensitivity rate ranging from 94 % to 100 % and a specificity rate ranging from 90 % to 95 % , was completed daily by two observers ( a clinician- research er and a nurse ) . The principal investigator ( SKI ) saw each patient with suspected delirium within 24 hours and established all final diagnoses of delirium based on fulfillment of the Confusion Assessment Method diagnostic criteria , which included the following : acute onset and fluctuating course ; inattention ; and either disorganized thinking or altered level of consciousness [ 42 ] . A case of delirium developing at any time during hospitalization was included in the analysis ; however , a given patient could only develop delirium once ( recurrent episodes of delirium were not counted when determining the relative-risk estimates ) . Definition of Variables We used clinical ly meaningful cutpoints to categorize variables . Patients were considered to have vision impairment if their corrected vision was worse than 20/70 on both near and distant binocular tests . Patients were considered to have hearing loss if they heard fewer than three of eight tones on the audioscope test ( tones at a hearing level of 40 dB and at frequencies of 500 , 1000 , 2000 , and 4000 Hz ) , had a score of 4 of 8 or less on the questions screening for hearing loss [ 37 , 38 ] , or wore a hearing aid . Patients were considered to have chronic cognitive impairment if they scored less than 24 of 30 on the Mini-Mental State Examination at admission [ 35 ] . The chronicity of the cognitive impairment in each patient with a score of less than 24 was confirmed by a modified Blessed Dementia Rating Scale score of 4 or more or by a duration of cognitive symptoms of at least 6 months . Illness severity was rated at admission using an APACHE II score [ 43 ] and a subjective overall rating by the nurse ( adapted from Charlson and colleagues ' observer-rated ordinal scale [ 39 ] ) trichotomized as mild , moderate , or severe . Severe illness was considered present if the nurse gave a rating of severe or the APACHE score exceeded 16 . An abnormal blood urea nitrogen/creatinine ratio , used as an index of dehydration , was defined as 18 or more [ 4 ] . Prominent depressive symptoms were considered present if the Geriatric Depression Scale score was equal to or exceeded the median score of 8 of 30 . The size of a patient 's social support network was estimated by the sum of the number of children , close relatives , and friends he or she saw at least once a month . A low number of social supports was indicated by six or fewer such contacts per month . Three social support typesinstrumental support , emotional support , and presence of a confidantewere rated as present or absent . Having a few support types was indicated by the presence of one or none of these support types . Validation Study To vali date the predictive model in an independent sample , a second cohort of patients was assembled . Patients Potential participants in the validation study included 202 patients who were enrolled from November 1989 through June 1990 in another ongoing study examining the frequency of functional decline in hospitalized elderly persons at Yale-New Haven Hospital . The inclusion and exclusion criteria for this study were identical to those for the study in the development cohort , except that patients with preexisting dementia were not excluded . For comparability with the initial development cohort , therefore , 25 patients ( 12 % ) with a documented history of dementia , Alzheimer disease , or chronic organic brain syndrome in their medical record were not considered eligible for the validation sample . Of the 177 eligible patients , 174 ( 98 % ) were included in the validation sample ; 3 patients were excluded because missing data did not allow assessment of the outcome of delirium . Procedure The clinical evaluation and identification of patients with delirium were similar in the two cohorts . In all but three instances , the same assessment instruments were used . Only near binocular vision ( Jaeger-type test ) , not distant vision , was tested in the validation cohort . For assessment of hearing , the Whisper test [ 44 ] was used . Hearing impairment was defined as present if the patient heard correctly fewer than 7 of 12 numbers on the Whisper test or wore a hearing aid . A shortened 15-item version of the Geriatric Depression Scale [ 45 ] was used . Significant depressive symptoms were considered present if the patient had a score that was equal to or exceeded the median of 4 of 15 . Statistical Analyses In bivariate analyses , rates of delirium were calculated when each risk factor was present or absent . Crude relative risks were determined as the number of events ( delirium ) per person-days of observation in the group with the risk factor present relative to the number of such events per person-days Objectives : To evaluate the efficacy and safety of short-term low-dose intravenous haloperidol for delirium prevention in critically ill elderly patients after noncardiac surgery . Design : Prospect i ve , r and omized , double-blind , and placebo-controlled trial in two centers . Setting : Intensive care units of two large tertiary teaching hospitals . Patients : Four hundred fifty-seven patients 65 yrs or older who were admitted to the intensive care unit after noncardiac surgery . Intervention : Haloperidol ( 0.5 mg intravenous bolus injection followed by continuous infusion at a rate of 0.1 mg/h for 12 hrs ; n = 229 ) or placebo ( n = 228 ) was r and omly administered from intensive care unit admission . Measures : The primary end point was the incidence of delirium within the first 7 days after surgery . Secondary end points included time to onset of delirium , number of delirium-free days , length of intensive care unit stay , all-cause 28-day mortality , and adverse events . Delirium was assessed using the confusion assessment method for the intensive care unit . Results : The incidence of delirium during the first 7 days after surgery was 15.3 % ( 35/229 ) in the haloperidol group and 23.2 % ( 53/228 ) in the control group ( p = .031 ) . The mean time to onset of delirium and the mean number of delirium-free days were significantly longer ( 6.2 days [ 95 % confidence interval 5.9−6.4 ] vs. 5.7 days [ 95 % confidence interval 5.4−6.0 ] ; p = .021 ; and 6.8 ± 0.5 days vs. 6.7 ± 0.8 days ; p = .027 , respectively ) , whereas the median length of intensive care unit stay was significantly shorter ( 21.3 hrs [ 95 % confidence interval 20.3−22.2 ] vs. 23.0 hrs [ 95 % confidence interval 20.9–25.1 ] ; p = .024 ) in the haloperidol group than in the control group . There was no significant difference with regard to all-cause 28-day mortality between the two groups ( 0.9 % [ 2/229 ] vs. 2.6 % [ 6/228 ] ; p = .175 ) . No drug-related side effects were documented . Conclusions : For elderly patients admitted to intensive care unit after noncardiac surgery , short-term prophylactic administration of low-dose intravenous haloperidol significantly decreased the incidence of postoperative delirium . The therapy was well-tolerated BACKGROUND Delirium is an important problem especially in older medical in patients . OBJECTIVE The authors asked whether delirium and its duration are associated with higher mortality in a 3-month follow-up period . METHOD In this prospect i ve cohort study , in patients age 65 and older were assessed every 48 hours with the Confusion Assessment Method . RESULTS Of 542 patients enrolled , 192 ( 35.4 % ) developed delirium . After 3 months , mortality in the delirium cohort was 25.9 % , and in the nondelirium cohort was 5.8 % . Delirium was independently associated with mortality , and increased by 11 % for every 48 hours of delirium . CONCLUSION Delirium and increased delirium duration s are significantly associated with higher mortality STUDY OBJECTIVE To compare propofol plus spinal anesthesia during spontaneous ventilation using the Laryngeal Mask Airway and propofol plus fentanyl anesthesia during mechanical ventilation with an endotracheal tube on quality of recovery after anesthesia . DESIGN Prospect i ve , r and omized study . SETTING Hirosaki National Hospital . PATIENTS 150 patients ( aged > 70 years ) undergoing total knee arthroplasty . INTERVENTIONS Patients were divided r and omly into two groups , to receive spontaneous ventilation with a Laryngeal Mask Airway during propofol-spinal anesthesia , or to receive propofol-fentanyl anesthesia with mechanical ventilation via endotracheal tube . MEASUREMENTS Quality of anesthesia recovery such as nausea , vomiting , headache , pain throat , hoarse voice , back pain , dizziness , feeling comfortable , dreaming , recovery times in recovery of anesthesia , recovery times , postoperative pain , confusion , was assessed . MAIN RESULTS The frequency of postoperative pain throat , hoarse voice , and nausea was significantly lower in the propofol-spinal anesthesia group than the propofol-fentanyl anesthesia group . The time to extubation , emergence , response to comm and s , and orientation were significantly faster ( p < 0.001 ) in the propofol-spinal anesthesia group than the propofol-fentanyl anesthesia group . The frequency of postoperative confusion occurring in the propofol-spinal anesthesia group during the first 24 hours was significantly lower than that of the propofol-fentanyl anesthesia group ( p = 0.03 ) . CONCLUSIONS Propofol-spinal anesthesia provided better and faster recovery than did propofol-fentanyl anesthesia for elderly patients undergoing total knee arthroplasty Objective : To demonstrate the feasibility of a placebo-controlled trial of antipsychotics for delirium in the intensive care unit and to test the hypothesis that antipsychotics would improve days alive without delirium or coma . Design : R and omized , double-blind , placebo-controlled trial . Setting : Six tertiary care medical centers in the US . Patients : One hundred one mechanically ventilated medical and surgical intensive care unit patients . Intervention : Patients were r and omly assigned to receive haloperidol or ziprasidone or placebo every 6 hrs for up to 14 days . Twice each day , frequency of study drug administration was adjusted according to delirium status , level of sedation , and side effects . Measurements and Main Outcomes : The primary end point was the number of days patients were alive without delirium or coma . During the 21-day study period , patients in the haloperidol group spent a similar number days alive without delirium or coma ( median [ interquartile range ] , 14.0 [ 6.0–18.0 ] days ) as did patients in the ziprasidone ( 15.0 [ 9.1–18.0 ] days ) and placebo groups ( 12.5 [ 1.2–17.2 ] days ; p = 0.66 ) . No differences were found in secondary clinical outcomes , including ventilator-free days ( p = .25 ) , hospital length of stay ( p = .68 ) , and mortality ( p = .81 ) . Ten ( 29 % ) patients in the haloperidol group reported symptoms consistent with akathisia , compared with six ( 20 % ) patients in the ziprasidone group and seven ( 19 % ) patients in the placebo group ( p = .60 ) , and a global measure of extrapyramidal symptoms was similar between treatment groups ( p = .46 ) . Conclusions : A r and omized , placebo-controlled trial of antipsychotics for delirium in mechanically ventilated intensive care unit patients is feasible . Treatment with antipsychotics in this limited pilot trial did not improve the number of days alive without delirium or coma , nor did it increase adverse outcomes . Thus , a large trial is needed to determine whether use of antipsychotics for intensive care unit delirium is appropriate . Trial Registration : Clinical Trials.gov , number NCT00096863 To compare the clinical efficacy of haloperidol and risperidone for the treatment of delirium , the authors performed a double-blind comparative study . Twenty-eight patients with delirium were recruited and r and omly assigned to receive a flexible-dose regimen of haloperidol or risperidone over 7 days . The severity of delirium was assessed by using Memorial Delirium Assessment Scale scores . Scores for each group decreased significantly over the study period . However , no significant differences in mean Memorial Delirium Assessment Scale scores between groups were found . The group-by-time effect was not significant . In addition , there was no significant difference in the frequency of response to the drugs between the two groups . One patient in the haloperidol group experienced mild akathisia , but no other patients reported clinical ly significant side effects . These data show no significant difference in the efficacy or response rate between haloperidol and risperidone in the treatment of delirium In this r and omized pilot clinical trial , the authors tested the hypothesis that using gabapentin as an add-on agent in the treatment of postoperative pain reduces the occurrence of postoperative delirium . Postoperative delirium occurred in 5/12 patients ( 42 % ) who received placebo vs 0/9 patients who received gabapentin , p = 0.045 . The reduction in delirium appears to be secondary to the opioid-sparing effect of gabapentin OBJECTIVE The objective of the study was to assess the efficacy and safety of second-generation antipsychotics olanzapine and risperidone vs. haloperidol in patients of delirium admitted to medical and surgical wards . METHODS Prospect i ve follow-up single-blind r and omized controlled trials were performed . Consecutive patients with delirium referred to the consultation-liaison psychiatry team were eligible for the study . The study sample comprised 64 patients , with 20 subjects in the haloperidol group , 21 subjects in the risperidone group and 23 subjects in the olanzapine group . A flexible dose regimen ( haloperidol -0.25 to 10 mg ; risperidone -0.25 to 4 mg ; olanzapine -1.25 to 20 mg ) was used . Delirium Rating Scale-Revised-98 ( DRS-R98 ) was used as the primary efficacy measure , and mini mental status examination ( MMSE ) was used as a secondary efficacy measure . RESULTS There was no significant difference in mean baseline DRS-R98 severity scores and MMSE scores between the three groups . However , there were a significant reduction in DRS-R98 severity scores and a significant improvement in MMSE scores over the period of 6 days , but there was no difference between the three groups . Four patients in the haloperidol group , six subjects in the risperidone group and two subjects in the olanzapine group experienced some side effects . CONCLUSIONS Risperidone and olanzapine are as efficacious as haloperidol in the treatment of delirium OBJECTIVE The purpose of this study was to examine the efficacy and side effects of haloperidol , chlorpromazine , and lorazepam for the treatment of the symptoms of delirium in adult AIDS patients in a r and omized , double-blind , comparison trial . METHOD Nondelirious , medically hospitalized AIDS patients ( N = 244 ) consented to participate in the study and were monitored prospect ively for the development of delirium . Patients entered the treatment phase of the study if they met DSM-III-R criteria for delirium and scored 13 or greater on the Delirium Rating Scale . Thirty patients were r and omly assigned to treatment with haloperidol ( N = 11 ) , chlorpromazine ( N = 13 ) , or lorazepam ( N = 6 ) . Efficacy and side effects associated with the treatment were measured with repeated assessment s using the Delirium Rating Scale , the Mini-Mental State , and the Extrapyramidal Symptom Rating Scale . RESULTS Treatment with either haloperidol or chlorpromazine in relatively low doses result ed in significant improvement in the symptoms of delirium as measured by the Delirium Rating Scale . No improvement in the symptoms of delirium was found in the lorazepam group . Cognitive function , as measured by the Mini-Mental State , improved significantly from baseline to day 2 for patients receiving chlorpromazine . Treatment with haloperidol or chlorpromazine was associated with an extremely low prevalence of extrapyramidal side effects . All patients receiving lorazepam , however , developed treatment-limiting adverse effects . Although only a small number of patients had been treated with lorazepam , the authors became sufficiently concerned with the adverse effects to terminate that arm of the protocol early . CONCLUSIONS Symptoms of delirium in medically hospitalized AIDS patients may be treated efficaciously with few side effects by using low-dose neuroleptics ( haloperidol or chlorpromazine ) . Lorazepam alone appears to be ineffective and associated with treatment-limiting adverse effects BACKGROUND Patients undergoing total hip or knee replacement surgery experience unmanaged pain during postoperative physiotherapy sessions . It was theorized that a baseline opioid would improve pain management . OBJECTIVES To examine the effectiveness of adding long-acting oral morphine to a routine postoperative regimen for total hip or knee replacement surgery . METHODS The present study was a double-blind , r and omized , placebo-controlled trial for patients undergoing total hip or knee replacement surgery . All patients received routine postoperative analgesia ; in addition , the treatment group received long-acting oral morphine 30 mg orally twice daily for three days , while the control group received placebo capsules . The primary end point was a decrease in pain scores by two points on a 0- to 10-point pain rating scale . Secondary end points included adverse effects , acute confusion , pain-related interferences in function and sleep , length of stay and patient satisfaction . RESULTS Two hundred patients were enrolled in the present study ( March 2004 to March 2006 ) . Although the groups were large enough to yield statistical significance , most pain scores did not reach the predetermined improvement for clinical significance . Additionally , there was an increase in opioid usage ( P<0.0001 ) , vomiting ( P=0.0148 ) and oversedation ( P=0.08 ) . There were no statistically significant changes in function or sleep . Improved satisfaction with pain management was minimal ( P=0.052 ) . DISCUSSION The present study was undertaken to determine the value of adding a long-acting opioid ( morphine ) to the usual care of patients undergoing total hip or total knee replacement surgery . The results yielded minimally improved pain scores and additional adverse effects ( vomiting and oversedation ) . Published research in which long-acting opioids ( oxycodone ) were used for similar postoperative procedures did not robustly report improved pain scores . In addition , patients using a long-acting opioid ( oxycodone ) during the postoperative period reported somnolence , dizziness and confusion . Statistically , the patients in the present study showed higher confusion scores and no improvement for pain-related interferences with activity or walking . The treatment group did report increased satisfaction ; however , the significance was weak . CONCLUSIONS Thirty milligrams twice per day of long-acting morphine from days 1 to 3 following total hip and total knee replacement surgery provided minimal improvements in pain scores , and more adverse effects in the treatment group . The overall strength of evidence for improved outcomes is minimal and thus not supported Fifty-seven patients , all over the age of 64 , with femoral neck fracture were r and omized to receive epidural or halothane anesthesia to see if the anesthetic technique influenced the incidence of postoperative confusion . All patients were lucid on admission . Using the American Psychiatric Association 's Diagnostic and Statistical Manual of Mental Disorders ( DSM-III ) as criteria for confusion , we found that 44 % of the patients developed confusion that correlated closely to a history of mental depression ( P < 0.01 ) and to the use of drugs with anticholinergic effect ( P < 0.005 ) . There was no difference in the incidence of confusion between the two anesthetic groups . In patients given halothane , however , early postoperative hypoxemia was associated with confusion ( P < 0.05 ) . Patients with confusion had significantly more postoperative complications and almost four times longer hospitalization times . It is concluded that anticholinergic medication and a history of mental depression are predominant risk factors for development of postoperative confusion and in this respect are more important than the anesthetic technique OBJECTIVES This was a pilot , phase 2a study to assess method ological feasibility and the safety and efficacy of donepezil in preventing postoperative delirium after elective total hip replacement surgery in older people without pre-existing dementia . The hypothesis was that donepezil would reduce the incidence of postoperative delirium . METHODS A double blind , placebo controlled , parallel group r and omized trial was undertaken . Patients were block r and omized pre-operatively to receive placebo or donepezil 5 mg immediately following surgery and every 24 h thereafter for a further three days . The main outcome was the incidence of delirium ( using the Delirium Symptom Interview ) . The secondary outcome was length of hospital stay . RESULTS Thirty-three patients ( mean age 67 years ; 17 males , 16 females ) completed the study ( 19 donepezil , 14 placebo ) . Donepezil was well tolerated with no serious adverse events . Postoperative delirium occurred in 21.2 % of subjects . Donepezil did not significantly reduce the incidence of delirium . The unadjusted risk ratio ( donepezil vs placebo ) for delirium was 0.29 ( 95 % CI = 0.06,1.30 ) ( chi(2 ) ( [ 1 ] ) = 3.06 ; p = 0.08 ) . Mean length of hospital stay was 9.9 days for the donepezil group vs 12.1 days in the placebo group ; difference in means = -2.2 days ( 95 % CI = -0.39,4.78 ) ( t([31 ] ) = 1.73 : p = 0.09 ) . CONCLUSIONS The experimental paradigm was feasible and acceptable . Donepezil did not significantly reduce the incidence of delirium or length of hospital stay , however for both outcomes there was a consistent trend suggesting possible benefit . The sample size required for a definitive trial ( 99 % power , alpha 0.05 ) would be 95 subjects per arm Background and Objectives : Intrathecal morphine is a widely used method for postoperative pain relief after major abdominal surgery . The aim of this r and omized , double-blinded study was to compare intrathecal morphine and intravenous PCA morphine for postoperative analgesia and recovery course after major colorectal surgery in elderly patients . Methods : After written informed consent , patients > 70 years of age were prospect ively and r and omly assigned to receive either preoperative intrathecal morphine ( 0.3 mg ) and postoperative patient-controlled ( PCA ) intravenous morphine ( IT morphine ) or PCA alone ( group control ) . Results are presented as mean ± SD ( 95 % confidence interval ) . Results : Twenty-six patients successfully completed the study in each group . In the IT morphine group , rate of awakening was delayed . Pain intensity and daily intravenous morphine consumption were significantly reduced 1 and 2 days after surgery in the IT morphine group ( P < .01 ) . Mental function ( assessed by Mini Mental State and Digit Symbol Substitution Test ) was similar in both groups . Episodes of postoperative delirium/confusion occurred similarly in both groups . Time to ileus resolution and time to ambulation without assistance did not differ between the 2 groups . The duration of hospitalization was 8.4 ± 1.7 ( 7 - 11 ) days and 7.9 ± 2.0 ( 6 - 9.9 ) days for control and IT morphine , respectively ( nonstatistical difference ) . Patients in the IT morphine group had longer time to awakening from anesthesia and experienced more sedation . Conclusions : Intrathecal morphine , as compared with intravenous PCA morphine alone , improves immediate postoperative pain and reduces parenteral morphine consumption but does not improve postoperative recovery in elderly patients after major colorectal surgery We investigated the influence of either propofol or desflurane on the incidence of postoperative cognitive dysfunction in a r and omised trial of 180 patients undergoing coronary artery bypass surgery . The primary outcome was incidence of postoperative cognitive dysfunction at 3 months , defined as ≥ 1 SD deterioration in two or more of 12 neurocognitive tests . Secondary outcomes included early postoperative cognitive dysfunction ( between days three and seven ) , delirium on day one , morbidity and length of hospital stay . Early postoperative cognitive dysfunction was significantly higher with propofol compared with desflurane ( 56/84 ( 67.5 % ) vs 41/83 ( 49.4 % ) , respectively , p = 0.018 ) , but this effect was not seen at 3 months ( 10/87 ( 11.2 % ) vs 9/90 ( 10.0 % ) , respectively . There was no difference in delirium ( 7/89 ( 7.9 % ) vs 12/91 ( 13.2 % ) , respectively , length of hospital stay ( median ( IQR [ range ] ) 7 ( 6‐9 [ 4‐15 ] ) vs 6 ( 5‐7 [ 5‐16 ) days , respectively or other morbidities . Desflurane was associated with reduced early cognitive dysfunction |
11,806 | 29,506,209 | Good evidence was found for behavior change maintenance effects in healthy inactive adults , and underlying BCTs .
This review provides translational evidence to improve research , intervention design , and service delivery in physical activity interventions , while highlighting the lack of fidelity measurement | Physical inactivity and sedentary behavior relate to poor health outcomes independently .
Healthy inactive adults are a key target population for prevention .
This systematic review and meta- analysis aim ed to evaluate the effectiveness of physical activity and /or sedentary behavior interventions , measured postintervention ( behavior change ) and at follow-up ( behavior change maintenance ) , to identify behavior change techniques ( BCT ) within , and report on fidelity . | Abstract Objective : To evaluate the effectiveness of combinations of three methods to promote physical activity . Design : R and omised controlled trial . Baseline assessment with post-intervention follow up at 12 weeks and 1 year . Setting : One urban general practice , 1995 - 7 . Participants : 523 adults aged 40 to 64 years , r and omised to four intervention groups and a control group . Interventions : Brief ( one interview ) or intensive ( six interviews over 12 weeks ) motivational interviewing based on the stages of change model of behaviour change , with or without financial incentive ( 30 vouchers entitling free access to leisure facilities ) . Main outcome measures : Physical activity score ; sessions of moderate and vigorous activity in the preceding four weeks . Results : Response rate was 81 % at 12 weeks and 85 % at one year . More participants in the intervention group reported increased physical activity scores at 12 weeks than controls ( 38 % v 16 % , difference 22 % , 95 % confidence interval for difference 13 % to 32 % ) , with a 55 % increase observed in those offered six interviews plus vouchers . Vigorous activity increased in 29 % of intervention participants and 11 % of controls ( difference 18 % , 10 % to 26 % ) , but differences between the intervention groups were not significant . Short term increases in activity were not sustained , regardless of intensity of intervention . Conclusions : The most effective intervention for promoting adoption of exercise was the most intensive . Even this did not promote long term adherence to exercise . Brief interventions promoting physical activity that are used by many schemes in the United Kingdom are of question able effectiveness . Key messages Schemes promoting physical activity are currently popular in general practice in Britain , but few have been rigorously evaluated and their effectiveness is unknown . In this study , the most effective intervention for promoting adoption of physical activity was the most intensive , involving six motivational interviews and a financial incentive A comparatively brief intervention ( one interview ) was only effective in the short term in around a third of participants Short term increases in physical activity were not maintained at one year follow up and even the most intensive intervention was ineffective in promoting long term adherence to increased physical activity . National and local government , health authorities , and primary healthcare teams should be cautious about current and future expenditure on , and implementation of , exercise prescription or referral BACKGROUND Using peer volunteers as delivery agents may improve translation of evidence -based physical activity promotion programs for older adults . This study examined whether tailored support from older peer volunteers could improve initiation and long-term maintenance of physical activity behavior . METHODS Participants were r and omized to 2 16-week , group-based programs : ( 1 ) peer-delivered , theory-based support for physical activity behavior change ; or ( 2 ) an intervention typically available in community setting s ( basic education , gym membership , and pedometer for self-monitoring ) , attention-matched with health education . Moderate-to-vigorous physical activity ( MVPA ) was assessed via daily self-report logs at baseline , at the end of the intervention ( 16 weeks ) , and at follow-up ( 18 months ) , with accelerometry validation ( RT3 ) in a r and om sub sample . RESULTS Seven peer volunteers and 81 sedentary adults were recruited . Retention at the end of the trial was 85 % and follow-up at 18 months was 61 % . Using intent-to-treat analyses , at 16 weeks , both groups had similar significant improvements in MVPA . At 18 months , the group supplemented with peer support had significantly more MVPA . CONCLUSIONS Trained peer volunteers may enhance long-term maintenance of physical activity gains from a community-based intervention . This approach has great potential to be adapted and delivered inexpensively in community setting Purpose . This study examined the broader use of a print-media intervention , which was previously shown to be effective at promoting physical activity to participants recruited from a regional Australian community , as a strategy suitable for a more diverse statewide population sample . Methods . Participants were r and omly selected adults who responded to a telephone interview conducted by the New South Wales Health Department and consented to participate in a r and omized controlled trial . Consenters were allocated to either intervention ( n = 361 ) or control ( n = 358 ) conditions . The intervention , a personalized letter plus stage-targeted booklets , was sent 1 week postbaseline . Data were collected via telephone interview at baseline and 2 and 8 months and were analyzed using repeated measures analysis of variance ( ANOVA ) and χ2 statistics . Results . The groups were similar at baseline ( mean age 43 ± 3 years ; 64 % women ) . Process evaluation showed high intervention recall ( 76 % at 2 months ) and high follow-up response rates ( > 85 % at 8 months ) were achieved . Nonsignificant increases in physical activity were observed ( F 1,719 = 2.18 , p = .14 ) . Discussion . A single mailing of stage-targeted print material s was not effective in promoting increases in physical activity among participants selected from the statewide population . Future research could examine how the effectiveness of print media might be enhanced , possibly by using supplementary media , community-based prompts , or other incentives Background Research ers theorize that interventions increase physical activity by influencing key theory-based mediators ( e.g. , behavioral processes ) . However , few studies have been adequately powered to examine the importance of mediators . Purpose This study examined both physical activity behavior and psychosocial mediators in a r and omized trial specifically powered to detect mediation . Methods Healthy , sedentary adults ( n = 448 ; 70 % Caucasian , 87 % women , mean age was 43 ) were r and omly assigned to either a 6-month print-based theory tailored physical activity intervention ( n = 224 ) or a 6-month health/wellness contact control arm ( n = 224 ) . Results The print intervention arm exhibited greater increases in physical activity than the control arm at 6 and 12 months ( p < .05 ) . Additionally , behavioral processes were found to be an important mediator of physical activity behavior . Conclusions It is important for research ers and practitioners to focus on increasing behavioral strategies for physical activity adoption . Future studies should examine other potential mediators of physical activity This study examined predictors of exercise maintenance following completion of a physical activity intervention . Sedentary adults recruited through newspaper advertisements were r and omly assigned to receive either ( a ) a motivation-matched intervention with feedback reports that were individually tailored ( IT ) to psychological variables from social cognitive theory and the Transtheoretical Model via computer expert system , or ( b ) a st and ard , print-based intervention ( ST ) . The intervention phase of the study included mailed assessment s and intervention material s at baseline , 1 , 3 , and 6 months . An assessment -only follow-up was conducted 6 months after the end of the intervention ( Month 12 ) . Participants were assessed for current physical activity participation , motivational readiness for physical activity , a number of psychological constructs posited to influence participation in physical activity ( e.g. , self-efficacy ) , and current affect . Significantly more participants in the IT condition met or exceeded exercise participation goals at the end of the intervention period and maintained , this level of physical activity through the Month 12 follow-up compared to ST participants . Prospect i ve analyses revealed significant differences in several psychological constructs both at program entry ( baseline ) and the end of the intervention period between individuals who maintained their physical activity participation through Month 12 and those who did not . Results suggest that the maintenance of physical activity following the end of an active intervention program , may be influenced by attitudes and behaviors acquired along with increased participation in physical activity , as well as by preexisting characteristics that individuals bring into treatment BACKGROUND The impact of a 6-month lifestyle change intervention on cardiovascular risk factors in obese , sedentary , postmenopausal women was examined . A secondary aim of this investigation was to determine whether the addition of self-control skills training to an empirically supported lifestyle change intervention would result in greater cardiovascular risk reduction . METHODS Forty-four women were r and omly assigned to receive either a lifestyle change or a lifestyle change with self-control skills intervention . Pretreatment and posttreatment weight loss , body composition , physical activity , cardiorespiratory fitness , diet , blood pressure ( BP ) , blood lipids , and psychosocial functioning were assessed . Also , at 1-year posttreatment , weight loss , body composition , self-reported physical activity , and psychosocial functioning were assessed . RESULTS The women significantly increased their physical activity ( + 39.6 % ) and cardiorespiratory fitness ( + 13.5 % ) and reduced their body weight ( -6.5 % ) , fat mass ( -7.4 % ) , body fat ( -2.4 % ) , BP ( SBP -6.2 % , DBP -9.2 % ) , total cholesterol ( -7.4 % ) , triglycerides ( -16.5 % ) , and low-density lipoprotein ( LDL ) cholesterol ( 9.1 % ) and improved their diet ( p < 0.05 ) . At the 1-year follow-up , women had regained approximately 63 % of their posttreatment weight loss ( p < 0.05 ) , but had maintained their previous increases in physical activity . Additionally , there were no significant changes in fat free mass , body fat , anxiety , or depression between the end of treatment and 1-year posttreatment . The addition of self-control skills training did not significantly improve cardiovascular risk reduction . CONCLUSIONS Lifestyle change interventions may be an effective means for reducing cardiovascular risk in obese , sedentary , postmenopausal women . However , greater attention should be devoted to the maintenance of these positive lifestyle changes Study objective : To determine if a self help intervention , delivered via written interactive material s ( the “ Walk in to Work Out ” pack ) , could increase active commuting behaviour ( walking and cycling ) . Design : R and omised controlled trial . The intervention group received the “ Walk in to Work Out ” pack , which contained written interactive material s based on the transtheoretical model of behaviour change , local information about distances and routes , and safety information . The control group received the pack six months later . Focus groups were also conducted after six months . Setting : Three workplaces in the city of Glasgow , Scotl and , UK . Participants : 295 employees who had been identified as thinking about , or doing some irregular , walking or cycling to work . Main results : The intervention group was almost twice as likely to increase walking to work as the control group at six months ( odds ratio of 1.93 , 95 % confidence intervals 1.06 to 3.52 ) . The intervention was not successful at increasing cycling . There were no distance travelled to work , gender , or age influences on the results . Twenty five per cent ( 95 % confidence intervals 17 % to 32 % ) of the intervention group , who received the pack at baseline , were regularly actively commuting at the 12 month follow up . Conclusion : The “ Walk in to Work Out ” pack was successful in increasing walking but not cycling . The environment for cycling must be improved before cycling will become a popular option Background The purpose of the study was to evaluate a 6-month intervention to promote office-employees ’ walking with pedometers and e-mail messages . Methods Participants were recruited by 10 occupational health care units ( OHC ) from 20 worksites with 2,230 employees . Voluntary and insufficiently physically active employees ( N = 241 ) were r and omized to a pedometer ( STEP , N = 123 ) and a comparison group ( COMP , N = 118 ) . STEP included one group meeting , log-monitored pedometer-use and six e-mail messages from OHC . COMP participated in data collection . Reach , effectiveness , adoption , implementation , maintenance ( RE- AIM ) and costs were assessed with question naires ( 0 , 2 , 6 , 12 months ) , process evaluation and interviews ( 12 months ) . Results The intervention reached 29 % ( N = 646 ) of employees in terms of participation willingness . Logistic regression showed that the proportion of walkers tended to increase more in STEP than in COMP at 2 months in “ walking for transportation ” ( Odds ratio 2.12 , 95%CI 0.94 to 4.81 ) and at 6 months in “ walking for leisure ” ( 1.86 , 95%CI 0.94 to 3.69 ) . Linear model revealed a modest increase in the mean duration of “ walking stairs ” at 2 and 6 months ( Geometric mean ratio 1.26 , 95%CI 0.98 to 1.61 ; 1.27 , 0.98 to 1.64 ) . Adoption and implementation succeeded as intended . At 12 months , some traces of the intervention were sustained in 15 worksites , and a slightly higher number of walkers in STEP in comparison with COMP was observed in “ walking stairs ” ( OR 2.24 , 95%CI 0.94 to 5.31 ) and in “ walking for leisure ” ( 2.07 , 95%CI 0.99 to 4.34 ) . The direct costs of the intervention were 43 Euros per participant . Conclusions The findings indicate only modest impact on some indicators of walking . Future studies should invest in reaching the employees , minimizing attrition rate and using objective walking assessment .Trial registerationIS RCT 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 aim of the project was to reach inactive people through primary care offices and motivate them to become more active for health purpose s. Physical activity question naires based on the transtheoretical model ( TM ) of behaviour change were h and ed out to every person entering one of five primary care offices . All inactive people were entered into a r and omised controlled trial ( RCT ) . Individuals assigned to the feedback group were given feedback from their physician concerning their physical activity level . In addition , the advice plus group received further advice and stage matched leaflets and was offered a 45-min counselling session . Changes in physical activity behaviour were measured 7 weeks as well as 14 months after the intervention . Physicians and patients alike reacted positively to the project . Ninety percent of patients entering the primary care offices were willing to participate . Ninety percent of inactive people agreed to be entered into the RCT . The follow-up rate in this trial was 82 % at 14 months . At 7 weeks , 35 % of patients in the feedback group were now classified as active and 38 % of patients in the advice plus group . At 14 months , 47 % of the subjects in both groups were active . Inactive people can be reached effectively through primary care offices . Patients receiving feedback from their physician concerning their physical activity level improved their behaviour to the same extent as patients who were given further advice and written material s , and were offered a counselling session Objective To assess the effectiveness of a primary care based programme of exercise on prescription among relatively inactive women over a two year period . Design R and omised controlled trial . Setting 17 primary care practice s in Wellington , New Zeal and Participants 1089 women aged 40 - 74 not undertaking 30 minutes of moderate intensity physical activity on at least five days of the week Intervention Brief physical activity intervention led by nurse with six month follow-up visit and monthly telephone support over nine months . Main outcome measure Physical activity assessed at baseline and 12 and 24 months . Secondary outcomes were quality of life ( SF-36 ) , weight , waist circumference , blood pressure , concentrations of fasting serum lipids , glycated haemoglobin ( HbA1c ) , glucose , insulin , and physical fitness . Results Mean age was 58.9 ( SD 7 ) years . Trial retention rates were 93 % and 89 % at 12 and 24 months , respectively . At baseline , 10 % of intervention participants and 11 % of control participants were achieving 150 minutes of at least moderate intensity physical activity a week . At 12 months rates increased to 43 % and 30 % and at 24 months to 39.3 % and 32.8 % ( P<0.001 ) , respectively . SF-36 physical functioning ( P=0.03 ) and mental health ( P<0.05 ) scores improved more in intervention compared with control participants , but role physical scores were significantly lower ( P<0.01 ) . There were no significant differences in clinical outcomes . More falls ( P<0.001 ) and injuries ( P=0.03 ) were recorded in the intervention group . Conclusions This programme of exercise on prescription increased physical activity and quality of life over two years , although falls and injuries also increased . This finding supports the use of exercise on prescription programmes as part of population strategies to reduce physical inactivity . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) ANZCTRN012605000490673 Introduction Large proportions of the population are not meeting recommended levels of physical activity and have increasingly sedentary lifestyles . Low levels of physical activity are predictive of poor health outcomes and time spent sedentary is related to a host of risk factors independently of physical activity levels . Building an evidence base of the best approaches to intervene in the lifestyles of inactive individuals is crucial in preventing long-term disease , disability and higher mortality rates . Methods and analysis Systematic search es will be conducted on all relevant data bases ( eg , PubMed , Scopus , CINAHL , PsycINFO ) . Studies will be included if they assess interventions aim ed at changing physical activity or sedentary behaviour levels in adults ( over 18 ) who are inactive and do not suffer from chronic conditions . Studies must also be r and omised controlled trials ( RCTs ) , have a primary outcome of physical activity or sedentary behaviour , and measure outcomes at least 6 months after intervention completion . Studies will be coded using the Behaviour Change Technique ( BCT ) taxonomy v1 and Template for Intervention Description and Replication ( TIDieR ) guidelines . 2 review ers will independently screen full-text articles and extract data on study characteristics , participants , BCTs , intervention features and outcome measures . Study quality will also be assessed independently by 2 review ers using the Cochrane risk of bias tool . A meta- analysis will be considered if there is sufficient homogeneity across outcomes . GRADE criteria will be used to assess quality of evidence . Dissemination This will be the first review to systematic ally appraise interventions aim ed at changing the physical activity or sedentary behaviour of inactive individuals using RCT design s with a 6-month follow-up post-intervention . This review will better inform intervention design ers targeting inactive population s and inform the design of a future complex intervention . Review registration number This protocol was registered with the International Prospect i ve Register of Systematic Review s ( PROSPERO ) on 17 October 2014 ( registration number : CRD42014014321 ) OBJECTIVE To evaluate the effects of a lifestyle intervention and a structured exercise intervention on physical activity in older adults . METHOD Participants were r and omly assigned to a lifestyle intervention ( n=60 ) , including an individualized home-based program supported by phone calls , or to a structured intervention ( n=60 ) consisting of three weekly supervised sessions . Results were compared with a control group ( n=66 ) . Physical activity was measured with self-report question naires , pedometers , and accelerometers before the start ( pretest ) , at the end ( 11 months , posttest ) , and after 23 months ( follow-up ) . The study took place in Belgium from March 2004 until April 2006 . RESULTS At posttest , both intervention groups had significantly increased their total physical activity compared with the control group . At follow-up , the lifestyle group showed significantly larger increases in active transportation and total steps than the control and structured group respectively . There were no longer significant differences between the structured intervention and the control group . CONCLUSIONS The structured and lifestyle interventions were equally effective at the end of the intervention . One year after the intervention the lifestyle group maintained a significant increase in physical activity , which highlights the potential of lifestyle programs in the battle against inactivity in older adults CONTEXT For decades , behavioral weight-loss treatments have been unsuccessful beyond the short term . Development and testing of innovative , theoretically based methods that depart from current failed practice s is a priority for behavioral medicine . OBJECTIVE To evaluate a new , theory-based protocol in which exercise support methods are employed to facilitate improvements in psychosocial predictors of controlled eating and sustained weight loss . METHODS Women with obesity were r and omized into either a comparison treatment that incorporated a print manual plus telephone follow-ups ( n = 55 ) or an experimental treatment of The Coach Approach exercise-support protocol followed after 2 months by group nutrition sessions focused on generalizing self-regulatory skills from an exercise support to a controlled eating context ( n = 55 ) . Repeated- measures analysis of variance contrasted group changes in weight , physical activity , fruit and vegetable intake , mood , and exercise- and eating-related self-regulation and self-efficacy over 24 months . Regression analyses determined salient interrelations of change scores over both the weight-loss phase ( baseline-month 6 ) and weight-loss maintenance phase ( month 6-month 24 ) . RESULTS Improvements in all psychological measures , physical activity , and fruit and vegetable intake were significantly greater in the experimental group where a mean weight loss of 5.7 kg ( 6.1 % of initial body weight ) occurred at month 6 , and was largely maintained at a loss of 5.1 kg ( 5.4 % ) through the full 24 months of the study . After establishing temporal intervals for changes in self-regulation , self-efficacy , and mood that best predicted improvements in physical activity and eating , a consoli date d multiple mediation model suggested that change in self-regulation best predicted weight loss , whereas change in self-efficacy best predicted maintenance of lost weight . CONCLUSIONS Because for most participants loss of weight remained greater than that required for health benefits , and costs for treatment administration were comparatively low , the experimental protocol was considered successful . After sufficient replication , physician referral and applications within health promotion and wellness setting s should be considered 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 Purpose . To assess the effectiveness of applying behavior change theory to a physical activity intervention for obese , sedentary women . Design . A 48-week r and omized controlled trial . Subjects were r and omized to one of two intervention groups . Setting . A university classroom and a local health club . Subjects . Fifty-eight sedentary , obese women . Interventions . A 24-week theory-based physical activity program that aims to change the way subjects think and behave in relation to physical activity ( treatment group , n = 29 ) and a traditionally structured exercise program ( control group , n = 29 ) . Measures . Question naires on physical activity , stage of change , processes of change , and self-efficacy were completed at baseline , 24 weeks , and 48 weeks . Results . Twenty-seven of the 29 participants in the treatment group and 17 participants in the control group completed the study . Analysis of variance revealed significant and positive changes in measures of eight processes of change , self-efficacy , physical activity , and cardiorespiratory fitness in the treatment group at 24 weeks . All but one of these changes were maintained at 48 weeks . In the control group , significant changes occurred in only two processes of change , and no change occurred in self-efficacy , physical activity , or cardiorespiratory fitness at 24 or 48 weeks . Conclusion . A theory-based intervention is more likely to change the way obese women think and behave in relation to physical activity than a traditional exercise program that does not incorporate behavior change theory OBJECTIVES To assess the long-term effectiveness of a telephone counseling intervention on physical activity and health-related quality of life in low-active older adults recruited through their primary care physician . DESIGN R and omized , controlled trial . SETTING Three primary care practice s from different socioeconomic regions of Auckl and , New Zeal and . PARTICIPANTS One hundred and eighty-six low-active adults ( aged 65 ) recruited from their primary care physicians ' patient data bases . INTERVENTION Eight telephone counseling sessions over 12 weeks based on increasing physical activity . Control patients received usual care . MEASUREMENTS Change in physical activity ( as measured using the Auckl and Heart Study Physical Activity Question naire ) and quality of life ( as measured using the Short Form-36 Health Survey ( SF-36 ) ) over a 12-month period . RESULTS Moderate leisure physical activity increased by 86.8 min/wk more in the intervention group than in the control group ( P=.007 ) . More participants in the intervention group reached 2.5 hours of moderate or vigorous leisure physical activity per week after 12 months ( 42 % vs 23 % , odds ratio=2.9 , 95 % confidence interval=1.33 - 6.32 , P=.007 ) . No differences on SF-36 measures were observed between the groups at 12 months . CONCLUSION Telephone-based physical activity counseling is effective at increasing physical activity over 12 months in previously low-active older adults OBJECTIVE Weight gain may follow altered eating habits and decreased physical activity in couples beginning to live together . Mutual support and willingness to accept changes in lifestyle at this stage may facilitate positive responses to health promotion . We aim ed to compare the effects of a diet and physical activity program in couples using a r and omized controlled trial . STUDY DESIGN AND SETTING Couples were r and omized to a control group or to one of two intervention groups in whom the program was either delivered mainly by mail or with a combination of mail-outs and interactive group sessions . RESULTS Diets , physical fitness , and blood cholesterol improved up to 12 months after beginning the 4-month program , mainly in the interactive group . In that group , at the end of the program , the estimated cost was 445.30 dollars ( 111.33 dollars/month ) per participant per unit change in outcome variables , only 0.03 dollars per participant per month more than the group receiving the program mainly by mail . One year after beginning the program , costs per participant per month were 38.37 dollars in the interactive group and 38.22 dollars in the group receiving the program mainly by mail-out . CONCLUSION The changes observed in cardiovascular risk factors could translate to a substantial cost-savings relating to health This study compared the long-term effectiveness of three physical activity counseling strategies among sedentary older adults : a 1-contact referral ( REFER ) , a 1-contact individualized walking program ( WALK ) , and multiple-contact , individually tailored , and need-supportive coaching based on the self-determination theory ( COACH ) . Participants ( n = 442 ) completed measurements before ( pretest ) , immediately after ( posttest ) , and 1 yr after ( follow-up test ) a 10-wk intervention . Linear mixed models demonstrated significant time-by-condition interaction effects from pre- to posttest . More specifically , WALK and COACH yielded larger increases in daily steps and self-reported physical activity than REFER . Similarly , self-reported physical activity increased more from pre- to follow-up test in WALK and COACH compared with REFER . Autonomous motivation mediated the effect of perceived need-support on physical activity , irrespective of counseling strategy . These results demonstrate the long-term effectiveness of both a 1-contact individualized walking program and a more time-consuming , need-supportive coaching , especially in comparison with a st and ard referral to local opportunities Objectives : Physical activity is a key factor for healthy ageing and obesity management . The aim of this study was to test the effect of implementation intentions ( IIs ) on physical activity and body weight among inactive obese older adults . Design and measures : At baseline , 101 obese ( classes I and II ) older adults were r and omised to an experimental or a control condition . IIs were delivered in the experimental condition in addition to the common intervention activities . Physical activity ( primary outcome ) was assessed by means of pedometers . The effect of IIs on body weight ( secondary outcome ) was also evaluated . Results : No main effects for IIs were observed for all outcomes ( ps > 0.21 ) . A significant time × condition interaction was observed for the number of steps per day ( p = 0.01 ) . At the 6-month follow-up , the improvement in physical activity was greater among participants in the experimental condition ( d = 0.59 ) . None of the measured cognitions moderated or mediated IIs . Conclusion : Results suggest that IIs could be appropriate to favour the maintenance of physical activity among inactive obese older adults . However , this technique seems to have limited impacts over and above common intervention activities on weight loss Abstract Objective : To measure the effect of behaviourally oriented counselling in general practice on healthy behaviour and biological risk factors in patients at increased risk of coronary heart disease . Design : Cluster r and omised controlled trial . Participants : 883 men and women selected for the presence of one or more modifiable risk factors : regular cigarette smoking , high serum cholesterol concentration ( 6.5 - 9.0 mmol/l ) , and high body mass index ( 25 - 35 ) combined with low physical activity . Intervention : Brief behavioural counselling , on the basis of the stage of change model , carried out by practice nurses to reduce smoking and dietary fat intake and to increase regular physical activity . Main outcome measures : Question naire measures of diet , exercise , and smoking habits , and blood pressure , serum total cholesterol concentration , weight , body mass index , and smoking cessation ( with biochemical validation ) at 4 and 12 months . Results : Favourable differences were recorded in the intervention group for dietary fat intake , regular exercise , and cigarettes smoked per day at 4 and 12 months . Systolic blood pressure was reduced to a greater extent in the intervention group at 4 but not at 12 months No differences were found between groups in changes in total serum cholesterol concentration , weight , body mass index , diastolic pressure , or smoking cessation . Conclusions : Brief behavioural counselling by practice nurses led to improvements in healthy behaviour . More extended counselling to help patients sustain and build on behaviour changes may be required before differences in biological risk factors emerge BACKGROUND Given the low rates of physical activity participation , innovative intervention approaches are needed to make a public health impact . METHODS The study was conducted at the Miriam Hospital/Brown Medical School in Providence , RI , and in communities of Southeastern Massachusetts from 2002 to 2005 . Previously sedentary women ( n = 280 ; mean age = 47.1 ; 94.6 % Caucasian ) were r and omly assigned to one of three conditions : ( 1 ) Choose to Move , a self-help printed booklet ( n = 93 ) , ( 2 ) Jumpstart , a motivationally tailored , print based intervention ( n = 95 ) ; or ( 3 ) Wellness , women 's health material s ( n = 92 ) . Face-to-face contact at months 3 ( M3 ) and 12 ( M12 ) occurred within participants ' communities in local libraries . RESULTS At M3 , participants in the Jumpstart condition reported significantly more minutes of physical activity per week ( M = 140.4 , SE = 14.82 ) than participants in the Wellness condition ( M = 98.1 , SE = 15.09 ) , ( t(275 ) = 2.00 , p < 0.05 ) . The Jumpstart arm showed a trend towards significance ( t(275 ) = 1.93 , p = 0.054 ) when compared with the CTM arm ( M = 99.5 , SE = 15.11 ) ; there was no significant difference between the CTM and Wellness arms ( t(275 ) = 0.07 , p = NS ) . At M12 , there were no significant differences ( F(2,275 ) = 0.147 , p = NS ) between any of the treatment arms . CONCLUSIONS Results suggest that print-based programs for physical activity may be efficacious short-term , but more research is needed to find approaches that are effective long-term . It is possible to deliver print-based programs through existing community infrastructures , however these approaches need further evaluation to examine maintenance effects apart from the dem and characteristics of a research study OBJECTIVES To compare the efficacy of a computer-based physical activity program ( Embodied Conversational Agent-ECA ) with that of a pedometer control condition in sedentary older adults . DESIGN Single-blind block-r and omized controlled trial stratified according to clinic site and health literacy status . SETTING Three urban ambulatory care practice s at Boston Medical Center between April 2009 and September 2011 . PARTICIPANTS Older adults ( N = 263 ; mean age 71.3 ; 61 % female ; 63 % African American ; 51 % high school diploma or less ) . INTERVENTION ECA participants were provided with portable tablet computers with touch screens to use for 2 months and were directed to connect their pedometers to the computer using a data cable and interact with a computer-animated virtual exercise coach daily to discuss walking and to set walking goals . Intervention participants were then given the opportunity to interact with the ECA in a kiosk in their clinic waiting room for the following 10 months . Control participants were given a control pedometer intervention that only tracked step counts for an equivalent period of time . Intervention participants were also provided with pedometers . MEASUREMENTS The primary outcome was average daily step count for the 30 days before the 12-month interview . Secondary outcomes were average daily step count for the 30 days before the 2-month interview . Outcomes were also stratified according to health literacy level . RESULTS ECA participants walked significantly more steps than control participants at 2 months ( adjusted mean 4,041 vs 3,499 steps/day , P = .01 ) , but this effect waned by 12 months ( 3,861 vs 3,383 , P = .09 ) . For participants with adequate health literacy , those in the ECA group walked significantly more than controls at both 2 months ( P = .03 ) and 12 months ( P = .02 ) , while those with inadequate health literacy failed to show significant differences between treatment groups at either time point . Intervention participants were highly satisfied with the program . CONCLUSION An automated exercise promotion system deployed from outpatient clinics increased walking among older adults over the short-term . Effective methods for long-term maintenance of behavior change are needed OBJECTIVE To increase walking activity in sedentary women . METHODS Women ( N = 253 ) were r and omly assigned to 1 of 3 groups : video education/control , brief telephone calls with no counseling , and telephone calls with counseling . Assessment s were made at baseline , 6 months , and 1 year . RESULTS All interventions increased the number of reported minutes walked and decreased the time to walk a mile . CONCLUSIONS The variability in the telephone counseling and brief telephone call groups seemed to suggest a group of participants who were high responders A home-based telephone and mail intervention was evaluated for its effectiveness in promoting walking in a sample of sedentary , ethnic minority women . One hundred twenty-five women ( ages 23 - 54 ) were r and omly assigned to behavioral or brief educational interventions . Women in the 8-week behavioral condition received behavior change material s through the mail and 6 structured telephone counseling sessions . Educational condition participants received a single 5-min telephone call and educational information . Both groups reported significantly increased walking at a 2-month posttest ( M change = 86 and 81 min per week for behavioral and educational groups , respectively ) and 5-month follow-up ( M change = 40 and 52 min per week ) . A 30-month follow-up of 50 participants indicated both groups continued to report more walking than at baseline . The behavioral intervention was not superior to the educational condition at any assessment point . The findings may be explained as ( a ) both interventions were equally effective , so extensive telephone counseling is unnecessary ; ( b ) changes over time reflected secular trends ; or ( c ) increases in self-reported walking may be due to socially desirable reporting . Other strategies need to be evaluated for promoting walking that are tailored to the needs of ethnic minority women OBJECTIVE To determine whether provision of individualised physical activity advice by an exercise specialist in general practice is effective in modifying physical activity and cardiovascular risk factors in older adults . DESIGN R and omised controlled trial of individualised physical activity advice , reinforced at three and six months ( intervention ) versus no advice ( control ) . SETTING Two general practice s in Adelaide , South Australia , 1996 . PARTICIPANTS 299 adults aged 60 years or more who were healthy , sedentary and living in the community . MAIN OUTCOME MEASURES Changes to physical activity ( frequency and duration of walking and vigorous exercise ) , selected cardiovascular risk factors ( blood pressure , body weight , serum lipid levels ) and quality of life over 12 months . RESULTS Self-reported physical activity increased over the 12 months in both groups ( P < 0.001 ) . The increase was greater for the intervention than the control group for all measures except time spent walking ( P < 0.05 ) . More intervention than control participants increased their intention to exercise ( P < 0.001 ) . Serum levels of total and low-density lipoprotein cholesterol and triglycerides fell significantly over the 12 months to a similar extent in the two groups . No other significant changes in cardiovascular risk factors were seen . Quality -of-life scores decreased over the 12 months . The decrease was significantly greater among intervention than control women , but not men , for emotional well-being ( P = 0.02 ) , physical well-being ( P = 0.04 ) and social functioning ( P = 0.04 ) . DISCUSSION Provision of general practice -based physical activity advice reinforced three-monthly produced a sustained increase in self-reported physical activity . However , there were no associated changes in clinical measures of cardiovascular risk factors and minimal changes in quality -of-life measures Purpose . To examine the extent to which theoretical fidelity , or precision in replicating theory-based recommendations , influenced the effectiveness of two walking programs based on social cognitive theory ( SCT ) . Design . Two-group r and omized controlled trial . Setting . College town in Virginia . Subjects . Sixty-one sedentary adult women . Intervention . Two 12-week e-mail – based walking programs were compared . The high fidelity program was design ed to more precisely follow SCT recommendations for operationalizing mastery procedures than the low fidelity program , which was design ed to simulate how mastery procedures were operationalized in most existing SCT-based physical activity programs . Treatment contact and walking prescription were controlled across groups . Measures . The 1-mile walk test of physical fitness and SCT measures were completed at baseline and posttest . Self-reported walking quantity was assessed at baseline , posttest , and 1-year follow-up . Walking logs were completed during the program . Process evaluation measures were completed at posttest . Results . Fifty women completed the study . The high fidelity group improved more than twice as much as the low fidelity group on 1-mile walk test time ( 86 vs. 32 seconds , p < .05 ) , goal setting ( p < .05 ) , and positive outcome expectations ( p < .05 ) and reported greater program satisfaction ( p < .01 ) . Conclusion . Theoretical fidelity could advance the quality of physical activity interventions , which have often shown small effects |
11,807 | 22,152,262 | The evidence around changing the way people who fall are managed within primary care practice s , and , layperson , peer or community delivered models was mixed .
IMPACT ON INDUSTRY Translating the evidence -base into practice involves changing the attitudes and behaviours of older people , healthcare professionals and organisations . | PROBLEM AND OBJECTIVE The translation of the evidence -base for preventing falls among community-dwelling older people into practice has been limited .
This study systematic ally review ed and synthesis ed the effectiveness of methods to implement falls prevention programmes with this population . | BACKGROUND Falling is a common and morbid condition among elderly persons . Effective strategies to prevent falls have been identified but are underutilized . METHODS Using a nonr and omized design , we compared rates of injuries from falls in a region of Connecticut where clinicians had been exposed to interventions to change clinical practice ( intervention region ) and in a region where clinicians had not been exposed to such interventions ( usual-care region ) . The interventions encouraged primary care clinicians and staff members involved in home care , outpatient rehabilitation , and senior centers to adopt effective risk assessment s and strategies for the prevention of falls ( e.g. , medication reduction and balance and gait training ) . The outcomes were rates of serious fall-related injuries ( hip and other fractures , head injuries , and joint dislocations ) and fall-related use of medical services per 1000 person-years among persons who were 70 years of age or older . The interventions occurred from 2001 to 2004 , and the evaluations took place from 2004 to 2006 . RESULTS Before the interventions , the adjusted rates of serious fall-related injuries ( per 1000 person-years ) were 31.2 in the usual-care region and 31.9 in the intervention region . During the evaluation period , the adjusted rates were 31.4 and 28.6 , respectively ( adjusted rate ratio , 0.91 ; 95 % Bayesian credibility interval , 0.88 to 0.94 ) . Between the preintervention period and the evaluation period , the rate of fall-related use of medical services increased from 68.1 to 83.3 per 1000 person-years in the usual-care region and from 70.7 to 74.2 in the intervention region ( adjusted rate ratio , 0.89 ; 95 % credibility interval , 0.86 to 0.92 ) . The percentages of clinicians who received intervention visits ranged from 62 % ( 131 of 212 primary care offices ) to 100 % ( 26 of 26 home care agencies ) . CONCLUSIONS Dissemination of evidence about fall prevention , coupled with interventions to change clinical practice , may reduce fall-related injuries in elderly persons The aim of this evaluation study was to assess the impact of peer-presented education sessions on the falls-related attitude , knowledge and behaviour of older people . The evaluation was undertaken on the Bellarine Peninsula in Victoria , Australia , and adopted a non-r and omised pre-test post-test design . Baseline , 3 and 12 months follow-up data were collected for 107 individuals who attended the education sessions and 116 controls , matched by age range and sex . The groups were not strictly equivalent at baseline , with the intervention group having a greater knowledge about falls and falls prevention . Analyses which controlled for baseline differences showed that those who attended the education sessions maintained a greater knowledge of factors that can prevent falls at 12 months follow-up . The intervention group also made more changes in and around their home to prevent falls by 3 and 12 months follow-up . Younger participants who reported a previous history of falls and having taken action to prevent falls were most likely to take additional action . The results can help target this type of education program and suggest that their major benefit may lie in providing those who voluntarily attend with the impetus to take the most effective preventative action OBJECTIVES To determine whether a practice -based intervention can improve care for falls , urinary incontinence , and cognitive impairment . DESIGN Controlled trial . SETTING Two community medical groups . PARTICIPANTS Community-dwelling patients ( 357 at intervention sites and 287 at control sites ) aged 75 and older identified as having difficulty with falls , incontinence , or cognitive impairment . INTERVENTION Intervention and control practice s received condition case-finding , but only intervention practice s received a multicomponent practice -change intervention . MEASUREMENTS Percentage of quality indicators satisfied measured using a 13-month medical record abstract ion . RESULTS Before the intervention , the quality of care was the same in intervention and control groups . Screening tripled the number of patients identified as needing care for falls , incontinence , or cognitive impairment . During the intervention , overall care for the three conditions was better in the intervention than the control group ( 41 % , 95 % confidence interval (CI)=35 - 46 % vs 25 % , 95 % CI=20 - 30 % , P<.001 ) . Intervention group patients received better care for falls ( 44 % vs 23 % , P<.001 ) and incontinence ( 37 % vs 22 % , P<.001 ) but not for cognitive impairment ( 44 % vs 41 % , P=.67 ) than control group patients . The intervention was more effective for conditions identified by screening than for conditions identified through usual care . CONCLUSION A practice -based intervention integrated into usual clinical care can improve primary care for falls and urinary incontinence , although even with the intervention , less than half of the recommended care for these conditions was provided . More-intensive interventions , such as embedding intervention components into an electronic medical record , will be needed to adequately improve care for falls and incontinence BACKGROUND Since falling is associated with serious morbidity among elderly people , we investigated whether the risk of falling could be reduced by modifying known risk factors . METHODS We studied 301 men and women living in the community who were at least 70 years of age and who had at least one of the following risk factors for falling : postural hypotension ; use of sedatives ; use of at least four prescription medications ; and impairment in arm or leg strength or range of motion , balance , ability to move safely from bed to chair or to the bathtub or toilet ( transfer skills ) , or gait . These subjects were given either a combination of adjustment in their medications , behavioral instructions , and exercise programs aim ed at modifying their risk factors ( intervention group , 153 subjects ) or usual health care plus social visits ( control group , 148 subjects ) . RESULTS During one year of follow-up , 35 percent of the intervention group fell , as compared with 47 percent of the control group ( P = 0.04 ) . The adjusted incidence-rate ratio for falling in the intervention group as compared with the control group was 0.69 ( 95 percent confidence interval , 0.52 to 0.90 ) . Among the subjects who had a particular risk factor at base line , a smaller percentage of those in the intervention group than of those in the control group still had the risk factor at the time of re assessment , as follows : at least four prescription medications , 63 percent versus 86 percent , P = 0.009 ; balance impairment , 21 percent versus 46 percent , P = 0.001 ; impairment in toilet-transfer skills , 49 percent versus 65 percent , P = 0.05 ; and gait impairment , 45 percent versus 62 percent , P = 0.07 . CONCLUSIONS The multiple-risk-factor intervention strategy result ed in a significant reduction in the risk of falling among elderly persons in the community . In addition , the proportion of persons who had the targeted risk factors for falling was reduced in the intervention group , as compared with the control group . Thus , risk-factor modification may partially explain the reduction in the risk of falling BACKGROUND AND PURPOSE An abundance of evidence suggests that interventions targeting fall risk factors are effective ; however , it remains unknown whether , or to what extent , this body of evidence has affected the clinical practice of physical therapy providers . The purpose s of this study were : ( 1 ) to describe knowledge of , and attitudes toward , fall risk factors and fall reduction strategies ; ( 2 ) to assess self-reported use of fall reduction strategies with patients ; and ( 3 ) to identify factors associated with increased use of fall reduction strategies with patients among physical therapy providers exposed to a behavioral change strategy . SUBJECTS AND METHODS A cross-sectional survey of physical therapy providers from hospital-based and freest and ing outpatient physical therapy facilities throughout north- central Connecticut was conducted between October 2002 and April 2003 . The participants were 94 physical therapy providers who had been exposed to the Connecticut Collaboration for Fall Prevention ( CCFP ) behavioral change effort . The CCFP program uses multicomponent professional behavioral change strategies to embed fall risk factor assessment and management , based on evidence from r and omized controlled trials , into the clinical care of older patients . A telephone question naire -- focusing on fall risk factor knowledge and attitudes and self-reported fall risk factor assessment and management practice s before and after exposure to the CCFP efforts -- was administered to consenting physical therapy providers . RESULTS Environmental hazards and gait and balance deficits were named as fall risk factors by 86 ( 91 % ) and 73 ( 78 % ) participants , respectively . All of the targeted risk factors were mentioned by at least 30 % of the participants . Sixty-four participants ( 68 % ) reported increased fall reduction practice behaviors . The area of multiple medications was noted most frequently , with 77 participants ( 82 % ) noting new practice s related to medication use . Only knowledge of fall risk factors and pre-CCFP behaviors were associated with increased fall reduction practice s. DISCUSSION AND CONCLUSION Physical therapy providers reported an increase in practice behaviors in response to the multicomponent behavioral change strategy . Knowledge of fall risk factors was associated with increased fall reduction practice behaviors , most likely due to the focused nature of the education strategy |
11,808 | 25,934,300 | Quetiapine IR caused sedation and increased rates of clinical ly significant weight gain , but no extrapyramidal effects were observed .
CONCLUSIONS Quetiapine IR has a small beneficial effect on overall psychotic symptoms over 2 - 12 weeks , but also leads to weight gain and sedation | BACKGROUND Immediate-release ( IR ) quetiapine has been used to treat schizophrenia since 1997 , although all the principal placebo-controlled trials have > 50 % missing outcome data .
New studies with relatively lower rates of participant withdrawal have since been published .
AIMS To assess the efficacy and adverse effects of quetiapine IR for schizophrenia , with consideration of outcome quality and clinical meaningfulness of results , and to examine the potential impact of missing data on the main efficacy findings . | OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of acute quetiapine monotherapy in adolescents with schizophrenia . METHODS Patients ages 13 - 17 years with an American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . , Text Revision ( DSM-IV-TR ) diagnosis of schizophrenia and a Positive and Negative Syndrome Scale ( PANSS ) total score ≥60 were r and omized to 6 weeks of quetiapine ( 400 or 800 mg/day ) or placebo treatment . The primary efficacy measure was change in PANSS total score from baseline to day 42 . Safety endpoints included adverse events and assessment s of clinical chemistry values , suicidality , and extrapyramidal symptoms . RESULTS The intent-to-treat population included 220 patients . Least-squares mean change in PANSS total score from baseline to endpoint was -27.31 with quetiapine 400 mg/day , -28.44 with quetiapine 800 mg/day , and -19.15 with placebo ( p=0.043 and 0.009 for quetiapine 400 and 800 mg/day , respectively , vs. placebo ; mixed-model , repeated- measures analysis ) . Several secondary efficacy outcomes , including Clinical Global Impressions-Improvement score , supported the primary outcome measure in demonstrating significantly greater improvement in quetiapine groups than in the placebo group . Mean changes in body weight at day 42 were 2.2 kg and 1.8 kg for quetiapine 400 and 800 mg/day , respectively , and -0.4 kg for placebo . Mean changes in certain clinical chemistry parameters , including total cholesterol and triglycerides , were numerically greater in the quetiapine groups than in the placebo group . Adverse events associated with quetiapine were mostly mild to moderate in intensity and were consistent with its known profile in adults with schizophrenia . CONCLUSIONS In this 6-week study of adolescent patients , quetiapine at doses of 400 and 800 mg/day provided significant improvements in symptoms associated with schizophrenia in adolescent patients , including the primary efficacy measure of PANSS total score change . Quetiapine was generally well tolerated with a profile broadly similar to that reported in adult and adolescent population s. CLINICAL TRIAL REGISTRATION INFORMATION Quetiapine Fumarate ( SEROQUEL ( ™ ) ) Compared to Placebo in the Treatment of Adolescent Patients With Schizophrenia ( ANCHOR 112 ) . Available at : http://www . clinical trials.gov/ct2/show/NCT00090324?term=quetiapine+112&rank=1 OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate We examined the potential risks and benefits of switching from olanzapine to quetiapine in mentally stable , obese , or overweight patients with schizophrenia or schizoaffective disorder . Patients receiving olanzapine were r and omized to continuing olanzapine treatment ( N = 68 ; 7.5–20 mg/day ) or switching to quetiapine ( N = 65 ; 300–800 mg/day ) . Time to relapse was the primary study objective ; secondary objectives included changes in weight , metabolic parameters , and psychiatric symptoms , and discontinuation rates . No significant difference in time to relapse was observed ( p = 0.293 ) , but significantly more patients remained on treatment in the olanzapine group compared with the quetiapine group ( 70.6 % vs 43.1 % ; p = 0.002 ) . Olanzapine-treated patients had significantly lower rates of study discontinuation for lack of efficacy and psychiatric adverse events ( AEs ) compared to quetiapine ( 2.94 % vs 15.38 % , p = 0.015 ) . Significantly more patients in the olanzapine group experienced an increase in BMI ≥1 kg/m2 . Olanzapine-treated patients experienced significantly greater increases in weight from Weeks 2 through 13 . Switching patients with stable disease from olanzapine to quetiapine did not significantly shorten time to relapse , but produced more frequent study discontinuations due to lack of efficacy or psychiatric AEs with moderate but variable improvement in weight and no significant between-group differences in mean changes in metabolic laboratory parameters In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials OBJECTIVE Potency equivalents for anti-psychotic drugs are required to guide clinical dosing and for design ing and interpreting research studies . Available dosing guidelines are limited by the methods and data from which they were generated . METHOD With a two-step Delphi method , the authors surveyed a diverse group of international clinical and research experts , seeking consensus regarding antipsychotic dosing . The authors determined median clinical dosing equivalents and recommended starting , target range , and maximum doses for 61 drugs , adjusted for selected clinical circumstances . RESULTS Participants ( N=43 ) from 18 countries provided dosing recommendations regarding treatment of psychotic disorders for 37 oral agents and 14 short-acting and 10 long-acting parenteral agents . With olanzapine 20 mg/day as reference , estimated clinical equivalency ratios of oral agents ranged from 0.025 for sulpiride to 10.0 for trifluperidol . Seventeen patient and treatment characteristics , including age , hepatic and renal function , illness stage and severity , sex , and diagnosis , were associated with dosing modifications . CONCLUSIONS In the absence of adequate prospect i ve , r and omized drug-drug comparisons , the present findings provide broad , international , expert consensus-based recommendations for most clinical ly employed antipsychotic drugs . They can support clinical practice , trial design , and interpretation of comparative antipsychotic trials OBJECTIVE Placebo response and the rate of failed clinical trials are increasing in schizophrenia , resembling previous experience with antidepressant clinical trials . In depression , the percent of patients r and omized to placebo was shown to be strongly associated with drug-placebo differences ( signal detection).We hypothesized that this factor would also be important in recent schizophrenia clinical trials . To test this hypothesis a data base of acute schizophrenia placebo-controlled studies conducted between 1997 and 2008 was constructed . The data base contained 27 studies , with 79 active treatment arms . As percentage of patients r and omized to placebo increased , mean placebo improvement decreased ( p = 0.047 ) and mean drug-placebo differences tended to increase ( p = 0.166 ) . The frequency of significant contrasts from studies with ≥ 25 % r and omized to placebo was 83.3 % , compared with 58.3 % in studies with < 25 % r and omized to placebo . Caveats to these findings include limited data and confounding of potentially influential factors . These limitations prevent definitive conclusions . However , results are consistent with previous findings in depression where having a higher percent of patients r and omized to placebo increased drug-placebo differences OBJECTIVES This study aim ed to demonstrate efficacy of once-daily extended release quetiapine fumarate ( quetiapine XR ) versus placebo in patients with acute schizophrenia . METHODS In this 6-week , r and omized , double-blind study ( 5077IL/0041 ) patients were r and omized to receive quetiapine XR ( 300 , 600 , or 800 mg/day ) , quetiapine fumarate immediate release ( quetiapine IR ) [ 300 or 600 mg/day ] , or placebo . Primary endpoint was change from baseline in the Positive and Negative Syndrome Scale ( PANSS ) total score at Day 42 . Secondary variables included PANSS response rate at Day 42 ( > /=30 % decrease in PANSS total score from baseline ) and Clinical Global Impressions Severity ( CGI-S ) and Improvement ( CGI-I ) ratings . Safety assessment s included adverse event ( AE ) reporting and laboratory measures . RESULTS Of 532 patients r and omized , 222 ( 41.7 % ) completed the study . Improvements in PANSS total scores from baseline to Day 42 across treatment groups were : quetiapine XR 300 mg/day -5.01 , 600 mg/day -13.01 and 800 mg/day -11.17 , quetiapine IR 300 mg/day -9.42 and 600 mg/day -6.97 , and placebo -5.19 ; the difference in change was statistically significant only for quetiapine XR 600 mg/day ( p = 0.033 ) . There were no statistically significant differences between active treatment groups and placebo for PANSS response rates . Several post hoc analyses were conducted to explain the study efficacy outcome but these were inconclusive . Quetiapine XR was generally well tolerated with the majority of AEs being mild or moderate in intensity and no unexpected AEs . CONCLUSIONS Superior efficacy of quetiapine XR versus placebo in patients with schizophrenia was demonstrated for quetiapine XR 600 mg/day . The safety and tolerability profile of quetiapine XR was similar to that of quetiapine IR BACKGROUND Current antipsychotics have only a limited effect on 2 core aspects of schizophrenia : negative symptoms and cognitive deficits . Minocycline is a second-generation tetracycline that has a beneficial effect in various neurologic disorders . Recent findings in animal models and human case reports suggest its potential for the treatment of schizophrenia . These findings may be linked to the effect of minocycline on the glutamatergic system , through inhibition of nitric oxide synthase and blocking of nitric oxide-induced neurotoxicity . Other proposed mechanisms of action include effects of minocycline on the dopaminergic system and its inhibition of microglial activation . OBJECTIVE To examine the efficacy of minocycline as an add-on treatment for alleviating negative and cognitive symptoms in early-phase schizophrenia . METHOD A longitudinal double-blind , r and omized , placebo-controlled design was used , and patients were followed for 6 months from August 2003 to March 2007 . Seventy early-phase schizophrenia patients ( according to DSM-IV ) were recruited and 54 were r and omly allocated in a 2:1 ratio to minocycline 200 mg/d . All patients had been initiated on treatment with an atypical antipsychotic < or = 14 days prior to study entry ( risperidone , olanzapine , quetiapine , or clozapine ; 200 - 600 mg/d chlorpromazine-equivalent doses ) . Clinical , cognitive , and functional assessment s were conducted , with the Scale for the Assessment of Negative Symptoms ( SANS ) as the primary outcome measure . RESULTS Minocycline was well tolerated , with few adverse events . It showed a beneficial effect on negative symptoms and general outcome ( evident in SANS , Clinical Global Impressions scale ) . A similar pattern was found for cognitive functioning , mainly in executive functions ( working memory , cognitive shifting , and cognitive planning ) . CONCLUSIONS Minocycline treatment was associated with improvement in negative symptoms and executive functioning , both related to frontal-lobe activity . Overall , the findings support the beneficial effect of minocycline add-on therapy in early-phase schizophrenia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00733057 Dropout in r and omised controlled trials is common and threatens the validity of results , as completers may differ from people who drop out . Differing dropout rates between treatment arms is sometimes called differential dropout or attrition . Although differential dropout can bias results , it does not always do so . Similarly , equal dropout may or may not lead to biased results . Depending on the type of missingness and the analysis used , one can get a biased estimate of the treatment effect with equal dropout rates and an unbiased estimate with unequal dropout rates . We reinforce this point with data from a r and omised controlled trial in patients with renal cancer and a simulation study Background Patient satisfaction with antipsychotic treatment is important . Limited evidence suggests that satisfaction is associated with symptom improvement and compliance . Predictors of patient satisfaction with antipsychotic medication were examined in a study of patients with a recent exacerbation of schizophrenia . Methods Data are from a r and omized , double-blind trial comparing risperidone ( n = 152 ) , quetiapine ( n = 156 ) , and placebo ( n = 73 ) . Medication Satisfaction Question naire ( MSQ ) was completed after 14 days of treatment and after 6 weeks at last study visit . Results Medication satisfaction at both time points was significantly associated in multiple regression analysis with improvement on 3 Positive and Negative Syndrome Scale ( PANSS ) factor scores ( positive symptoms p < .01 ; uncontrolled hostility/excitement , p < .0005 ; anxiety/depression , p < .04 ) and treatment with risperidone ( p < .03 ) ; at day 14 , significant association was also found with older age ( p = .01 ) . At both time points , predictor variables explained over 30 % of the variance in medication satisfaction . Change in Hamilton Depression Scale , prolactin levels , sex , and reported adverse events of extrapyramidal symptoms , sedation , and movement disorders were not significant predictors of satisfaction . Lower level of medication satisfaction at day 14 was associated with earlier discontinuation in the trial at week 6 end point . A focused principal components analysis of PANSS factors and MSQ suggested that medication satisfaction relates to 3 groups of factors in descending order of magnitude : lower levels of ( a ) uncontrolled hostility/excitement , ( b ) positive symptoms , and ( c ) negative symptoms , disorganized thoughts , and anxiety/depression . Conclusion Results give further support that treatment satisfaction is positively associated with symptom improvement , particularly psychotic symptoms , and suggest that satisfaction may also be related to compliance , as those who were more satisfied remained in the trial for a longer period of time . Trial registration numberTrial registration number Background : Linking of the Clinical Global Impression ( CGI ) Scale and the Positive and Negative Syndrome Scale ( PANSS ) was performed within a naturalistic sample . Furthermore , these linking results were compared with those derived from r and omized controlled trials to examine if the baseline severity might influence the linking results . Methods : Biweekly PANSS and CGI ratings were performed from admission to discharge in 398 schizophrenia patients treated within a naturalistic study . Equipercentile linking was performed using the statistical program , R 2.8.1 . To evaluate how the naturalistic study design would influence linkage results , a so-called study sample was computed with patients of the naturalistic study fulfilling common inclusion criteria of r and omized controlled trials ( n = 199 ) . Patients not fulfilling these criteria ( less ill sample ) and those fulfilling the criteria ( study sample ) were compared using confidence intervals . Results : We found a considerable difference between the linking of the CGI severity score and the PANSS total score comparing the less ill sample and the study sample . Being considered " mildly ill " at admission in the less ill sample corresponded to a PANSS total score of 47 points and to a PANSS total score of 67 points in the study sample . Considering the linking of the CGI improvement score and PANSS changes , similar results were found for CGI improvement ratings ranging from " very much improved " to " minimally improved . " Conclusions : Despite considerable differences , a 50 % PANSS reduction was found to correspond to a clinical rating of much improved , which seems to be a suitable definition for response in clinical drug trials OBJECTIVE This study compared the effects of atypical antipsychotics ( risperidone or quetiapine ) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization . METHODS This international , r and omized , double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase . Recently exacerbated patients with schizophrenia or schizoaffective disorder ( DSM-IV ) were r and omized ( 2:2:1 ) to risperidone ( n = 153 ) , quetiapine ( n = 156 ) , or placebo ( n = 73 ) . Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5 , with the ability to increase to 600 or 800 mg/day of quetiapine on day 8 . The main outcome measures were the total Positive and Negative Syndrome Scale ( PANSS ) and need for additional psychotropic medications . RESULTS Monotherapy Phase : The combined atypical antipsychotic group ( n = 308 ) reached borderline superiority to placebo ( n = 71 ) at the 2-week endpoint on mean change in total PANSS score ( -24.1 + /- 1.2 and -20.2 + /- 2.0 , respectively ; p = 0.067 ) . The change in the atypical group was driven by the improvement with risperidone ( -27.7 + /- 1.5 vs. -20.2 + /- 2.0 with placebo , p < 0.01 ; and vs. -20.5 + /- 1.5 with quetiapine , p < 0.01 ) ; the improvement with quetiapine was similar to placebo , p = 0.879 . Results were similar on other efficacy endpoints . Additive Therapy Phase : Additional psychotropics were prescribed to fewer ( p < 0.01 ) risperidone ( 36 % ) than quetiapine ( 53 % ) or placebo patients ( 59 % ) . The overall discontinuation rate was 18 % , 26 % , and 38 % , respectively . Risperidone , compared with placebo , was associated with more parkinsonism , akathisia , plasma prolactin changes , and weight gain ; while quetiapine was associated with more somnolence , sedation , dizziness , constipation , tachycardia , thyroid dysregulation , and weight gain . CONCLUSION While the combined atypical antipsychotic group did not experience greater improvements than the placebo group , risperidone , but not quetiapine , was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder , with no unexpected tolerability findings This was a r and omized , flexible-dose , rater-blind , parallel-group , quasi-naturalistic trial comparing the efficacy , safety , and tolerability of quetiapine , risperidone , and olanzapine in patients with schizophrenia hospitalized for severe psychotic symptoms . Seventy-five patients were r and omized to quetiapine ( n=25 ) , risperidone ( n=25 ) , or olanzapine ( n=25 ) . Mean doses at Week 8 were : 590.0 mg/day quetiapine ; 5.1 mg/day risperidone ; 15.1 mg/day olanzapine . Four quetiapine , five risperidone , and five olanzapine patients discontinued prior to Week 8 . There were no significant differences between groups in the primary efficacy measures of improvement from baseline in Positive and Negative Syndrome Scale ( PANSS ) total score at Week 8 in the per protocol ( PP ) population and the number of completers who experienced > or=40 % improvement on the same scale . PP and intent-to-treat analyses showed significant improvement from baseline in each component of a PANSS-derived battery , without significant differences between treatments . No quetiapine patients , one risperidone , and four olanzapine patients reported an adverse event ( AE ) of moderate intensity ; no severe AEs were reported . A linear mixed model for repeated measures showed an effect of treatment on body weight , with significant differences favoring quetiapine over risperidone and olanzapine . Simpson-Angus Scale scores were significantly worse with risperidone compared with both olanzapine and quetiapine at Week 3 and compared with quetiapine thereafter . Use of concomitant medications for anxiety or tension was significantly less frequent with quetiapine . In conclusion , quetiapine , risperidone , and olanzapine have similar efficacy in schizophrenia , but there are drug-specific differences for some AEs and in the use of concomitant medication that differentiate these agents OBJECTIVE To evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) in a 6-week , double-blind , r and omized study . METHOD Patients with a DSM-IV diagnosis of acute schizophrenia were r and omly assigned to fixed-dose quetiapine XR 400 , 600 , or 800 mg/day ( once daily in the evening ) , quetiapine immediate release ( IR ) 400 mg/day ( 200 mg twice daily ) , or placebo . Dual-matched placebo was used to maintain blinding . Quetiapine XR target doses were reached by day 2 ( 400 and 600 mg ) and day 3 ( 800 mg ) . The primary endpoint was least squares mean change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score . PANSS response rate ( percentage of patients with > or = 30 % reduction in total score ) , Clinical Global Impressions-Improvement scale ( CGI-I ) response rate ( percentage of patients with score < or = 3 ) , change in CGI-Severity of Illness ( CGI-S ) , and adverse events ( AEs ) were also assessed . The study was conducted from November 2004 to December 2005 . RESULTS 588 patients were enrolled and 446 ( 76 % ) completed the study . Improvement in PANSS total score at week 6 was significant versus placebo ( -18.8 ) in all groups : -24.8 ( p = .03 ) , -30.9 ( p < .001 ) , and -31.3 ( p < .001 ) for quetiapine XR 400 , 600 , and 800 mg , respectively , and -26.6 ( p = .004 ) for quetiapine IR . There were also statistically significant differences in PANSS and CGI-I response rates for all active treatments versus placebo ( all p < .05 ) . The most common AEs in all quetiapine groups were somnolence and dizziness ; there were no unexpected AEs with quetiapine XR . Incidence of AEs potentially related to extrapyramidal symptoms was similar to placebo . CONCLUSION Once-daily quetiapine XR ( 400 - 800 mg/day ) was effective versus placebo in patients with acute schizophrenia . Treatment , including rapid dose escalation , was well tolerated , with a therapeutically effective dose reached by day 2 . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00206115 OBJECTIVE The extent to which noncompletion of a clinical trial relates to outcomes has implication s for choosing the most appropriate method for contending with missing data due to dropout . We examined whether dropout relates to outcome in clinical trials of antipsychotic medication . METHODS Data from 5 large clinical trials of schizophrenia ( n=3483 ) were examined separately . Patients were aggregated into groups based on their final study visit . Group mean Positive and Negative Syndrome Scale ( PANSS ) total scores for each visit were computed and graphed . Change from baseline to end point for each group was computed and examined using ANCOVA . Cox regression modeling was used to examine baseline PANSS total and change as predictors of time to dropout . RESULTS In all 5 trials there was a statistically significantly relationship between time in trial and improvement . The longer the patients remained in the trial the more that they improved , with trial completers showing the most improvement at each time point . Higher baseline PANSS scores and symptom deterioration indicated by increased PANSS preceding the final study visit prior to dropout corresponded significantly with a greater likelihood of dropout . CONCLUSIONS Dropout in clinical trials of antipsychotic medications corresponds with efficacy outcomes , the dynamics of symptom change and baseline symptom severity . Therefore , methods for statistical analysis should examine both efficacy and dropout and can not assume that missing data due to dropout are completely at r and om The effect of two atypical antipsychotics on QTc intervals ( heart rate-corrected QT interval ) was evaluated . Patients ( N=109 ) with schizophrenia ( 79 % ) or schizoaffective disorder ( 21 % ) were r and omly assigned in 2 : 2 : 1 ratio to paliperidone extended release ( ER ) , quetiapine , or placebo . Doses of 12 and 18 mg/day of paliperidone ER were compared with quetiapine 800 mg/day . Least-squares mean change from baseline in population -specific linear-derived correction method from baseline to days 6–7 at individual tmax was 5.1 ms less [ 90 % confidence interval : −9.2 to −0.9 ] with paliperidone ER 12 mg/day than with quetiapine 800 mg/day . On the basis of a prespecified 10-ms noninferiority margin , paliperidone ER was thus declared noninferior to quetiapine ( primary analysis ) . Mean change in population -specific linear-derived correction method from baseline to days 11–12 at individual tmax was 2.3 ms less ( 90 % confidence interval : −6.8 to 2.3 ) with paliperidone ER 18 mg/day than with quetiapine 800 mg/day . Treatment-emergent adverse events occurred in 36 ( 82 % ) patients treated with paliperidone ER , 41 ( 95 % ) patients treated with quetiapine , and 14 ( 64 % ) patients treated with placebo . No adverse events of a proarrhythmic nature were noted . The effect on the QTc interval in patients with schizophrenia or schizoaffective disorder was comparable between paliperidone ER 12 mg/day ( maximum recommended dose ) , paliperidone ER 18 mg/day ( supratherapeutic dose ) , and quetiapine 800 mg/day Rationale Quetiapine is increasingly used for the treatment of patients with psychosis and bipolar disorder . However , the neurobiological mechanisms , which may account for the favourable risk/benefit profile of this drug , are not entirely understood . Objectives Transcranial magnetic stimulation was used to investigate the effects of acute and repeated administration of quetiapine on cortical excitability in healthy volunteers . Material s and methods Within a double-blind , placebo-controlled , r and omized cross-over design motor threshold , intracortical inhibition , intracortical facilitation and cortical silent period were studied in 15 healthy volunteers before and after a single dose of placebo and 100 mg quetiapine . Additional measurements were performed after 5 days of daily intake of 100 mg quetiapine . Results We observed a significant prolongation of the cortical silent period after a single dose of quetiapine , whereas the placebo had no effects . After repeated administration , there was a trend towards CSP prolongation , which did not reach significance . However , plasma concentrations at this time point were relatively low , as measurements were performed 15 h after the last drug intake . Other parameters of cortical excitability remained unaffected . Conclusions By lengthening CSP without affecting MT , ICI and ICF , quetiapine demonstrates a unique neurophysiological profile which differs distinctively from brain excitability profiles of typical antipsychotics such as haloperidol . Provided that the CSP prolongation reflects the antipsychotic potential of quetiapine , TMS may be developed as a tool to monitor neurobiological effects of quetiapine treatment in schizophrenic patients and to explore the efficacy of other antipsychotic drugs with a similar mode of action Rationale Increased activity of the hypothalamic – pituitary – adrenal ( HPA ) axis is an important aspect of the pathophysiology of major depression and schizophrenia . Despite the usefulness of atypical antipsychotics in the treatment of depression and their positive influence on cognitive functioning possibly related to their impact on cortisol , little is known about their effect on HPA axis function . Objective Therefore , this double-blind , placebo-controlled , r and omized cross-over study investigated the influence of the atypical antipsychotics quetiapine and olanzapine in comparison with haloperidol and placebo on plasma adrenocorticotropic hormone ( ACTH ) , cortisol , and prolactin levels . Eleven healthy male volunteers were studied during four sessions one week apart , orally receiving placebo , quetiapine ( 50 mg ) , olanzapine ( 5 mg ) , or haloperidol ( 3 mg ) . Blood sample s were taken at hourly intervals from 0900 until 1700 hours . For ACTH , cortisol , and prolactin a significant effect of treatment condition ( p≤0.005 ; p≤0.035 ; p≤0.0001 , respectively ) for area under the curve ( AUC ) was found . In comparison to placebo , quetiapine and olanzapine significantly reduced ACTH ( p≤0.002 ; p≤0.05 , respectively ) and cortisol ( p≤0.005 ; p≤0.03 , respectively ) . No effect of haloperidol on AUC of ACTH or cortisol levels was observed . In comparison with placebo , haloperidol ( p≤0.0001 ) and olanzapine ( p≤0.0001 ) elevated AUC of prolactin plasma levels , whereas no significant effect was observed for quetiapine as a main effect of treatment condition . The atypical antipsychotics ’ strong influence on HPA-function with pronounced ACTH and cortisol lowering is possibly related to the atypicals ’ blockade of serotonergic receptors , but blockade of adrenergic or histaminergic receptors may play a role as well . The observed HPA-axis down-regulation may be clinical ly important for the atypicals ’ effects on depressive symptomatology and cognitive functioning Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse . An open-label , r and omized , active-controlled , 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone , olanzapine , or conventional neuroleptics to risperidone long-acting injectable ( RLAI ) or oral quetiapine . Primary effectiveness evaluation was time-to-relapse . Safety evaluations included adverse events ( AEs ) reported for the duration of the study , Extrapyramidal Symptom Rating Scale ( ESRS ) , clinical laboratory tests , and vital signs . A total of 666 patients ( n=329 RLAI , n=337 quetiapine ) were evaluable for effectiveness measures . Baseline demographics were similar between treatment groups . Kaplan – Meier estimate of time-to-relapse was significantly longer with RLAI ( p<0.0001 ) . Relapse occurred in 16.5 % of patients with RLAI and 31.3 % with quetiapine . RLAI and quetiapine were both safe and well tolerated . Weight gain affected 7 % of patients with RLAI and 6 % with quetiapine , with mean end point increases of 1.25±6.61 and 0±6.55 kg , respectively . There were no significant between-group differences in weight gain . ESRS total scores decreased similarly after r and omization to either RLAI or quetiapine . Extrapyramidal AEs occurred in 10 % of patients with RLAI and 6 % with quetiapine . Treatment-emergent potentially prolactin-related AEs were reported in 15 ( 5 % ) patients with RLAI and 5 ( 2 % ) patients with quetiapine ; hyperprolactinemia was reported in 43 ( 13.1 % ) patients with RLAI and 5 ( 1.5 % ) patients with quetiapine . Somnolence occurred in 2 % of patients with RLAI and 11 % with quetiapine . To our knowledge , this is the first report of a r and omized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy . Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was significantly longer in patients r and omized to RLAI compared with those r and omized to oral quetiapine . Both antipsychotics were generally well tolerated OBJECTIVE Combining antipsychotics is common practice in the treatment of schizophrenia . This study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and schizoaffective disorder . METHOD In this multicenter , double-blind , 16-week , placebo-controlled study conducted at 43 American sites from July 2006 to October 2007 , patients with chronic , stable schizophrenia or schizoaffective disorder diagnosed with DSM-IV-TR were r and omly assigned to receive aripiprazole ( 2 - 15 mg/d ) or placebo in addition to a stable regimen of quetiapine ( 400 - 800 mg/d ) or risperidone ( 4 - 8 mg/d ) . The primary outcome measure was the mean change from baseline to endpoint ( week 16 , last observation carried forward ) in the Positive and Negative Syndrome Scale ( PANSS ) total score . RESULTS 323 subjects being treated with either risperidone ( n = 177 ) or quetiapine ( n = 146 ) were r and omly assigned to receive adjunctive aripiprazole ( n = 168 ) or placebo ( n = 155 ) . Baseline characteristics were similar ( mean PANSS total score : aripiprazole , 74.5 ; placebo , 75.9 ) except for history of suicide attempts ( aripiprazole , 27 % ; placebo , 40 % ) . Nearly 70 % of subjects in each arm completed the trial . Adjunctive aripiprazole and placebo groups were similar in the mean change from baseline to endpoint in the PANSS total score ( aripiprazole , -8.8 ; placebo , -8.9 ; P = .942 ) . The incidence of treatment-emergent adverse events was similar between groups . Mean changes in Simpson-Angus Scale , Abnormal Involuntary Movement Scale , and Barnes Akathisia Rating Scale scores were not statistically significantly different . Adjunctive aripiprazole was associated with statistically significantly greater decreases in mean serum prolactin levels from baseline than was adjunctive placebo ( -12.6 ng/mL for aripiprazole vs -2.2 ng/mL for placebo ; P < .001 ) , an effect that was seen in the risperidone subgroup ( -18.7 ng/mL vs -1.9 ng/mL ; P < .001 ) but not in the quetiapine subgroup ( -3.01 ng/mL vs + 0.15 ng/mL ; P = .104 ) . CONCLUSIONS The addition of aripiprazole to risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was generally safe and well tolerated . Further research is warranted to explore whether antipsychotic combination therapy offers benefits to particular patient population s-for example , in cases of hyperprolactinemia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00325689 We evaluated the effects of ICI 204,636 in 12 hospitalized patients with schizophrenia in a double-blind , placebo-controlled , parallel-group , rising-dose study . Patients met the Diagnostic and Statistical Manual of Mental Disorders , Third Edition , Revised criteria for chronic or subchronic schizophrenia and had a total score > or = 30 on the 18-item Brief Psychiatric Rating Scale ( BPRS ) and a score > or = 3 on the Clinical Global Impression ( CGI ) Severity of Illness item . Patients received 21 days of double-blind treatment with increasing doses of ICI 204,636 ( 25 to 250 mg/d ) or placebo . Efficacy was assessed using the BPRS and CGI . Response to treatment was defined as a > or = 30 % decrease in the BPRS total score from baseline . Extrapyramidal symptoms and abnormal involuntary movements were assessed using the Simpson Scale and Abnormal Involuntary Movement Scale . Changes from baseline in the BPRS and CGI were significantly greater at end point for patients who received ICI 204,636 versus placebo ( BPRS , -20.9 vs -4.8 ; CGI , -2.9 vs -1.0 ; P < 0.05 , analysis of covariance ; P < or = 0.06 , Wilcoxon rank sum test ) . All patients in the ICI 204,636 group responded to treatment ( P < 0.10 ) versus only two patients in the placebo group . Mild somnolence occurred in 50 % of ICI 204,636-treated patients . No treatment-emergent extrapyramidal symptoms or dystonic reactions were observed . ICI 204,636 showed efficacy in the positive and negative symptoms of schizophrenia and was well tolerated OBJECTIVE To demonstrate the efficacy of once-daily extended release quetiapine fumarate ( quetiapine XR ) versus placebo in adults with acute exacerbation of schizophrenia . METHODS A 6-week , double-blind , r and omized , placebo-controlled study . In- or out- patients with a DSM-IV diagnosis of schizophrenia were r and omized to fixed-dose quetiapine XR 400 , 600 , or 800 mg/day , quetiapine immediate release ( IR ) 800 mg/day , or placebo . Primary endpoint was change from baseline in Positive and Negative Syndrome Scale ( PANSS ) total score at Week 6 . Other efficacy assessment s included Clinical Global Impressions ( CGI ) of Severity ( CGI-S ) and of Improvement ( CGI-I ) ratings . Safety assessment s included adverse event ( AE ) reporting and laboratory measures . RESULTS 565 patients were r and omized ; 333 ( 58.9 % ) completed the study . Greater numeric improvements in PANSS total score were seen for quetiapine XR ( all doses ) and quetiapine IR versus placebo at Week 6 ; the differences were not statistically significant . Secondary efficacy endpoint results were similar . There was not a high placebo response in this study , but rather an attenuation of drug effect . In general , quetiapine XR was well tolerated over 6-weeks ' treatment ; there were no unexpected AEs . CONCLUSION The efficacy of quetiapine XR ( 400 , 600 , and 800 mg/day ) was not established at Week 6 . Quetiapine IR , an agent with established efficacy in schizophrenia , also did not separate from placebo at endpoint . Therefore , this is considered a failed study and possible reasons for this are discussed . Quetiapine XR was generally well tolerated and its safety profile was consistent with the known profile of quetiapine In this paper we investigate mortality in short-term placebo-controlled trials conducted to demonstrate efficacy and safety of atypical antipsychotic drugs for the treatment of schizophrenic patients in the acute phase of illness . Arguments are provided , why short-term placebo-controlled studies are required . This is an integrated analysis of results from r and omized placebo-controlled trials conducted pre-licensing for risperidone , olanzapine , quetiapine IR , ziprasidone , risperidone consta , aripiprazole , paliperidone , and quetiapine XR . Information was retrieved from study publications , EPAR , and from the FDA SBA , all in the public domain . 7553 patients were r and omized in the remaining 23 short-term acute phase clinical trials . 2/5738 patients died after having been r and omized to an active treatment . 5/1815 died in the placebo group . The crude odds-ratio for an increased death risk with placebo treatment is 7.92 ( 95 % confidence interval ( 1.45 to 40.87 ) , two sided P=0.0134 ) . Death narratives show : ( i ) both deaths in active treatment groups occurred during r and omized treatment period , ( ii ) two deaths in the placebo group of a trial in the elderly were observed in patients with severe co-morbidities not usually included in a r and omized trial , and ( iii ) two further deaths in the placebo groups occurred 9 and 23 days after the end of the r and omized treatment period . Under these circumstances the crude odds-ratio for an increased risk of death for patient with placebo as compared to active treatment is 1.58 ( 95 % confidence interval ( 0.14 - 17.45 ) , two sided P=0.71 ) . Confidence intervals are generally wide indicating a still limited knowledge about a potential increase in mortality with placebo treatment . Unless , however , society is willing to take the risk that ineffective drugs are licensed and cause undetected harm thereafter , or is willing to restrict licensing to drugs that are superior to current treatments , short-term placebo-controlled trials in the acute phase of schizophrenia are necessary . Measures are proposed to minimize risks BACKGROUND Quetiapine fumarate ( Seroquel [ ICI 204,636 ] ) is an atypical dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine2 ( 5-HT2 ) receptors than for D2 dopamine receptors ; its efficacy in patients with schizophrenia was shown in early phase 2 trials ( maximum dose , 750 mg/d ) . METHODS In this multicenter , double-blind , placebo-controlled trial , 286 patients hospitalized with chronic or subchronic schizophrenia ( DSM-III-R ) were r and omized to 6 weeks of treatment with high-dose quetiapine fumarate ( < or = 750 mg/d ) , n = 96 ; low-dose quetiapine fumarate ( < or = 250 mg/d ) , n = 94 ; or placebo , n = 96 . The Brief Psychiatric Rating Scale ( BPRS ) and Clinical Global Impression Severity of Illness item scores were the primary efficacy variables . Secondary efficacy variables included the BPRS positive-symptom cluster score , the Modified Scale for the Assessment of Negative Symptoms summary score ( United States only ) , and the total score from the negative scale of the Positive and Negative Syndrome Scale ( Europe only ) . Scores were analyzed using an analysis of covariance for change from baseline at end point with last observations carried forward . The model included baseline score ( covariate ) , center , and treatment . Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the Barnes Akathisia Scale ; abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale . Frequency distributions of grouped change-from-baseline scores were analyzed using chi 2 tests . RESULTS Of 280 patients in whom the efficacy of quetiapine was evaluated , 159 ( 42 % of those receiving high-dose treatment ; 57 % , low-dose treatment ; and 59 % , placebo ) withdrew before trial completion , primarily because of treatment failure . Significant ( P < .001 , BPRS ; P = .003 , Clinical Global Impression Severity of Illness item ; and P = .003 , BPRS positive-symptom cluster ) differences were identified between patients receiving high-dose quetiapine and placebo for both primary efficacy variables , with end point differences in the BPRS positive-symptom cluster score showing quetiapine 's consistency in reducing positive symptoms . The reduction of negative symptoms was less consistent ; high-dose quetiapine was superior on the Modified Scale for the Assessment of Negative Symptoms but not on the negative scale of the Positive and Negative Syndrome Scale . Quetiapine was well tolerated and did not induce extrapyramidal symptoms , sustained elevations of prolactin , or clinical ly significant changes in hematologic parameters . CONCLUSIONS Quetiapine is an effective antipsychotic with a favorable safety profile . The optimum dose is probably greater than 250 mg/d IT IS A commonly accepted notion among some clinicians and most clinical investigators that the doctors ' belief system , ie , his conviction as to the efficacy of his treatment and the treatability of his patient , can influence the outcome of treatment . 1 - 4 Despite some notes of reservation 5 the double-blind design has been considered an adequate means of controlling the effect of the doctors ' belief system on outcome . 6 - 8 While it may be true that the double-blind keeps the doctor in the dark , it by no means guarantees a state of clinical neutrality and intellectual stasis . The double-blind design can not stop the doctor from attempting to guess which active agent his patient is receiving , or if his patient is receiving an active agent at all . The doctors ' guess may thus introduce a systematic bias which can nullify the intent of the double-blind design . This double-blind , double-dummy study ( D1444C00146 ) evaluated the efficacy and safety of switching patients with clinical ly stable schizophrenia from quetiapine immediate release ( IR ) to the same dose of once-daily extended release quetiapine fumarate ( quetiapine XR ) . Patients received quetiapine IR 400–800 mg/day twice daily for 4 weeks , and were then r and omized ( 2 : 1 ) to a once-daily equivalent dose of quetiapine XR or maintained on IR for 6 weeks . The primary variable was the proportion of patients who discontinued treatment owing to lack of efficacy or whose Positive and Negative Syndrome Scale scores increased by at least 20 % from r and omization to any visit . In total , 497 patients were r and omized to quetiapine XR ( n=331 ) or IR ( n=166 ) . Noninferiority ( 6 % margin ; one-sided test , 2.5 % significance level ) was narrowly missed for the primary efficacy variable for the modified intention-to-treat population ( 9.1 % , quetiapine XR ; 7.2 % , quetiapine IR ; difference 1.86 % ; 95 % confidence interval : −3.78 , 6.57 ; P=0.0431 ) , but was shown for the per- protocol population ( 5.3 % , quetiapine XR ; 6.2 % , quetiapine IR ; difference : −0.83 % ; 95 % confidence interval : −6.75 , 3.71 ; P=0.0017 ) . Serious adverse event incidence was low for quetiapine XR and IR ; there were no unexpected adverse events . In conclusion , efficacy was maintained without compromising safety/tolerability when switching patients with stable schizophrenia from twice-daily quetiapine IR to once-daily quetiapine XR ( 400–800 mg/day ) Background : Persistent neuroleptic-induced movement disorders limit effective pharmacological management of psychotic disorders . Although antipsychotic switching is a common strategy for managing extrapyramidal side effects ( EPSs ) , there is insufficient empirical support to guide the clinician . We design ed the present study to examine whether patients with preexisting EPS switched to quetiapine would show greater reduction in EPS compared with control patients . Methods : Twenty-two patients with schizophrenia meeting clinical criteria for tardive dyskinesia or coexisting parkinsonism were r and omized either to switch from their current antipsychotic to quetiapine ( n = 13 ) or to remain on their current treatment ( n = 9 ) . A battery of st and ard clinical assessment s for EPS along with electromechanical instrumental measures was administered before r and omization and again 1 and 3 months postr and omization . Results : We observed significant reduction in parkinsonism ( P < 0.001 ) and akathisia ( P = 0.02 ) based on clinical assessment s and dyskinesia ( P < 0.05 ) based on instrumental assessment for the quetiapine group . Subjects remaining on current treatment exhibited an increase in rigidity ( P < 0.05 ) based on instrumental measures . Conclusions : These findings support the switching to quetiapine in the management of preexisting neuroleptic-induced extrapyramidal side effects INTRODUCTION Symptom amelioration in older patients with very late onset schizophrenia-like psychosis ( VLOSLP ) is often difficult , with limited psychotropic response reports yielding variable findings . Information about atypical ( second generation ) antipsychotic use in this population is scant . METHODS A consecutive sample of geriatric psychiatry out patients and in patients with psychotic disorders were retrospectively identified over a 31-month period based on systematic information abstract ion from an electronic medical record ( e-record ) . After exclusion criteria were applied , 8/138 out patients and 13/362 in patients met inclusion criteria for VLOSLP and had been naturalistically treated with an atypical antipsychotic during hospitalization or nine months of outpatient care . M and atorily completed e-record st and ardized symptom severity response ratings were converted into positive treatment response thresholds . RESULTS 38 % of out patients and 77 % of in patients ( mean age = 76 years for both groups ; mean age of onset of psychosis = 70 years for out patients and 74 years for in patients ) met criteria for positive treatment response to an atypical antipsychotic ( either aripiprazole , olanzapine , quetiapine , or risperidone ) with sign/symptom amelioration , rather than eradication . CONCLUSIONS Various atypical antipsychotics at geriatric doses yielded a positive treatment response in nearly two-thirds of VLOSLP patients . Patients with less chronic , more severe symptoms responded at a higher rate . Prospect i ve , double-blind , placebo-controlled trials with representative subject sample s are needed to vali date these preliminary findings Five fixed doses of the atypical antipsychotic " Seroquel " ( quetiapine ) were evaluated to delineate a dose-response relationship , as measured by changes from baseline in Brief Psychiatric Rating Scale ( BPRS ) , Clinical Global Impression ( CGI ) , and Modified Scale for the Assessment of Negative Symptoms ( SANS ) summary scores , and to compare efficacy and tolerability opposite placebo and haloperidol . Three hundred sixty-one patients from 26 North American centers entered this double-blind , placebo-controlled trial with acute exacerbation of chronic schizophrenia ( DSM-III-R ) . Patients who completed a single-blind , placebo washout phase were r and omized to double-blind treatment with quetiapine ( 75 , 150 , 300 , 600 , or 750 mg daily ) , haloperidol ( 12 mg daily ) , or placebo and evaluated weekly for 6 weeks . At end point , significant differences ( p < 0.05 , analysis of covariance ) in adjusted mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total , BPRS positive-symptom cluster , and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score . Differences between quetiapine and haloperidol were not significant . Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables . Notably , no significant safety concerns were identified as dose increased . Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations . Quetiapine is well tolerated and clinical ly effective in the treatment of schizophrenia . It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day OBJECTIVE The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization . METHOD In a 6-week double-blind study , in patients with a recent exacerbation of schizophrenia were r and omly assigned to treatment with paliperidone extended-release , quetiapine , or placebo . A 2-week monotherapy phase was followed by a 4-week additive-therapy phase . Target doses were at the upper end of recommended ranges : paliperidone extended-release , 9 or 12 mg/day , and quetiapine , 600 or 800 mg/day . The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale ( PANSS ) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint . RESULTS Six-week completion rates were 77.5 % ( 124/160 ) with paliperidone extended-release , 66.7 % ( 106/159 ) quetiapine , and 63.8 % ( 51/80 ) placebo . Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 ( -11.4 versus -8.2 ) through the monotherapy phase endpoint ( -23.4 versus -17.1 ) . Only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks . At the 6-week study endpoint , there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy ( predominantly other antipsychotics ) . Common adverse events with paliperidone extended-release , quetiapine , and placebo , respectively , were tremor ( 13.9 % , 5.0 % , 7.5 % ) , somnolence ( 8.9 % , 11.9 % , 1.3 % ) , insomnia ( 10.1 % , 9.4 % , 11.3 % ) , and headache ( 12.0 % , 7.5 % , 13.8 % ) . Six-week adverse event-related discontinuation rates were 6.3 % , 10.1 % , and 6.3 % , respectively , in the paliperidone extended-release , quetiapine , and placebo groups . CONCLUSIONS Compared with quetiapine , paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization , with no unexpected tolerability findings ABSTRACT Objective : The use of adjunctive psychotropics and the costs of polypharmacy in patients r and omized to receive risperidone or quetiapine were compared in a placebo-controlled double-blind study conducted in India , Romania , and the United States . Methods : The efficacy and safety of risperidone , quetiapine , and placebo were compared in a 14-day monotherapy phase in patients experiencing an acute exacerbation of symptoms of schizophrenia or schizoaffective disorder . This was followed by a 28-day , additive-therapy phase during which addition of antipsychotics or other psychotropic medications was permitted . Risperidone was received by 153 patients in the monotherapy phase and 133 in the additive therapy phase , quetiapine by 156 and 122 , respectively , and placebo by 73 and 53 . Rates of polypharmacy were examined using the Cochran – Mantel – Haenszel , Kaplan – Meier , and Cox regression methods . Costs of polypharmacy were analyzed by nonparametric Wilcoxon 2- sample tests . Results : Primary study results have been reported elsewhere ( Potkin et al. , Schizophr Res 2006;85:254 - 65 ) . Mean ( ±SD ) doses at the additive-therapy baseline were 4.7 ± 0.9 mg/day of risperidone and 579.0 ± 128.9 mg/day of quetiapine . Additional psychotropics were received by 36 % of the risperidone group , 58 % of the quetiapine group ( p < 0.01 ) , and by 58 % of the placebo group . Antipsychotics accounted for > 95 % of the added psychotropics , the most common being olanzapine and haloperidol . The relative risk ( quetiapine vs. risperidone ) for antipsychotic polypharmacy was 1.90 ( p = 0.001 ; 95 % CI 1.29 , 2.80 ) . The mean projected cost of additional antipsychotics per r and omized patient during the additive-therapy phase was $ 57.03 in the risperidone group and $ 101.64 in the quetiapine group ( p < 0.01 ) . Conclusions : The results confirm earlier reports of higher rates of polypharmacy with quetiapine than with risperidone . The findings also reveal substantial between-treatment differences in costs associated with polypharmacy . Limitations of the study include that the study was of short duration and that a high proportion of patients were recruited from countries other than the United States Objective : To compare the efficacy and adverse effect profiles of 2 widely used atypical antipsychotics in the short-term phase of first-episode schizophrenia in patients who were treatment-naive . A secondary objective was to establish the effective dose of these drugs in this context . Methods : A total of 72 patients with a first episode of schizophreniform psychosis ( schizophrenia spectrum disorder ) with less than 2 weeks of exposure to antipsychotic medication were r and omized to quetiapine or risperidone in a single-blind 12-week controlled trial . Psychopathologic diagnoses and adverse effects were assessed by blinded raters at 4 weekly intervals . Medication was administered by a specialized clinical team following dosing guidelines . Data were analyzed using an intention-to-treat paradigm . Results : Both quetiapine and risperidone were associated with a reduction in immediate symptoms and relatively few adverse effects other than weight gain . There was no statistically significant difference between the 2 compounds in adverse effects , relative efficacies , or adherence to treatment . The median ( SD ) time to cessation for patients r and omized to quetiapine was 65.3 ( 41.85 ) days and that for risperidone was 82.5 ( 44.88 ) days . There was no statistically significant difference between time to discontinuation for the 2 compounds . The mean daily doses prescribed were 375 mg of quetiapine and 2.72 mg of risperidone . Conclusions : Quetiapine and risperidone are both effective treatments in first-episode schizophrenia at doses lower than those used in patients with long-term schizophrenia and are similar in efficacy and the incidence of adverse effects ICI 204,636 is a new , potentially atypical antipsychotic . In early phase II trials , the antipsychotic was well tolerated and results suggested efficacy in the treatment of the positive and negative symptoms of schizophrenia . The efficacy and safety of ICI 204,636 were evaluated on a larger scale in a 6-week , multicenter , double-blind trial . Hospitalized patients who met DSM-III-R criteria for chronic or subchronic schizophrenia with acute exacerbation , as well as other criteria , were r and omized to ICI 204,636 ( 75 to 750 mg daily ) ( N = 54 ) or placebo ( N = 55 ) . Patients were assessed weekly by use of the Brief Psychiatric Rating Scale ( BPRS ) , Scale for the Assessment of Negative Symptoms ( SANS ) , and Clinical Global Impression Scale ( CGI ) for efficacy and the Simpson Scale and Abnormal Involuntary Movement Scale for extrapyramidal side effects ( EPS ) . Significant differences ( p < or = 0.05 ) between treatment groups , which favored ICI 204,636 , were identified throughout the trial . Endpoint differences were significant ( by analysis of covariance ) for BPRS factor IV ( activation ) and SANS scores and were marginally significant for total BPRS , BPRS factor III ( thought disturbance ) , BPRS positive-symptom cluster , and CGI Severity of Illness item scores ( p = 0.07 , 0.09 , 0.06 , and 0.09 , respectively ) . ICI 204,636 was well tolerated , although it was associated with mild transient increases in alanine aminotransferase and a higher incidence of somnolence and anticholinergic effects compared with placebo . In the dose range studied , treatment with ICI 204,636 did not induce EPS as determined by analysis of Simpson Scale total scores and lack of treatment-emergent acute dystonic reactions . Furthermore , ICI 204,636 did not produce sustained levels of prolactin ; the mean change from baseline at endpoint ( -7.2 micrograms/L ) was comparable ( p = 0.44 ) to that for placebo ( -8.2 micrograms/L ) . These findings distinguish ICI 204,636 from st and ard antipsychotics and confirm pre clinical predictions that ICI 204,636 is an atypical antipsychotic Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment . Design 12 month r and omised , double blind , placebo controlled trial . Setting Early psychosis outpatient clinics in Hong Kong . Participants 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis . Interventions Patients received either maintenance treatment with quetiapine ( 400 mg/day ) or placebo and were followed up for the next 12 months or until a relapse occurred . Main outcome measure Relapse assessed monthly and defined as re-emergence of psychotic symptoms ( delusions , conceptual disorganisation , hallucinations , suspiciousness , and unusual thought content ) according to predefined thresholds . Results 178 patients were r and omised ( 89 to quetiapine and 89 to placebo ) . The Kaplan-Meier estimate of the risk of relapse at 12 months was 41 % ( 95 % confidence interval 29 % to 53 % ) for the quetiapine group and 79 % ( 68 % to 90 % ) for the placebo group ( P<0.001 ) . Although quetiapine was generally well tolerated , the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group ( 18 % ; 16/89 ) than in the placebo group ( 8 % ; 7/89 ) ( relative risk 2.29 , 95 % confidence interval 0.99 to 5.28 ; χ2=3.20 , df=1 ; P=0.07 ) . Conclusion In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment , maintenance treatment with quetiapine compared with placebo result ed in a substantially lower rate of relapse during the following year . Trial registration Clinical trials NCT00334035 Objective : The objective of this study was to report the long-term remission results from the ConstaTRE relapse prevention trial , in which clinical ly stable adults with schizophrenia or schizoaffective disorder treated with oral risperidone , olanzapine , or oral conventional antipsychotics were r and omized to risperidone long-acting injectable ( RLAI ) or oral quetiapine , dosed according to package-insert recommendations . Methods : In the ConstaTRE trial , efficacy and tolerability were recorded for up to 24 months . This post hoc analysis presents remission data , defined , according to the Schizophrenia Working Group criteria , as achieving and maintaining eight core symptoms of schizophrenia that are mild or less over 6 months . Additional secondary outcome measures are also presented . Results : A total of 710 patients were r and omized to RLAI ( n = 355 ) or quetiapine ( n = 355 ) . Mean mode ± st and ard deviation ( SD ) drug doses were RLAI 33 ± 10 mg every 2 weeks and quetiapine 413 ± 159 mg daily . Full remission was achieved by 51.1 % of patients with RLAI and 39.3 % with quetiapine ( p = 0.003 ) . Mean ± SD of full remission duration s were not significantly different with RLAI ( 540 ± 181 days ) and quetiapine ( 508 ± 188 days ) . Overall tolerability was similar between treatment groups . Conclusions : Among stable patients with schizophrenia or schizoaffective disorder , remission was more likely after switching to RLAI than quetiapine Missing outcome data is a major threat in meta-analytical studies of schizophrenia . Most clinical trials in psychiatry report only continuous outcome measures and express the effect of an intervention as a difference of means . However , these results are difficult to interpret for clinicians . Converting continuous data to binary response rates is one possible solution to the problem . Based on means and st and ard deviations for a continuous outcome , we examined the performance of an imputation method to define a dichotomous outcome using original individual patients ' data from 16 r and omized trials ( 6276 participants ) comparing antipsychotic drugs in schizophrenia . We concluded that the imputed values re-captured in a reasonable degree the observed values providing a simple and practical alternative method ological choice for imputation of missing binary data in schizophrenia trials ; nevertheless , the imputation method tended to introduce biases , especially for extreme risks and large treatment differences INTRODUCTION This long-term , r and omized , double-blind , placebo-controlled study examined the efficacy of extended release quetiapine fumarate ( quetiapine XR ) in preventing psychotic relapse in schizophrenia . METHODS Three hundred twenty-seven clinical ly stable patients with schizophrenia were switched to open-label quetiapine XR ( 300 mg on Day 1 , 600 mg on Day 2 , followed by flexible dosing [ 400 - 800mg/day ] ) for a 16-week stabilization phase . Thereafter , patients who were clinical ly stable for four months were r and omized to flexible doses of quetiapine XR ( 400 - 800mg/day ) or placebo . Primary endpoint was time to first schizophrenia relapse after r and omization . Secondary endpoints included risk of relapse at six months . Interim analyses were planned after 45 and 60 relapses and final analysis after 90 relapses . Maximal treatment time was one year . RESULTS The study was terminated after the first interim analysis showed a significant difference between r and omized treatment groups . Time to relapse was significantly longer in quetiapine XR-treated patients versus placebo ( hazard ratio 0.16 [ 95 % confidence interval 0.08 , 0.34 ] ; p=0.001 ) . Fewer quetiapine XR-treated patients relapsed versus those receiving placebo ( 10.7 % vs. 41.4 % , respectively ) . Estimated risk of relapse at six months was significantly lower with quetiapine XR ( 14.3 % ) compared with placebo ( 68.2 % ; p=0.0001 ) . The incidence of treatment-related adverse events ( AEs ) was similar between quetiapine XR and placebo groups ( 18 % and 21 % of patients , respectively ) and only one percent of patients in each group withdrew because of AEs . CONCLUSION Once-daily quetiapine XR ( 400 - 800mg/day ) was effective in preventing relapse in patients with clinical ly stable schizophrenia . Quetiapine XR was well tolerated during longer-term use Objective . The purpose of this investigation was to assess the cognitive effects of adjuvant hormone replacement therapy ( HRT ) when used to treat premenopausal women with chronic schizophrenia using an 8-week , double-blind , placebo-controlled , r and omized trial . Method . Women of childbearing age with chronic schizophrenia were recruited and r and omized into placebo and HRT groups , the latter of which was administered 0.625 mg of conjugated oestrogen with 2.5 mg of medroxyprogesterone acetate daily . Each group contained 14 subjects . The principal outcome measure was a cognitive function assessment comprised of the following ; the Immediate Visual Recognition Scale , List Recall Scale , Oral Fluency Test , Trail-Making Tests A and B , and Digit Symbol Test . Psychopathology was measured using the Scale for the Assessment of Negative Symptoms ( SANS ) and the Calgary Depression Scale for Schizophrenia . Extrapyramidal symptoms were evaluated using the Drug-Induced Extra-Pyramidal Symptoms Scale . Results . Improvements in SANS and in cognitive function as assessed using the List Recall Scale , Oral Fluency Test , and Trail-Making Test A , were significantly greater in the HRT group than in the placebo group . Conclusion . The results of this study suggest that short-term HRT is an effective adjuvant modality for improving cognitive function in women of childbearing age with chronic schizophrenia The gold st and ard for evidence in psychiatry , as elsewhere in medicine , is often considered to be the r and omized , placebo-controlled , double-blind study . The use of blinding or masking plays a key role in these design s by addressing the problem of expectancy . First , if participants anticipate greater benefit from a particular treatment , they may be more likely to respond to it , which is considered a component of placebo response . Not surprisingly , participants have been found to report greater anticipated benefits when they were r and omized to enter an active-comparator , versus a placebo-comparator , study ( 1 ) . Likewise , raters may anticipate greater benefit from active drug and thus favor it in their ratings , whether consciously or unconsciously . Greater response rates in both active and placebo arms occur when a greater proportion of participants receive active treatment — that is , when patients ( 1 ) or raters ( 2 ) expect more participants to benefit . Double-blinding , typically by providing drug and placebo in identical capsules , is intended to minimize the impact of expectancy and the related concept of credibility . The blind may be compromised in a variety of ways , however , beginning with differences in medication taste or smell . Of particular concern may be the emergence of adverse effects , particularly when those adverse effects are known to be associated with a specific medication . The requirement that informed consent forms delineate common adverse effects may increase this risk ( 3 ) . Indeed , when the degree of unblinding is assessed in antidepressant trials , multiple reports suggest that it is extensive : at least three-quarters of patients are typically able to correctly guess at their treatment assignment ( 4 , 5 ) . Moreover , even the sudden absence of adverse effects may contribute to unblinding , as might occur when a participant stabilized on a sedating medication is abruptly switched to placebo at r and omization in a relapse-prevention study . If such unblinding occurs , does it meaningfully affect trial results ? A meta- analysis of antidepressant trials using active placebos , such as those with antihistaminergic or anticholinergic effects , suggested smaller effect sizes than those observed in the presumably less blinded trials with inert placebo ( 6 ) . Estimating the potential impact in published studies is difficult , but certain findings when results are stratified by potentially unblinding adverse effects raise concern . In a trial of quetiapine in bipolar depression ( 7 ) , for example , when investigators examined only the groups reporting sedation , mean change in the Montgomery-Åsberg Depression Rating Scale total score at week 8 was -18.8 in the quetiapine groups ( N=195 ) and -18.9 in the placebo group ( N=24 ) . Conversely , when the subset of participants without sedation were examined , the mean change in the Montgomery-Åsberg Depression Rating Scale total score was -19.3 and -11.7 in the quetiapine and placebo groups , respectively . While only a small subset of patients were in the placebo/sedation arm , the disparity in placebo response might suggest that clinical raters were attempting to “ guess ” at treatment assignment . Unfortunately , for psychotropic drugs , CNS side effects may be inevitable . Therefore , we call for more uniform application of st and ards in the design , reporting , and review of clinical trials . 1 . Consistent with CONSORT ( 8) and international guidelines ( 9 ) , participants and raters should be asked to guess treatment assignment , and the degree of true and false unblinding should be reported in the primary publication of results . Statistical |
11,809 | 27,460,637 | Exercise seems beneficial in reducing oedema volume in BCRL .
IPC seems beneficial in helping to reduce the oedema volume in the acute phase of treatment .
Compression sleeves do not aid in the volume reduction in the acute phase ; however , they do prevent additional swelling | The aim of the present study was to evaluate the effects of compression b and ages , sleeves , intermittent pneumatic compression ( IPC ) and active exercise on the reduction of breast cancer-related lymphoedema ( BCRL ) . | Goals of workThe purpose of this study is to compare the treatment and retention effects between st and ard decongestive lymphatic therapy ( DLT ) combined with pneumatic compression ( PC ) and modified DLT , in which the use of a short-stretch b and age is replaced with the use of Kinesio tape ( K-tape ) combined with PC . Material s and methods Forty-one patients with unilateral breast-cancer-related lymphedema for at least 3 months were r and omly grouped into the DLT group ( b and age group , N = 21 ) or the modified DLT group ( K-tape group , N = 20 ) . Skin care , 30-min manual lymphatic drainage , 1-h pneumatic compression therapy , application of a short-stretch b and age or K-tape for each group , and a 20-min physical therapy exercise were given during every treatment session . Patient evaluation items included physical therapy assessment , limb size , water composition of the upper extremity , lymphedema-related symptoms , quality of life , and patients ’ acceptance to the b and age or tape . Main results There was no significant difference between groups in all outcome variables ( P > 0.05 ) through the whole study period . Excess limb size ( circumference and water displacement ) and excess water composition were reduced significantly in the b and age group ; excess circumference and excess water composition were reduced significantly in the tape group . The acceptance of K-tape was better than the b and age , and benefits included longer wearing time , less difficulty in usage , and increased comfort and convenience ( P < 0.05 ) . Conclusions The study results suggest that K-tape could replace the b and age in DLT , and it could be an alternative choice for the breast-cancer-related lymphedema patient with poor short-stretch b and age compliance after 1-month intervention . If the intervention period was prolonged , we might get different conclusion . Moreover , these two treatment protocol s are inefficient and cost time in application . More efficient treatment protocol is needed for clinical practice BACKGROUND Lymphedema following breast cancer treatment is one of the most morbid conditions affecting breast cancer survivors . Currently , no therapy completely cures this condition . Comprehensive Decongestive Therapy ( CDT ) , a novel physiotherapeutic method offers promising results in managing this condition . This therapy is being widely used in the West . Till date , there are no studies evaluating the effectiveness and feasibility of this therapy in the east . MATERIAL S AND METHODS The therapeutic responses of 25 patients with postmastectomy lymphedema were analyzed prospect ively in this study . Each patient received an intensive phase of therapy for eight days from trained physiotherapists , which included manual lymphatic drainage , multi layered compression b and aging , exercises , and skin care . Instruction in self management techniques were given to the patients on completion of intensive therapy . The patients were followed up for three months . Changes in the volume of the edematous limb were assessed with a geometric approximation derived from serial circumference measurements of the limb and by water displacement volumetry . Changes in skin and sub cutis thickness were assessed using high frequency ultrasound . RESULTS The reduction in limb volume observed after therapy was 32.3 % and 42 % of the excess , by measurement and volumetry , respectively . The maximum reduction was obtained after the intensive phase . The reduction in skin and subcutis thickness of the edematous limb followed the same pattern as volume reduction . Patients could maintain the reduction obtained by strictly following the protocol s of the maintenance phase . CONCLUSIONS CDT combined with long-term self management is effective in treating post mastectomy lymphedema . The tropical climate is a major factor limiting the regular use of b and ages by the patients Background Women who develop secondary arm lymphoedema subsequent to treatment associated with breast cancer require life-long management for a range of symptoms including arm swelling , heaviness , tightness in the arm and sometimes the chest , upper body impairment and changes to a range of parameters relating to quality of life . While exercise under controlled conditions has had positive outcomes , the impact of yoga has not been investigated . The aim of this study is to determine the effectiveness of yoga in the physical and psycho-social domains , in the hope that women can be offered another safe , holistic modality to help control many , if not all , of the effects of secondary arm lymphoedema . Methods and design A r and omised controlled pilot trial will be conducted in Hobart and Launceston with a total of 40 women receiving either yoga intervention or current best practice care . Intervention will consist of eight weeks of a weekly teacher-led yoga class with a home-based daily yoga practice delivered by DVD . Primary outcome measures will be the effects of yoga on lymphoedema and its associated symptoms and quality of life . Secondary outcome measures will be range of motion of the arm and thoracic spine , shoulder strength , and weekly and daily physical activity . Primary and secondary outcomes will be measured at baseline , weeks four , eight and a four week follow up at week twelve . Range of motion of the spine , in a self-nominated group , will be measured at baseline , weeks eight and twelve . A further outcome will be the women ’s perceptions of the yoga collected by interview at week eight . Discussion The results of this trial will provide information on the safety and effectiveness of yoga for women with secondary arm lymphoedema from breast cancer treatment . It will also inform methodology for future , larger trials . Trial registration The incidence of breast cancer (BC)‐related lymphedema ( LE ) ranges from 7 % to 47 % . Successful management of LE relies on early diagnosis using sensitive measurement techniques . In the current study , the authors demonstrated the effectiveness of a surveillance program that included preoperative limb volume measurement and interval postoperative follow‐up to detect and treat sub clinical LE Objective : To compare the long-term efficacy of pneumatic compression and low-level laser therapies in the management of postmastectomy lymphoedema . Design : R and omized controlled trial . Setting : Department of Physical Medicine and Rehabilitation of Cukurova University , Turkey . Subjects : Forty-seven patients with postmastectomy lymphoedema were enrolled in the study . Interventions : Patients were r and omly allocated to pneumatic compression ( group I , n=24 ) and low-level laser ( group II , n=23 ) groups . Group I received 2 hours of compression therapy and group II received 20 minutes of laser therapy for four weeks . All patients were advised to perform daily limb exercises . Main measures : Demographic features , difference between sum of the circumferences of affected and unaffected limbs ( ▵ C ) , pain with visual analogue scale and grip strength were recorded . Results : Mean age of the patients was 48.3 ( 10.4 ) years . ▵ C decreased significantly at one , three and six months within both groups , and the decrease was still significant at month 12 only in group II ( P = 0.004 ) . Improvement of group II was greater than that of group I post treatment ( P = 0.04 ) and at month 12 after 12 months ( P = 0.02 ) . Pain was significantly reduced in group I only at posttreatment evaluation , whereas in group II it was significant post treatment and at follow-up visits . No significant difference was detected in pain scores between the two groups . Grip strength was improved in both groups , but the differences between groups were not significant . Conclusions : Patients in both groups improved after the interventions . Group II had better long-term results than group I. Low-level laser might be a useful modality in the treatment of postmastectomy lymphoedema We examined the effects of low stretch compression b and aging ( CB ) alone or in combination with manual lymph drainage ( MLD ) in 38 female patients with arm lymphedema after treatment for breast cancer . After CB therapy for 2 weeks ( Part I ) , the patients were allocated to either CB or CB + MLD for 1 week ( Part II ) . Arm volume and subjective assessment s of pain , heaviness and tension were measured . The mean lymphedema volume reduction for the total group during Part I was 188 ml ( p < 0.001 ) , a mean reduction of 26 % ( p < 0.001 ) . During Part II the volume reduction in the CB + MLD group was 47 ml ( p < 0.001 ) and in CB group 20 ml . These differences were not significant ( p = 0.07 ) . A percentage reduction of 11 % ( p < 0.001 ) in the CB + MLD group and 4 % in the CB group was significantly different ( p = 0.04 ) . In both the CB and the CB + MLD group , a decrease of feeling of heaviness ( p < 0.006 and p < 0.001 , respectively ) and tension ( p < 0.001 for both ) in the arm was found , but only the CB + MLD group showed decreased pain ( p < 0.03 ) . Low stretch compression b and aging is an effective treatment giving volume reduction of slight or moderate arm lymphedema in women treated for breast cancer . Manual lymph drainage adds a positive effect We compared manual lymph drainage ( MLD ) with sequential pneumatic compression ( SPC ) for treatment of unilateral arm lymphedema in 28 women previously treated for breast cancer . After 2 weeks of therapy with a st and ard compression sleeve ( Part I ) with maintenance of a steady arm volume , each patient was r and omly assigned to either one of two treatment regimens ( Part II ) . MLD was performed according to the Vodder technique for 45 min/day and SPC was performed with a pressure of 40 - 60 mmHg for 2 hours/day . Both treatments were carried out for 2 weeks . Arm volume was measured by water displacement . Arm mobility , strength , and subjective assessment s were also determined . Lymphedema was reduced by 49 ml ( 7 % reduction ) ( p = 0.01 ) in the total group during Part I. During Part II , the MLD group decreased by 75 ml ( 15 % reduction ) ( p < 0.001 ) and the SPC group by 28 ml ( 7 % reduction ) ( p = 0.03 ) . The total group reported a decrease of tension ( p = 0.004 ) and heaviness ( p = 0.01 ) during Part I. During Part II , only the MLD group reported a further decrease of tension ( p = 0.01 ) and heaviness ( p = 0.008 ) . MLD and SPC each significantly decreased arm volume but no significant difference was detected between the two treatment methods Lymphedema is a chronic and progressive long-term adverse effect of breast cancer treatment commonly defined by swelling of the affected arm . Current clinical guidelines indicate that women with and at risk for lymphedema should protect the affected arm from overuse . In clinical practice , this often translates into risk aversive guidance to avoid using the arm . This could lead to a disuse pattern that may increase the likelihood of injury from common activities of daily living . Further , such guidance poses an additional barrier to staying physically active , potentially translating to weight gain , which has been shown to be associated with worse clinical course for women with lymphedema . We hypothesize that a program of slowly progressive strength training with no upper limit on the amount of weight that may be lifted would gradually increase the physiologic capacity of the arm so that common activities represent a decreasing percentage of maximal capacity . Theoretically , this increased capacity should decrease the risk that daily activities put stress on the lymphatic system of the affected side . The Physical Activity and Lymphedema ( PAL ) Trial is a recently completed r and omized controlled exercise intervention trial that recruited 295 breast cancer survivors ( 141 with lymphedema at study entry , 154 at risk for lymphedema at study entry ) . The purpose of this report is to provide detail regarding the study design , statistical design , and protocol of the PAL trial Background Secondary arm lymphoedema continues to affect at least 20 % of women after treatment for breast cancer requiring lifelong professional treatment and self-management . The holistic practice of yoga may offer benefits as an adjunct self-management option . The aim of this small pilot trial was to gain preliminary data to determine the effect of yoga on women with stage one breast cancer-related lymphoedema ( BCRL ) . This paper reports the results for the primary and secondary outcomes . Methods Participants were r and omised , after baseline testing , to receive either an 8-week yoga intervention ( n = 15 ) , consisting of a weekly 90-minute teacher-led class and a 40-minute daily session delivered by DVD , or to a usual care wait-listed control group ( n = 13 ) . Primary outcome measures were : arm volume of lymphoedema measured by circumference and extra-cellular fluid measured by bioimpedance spectroscopy . Secondary outcome measures were : tissue in duration measured by tonometry ; levels of sensations , pain , fatigue , and their limiting effects all measured by a visual analogue scale ( VAS ) and quality of life based on the Lymphoedema Quality of Life Tool ( LYMQOL ) . Measurements were conducted at baseline , week 8 ( post-intervention ) and week 12 ( four weeks after cessation of the intervention ) . Results At week 8 , the intervention group had a greater decrease in tissue in duration of the affected upper arm compared to the control group ( p = 0.050 ) , as well as a greater reduction in the symptom sub-scale for QOL ( p = 0.038 ) . There was no difference in arm volume of lymphoedema or extra-cellular fluid between groups at week 8 ; however , at week 12 , arm volume increased more for the intervention group than the control group ( p = 0.032 ) . Conclusions An 8-week yoga intervention reduced tissue in duration of the affected upper arm and decreased the QOL sub-scale of symptoms . Arm volume of lymphoedema and extra-cellular fluid did not increase . These benefits did not last on cessation of the intervention when arm volume of lymphoedema increased . Further research trials with a longer duration , higher levels of lymphoedema and larger numbers are warranted before definitive conclusions can be made Background Breast-cancer-related lymphoedema , either caused by the tumour itself or its therapy , can be found in approximately 24 % of all patients . It results in disabilities , psychological distress and reduced quality of life . Therefore , proper therapy for this entity is very important . Guidelines recommend a therapy in two phases , an intensive phase I for 3 weeks for volume reduction and , between the cycles of phase I , a reduced phase II to maintain the result . During phase I therapy , manual lymphatic drainage often can not be administered on weekends or holidays ; only a reduced therapy , mainly by application of a more or less passive compression by b and aging , is administered . For this , conventional low-stretch b and ages are hitherto being used . Several attempts have been made to overcome this disadvantage by either impregnating or covering the b and age with sticky or adhesive substances such as india rubber , elastomeres , polyacrylates , etc . Recently , new b and ages are available , which are drenched with alginate that becomes semi-rigid after drying for approximately 6 h. It was the aim of this study to compare alginate b and aging to a conventional lymphologic-multilayered low-stretch b and aging with individual supportive lining as to their effect concerning their congestive capacity in exactly delimited time periods of reduced decongestive therapy as well as the patients ’ tolerance . Material s and methods From December 2007 until May 2008 , 61 female patients with a one-sided lymphoedema of the axillary tributary region after axillar dissection who underwent a phase I complex decongestive therapy were prospect ively selected for our investigation . On weekends , group A got the conventional low-stretch compressive b and aging , whereas group B got an alginate semi-rigid b and age . Arm volumes were measured before and after these b and ages were applied . Additionally , the subjective sensations of the skin caused by the compression were measured by means of a five-level Likert scale . Results and conclusions The initial volumes ( V0 ) of the two groups ( A , 2,939.0 ml ± 569.182 ; B , 3,062.6 ml ± 539.161 ) varied within the same magnitude , with somewhat smaller values in group A. The same was true for the final volumes ( V6 ) , measured at day 22 ( A , 2,674.5 ml ± 480.427 ; B , 2,740.1 ml ± 503.593 ) . During the weekends , the arm volumes re-increased ( first weekend : A , 16.4 ml vs. B , 4.7 ml ; second weekend : A , 14.2 ml vs. B , 2.7 ml ; third weekend : A , 7.5 ml vs. B , 1.1 ml ) . A significantly smaller volume increase appeared in the alginate group during the weekends . There were no serious side effects in both groups . Concerning the patients ’ comfort , the values of the alginate group were clearly better than those of the conventionally b and aged group . Additionally , the volume changes in the alginate group revealed fewer fluctuations . As a summary , one can state that a good alternative to the conventional b and aging is available with the alginate b and ages , bringing distinct advantages for the patients when administered properly 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 AIMS . Lymphedema is a common complication with breast cancer treatment that does not have a definite cure . Our objective was to determine the efficacy of autologous stem cells ( ASC ) in the treatment of lymphedema secondary to mastectomy and axillary lymphadenectomy in comparison with traditional decongestive treatment with compression sleeves . METHODS . A prospect i ve study including 20 women with lymphedema secondary to breast cancer surgery with axillary lymphadenectomy was conducted . Women were assigned at r and om to one of two groups . One group of 10 women was injected with ASC in the affected arm , whereas the other 10 women comprised the control group and received traditional compression sleeve therapy ( CST ) . The follow-up for both groups was 12 weeks . Pain , sensitivity and mobility were assessed before and after therapy . RESULTS . There was improvement in the volume of lymphedema in both groups , with no significant difference . In the ASC group there was an overall volume reduction during the follow-up , whereas in the CST group lymphedema recurred after the compression sleeve was removed . CONCLUSIONS . Our findings suggest that ASC injection for patients with lymphedema can be an effective treatment . It reduces arm volume and associated co-morbidities of pain and decreased sensitivity . Traditional CST was also effective for lymphedema reduction , but it was dependent on continuous use of the treatment Disruption of the lymphatic circulation through breast carcinoma‐associated axillary lymph node dissection , with or without radiation therapy , reportedly is the most common cause of lymphedema in developed countries . There is no cure for breast carcinoma‐associated lymphedema . Although intermittent pneumatic compression ( IPC ) has been acknowledged as a potential component of the multidisciplinary therapeutic strategy in the treatment of patients with breast carcinoma‐associated lymphedema , prospect i ve study of its adjunctive safety and efficacy is required Trial design : A r and omized controlled trial was performed to evaluate the effect of the combination of compression therapy with active exercising using a facilitating apparatus on arm lymphedema . Method : Twenty women with a mean age of 63.3 years were evaluated ; all had lymphedema result ing from breast cancer treatment . The inclusion criterion was a difference of 200 mL in size between arms . The apparatus used , called ' pulley system ' , is a vertical iron wheel fixed on a support at a distance of 10 cm from the patient 's body . Participants were su bmi tted to two series of active exercises using this facilitating device , one series using a compression sleeve and the other without . Each series consisted of four 12-minute sessions of exercises separated by 3-minute rest intervals . Volumetry was performed before and after each series of exercises . The paired t-test was utilized for statistical analysis ( p-value < 0.05 ) . Results : A significant mean reduction ( p-value < 0.007 ) and non-significant mean increase ( p-value < 0.2 ) in volumes were observed during exercising with and without compression , respectively . Conclusion : Controlled active exercising utilizing a facilitating apparatus while wearing a compression sleeve reduces the size of lymphedematous arms Introduction Secondary lymphedema affects approximately 40 % of women treated for breast cancer and is recognized as a major problem associated with the therapy of malignant tumors . Consequently , new therapeutic methods are constantly being sought to effectively eliminate the condition . One of the new forms of edema management , especially in the initial stages of edematous development , is Kinesiology Taping ( KT ) . Aim of the study The aim of the study was to assess the effects of KT applications on the extent of lymphedema of the upper extremity in women post cancer treatment . Material and methods The study group consisted of 28 women after axillary lymphadenectomy due to breast cancer . All the patients were diagnosed with grade I secondary lymphedema . Kinesiology Taping was applied to a total of 14 r and omly selected women . The remaining 14 patients constituted a control group . The extent of lymphedema was measured using a centimeter tape and Limb Volumes Professional 5.0 software . Results A significant reduction in the extent of lymphedema ( p = 0.0009 ) was achieved in the KT group between baseline and post-treatment assessment s. No such reduction , however , was found in the control group ( p = 0.36 ) . Conclusions Kinesiology Taping applications are an effective method of early-stage edema management . Kinesiology Taping may be a safe new therapeutic option in patients who are contraindicated for the use of other methods OBJECTIVE Short stretch b and ages are very effective in the initial management of arm lymphedema . However , no studies to date have measured the pressure required to achieve specific amounts of volume reduction . The purpose of this study was to determine whether there is a difference between low and high-pressure b and aging in terms of therapeutically intended volume reduction of the compressed arm . METHODS Experimental , r and omized and comparative study with two study -groups consisting of high and low initial interface pressure b and ages . Thirty-six hospitalized patients in Nij Smellinghe hospital suffering from moderate to severe unilateral breast cancer-related lymphedema not responsive to outpatient treatment were included . Bilateral arm volume was measured by inverse water volumetry before , after two hours and after 24 hours of b and aging . The amount of edema was calculated by subtracting the volume of the diseased arm from that of the contralateral side . Sub-b and age pressure was measured after b and age application and two hours later . B and ages were then re-applied and the pressure was measured again . Twenty-four hours later , the pressure measurement was repeated and b and ages were removed for final volumetry . Patients were r and omized into two groups : group A received low pressure b and ages ( 20 - 30 mm Hg ) and group B received high pressure b and ages ( 44 - 58 mm Hg ) . The main outcome measures were reduction of arm volume and edema volume in the affected arm in both study groups . Secondary outcome parameters were changes in sub-b and age pressure and patient comfort . RESULTS Median arm volume reduction after two and 24 hours was 104.5 mL ( 95 % confidence interval [ CI ] , 51.2 - 184.2 ) ( -2.5 % ) ( P < .0001 ) and 217 mL ( 95 % CI , 143.9 - 280.2 ) ( -5.2 % ) ( P < .01 ) for group A and 56.5 mL ( 95 % CI , -2.7 - 123.1 ) ( n.s . ) and 167.5 mL ( 95 % CI , 105.2 - 316.1 ) ( -4.2 % ) ( P < .01 ) for group B , respectively . There was no statistically significant difference between the volume changes in group A and group B. After 24 hours , edema decreased by median percentage of 9.2 % in group A and 4.8 % in group B ( n.s . ) . B and ages in group A were better tolerated . The sub-b and age pressure drop in the first two hours was between 41 % and 48 % in both treatment groups at both measuring sites . After 24 hours , the pressure drop was between 55 % and 63 % . No proximal swelling above the b and age was observed . CONCLUSIONS Inelastic , multi-layer , multi-component compression b and ages with lower pressure ( 20 - 30 mm Hg ) are better tolerated and achieve the same amount of arm volume reduction as b and ages applied with higher pressure ( 44 - 58 mm Hg ) in the first 24 hours PURPOSE To examine the effect of a progressive upper-body exercise program on lymphedema secondary to breast cancer treatment . METHODS Fourteen breast cancer survivors with unilateral upper extremity lymphedema were r and omly assigned to an exercise ( n = 7 ) or control group ( n = 7 ) . The exercise group followed a progressive , 8-week upper-body exercise program consisting of resistance training plus aerobic exercise using a Monark Rehab Trainer arm ergometer . Lymphedema was assessed by arm circumference and measurement of arm volume by water displacement . Patients were evaluated on five occasions over the experimental period . The Medical Outcomes Trust Short-Form 36 Survey was used to measure quality of life before and after the intervention . Significance was set at alpha < or = 0.01 . RESULTS No changes were found in arm circumference or arm volume as a result of the exercise program . Three of the quality -of-life domains showed trends toward increases in the exercise group : physical functioning ( P = .050 ) , general health ( P = .048 ) , and vitality ( P = .023 ) . Mental health increased , although not significantly , for all subjects ( P = .019 ) . Arm volume measured by water displacement was correlated with calculated arm volume ( r = .973 , P < .001 ) , although the exercise and control group means were significantly different ( P < .001 ) . CONCLUSIONS Participation in an upper-body exercise program caused no changes in arm circumference or arm volume in women with lymphedema after breast cancer , and they may have experienced an increase in quality of life . Additional studies should be done in this area to determine the optimum training program BACKGROUND The aim of this prospect i ve cohort study of women attending a rehabilitation course at the Dallund Rehabilitation Centre was to explore the emotional and psychological aspects of living with lymphoedema , expressed as psychological distress , poorer quality of life and poorer self-reported health . METHODS Between November 2002 and January 2007 within the FOCARE study , self-completed question naires were collected 3 weeks before and 6 and 12 months after the rehabilitation course to elicit sociodemographic , physical and lifestyle information and responses to three psychometric tests . The population consisted of 633 women , 125 with and 508 without verified lymphoedema ( time since surgery , 1 month-5 years ) . The population was reduced to 553 women at the first follow-up and 494 at the second . RESULTS Multivariate analysis showed that , in comparison with women without lymphoedema , those with lymphoedema had a 14 % higher risk for scoring one level higher on the POMS-SF test , a 9 % higher probability of scoring one point lower on the quality of life scale and a 29 % higher likelihood of reporting poorer or bad health than women without lymphoedema . These findings were seen at all three measurement times . CONCLUSIONS In this cohort of women with breast cancer , women with lymphoedema after surgery for breast cancer had significantly worse overall emotional well-being and adjustment to life compared to women without lymphoedema Background Treatment of lymphedema is based on intensive decongestive physiotherapy followed by a long-term maintenance treatment . We analyzed the factors influencing lymphedema volume during maintenance treatment . Method Prospect i ve cohort of 537 patients with secondary arm lymphedema were recruited in a single lymphology unit and followed for 12 months . Lymphedema volume was recorded prior to and at the end of intensive treatment , and at month 6 and month 12 follow-up visits . Multivariate models were fitted to analyze the respective role of the three components of complete decongestive therapy , i.e. manual lymph drainage , low stretch b and age , and elastic sleeve , on lymphedema volume during the 1-year maintenance phase therapy . Results Mean volume of lymphedema was 1,054 ± 633 ml prior and 647 ± 351 ml after intensive decongestive physiotherapy . During the 1-year maintenance phase therapy , the mean lymphedema volume slightly increased ( 84 ml—95 % confidence interval [ CI ] : 56–113 ) . Fifty-two percent of patients had their lymphedema volume increased above 10 % from their value at the end of the intensive decongestive physiotherapy treatment phase . Non-compliance to low stretch b and age and elastic sleeve were risk factors for an increased lymphedema after 1-year of maintenance treatment ( RR : 1.55 [ 95 % CI : 1.3–1.76 ] ; P < 0.0001 and RR : 1.61 ( 95 % CI : 1.25–1.82 ) ; P = 0.002 , respectively ) . Non-compliance to MLD was not a risk factor ( RR : 0.99 [ 95 % CI : 0.77–1.2 ] ; P = 0.91 ) . Conclusion During maintenance phase after intensive decongestive physiotherapy , compliance to the use of elastic sleeve and low stretch b and age should be required to stabilize lymphedema volume OBJECTIVE To investigate the differences between the effects of complex decongestive physiotherapy with and without active resistive exercise for the treatment of patients with breast cancer-related lymphedema ( BCRL ) . DESIGN R and omized control-group study . SETTING An outpatient rehabilitation clinic . PARTICIPANTS Patients ( N=40 ) with diagnosed BCRL . INTERVENTIONS Patients were r and omly assigned to either the active resistive exercise group or the nonactive resistive exercise group . In the active resistive exercise group , after complex decongestive physiotherapy , active resistive exercise was performed for 15min/d , 5 days a week for 8 weeks . The nonactive resistive exercise group performed only complex decongestive physiotherapy . MAIN OUTCOME MEASURES The circumferences of the upper limbs ( proximal , distal , and total ) for the volume changes , and the Short Form-36 version 2 question naire for the quality of life ( QOL ) at pretreatment and 8 weeks posttreatment for each patient . RESULTS The volume of the proximal part of the arm was significantly more reduced in the active resistive exercise group than that of the nonactive resistive exercise group ( P<.05 ) . In the active resistive exercise group , there was significantly more improvement in physical health and general health , as compared with that of the nonactive resistive exercise group ( P<.05 ) . CONCLUSIONS For the treatment of patients with BCRL , active resistive exercise with complex decongestive physiotherapy did not cause additional swelling , and it significantly reduced proximal arm volume and helped improve QOL It is well documented that resistance exercise can be performed by patients with breast cancer-related arm lymphedema . The aim of this pilot study was to evaluate the feasibility and safety of a 12-week self-administered weight lifting program for arm and shoulder , and its influence on arm lymphedema status , upper extremity muscle strength , and disability . Twenty-three patients with breast cancer-related arm lymphedema performed the program 3 times/week . The weight resistance levels were individually adjusted for shoulder flexion and adduction , and elbow extension and flexion corresponding to a repetition range of 8 - 12 repetition maximum . A log book was used to evaluate adherence to the program , wearing of compression sleeve and perceived exertion . Measurements were performed before a 2-week control period without intervention , and before and after intervention , and with arm volume measurements every fortnight to check for adverse events . Results revealed no significant changes during the control period . Adherence to the intervention program was excellent , and two adverse events were registered during the first weeks . After intervention , an increase of shoulder and arm strength ( measured by an isometric muscle strength device ) was found in all exercises ( p = 0.001 - 0.003 ) . A reduction of excess volume was shown , in ml ( p = 0.03 ) and percentage ( p = 0.005 ) , measured by water displacement method . A tendency towards reduction ( p = 0.07 ) of fat tissue in the upper arm ( n = 10 ) in both arms was found measured by MRI . In this pilot study , we concluded that a home-based weight-lifting program performed by patients with breast cancer-related arm lymphedema is feasible and safe providing that the program includes regular follow-up for safety There is no cure for breast cancer related lymphedema . This study was conducted to compare two treatment methods for postmastectomy lymphedema : Complex Decongestive Therapy ( CDT ) and Modified CDT ( MCDT ) combined with Intermittent Pneumatic Compression ( IPC ) . One hundred and twelve patients referred to the Lymphedema Clinic of the Iranian Center for Breast Cancer in 2008 , were included in a r and omized clinical trial . They were r and omly allocated into two equal groups receiving daily CDT alone or in combination with IPC . The volume reduction of the upper limb was measured by water displacement volumetry . No statistically significant differences in demographic and clinical variables between the two groups were observed . During the intensive phase ( phase I ) of treatment , CDT alone yielded a significantly higher mean volume reduction than the combination modality ( 43.1 % vs. 37.5 % ; p = 0.036 ) . Limb volume measured three months following treatment , showed 16.9 % volume reduction by CDT alone , and 7.5 % reduction by MCDT plus IPC . This study demonstrated that the use of CDT alone , or in combination with IPC significantly reduced limb volume in patients with post mastectomy lymphedema . CDT alone provided better results in both treatment phases . Further studies will help to define the role of multidisciplinary approaches in the management of postmastectomy lymphedema PURPOSE / OBJECTIVES To examine the impact of advanced practice nurse (APN)-administered low-level laser therapy ( LLLT ) as both a st and -alone and complementary treatment for arm volume , symptoms , and quality of life ( QOL ) in women with breast cancer-related lymphedema . DESIGN A three-group , pilot , r and omized clinical trial . SETTING A private rehabilitation practice in the southeastern United States . SAMPLE 46 breast cancer survivors with treatment-related lymphedema . METHODS Patients were screened for eligibility and then r and omized to either manual lymphatic drainage ( MLD ) for 40 minutes , LLLT for 20 minutes , or 20 minutes of MLD followed by 20 minutes of LLLT . Compression b and aging was applied after each treatment . Data were collected pretreatment , daily , weekly , and at the end of treatment . MAIN RESEARCH VARIABLES Independent variables consisted of three types of APN-administered lymphedema treatment . Outcome variables included limb volume , extracellular fluid , psychological and physical symptoms , and QOL . FINDINGS No statistically significant between-group differences were found in volume reduction ; however , all groups had clinical ly and statistically significant reduction in volume . No group differences were noted in psychological and physical symptoms or QOL ; however , treatment-related improvements were noted in symptom burden within all groups . Skin improvement was noted in each group that received LLLT . CONCLUSIONS LLLT with b and aging may offer a time-saving therapeutic option to conventional MLD . Alternatively , compression b and aging alone could account for the demonstrated volume reduction . IMPLICATION S FOR NURSING APNs can effectively treat lymphedema . APNs in private healthcare practice s can serve as valuable research collaborators . KNOWLEDGE TRANSLATION Lasers may provide effective , less burdensome treatment for lymphedema . APNs with lymphedema certification can effectively treat this patient population with the use of LLLT . In addition , bioelectrical impedance and tape measurements can be used to assess lymphedema PURPOSE Because of its morbidity and chronicity , arm lymphedema remains a concerning complication of breast cancer treatment . Although massage-based decongestive therapy is often recommended , r and omized trials have not consistently demonstrated benefit over more conservative measures . PATIENTS AND METHODS Women previously treated for breast cancer with lymphedema were enrolled from six institutions . Volumes were calculated from circumference measurements . Patients with a minimum of 10 % volume difference between their arms were r and omly assigned to either compression garments ( control ) or daily manual lymphatic drainage and b and aging followed by compression garments ( experimental ) . The primary outcome was percent reduction in excess arm volume from baseline to 6 weeks . RESULTS A total of 103 women were r and omly assigned , and 95 were evaluable . Mean reduction of excess arm volume was 29.0 % in the experimental group and 22.6 % in the control group ( difference , 6.4 % ; 95 % CI , -6.8 % to 20.5 % ; P = .34 ) . Absolute volume loss was 250 mL and 143 mL in the experimental and control groups , respectively ( difference , 107 mL ; 95 % CI , 13 to 203 mL ; P = .03 ) . There was no difference between groups in the proportion of patients losing 50 % or greater excess arm volume . Quality of life ( Short Form-36 Health Survey ) and arm function were not different between groups . CONCLUSION This trial was unable to demonstrate a significant improvement in lymphedema with decongestive therapy compared with a more conservative approach . The failure to detect a difference may have been a result of the relatively small size of our trial AIM The optimal pressure to reduce chronic extremity swelling is still a matter of debate . The aim of this paper was to measure volume reduction of a swollen extremity depending on the amount of pressure exerted by compression stockings and inelastic b and ages . METHODS Thirty-six patients with unilateral breast cancer related arm lymphedema were investigated in a lymph clinic in the Netherl and s , 42 legs with chronic edema of the lower extremities were examined in a phlebological centre in Italy . The arm- patients were r and omized to receive inelastic arm b and ages with a pressure between 20 - 30 mmHg or 44 - 68 mmHg . The leg patients were either treated with compression stockings ( 23 - 32 mmHg ) or with inelastic b and ages ( pressure 53 - 88 mmHg ) . Water-displacement volumetry and measurement of leg circumference was performed before and after compression . RESULTS In the arm- patients low pressure after 2 hours achieved a higher degree of volume reduction ( -2.3 % , 95 % CI 1.0 - 3.6 ) than high pressure ( -1.5 % , 95 % CI 0.2 - 2.8 ) ( n.s . ) . In patients with leg edema compression stockings in the range between 20 and 40 mmHg showed a positive correlation between exerted pressure and volume reduction , b and ages applied with an initial resting pressure of more than 60 mm Hg result ed in a decreasing volume reduction . CONCLUSION There is obviously an upper limit beyond which further increase of compression pressure seems counterproductive . For inelastic b and ages this upper limit is around 30 Hg on the upper and around 50 - 60 mmHg on the lower extremity The cycle time and number of chambers in the pneumatic sleeve may influence the outcome of lymphedema therapy with intermittent compression devices . The aim of our study was to assess efficacy of several commonly used different IPC protocol s on edema volume reduction in women with postmastectomy lymphedema . Fixty-seven ( 57 ) women with secondary arm lymphedema ( age 39 - 80 ) were selected to the study . Women were r and omly assigned to two study groups with different IPC cycle times : I--90:90s and II--45:15s . Both groups were then r and omly divided into two subgroups with different sleeves : A--1 chamber sleeve ( 28 women ) and B--3 chamber sleeve ( 29 women ) . All women underwent IPC treatment for 5 weeks , 5 times a week for 1 hour ( 25 sessions ) . Arm volume measurements were performed before and after each IPC session . Significant reduction of edema volume was observed in all therapeutic subgroups , regardless of cycle times and number of chambers . In the group with short IPC cycle , better efficacy was noticed with 3-chamber sleeve . IPC is an effective method of volume reduction in women with postmastectomy arm lymphedema regardless of cycle times and number of sleeve chambers Purpose This study evaluated the acute effect of massage and compression components of lymphoedema treatment in women with and without arm lymphoedema secondary to breast cancer from a single treatment session . Methods Women with ( n = 15 ) and without ( n = 15 ) lymphoedema underwent a single session of lymphatic massage . Following the session , women were r and omised to receive or not receive a compression sleeve . Measurements were taken prior to , during , and following the massage as well as 30 min after completion of the massage . Bioimpedance spectrometry ( BIS ) was used to measure changes in extracellular fluid volume of all limbs as well as 10-cm segments within the upper limbs ; perometry was used to measure changes in total upper limb volume as well as 10-cm segments within the limb . Results There were no significant changes after massage with or without compression . The median ( and interquartile range ) BIS ratios ( unaffected : affected ) for the whole upper limb for women with lymphoedema changed from 1.152 ( 1.053 to 1.422 ) to 1.192 ( 1.045 to 1.410 ) after massage , while the control group changed from 1.024 ( 0.998 to 1.047 ) to 1.041 ( 0.982 to 1.07 ) . The median change in both the BIS ratio and the total arm volume measured with perometry from prior to the massage to following 30-min rest changed < 2 % , irrespective of whether women used a compression garment and whether women presented with or without lymphoedema . Examination of 10-cm segments within the arm also revealed no significant change in BIS ratio from one segment to the next . Conclusion Massage alone or the application of compression after a single session of lymphatic massage was ineffective for reducing lymphoedema Background Lymphedema as a result of curative surgery for breast cancer can lead to long-term morbidity . Decongestive lymphatic therapy ( DLT ) is recognized as an optimal management strategy for patients with moderate symptomatologies , but there is little data in regard to the most effective means of providing compression therapy within a DLT protocol . We conducted a r and omized trial of two forms of compression therapy within the initial treatment phase of a DLT protocol for breast cancer-related lymphedema . Methods Subjects were required to have mild – moderate lymphedema ( 10–40 % volume difference ) acquired as a result of curative breast cancer surgery and were r and omized to compression b and aging or garments within the initial treatment phase of a DLT protocol . Primary endpoint was change in affected limb volume assessed via volumetry , and secondary endpoints were symptom control and upper extremity function assessed via visual analogue scales and the Disabilities of the Arm , Shoulder and H and ( DASH ) question naire , respectively . Endpoints were assessed at day 10 of treatment and at 3 months and compared to baseline . Results Twenty-one subjects were available for analysis . The group receiving b and aging experienced greater median volume reductions at 10 days ( 70 vs. 5 mL ; p = 0.387 ) and at 3 months ( 97.5 vs. 50 mL ; p = 0.182 ) . The b and aging group also experienced a greater increase in median DASH scores at 10 days ( + 20.9 vs. + 5 ; p = 0.143 ) and at 3 months ( + 18.4 vs. + 3.3 ; p = 0.065 ) . Conclusion Within the initial treatment phase of a DLT protocol for acquired , breast cancer-related lymphedema , compression b and aging may lead to greater volume reduction but worse upper extremity functional status ( higher DASH scores ) as compared to compression garments Objective Chronic lymphedema occurs frequently in breast cancer patients and is associated with significant morbidity and reduced quality -of-life . In this pilot study , the authors ( 1 ) addressed whether conducting a larger r and omized controlled trial of aqua lymphatic therapy ( ALT ) would be feasible and ( 2 ) estimated the extent to which ALT combined with home-based exercise compared with home-based exercise alone would reduce arm disability in patients with breast cancer – related lymphedema . Design Twenty-five women with breast cancer – related lymphedema were r and omized to either ALT in addition to a home l and -based exercise program ( ALT group ; n = 13 ) or to a home l and -based exercise program alone ( control group ; n = 12 ) . The participants were evaluated before and after a 12-wk intervention period composed of weekly pool exercise sessions . Main outcome measures were arm volume , arm disability , pain , and quality -of-life . Results At follow-up , there was no statistical difference between the control and ALT groups in any of the outcomes , except for present pain intensity . At the end of the study period , there was no change in the lymphedematous limb volume in either group . Grip strength was improved in both groups . Only the ALT group showed a statistically significant difference with a reduction in pain intensity score and arm disability . Furthermore , quality -of-life significantly improved only in the ALT group . Conclusions Conducting a larger r and omized controlled trial would be feasible . In comparison with the beginning of the intervention , the participants in the ALT group showed significant beneficial changes after 12 wks of treatment , whereas the control group did not improve . ALT did not make the lymphedema volume worse and therefore may serve as a safe alternative to l and -based treatments of breast cancer – related lymphedema Clinical trials of the effect of physical exercise on breast cancer related arm lymphedema ( ALE ) are very rare . The aim of this study was to examine if controlled low intensity arm exercises with weights , with or without a compression sleeve , influence breast cancer related ALE . Thirty-one breast cancer treated patients with small or moderate ALE were included in the study . A specifically design ed arm exercise program was performed with or without compression sleeve on different days and in a r and omized order . Measurements were performed before , directly after and 24 hours after the exercise intervention , with water displacement method and multiple frequency bioelectrical impedance analysis ( n=10 ) for volume of the arms and Borg 's scale for perceived exertion during training . There was an increase of total arm volume of the lymphedema arm immediately after the exercise intervention for both with and without sleeve conditions ( p < 0.01 ) . At 24 hours , no volume increase was found compared to pre-exercise and both groups showed tendency towards reduced lymphedema relative volume ( p < 0.05 ) . The patient 's rating of perceived exertion was low regardless of whether a sleeve was worn , but was significantly higher when exercising with the sleeve . We conclude that low intensity exercises can be performed by patients with arm lymphedema without risk of worsening the edema . Exercises without the sleeve may be of benefit provided compression sleeve is worn regularly PURPOSE To determine the prevalence of and contributing factors for chronic arm morbidity including lymphedema in breast cancer patients after treatment and to assess the impact of arm morbidity on quality of life ( QOL ) . PATIENTS AND METHODS A four- question screening question naire was developed and mailed to a r and om sample of 744 breast cancer patients treated curatively in two cancer centers from 1993 to 1997 . Patients were without recurrence and at least 2 years from diagnosis . Respondents were classified as with or without arm-related symptoms on the basis of the survey . Stratified r and om sample s from each group were then invited for a detailed assessment of their symptoms and signs , including the presence of lymphedema . Their QOL was assessed by the European Organization for Research and Treatment of Cancer QOL Question naire C-30 and by a detailed arm problem question naire that assessed various aspects of daily arm functioning . RESULTS Approximately half of all screened patients were symptomatic and 12.5 % of all assessed patients had lymphedema . Axillary dissection ( AD ) and axillary radiotherapy ( RT ) after dissection were statistically significantly related to the occurrence of arm symptoms ( odds ratio for AD = 3.3 , P < .001 ; odds ratio for RT = 3.1 , P < .001 ) . Symptomatic patients and patients with lymphedema both had impaired QOL compared with asymptomatic patients . CONCLUSION Treatment for breast cancer is associated with considerable arm morbidity , which has a negative impact on QOL . Arm morbidity should be carefully monitored in future studies involving local treatment modalities for breast cancer |
11,810 | 26,689,385 | The results showed that research into online psychological crisis intervention has been conducted in several different countries , especially the Netherl and s and Australia , and that the users of these tools benefit from them .
Online crisis interventions have been developed and research ed in many countries around the world . | INTRODUCTION The world 's population is often assailed by crises of various orders .
Disasters caused by nature and by humans themselves also impact on people 's mental health .
Psychological crises , such as suicide attempts , represent a growing problem in mental health .
When faced with such scenarios , specific strategies of crisis intervention are both appropriate and necessary .
OBJECTIVE To conduct a systematic review of the literature dealing with online psychological crisis intervention , describing and discussing their operational design , specific characteristics and applications . | Online therapy offers many advantages over face-to-face therapy . Interapy includes psychoeducation , screening , effect measures , and a protocol -driven treatment via the Internet for people suffering from posttraumatic stress . The present article reports the results of a controlled trial on the Internet-driven treatment of posttraumatic stress and grief in a group of people who manifested mild to relatively severe trauma symptoms . Participants in the treatment condition ( n=69 ) improved significantly more than participants in the waiting-list control condition ( n=32 ) on trauma-related symptoms and general psychopathology . The effect sizes were large . On most subscales , more than 50 % of the treated participants showed reliable change and clinical ly significant improvement , with the highest percentages being found for depression and avoidance Background Posttraumatic stress disorder ( PTSD ) develops in 10 - 20 % of injury patients . We developed a novel , self-guided Internet-based intervention ( called Trauma TIPS ) based on techniques from cognitive behavioral therapy ( CBT ) to prevent the onset of PTSD symptoms . Objective To determine whether Trauma TIPS is effective in preventing the onset of PTSD symptoms in injury patients . Methods Adult , level 1 trauma center patients were r and omly assigned to receive the fully automated Trauma TIPS Internet intervention ( n=151 ) or to receive no early intervention ( n=149 ) . Trauma TIPS consisted of psychoeducation , in vivo exposure , and stress management techniques . Both groups were free to use care as usual ( non protocol ized talks with hospital staff ) . PTSD symptom severity was assessed at 1 , 3 , 6 , and 12 months post injury with a clinical interview ( Clinician-Administered PTSD Scale ) by blinded trained interviewers and self-report instrument ( Impact of Event Scale — Revised ) . Secondary outcomes were acute anxiety and arousal ( assessed online ) , self-reported depressive and anxiety symptoms ( Hospital Anxiety and Depression Scale ) , and mental health care utilization . Intervention usage was documented . Results The mean number of intervention logins was 1.7 , SD 2.5 , median 1 , interquartile range ( IQR ) 1 - 2 . Thirty-four patients in the intervention group did not log in ( 22.5 % ) , 63 ( 41.7 % ) logged in once , and 54 ( 35.8 % ) logged in multiple times ( mean 3.6 , SD 3.5 , median 3 , IQR 2 - 4 ) . On clinician-assessed and self-reported PTSD symptoms , both the intervention and control group showed a significant decrease over time ( P<.001 ) without significant differences in trend . PTSD at 12 months was diagnosed in 4.7 % of controls and 4.4 % of intervention group patients . There were no group differences on anxiety or depressive symptoms over time . Post hoc analyses using latent growth mixture modeling showed a significant decrease in PTSD symptoms in a subgroup of patients with severe initial symptoms ( n=20 ) ( P<.001 ) . Conclusions Our results do not support the efficacy of the Trauma TIPS Internet-based early intervention in the prevention of PTSD symptoms for an unselected population of injury patients . Moreover , uptake was relatively low since one-fifth of individuals did not log in to the intervention . Future research should therefore focus on innovative strategies to increase intervention usage , for example , adding gameplay , embedding it in a blended care context , and targeting high-risk individuals who are more likely to benefit from the intervention . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 57754429 ; http://www.controlled-trials.com/IS RCT N57754429 ( Archived by WebCite at http://webcitation.org/6FeJtJJyD ) Background Suicide , attempted suicide and suicidal thoughts are major public health problems worldwide . Effective face-to-face treatments are Cognitive Behavioural Therapy ( CBT ) , Dialectical Behavioural Therapy ( DBT ) and Problem Solving Treatment ( PST ) . However , about two-thirds of persons who die by suicide have not been in contact with mental health care services in the preceding year , and many have never been treated . Furthermore , many patients do not disclose their suicidal thoughts to their care provider . This may be out of shame , due to fear of stigma or due to lack of trust in ( mental ) health care . Since many suicidal individuals seek information online , the internet provides an opportunity to reach suicidal individuals who would not be contacted otherwise . By providing a self-help intervention online , persons can anonymously learn to gain control over their suicidal thoughts . There is convincing evidence that self-help is effective for a number of mental disorders . In this study the effectiveness for suicidal thoughts is examined . Methods / Design In this study , a recently developed self-help intervention will be evaluated in a R and omized Controlled Trial . The intervention is based on Cognitive Behavioural Therapy and is aim ed at subjects who experience mild to moderate suicidal thoughts . This is defined as a score between 1 and 26 on the Beck Scale for Suicidal Ideation ( BSS ) . Higher and lower scores are excluded . In addition , severely depressed subjects are excluded . In total , 260 subjects will be r and omly allocated to the intervention-condition ( N = 130 ) or to the information-control condition ( N = 130 ) . Self-report question naires will be filled out at baseline , 6 weeks after baseline and 18 weeks after baseline . Primary outcome measure is the reduction in frequency and intensity of suicidal thoughts . Secondary outcome measures are the reduction of hopelessness , anxiety and depression , sleeplessness , worry and quality of life measures . Discussion This study is the first to evaluate the effectiveness of a web-based self-help intervention for suicidal thoughts . Several limitations and strengths of the design are discussed . Trial Registration Netherl and s Trial Register , OBJECTIVE The aim of this article was to evaluate the effectiveness of an information provision web-based early intervention via a r and omized controlled trial for children and their parents following pediatric unintentional injury . METHOD Participants were r and omly assigned to an intervention ( n = 29 ) or a control group ( n = 27 ) following baseline measurements . Further assessment was taken at 4 - 6 weeks and 6 months post-trauma event . RESULTS Analyses revealed that children within the intervention group reported improved anxiety , in comparison to a worsening of symptoms for children in the control group . Furthermore , children who had higher baseline trauma scores reported the intervention to be helpful . CONCLUSIONS The intervention showed promising results in its ability to aid child recovery OBJECTIVE The authors report an 8-week r and omized , controlled proof-of-concept trial of a new therapist-assisted , Internet-based , self-management cognitive behavior therapy versus Internet-based supportive counseling for posttraumatic stress disorder ( PTSD ) . METHOD Service members with PTSD from the attack on the Pentagon on September 11th or the Iraq War were r and omly assigned to self-management cognitive behavior therapy ( N=24 ) or supportive counseling ( N=21 ) . RESULTS The dropout rate was similar to regular cognitive behavior therapy ( 30 % ) and unrelated to treatment arm . In the intent-to-treat group , self-management cognitive behavior therapy led to sharper declines in daily log-on ratings of PTSD symptoms and global depression . In the completer group , self-management cognitive behavior therapy led to greater reductions in PTSD , depression , and anxiety scores at 6 months . One-third of those who completed self-management cognitive behavior therapy achieved high-end state functioning at 6 months . CONCLUSIONS Self-management cognitive behavior therapy may be a way of delivering effective treatment to large numbers with unmet needs and barriers to care This study compared the efficacy of an Internet-based , 8-week self-help program for traumatic event-related consequences ( SHTC ) ( n = 13 ) to a wait-list ( WL ) condition ( n = 14 ) . The SHTC consisted of cognitive-behavioral modules that progressed from the least anxiety-provoking component ( i.e. , information ) to the most anxiety-provoking ( i.e. , exposure ) . Participants were those who had experienced a traumatic event and had been experiencing sub clinical levels of symptoms associated with the event . Participants mastered the material in each module before proceeding to the next module . Pre- and post-treatment assessment s revealed that SHTC participants decreased avoidance behavior , frequency of intrusive symptoms , state anxiety , and depressive symptoms , and increased coping skills and coping self-efficacy significantly more than WL participants . SHTC participants demonstrated more clinical ly significant improvement than WL individuals Background Suicidal ideation is highly prevalent , but often remains untreated . The Internet can be used to provide accessible interventions . Objective To evaluate the cost-effectiveness of an online , unguided , self-help intervention for reducing suicidal ideation . Methods A total of 236 adults with mild to moderate suicidal thoughts , defined as scores between 1 - 26 on the Beck Scale for Suicide Ideation ( BSS ) , were recruited in the general population and r and omized to the intervention ( n = 116 ) or to a waitlist , information-only , control group ( n = 120 ) . The intervention aim ed to decrease the frequency and intensity of suicidal ideation and consisted of 6 modules based on cognitive behavioral techniques . Participants in both groups had unrestricted access to care as usual . Assessment s took place at baseline and 6 weeks later ( post-test ) . All question naires were self-report and administered via the Internet . Treatment response was defined as a clinical ly significant decrease in suicidal ideation on the BSS . Total per-participant costs encompassed costs of health service uptake , participants ’ out-of-pocket expenses , costs stemming from production losses , and intervention costs . These were expressed in Euros ( € ) for the reference year 2009 . Results At post-test , treatment response was 35.3 % and 20.8 % in the experimental and control conditions , respectively . The incremental effectiveness was 0.35 − 0.21 = 0.15 ( SE 0.06 , P = .01 ) . The annualized incremental costs were −€5039 per participant . Therefore , the mean incremental cost-effectiveness ratio ( ICER ) was estimated to be −€5039/0.15 = −€34,727 after rounding ( US −$41,325 ) for an additional treatment response , indicating annual cost savings per treatment responder . Conclusions This is the first trial to indicate that online self-help to reduce suicidal ideation is feasible , effective , and cost saving . Limitations included reliance on self-report and a short timeframe ( 6 weeks ) . Therefore , replication with a longer follow-up period is recommended |
11,811 | 28,736,102 | Olanzapine was superior to haloperidol and risperidone for reduction of negative symptoms .
Several second-generation antipsychotics were superior to haloperidol in terms of all-cause discontinuation .
Olanzapine was associated with at least one use of drugs to treat parkinsonian symptoms and quetiapine with less akathisia than haloperidol , aripiprazole , risperidone , and olanzapine , but , again , evidence was very low to low quality .
Molindone was superior to risperidone , haloperidol , and olanzapine in terms of weight gain , and superior to risperidone in terms of increase in prolactin release .
INTERPREATION Haloperidol seems to be a suboptimum treatment option for acute treatment of first-episode schizophrenia , but we found little difference between second-generation antipsychotics . | BACKGROUND The first episode of schizophrenia is a pivotal phase of this debilitating illness .
Which drug to use remains controversial without a summary of all direct or indirect comparisons of drugs .
We did a systematic review with pairwise and network meta-analyses of efficacy and tolerability . | Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics , and to be more sensitive to developing extrapyramidal side-effects . The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol . Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms . Patients were r and omly assigned under double-blind conditions to receive risperidone ( n=143 ) or haloperidol ( n=146 ) for 8 wk . The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale ( PANSS ) negative score between treatment groups ; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores , and several other measures of psychopathology and general functioning . The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale ( SAS ) compared between treatment groups . The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms . Secondary tolerability criteria were the other extrapyramidal symptoms , measured with the Hillside Akathisia Scale ( HAS ) and the Abnormal Involuntary Movement Scale ( AIMS ) . The average mean daily doses were 3.8 mg ( s.d.=1.5 ) for risperidone and 3.7 mg ( s.d.=1.5 ) for haloperidol . There were similar , significant improvements in both treatment groups in the primary and secondary efficacy criteria . At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [ SAS : risperidone 36.5 % of patients ; haloperidol 51.5 % of patients ; likelihood ratio test , chi2(1)=7.8 , p=0.005 ] . There were significantly fewer drop-outs [ risperidone n=55 , drop-out rate=38.5 % ; haloperidol n=79 , drop-out rate=54.1 % , chi2(1)=7.1 , p=0.009 ] and a longer non-discontinuation time [ risperidone : average of 50.8 d to drop-out ; haloperidol : average of 44.0 d to drop-out ; log rank test , chi2(1)=6.4 , p=0.011 ] in the risperidone group . Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia . Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients OBJECTIVE Potency equivalents for anti-psychotic drugs are required to guide clinical dosing and for design ing and interpreting research studies . Available dosing guidelines are limited by the methods and data from which they were generated . METHOD With a two-step Delphi method , the authors surveyed a diverse group of international clinical and research experts , seeking consensus regarding antipsychotic dosing . The authors determined median clinical dosing equivalents and recommended starting , target range , and maximum doses for 61 drugs , adjusted for selected clinical circumstances . RESULTS Participants ( N=43 ) from 18 countries provided dosing recommendations regarding treatment of psychotic disorders for 37 oral agents and 14 short-acting and 10 long-acting parenteral agents . With olanzapine 20 mg/day as reference , estimated clinical equivalency ratios of oral agents ranged from 0.025 for sulpiride to 10.0 for trifluperidol . Seventeen patient and treatment characteristics , including age , hepatic and renal function , illness stage and severity , sex , and diagnosis , were associated with dosing modifications . CONCLUSIONS In the absence of adequate prospect i ve , r and omized drug-drug comparisons , the present findings provide broad , international , expert consensus-based recommendations for most clinical ly employed antipsychotic drugs . They can support clinical practice , trial design , and interpretation of comparative antipsychotic trials An international , multicenter , double-blind study was conducted in 183 patients with a first psychotic episode ( provisional schizophreniform disorder or schizophrenia ; DSM-III-R ) treated with flexible doses of risperidone or haloperidol for 6 weeks . At endpoint , 63 percent of risperidone-treated patients and 56 percent of haloperidol-treated patients were clinical ly improved ( > or = 50 % reduction in Positive and Negative Syndrome Scale total scores ) . Risperidone was better tolerated than haloperidol : the severity of extrapyramidal symptoms was significantly lower in the risperidone-treated patients ; significantly fewer risperidone-treated patients required antiparkinsonian medication ; and significantly fewer discontinued treatment because of adverse events . A post hoc analysis revealed that low doses of these antipsychotics were efficacious in some patients . Furthermore , the severity of extrapyramidal symptoms and the use of antiparkinsonian medications were significantly lower in patients receiving low doses ( maximum , < or = 6 mg/day ) than high doses ( maximum , > 6 mg/day ) of risperidone or haloperidol . These findings are consistent with the suggestion that patients with a first psychotic episode may require low doses of antipsychotic medications . Studies design ed specifically to compare low and high doses of antipsychotics are warranted to help optimize treatment for these patients OBJECTIVE This multicenter , double-blind , placebo-controlled study evaluated the efficacy and safety of three doses of sertindole ( 12 , 20 , and 24 mg/day ) and haloperidol ( 4 , 8 , and 16 mg/day ) in the treatment of psychotic symptoms for 497 hospitalized patients with schizophrenia . METHOD The patients were r and omly assigned to one of the medication groups and received treatment for 8 weeks . Changes in Positive and Negative Syndrome Scale , Scale for the Assessment of Negative Symptoms , Brief Psychiatric Rating Scale , and Clinical Global Impression scores were used as evaluations of treatment efficacy . Three rating scales were used to assess extrapyramidal symptoms as well as the occurrence of adverse events and the use of medications related to extrapyramidal symptoms . RESULTS Both sertindole and haloperidol were comparably effective in the treatment of psychosis , and all dose levels were significantly more effective than placebo . For the treatment of negative symptoms , only sertindole , 20 mg/day , was significantly more effective than placebo . For all extrapyramidal symptom measures , sertindole was clinical ly and statistically indistinguishable from placebo , and rates of extrapyramidal symptoms were not dose related . All dose levels of haloperidol produced significantly more extrapyramidal symptoms than placebo or sertindole . Adverse events associated with sertindole treatment were mild in severity . CONCLUSIONS Sertindole is a new antipsychotic agent effective for the treatment of both the positive and negative symptoms of schizophrenia , with motor side effects that are indistinguishable from those associated with placebo The mechanism of action of a relatively new antipsychotic drug-Risperidone differs from conventional antipsychotics like Haloperidol . We compared low dosages of Risperidone with near equivalent dosages of Haloperidol in first episode drug naive Acute and Transient Psychotic disorder . A single blind r and omised four-week study protocol was employed . Highly significant and comparable efficacy as assessed by Brief Psychiatric Rating Scale and Global Assessment of Functioning Scale was seen at the end of the Study protocol in both the groups . Risperidone had significantly , an early onset of action on some of the positive as well as negative symptoms with less incidence of Extrapyramidal Symptoms in comparison to Haloperidol . We conclude that Risperidone may represent a potential useful first line agent in the treatment of Acute and Transient Psychotic Disorder BACKGROUND Studies on the effects of antipsychotics on cognitive deficits in schizophrenia mostly suggest a superior effect of atypical over typical compounds , although findings are inconsistent and effect sizes small . Several method ological issues , such as heterogeneous patient sample s , incomparable drug doses , effects of prior medication , construct validity , and retest effects on neuropsychological tasks , confound most results and the comparability between studies . Consequently , the conclusion concerning effects of antipsychotics on cognition is still equivocal . OBJECTIVE The present r and omized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic ( zuclopenthixol ) and an atypical antipsychotic ( risperidone ) in a homogeneous group of drug-naive first-episode schizophrenic patients in a longitudinal setting . METHODS First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment ( N=25 ) were r and omly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design . Cognitive functions were examined both when patients were drug-naive , and after 13 weeks of treatment . A comprehensive neuropsychological battery was used in order to optimize construct validity , and principal components of cognitive functions were extrapolated in order to reduce type I errors . A healthy control group was tested at baseline and after 13 weeks , in order to examine retest effects . The cognitive domains studied were executive functions , selective attention , and reaction time . RESULTS The patients showed considerable cognitive deficits when drug-naive . There were few differential effects of risperidone and zuclopenthixol on cognitive deficits , except for a differential significance , respectively , tendency towards improved reaction and movement times in the risperidone group , and a lack of such in the zuclopenthixol group . These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls . CONCLUSION The study underscores the importance of examining impact of factors , such as clinical improvement , extrapyramidal side effects , anticholinergic medication and retest effects in longitudinal efficacy studies . This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naive schizophrenia patients after 3 months of medication , because neither could be distinguished from retest effects of the healthy control group OBJECTIVE R and omized controlled drug trials have demonstrated that antipsychotic medication is effective to rapidly improve psychotic symptomatology in first-episode psychosis . However , these results may not be generalizable to routine clinical practice . We evaluated the effectiveness , tolerability , and safety of olanza-pine , risperidone , and haloperidol in individuals with first-episode nonaffective psychosis who are representative of clinical practice and who are treated in routine clinical setting s. METHOD 172 patients participated in a practical clinical trial and were r and omly assigned to haloperidol ( N = 56 ) , risperidone ( N = 61 ) , and olanzapine ( N = 55 ) . The mean modal daily doses were 5.4 mg/day for halo-peridol , 4 mg/day for risperidone , and 15.3 mg/day for olanzapine ; 98.3 % of subjects were drug naive at baseline . Data from clinical measures of treatment response and tolerability and safety data from the 6-week acute phase of a large epidemiologic and longitudinal ( February 2001 to February 2005 ) intervention program of first-episode psychosis ( schizophrenia spectrum disorders , DSM-IV criteria ) are reported . RESULTS All 3 treatments showed similar effectiveness in reducing the severity of general , negative , and positive symptomatology after 6 weeks of treatment , as reported by mean change in total Clinical Global Impressions-Severity of Illness scale , Brief Psychiatric Rating Scale ( BPRS ) , Scale for the Assessment of Positive Symptoms , and Scale for the Assessment of Negative Symptoms scores between baseline and 6 weeks . The proportion of study subjects responding , defined as 40 % or greater BPRS total score improvement from baseline , was 57.1 % ( N = 32 of 56 ) haloperidol , 52.5 % ( N = 32 of 61 ) risperidone , and 63.6 % ( N = 35 of 55 ) olanzapine , with no statistical differences among groups . The frequency of extrapyramidal symptoms ( chi(2 ) = 24.519 ; p < .001 ) and concomitant anticholinergic medication use ( chi(2 ) = 57.842 ; p < .0001 ) was greater with haloperidol than olanzapine or risperidone . Olanzapine-treated patients had significantly more weight gain compared with the haloperidol and risperidone groups ( p < .001 ) . CONCLUSION Relatively low doses of haloperidol , risperidone , and olanzapine are equally effective for the acute treatment of first-episode nonaffective psychosis under usual conditions of real clinical practice OBJECTIVE This study examined the treatment response of patients with first-episode schizophrenia and schizoaffective disorder and potential predictors of response . METHOD First-episode patients were assessed on measures of psychopathology , cognition , social functioning , and biological parameters and treated according to a st and ardized algorithm . RESULTS One hundred eighteen patients ( 52 % male , mean age 25.2 years ) entered the study . The cumulative percentage of patients responding by 1 year was 87 % ; the median time to response was 9 weeks . The following variables were significantly associated with less likelihood of response to treatment : male sex , obstetric complications , more severe hallucinations and delusions , poorer attention at baseline , and the development of parkinsonism during antipsychotic treatment . Variables not significantly related to treatment response were diagnosis ( schizophrenia versus schizoaffective disorder ) , premorbid functioning , duration of psychotic symptoms prior to study entry , baseline disorganization , negative and depressive symptoms , baseline motor function , akathisia and dystonia during treatment , growth hormone and homovanillic acid measures , psychotic symptom activation to methylpheni date , and magnetic resonance measures . CONCLUSIONS Patients with first-episode schizophrenia and schizoaffective disorder have high rates of response to antipsychotic treatment ; there are specific clinical and pathobiologic predictors of response BACKGROUND Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia ; however , their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated . We aim ed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol , in first-episode schizophrenia . METHODS We did an open r and omised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites , in 14 countries . Eligible patients were aged 18 - 40 years , and met diagnostic criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . 498 patients were r and omly assigned by a web-based online system to haloperidol ( 1 - 4 mg per day ; n=103 ) , amisulpride ( 200 - 800 mg per day ; n=104 ) , olanzapine ( 5 - 20 mg per day ; n=105 ) , quetiapine ( 200 - 750 mg per day ; n=104 ) , or ziprasidone ( 40 - 160 mg per day ; n=82 ) ; follow-up was at 1 year . The primary outcome measure was all-cause treatment discontinuation . Patients and their treating physicians were not blinded to the assigned treatment . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N68736636 . FINDINGS The number of patients who discontinued treatment for any cause within 12 months was 63 ( Kaplan-Meier estimate 72 % ) for haloperidol , 32 ( 40 % ) for amisulpride , 30 ( 33 % ) for olanzapine , 51 ( 53 % ) for quetiapine , and 31 ( 45 % ) for ziprasidone . Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride ( hazard ratio [ HR ] 0.37 , [ 95 % CI 0.24 - 0.57 ] ) , olanzapine ( HR 0.28 [ 0.18 - 0.43 ] ) , quetiapine ( HR 0.52 [ 0.35 - 0.76 ] ) , and ziprasidone ( HR 0.51 [ 0.32 - 0.81 ] ) . However , symptom reductions were virtually the same in all the groups , at around 60 % . INTERPRETATION This pragmatic trial suggests that clinical ly meaningful antipsychotic treatment of first-episode of schizophrenia is achievable , for at least 1 year . However , we can not conclude that second-generation drugs are more efficacious than is haloperidol , since discontinuation rates are not necessarily consistent with symptomatic improvement While haloperidol is still widely used in the treatment of psychoses , the optimal daily dose remains a topic of controversy , particularly in first-episode psychosis . Previous studies have suggested that doses as low as 2 mg/d may be effective , whereas others have indicated superiority for higher over lower doses . This double-blinded , r and omized controlled study compared the efficacy and tolerability of 2 vs. 8 mg/d of haloperidol over 6 wk in 40 subjects with first-episode psychosis . Both treatments were equally effective in reducing the PANSS Total and subscale scores . The low dose of haloperidol was better tolerated , with fewer extrapyramidal side-effects , less frequent use of anticholinergic medication and smaller elevations in prolactin levels . Using a low dose of haloperidol is at least as effective as , and better tolerated than a high dose of haloperidol in the treatment of first-episode psychosis Background Schizophrenia is a chronic disease of global importance . The second-generation antipsychotic quetiapine has a favorable side-effect profile , however , its clinical effectiveness has been called into question when compared with first-generation antipsychotics such as haloperidol . This study evaluates the efficacy and tolerability of quetiapine versus haloperidol for first-episode schizophrenia in the outpatient setting . Methods 156 adult patients with first-episode schizophrenia participated in an outpatient clinical trial and were r and omized to quetiapine ( 200 mg/d ; n = 78 ) or haloperidol ( 5 mg/d ; n = 78 ) . The study medications were titrated to a mean daily dose of 705 mg for quetiapeine and 14 mg for haloperidol . The patients were assessed at baseline , six weeks , and twelve weeks . The primary outcome measures were positive and negative scores of the Positive and Negative Syndrome Scale ( PANSS ) . Secondary measures were Global Assessment of Functioning ( GAF ) scale for overall psychosocial functioning , and Simpson-Angus Scale ( SAS ) for extra-pyramidal symptoms . Results At twelve weeks , the quetiapine group had a greater decrease in PANSS positive ( 18.9 vs. 15.3 , p = 0.013 ) and negative scores ( 15.5 vs. 11.6 , p = 0.012 ) , however , haloperidol showed a greater decrease in general psychopathology score ( 23.8 vs. 27.7 , p = 0.012 ) . No significant difference between groups were found for total PANSS ( 58.3 vs. 54.8 , p = 0.24 ) and GAF ( 45.7 vs. 46.2 , p = 0.79 ) . ANOVA identified significant group interactions on PANSS positive ( F = 18.72 , df = 1.6,52.4 , p < 0.0001 ) , negative ( F = 5.20 , df = 1.1,35.7 , p < 0.0001 ) , depression/anxiety ( F = 106.49 , df = 1.14,37.8 , p < 0.0001 ) , and total scores ( F = 7.51 , df = 1.4,45.6 , p = 0.001 ) . SAS ( 8.62 vs. 0.26 , p < 0.0001 ) and adverse events of akathisia ( 78 % vs. 0 % , p = 0.000 ) , parkinsonism ( 66.6 % vs. 0 % , p < 0.0001 ) , and fatigue ( 84.6 % vs. 66.6 % , p = 0.009 ) were greater in haloperidol compared to quetiapine , whereas headache was more common in quetiapine treated patients ( 11.5 % vs. 35.9 % , p < 0.0001 ) . Conclusions Quetiapine has greater efficacy for positive and negative symptoms with less extra-pyramidal symptoms than haloperidol when used for first-episode schizophrenia in the outpatient setting Research findings are particularly important for medication choice for first-episode patients as individual prior medication response to guide treatment decisions is unavailable . We describe the first large-scale double-masked r and omized comparison with first-episode patients of aripiprazole and risperidone , 2 commonly used first-episode treatment agents . One hundred ninety-eight participants aged 15 - 40 years with schizophrenia , schizophreniform disorder , schizoaffective disorder or psychotic disorder Not Otherwise Specified , and who had been treated in their lifetime with antipsychotics for 2 weeks or less were r and omly assigned to double-masked aripiprazole ( 5 - 30 mg/d ) or risperidone ( 1 - 6 mg/d ) and followed for 12 weeks . Positive symptom response rates did not differ ( 62.8 % vs 56.8 % ) nor did time to response . Aripiprazole-treated participants had better negative symptom outcomes but experienced more akathisia . Body mass index change did not differ between treatments but advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol , fasting glucose , and prolactin levels . Post hoc analyses suggested advantages for aripiprazole on depressed mood . Overall , if the potential for akathisia is a concern , low-dose risperidone as used in this trial maybe a preferred choice over aripiprazole . Otherwise , aripiprazole would be the preferred choice over risperidone in most situations based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications In a r and omised double-blind study , 46 first episode schizophrenics were given pimozide or flupenthixol for up to 5 weeks ; the mean daily dose at the end was 18.8 mg pimozide and 20 mg flupenthixol . There were no significant between-drug differences in the effect on mental state or behaviour ; positive schizophrenic symptoms responded to treatment , negative symptoms did not . Most patients required anti-Parkinsonian medication . Poor response was associated with ' organicity ' . A switch to maintenance therapy after 5 weeks , the outcome of successful treatment and patient cooperation , was achieved in only 54 % . There was no relationship between plasma prolactin levels and severity of schizophrenic symptoms in unmedicated patients . Pimozide produced greater elevation of plasma prolactin . Plasma neuroleptic levels showed drug compliance was satisfactory throughout in only 54 % OBJECTIVE Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder . This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large , controlled clinical trial . METHOD Patients with first-episode psychosis ( N=263 ) were r and omly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks . Domains measured included psychopathology , psychosocial variables , neurocognitive functioning , and brain morphology and metabolism . This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase . RESULTS Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity , which did not differ significantly in last-observation-carried-forward analyses . However , in a mixed-model analysis , olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating . Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain , compared with the haloperidol-treated patients . Overall , significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study ( 67 % versus 54 % ) . CONCLUSIONS As expected on the basis of previous studies , both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis . However , olanzapine had several relative advantages in therapeutic response . Although the nature of adverse events differed between the two agents , retention in the study was greater with olanzapine . Retention in treatment is important in this patient population , given their risk of relapse . Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia The purported advantages of second-generation or ‘ atypical ’ antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia . This flexible-dose study examined efficacy and safety in a r and omized , double-blind , 52-week trial , comparing chlorpromazine ( CPZ ) and clozapine ( CLZ ) in treatment naive patients experiencing their first episode of schizophrenia . In all , 160 in patients with first-episode schizophrenia or schizophreniform disorder were r and omized to CPZ or CLZ and followed them for 52 weeks or until dropout . The primary efficacy measure was time to first remission and proportion of time remaining in remission . The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects . Of these first-episode patients , 80 % achieved remission within 1 year ( 79 % CPZ , 81 % CLZ ) . The Kaplan – Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ ( χ2(1)=5.56 , p=0.02 ) . Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group . At 12 weeks , CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any . These symptom differences remained significant when controlling for EPS differences . By 52 weeks many of the symptom differences between groups were no longer significantly different . Generally , CLZ produced fewer side effects than CPZ , particularly extrapyramidal side effects . There was no significant difference between treatments in weight change or glucose metabolism . For each prior year of untreated psychosis , there was a 15 % decrease in the odds of achieving remission ( OR=0.85 ; CI 0.75–0.95 ) . A high proportion of first-episode patients remitted within 1 year . We detected no difference in the proportion of first-episode patients receiving CLZ or CPZ that achieved remission . However , first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ . While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks , the two treatment groups seemed to converge by 1 year . Longer duration of untreated psychosis was associated with lower odds of achieving remission OBJECTIVE This 52-week r and omized , double-blind , flexible-dose , multicenter study evaluated the overall effectiveness ( as measured by treatment discontinuation rates ) of olanzapine , quetiapine , and risperidone in patients early in the course of psychotic illness . METHOD Patients were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) , quetiapine ( 100 - 800 mg/day ) , or risperidone ( 0.5 - 4 mg/day ) administered in twice-daily doses . Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks ( primary outcome measure ) based on a prespecified noninferiority margin of 20 % . RESULTS A total of 400 patients were r and omly assigned to treatment with olanzapine ( N=133 ) , quetiapine ( N=134 ) , or risperidone ( N=133 ) . The mean modal prescribed daily doses were 11.7 mg for olanzapine , 506 mg for quetiapine , and 2.4 mg for risperidone . At week 52 , all-cause treatment discontinuation rates were 68.4 % , 70.9 % , and 71.4 % for olanzapine , quetiapine , and risperidone , respectively . Reductions in total score on the Positive and Negative Syndrome Scale ( PANSS ) were similar for the three treatment groups , but reductions in PANSS positive subscale scores were greater in the olanzapine group ( at 12 weeks and at 52 weeks or withdrawal from study ) and the risperidone group ( at 12 weeks ) . The most common elicited adverse events for olanzapine were drowsiness ( 53 % ) , weight gain ( 51 % ) , and insomnia ( 38 % ) ; for quetiapine , drowsiness ( 58 % ) , increased sleep hours ( 42 % ) , and weight gain ( 40 % ) ; and for risperidone , drowsiness ( 50 % ) , menstrual irregularities in women ( 47 % ) , and weight gain ( 41 % ) . CONCLUSIONS Olanzapine , quetiapine , and risperidone demonstrated comparable effectiveness in early-psychosis patients , as indicated by similar rates of all-cause treatment discontinuation Objective : Cognitive deficits , particularly those related to executive function and behavioural control , are a core feature of patients with schizophrenia and implicate disturbances of the prefrontal cortex ( PFC ) . Consistent with this , functional imaging studies have identified abnormalities of PFC activity in chronically affected patients . The objective of the current study was to investigate executive-control related neural activity from first onset of the illness through to symptom stabilization . Method : The authors examined eight neuroleptic-naïve first-episode psychosis ( FEP ) patients within 3 days of first presentation and eight healthy agepremorbid-IQ , and gender-matched controls ( CTL ) . All FEP patients were later confirmed with a diagnosis of schizophrenia . Subjects underwent H2 - 15O positron emission tomography ( PET ) while performing the Stroop interference task that has previously been shown to engage the PFC in healthy sample s. In a double-blind paradigm , FEP patients were r and omly treated with either haloperidol or risperidone for 8 weeks , after which CTLs and all but one of the FEP patients were re-scanned . Results : Behaviorally , there was no change in task performance from baseline to follow up for either the FEPs or CTLs . However , there were significant changes in functional activation in both groups across the same period . For CTLs , task-performance was associated with greater recruitment of posterior brain regions at follow up compared to baseline , while for FEP this involved greater recruitment frontal regions . Concurrently , FEP also showed significant improvement in positive symptomatology . Conclusions : These findings suggest that disturbances of the PFC often seen in FEP may be , at least partially , associated with acute symptom expression . However , it is still unclear whether this increase in frontal activity is due to symptom stabilization per se , the effects of medication , a lack of neurophysiological ‘ learning ’ with experience/ practice , or a combination of these factors . In the context of the CTLs performance , we interpret the patient findings as reflective of greater neurophysiological effort required for task accomplishment relative to the learned , more automated , processing apparent in the CTLs Objective : To compare the efficacy and adverse effect profiles of 2 widely used atypical antipsychotics in the short-term phase of first-episode schizophrenia in patients who were treatment-naive . A secondary objective was to establish the effective dose of these drugs in this context . Methods : A total of 72 patients with a first episode of schizophreniform psychosis ( schizophrenia spectrum disorder ) with less than 2 weeks of exposure to antipsychotic medication were r and omized to quetiapine or risperidone in a single-blind 12-week controlled trial . Psychopathologic diagnoses and adverse effects were assessed by blinded raters at 4 weekly intervals . Medication was administered by a specialized clinical team following dosing guidelines . Data were analyzed using an intention-to-treat paradigm . Results : Both quetiapine and risperidone were associated with a reduction in immediate symptoms and relatively few adverse effects other than weight gain . There was no statistically significant difference between the 2 compounds in adverse effects , relative efficacies , or adherence to treatment . The median ( SD ) time to cessation for patients r and omized to quetiapine was 65.3 ( 41.85 ) days and that for risperidone was 82.5 ( 44.88 ) days . There was no statistically significant difference between time to discontinuation for the 2 compounds . The mean daily doses prescribed were 375 mg of quetiapine and 2.72 mg of risperidone . Conclusions : Quetiapine and risperidone are both effective treatments in first-episode schizophrenia at doses lower than those used in patients with long-term schizophrenia and are similar in efficacy and the incidence of adverse effects OBJECTIVE To compare the impact of sertindole and haloperidol on cognitive function in patients suffering from schizophrenia . METHODS In a 12 week trial , of the 40 patients r and omised to treatment , 34 ( 17 sertindole and 17 haloperidol ) were included in the analysis set . Cognitive sub-processes were investigated with the Reaction Time Decomposition ( RTD ) method and the Wisconsin Card Sorting Test ( WCST ) , at baseline , Week 4 and Week 12 . RESULTS In executive function , i.e. set shifting tasks , sertindole reversed cognitive deficits significantly more than haloperidol . It was demonstrated that this atypical drug improved cognitive processing independently of motor function . Patients receiving sertindole markedly improved on the RTD task at Week 4 and continued to improve ( although at a slower rate ) at Week 12 , those patients receiving haloperidol showed marked impairment at Week 4 with partial recovery by Week 12 . CONCLUSION The study demonstrated two distinct processes of action on cognition between sertindole and haloperidol and the marked beneficial effects of sertindole , particularly in parameters that are regarded as schizophrenia-related cognitive disturbances OBJECTIVE To examine the course and potential predictors of treatment response in the early phase of schizophrenia . DESIGN Prospect i ve study of an inception cohort . SETTING Psychiatric division of an academic medical center with a suburban metropolitan catchment area . PATIENTS AND INTERVENTION Seventy first-episode patients who had undergone four biologic assessment procedures ( brain magnetic resonance imaging , behavioral response to methylpheni date hydrochloride , growth hormone levels , eye tracking ) were treated with a st and ardized antipsychotic drug protocol until recovery . Response was measured in terms of psychopathology and degree of remission . RESULTS Using survival analysis , the proportion of patients remitting by 1 year was estimated at 83 % . Mean and median times to remission were 35.7 weeks and 11 weeks , respectively . No baseline demographic or psychopathologic measure significantly predicted time to or level of remission . However , males tended to be nonresponders to treatment and have diagnoses of schizophrenia rather than schizoaffective disorder . Brain pathomorphology and abnormal basal growth hormone significantly predicted time to remission . CONCLUSIONS These results indicate that the antipsychotic treatment response of first-episode schizophrenics is better than chronic multiepisode patients and suggest that specific pathobiologic markers reflect pathophysiologic processes that mediate antipsychotic treatment response The aim of this study was to compare the 12-month effectiveness of several second-generation antipsychotic drugs , with that of haloperidol in never-treated patients with first-episode psychosis . In total , 114 patients without life time exposure to any psychotropic medication were r and omized to haloperidol , olanzapine , risperidone , quetiapine or ziprasidone . Primary outcome was time to all-cause discontinuation . Secondary outcomes included discontinuation rates and symptom change as measured by the Positive and Negative Syndrome Scale ( PANSS ) . The overall discontinuation rate 64 % . At 12 months , the proportion of patients discontinuing treatment was 40.0 % for olanzapine , 56.5 % for quetiapine , 64.0 % for risperidone , 80.0 % for ziprasidone and 85.7 % for haloperidol . Mean time to antipsychotic discontinuation was higher in patients r and omized to second-generation antipsychotics than in those taking haloperidol . Significantly lower discontinuation was noted in patients on olanzapine than on haloperidol , or ziprasidone . Our results suggest that olanzapine might lead to longer treatment continuation in treatment naïve FEP patients than haloperidol and , possibly ziprasidone . Global psychopathology was significantly less reduced by haloperidol than with each individual SGA in this earliest phase of treatment OBJECTIVE Atypical ( second-generation ) antipsychotics are considered st and ard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder . However , the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated . This study compared the efficacy and safety of two second-generation antipsychotics ( olanzapine and risperidone ) with a first-generation antipsychotic ( molindone ) in the treatment of early-onset schizophrenia and schizoaffective disorder . METHOD This double-blind multisite trial r and omly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine ( 2.5 - 20 mg/day ) , risperidone ( 0.5 - 6 mg/day ) , or molindone ( 10 - 140 mg/day , plus 1 mg/day of benztropine ) for 8 weeks . The primary outcome was response to treatment , defined as a Clinical Global Impression ( CGI ) improvement score of 1 or 2 and > or=20 % reduction in Positive and Negative Syndrome Scale ( PANSS ) total score after 8 weeks of treatment . RESULTS In total , 119 youth were r and omly assigned to treatment . Of these subjects , 116 received at least one dose of treatment and thus were available for analysis . No significant differences were found among treatment groups in response rates ( molindone : 50 % ; olanzapine : 34 % ; risperidone : 46 % ) or magnitude of symptom reduction . Olanzapine and risperidone were associated with significantly greater weight gain . Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol , low density lipoprotein , insulin , and liver transaminase levels . Molindone led to more self-reports of akathisia . CONCLUSIONS Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder . Adverse effects were frequent but differed among medications . The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia and schizoaffective disorder . The safety findings related to weight gain and metabolic problems raise important public health concerns , given the widespread use of second-generation antipsychotics in youth for nonpsychotic disorders |
11,812 | 27,262,383 | Adoption , implementation , and maintenance reporting did not vary among levels . | Sugar-sweetened beverage ( SSB ) consumption among children and adolescents is a determinant of childhood obesity .
Many programs to reduce consumption across the socioecological model report significant positive results ; however , the generalizability of the results , including whether reporting differences exist among socioecological strategy levels , is unknown .
This systematic review aim ed to examine the extent to which studies reported internal and external validity indicators defined by the reach , effectiveness , adoption , implementation , and maintenance ( RE- AIM ) model and assess reporting differences by socioecological level : Intrapersonal/interpersonal ( Level 1 ) , environmental/policy ( Level 2 ) , and multilevel ( Combined Level ) . | OBJECTIVE Great Taste , Less Waste ( GTLW ) , a communications campaign , capitalized on the synergy between healthy eating and eco-friendly behaviors to motivate children to bring more fruits and vegetables and fewer sugar-sweetened beverages ( SSBs ) to school . METHODS A cluster-r and omized trial in Eastern Massachusetts elementary schools in 2011 - 2012 tested the hypothesis that GTLW would improve the quality of foods from home more than a nutrition-only campaign -- Foods 2 Choose (F2C)--or control . Lunch and snack items from home were measured at baseline and 7 months later using digital photography . Mixed linear models compared change in mean servings of fruits , vegetables , and SSBs among groups , and change in mean prevalence of packaging type . Change in prevalence of food items of interest was compared among groups using generalized linear models . RESULTS Five hundred and eighty-two third and fourth grade rs from 82 classrooms in 12 schools participated . At follow-up , no significant differences were observed between groups in change in mean servings or change in prevalence of items of interest . No packaging differences were observed . CONCLUSION GTLW was well received , but no significant changes were observed in the quality of food brought to school . Whether classrooms are an effective environment for change remains to be explored . Clinical Trials.gov identifier : NCT0157384 Aims : The aim of this pilot study was to investigate the feasibility and effectiveness of placing water coolers on sugar-sweetened beverage sales at secondary schools ( age 12–18 years ) in the city of Zwolle , the Netherl and s. Methods : Six schools , hosting 5,866 pupils , were divided in three intervention and three control schools . In the intervention schools , water coolers were placed in the canteen . Hidden observations were performed in one school to study the intervention ’s feasibility , and school personnel was interviewed . Beverage sales were monitored before and during the intervention . After the intervention period , 366 class 1 and 2 pupils completed a question naire about their drinking habits ( response rate 81 % ) . Results : Placement of water coolers appeared to be a feasible intervention at secondary schools . However , it did not affect sales of sugar-sweetened beverages at schools . Although mean intake of sugar-sweetened beverages at school was high , more than 500 ml/day for boys , and more than 250 ml/day for girls , only a minority of these quantities was purchased at school . Conclusion : We conclude that placing water coolers as a single-issue intervention in secondary school canteens should not be prioritized in the combat against obesity Background The prevalence of overweight and obesity in children has at least doubled in the past 25 years with a major impact on health . In 2005 a prevention protocol was developed applicable within Youth Health Care . This study aims to assess the effects of this protocol on prevalence of overweight and health behaviour among children . Methods and design A cluster r and omised controlled trial is conducted among 5-year-old children included by 44 Youth Health Care teams r and omised within 9 Municipal Health Services . The teams are r and omly allocated to the intervention or control group . The teams measure the weight and height of all children . When a child in the intervention group is detected with overweight according to the international age and gender specific cut-off points of BMI , the prevention protocol is applied . According to this protocol parents of overweight children are invited for up to three counselling sessions during which they receive personal advice about a healthy lifestyle , and are motivated for and assisted in behavioural change . The primary outcome measures are Body Mass Index and waist circumference of the children . Parents will complete question naires to assess secondary outcome measures : levels of overweight inducing/reducing behaviours ( i.e. being physically active , having breakfast , drinking sweet beverages and watching television/playing computer games ) , parenting styles , parenting practice s , and attitudes of parents regarding these behaviours , health-related quality of life of the children , and possible negative side effects of the prevention protocol . Data will be collected at baseline ( when the children are aged 5 years ) , and after 12 and 24 months of follow-up . Additionally , a process and a cost-effectiveness evaluation will be conducted . Discussion In this study called ' Be active , eat right ' we evaluate an overweight prevention protocol for use in the setting of Youth Health Care . It is hypothesized that the use of this protocol will result in a healthier lifestyle of the children and an improved BMI and waist circumference . Trial registration Current Controlled Trials IS RCT OBJECTIVE . The study tested whether a combined environmental and educational intervention solely promoting water consumption was effective in preventing overweight among children in elementary school . METHODS . The participants in this r and omized , controlled cluster trial were second- and third- grade rs from 32 elementary schools in socially deprived areas of 2 German cities . Water fountains were installed and teachers presented 4 prepared classroom lessons in the intervention group schools ( N = 17 ) to promote water consumption . Control group schools ( N = 15 ) did not receive any intervention . The prevalence of overweight ( defined according to the International Obesity Task Force criteria ) , BMI SD scores , and beverage consumption ( in glasses per day ; 1 glass was defined as 200 mL ) self-reported in 24-hour recall question naires , were determined before ( baseline ) and after the intervention . In addition , the water flow of the fountains was measured during the intervention period of 1 school year ( August 2006 to June 2007 ) . RESULTS . Data on 2950 children ( intervention group : N = 1641 ; control group : N = 1309 ; age , mean ± SD : 8.3 ± 0.7 years ) were analyzed . After the intervention , the risk of overweight was reduced by 31 % in the intervention group , compared with the control group , with adjustment for baseline prevalence of overweight and clustering according to school . Changes in BMI SD scores did not differ between the intervention group and the control group . Water consumption after the intervention was 1.1 glasses per day greater in the intervention group . No intervention effect on juice and soft drink consumption was found . Daily water flow of the fountains indicated lasting use during the entire intervention period , but to varying extent . CONCLUSION . Our environmental and educational , school-based intervention proved to be effective in the prevention of overweight among children in elementary school , even in a population from socially deprived areas OBJECTIVES The objectives of this pilot study were to compare the dietary , physiological and metabolic effects of 12-week modified carbohydrate nutrition intervention when disseminated in an individualized home-based format versus a group classroom-based format . METHODS Twenty-three overweight ( > /=85(th ) percentile BMI ) Latina adolescent females ( 12 - 17 years of age ) were r and omized to a 12-week modified carbohydrate dietary intervention delivered in either an individualized home-based format ( n = 11 ) or a group classroom-based format ( n = 12 ) . Anthropometrics , dietary intake by 3-day diet records , insulin dynamics by extended 3-hour Oral Glucose Tolerance test ( OGTT ) and body composition by Dual energy X-ray absorptiometry ( DXA ) were measured before and after intervention ; 24-hour diet recalls were collected once or twice per month throughout the program . RESULTS Mixed modeling showed no significant differences in changes in dietary intake between intervention groups , but both groups significantly reduced intake of added sugar , sugary beverages and refined carbohydrates by 33 % , 66 % , and 35 % , respectively , and dietary fiber significantly increased by 44 % ( p < 0.01 ) throughout the 12 weeks . There was a significant time effect for BMI z-scores within each intervention group ( p < 0.05 ) . There was no significant time*intervention group interaction for any of the physiological or metabolic variables , indicating that change over time was not significantly different between intervention groups . CONCLUSIONS Although a culturally tailored , modified carbohydrate dietary intervention led to significant improvements in dietary intake and BMI z-scores , the extremely intensive , individualized , home-based program was no more effective at improving diet , decreasing adiposity or reducing type 2 diabetes risk factors than the traditional classroom-based format BACKGROUND Secondary school students often do not drink sufficient quantities of water during the school day to prevent dehydration , promote learning and good health . The study aim ed to measure the effect of health promotion and the free provision of cooled filtered water on the consumption of water and soft drinks . It also aim ed to explore students ' views of drinking water provision . METHODS A study was conducted with three secondary schools in North Tyneside . Over a 3 month period one school was given cooled filtered water and active promotion ( W + P ) , another had water only ( W ) . The control school ( C ) took part in post-intervention focus group work . RESULTS The average volume of water drunk by students , in school ' W + P ' was greater ( P = 0.05 ) than that drunk in school ' W ' and control school ' C ' . The volume of soft drinks purchased by students in all three schools before and during the intervention remained static . Focus group data revealed that students viewed their existing water provision as poor and wanted sufficient supplies of cooled filtered water in school . CONCLUSIONS This pilot study indicates that active promotion of water drinking increased consumption of water by secondary school students . Further developments of the project are suggested Background Computer tailoring may be a promising technique for prevention of overweight in adolescents . However , very few well-developed , evidence -based computer-tailored interventions are available for this target group . We developed and evaluated a computer-tailored intervention for adolescents targeting energy balance-related behaviours : i.e. consumption of snacks , sugar-sweetened beverages , fruit , vegetables , and fibre , physical activity , and sedentary behaviours . This paper describes the planned development of a school-based computer-tailored intervention aim ed at improving energy balance-related behaviours in order to prevent excessive weight gain in adolescents , and the protocol for evaluating this intervention . Methods / design Intervention development : Informed by the Pre caution Adoption Process Model and the Theory of Planned Behaviour , the computer-tailored intervention provided feedback on personal behaviour and suggestions on how to modify it . The intervention ( VETisnietVET translated as ' FATaintPHAT ' ) has been developed for use in the first year of secondary school during eight lessons . Evaluation design : The intervention will be evaluated in a cluster-r and omised trial including 20 schools with a 4-months and a 2-years follow-up . Outcome measures are BMI , waist circumference , energy balance-related behaviours , and potential determinants of these behaviours . Process measures are appreciation of and satisfaction with the program , exposure to the program 's content , and implementation facilitators and barriers measured among students and teachers . Discussion This project result ed in a theory and evidence -based intervention that can be implemented in a school setting . A large-scale r and omised controlled trial with a short and long-term follow-up will provide sound statements about the effectiveness of this computer-tailored intervention in adolescents . Trial Registration IS RCT OBJECTIVE To explore whether the effects on dietary behaviours of a computer-tailored intervention aim ed to prevent excessive weight gain among adolescents , FATaintPHAT , were moderated by sociodemographic , cognitive and home environmental factors . DESIGN A two-group cluster r and omized trial . Potential moderation of the outcome measures ( consumption of sugar-sweetened beverages , snacks , fruits and vegetables ) was studied by gender , education level , ethnicity , awareness of risk behaviour , intention and home availability . SETTING Twenty schools in the Netherl and s. SUBJECTS Students ( n 883 ) aged 12 - 13 years . RESULTS Of the twenty-four interactions tested , only three were significant . The intervention effect on sugar-sweetened beverages was moderated by level of education ( P = 0·009 ) ; intervention effects were found only among academic preparatory students . The intervention effects on fruit and vegetable intake were moderated by awareness of fruit intake ( P < 0·001 ) and home availability of vegetables ( P = 0·007 ) ; an effect on fruit intake was found only among students who were aware of their low fruit intake at baseline and an effect on vegetable consumption was found only among students who reported that vegetables were always available at their home . CONCLUSIONS The effects of the intervention generally did not differ between sociodemographic subgroups . The moderation by home availability illustrates that the environment may influence the effects of educational interventions BACKGROUND During the nutrition transition in Chile , dietary changes were marked by increased consumption of high-energy , nutrient-poor products , including sugar-sweetened beverages ( SSBs ) . Obesity is now the primary nutritional problem in posttransitional Chile . OBJECTIVE We conducted a r and omized controlled trial to examine the effects on body composition of delivering milk beverages to the homes of overweight and obese children to displace SSBs . DESIGN We r and omly assigned 98 children aged 8 - 10 y who regularly consumed SSBs to intervention and control groups . During a 16-wk intervention , children were instructed to drink 3 servings/d ( approximately 200 g per serving ) of the milk delivered to their homes and to not consume SSBs . Body composition was measured by dual-energy X-ray absorptiometry . Data were analyzed by multiple regression analysis according to the intention-to-treat principle . RESULTS For the intervention group , milk consumption increased by a mean ( + /- SEM ) of 452.5 + /- 37.7 g/d ( P < 0.0001 ) , and consumption of SSBs decreased by -711.0 + /- 33.7 g/d ( P < 0.0001 ) . For the control group , milk consumption did not change , and consumption of SSBs increased by 71.9 + /- 33.6 g/d ( P = 0.04 ) . Changes in percentage body fat , the primary endpoint , did not differ between groups . Nevertheless , the mean ( + /- SE ) accretion of lean body mass was greater ( P = 0.04 ) in the intervention ( 0.92 + /- 0.10 kg ) than in the control ( 0.62 + /- 0.11 kg ) group . The increase in height was also greater ( P = 0.01 ) in the intervention group ( 2.50 + /- 0.21 cm ) than in the control group ( 1.77 + /- 0.20 cm ) for boys but not for girls . CONCLUSION Replacing habitual consumption of SSBs with milk may have beneficial effects on lean body mass and growth in children , despite no changes in percentage body fat . This trial was registered at clinical trials.gov as NCT00149695 Objective To evaluate the effectiveness of a school-based intervention involving the families and teachers that aim ed to promote healthy eating habits in adolescents ; the ultimate aim of the intervention was to reduce the increase in body mass index ( BMI ) of the students . Design Paired cluster r and omized school-based trial conducted with a sample of fifth grade rs . Setting Twenty classes were r and omly assigned into either an intervention group or a control group . Participants From a total of 574 eligible students , 559 students participated in the study ( intervention : 10 classes with 277 participants ; control : 10 classes with 282 participants ) . The mean age of students was 11 years . Intervention Students attended 9 nutritional education sessions during the 2010 academic year . Parents/guardians and teachers received information on the same subjects . Main Outcome Measurement Changes in BMI and percentage of body fat . Results Intention-to-treat analysis showed that changes in BMI were not significantly different between the 2 groups ( β = 0.003 ; p = 0.75 ) . There was a major reduction in the consumption of sugar-sweetened beverages and cookies in the intervention group ; students in this group also consumed more fruits . Conclusion Encouraging the adoption of healthy eating habits promoted important changes in the adolescent diet , but this did not lead to a reduction in BMI gain . Strategies based exclusively on the quality of diet may not reduce weight gain among adolescents . Trial Registration Clinical trials.gov NCT01046474 OBJECTIVE To determine whether a multicomponent health promotion intervention for Dutch adolescents ( defined as persons between 12 and 14 years of age ) would be successful in influencing body composition and dietary and physical activity behavior in both the short and long terms . DESIGN R and omized controlled trial . SETTING Ten intervention and 8 control prevocational secondary schools . PARTICIPANTS A total of 1108 adolescents ( mean age , 12.7 years ) . Intervention An interdisciplinary program with an adapted curriculum for 11 lessons in biology and physical education and environmental change options . MAIN OUTCOME MEASURES Body height and weight , waist circumference , 4 skinfold thickness measurements , and dietary and physical activity behavior data . RESULTS Multilevel analyses showed that the intervention remained effective in preventing unfavorable increases in important measures of body composition after 20-month follow-up in girls ( biceps skinfold and sum of 4 skinfolds ) and boys ( triceps , biceps , and subscapular skinfolds ) . Consumption of sugar-containing beverages was significantly lower in intervention schools both after intervention ( boys : -287 mL/d ; 95 % confidence interval [ CI ] , -527 to -47 ; girls : -249 ; -400 to -98 ) and at 12-month follow-up ( boys : -233 ; -371 to -95 ; girls : -271 ; -390 to -153 ) . For boys , screen-viewing behavior was significantly lower in the intervention group after 20 months ( -25 min/d ; 95 % CI , -50 to -0.3 ) . No significant intervention effects on consumption of snacks or active commuting to school were found . CONCLUSION The Dutch Obesity Intervention in Teenagers program result ed in beneficial effects on the sum of skinfold thickness measurements in girls and consumption of sugar-containing beverages in both boys and girls in both the short and long terms OBJECTIVE To study the effects of school lessons about healthy food on adolescents ' self-reported beliefs and behaviour regarding the purchase and consumption of soft drinks , water and extra foods , including sweets and snacks . The lessons were combined with the introduction of lower-calorie foods , food labelling and price reductions in school vending machines . DESIGN A cluster-r and omized controlled design was used to allocate schools to an experimental group ( i.e. lessons and changes to school vending machines ) and a control group ( i.e. ' care as usual ' ) . Question naires were used pre-test and post-test to assess students ' self-reported purchase of extra products and their knowledge and beliefs regarding the consumption of low-calorie products . SETTING Secondary schools in the Netherl and s. SUBJECTS Twelve schools participated in the experimental group ( 303 students ) and fourteen in the control group ( 311 students ) . The students ' mean age was 13.6 years , 71.5 % were of native Dutch origin and mean BMI was 18.9 kg/m(2 ) . RESULTS At post-test , the experimental group knew significantly more about healthy food than the control group . Fewer students in the experimental group ( 43 % ) than in the control group ( 56 % ) reported bringing soft drinks from home . There was no significant effect on attitude , social norm , perceived behavioural control and intention regarding the consumption of low-calorie extra products . CONCLUSIONS The intervention had limited effects on students ' knowledge and self-reported behaviour , and no effect on their beliefs regarding low-calorie beverages , sweets or snacks . We recommend a combined educational and environmental intervention of longer duration and engaging parents . More research into the effects of such interventions is needed Background This study evaluates the effects of an intervention performed by youth health care professionals on child health behaviors . The intervention consisted of offering healthy lifestyle counseling to parents of overweight ( not obese ) 5-year-old children . Effects of the intervention on the child having breakfast , drinking sweet beverages , watching television and playing outside were evaluated . Methods Data were collected with the ' Be active , eat right ’ study , a cluster r and omized controlled trial among nine youth health care centers in the Netherl and s. Parents of overweight children received lifestyle counseling according to the intervention protocol in the intervention condition ( n = 349 ) and usual care in the control condition ( n = 288 ) . Parents completed question naires regarding demographic characteristics , health behaviors and the home environment at baseline and at 2-year follow-up . Cluster adjusted regression models were applied ; interaction terms were explored . Results The population for analysis consisted of 38.1 % boys ; mean age 5.8 [ sd 0.4 ] years ; mean BMI SDS 1.9 [ sd 0.4 ] . There were no significant differences in the number of minutes of outside play or television viewing a day between children in the intervention and the control condition . Also , the odds ratio for having breakfast daily or drinking two or less glasses of sweet beverages a day showed no significant differences between the two conditions . Additional analyses showed that the odds ratio for drinking less than two glasses of sweet beverages at follow-up compared with baseline was significantly higher for children in both the intervention ( p < 0.001 ) and the control condition ( p = 0.029 ) . Conclusions Comparison of the children in the two conditions showed that the intervention does not contribute to a change in health behaviors . Further studies are needed to investigate opportunities to adjust the intervention protocol , such as integration of elements in the regular well-child visit . The intervention protocol for youth health care may become part of a broader approach to tackle childhood overweight and obesity . Trial registration Current Controlled Trials IS RCT OBJECTIVE To examine change in high school students ' beverage consumption patterns pre- and post-intervention of reduced availability of sugar-sweetened beverages ( SSB ) and diet soda in school food venues . DESIGN A prospect i ve , quasi-experimental , nonr and omized study design . SETTING Public high schools . PARTICIPANTS A convenience sample from control ( n = 221 ) and intervention ( n = 235 ) high schools . INTERVENTION Schools aim ed to reduce ( n = 4 ) or not change ( n = 3 ) availability of SSB and diet soda in food venues for 1 school year . MAIN OUTCOME MEASURES Subjects ' beverage servings/day was determined from a food frequency question naire pre- and post-intervention . ANALYSIS Two-by-two mixed analysis of variance model compared pre- to post-intervention servings/day between control and intervention subjects , stratified by gender . RESULTS Consumption of SSB decreased in both intervention and control boys ( F = 53.69 , P < .05 ) and girls ( F = 22.87 , P < .05 ) . Intervention girls decreased diet soda consumption as compared to control girls ( F = 6.57 , P < .05 ) . CONCLUSION AND IMPLICATION S Reducing availability of SSB in schools did not result in a greater decrease in SSB consumption by intervention as compared to control subjects . The impact of reducing availability of SSB at school may be limited . A better underst and ing of beverage consumption patterns may be needed to determine the efficacy of school food policies on those youth susceptible to obesity Objective : To describe the effects of URMEL-ICE , a German school-based intervention for overweight prevention , on children ’s BMI and other measures of fat mass . Methods : A cluster-r and omised controlled design was used . The intervention which focused on physical activity , TV time and soft drink consumption was integrated into a second- grade curriculum and was implemented by classroom teachers themselves . It comprised 29 teaching lessons , 2 short exercise blocks per day and 6 family homework lessons . BMI was assessed as primary outcome measure , waist circumference and skinfold thickness as secondary outcomes . Data of 945 children were analysed . Results : Multivariate analyses adjusted for baseline values showed no statistically significant effect of the intervention on BMI , but on waist circumference ( –0.85 ; 95 % confidence interval ( 95 % CI ) –1.59 to –0.12 ) and subscapular skinfold thickness ( –0.64 ; 95 % CI –1.25 to –0.02 ) . After additional adjustment for individual time lag between baseline and follow-up , these effects were reduced to –0.60 ( 95 % CI –1.25 to 0.05 ) and –0.61 ( 95 % CI –1.26 to 0.04 ) and lost their statistical significance . Conclusion : This study contributes to the field of r and omised school-based studies on overweight prevention and shows that within a 1-year , integrated intervention no effect on BMI , but a tendency towards effects on fat mass can be achieved Relatively little research has assessed the association between obesogenic behaviors in parents and their children . The objective of the present analysis was to examine cross-sectional associations in television (TV)/video viewing , sugar-sweetened beverage intake , and fast food intake between mothers and their preschool aged children . We studied baseline data among 428 participants in High Five for Kids , a r and omized controlled trial of behavior change among overweight and obese children of ages 2 - 6.9 years . The main exposures were whether mothers viewed TV/videos < 1 h/day , drank < 1 serving/day of sugar-sweetened beverages , and ate fast food < 1 time/week . The main outcomes were whether children met these goals for the same behaviors . Using multivariate logistic regression adjusted for maternal and child characteristics , we estimated odds ratios of children meeting the behavioral goals . The majority of mothers ate fast food < 1 time/week ( 73 % ) and drank < 1 serving/day of sugar-sweetened beverages ( 73 % ) , while few mothers viewed < 1 h/day of TV/videos ( 31 % ) . Most children met the fast food goal ( 68 % ) , but not the goals for sugar-sweetened beverages ( 31 % ) or TV/video viewing ( 13 % ) . In adjusted models , the odds ratios for a child meeting the goal were 3.2 ( 95 % confidence interval ( CI ) 1.7 , 6.2 ) for TV/video viewing , 5.8 ( 95 % CI 2.8 , 12.0 ) for sugar-sweetened beverage intake , and 17.5 ( 95 % CI 9.8 , 31.2 ) for fast food intake if their mothers met the goal for the same behavior . Obesogenic behaviors of mothers and preschool aged children were strongly associated . Our findings lend support to obesity prevention strategies that target parental behavior and the family environment Objective : The present study aim ed at investigating the influence of food availability , rules and television viewing habits on eating behaviours in adolescents . Design : Cross-sectional study . Setting : Four r and omly selected middle schools . Subjects : A sample of 534 seventh and eighth grade rs . Interventions : Vali date d question naires were used to measure the family environment and fat , soft drink and fruit consumption . Hierarchical regression analyses on fat , soft drink and fruit consumption , with demographic and psychosocial variables entered as the first and environmental factors as the second block were conducted in boys and girls . Results : Boys with more unhealthy products available at home consumed more fat ( P⩽0.001 , 95 % CI : 8.2–29.4 ) and more soft drinks ( P⩽0.01 , 95 % CI : 0.2–1.4 ) . Boys who reported better television viewing habits ate more fruit ( P⩽0.001 , 95 % CI : −1.7 to −0.5 ) . Girls who reported better television viewing habits consumed less fat ( P⩽0.01 , 95 % CI : 1.4–9.0 ) and more fruit ( P⩽0.05 , 95 % CI : −1.0 to −0.1 ) . Girls who reported higher availability of healthy products at home ( P⩽0.05 , 95 % CI : 0.3–3.1 ) and more food rules ( P⩽0.001 , 95 % CI : −1.8 to −0.5 ) , consumed more fruit . Environmental factors were poor predictors of soft drink consumption among girls . Conclusion : Availability of (un)healthy food products , family food rules and TV viewing habits were related to one or more eating behaviours in boys or girls . Although home environmental factors can play an important role in influencing adolescents ’ eating behaviours , these factors were generally less predictive than demographic and psychosocial variables . Sponsorship : Ghent University and Policy Research Centre Sport , Physical Activity and Health funded by the Flemish Government Background and purpose : The lack of effective school-based interventions for preventing obesity in children has caused a call for longer duration of interventions and better reporting on design and evaluation methodology . The purpose of this paper is to present the development of the intervention , the design of the effectiveness study , and the test-retest reliability of the main outcome measures in the HEalth In Adolescents ( HEIA ) study . Methods / design : The HEIA intervention programme was developed based on literature review s , a social ecological framework , and focus groups . The intervention aim ed to increase total physical activity ( PA ) and consumption of fruit and vegetables and to decrease screen time and consumption of sugar-sweetened beverages . The intervention programme consisted of a classroom component , including dietary behaviour lessons , computer tailoring , fruit/vegetable and PA breaks , and posters , and an environmental component including active transport campaigns , equipment , suggestions for easy improvements of schoolyards , inspirational courses for teachers ( all with regards to PA ) , and fact sheets to parents . The effect of the intervention programme is evaluated in a cluster r and omised controlled trial design ( intervention = 12 schools , control = 25 schools ) including process evaluation . Main outcomes include anthropometry , PA , screen time , and consumption of fruit , vegetables , and sugar-sweetened beverages . A 2-week test— retest study was conducted among 114 pupils . Determinants of the behaviours were assessed . Similar data were collected from parents . Children ’s PA was measured objective ly by accelerometers . Conclusions : The HEIA study represents a theoretically informed r and omised trial comprising a comprehensive set of multilevel intervention components with a thorough evaluation using reliable outcome measures . The study will contribute to a better underst and ing of determinants of healthy weight development among young people and how such determinants can be modified Background Interventions conducted in school-aged children often involve parents , but few studies have reported effects on parents ’ own behaviour as a result of these interventions . Objective To determine if a multi-component , cluster r and omized controlled trial targeting 11–13 year olds influenced their consumption of fruit , vegetables , sugar-sweetened soft drinks and fruit drinks , and to explore whether the results varied by gender , adolescent weight status or parental educational level . A final aim was to assess whether the parents ’ intakes were affected by the intervention . Design Participants were 1,418 adolescents , 849 mothers and 680 fathers . Baseline and post-intervention data from the 20 months intervention study HEIA ( HEalth In Adolescents ) were included . Data were collected assessing frequency ( and amounts ; beverages only ) . Results No significant differences were found at baseline between the intervention and control groups , except for the parental groups ( educational level and intakes ) . At post-intervention , the adolescents in the intervention group consumed fruit more frequently ( P<0.001 ) and had a lower intake of sugar-sweetened fruit drinks compared to the control group ( P=0.02 ) . The parental educational level moderated the effect on intake of sugar-sweetened fruit drinks in adolescents . The intake was less frequent in the intervention groups compared to the control groups ( P=0.02 ) for those who had parents with low and medium educational level . Furthermore , the intervention may have affected mothers ’ fruit intake and the vegetable intake in higher educated fathers . Conclusion Favourable effects in favour of the intervention group were found for intake of fruit and sugar-sweetened fruit drinks among the adolescents in the HEIA study . Our results indicate that it is possible to reduce adolescents ’ intake of sugar-sweetened fruit drinks across parental education , and potentially affect sub-groups of parents Background Cardiovascular disease and type 2 diabetes are examples of chronic diseases that impose significant morbidity and mortality in the general population worldwide . Most chronic diseases are associated with underlying preventable risk factors , such as elevated blood pressure , high blood glucose or glucose intolerance , high lipid levels , physical inactivity , excessive sedentary behaviours , and overweight/obesity . The occurrence of intermediate outcomes during childhood increases the risk of disease in adulthood . Sugar-sweetened beverages are known to be significant sources of additional caloric intake , and given recent attention to their contribution in the development of chronic diseases , a systematic review is warranted . We will assess whether the consumption of sugar-sweetened beverages in children is associated with adverse health outcomes and what the potential moderating factors are . Methods / Design Of interest are studies addressing sugar-sweetened beverage consumption , taking a broad perspective . Both direct consumption studies as well as those evaluating interventions that influence consumption ( e.g. school policy , educational ) will be relevant . Non-specific or multi-faceted behavioural , educational , or policy interventions may also be included subject to the level of evidence that exists for the other interventions /exposures . Comparisons of interest and endpoints of interest are pre-specified . We will include r and omized controlled trials , controlled clinical trials , interrupted time series studies , controlled before-after studies , prospect i ve and retrospective comparative cohort studies , case – control studies , and nested case – control design s. The MEDLINE ® , Embase , The Cochrane Library , CINAHL , ERIC , and PsycINFO ® data bases and grey literature sources will be search ed . The processes for selecting studies , abstract ing data , and resolving conflicts are described . We will assess risk of bias using design -specific tools . To determine sets of confounding variables that should be adjusted for , we have developed causal directed acyclic graphs and will use those to inform our risk of bias assessment s. Meta- analysis will be conducted where appropriate ; parameters for exploring statistical heterogeneity and effect modifiers are pre-specified . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach will be used to determine the quality of evidence for outcomes . Systematic review registration PROSPERO CRD42014009641 BACKGROUND Providing drinking water to U.S. children during school meals is a recommended health promotion strategy and part of national nutrition policy . Urban school systems have struggled with providing drinking water to children , and little is known about how to ensure that water is served , particularly in afterschool setting s. PURPOSE To assess the effectiveness of an intervention design ed to promote water as the beverage of choice in afterschool programs . DESIGN The Out of School Nutrition and Physical Activity Initiative ( OSNAP ) used a community-based collaboration and low-cost strategies to provide water after school . A group RCT was used to evaluate the intervention . Data were collected in 2010 - 2011 and analyzed in 2011 . SETTING / PARTICIPANTS Twenty afterschool programs in Boston were r and omized to intervention or control ( delayed intervention ) . INTERVENTION Intervention sites participated in learning collaboratives focused on policy and environmental changes to increase healthy eating , drinking , and physical activity opportunities during afterschool time ( material s available at www.osnap.org ) . Collaboration between Boston Public Schools Food and Nutrition Services , afterschool staff , and research ers established water-delivery systems to ensure children were served water during snack time . MAIN OUTCOME MEASURES Average ounces of water served to children per day was recorded by direct observation at each program at baseline and 6-month follow-up over 5 consecutive school days . Secondary measures directly observed included ounces of other beverages served , other snack components , and water-delivery system . RESULTS Participation in the intervention was associated with an increased average volume of water served ( + 3.6 ounces/day ; p=0.01 ) during snack . On average , the intervention led to a daily decrease of 60.9 kcals from beverages served during snack ( p=0.03 ) . CONCLUSIONS This study indicates the OSNAP intervention , including strategies to overcome structural barriers and collaboration with key actors , can increase offerings of water during afterschool snack . OSNAP appears to be an effective strategy to provide water in afterschool setting s that can be helpful in implementing new U.S. Department of Agriculture guidelines regarding water availability during lunch and afterschool snack BACKGROUND The objective of this study , focused on parents and children to reduce sedentary behavior , consumption of soft drinks and high-fat and salt containing snacks , and increase the consumption of fruits and vegetables , was to assess the effect of a six month intervention and an 18 month follow-up intervention on the body mass index , food consumption and physical activity of 2nd and 3rd grade elementary school children . METHODS This was a r and omized cluster controlled trial . School children were selected from 2nd and 3rd ( n = 532 ) grade . MEASUREMENTS BMI z-score for age and sex was calculated and classified according to the WHO ( 2006 ) . Abdominal obesity was defined as WC > 90th of NHANES III . RESULTS At six months of the study differences were observed in BMI , -0.82 ( p = 0.0001 ) . At 24 months , results such as an increase of z-score BMI and waist circumference , a decrease in abdominal obesity , eighth per cent remission and an incidence of 18 % of overweight and obesity were observed . Additionally , an increase ( p = 0.007 ) in vegetable intake and physical activity ( p = 0.0001 ) was also reported , along with a decrease in sedentary activities and the consumption of snacks high in fat and salt . CONCLUSIONS The results of this study indicate that with a comprehensive intervention there is a positive response to lifestyle changes and a reduction of abdominal obesity Background Only limited data are available on the development , implementation , and evaluation processes of weight gain prevention programs in adolescents . To be able to learn from successes and failures of such interventions , integral written and published reports are needed . Methods Applying the Intervention Mapping ( IM ) protocol , this paper describes the development , implementation , and evaluation of the Dutch Obesity Intervention in Teenagers ( DOiT ) , a school-based intervention program aim ed at the prevention of excessive weight gain . The intervention focussed on the following health behaviours : ( 1 ) reduction of the consumption of sugar-sweetened beverages , ( 2 ) reduction of energy intake derived from snacks , ( 3 ) decrease of levels of sedentary behaviour , and ( 4 ) increase of levels of physical activity ( i.e. active transport behaviour and sports participation).The intervention program consisted of an individual classroom-based component ( i.e. an educational program , covering 11 lessons of both biology and physical education classes ) , and an environmental component ( i.e. encouraging and supporting changes at the school canteens , as well as offering additional physical education classes).We evaluated the effectiveness of the intervention program using a r and omised controlled trial design . We assessed the effects of the intervention on body composition ( primary outcome measure ) , as well as on behaviour , behavioural determinants , and aerobic fitness ( secondary outcome measures ) . Furthermore , we conducted a process evaluation . Discussion The development of the DOiT-intervention result ed in a comprehensive school-based weight gain prevention program , tailored to the needs of Dutch adolescents from low socio-economic background Introduction Although several studies suggest that drinking water may help prevent obesity , no US studies have examined the effect of school drinking water provision and promotion on student beverage intake . We assessed the acceptability , feasibility , and outcomes of a school-based intervention to improve drinking water consumption among adolescents . Methods The 5-week program , conducted in a Los Angeles middle school in 2008 , consisted of providing cold , filtered drinking water in cafeterias ; distributing reusable water bottles to students and staff ; conducting school promotional activities ; and providing education . Self-reported consumption of water , nondiet soda , sports drinks , and 100 % fruit juice was assessed by conducting surveys among students ( n = 876 ) , preintervention and at 1 week and 2 months postintervention , from the intervention school and the comparison school . Daily water ( in gallons ) distributed in the cafeteria during the intervention was recorded . Results After adjusting for sociodemographic characteristics and baseline intake of water at school , the odds of drinking water at school were higher for students at the intervention school than students at the comparison school . Students from the intervention school had higher adjusted odds of drinking water from fountains and from reusable water bottles at school than students from the comparison school . Intervention effects for other beverages were not significant . Conclusion Provision of filtered , chilled drinking water in school cafeterias coupled with promotion and education is associated with increased consumption of drinking water at school . A r and omized controlled trial is necessary to assess the intervention 's influence on students ' consumption of water and sugar-sweetened beverages , as well as obesity-related outcomes OBJECTIVE To determine whether an educational programme aim ed at discouraging students from drinking sugar-sweetened beverages could prevent excessive weight gain . DESIGN Forty-seven classes in twenty-two schools were r and omised as intervention or control . SUBJECTS Participants were 1140 , 9 - 12-year-old fourth grade rs ( 435 in the intervention group and 608 in the control group ) . Sugar-sweetened beverages and juice intake were measured through one 24 h recall at baseline and another at the end of the trial . The main outcome was the change in BMI ( BMI = weight (kg)/height ( m2 ) ) , measured at the beginning and at the end of the school year . Intention-to-treat analysis was performed taking into account the cluster ( classes ) effect . RESULTS A statistically significant decrease in the daily consumption of carbonated drinks in the intervention compared to control ( mean difference = -56 ml ; 95 % CI -119 , -7 ml ) was followed by a non-significant overall reduction in BMI , P = 0.33 . However , among those students overweight at baseline , the intervention group showed greater BMI reduction ( -0.4 kg/m2 compared with -0.2 kg/m2 in the control group ( P = 0.11 ) ) , and this difference was statistically significant among girls ( P = 0.009 ) . Fruit juice consumption was slightly increased in the intervention group ( P = 0.08 ) , but not among girls . CONCLUSION Decreasing sugar-sweetened beverages intake significantly reduced BMI among overweight children , and mainly among girls . Efforts to reduce energy intake through liquids need to emphasise overall sweetened beverages and addition of sugar on juices OBJECTIVE We examined whether drinking water per se is associated with drinking less of other beverages and whether changes in BMI are associated with the intake of water and other beverages . DESIGN Secondary analysis of a r and omized trial of fourth grade rs followed over 1 year . SETTING Public schools in the metropolitan area of Rio de Janeiro , Brazil . SUBJECTS Participants were 1134 students aged 10 - 11 years . RESULTS At baseline , a higher frequency of water consumption was associated with a greater daily intake of fruit juice ( P = 0.02 ) and a higher daily frequency of milk ( P = 0.005 ) . In the intervention group , the baseline frequency of water consumption was negatively associated with weight change over 1 year but without statistical significance ( coefficient = -0.08 kg/m2 ; 95 % CI -0.37 , 0.24 kg/m2 ) , whereas fruit juice intake frequency was positively associated with weight change : each increase in fruit juice intake of 1 glass/d was associated with a BMI increase of 0.16 ( 95 % CI 0.02 , 0.30 ) kg/m2 . CONCLUSIONS Our findings do not support a protective effect of water consumption on BMI , but confirm consumption of juice drinks as a risk factor for BMI gain . Students who reported high water consumption also reported high intake of other beverages ; therefore , the promotion of water consumption per se would not prevent excessive weight gain Objective To assess the long term effects of an obesity prevention programme in schools . Design Longitudinal results after a cluster r and omised controlled trial . Setting Schools in southwest Engl and . Participants Of the original sample of 644 children aged 7 - 11 , 511 children were tracked and measurements were obtained from 434 children three years after baseline . Intervention The intervention was conducted over one school year , with four sessions of focused education promoting a healthy diet and discouraging the consumption of carbonated drinks . Main outcome measures Anthropometric measures of height , weight , and waist circumference . Body mass index ( BMI ) converted to z scores ( SD scores ) and to centile values with growth reference curves . Waist circumference was also converted to z scores ( SD scores ) . Results At three years after baseline the age and sex specific BMI z scores ( SD scores ) had increased in the control group by 0.10 ( SD 0.53 ) but decreased in the intervention group by −0.01 ( SD 0.58 ) , with a mean difference of 0.10 ( 95 % confidence interval −0.00 to 0.21 , P=0.06 ) . The prevalence of overweight increased in both the intervention and control group at three years and the significant difference between the groups seen at 12 months was no longer evident . The BMI increased in the control group by 2.14 ( SD 1.64 ) and the intervention group by 1.88 ( SD 1.71 ) , with mean difference of 0.26 ( −0.07 to 0.58 , P= 0.12 ) . The waist circumference increased in both groups after three years with a mean difference of 0.09 ( −0.06 to 0.26 , P=0.25 ) . Conclusions These longitudinal results show that after a simple year long intervention the difference in prevalence of overweight in children seen at 12 months was not sustained at three years BACKGROUND Vending machines account for food sales and revenue in schools . We examined 3 strategies for promoting the sale of lower-calorie food products from vending machines in high schools in the Netherl and s. METHODS A school-based r and omized controlled trial was conducted in 13 experimental schools and 15 control schools . Three strategies were tested within each experimental school : increasing the availability of lower-calorie products in vending machines , labeling products , and reducing the price of lower-calorie products . The experimental schools introduced the strategies in 3 consecutive phases , with phase 3 incorporating all 3 strategies . The control schools remained the same . The sales volumes from the vending machines were registered . Products were grouped into ( 1 ) extra foods containing empty calories , for example , c and ies and potato chips , ( 2 ) nutrient-rich basic foods , and ( 3 ) beverages . They were also divided into favorable , moderately unfavorable , and unfavorable products . RESULTS Total sales volumes for experimental and control schools did not differ significantly for the extra and beverage products . Proportionally , the higher availability of lower-calorie extra products in the experimental schools led to higher sales of moderately unfavorable extra products than in the control schools , and to higher sales of favorable extra products in experimental schools where students have to stay during breaks . Together , availability , labeling , and price reduction raised the proportional sales of favorable beverages . CONCLUSION Results indicate that when the availability of lower-calorie foods is increased and is also combined with labeling and reduced prices , students make healthier choices without buying more or fewer products from school vending machines . Changes to school vending machines help to create a healthy school environment PURPOSE We used principles of community-based participatory research to develop and pilot test a 5-week intervention for middle school students , Students for Nutrition and eXercise ( SNaX ) . SNaX aim ed to translate school obesity-prevention policies into practice with peer advocacy of healthy eating and school cafeteria changes . METHODS A total 425 seventh grade rs ( 63 % of all seventh grade rs ) in the intervention school were surveyed at baseline regarding cafeteria attitudes and sugar-sweetened beverage consumption ; of the 425 students , 399 ( 94 % ) were surveyed again at 1-month post-intervention . School cafeteria records were obtained from two schools : the intervention school and a nonr and omized selected comparison school with similar student socio-demographic characteristics . RESULTS A total of 140 students in the intervention school were trained as peer advocates . In the intervention school , cafeteria attitudes among peer advocates significantly improved over time ( approximately one-third of a st and ard deviation ) , whereas cafeteria attitudes of non-peer advocates remained stable ; the improvement among peer advocates was significantly greater than the pre-post-change for non-peer advocates ( b = .71 , p < .001 ) . Peer advocates significantly reduced their sugar-sweetened beverage intake ( sports and fruit drinks ) , from 33 % before intervention to 21 % after intervention ( p = .03 ) . Cafeteria records indicated that servings of fruit and healthier entrées ( salads , s and wiches , and yogurt parfaits ) significantly decreased in the comparison school and significantly increased in the intervention school ; the magnitude of changes differed significantly between the schools ( p < .001 ) . CONCLUSIONS As compared with the non-peer advocates , peer advocates appeared to benefit more from the intervention . Future research should consider engaging parents , students , and other key community stakeholders to determine acceptable and sustainable cafeteria changes Motivational interviewing ( MI ) shows promise for pediatric obesity prevention , but few studies address parental perceptions of MI . The aim of this study was to identify correlates of parental perceptions of helpfulness of and satisfaction with a MI-based pediatric obesity prevention intervention . We studied 253 children 2 to 6 years of age in the intervention arm of High Five for Kids , a primary care – based r and omized controlled trial . In multivariable models , parents born outside the United States ( odds ratio [ OR ] = 8.81 ; 95 % confidence interval [ CI ] = 2.44 , 31.8 ) , with lower household income ( OR = 3.60 ; 95 % CI = 1.03 , 12.55 ) , and with higher BMI ( OR = 2.86 ; 95 % CI = 1.07 , 7.65 ) were more likely to perceive MI-based visits as helpful in improving children ’s obesity-related behaviors after the first year of the intervention . Parents of female ( vs male ) , black ( vs white ) , and Latino ( vs white ) children had lower intervention satisfaction . Our findings underscore the importance of tailoring pediatric obesity prevention efforts to target population 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 Objective The objective of this study is to assess population -level trends in children 's dietary intake and weight status before and after the implementation of a provincial school nutrition policy in the province of Nova Scotia , Canada . Method Self-reported dietary behavior and nutrient intake and measured body mass index were collected as part of a population -level study with grade 5 students in 2003 ( n = 5215 ) and 2011 ( 5508 ) , prior to and following implementation of the policy . We applied r and om effects regression methods to assess the effect of the policy on dietary and health outcomes . Results In 2011 , students reported consuming more milk products , while there was no difference in mean consumption of vegetables and fruits in adjusted models . Adjusted regression analysis revealed a statistically significant decrease in sugar-sweetened beverage consumption . Despite significant temporal decreases in dietary energy intake and increases in diet quality , prevalence rates of overweight and obesity continued to increase . Conclusion This population -level intervention research suggests a positive influence of school nutrition policies on diet quality , energy intake and healthy beverage consumption , and that more action beyond schools is needed to curb the increases in the prevalence of childhood obesity 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 OBJECTIVES We examined the effect of an intervention to provide caloric information about sugar-sweetened beverages ( SSBs ) on the number of SSB purchases . METHODS We used a case-crossover design with 4 corner stores located in low-income , predominately Black neighborhoods in Baltimore , Maryl and . The intervention r and omly posted 1 of 3 signs with the following caloric information : ( 1 ) absolute caloric count , ( 2 ) percentage of total recommended daily intake , and ( 3 ) physical activity equivalent . We collected data for 1600 beverage sales by Black adolescents , aged 12 - 18 years , including 400 during a baseline period and 400 for each of the 3 caloric condition interventions . RESULTS Providing Black adolescents with any caloric information significantly reduced the odds of SSB purchases relative to the baseline ( odds ratio [ OR ] = 0.56 ; 95 % confidence interval [ CI ] = 0.36 , 0.89 ) . When examining the 3 caloric conditions separately , the significant effect was observed when caloric information was provided as a physical activity equivalent ( OR = 0.51 ; 95 % CI = 0.31 , 0.85 ) . CONCLUSIONS Providing easily underst and able caloric information -- particularly a physical activity equivalent -- may reduce calorie intake from SSBs among low-income , Black adolescents Background . Primary care is an ideal setting to treat pediatric obesity . Effective , low-intensity ( ≤25 contact hours over 6 months ) interventions that reduce st and ardized body mass index ( z- BMI ) and can be delivered by primary care providers are needed . Objective . This pilot r and omized controlled trial investigated the effect of 3 low-intensity ( ≤25 contact hours over 6 months ) pediatric obesity treatments on z- BMI . Methods . Twenty-two families ( children 8.0 ± 1.8 years , z- BMI of 2.34 ± 0.48 ) were r and omized into 1 of 3 , 6-month , low-intensity conditions : newsletter ( N ) , newsletter and growth monitoring ( N + GM ) , or newsletter and growth monitoring plus family-based behavioral counseling ( N + GM + BC ) . Anthropometrics and child eating and leisure-time behaviors were measured . Results . Mixed-factor analyses of variance found a significant ( P < .05 ) main effect of time for z- BMI and servings per day of sugar sweetened beverages , with both decreasing over time . Conclusion . Low-intensity obesity treatments can reduce z- BMI and may be more feasible in primary care OBJECTIVE The objective of this study was to examine the efficacy of U.S. primary care paediatric obesity treatment recommendations , within two r and omized trials . METHODS Between November 2005 to September 2007 , 182 families ( children aged 4 - 9 years , body mass index [ BMI ] ≥85th percentile ) were recruited for two separate trials and r and omized within trial to a 6-month intervention . Each trial had one intervention that increased child growth-monitoring frequency and feedback to families ( GROWTH MONITORING ) . Each trial also had two interventions , combining GROWTH MONITORING with an eight-session , behavioural , parent-only intervention targeting two energy-balance behaviours ( Trial 1 : reducing snack foods and sugar-sweetened beverages [ DECREASE ] , and increasing fruits , vegetables and low-fat dairy [ INCREASE ] ; Trial 2 : decreasing sugar-sweetened beverages and increasing physical activity [ TRADITIONAL ] and increasing low-fat milk consumption and reducing television watching [ SUBSTITUTES ] ) . Child st and ardized BMI ( Z BMI ) and energy intake were assessed at 0 , 6 and 12 months . RESULTS In both trials , main effects of time were found for Z BMI , which decreased at 6 and 12 months ( P < 0.01 ) . In Trial 1 , Z BMI reduced from 0 to 6 months , which was maintained from 6 to 12 months ( ΔZ BMI 0 to 12 months = -0.12 ± 0.22 ) . In Trial 2 , Z BMI reduced from 0 to 6 and from 6 to 12 months ( ΔZ BMI 0 - 12 months = -0.16 ± 0.31 ) . For energy intake , main effects of time were found in both trials and intake reduced from 0 to 6 months ( P < 0.05 ) , with Trial 1 reducing intake from 0 to 12 months ( P < 0.05 ) . CONCLUSIONS All interventions improved weight status . Future research should examine effectiveness and translatability of these approaches into primary care setting OBJECTIVES We examined the ways in which adolescents altered the type and size of their purchases of sugar-sweetened beverages ( SSBs ) , together with whether the effects persisted after removing caloric information signs in stores . METHODS We used a case-crossover design with 6 stores located in low-income Black neighborhoods in Baltimore , Maryl and , from 2012 to 2013 . The intervention used 1 of 4 r and omly posted signs with caloric information : absolute calories , number of teaspoons of sugar , and number of minutes of running or miles of walking necessary to burn off a beverage . We collected data for 4516 purchases by Black adolescents , including both baseline and postintervention periods with no signs posted . RESULTS We found that providing caloric information significantly reduced the number of total beverage calories purchased , the likelihood of buying an SSB , and the likelihood of buying an SSB greater than 16 ounces ( P < .05 ) . After removing the signs , the quantity , volume , and number of calories from SSB purchases remained lower than baseline ( P < .05 ) . CONCLUSIONS Providing caloric information was associated with purchasing a smaller SSB , switching to a beverage with no calories , or opting to not purchase a beverage ; there was a persistent effect on reducing SSB purchases after signs were removed 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 The aim of the present study was to evaluate the effects of a middle school physical activity and healthy eating intervention , including an environmental and computer-tailored component , and to investigate the effects of parental involvement . A r and om sample of 15 schools with seventh and eight grade rs was r and omly assigned to one of three conditions : ( i ) intervention with parental involvement , ( ii ) intervention alone and ( iii ) control group . In 10 schools , an intervention , combining environmental changes with computer-tailored feedback , was implemented over 2 school years . In five intervention schools , increased parental support was added . Physical activity was measured with question naires in the total sample and with accelerometers in a sub- sample of children . Fat intake , fruit , water and soft drink consumption were measured using food-frequency question naires . Results showed significant positive intervention effects on physical activity in both genders and on fat intake in girls . Parental involvement did not increase intervention effects . It can be concluded that physical activity and eating behaviours of middle school children can be improved by school-based strategies combining environmental and personal interventions . The use of personalized computer-tailored interventions seems to be a promising tool for targeting adolescents but needs to be further explored OBJECTIVE Document the impact of Let 's Go ! , a multi setting community-based childhood obesity prevention program on participants in 12 communities in Maine . METHODS The study used repeated r and om telephone surveys with 800 parents of children to measure awareness of messages and child behaviors . Surveys were conducted in schools , child care programs , and afterschool programs to track changes in policies and environments . RESULTS Findings show improvements from 2007 to 2011 : Children consuming fruits and vegetables increased from 18 % , 95 % CI [ 15 , 21 ] , to 26 % [ 23 , 30 ] ( p < .001 ) ; children limiting sugary drinks increased from 63 % [ 59 , 67 ] to 69 % [ 65 , 73 ] ( p = .011 ) ; and parent awareness of the program grew from 10 % [ 7 , 12 ] to 47 % [ 43 , 51 ] ( p < .001 ) . Participating sites implemented widespread changes to promote healthy behaviors . CONCLUSIONS A multi setting , community-based intervention with a consistent message can positively impact behaviors that lead to childhood obesity BACKGROUND Mobile technologies have wide-scale reach and disseminability , but no known studies have examined mobile technologies as a st and -alone tool to improve obesity-related behaviors of at-risk youth . PURPOSE To test a 12-week mobile technology intervention for use and estimate effect sizes for a fully powered trial . METHODS Fifty-one low-income , racial/ethnic-minority girls aged 9 - 14 years were r and omized to a mobile technology ( n=26 ) or control ( n=25 ) condition . Both conditions lasted 12 weeks and targeted fruits/vegetables ( FVs ; Weeks 1 - 4 ) ; sugar-sweetened beverages ( SSBs ; Weeks 5 - 8 ) , and screen time ( Weeks 9 - 12 ) . The mobile intervention prompted real-time goal setting and self-monitoring and provided tips , feedback , and positive reinforcement related to the target behaviors . Controls received the same content in a written manual but no prompting . Outcomes included device utilization and effect size estimates of FVs , SSBs , screen time , and BMI . Data were collected and analyzed in 2011 - 2012 . RESULTS Mobile technology girls used the program on 63 % of days and exhibited trends toward increased FVs ( + 0.88 , p=0.08 ) and decreased SSBs ( -0.33 , p=0.09 ) . The adjusted difference between groups of 1.0 servings of FVs ( p=0.13 ) and 0.35 servings of SSBs ( p=0.25 ) indicated small to moderate effects of the intervention ( Cohen 's d=0.44 and -0.34 , respectively ) . No differences were observed for screen time or BMI . CONCLUSIONS A st and -alone mobile app may produce small to moderate effects for FVs and SSBs . Given the extensive reach of mobile devices , this pilot study demonstrates the need for larger-scale testing of similar programs to address obesity-related behaviors in high-risk youth 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 < .02 ) . CONCLUSIONS AND IMPLICATION S Short message service may be a useful tool for 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 OBJECTIVE : By the preschool years , racial/ethnic disparities in obesity prevalence are already present . The objective of this study was to examine racial/ethnic differences in early-life risk factors for childhood obesity . METHODS : A total of 1343 white , 355 black , and 128 Hispanic mother – child pairs were studied in a prospect i ve study . Mother 's reported child 's race/ethnicity . The main outcome measures were risk factors from the prenatal period through 4 years old that are known to be associated with child obesity . RESULTS : In multivariable models , compared with their white counterparts , black and Hispanic children exhibited a range of risk factors related to child obesity . In pregnancy , these included higher rates of maternal depression ( odds ratio [ OR ] : 1.55 for black , 1.89 for Hispanic ) ; in infancy more rapid weight gain ( OR : 2.01 for black , 1.75 for Hispanic ) , more likely to introduce solid foods before 4 months of age ( OR : 1.91 for black , 2.04 for Hispanic ) , and higher rates of maternal restrictive feeding practice s ( OR : 2.59 for black , 3.35 for Hispanic ) ; and after 2 years old , more televisions in their bedrooms ( OR : 7.65 for black , 7.99 for Hispanic ) , higher intake of sugar-sweetened beverages ( OR : 4.11 for black , 2.48 for Hispanic ) , and higher intake of fast food ( OR : 1.65 for black , 3.14 for Hispanic ) . Black and Hispanic children also had lower rates of exclusive breastfeeding and were less likely to sleep at least 12 hours/day in infancy . CONCLUSIONS : Racial/ethnic differences in risk factors for obesity exist prenatally and in early childhood . Racial/ethnic disparities in childhood obesity may be determined by factors that operate at the earliest stages of life |
11,813 | 16,034,883 | However , in the other RCT , no statistically significant differences between treatment and control groups were shown for multiple outcome measures .
There is inconsistent evidence to support the use of TENS as a single treatment in the management of chronic LBP . | BACKGROUND Chronic low-back pain ( LBP ) affects a significant proportion of the population .
Transcutaneous electrical nerve stimulation ( TENS ) was introduced more than 30 years ago as an adjunct to the pharmacological management of pain .
However , despite its widespread use , the usefulness of TENS in chronic LBP is still controversial .
OBJECTIVES The aim of this systematic review was to determine the effectiveness of TENS in the management of chronic LBP . | & NA ; The placebo effect of transcutaneous electrical stimulation was studied in 93 patients in a double‐blind cross‐over trial using a genuine stimulator and a placebo machine . Placebo analgesic effects occurred in 32 % of trials , as compared with 48 % for actual stimulation . The placebo effect of the transcutaneous electrical stimulator is similar to the placebo effect that is noted in other double‐blind studies in which medicationms are used BACKGROUND AND PURPOSE The prescriptive validity of a treatment-oriented extension-mobilization category for patients with low back syndrome ( LBS ) was examined . SUBJECTS Of a total of 39 patients with LBS referred for physical therapy , 24 patients ( 14 male , 10 female ) , aged 14 to 50 years ( means = 31.3 , SD = 11.6 ) , were classified as having signs and symptoms indicating treatment with an extension-mobilization approach . The remaining subjects were dismissed from the study . Patients in the extension-mobilization category were r and omly assigned to either an experimental ( treatment ) group ( n = 14 ) or a comparison group ( n = 10 ) . METHODS The experimental and comparison group subjects were treated with either mobilization and extension ( a treatment matched to the category ) or a flexion exercise regimen ( an unmatched treatment ) . Outcome was assessed with a modified Oswestry Low Back Pain Question naire administered initially and at 3 and 5 days after initiation of treatment . Data were analyzed with a 2 x 3 ( treatment group x treatment period ) analysis of variance . RESULTS The subjects ' rate of improvement , as indicated by the Oswestry question naire scores , was dependent on the treatment group to which they were assigned . Subjects treated with extension and mobilization positively responded at a faster rate than did those treated with a flexion-oriented program . CONCLUSION AND DISCUSSION This study illustrates that a priori classification of selected patients with LBS into a treatment category of extension and mobilization and subsequently treating the patients accordingly with specified interventions can be an effective approach to conservative management of selected patients Therapeutic trials often attempt to “ blind ” patient and investigator to the true nature of treatments received , reducing the influences of conscious or subconscious prejudices . In drug trials , this is accomplished with placebo tablets , but blinding in trials of physical treatments is more problematic . This issue arose in a clinical trial of transcutaneous electrical nerve stimulation ( TENS ) for patients with chronic low back pain . Several study design features were incorporated to promote blinding : use of sham TENS units visually identical with real units , exclusion of potential subjects with previous TENS experience , avoidance of a crossover design and use of identical visit frequency , instructions and modifications in electrode placement . Subjects were asked not to discuss treatments with the clinicians who performed outcome assessment s. Both patients and clinicians were asked to guess actual treatment assignments at the trial 's end . Every patient in the true TENS group believed the unit was functioning properly , but the degree of certainty varied . In the sham TENS group , 84 % also believed they had functioning units , but their certainty was significantly less than in the active treatment group . Differences in patient perceptions did not affect compliance , as the two groups had similar dropout rates , appointment compliance , days of TENS use and daily duration of TENS use . Clinicians guessed treatments correctly 61 % of the time ( as opposed to 50 % expected by chance ) , again suggesting partial success in blinding . These efforts at blinding may partly explain the negative trial results for TENS efficacy . We conclude that complete blinding is difficult to achieve because of sensory difference in treatment and unintended communication between patient and examiner . Nonetheless , trials of physical treatments can achieve partial blinding with the techniques described here , and the success of blinding can be assessed with simple questions at study completion OBJECTIVES To determine the efficacy of a complementary analgesic modality , percutaneous electrical nerve stimulation ( PENS ) , for the treatment of chronic low back pain ( CLBP ) in community-dwelling older adults . DESIGN R and omized , controlled clinical trial . SETTING University of Pittsburgh Pain Evaluation and Treatment Institute . PARTICIPANTS Thirty-four English speaking , community-dwelling adults aged 65 and older with CLBP of at least moderate intensity experienced every day or almost every day . INTERVENTION Subjects were r and omized to receive twice-weekly PENS and physical therapy ( PT ) or sham PENS and physical therapy for 6 weeks . MEASUREMENTS At baseline , immediately after the 6-week intervention period , and 3 months later , the primary outcome measures pain intensity and pain-related disability were assessed . The secondary outcome measures physical performance ( timed chair rise , functional reach , gait speed , static and isoinertial lifting ) , psychosocial factors ( mood , sleep , and life control ) , and cognitive function ( measures of attention , concentration , and mental flexibility ) were also collected . RESULTS Subjects r and omized to PENS plus PT displayed significant reductions in pain intensity measures from pre- to posttreatment ( P < .001 ) , but the sham PENS plus PT group did not ( P = .94 ) . These pain reduction effects were maintained at 3-month follow-up . Similarly , significant reductions in pain-related disability were observed at posttreatment ( P = .002 ) for the PENS plus PT group and were maintained at follow-up , but the sham PENS plus PT group did not show reductions in pain-related disability ( P = .81 ) . Of the secondary outcome measures , psychosocial function , timed chair rise , and isoinertial lifting endurance also improved significantly at posttreatment for the PENS plus PT group , and their improvement was sustained at 3-month follow-up , but the sham PENS plus PT did not display significant changes on these measures after treatment . CONCLUSION This preliminary study suggests that PENS may be a promising treatment modality for community-dwelling older adults with CLBP , as demonstrated by reduction in pain intensity and self-reported disability , and improvement in mood , life control , and physical performance . Larger studies with longer duration of follow-up are needed to vali date these findings and support the use of PENS in clinical practice OBJECTIVE To investigate to what extent a single 60-minute session of transcutaneous electrical nerve stimulation ( TENS ) would modify chronic clinical pain , acute experimental pain , and the flexion reflex evoked in chronic low back pain patients . STUDY DESIGN Thirty young subjects with chronic low back pain were r and omly allocated to two groups , receiving either TENS or placebo stimulation to the lumbosacral region for 60 minutes . The flexion reflex was elicited by an electrical stimulation applied to the subject 's right sole and recorded electromyographically from the biceps femoris and the tibialis anterior muscles . MAIN OUTCOME MEASURES Subjective sensation of low back pain and the electrically induced pain were measured by two separate visual analog scales , termed VAS(LBP ) and VAS(FR ) , respectively . Data obtained before , during , and 60 minutes after TENS and placebo stimulations were analyzed using repeated measures ANOVA . RESULTS The VAS(LBP ) score was significantly reduced to 63.1 % of the prestimulation value after TENS ( p<.001 ) , but the reduction was negligible after placebo stimulation ( to 96.7 % , p = .786 ) . In contrast , no significant change was found in the VASFR score ( p = .666 ) and the flexion reflex area ( p = .062 ) during and after stimulation within each group and between the two groups ( p = .133 for VASFR and p = .215 for flexion reflex area ) . CONCLUSIONS The same TENS protocol had different degrees of antinociceptive influence on chronic and acute pain in chronic low back pain patients BACKGROUND Electrical stimulation of peripheral nerves produces acute analgesic effects . This r and omized , sham-controlled , crossover study was design ed to evaluate the effect of differing duration s of electrical stimulation on the analgesic response to percutaneous electrical nerve stimulation in 75 consenting patients with low back pain . METHODS All patients received electrical stimulation for four different time intervals ( 0 , 15 , 30 , and 45 min ) in a r and om sequence over the course of an 11-week study period . All active percutaneous electrical nerve stimulation treatments were administered using alternating frequencies of 15 and 30 Hz three times per week for 2 consecutive weeks . The pre study assessment s included the health status survey short form question naire and 10-cm visual analog scale scores for pain , physical activity , and quality of sleep , with 0 being the best and 10 being the worst . The pain scoring was repeated 5 - 10 min after each 60-min study session and 24 h after the last treatment session with each of the four methods . The daily oral analgesic requirements were assessed during each of the four treatment blocks . At the end of each 2-week treatment block , the question naire was repeated . RESULTS Electrical stimulation using percutaneously placed needles produced short-term improvements in the visual analog scale pain , physical activity , and quality of sleep scores , and a reduction in the oral analgesic requirements . The 30-min and 45-min duration s of electrical stimulation produced similar hypoalgesic effects ( 48+/-21 % and 46+/-19 % , respectively ) and were significantly more effective than either 15 min ( 21+/-17 % ) or 0 min ( 10+/-11 % ) . The 30- and 45-min treatments were also more effective in improving physical activity and sleep scores over the course of the 2-week treatment period . In contrast to the sham treatment ( 0 min ) , the health status survey short form revealed that electrical stimulation for 15 to 45 min three times per week for 2 weeks improved patient function . CONCLUSION The recommended duration of electrical stimulation with percutaneous electrical nerve stimulation therapy is 30 min & NA ; It has recently been shown that ice massage of the web between the thumb and index finger produces significantly greater relief of dental pain than a placebo control procedure . These results indicate that ice massage may be comparable to transcutaneous electrical stimulation ( TES ) and acupuncture , and may be mediated by similar neural mechanisms . The purpose of this study was to examine the relative effectiveness of ice massage and TES for the relief of low‐back pain . Patients suffering chronic low‐back pain were treated with both ice massage and TES . The order of treatments was balanced , and changes in the intensity of pain were measured with the McGill Pain Question naire ( MPQ ) . The results show that both methods are equally effective : based on the Pain Rating Index of the MPQ , 67–69 % of patients obtained pain relief greater than 33 % with each method . The results indicate that ice massage is an effective therapeutic tool , and appears to be more effective than TES for some patients . It may also serve as an additional sensory‐modulation method to alternate with TES to overcome adaptation effects . Evidence that cold signals are transmitted to the spinal cord exclusively by A‐delta fibers and not by C fibers suggests that ice massage provides a potential method for differentiating among the multiple feedback systems that mediate analgesia produced by different forms of intense sensory input A prospect i ve , r and omized , double-blind , placebo-controlled clinical trial was performed to investigate the efficacy of electrical muscle stimulation when combined with a therapist-guided , st and ardized exercise therapy program in the treatment of nonacute low back pain . Eighty patients with low back pain of at least 6 weeks ' duration were r and omized into the following 2 groups : st and ardized exercise therapy with functional electrical muscle stimulation or st and ardized exercise therapy with placebo electrical stimulation . Subjects were evaluated at baseline , 2 months , and 6 months with a st and ardized back pain question naire and objective measurements of lumbar spine function . Exercise therapy was continued for 6 months , but electrical stimulation was discontinued at the 2-month interval . Of the 80 patients initially enrolled , 42 discontinued or withdrew before completing the entire study protocol . At the 2-month follow-up interval , subjects in the treatment group had statistically significantly improved lumbar spine function compared with the control subjects . This effect continued during the last 4 months of the study after electrical stimulation had been discontinued . This suggests that electrical muscle stimulation can be an effective adjunctive treatment modality for nonacute low back pain . The effects of this combined therapy seem to last beyond the duration of electrical stimulation treatment Patients with acute or chronic low back pain were treated in a double-blind study that compared transcutaneous electrical nerve stimulation at intense levels and gentle , mechanically administered massage . Transcutaneous electrical nerve stimulation produced significantly greater pain relief , based on two measures of the McGill Pain Question naire , and significant improvement in straight leg raising . There were no significant differences between the two groups in backflexion scores . Pain-relief scores and range-of-motion scores were significantly correlated . The results indicate that pain-relief scores provide valuable information and can easily be obtained from patients for whom pain is a major symptom STUDY DESIGN A r and omized trial design ed to compare interferential therapy with motorized lumbar traction and massage management for low back pain in a primary care setting . OBJECTIVE To measure and compare the outcome of interferential therapy and management by motorized lumbar traction and massage . SUMMARY OF BACKGROUND DATA Management of low back pain by interferential therapy and motorized lumbar traction and massage is common in Germany . No reports of previous r and omized trials for the outcome from interferential therapy were found . METHODS Consenting patients were r and omly assigned into one of two groups . A pretreatment interview was performed by the patient using a computer-based question naire . It also incorporated the Oswestry Disability Index and a pain visual analog scale . Management consisted of six sessions over a 2- to 3-week period . Oswestry Disability Indexes and pain visual analog scale scores also were obtained immediately after and at 3 months after treatment . RESULTS A total of 152 patients were recruited . The two treatment groups had similar demographic and clinical baseline characteristics . The mean Oswestry Disability Index before treatment was 30 for both groups ( n = 147 ) . After treatment , this had dropped to 25 , and , at 3 months , were 21 ( interferential therapy ) and 22 ( motorized lumbar traction and massage ) . The mean pain visual analog scale score before treatment was 50 ( interferential therapy ) and 51 ( motorized lumbar traction and massage ) . This had dropped , respectively , to 46 and 44 after treatment and to 42 and 39 at 3 months . CONCLUSIONS This study shows a progressive fall in Oswestry Disability Index and pain visual analog scale scores in patients with low back pain treated with either-interferential therapy or motorized lumbar traction and massage . There was no difference in the improvement between the two groups at the end of treatment . Although there is evidence from several trials that traction alone is ineffective in the management of low back pain , this study could not exclude some effect from the concomitant massage A number of treatments are widely prescribed for chronic back pain , but few have been rigorously evaluated . We examined the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) , a program of stretching exercises , or a combination of both for low back pain . Patients with chronic low back pain ( median duration , 4.1 years ) were r and omly assigned to receive daily treatment with TENS ( n = 36 ) , sham TENS ( n = 36 ) , TENS plus a program of exercises ( n = 37 ) , or sham TENS plus exercises ( n = 36 ) . After one month no clinical ly or statistically significant treatment effect of TENS was found on any of 11 indicators of outcome measuring pain , function , and back flexion ; there was no interactive effect of TENS with exercise . Overall improvement in pain indicators was 47 percent with TENS and 42 percent with sham TENS ( P not significant ) . The 95 percent confidence intervals for group differences excluded a major clinical benefit of TENS for most outcomes . By contrast , after one month patients in the exercise groups had significant improvement in self-rated pain scores , reduction in the frequency of pain , and greater levels of activity as compared with patients in the groups that did not exercise . The mean reported improvement in pain scores was 52 percent in the exercise groups and 37 percent in the nonexercise groups ( P = 0.02 ) . Two months after the active intervention , however , most patients had discontinued the exercises , and the initial improvements were gone . We conclude that for patients with chronic low back pain , treatment with TENS is no more effective than treatment with a placebo , and TENS adds no apparent benefit to that of exercise alone Bloodworth DM , Nguyen BN , Garver W , Moss F , Pedroza C , Tran T , Chiou-Tan FY : Comparison of stochastic vs. conventional transcutaneous electrical stimulation for pain modulation in patients with electromyographically documented radiculopathy . Am J Phys Med Rehabil 2004;83:584–591 . Objective : To determine if a transcutaneous electrical stimulation ( TENS ) unit modified to deliver electrical impulses at r and om ( R ) or stochastic frequency , called TENS-R , provided better pain relief than conventional TENS . Design : A prospect i ve , r and omized , double-blinded , placebo-controlled study at an urban teaching hospital . A total of 13 adult subjects with radiculopathy on electromyogram and chronic radicular pain rated pain before and after walking 100 feet with proximal ( axial ) placement of TENS leads with r and omized setting s on conventional TENS , placebo , or TENS-R and , subsequently , with distal ( limb ) placement of TENS leads with r and omized setting s , all on the same day . The pain measures used were the McGill Pain Question naire , parts 1 and 2 , and the Visual Analog Scale . The functional measure was speed of walking . Results : Four men and seven women completed the study pain scores , measured by McGill Pain Question naire part 2 , significantly improved when the patient used TENS-R vs. conventional TENS ( P = 0.006 , analysis of variance ) . Placement of TENS electrodes on the back significantly decreased pain compared with lead placement on the legs for McGill Pain Question naire part 1 ( P = 0.007 ) , McGill Pain Question naire part 2 ( P = 0.042 ) , and the Visual Analog Scale ( P = 0.026 ) measures . Conclusions : Qualitative pain scores significantly improved when the patient used TENS-R vs. conventional TENS . Lead placement of any TENS modality over the back vs. over the leg improved all pain scores Sixty patients aged 60 or over with back pain for at least 6 months were recruited from General Practitioner referrals and r and omized to 4 weeks of treatment with acupuncture or transcutaneous electrical nerve stimulation ( TENS ) . All treatments were administered by the same physiotherapist and both groups had the same contact with him . The following were measured at baseline , completion and at a 3-month follow-up by an independent observer blinded to treatment received : ( 1 ) pain severity on visual analogue scale ( VAS ) ; ( 2 ) pain subscale of Nottingham Health Profile ( NHP ) ; ( 3 ) number of analgesic tablets consumed in previous week ; ( 4 ) spinal flexion from C7 to S1 . Thirty-two patients were r and omized to acupuncture and 28 to TENS ; only three withdrew ( two from acupuncture , one from TENS ) . Significant improvements were shown on VAS ( P < 0.001 ) , NHP ( P < 0.001 ) and tablet count ( P < 0.05 ) between baseline and completion in both groups , these improvements remaining significant comparing baseline with follow-up with a further non-significant improvement in VAS and NHP in the acupuncture group . The acupuncture but not the TENS patients showed a small but statistically significant improvement ( P < 0.05 ) in mean spinal flexion between baseline and completion which was not maintained at follow-up . Thus in these elderly patients with chronic back pain both acupuncture and TENS had demonstrable benefits which outlasted the treatment period . Acupuncture may improve spinal flexion . This trial can not exclude the possibility that both treatments are ' placebos ' The authors report the results of a r and omized controlled trial to examine the effectiveness of transcutaneous electrical nerve stimulation ( TENS/CODETRON ) when added to a st and ard exercise program for industrial workers with acute low back pain ( LBP ) . Fifty-eight work-injured patients with LBP of 3 - 10 weeks duration were r and omized into two groups that received actual or placebo stimulation in combination with the exercise regimen . The groups were compared on the primary outcome measures of disability , pain , and return to work . No significant differences between the experimental and placebo groups were discovered on any of the measured outcomes . Exercise alone , when continued over 4 weeks , reduced disability and pain scores significantly . Under the experimental conditions of this trial , no additional benefits of TENS/CODETRON were detected when added to an active exercise regimen Objective : To investigate the hypoalgesic effects of transcutaneous electrical nerve stimulation ( TENS ) upon low back pain ( LBP ) in people with multiple sclerosis ( MS ) . Design : A r and omized double-blind placebo controlled clinical pilot study . Subjects and setting : Fifteen people with MS were recruited and r and omly allocated to one of the following groups under double blind conditions ( n = 5 per group ) : TENS 1 ( 4 Hz , 200 µs ) , TENS 2 ( 110 Hz , 200 µs ) , placebo TENS . Interventions : Treatment was applied for 45 minutes three times a week for six weeks with a four-week follow-up . Outcome measures : The following outcome measures were taken at weeks 1 , 6 , and 10 : visual analogue scale ( VAS ) ( for current LBP , right leg pain , left leg pain ) ; Leeds Multiple Sclerosis Quality of Life Question naire ; Rol and Morris Disability Question naire ; Short Form-36 ( SF-36 ) Version 1 ; and the McGill Pain Question naire ( MPQ ) . VAS for current LBP , right and left leg pain were also taken before and after treatment , and once a week during the follow-up period . Results : Analysis showed no statistically significant effects for any of the data . However , both active treatment groups showed a trend of improvement in the majority of the outcome measures . Conclusion : Active TENS was more effective than placebo TENS in decreasing VAS scores following each treatment although results were not statistically significant . Further work in this area is warranted and should include a larger number of participants in the form of a r and omized controlled clinical trial to determine the efficacy of this modality CONTEXT Low back pain ( LBP ) contributes to considerable disability and lost wages in the United States . Commonly used opioid and nonopioid analgesic drugs produce adverse effects and are of limited long-term benefit in the management of this patient population . OBJECTIVE To compare the effectiveness of a novel nonpharmacologic pain therapy , percutaneous electrical nerve stimulation ( PENS ) , with transcutaneous electrical nerve stimulation ( TENS ) and flexion-extension exercise therapies in patients with long-term LBP . DESIGN A r and omized , single-blinded , sham-controlled , crossover study from March 1997 to December 1997 . SETTING An ambulatory pain management center at a university medical center . PATIENTS Twenty-nine men and 31 women with LBP secondary to degenerative disk disease . INTERVENTIONS Four therapeutic modalities ( sham-PENS , PENS , TENS , and exercise therapies ) were each administered for a period of 30 minutes 3 times a week for 3 weeks . MAIN OUTCOME MEASURES Pretreatment and posttreatment visual analog scale ( VAS ) scores for pain , physical activity , and quality of sleep ; daily analgesic medication usage ; a global patient assessment question naire ; and Health Status Survey Short Form ( SF-36 ) . RESULTS PENS was significantly more effective in decreasing VAS pain scores after each treatment than sham-PENS , TENS , and exercise therapies ( after-treatment mean + /- SD VAS for pain , 3.4+/-1.4 cm , 5.5+/-1.9 cm , 5.6+/-1.9 cm , and 6.4+/-1.9 cm , respectively ) . The average + /- SD daily oral intake of nonopioid analgesics ( 2.6+/-1.4 pills per day ) was decreased to 1.3+/-1.0 pills per day with PENS ( P<.008 ) compared with 2.5+/-1.1 , 2.2+/-1.0 , and 2.6+/-1.2 pills per day with sham-PENS , TENS , and exercise , respectively . Compared with the other 3 modalities , 91 % of the patients reported that PENS was the most effective in decreasing their LBP . The PENS therapy was also significantly more effective in improving physical activity , quality of sleep , and sense of well-being ( P<.05 for each ) . The SF-36 survey confirmed that PENS improved posttreatment function more than sham-PENS , TENS , and exercise . CONCLUSIONS In this sham-controlled study , PENS was more effective than TENS or exercise therapy in providing short-term pain relief and improved physical function in patients with long-term LBP Hsieh RL , Lee WC : One-shot percutaneous electrical nerve stimulation vs. transcutaneous electrical nerve stimulation for low back pain : Comparison of therapeutic effects . Am J Phys Med Rehabil 2002;81:838–843 . Objective To investigate the therapeutic effects of one shot of low-frequency percutaneous electrical nerve stimulation vs. one shot of transcutaneous electrical nerve stimulation in patients with low back pain . Design In total , 133 low back pain patients were recruited for this r and omized , control study . Group 1 patients received medication only . Group 2 patients received medication plus one shot of percutaneous electrical nerve stimulation . Group 3 patients received medication plus one shot of transcutaneous electrical nerve stimulation . Therapeutic effects were measured using a visual analog scale , body surface score , pain pressure threshold , and the Quebec Back Pain Disability Scale . Results Immediately after one-shot treatment , the visual analog scale improved 1.53 units and the body surface score improved 3.06 units in the percutaneous electrical nerve stimulation group . In the transcutaneous electrical nerve stimulation group , the visual analog scale improved 1.50 units and the body surface score improved 3.98 units . The improvements did not differ between the two groups . There were no differences in improvement at 3 days or 1 wk after the treatment among the three groups . Conclusions Simple one-shot treatment with percutaneous electrical nerve stimulation or transcutaneous electrical nerve stimulation provided immediate pain relief for low back pain patients . One-shot transcutaneous electrical nerve stimulation treatment is recommended due to the rarity of side effects and its convenient application OBJECTIVES A preliminary examination of NMES and combined NMES/TENS for the management of chronic back pain . DESIGN Double-blind , placebo-controlled , r and omized repeated measures . SUBJECTS AND SETTING Consecutive sample of 24 chronic back pain patients ( 16 women and 8 men ) attending an outpatient pain clinic ( mean age 51.67 years , mean pain duration 3.83 years ) . All treatments were administered at home . INTERVENTIONS Subjects self-administered NMES , combined NMES/TENS , TENS , and placebo treatments . Each treatment had a duration of 5 consecutive hours per day over 2 consecutive days , with a 2-day hiatus between treatments to minimize carryover effects . MAIN OUTCOME MEASURES Pain reduction was assessed through pretreatment to posttreatment differences on the Present Pain Intensity ( PPI ) scale , and a visual analogue scale of Pain Intensity ( VAS-I ) . Posttreatment pain relief was assessed using a visual analogue scale of Pain Relief ( VAS-R ) . RESULTS Combined treatment , NMES , and TENS each produced significant pretreatment to posttreatment reductions in pain intensity as measured by both the PPI and VAS-I ( p < .05 ) . Combined treatment was superior to placebo on pain reduction ( p = .001 , p = .016 ) as well as pain relief ( p < .001 ) . Combined treatment was also superior to both TENS and NMES for pain reduction and pain relief ( p < .01 ) . NMES and TENS were superior only to placebo for pain relief ( p < .001 ) . CONCLUSIONS Combined NMES/TENS treatment consistently produced greater pain reduction and pain relief than placebo , TENS , or NMES . NMES alone , although less effective , did produce as much pain relief as TENS . Although preliminary , this pattern of results suggests that combined NMES/TENS may be a valuable adjunct in the management of chronic back pain . Further research investigating the effectiveness of both NMES and combined NMES/TENS seems warranted The objective of this study was to compare the effectiveness of electroacupuncture and TENS for low back pain when the electroacupuncture is applied in a clinical ly realistic manner . The study was design ed as an evaluator-blinded r and omised controlled trial ( RCT ) . The study was performed at the Tsukuba College of Technology Clinic in Japan . Twenty subjects , who suffered from low back pain ( LBP ) without sciatica , were recruited , using leaflets in Tsukuba city . Subjects were allocated to either an electroacupuncture ( EA ) group ( 10 patients ) or a transcutaneous electrical nerve stimulation ( TENS ) group ( 10 patients ) . The procedure for EA was in accordance with st and ard practice at our clinic . The main outcome measures were a pain relief scale ( 100 mm visual analogue scale : VAS ) and a LBP score recommended by the Japanese Orthopaedic Association ( JOA Score ) . Mean VAS value during the 2-weeks experimental period of the EA group was significantly smaller than that of the TENS group ( 65 mm vs 86 mm ; 95 % CI , 4.126 – 37.953 ) . JOA Score in the EA group improved significantly while that in the TENS group showed no change . Although some placebo effect may be included , EA appeared more useful than TENS in the short-term effect on low back pain . We suggest that more realistic acupuncture interventions based on st and ard practice should be employed in pragmatic RCTs A study of 31 healthy volunteers was done to test the hypothesis that analgesia produced by low frequency/high intensity ( LoF/Hil ) transcutaneous electrical nerve stimulation ( TENS ) is mediated by release of beta-endorphin ( beta-E ) . After r and omization , Group 1 ( n = 10 ) received no stimulation ( placebo ) ; Group 2 ( n = 9 ) received 30 minutes of high frequency/low intensity ( HiF/Lol ) TENS ; and Group 3 ( n = 12 ) received 30 minutes of low frequency/high density ( LoF/Hil ) TENS . Blood pressure , pulse , plasma beta-E levels , and evoked potential response were measured before and after treatment . Mean plasma beta-E increased with treatment in Groups 2 and 3 and fell in Group 1 , but the difference between the groups was not statistically significant . Sixty-seven percent of Groups 2 and 3 showed an increase in plasma beta-E levels compared with 30 percent in Group 1 ( two- sample test of proportions , p less than .05 ) . Evoked potential response , a measure of pain threshold , varied directly with plasma beta-E level independent of the type of treatment applied . This study did not demonstrate a difference between the effects of HiF/Lol versus Lof/Hil TENS on plasma beta-E in healthy subjects Abstract The aim of this study was to investigate the hypothesis that the perception of the apparent amount of voluntary control over muscle activity determines the efficacy of EMG biofeedback treatment in back-pain patients . Twenty-four patients with nonorganic or minor organic back pain were r and omly assigned to three training conditions : low-success , high-success and linear feedback of training performance . Contrary to expectations about the relationship between perceived control over muscle tension and pain , no differences in the effects of treatment were found between these three experimental groups . Statistically and clinical ly significant treatment gains were , however , found in all groups . Thus , the hypothesis of a relationship between perceived muscle tension reduction and pain reports in chronic back-pain patients is not confirmed . After a close analysis of the training sessions , and the muscle activity reduction actually obtained , an alternative hypothesis about EMG biofeedback training procedures is formulated The long-term effect of percutaneous electrical nerve stimulation ( PENS ) on chronic low back pain ( LBP ) is unclear . We evaluated the number of sessions for which PENS should be performed to alleviate chronic LBP and how long analgesia is sustained . Patients underwent treatment on a twice-weekly schedule for 8 wk . Group A ( n = 18 ) received PENS for 8 wk , group B ( n = 17 ) received PENS for the first 4 wk and transcutaneous electrical nerve stimulation ( TENS ) for the second 4 wk , and group C ( n = 18 ) received TENS for 8 wk . Pain level , degree of physical impairment , and the daily intake of nonsteroidal antiinflammatory drugs ( NSAIDs ) were assessed before the first treatment , 3 days after Week 2 , Week 4 , and Week 8 treatments , and at 1 and 2 mo after the sessions . During PENS therapy , the pain level decreased significantly from Week 2 in Groups A and B ( P < 0.05 or 0.01 ) , and physical impairment and required NSAIDs decreased significantly from Week 4 ( P < 0.05 or 0.01 ) in Group A but only at Week 4 in Group B ( P < 0.05 or 0.01 ) . These effects were sustained until 1-mo follow-up ( P < 0.01 ) in Group A but not in Group B ; these effects were not observed at 2-mo follow-up even in Group A. In Group C , pain level decreased significantly only at Week 8 ( P < 0.05 ) . Our results indicate that repeated PENS is more effective than TENS for chronic LBP but must be continued to sustain the analgesic effect Summary The analgesic effects of high frequency transcutaneous electrical nerve stimulation ( TNS ) , “ acupuncture-like ” TNS and placebo TNS were evaluated in 33 patients with rheumatoid arthritis and chronic h and pain using a r and omized , double-blind , non-crossover design . An oscilloscope was employed to monitor the stimulator output in the TNS treatment groups and to provide strong suggestion and a focus of attention in the placebo treatment group . The two forms of TNS were applied at the highest intensity that could be tolerated by patients . Assessment s of resting pain , joint tenderness , grip strength and grip pain were made before and after treatment . The pain and joint tenderness measurements showed high frequency TNS , “ acupuncture-like ” TNS and placebo TNS to be equally effective in producing analgesia of similar degree and trend over time . The grip strength measurements showed no significant change . The results obtained with placebo are probably due to the suggestion and attention effects of the visual stimulus . The implication s of these results in respect to pain control pathways are discussed . Although TNS given at high intensity was shown to be no better than placebo applied with strong suggestion , this does not preclude its use as a method of pain control in rheumatoid arthritis & NA ; Fifty‐four patients treated in a 3‐week inpatient rehabilitation program were r and omly assigned to and accepted treatment with electroacupuncture ( n = 17 ) , TENS ( low intensity transcutaneous nerve stimulation , n = 18 ) , and TENS dead‐battery ( placebo , n = 18 ) . Outcome measures included estimates of pain ( on a Visual Analogue Scale ) and disability by both physician and patient , physical measures of trunk strength and spine range of motion , as well as the patient 's perceptions of the relative contribution of the education , exercise training , and the electrical stimulation . Analyses of variance were utilized to determine effects of treatment ( electroacupuncture , TENS , placebo ) across time ( admission , discharge , and return ) for the outcome measures . There were no significant differences between treatment groups with respect to their overall rehabilitation . All 3 treatment groups ranked the contribution of the education as being greater than the electrical stimulation . However , the electroacupuncture group consistently demonstrated greater improvement on the outcome measures than the other treatment groups . For the visual analogue scale measure of average pain , there was a statistical trend at the return visit suggesting that the acupuncture group was experiencing less pain & NA ; Part I of our earlier pilot study demonstrated that patients preferred modulated stimulation forms — frequency modulation and burst — rather than conventional continuous mode . To assess whether long‐term therapeutic effects vali date the immediate test results , this trial was performed in 14 patients with 21 pain conditions . Considering the results of the pilot study , the test stimulator was modified and 4 different forms of transcutaneous electrical nerve stimulation were r and omly delivered to each patient who was blind to the modes of stimulation for 20 min . A second observer assessed the pain scores using visual analogue scales . The stimulation modes employed were : ( 1 ) conventional continuous stimulation ( continuous pulses with a constant frequency of 70 Hz ) , ( 2 ) burst stimulation ( 80 msec long trains of pulses , each train consisting of 8 pulses , with an internal frequency of 90 Hz repeated 1.3 times a second ) , ( 3 ) high‐rate frequency modulation , HRFM ( continuous pulses changed from 90 Hz to 55 Hz over 90 msec , 1.3 times a second ) , ( 4 ) low‐rate frequency modulation , LRFM ( continuous pulses changed from 60 Hz to 20 Hz over 90 msec , 1.3 times a second ) . After the test treatment of 4 sessions in the clinic , depending on the pain scores and duration of pain relief recorded , the most effective stimulation mode was determined for each patient and a portable stimulator preset appropriately for that mode was given to be used at home , under our supervision , for 3 months . Fourteen pain conditions out of 21 ( 66 % ) responded well to the therapy ; the majority preferred was the HRFM and burst‐type stimulation . These results vali date the initial testing of different stimulation modes before assessing long‐term stimulation therapy & NA ; Although high‐frequency low‐intensity transcutaneous electric nerve stimulation ( TENS ) has been extensively used to relieve low back pain , experimental studies of its effectiveness have yielded contradictory findings mainly due to method ological problems in pain evaluation and placebo control . In the present study , separate visual analog scales ( VAS ) were used to measure the sensory‐discriminative and motivational‐affective components of low back pain . Forty‐two subjects were r and omly assigned to 1 of 3 groups : TENS , placebo‐TENS , and no treatment ( control ) . In order to measure the short‐term effect of TENS , VAS pain ratings were taken before and after each treatment session . Also , to measure long‐term effects , patients rated their pain at home every 2 h throughout a 3‐day period before and 1 week , 3 months and 6 months after the treatment sessions . In comparing the pain evaluations made immediately before and after each treatment session , TENS and placebo‐TENS significantly reduced both the intensity and unpleasantness of chronic low back pain . TENS was significantly more efficient than placebo‐TENS in reducing pain intensity but not pain unpleasantness . TENS also produced a significant additive effect over repetitive treatment sessions for pain intensity and relative pain unpleasantness . This additive effect was not found for placebo‐TENS . When evaluated at home , pain intensity was significantly reduced more by TENS than placebo‐TENS 1 week after the end of treatment , but not 3 months and 6 months later . At home evaluation of pain unpleasantness in the TENS group was never different from the placebo‐TENS group . These results suggest that TENS reduces both the sensory‐discriminative and motivational‐af‐fective components of low back pain in the short term but that much of the reduction in the affective component may be a placebo effect . We conclude that TENS should be used as a short‐term analgesic procedure in a multidisciplinary program for low back pain rather than as an exclusive or long‐term treatment OBJECTIVE To determine the efficacy of interferential therapy ( IFT ) electrode placement technique compared with a control treatment in subjects with acute low back pain ( LBP ) . DESIGN Single-blind , r and omized , controlled trial with a 3-month follow-up . SETTING Outpatient physiotherapy departments in hospital and university setting s. PATIENTS A r and om sample of 60 eligible patients with back pain ( 28 men , 32 women ) were recruited by general practitioners and self-referral for physiotherapy treatment and r and omly assigned to 1 of 3 groups . INTERVENTIONS ( 1 ) " IFT painful area " and The Back Book , ( 2 ) " IFT spinal nerve " and The Back Book , and ( 3 ) " Control , " The Back Book only . St and ardized IFT stimulation parameters were used : carrier frequency 3.85 kHz ; 140 Hz constant ; pulse duration 130 micros ; 30 minutes ' duration . MAIN OUTCOME MEASURES Pain Rating Index , Rol and -Morris Disability Question naire ( RMDQ ) , and EuroQol were completed by subjects pretreatment , at discharge , and 3-month follow-up . RESULTS All groups had significant improvements in all outcomes at follow-up . Subjects managed by IFT spinal nerve and The Back Book displayed both a statistically significant ( p = .030 ) and clinical ly meaningful reduction in functional disability ( RMDQ ) , compared with management via IFT painful area and The Back Book combined or The Back Book alone . CONCLUSIONS The findings showed that IFT electrode placement technique affects LBP-specific functional disability , providing preliminary implication s for future clinical studies Abstract Low back pain is one of the most significant medical and socioeconomic problems in modern society . International guidelines call for evidence -based management for the pain and disability associated with musculoskeletal disorders . The purpose of this r and omized controlled trial is to address the question of efficacy and appropriateness of vertebral axial decompression ( VAX-D ) therapy , a new technology that has been shown in clinical research to create negative intradiscal pressures , and has been shown to be effective in treating patients presenting with chronic low back pain ( > 3 months duration ) with associated leg pain . Successful outcome was defined as a 50 % reduction in pain utilizing a 10 cm Visual Analog Pain Scale and an improvement in the level of functioning as measured by patient-nominated disability ratings . Patients were r and omly assigned to VAX-D or to TENS which was used as a control treatment or placebo . The TENS treatment demonstrated a success rate of 0 % , while VAX-D demonstrated a success rate of 68.4 % ( p < 0.001 ) . A statistically significant reduction in pain and improvement in functional outcome was obtained in patients with chronic low back pain treated with VAX-D. [ Neurol Res 2001 ; 23 : 780 - 784 |
11,814 | 30,154,897 | For endpoints correlated with higher adherence ( e.g. , a reduction in blood pressure ) , a nonsignificant benefit was observed for FDCs .
Moreover , it was demonstrated that higher adherence can lead to a lower risk of cardiovascular events .
Conclusions In comparison with FECs , the FDC treatment is associated with a significant improvement in the cooperation between a doctor and a patient and with increased patients ' adherence to the treatment schedule | Introduction Clinical studies have revealed that fixed-dose combinations ( FDCs ) of drugs can have a better effect on blood pressure than free-equivalent combinations ( FECs ) .
Our objectives were to perform an up-to- date assessment of the effectiveness of FDCs and FECs in antihypertensive therapy , to provide more accurate results by using a stratified meta- analysis . | BACKGROUND Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events . Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure . METHODS In the Cardiovascular Health Study , 5888 adults 65 years and older were recruited from 4 US centers . At baseline in 1989 - 1990 , participants underwent an extensive examination , and all subsequent cardiovascular events were ascertained and classified . RESULTS At baseline , 1961 men and 2941 women were at risk for an incident myocardial infa rct ion or stroke . During follow-up that averaged 6.7 years , 572 subjects had a coronary event , 385 had a stroke , and 896 died . After adjustment for potential confounders , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and pulse pressure were directly associated with the risk of incident myocardial infa rct ion and stroke . Only SBP was associated with total mortality . Importantly , SBP was a better predictor of cardiovascular events than DBP or pulse pressure . In the adjusted model for myocardial infa rct ion , a 1-SD change in SBP , DBP , and pulse pressure was associated with hazard ratios ( 95 % confidence intervals ) of 1.24 ( 1.15 - 1.35 ) , 1.13 ( 1.04 - 1.22 ) , and 1.21 ( 1.12 - 1.31 ) , respectively ; and adding pulse pressure or DBP to the model did not improve the fit . For stroke , the hazard ratios ( 95 % confidence intervals ) were 1.34 ( 1.21 - 1.47 ) with SBP , 1.29 ( 1.17 - 1.42 ) with DBP , and 1.21 ( 1.10 - 1.34 ) with pulse pressure . The association between blood pressure level and cardiovascular disease risk was generally linear ; specifically , there was no evidence of a J-shaped relationship . In those with treated hypertension , the hazard ratios for the association of SBP with the risks for myocardial infa rct ion and stroke were less pronounced than in those without treated hypertension . CONCLUSION In this population -based study of older adults , although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events , SBP was the best single predictor of cardiovascular events The effect of conventional propranolol and bendrofluazide tablets given twice daily has been compared with an equivalent dosage combined in a single capsule given twice daily in fourteen patients with essential hypertension . Good blood pressure control was achieved on both regimes in the majority of patients and there was no significant difference in treatment response between the two regimes . Use of the combined capsule is convenient and may improve patient compliance BACKGROUND Short-term studies have suggested that the use of initial combination therapy for the control of blood pressure improves early effectiveness . We tested whether a combination of aliskiren and amlodipine is superior to each monotherapy in early control of blood pressure without excess of adverse events , and if initial control by monotherapy impairs subsequent control by combination therapy . METHODS We did a double-blind , r and omised , parallel-group , superiority trial at 146 primary and secondary care sites in ten countries , with enrolment from Nov 28 , 2008 , to July 15 , 2009 . Patients eligible for enrolment had essential hypertension , were aged 18 years or older , and had systolic blood pressure between 150 and 180 mm Hg . Patients were r and omly assigned ( 1:1:2 ) to treatment with 150 mg aliskiren plus placebo , 5 mg amlodipine plus placebo , or 150 mg aliskiren plus 5 mg amlodipine . R and om assignment was through a central interactive voice response system and treatment allocation was masked from the patients . From 16 - 32 weeks , all patients received combination therapy with 300 mg aliskiren plus 10 mg amlodipine . Our primary endpoints , assessed on an intention-to-treat basis ( ie , in patients who received the allocated treatment ) , were the adjusted mean reduction in systolic blood pressure from baseline over 8 to 24 weeks , and then the final reduction at 24 weeks . This trial is registered with Clinical Trials.gov , number NCT00797862 . FINDINGS 318 patients were r and omly assigned to aliskiren , 316 to amlodipine , and 620 to aliskiren plus amlodipine . 315 patients initially allocated to aliskiren , 315 allocated to amlodipine , and 617 allocated to aliskiren plus amlodipine were available for analysis . Patients given initial combination therapy had a 6·5 mm Hg ( 95 % CI 5·3 to 7·7 ) greater reduction in mean systolic blood pressure than the monotherapy groups ( p<0·0001 ) . At 24 weeks , when all patients were on combination treatment , the difference was 1·4 mm Hg ( 95 % CI -0·05 to 2·9 ; p=0·059 ) . Adverse events caused withdrawal of 85 patients ( 14 % ) from the initial aliskiren plus amlodipine group , 45 ( 14 % ) from the aliskiren group , and 58 ( 18 % ) from the amlodipine group . Adverse events were peripheral oedema , hypotension , or orthostatic hypotension . INTERPRETATION We believe that routine initial reduction in blood pressure ( > 150 mm Hg ) with a combination such as aliskiren plus amlodipine can be recommended . FUNDING Novartis Pharma AG ABSTRACT Objective : Free combination hypertension medication is associated with a lower compliance and less persistence compared to fixed combination therapy and can , therefore , be associated with insufficient blood pressure reductions . This non-r and omized study investigated whether valsartan 160 mg/ hydrochlorothiazide 25 mg ( Val 160/HCTZ 25 ) in fixed dose combination could provide additional blood pressure control in hypertensive patients not adequately controlled by the free combination of c and esartan 32 mg plus HCTZ 25 mg . Research design and methods : One hundred and ninety-seven patients with a mean sitting diastolic blood pressure ( MSDBP ) between 100 and 110 mmHg entered a 4-week treatment phase with 32 mg of c and esartan in free combination with 25 mg of HCTZ once daily . One hundred and thirty-eight patients with uncontrolled BP at Week 4 , entered a second 4-week treatment phase with Val160/ HCTZ 25 once daily . Main outcome measures : The primary efficacy parameter was the reduction in MSDBP at trough between Week 4 and Week 8 in the intent-to-treat population . Results : At baseline , MSDBP was 103.0 ± 2.8 mmHg . After Week 4 , MSDBP had decreased to 93.8 ± 4.5 mmHg . Subsequent treatment with Val 160/HCTZ 25 for 4 weeks reduced MSDBP to 88.7 ± 8.6 mmHg . This represented an additional decrease in MSDBP of 5.1 ± 7.9 mmHg ( p < 0.0001 ) . Val 160/ HCTZ 25 reduced mean sitting systolic BP by 3.4 ± 13.0 mmHg ( p = 0.0029 ) . Conclusions : The fixed dose combination of valsartan 160/HCTZ 25 mg provided a statistically and clinical ly significant additional BP reduction in patients not controlled by the free combination of c and esartan 32 mg and HCTZ 25 mg The importance of number of tablets for patient compliance was investigated in 160 patients with mild-moderate essential hypertension treated with a beta-adrenoceptor blocker and a thiazide diuretic . Mean BP at entry 146 + /- 16/92 + /- 8 mm Hg . All patients were given pindolol 10 mg and clopamide 5 mg in one combination tablet or in separate tablets for 4 months respectively . Approximately 90 % of the patients took greater than 90 % of the prescribed dose throughout the study . Mean BP decreased progressively and heart rate increased slightly . Side effects were more frequently reported during the first month of the study than previously , and 30 patients discontinued the treatment . No differences in this respect were seen between 1 and 2 tablets daily . Approximately 75 % of the patients preferred 1 tablet daily , but combining two drugs in one tablet had no effect upon compliance OBJECTIVES To assess medication adherence , persistence , and costs between cohorts of patients in managed care setting s using a fixed-dose combination ( FDC ) or individual components ( IC ) of valsartan and hydrochlorothiazide in an insurance cl aims data base . METHODS Medical and prescription cl aims for hypertensive patients using a combination of valsartan and HCTZ were identified from the IHCIS National Managed Care Benchmark Data base via a retrospective cohort analysis . Study subjects had at least 110 days prior to start of study medications during which no other antihypertensive medications were prescribed , and were followed for 12 months . Cl aims for 8711 adult patients were analyzed for adherence , persistence and costs . General linear regression was conducted to detect differences in adherence among groups . Covariates included age , gender , persistence , number on concomitant cardiovascular drugs , and number of cardiovascular diagnoses . RESULTS Most subjects used an FDC product ( N=8150 , 93.6 % ) vs. the IC ( N=561 , 6.4 % ) . The FDC group had a larger portion of males and less concomitant cardiovascular medications or disease . A r and om sample of 1628 of the FDC subjects had improved values for medication adherence compared to the IC group ( 62.1 vs. 53.0 % , p<0.001 ) and persistence values were improved at both 180 days ( 73 vs. 28 % , p<0.001 ) and 365 days ( 54 vs. 19 % , p<0.001 ) . Both prescription drug costs ( $ 1587 vs. $ 2050 , p<0.001 ) and medical costs ( $ 3343 vs. $ 3817 , p<0.001 ) were lower in the FDC cohorts . CONCLUSIONS The use of fixed-dose therapy in hypertension may lead to increased adherence and persistence with a positive financial impact on both prescription and total medical costs . As with any retrospective cl aims data base analysis , unobserved systematic differences between the two medication groups may exist 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 Background and Purpose — The benefits of antihypertensive ( AH ) drugs on the risks of major cardiovascular outcomes have been demonstrated in clinical trials . However , approximately half of hypertensive patients do not adhere well to their prescribed AH therapy in actual practice . The purpose of this study was to assess the impact of adherence to AH agents on the incidence of cerebrovascular disease ( CD ) in real-world practice . Methods — A cohort of 83 267 hypertensive patients was reconstructed from the Régie de l'assurance maladie du Québec data bases . Subjects included were between 45 and 85 years old , initially free of cardiovascular disease , and newly treated for hypertension with AH agents between 1999 and 2004 . A nested case – control design was conducted to study CD occurrence . Every case was matched for age and duration of follow-up with up to 15 r and omly selected control subjects . The adherence to AH drugs was measured by calculating the medication possession ratio . Conditional logistic regression models were performed to assess the association between adherence to AH agents and CD adjusting for various potential confounders . Results — At cohort entry , the mean patient age was 65 years , 37.3 % were male , 8.6 % had diabetes , and 19.5 % had dyslipidemia . High adherence ( ≥80 % ) to AH drugs significantly decreased the risk of CD by 22 % ( rate ratio , 0.78 ; 95 % CI , 0.70 to 0.87 ) compared with lower adherence . Male gender , occurrence of cardiovascular disease during follow-up , and dyslipidemia were risk factors for CD . Conclusion — High adherence to AH therapy is associated with a reduced risk of CD outside the context of clinical trials in primary prevention Objective : To assess efficacy and tolerability of c and esartan cilexetil ( CC ) plus hydrochlorothiazide ( HCTZ ) fixed combination vs previous monotherapy ( PM ) plus HCTZ in hypertension . Design and Methods : After 2 - 4 weeks of run in , 409 out patients ( diastolic blood pressure , DBP > 90 and ≤⃒110 mmHg ; systolic blood pressure , SBP ≤⃒180 mmHg ) , aged 26 - 79 years , under monotherapy , were r and omized in a PROBE multicenter trial to CC 16 mg plus HCTZ 12.5 mg or PM plus HCTZ 12.5 mg for 8 weeks . HCTZ was doubled after the first 4 weeks in non-responders ( DBP ≥90 mmHg or SBP > 180 mmHg ) . Results : Automatic oscillometric ( Omron 705 CP ) DBP and SBP were similarly reduced by CC + HCTZ and PM + HCTZ after 4 ( 12/15 and 10/13 mmHg ) and 8 weeks ( 13/20 and 12/18 mmHg ) in the intention-to-treat ( ITT , n = 398 ) population . HCTZ dose was doubled in 18.1 and 31.2 % of patients in the CC + HCTZ and PM + HCTZ group , respectively ( p < 0.05 ) . Rate of normalized patients ( DBP < 90 and /or SBP < 140 mmHg ) after 8 weeks of treatment was greater ( p < 0.05 ) under CC + HCTZ ( 82.0 vs 72.6 % vs PM + HCTZ ) . Pulse pressure was comparably reduced by CC + HCTZ and PM + HCTZ , at 4 ( 3 mmHg for both ) and 8 weeks ( 7 and 6 mmHg , respectively ) . Heart rate was unchanged . Results of per- protocol analysis ( n = 316 ) did not differ from those of ITT analysis . Rate of adverse events was low and comparable between groups . Conclusions : CC plus HCTZ fixed combination is an effective and safe alternative to other antihypertensive drugs , given either as monotherapy or in combination when they do not satisfactorily control patient 's blood pressure This 8-week , r and omized , double-blind , controlled study compared efficacy and tolerability of telmisartan/amlodipine ( T/A ) single-pill combination ( SPC ) vs the respective monotherapies in 858 patients with severe hypertension ( systolic/diastolic blood pressure [ SBP/DBP ] ≥180/95 mm Hg ) . At 8 weeks , T/A provided significantly greater reductions from baseline in seated trough cuff SBP/DBP ( -47.5 mm Hg/-18.7 mm Hg ) vs T ( P<.0001 ) or A ( P=.0002 ) monotherapy ; superior reductions were also evident at 1 , 2 , 4 , and 6 weeks . Blood pressure ( BP ) goal and response rates were consistently higher with T/A vs T or A. T/A was well tolerated , with less frequent treatment-related adverse events vs A ( 12.6 % vs 16.4 % ) and a numerically lower incidence of peripheral edema and treatment discontinuation . In conclusion , treatment of patients with substantially elevated BP with T/A SPCs result ed in high and significantly greater BP reductions and higher BP goal and response rates than the respective monotherapies . T/A SPCs were well tolerated A double-blind , within-patient study was carried out in 23 newly diagnosed patients with mild to moderate hypertension ( diastolic blood pressure of at least 100 mmHg ) to compare the antihypertensive effects of atenolol ( 100 mg ) and chlorthalidone ( 25 mg ) given in free and fixed combination . After a 4-week placebo run-in period , patients received each of the two active treatments and also placebo for periods of 4 weeks , the treatment sequence being r and omized . A single daily drug dose was taken 24 to 28 hours before each blood pressure measurement at 2-weekly intervals . The results showed that both active drug combinations lowered lying , st and ing and post-exercise blood pressure significantly and there was no statistical difference between the two forms of treatment . Two-thirds of the patients were adequately controlled with the single daily dose regimen and few side-effects were reported Blood pressure ( BP ) control rates around the world are suboptimal . Part 2 of the National Health and Nutrition Educational Survey ( NHANES ) III indicates that only 27.4 % of hypertensive Americans aged 18 to 74 years have a BP of < 140/90 mm Hg . We wanted to assess BP control during the first 2 years and to describe the baseline characteristics of patients enrolled in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints ( CONVINCE ) Study , an international clinical trial that compares outcomes in hypertensive patients r and omized to initial treatment with either controlled-onset extended-release verapamil or the investigator ’s choice of atenolol or hydrochlorothiazide . At r and omization , BP was < 140/90 mm Hg in only 20.3 % of the 16 602 subjects ( average±SD age 65.6±7.4 years ; 56 % women , 84 % white/7 % black/7 % Hispanic ) . The average BP at enrollment was 148/85 mm Hg for patients taking BP medications ( n=13 879 ) and 161/94 mm Hg for previously untreated patients ( n=2723 ) . After medication titration , with a transtelephonic computer that recommended an increase in the dose or number of antihypertensive agents whenever the BP was 140/90 mm Hg , 84.8 % of the subjects attained the goal BP . During 2 years of treatment , BP control was maintained in 67 % to 69 % of the subjects ( 69 % to 71 % for systolic BP of < 140 mm Hg and 90 % for diastolic BP of < 90 mm Hg ) . These data suggest that the control of systolic BP is more difficult than the control of diastolic BP . The US national goal of having 50 % of hypertensives with a BP of < 140/90 mm Hg may be achievable if a forced titration strategy is used . Interested investigators , free care and medications , and well-educated subjects may make the attainment of such a goal easier in the CONVINCE study than in the general population |
11,815 | 30,264,539 | Our analyses suggest that fatigue is a frequent , independent nonmotor symptom in PD appearing early and persisting throughout the disease course , and that establishing uniform diagnostic criteria for PD-related fatigue is critical .
In addition , several nonmotor symptoms appear to be associated with fatigue and negatively impact quality of life .
Pharmacological and nonpharmacological interventions targeting fatigue and associated symptoms may improve quality of life in patients with PD . | We conducted a systematic review and meta- analysis aim ed at establishing robust prevalence estimates and identifying clinical correlates of fatigue in PD . | BACKGROUND The ADAGIO study investigated whether rasagiline has disease-modifying effects in Parkinson 's disease . Rasagiline 1 mg per day , but not 2 mg per day , was shown to be efficacious in the primary analysis . Here , we report additional secondary and post-hoc analyses of the ADAGIO study . METHODS ADAGIO was a placebo-controlled , double-blind , multicentre , delayed-start study , in which 1176 patients with untreated early Parkinson 's disease were r and omly assigned to receive rasagiline 1 mg or 2 mg per day for 72 weeks ( early-start groups ) or placebo for 36 weeks followed by rasagiline 1 mg or 2 mg per day for 36 weeks ( delayed-start groups ) . We assessed the need for additional antiparkinsonian therapy and changes in non-motor experiences of daily living and fatigue scales ( prespecified outcomes ) and changes in unified Parkinson 's disease rating scale ( UPDRS ) scores and subscores in placebo and active groups ( post-hoc outcomes ) . The ADAGIO study is registered with Clinical Trials.gov , number NCT00256204 . FINDINGS The need for additional antiparkinsonian therapy was reduced with rasagiline 1 mg ( 25 of 288 [ 9 % ] patients ) and 2 mg ( 26 of 293 [ 9 % ] ) versus placebo ( 108 of 593 [ 18 % ] ; odds ratio for 1 mg rasagiline vs placebo 0·41 , 95 % CI 0·25 - 0·65 , p=0·0002 ; 2 mg rasagiline vs placebo 0·41 , 0·26 - 0·64 , p=0·0001 ) . At week 36 , both doses significantly improved UPDRS motor subscores compared with placebo ( 1 mg rasagiline mean difference -1·88 [ SE 0·35 ] ; 2 mg rasagiline -2·18 [ 0·35 ] ; both p<0·0001 ) and activities of daily living subscores ( ADL ; 1 mg rasagiline -0·86 [ 0·18 ] ; 2 mg rasagiline -0·88 [ 0·18 ] ; both p<0·0001 ) , and 1 mg rasagiline significantly improved UPDRS mentation subscore ( -0·22 [ 0·08 ] ; p=0·004 ) . At week 72 , the only significant difference between early-start and delayed-start groups was for ADL subscore with the 1 mg dose ( -0·62 [ 0·29 ] ; p=0·035 ) . When assessed for the effect on non-motor symptoms at week 36 , both doses showed benefits on the Parkinson fatigue scale versus placebo ( 1 mg rasagiline mean difference -0·14 [ SE 0·05 ] , p=0·0032 ; 2 mg rasagiline -0·19 [ 0·05 ] , p<0·0001 ) , and the 1 mg dose showed benefits on the scale for non-motor experiences of daily living compared with placebo ( mean difference -0·33 [ 0·17 ] ; p=0·049 ) . The rate of progression of total UPDRS score for patients in the placebo group was 4·3 points [ SE 0·3 ] over 36 weeks , with extrapolation to about 6 units per year . In the placebo group , patients with the lowest quartile of baseline UPDRS scores ( ≤14 ; n=160 ) progressed more slowly than did those with highest scores ( > 25·5 ; n=145 ; mean difference -3·46 [ SE 0·77 ] ; p<0·0001 ) . INTERPRETATION These findings show that rasagiline delayed the need for symptomatic antiparkinsonian drugs and emphasise the contribution of the UPDRS ADL in the response of the rasagiline 1 mg per day early-start versus delayed-start group . The rate of UPDRS deterioration was less than was anticipated from previous studies and correlated with baseline severity . Underst and ing of the pattern of UPDRS deterioration is essential to assess disease modification . FUNDING Teva Pharmaceutical Industries and H Lundbeck BACKGROUND AND PURPOSE Fatigue is a common and disabling non-motor symptom in Parkinson 's disease ( PD ) . The pathogenesis is unknown , and the treatment options are limited . The aim of the present study was to investigate the development of fatigue during the first year after diagnosis . METHODS The study design was a prospect i ve , controlled population -based longitudinal cohort study , comprising 181 de novo , drug-naïve patients with PD and 162 control participants . PD was diagnosed according to the Gelb criteria . Fatigue was assessed by the Fatigue Severity Scale ( FSS ) . Both groups were assessed for fatigue at baseline and after 1 year . RESULTS Patients reported more fatigue than the control subjects at baseline and at the 1-year follow-up evaluation . The FSS scores in the patient group improved from a mean score of 4.4 ( SD 1.6 ) to 4.0 ( SD 1.6 ) . Patients with fatigue at baseline received higher doses of dopaminergic medication during follow-up . Patients who received dopamine agonists improved slightly more than patients who received levodopa . A regression analysis did not show a correlation between an improvement in fatigue and a change in disease severity , depressive symptoms , sleep problems , apathy or cognitive impairment . CONCLUSION Fatigue is a common symptom in PD , also in early , untreated patients . During the first year of observation , an improvement in the fatigue scores was found . The improvement could not be attributed to a change in disease severity or depressive symptoms . The results indicate a better effect of dopamine agonists than of levodopa . This may have implication s for treatment in patients with PD-associated fatigue Objective : To evaluate if mental fatigue is a symptom that appears independently from other clinical features in patients with Parkinson disease ( PD ) , and to study if fatigue is persistent over time in these patients . Methods : In 1993 , 233 patients with PD were included in a community-based study of fatigue and followed prospect ively over 8 years . Fatigue was measured by a combination of a seven-point scale and parts of the Nottingham Health Profile ( NHP ) at baseline and after 4 and 8 years . In addition , the Fatigue Severity Scale ( FSS ) was used to evaluate fatigue in 2001 . Population -averaged logistic regression models for correlated data were performed to study the relationship between fatigue and various demographic and clinical variables . Results : In patients who were followed throughout the 8-year study period , fatigue increased from 35.7 % in 1993 to 42.9 % in 1997 and 55.7 % in 2001 . Fatigue was related to disease progression , depression , and excessive daytime sleepiness ( EDS ) . However , the prevalence of fatigue in patients without depression and EDS remained high and increased from 32.1 % to 38.9 % during the study period . For about 44 % of the patients with fatigue the presence of this symptom varied during the study period , as it was persistent in 56 % of the patients with fatigue . Conclusions : The authors confirmed the high prevalence of mental fatigue in patients with Parkinson disease ( PD ) . Fatigue is related to other non-motor features such as depression and excessive daytime sleepiness , but can not be explained by this comorbidity alone . In more than half of the patients mental fatigue is persistent and seems to be an independent symptom that develops parallel to the progressive neurodegenerative disorder of PD BACKGROUND Fatigue is one of the most disabling non-motor symptoms for people with Parkinson 's disease . Exercise may modify fatigue . This study examines prescribed exercise effects on physical activity levels , well-being , and fatigue in Parkinson 's disease . METHODS In this single-blinded trial , participants were r and omly assigned to either a 12 week community exercise program or control group . Primary outcome measures were fatigue ( Fatigue Severity Scale ) and physical activity . RESULTS Thirty-nine people with Parkinson 's disease were included : 20 in exercise and 19 in control . Sixty-five percent of the study group were fatigued ( n = 24 , mean 4.02 , SD 1.48 ) . Increased fatigue was associated with lower mobility and activity ( P < .05 ) . Individuals participated in a mean of 15 ( SD 10 ) exercise sessions with no significant change in fatigue , mobility , well-being , or physical activity after exercise ( P ≥ .05 ) . CONCLUSION Participation in weekly exercise did not improve fatigue in people with Parkinson 's Disease Objectives : Fatigue is common in Parkinson 's disease ( PD ) , causing serious negative effects on quality of life . Despite its clinical importance , the nature of fatigue in PD is poorly understood because its underlying neurobiology is unknown . Fatigue can be more complicated in advanced PD because of its chronicity . In order to find features that are innate to fatigue in PD , it would be useful to conduct a study looking at de novo PD . Assessing fatigue in de novo patients allows excluding at least one confounding factor . Methods : We prospect ively investigated 87 drug-naïve PD patients . Thirty-nine patients ( 44.8 % ) were found to have fatigue around the time of diagnosis of PD . Results : We found that depression and difficulties with activities of daily living were independent risk factors for fatigue ; however , motor dysfunction was not related . Clinical ly meaningful responses to dopaminergic medication were observed . Discussion : Our study determined that fatigue occurs in the early stages of PD . It can inform clinical decision-making to significantly benefit PD patients with fatigue BACKGROUND Fatigue affects 40 % to 50 % of all PD patients and is a leading cause of disability , with no clearly established or efficacious established treatments . METHODS In this double-blinded , placebo-controlled , pilot trial , we investigated whether rasagiline improved fatigue among PD patients . Subjects were r and omized to 1 mg daily of rasagiline or placebo for 12 weeks . The primary endpoint was a change in the Modified Fatigue Impact Scale from baseline to week 12 . RESULTS Thirty PD subjects ( 16 men ) , with Modified Fatigue Impact Scale baseline score of 67 ± 15 , were r and omized ( 16 to rasagiline vs. 14 to placebo ) . Significant improvement was noted in the mean Modified Fatigue Impact Scale score of the rasagiline group ( 12 points ) as compared to placebo ( 8.5 points ) from baseline to week 12 ( P = 0.003 ) . CONCLUSION In this pilot study , rasagiline at a dose of 1 mg per day improved fatigue . Larger r and omized studies are needed to confirm this finding OBJECTIVE To identify the motor and non-motor factors that are associated with health related quality of life ( HR-QOL ) in a subgroup of Parkinson 's disease ( PD ) patients with Levodopa therapy in early clinical stages . METHODS 391 Levodopa exposed patients were evaluated during the baseline assessment of a clinical trial in China . HR-QOL was measured by the Short Form 36 ( SF-36 ) . Motor and non-motor variables were determined during a structured interview and by clinical examination by movement disorder specialists . Multiple regression analyses were used to determine which variables were associated with low levels of HR-QOL . RESULTS Even if excluding non-motor variables from the regression model , motor factors , particularly motor deficits ( measured by motor score of UPDRS ) , rigidity ( measured by item 22 of UPDRS ) , and disease severity ( measured by Hoehn&Yahr scale ) , explained only 18.9 % of the variance of total SF-36 score . Whereas , when non-motor variables were included in the model , especially depression ( measured by CES-D ) , sleep disturbances ( measured by PSQ-I ) , and fatigue ( measured by FSS ) , 61.7 % of the variance of SF-36 score could be explained . Two motor variables , UPDRS motor score and Hoehn&Yahr score , were also contributed to the model , however , the 95 % confidence intervals ( CIs ) of these two motor factors were wide and included the null value ( CIs -0.282 , 0.019 for UPDRS motor score , and CIs -4.043 , 0.856 for Hoehn&Yahr score ) . Neither , did higher daily levodopa dose contribute significantly to both models predicting SF-36 score . CONCLUSIONS In our sample patients with levodopa therapy , motor disability and severity of parkinsonism contributed to a lesser extent to patients ' self-report distress , within the first 5 years of disease onset . The clinical factors that showed the highest predictive value for worsen HR-QOL were non-motor symptoms , such as depression , sleep disorders , and fatigue . Great effort should be made to recognize and treat those conditions , thus improving all aspects of PD and giving these patients as a good HR-QOL as possible Objectives : Fatigue is a complaint frequently encountered among patients with Parkinson ’s disease ( PD ) . Considering the possible relationship between fatigue and dopaminergic dysfuncion , we investigated the effect of pergolide mesilate ( a D2 and D1 dopamine receptor agonist ) and bromocriptine ( a D2 selective dopamine receptor ) in patients with PD . Methods : We evaluated 41 patients with PD and controls . We assessed the degree of fatigue by using a fatigue scale . The severity of PD was evaluated by the Hoehn and Yahr Scale and the unified Parkinson ’s disease rating scale ( UPDRS ) . Results : After five weeks from prescription , patients taking pergolide mesilate showed significant improvement in the fatigue scale ( from 5.1 ± 0.7 to 4.4 ± 0.55 , p < 0.05 , ) but patients taking bromocriptine did not ( from 4.8 ± 0.9 to 4.7 ± 0.8 ) . Conclusions : Our study suggested the possibility of functional correlation between fatigue and D1 receptor in patients with PD Background : Fatigue is a common complaint in Parkinson disease ( PD ) . We investigated fatigue in a cohort of previously untreated patients with early PD enrolled in the Earlier vs Later Levodopa ( ELLDOPA ) clinical trial . Methods : A total of 361 patients were enrolled in the r and omized , double-blind , placebo-controlled ELLDOPA trial and assigned to receive placebo or carbidopa-levodopa 37.5/150 mg , 75/300 mg , or 150/600 mg daily for 40 weeks , followed by a 2-week medication washout period . Subjects who scored > 4 on the Fatigue Severity Scale were classified as fatigued . PD severity was assessed using the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Hoehn-Yahr scale , and Schwab-Engl and Activities of Daily Living Scale . A subgroup of subjects underwent [123I]-β-CIT SPECT to measure striatal dopamine transporter density . Results : Of the 349 ELLDOPA subjects who completed fatigue measures , 128 were classified as fatigued at baseline . The fatigued group was significantly more impaired neurologically ( UPDRS , all subscales and Hoehn and Yahr staging ) and functionally ( Schwab-Engl and Scale ) but no significant differences were observed in β-CIT measurements between the two groups . Analysis of covariance showed a greater increase in fatigue score from baseline to the end of the 2-week washout in the placebo group ( 0.75 points ) than in the three groups receiving levodopa ( increases of 0.30 [ 150 mg/day ] , 0.36 [ 300 mg/day ] , and 0.33 [ 600 mg/day ] ; p = 0.03 for heterogeneity ) . Conclusions : Fatigue is a frequent symptom in early , untreated , non-depressed patients with Parkinson disease ( PD ) , affecting over 1/3 of the patients in this cohort at baseline and 50 % by week 42 . Fatigue was associated with the severity of PD , and progressed less in patients treated with levodopa Background : Fatigue is a major nonmotor symptom in Parkinson disease ( PD ) . It is associated with reduced activity and lower quality of life . Objective : To determine if modafinil improves subjective fatigue and physical fatigability in PD . Methods : Nineteen PD patients who reported significant fatigue in the Multidimensional Fatigue Inventory ( MFI ) participated in this 8-week study . Subjects took their regular medications and were r and omly assigned to the treatment group ( 9 subjects , modafinil 100-mg capsule BID ) or placebo group ( 10 subjects ) . We used the MFI to measure subjective fatigue and used finger tapping and intermittent force generation to evaluate physical fatigability . Subjects also completed the Epworth Sleepiness Scale ( ESS ) and the Center of Epidemiological Study -Depression Scale . Results : There were no significant differences at baseline and at 1 month in finger tapping and ESS between the modafinil and placebo groups . At 2 months , the modafinil group had a higher tapping frequency ( P < 0.05 ) , shorter dwell time ( P < 0.05 ) , and less fatigability in finger tapping and tended to have lower ESS scores ( P < 0.12 ) than the placebo group . However , there was no difference between groups over time for any dimension of the MFI . Conclusions : This small study demonstrated that although modafinil may be effective in reducing physical fatigability in PD , it did not improve fatigue symptoms OBJECTIVES To determine ( a ) the relationship between physical and somatoform complaints , distress , life satisfaction and ageing in the female community and ( b ) to identify their psychosocial determinants . METHODS Two stratified r and om sample s of the German female population ( total of 2771 women ) were investigated by st and ardised question naires of complaints ( MFI-20 , GBB ) , distress ( HADS ) and life satisfaction ( LSQ ) . RESULTS When participants were divided into six age groups ( 18 - 30 , 31 - 40 , 41 - 50 , 51 - 60 , 61 - 70 , > 70 years ) , we found a continuous increase of physical , mental and general fatigue , inactivity and reduced motivation . Age-associated increases were also observed for exhaustion , cardiovascular and musculoskeletal complaints , but not for gastrointestinal complaints . This was accompanied by a reduced satisfaction with health and sexuality and increased depression and anxiety scores . Marked increases of complaints were mostly found in the sixth decade . However , depression already increased in the fourth decade , musculoskeletal complaints and reduced motivation peaked in the fifth decade , whereas mental fatigue did not increase significantly before the seventh decade followed by a rise of anxiety in women over 70 years . Most consistently , complaints were predicted by a combination of negative subjective health , higher age , lack of a partnership , and additional sociodemographic vulnerability ( unemployment , low income , residence ) and protective ( religion ) factors . CONCLUSIONS Community data provide important reference points in evaluating the ageing female . Based on regression analyses , we could also demonstrate the contribution of psychosocial vulnerability and protective factors to the development of age-related symptoms BACKGROUND AND PURPOSE A comprehensive study of both fatigue and excessive daytime sleepiness ( EDS ) in association with Parkinson 's disease (PD)-related symptoms and treatment has not been performed yet . To assess the frequency and severity of fatigue and EDS in patients with idiopathic PD and to study their relation to motor and non-motor symptoms and dopaminergic treatment . METHODS We prospect ively assessed Fatigue Severity Scale ( FSS ) scores , Epworth Sleepiness Scale ( ESS ) scores , Beck Depression Inventory ( BDI ) scores , severity ( Unified PD Rating Scale , UPDRS , part III ; Hoehn & Yahr staging ) and duration of the disease , and the current dopaminergic treatment in 88 consecutive patients with idiopathic PD . RESULTS Fatigue was found in 52 ( 59 % ) , EDS in 42 ( 48 % ) , and both complaints in 31 ( 35 % ) patients . Fatigued patients had higher UPDRS III scores ( 23.5 ± 11.1 vs. 18.6 ± 7.6 , P = 0.03 ) , higher Hoehn & Yahr staging ( 2.4 ± 0.9 vs. 2.1 ± 0.7 , P = 0.03 ) , and higher BDI scores ( 13.4 ± 7.1 vs. 9.1 ± 5.8 , P = 0.004 ) than non-fatigued patients . In contrast , UPDRS III , Hoehn & Yahr , and BDI scores did not differ between patients with or without EDS . However , the type of dopaminergic treatment ( levodopa monotherapy versus combination of levodopa/dopamine agonists ) was associated with significant differences in ESS ( 8.5 ± 5.2 vs. 10.8 ± 4.3 , P = 0.04 ) , but not FSS scores ( 4.1 ± 1.5 vs. 4.3 ± 1.5 , P = 0.55 ) . Disease duration correlated with ESS scores ( r = 0.32 , P = 0.003 ) , but not with FSS scores ( r = -0.02 , P = 0.82 ) . CONCLUSIONS In PD , there is a significant overlap of fatigue and EDS , but the two symptoms are differently correlated with the severity of motor symptoms , disease duration , depression , and dopaminergic treatment UNLABELLED Objective background : The Montreal Cognitive Assessment ( MoCA ) is a question naire that has been developed to help physicians around the world diagnose a patient 's cognitive ability . Available in multiple language s and for use in multiple countries worldwide , the goal of this study was to vali date the alternate versions 2 and 3 of the French MoCA test to assist physicians in the detection of mild cognitive impairment ( MCI ) , while decreasing the learning effect upon frequent testing . METHODS A validation study was conducted at the MoCA Clinic and Institute in Québec , Canada . The subject population consisted of 25 patients diagnosed with MCI meeting Petersen criteria and 25 healthy subjects serving as the normal control ( NC ) group . Three MoCA test versions were administered in the French language in r and om order within one session . Scores obtained in all three versions in MCI and NC groups were assessed for reliability and consistency from one version to the next . RESULTS On average , scores obtained in each subject group ( MCI and NC ) fell within their corresponding diagnostic ranges ( score above 26 points for NC patients versus scores below 26 points for MCI patients ) . Difference in scores observed between the original French MoCA version and the two alternate versions in each subject cohort were minimal and not considered clinical ly significant . CONCLUSIONS All three test versions of the French MoCA are considered equivalent in diagnostic reliability and consistency and contribute to decreasing the potential learning effect when patients are required to repeat the test frequently OBJECTIVES To determine ( a ) the relationship between physical and somatoform complaints , distress and life satisfaction and ageing in the male community and ( b ) their psychosocial determinants . METHODS Two stratified r and om sample s of the German male population ( total of 2,182 men ) were investigated by st and ardised question naires of complaints ( MFI-20 , GBB ) , distress ( HADS ) and life satisfaction . RESULTS When participants were grouped into six age groups ( 18 - 30 , 31 - 40 , 41 - 50 , 51 - 60 , 61 - 70 , > 70 years ) , we found a continuous increase of physical , mental and general fatigue , and a reduced activity and motivation associated with age . Exhaustion , cardiovascular and musculoskeletal complaints also increased . This was accompanied by a reduced health satisfaction and increased depression scores . Marked increases of certain complaints occurred in specific age groups . CONCLUSIONS Community data provide important reference points in evaluating the ageing male . Based on regression analyses we could also demonstrate the contribution of psychosocial vulnerability and protective factors to the development of age-related symptoms Objective : To compare the tremorlytic properties of pramipexole , a non-ergoline dopamine agonist to those of placebo as add on medication in patients with Parkinson 's disease . Methods : Eighty four patients with early or advanced Parkinson 's disease and marked , drug resistant tremor under a stable and optimised antiparkinsonian medication were included in a double blind , r and omised , placebo controlled , multicentre study and assigned to add on treatment ( 7 week dose titration interval , 4 week maintenance period ) with either pramipexole ( n=44 ) or placebo ( n=40 ) as adjunct . The primary end point was the absolute change in tremor score , defined as the sum of tremor related items ( 16 , 20 , 21 ) of the unified Parkinson 's disease rating scale ( UPDRS ) in “ on ” periods . Secondary end points included the percentage change in tremor score , the absolute and percentage changes in long term EMG tremor registration , and the change in tremor self rating scales . Safety and tolerability were assessed on the basis of adverse events , laboratory tests , ECG , and vital signs . Results : Pramipexole was significantly superior to placebo with a difference between treatment groups in the mean absolute change in tremor score of −4.4 ( 95 % confidence interval ( 95 % CI ) −6.2 to −2.5 ) ( p<0.0001 ) , corresponding to a difference in the mean percentage change of −34.7 % in favour of pramipexole . The secondary end points were consistent with the significant change in tremor score and provided further evidence for the benefit of pramipexole compared with placebo . Long term EMG registration as an objective measure showed a difference in mean absolute change in tremor occurrence of −15.2 % ( 95%CI −21.4 to −9.0 ) ( p<0.0001 ) , and a difference in the mean percentage change of −45.7 % in favour of pramipexole . The treatment effects increased during dose titration and remained stable during the 4 week maintenance dose period until the end of the study . The average daily pramipexole dose during maintenance was 4.1 ( SD 0.9 ) mg . Safety analysis showed an increased rate of fatigue , insomnia , nausea , abdominal pain , and headache under pramipexole , comparable with previous studies . Conclusion : Pramipexole proved to be an effective agent for patients with Parkinson 's disease and drug resistant tremor OBJECTIVE The aim of this multicenter cross-sectional study was to assess the relation between fatigue in a large number of Japanese patients with Parkinson 's disease ( PD ) and drugs taken to treat PD . METHOD We used the 16-item Parkinson Fatigue Scale ( PFS-16 ) , which was design ed to assess fatigue exclusively associated with PD . Multiple logistic regression analyses were used to assess the relation between antiparkinson drugs and fatigue in PD . RESULTS A total of 350 non-demented PD patients were enrolled . Fatigue ( PFS score of ≥4 ) was revealed in 319 patients ( 91 % ) . Pramipexole was administered to 24 % of PD patients . Multiple logistic regression analysis revealed that the administration of Pramipexole was significantly related to low rates of fatigue in PD patients with Hoehn and Yahr stage <3 ( p=0.011 , odds ratio=5.23 , 95 % confidence interval ; 1.47 - 18.63 ) . CONCLUSION The reduced fatigue in PD patients was observed in taking Pramipexole The objective was to compare the prevalence and severity of fatigue in patients with Parkinson 's disease ( PD ) with that in two control groups , one consisting of r and omly chosen control subjects of the same age and sex distribution and the other consisting of patients with coxarthrosis waiting to receive total hip replacement . We also explored the possible correlation of demographic and clinical data to the presence and severity of fatigue . Sixty‐six patients with PD , 131 r and omly chosen controls and 79 patients with coxarthrosis , waiting to receive total hip replacement , were evaluated for fatigue . Patients and controls with a depressive mood disorder or cognitive impairment had been excluded from the study . Fatigue was measured by the Fatigue Severity Scale ( FSS ) . For the patients with PD the mean total FSS score was 4.1 , compared with 2.7 amongst the r and omly chosen control group and 2.9 in the group consisting of patients with coxarthrosis . Fifty per cent of the patients with PD had a mean total FSS score of 4 or higher , compared with 25 % in both of the two control groups . There was no correlation between pain , presence of self‐reported nocturnal sleep disorders or duration of PD and fatigue . The patients with fatigue did have a more advanced disease , measured both by Unified Parkinson 's Disease Rating Scale score and Hoehn and Yahr stage . Although the univariate analyses indicated that more severe parkinsonism was correlated to the symptom , the multivariate analysis showed that none of the studied variables were significant explanatory factors for fatigue . Fatigue is a common symptom in patients with PD without depression or dementia . The study indicates that fatigue is an independent symptom of the disease without relation to other motor or non‐motor symptoms Population norms for interpretation of fatigue measurements have been lacking , and the sociodemographic associations of fatigue are poorly documented . A r and om sample of 3500 Norwegians , aged 19 - 80 years , was therefore investigated . A mailed question naire included the fatigue question naire ( 11 items ) in which the sum score of the responses ( each scored 0 , 1 , 2 , 3 ) is design ated as total fatigue ( TF ) . Sixty-seven percent of those receiving the question naire responded . Women ( TF mean=12.6 ) were more fatigued than men ( TF mean=11.9 ) , and 11.4 % reported substantial fatigue lasting 6 months or longer . TF and age were weakly correlated ( men : r=0.17 ; women : r=0.09 ) . No firm associations between fatigue and social variables were found . Disabled and subjects reporting health problems were more fatigued than subjects at work or in good health . Fatigue is highly prevalent in somatic and psychiatric disorders , but is often neglected . This national representative sample provides age- and gender-specific norms that will allow for comparisons and interpretations of fatigue scores in future studies The Unified Parkinson 's Disease Rating Scale ( UPDRS ) is the main outcome measure in clinical trials of Parkinson 's disease ( PD ) . The minimal change that represents a clinical ly meaningful improvement is unknown . The objective of this study was to determine the minimal change on the UPDRS that represents a clinical ly meaningful improvement in early PD after 6 months of treatment . Data from two independent r and omized treatment trials over 6 months involving 603 patients with de novo PD were analyzed to determine the minimal clinical ly important change ( MCIC ) , referred to the status before treatment , for the UPDRS motor , activities of daily living ( ADL ) , and total scores . An anchor-based method using ratings on a seven-point global clinical improvement was used . A change of five points on the UPDRS motor part was found to be the most appropriate cutoff score for all Hoehn and Yahr stages I to III , and a change of eight points for the UDPRS total score . For the UDPRS ADL score , an MCIC of two points for Hoehn and Yahr stages I/I.5 and II and of three points for Hoehn and Yahr stage II.5/III was the most appropriate cutoff score . These data give the first estimate for cutoffs defining clinical ly important changes in UPDRS ADL and motor scores . Further studies using larger data bases from more diverse study population s are encouraged to better define and solidify the MCIC for the UPDRS OBJECTIVE To examine the burden of Parkinson 's Disease ( PD ) on society , family , and the individual . SETTING In-home interviews in Central North Carolina . DESIGN A cross-sectional , descriptive study . PARTICIPANTS A total of 109 people with PD . MEASURES St and ard instruments used to assess income , health status , health-related costs , and household activities . SAMPLE The sample was weighted toward individuals who were within the first 5 years of post-PD diagnosis . RESULTS The total per capita societal burden was approximately $ 6000 per year , the greatest single element of which was compensation for earnings loss for those less than age 65 . Government insurance covered 85 % of our sample . The largest components of family burden were the burden of providing informal caregiving and that of earnings loss . Spouses providing informal care did so a mean of 22 hours per week . Compared with a r and om sample of older people , our respondents spent much less time on house and yard work . CONCLUSION The direct costs of the disease reflect a small portion of the burden . The hidden costs , in the form of lost wages , informal care , and changing roles are substantial . Their magnitude is even more important when we consider that the family generally lives on a fixed income , and the caregiver is an older aged spouse . Medical practitioners will best be able to intervene if they look holistically at the patient with this disease . When treating symptoms themselves , practitioners need to be aware of the high level of pain , fatigue , and depression associated with PD , even in the early stages . The results demonstrate clearly that family relationships are affected early , indicating the importance of providing early referrals to services such as home health , social workers/counseling , and well as PD support groups BACKGROUND Depression , anxiety , fatigue and sleep disorders occur commonly in patients with Parkinson 's disease ( PD ) . These non-motor symptoms often contribute to the reduction of functional abilities in PD patients . OBJECTIVE This study was design ed to evaluate the diagnostic accuracy of the treating neurologist for a variety of behavioral symptoms commonly associated with PD . METHODS A prospect i ve evaluation of 101 patients with PD selected in no particular order was conducted . All patients were evaluated with the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Hoehn & Yahr Stage ( H/Y ) , and the Schwab & Engl and Scale ( S/E ) . The patients completed a brief screening question naire for depression and anxiety followed by the administration of a battery of st and ardized tests including the Beck Depression Inventory ( BDI ) , Beck Anxiety Inventory ( BAI ) , Fatigue Severity Scale ( FSS ) , and the Pittsburgh Sleep Quality Inventory ( PSQI ) . RESULTS St and ardized testing showed evidence of a problem with depression in 44 % of patients , anxiety in 39 % , fatigue in 42 % and sleep disturbance in 43 % . The prevalence of these conditions , identified by the treating neurologist was lower : 21 % with depression , 19 % with anxiety , 14 % with fatigue and 39 % with sleep disturbance . The diagnostic accuracy for the treating neurologists was 35 % for depression , 42 % for anxiety , 25 % for fatigue , and 60 % for sleep disturbance . CONCLUSION This study demonstrates that during routine office visits , neurologists failed to identify the presence of depression , anxiety , and fatigue more than half of the time and failed to recognize sleep disturbance in 40 % of patients . Awareness of the likelihood of underrecognition of behavioral symptoms in PD should generate approaches to improve diagnostic accuracy and facilitate timely therapeutic interventions Fatigue is a common nonmotor symptom in idiopathic Parkinson disease ( IPD ) that can prominently affect everyday function . This study was a r and omized , double-blind , placebo-controlled trial evaluating methylpheni date for the treatment of fatigue in patients with IPD maintained on their regular medications . Thirty-six patients were r and omized to receive either methylpheni date ( 10 mg three times per day ; n = 17 ) or placebo ( n = 19 ) for 6 weeks . Primary outcomes were the change from baseline on two separate self-report fatigue question naires : the Fatigue Severity Scale ( FSS ) and the Multidimensional Fatigue Inventory ( MFI ) . Secondary outcomes included the Unified Parkinson Disease Rating Scale ( UPDRS ) motor score and the five individual domains of the MFI . Fourteen patients in the methylpheni date group and 16 patients in the control group remained on the intervention for the entire study period . In the treatment arm , mean FSS score was reduced by 6.5 points ( from a baseline of 43.8 ) and mean MFI score was reduced by 8.4 points ( from a baseline of 51.0 ) . Both these reductions were significant ( P < 0.04 ) . Smaller reductions in the placebo group were nonsignificant . Mean UPDRS motor score did not change significantly in either group . Analysis of MFI subscores showed a significant reduction in General Fatigue in the methylpheni date group ( P < 0.001 ) . Overall , adverse effects of medication were more frequent in the placebo group . In conclusion , methylpheni date was effective in lowering fatigue scores in patients with IPD following a 6-week treatment period |
11,816 | 30,565,381 | Altruism , personal health benefits , access to health care , monetary benefit , knowledge , social support and trust were the most important reasons for participation .
Primary reasons for non‐participation were safety concerns , inconvenience , stigmatisation , lack of social support , confidentiality concerns , physical pain , efficacy concerns and distrust .
Stigmatisation was a major concern in relation to HIV research .
Reasons were similar across different regions , gender , non‐patient or patient participants and real or hypothetical study design s. Conclusions Addressing factors that affect (non‐)participation in the planning process and during the conduct of research may enhance voluntary consent to participation and reduce barriers for potential participants | Abstract Objectives To systematic ally review reasons for the willingness to participate in biomedical human subjects research in low‐ and middle‐income countries ( LMICs ) . | Background Medical research must involve the participation of human subjects . Knowledge of patients ' perspectives and concerns with their involvement in research would enhance recruitment efforts , improve the informed consent process , and enhance the overall trust between patients and investigators . Several studies have examined the views of patients from Western countries . There is limited empirical research involving the perspectives of individuals from developing countries . The purpose of this study is to examine the attitudes of Egyptian individuals toward medical research . Such information would help clarify the type and extent of concerns regarding research participation of individuals from cultural , economic , and political background s that differ from those in developed countries . Methods We conducted semi-structured interviews with 15 Egyptian individuals recruited from the outpatient setting s ( public and private ) at Ain Shams University in Cairo , Egypt . Interviews were taped , transcribed , and translated . Thematic analysis followed . Results All individuals valued the importance of medical research ; however most would not participate in research that involved more than minimal risk . Individuals were comfortable with studies involving surveys and blood sampling , but many viewed drug trials as being too risky . All participants valued the concept of informed consent , as they thought that their permission to be in a research study was paramount . Many participants had discomfort with or difficulty in the underst and ing several research concepts : r and omization , double-blind , and clinical equipoise . Trust in the physicians performing research was important in deciding to participate in clinical research . The small sample size and the selection bias associated with obtaining information from only those who agreed to participate in a research study represent limitations in this study . Conclusion Overall , individuals in our sample recognize the value of medical research and have a great deal of trust regarding medical research and their participation in research . There were , however , concerns with the level of research risks associated with several types of medical research . Many also demonstrated confusion with certain research method ologies . We recommend 1 ) enhanced educational efforts regarding general research concepts to enhance the validity of informed consent and 2 ) further survey studies in other areas of Egypt to determine the generalizability of our results Introduction HIV epidemics in sub-Saharan Africa are generalized , but high-risk subgroups exist within these epidemics . A recent study among fisher-folk communities ( FFC ) in Ug and a showed high HIV prevalence ( 28.8 % ) and incidence ( 4.9/100 person-years ) . However , those findings may not reflect population -wide HIV rates in FFC since the study population was selected for high-risk behaviour . Methods Between September 2011 and March 2013 , we conducted a community-based cohort study to determine the population representative HIV rates and willingness to participate ( WTP ) in hypothetical vaccine trials among FFC , Ug and a. At baseline ( September 2011–January 2012 ) , a household enumeration census was done in eight fishing communities ( one lakeshore and seven isl and s ) , after which a r and om sample of 2200 participants aged 18–49 years was selected from 5360 individuals . Interviewer-administered question naire data were collected on HIV risk behaviours and WTP , and venous blood was collected for HIV testing using rapid HIV tests with enzyme-linked immunosorbent assay ( EIA ) confirmation . Adjusted prevalence proportion ratios ( adj . PPRs ) of HIV prevalence were determined using log-binomial regression models . Results Overall baseline HIV prevalence was 26.7 % and was higher in women than men ( 32.6 % vs. 20.8 % , p<0.0001 ) . Prevalence was lower among fishermen ( 22.4 % ) than housewives ( 32.1 % ) , farmers ( 33.1 % ) and bar/lodge/restaurant workers ( 37 % ) . The adj . PPR of HIV was higher among women than men ( adj . PPR = 1.50 , 95 % ; 1.20 , 1.87 ) and participants aged 30–39 years ( adj . PPR=1.40 , 95 % ; 1.10 , 1.79 ) and 40–49 years ( adj . PPR=1.41 , 95 % ; 1.04 , 1.92 ) compared to those aged 18–24 years . Other factors associated with HIV prevalence included low education , previous marriage , polygamous marriage , alcohol and marijuana use before sex . WTP in hypothetical vaccine trials was 89.3 % and was higher in men than women ( 91.2 % vs. 87.3 % , p=0.004 ) and among isl and communities compared to lakeshore ones ( 90.4 % vs. 85.8 % , p=0.004 ) . Conclusions The HIV prevalence in the general fisher-folk population in Ug and a is similar to that observed in the “ high-risk ” fisher folk . FFC have very high levels of willingness to participate in future HIV vaccine trials BACKGROUND In setting s where multiple HIV prevention trials are conducted in close proximity , trial participants may attempt to enroll in more than one trial simultaneously . Co-enrollment impacts on participant 's safety and validity of trial results . We describe our experience , remedial action taken , inter-organizational collaboration and lessons learnt following the identification of co-enrolled participants . EXPERIENCES Between February and April 2008 , we identified 185 of the 398 enrolled participants as ineligible . In violation of the study protocol exclusion criteria , there was simultaneous enrollment in another HIV prevention trial ( ineligible co-enrolled , n=135 ) , and enrollment of women who had participated in a microbicide trial within the past 12 months ( ineligible not co-enrolled , n=50 ) . Following a complete audit of all enrolled participants , ineligible participants were discontinued via study exit visits from trial follow-up . Custom- design ed education program on co-enrollment impacting on participants ' safety and validity of the trial results was implemented . Shared electronic data base between research units was established to enable verification of each volunteer 's trial participation and to prevent future co-enrollments . LESSONS LEARNT Interviews with ineligible enrolled women revealed that high- quality care , financial incentives , altruistic motives , preference for sex with gel , wanting to increase their likelihood of receiving active gel , perceived low risk of discovery and peer pressure are the reasons for their enrollment in the CAPRISA 004 trial . CONCLUSION Instituting education programs based on the reasons reported by women for seeking enrollment in more than one trial and using a shared central data base system to identify co-enrollments have effectively prevented further co-enrollments Background and Purpose — Most stroke rehabilitation studies have been performed in high-income countries . The aim of this study was to identify the main barriers for patient inclusion in a research protocol performed in Brazil . Methods — We evaluated reasons for exclusion of patients in a pilot , r and omized , double-blinded clinical trial of stroke rehabilitation . Descriptive statistical analysis was performed . Results — Only 5.6 % of 571 screened patients were included . Recurrent stroke was responsible for exclusion of 45.4 % of potentially eligible patients . Conclusions — Recurrent stroke represented a big barrier to enroll patients in the protocol . External validity of rehabilitation trials will benefit from definition of study criteria according to regional characteristics of patients , including rates of recurrent stroke . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01333579 Background In the past , clinical study participants have suffered from the experiments that they were subjected to . Study subjects may not underst and the study process or may participate in clinical studies because they do not have access to medical care . The objectives of the present study were 1 . to analyze the motives that might cause a volunteer to participate as a study subject ; 2 . to identify the social-demographic profile of this study subjects ; and 3 . to determine whether the motives to volunteer as a study subject are in accordance with the established legal and ethical principles for research in Brazil . Methods Mixed- methods research was used ( a qualitative-quantitative approach ) . A sample of 80 volunteers underwent a semi-structured interview , which was based on a survey script that was elaborated from discussion s with key informants . The sample was r and omly selected from a data base of clinical study volunteers that was provided by Brazilian clinical study centers . The interviews were recorded and transcribed . Descriptive statistics were used for content analysis , including contingency tables with hypothesis testing . Results The motivations for clinical study participation were linked to types of benefit . The most frequently encountered motivations were financial gain and therapeutic alternative . Altruism was not a common motivator , and when altruism was present , it was observed as a secondary motivator . All participants reported that they understood the Informed Consent Statement ( ICS ) . However , only two parts of the form were remembered by all of the volunteers : the section on being able to leave the study at any point and the section that stated that there would be some responsible professional at their disposal for the entirety of the study . Conclusions The present study shows that study participants are primarily motivated by personal benefit when volunteering to participate in clinical studies . Whether these study participants had an integral underst and ing of the ICS is not clear Background Mexico has the highest adult overweight and obesity prevalence in the Americas ; 23.8 % of children < 5 years old are at risk for overweight and 9.7 % are already overweight or obese . Creciendo Sanos was a pilot intervention to prevent obesity among preschoolers in Instituto Mexicano del Seguro Social ( IMSS ) clinics . Methods We r and omized 4 IMSS primary care clinics to either 6 weekly educational sessions promoting healthful nutrition and physical activity or usual care . We recruited 306 parent-child pairs : 168 intervention , 138 usual care . Children were 2 - 5 years old with WHO body mass index ( BMI ) z-score 0 - 3 . We measured children ’s height and weight and parents reported children ’s diet and physical activity at baseline and 3 and 6-month follow-up . We analyzed behavioral and BMI outcomes with generalized mixed models incorporating multiple imputation for missing values . Results 93 ( 55 % ) intervention and 96 ( 70 % ) usual care families completed 3 and 6-month follow-up . At 3 months , intervention v. usual care children increased vegetables by 6.3 servings/week ( 95 % CI , 1.8 , 10.8 ) . In stratified analyses , intervention participants with high program adherence ( 5 - 6 sessions ) decreased snacks and screen time and increased vegetables v. usual care . No further effects on behavioral outcomes or BMI were observed . Transportation time and expenses were barriers to adherence . 90 % of parents who completed the post-intervention survey were satisfied with the program . Conclusions Although satisfaction was high among participants , barriers to participation and retention included transportation cost and time . In intention to treat analyses , we found intervention effects on vegetable intake , but not other behaviors or BMI .Trial registration Clinical Trials.gov NCT01539070.Comisión Nacional de Investigación Científica del IMSS : 2009 - 785 - 120 The study objective was to assess willingness of men who have sex with men ( MSM ) enrollled in a vaccine preparedness study ( ' Projeto Rio ' ) to participate in phase III anti-HIV/AIDS vaccine trials . Overall , 57 % of Projeto Rio participants stated they would participate in a putative vaccine trial . MSM who reported commercial sex work were significantly ( p<0.05 ) more likely to engage in risky behaviours than others . In bivariate analysis , commercial sex workers ( CSWs ) were significantly ( p<0.05 ) more likely than non-commercial sex workers ( NCSWs ) to be willing to participate in vaccine trials ( 62.6 % versus 51.4 % ) . Among those willing , CSWs reported significantly more often ( p<0.05 ) ( 50.5 % ) than NCSWs ( 38.0 % ) that they would enroll to protect themselves from HIV . In multivariate analyses , variables associated with willingness to participate ( WTP ) were lower educational level , positive serology for syphilis , and ' engagement , under the influence of alcohol , in risky sexual practice s that would normally be avoided ' , but not commercial sex work . The potential enrollment in vaccine trials of MSM CWSs , as well as participants of low socio-economic status and high risk , seems thus to be possible Background During the last decade , the number of clinical trials conducted in sub-Saharan Africa has increased significantly which has helped to address priority health problems in the region . Navrongo health research centre since it was established in 1989 , has conducted several trial studies including rectal artesunate trial in the Kassena-Nankana districts . However , there is little evidence -based for assessing the impact of new drug trials . This study explored factors that motivate parents to allow their children to participate in new drug trials in northern Ghana . Method The study used both quantitative and qualitative methods . The participants were r and omly selected from among parents whose children were enrolled in a new drug trial conducted in the Kassena-Nankana districts between 2000 and 2003 . QSR Nvivo 9 software was used to code the qualitative data into themes before analysis while STATA software Version 11.2 © was used to analyze the quantitative data . Results The results showed that majority ( 95.9 % ) of the parents were willing to allow their children to be enrolled in future new drug trials . The main factors motivating their willingness to allow their children to be enrolled in these trials were quality of health care services offered to trial participants ( 92.9 % ) , detail medical examination ( 90.8 % ) , promptness of care provided ( 94.4 % ) and quality of drugs ( 91.9 % ) . Other factors mentioned included disease prevention ( 99.5 % ) and improved living st and ard ( 96.1 % ) . Parents reported that the conduct of these trials had reduced the frequency of disease occurrences in the communities because of the quality of health care services provided to the children recruited into these trial studies . Conclusion Though the implementation of clinical trials in the study area is believed to have positive impact on health status of people particularly trial participants , measures should however be taken to address safety and likely side effects of new drugs given to trial participants during these trial studies There is widespread evidence that male partners influence women ’s ability and willingness to join HIV prevention trials and to use female-controlled prevention strategies such as microbicide gels . VOICE-C was an ancillary study to the Microbicide Trials Network ’s VOICE trial at the Johannesburg site that explored social and structural factors influencing women ’s use of study tablets and vaginal gel . Qualitative data were analyzed from 102 r and omly-selected VOICE participants interviewed through in-depth interviews ( IDI , n = 41 ) ; ethnographic interviews ( n = 21 ) or focus group discussion s ( FGD , n = 40 ) and 22 male partners interviewed in 14 IDI and 2 FGD . Male partners ’ “ underst and ing ” pervaded as a central explanation for how male partners directly and indirectly influenced their female partners ’ trial participation and product use , irrespective of assignment to the gel or tablet study groups . The meaning behind “ underst and ing ” in this context was described by both men and women in two important and complementary ways : ( 1 ) “ comprehension ” of the study purpose including biological properties or effects of the products , and ( 2 ) “ support/agreeability ” for female partners being study participants or using products . During analysis a third dimension of “ underst and ing ” emerged as men ’s acceptance of larger shifts in gender roles and relationship power , and the potential implication s of women ’s increased access to biomedical knowledge , services and prevention methods . Despite displays of some female agency to negotiate and use HIV prevention methods , male partners still have a critical influence on women ’s ability and willingness to do so . Efforts to increase their underst and ing of research goals , study design and products ’ mechanisms of action could ameliorate distrust , empower men to serve as product advocates , adherence buddies , and foster greater adherence support for women in situations where it is needed . Strategies to address gender norms and the broader implication s these have for female-initiated HIV prevention should likewise be integrated into future research and program activities Background To explore adolescent HIV risk perception , HIV vaccine knowledge , willingness to participate in future HIV vaccine clinical trials , and the factors that influence willingness to participate among high school students in Soweto , South Africa , we recruited school-going youth through r and omly selected local high schools . All pupils within the selected schools from whom parental consent and child assent could be obtained were eligible for participation . A self-administered , facilitated question naire was completed by all participants . Findings Perception of adolescent HIV risk was high . Some misconceptions regarding vaccine research were common , particularly regarding placebo and potential eligibility criteria for prophylactic vaccine trials . Of 240 responses to the willingness item , 84 ( 35 % ) indicated they were " probably willing " and 126 ( 52.5 % ) that they were " definitely willing to participate " . There were no significant differences in willingness by gender , age , school grade , or institution . Factors that were rated as " very important " in determining willingness included receiving current information about HIV research [ n = 201 ( 88.9 % ) ] , doing something to honour people who have HIV or have died of AIDS [ n = 168 ( 70.9 % ) ] , getting free counselling and testing [ n = 167 ( 70.5 ) ] , that participants may receive some protection against HIV infection from the vaccine [ n = 160 ( 70.2 % ) ] , and improving motivation to avoid risky behaviour [ n = 134 ( 59 % ) ] . ConclusionS oweto school-going youth report high degrees of willingness to participate in HIV vaccine trials . This may be related to the high levels of adolescent HIV risk perception . Whether hypothetical willingness translates to participation will await data from adolescent HIV vaccine trials Background Eventual control of HIV/AIDS is believed to be ultimately dependent on a safe , effective and affordable vaccine . Participation of sub-Saharan Africa in the conduct of HIV trials is crucial as this region still experiences high HIV incidences . We describe the experience of recruiting and retaining volunteers in the first HIV vaccine trial ( HIVIS03 ) in Tanzania . Methods In this trial enrolled volunteers from amongst Police Officers ( POs ) in Dar es Salaam were primed with HIV-1 DNA vaccine at months 0 , 1 and 3 ; and boosted with HIV-1 MVA vaccine at months 9 and 21 . A stepwise education provision/sensitization approach was employed to eventual recruitment . Having identified a “ core ” group of POs keen on HIV prevention activities , those interested to participate in the vaccine trial were invited for a first screening session that comprised of provision of detailed study information and medical evaluation . In the second screening session results of the initial assessment were provided and those eligible were assessed for willingness to participate ( WTP ) . Those willing were consented and eventually r and omized into the trial having met the eligibility criteria . Voluntary participation was emphasized throughout . Results Out of 408 POs who formed the core group , 364 ( 89.0 % ) attended the educational sessions . 263 out of 364 ( 72.2 % ) indicated willingness to participate in the HIV vaccine trial . 98 % of those indicating WTP attended the pre-screening workshops . 220 ( 85.0 % ) indicated willingness to undergo first screening and 177 POs attended for initial screenings , of whom 162 ( 91.5 % ) underwent both clinical and laboratory screenings . 119 volunteers ( 73.5 % ) were eligible for the study . 79 were r and omized into the trial , while 19 did not turn up , the major reason being partner/family advice . 60 volunteers including 15 females were recruited during a one-year period . All participated in the planned progress up date s workshops . Retention into the schedule was : 98 % for the 3 DNA/placebo vaccinations , while it was 83 % and 73 % for the first and second MVA/placebo vaccinations respectively . Conclusion In this first HIV vaccine trial in Tanzania , we successfully recruited the volunteers and there was no significant loss to follow up . Close contact and up date s on study progress facilitated the observed retention rates . Trial registration numbersIS RCT N90053831 ISRNCT01132976 and Background Community consultation is increasingly recommended , and in some cases , required by ethical review boards for research that involves higher levels of ethical risk such as international research and research with vulnerable population s. In design ing a r and omised control trial of a mental health intervention using a wait list control , we consulted the community where the research would be undertaken prior to finalising the study protocol . The study sites were two conflict-affected locations : Grozny in the Chechen Republic and Kitchanga in eastern Democratic Republic of Congo . Methods Group discussion s with a range of community members were held in both study sites . Facilitators used a prepared set of questions to guide the discussion s and to solicit feedback on the value of the research as well as on the study design . Specific questions were asked about enablers and barriers to participation in the research . Results Six groups were held in Grozny and thirteen in Kitchanga . The majority of individuals and groups consulted supported the research , and understood the purpose . In Grozny , the main concern raised was the length of the waiting period . Barriers to both waiting and returning for follow up were identified . In Kitchanga , there was a strong reaction against the wait list control and against r and omisation . The consultations provided information on unanticipated harms to the community , allowing changes to the study design to mitigate these harms and increase acceptability of the study . It also served to inform the community of the study , and through engaging with them early , helped promote legitimacy and joint responsibility . Conclusion Community consultation prior to finalising the study design for a mental health intervention trial in two humanitarian setting s proved feasible . Our experience reinforces the importance of community consultation before the study design is finalised and the importance of broad consultation that includes both community leaders and the potential study participants OBJECTIVE To evaluate novel eligibility criteria and outreach methods to identify and recruit women at high risk of HIV-1 infection in the Caribbean . METHODS A prospect i ve cohort study was conducted in 2009 - 2012 among 799 female commercial sex workers in the Dominican Republic , Haiti , and Puerto Rico . Minimum eligibility criteria included exchange of sex for goods , services , or money in the previous 6 months and unprotected vaginal or anal sex with a man during the same period . Sites used local epidemiology to develop more stringent eligibility criteria and recruitment strategies . Participants were asked questions about HIV/AIDS and their level of concern about participating in an HIV vaccine trial . Logistic regression modeling was used to assess predictors of prevalent HIV infection and willingness to participate in a future HIV vaccine study . RESULTS HIV prevalence at screening was 4.6 % . Crack cocaine use [ odds ratio ( OR ) = 4.2 , 95 % confidence interval ( CI ) ( 1.8 - 9.0 ) ] was associated with and having sex with clients in a hotel or motel [ OR = 0.5 , CI ( 0.3 - 1.0 ) ] was inversely associated with HIV infection . A total of 88.9 % of enrolled women were definitely or probably willing to participate in a future HIV vaccine trial . CONCLUSIONS This study indicated that local eligibility criteria and recruitment methods can be developed to identify and recruit commercial sex workers with higher HIV prevalence than the general population who express willingness to join an HIV vaccine trial High levels of adherence in clinical trials are essential for producing accurate intervention efficacy estimates . Adherence to clinical trial products and procedures is dependent on the motivations that drive participants . Data are presented to document reasons for trial participation and adherence to daily aciclovir for HSV-2 and HIV-1 genital shedding suppression among 300 HIV-1/HSV-2 seropositive women in South Africa . In-depth interviews after exit from the trial with 31 r and omly selected women stratified by age and time since HIV diagnosis confirmed high levels of adherence measured during the trial . Main reasons for trial participation were related to seeking high- quality health care , which explains high levels of adherence in both study arms . Concerns that women would abuse reimbursements , fabricate data , and share or dump pills were not corroborated . Altruism is not a primary motivator in these setting s where access to quality services is an issue . This study provides further evidence that good adherence of daily medication is possible in developing countries , particularly where study activities resonate with participants or fill an unmet need AIM This study aims to provide information on the accrual rate and to identify the reasons for non-enrollment of oral cancer patients into a clinical trial . SETTING AND DESIGN Prospect i ve study conducted at the Tertiary Cancer Centre ( India ) . MATERIAL S AND METHODS Patients eligible and screened for the oral cancer adjuvant therapy ( OCAT ) were logged prospect ively and reasons for non-enrollment were documented which were broadly divided into patient and trial related . STATISTICAL ANALYSIS USED Demographic characteristics of the non-enrolees were compared with the enrolled . Factors predicting non-enrollment were analyzed using multivariate logistic regression test . RESULTS A total of 1335 patients with locally advanced cancer of the oral cavity were screened of whom 498 ( 37 % ) could be enrolled . Among non enrolled 837 patients , 182 ( 22 % ) had the trial-related reasons and 655 ( 78 % ) had patient-related reasons . Most important patient-related reasons were patients ' preference of taking treatment closer to their native place ( 26.2 % ) , lack of interest ( 16.8 % ) in trial participation . Anticipated poor compliance to treatment ( 5.9 % ) and follow-up ( 6.6 % ) , inability to start treatment in time ( 6.2 % ) were important trial-related reasons for non-enrollment . Multivariate analysis identified the genders ( female ) , education ( illiterate ) , occupation ( laborer ) and non availability of support system in the city as significant predictors of non-enrollment . CONCLUSIONS Both trial design and patient factors were important causes of non enrollment in eligible patients . Patients ' need for being closer to home and refusal to participate were the most common reasons for non-enrollment OBJECTIVES To identify dem and for Vi typhoid fever vaccine for school-age children ; obstacles and enabling factors for vaccine delivery ; and socio-behavioural factors associated with trial participation and possible predictors of future vaccine acceptance , in Hue City , Viet Nam . METHODS Pre- and post-trial surveys of r and omly selected households with children aged 6 - 17 years . Simple multinomial logistic analyses for ratios of relative risks ( RRR ) and significance on trial participation by demographics and variables related to typhoid fever , vaccination , and pre-trial experiences with information and consents . Multiple logistic regressions to assess differences in participation based on child 's characteristics . RESULTS As many as 62.6 % of households let all school age children participate , 10.2 % let some participate , and 26.8 % let none of their children participate in the trial . Factors associated with all children participating included past use of healthcare facilities ( RRR , 0.45 ; 95 % CI , 0.24 - 0.83 ) , knowledge of vaccines ( RRR , 0.17 ; 95 % CI , 0.03 - 0.86 ) , and perceived causes of typhoid fever ( RRR , 0.90 ; 95 % CI , 0.81 - 0.99 ) . Factors associated with some children participating included utilization of healthcare facilities ( RRR , 0.08 ; 95 % CI , 0.01 - 0.66 ) and perceived severity of typhoid fever ( RRR , 0.64 ; 95 % CI 0.46 - 0.88 ) . Participation was associated with satisfaction regarding pre-vaccination information and consent procedures . Children and adolescents were active decision-makers . Only 14 of 461 ( 2.2 % ) respondents would not use the Vi vaccine in the future for their child(ren ) . CONCLUSIONS Inter-related factors contribute to participation in a clinical vaccine trial , which may differ from desire to participate in a public health campaign . Educational campaigns need to be targeted to children and adolescents , and consideration for assent procedures for minors . Obtaining informed consent may affect trial participation within a social and political system unaccustomed to these procedures Successful recruitment and retention of HIV-uninfected at-risk participants are essential for HIV vaccine efficacy trials . A multicountry vaccine preparedness study was started in 2003 to assess enrollment and retention of HIV-negative high-risk participants and to assess their willingness to participate in future vaccine efficacy trials . HIV-negative high-risk adults were recruited in the Caribbean , in Southern Africa , and in Latin America , and were followed for 1 year . Participants included men who have sex with men , heterosexual men and women , and female sex workers . History of sexually transmitted infections and sexual risk behaviors were recorded with HIV testing at 0 , 6 , and 12 months , and willingness to participate in future vaccine trials was recorded at 0 and 12 months . Recruitment , retention , and willingness to participate in future trials were excellent at 3 of the 6 sites , with consistent declines in risk behaviors across cohorts over time . Although not powered to measure seroincidence , HIV seroincidence rates per 100 person-years ( 95 % confidence interval [ CI ] ) were as follows : 2.3 ( 95 % CI : 0.3 to 8.2 ) in Botswana , 0.5 ( 95 % CI : 0 to 2.9 ) in the Dominican Republic , and 3.1 ( 95 % CI : 1.1 to 6.8 ) in Peru . The HIV Vaccine Trials Network 903 study helped to develop clinical trial site capacity , with a focus on recruitment and retention of high-risk women in the Americas , and improved network and site expertise about large-scale HIV vaccine efficacy trials Summary : To assess women 's interests and concerns regarding participation in trials of microbicides in Chiang Rai , Thail and , we administered structured question naires . Before answering the question naire , women attended an educational session on microbicides and clinical trials . Of 370 participants , 82 % correctly answered 8 or more of the 11 overall comprehension questions , indicating an adequate knowledge base among the women from which to answer questions about attitudes toward microbicide trials . The most common motivations for participating in a trial were “ getting tested for HIV ” and “ doing something good for women 's health . ” The greatest barrier to participation was women 's fear that if they proposed use of a microbicide , their husb and s might feel protected and thereby have more sex partners . Overall , 6.2 % said they would be “ definitely willing to participate , ” and 66.8 % said they wanted to participate but wanted to think about it . Most women previously unacquainted with the concept of microbicides or clinical trial design displayed adequate knowledge of these subjects after the short educational session . If women 's initial reactions are vali date d by actual willingness , surveys could prove valuable for selecting sites for microbicide trials , estimating enrollment rates , and tailoring trials to make them most acceptable to women Summary : In preparation for HIV vaccine trials , knowledge about vaccines , willingness to participate in a vaccine study , and motivations for participation must be assessed . The Preparation for AIDS Vaccine Evaluation study assessed knowledge about vaccines and vaccine trials and willingness to participate in a hypothetical trial in 1,182 Ug and an military men ( aged 18‐30 years ) . Participants received education about vaccine trials and were interviewed during 24 months of follow‐up observation . Its key findings are that : 1 ) throughout follow‐up , most participants expressed willingness to participate in a hypothetical HIV vaccine trial ; 2 ) participants are familiar with vaccines but do not clearly distinguish the use of vaccines for prevention or curing ; 3 ) the most common reason given for being interested in participating in a vaccine trial was to be protected from HIV/AIDS ; 4 ) trials ' procedures ( e.g. , placebos , r and omization , and blinding ) were unfamiliar ; and 5 ) knowledge about trials ' procedures increased incrementally over follow‐up , but at different rates for different concepts . These data demonstrate that potential vaccine trials ' participants may benefit from vaccine trial education if adequate time is allowed to ensure that participants are able to master the complex information required for trial participation In preparation for trials of new HIV prevention methods , willingness to participate ( WTP ) was assessed in Beira , Mozambique . A totla of 1 019 women participating in an HIV incidence study , and 97 men participating in a separate WTP survey , were interviewed . When comparing the answers to questions that were identical in the two studies , WTP was higher among women than men for all prevention methods . Among women , WTP was highest for trials evaluating daily oral pre-exposure prophylaxis ( PrEP ; 84.4 % reporting very likely to participate ) , followed by vaccination ( 77.8 % ) , daily vaginal gel use ( 67.7 % ) , coital vaginal gel use ( 67.1 % ) and monthly vaginal ring use ( 47.7 % ) . Among men , WTP was highest for trials evaluating vaccination ( 57.6 % ) , followed by daily vaginal gel use for female sexual partners ( 52.5 % ) , daily oral PrEP ( 49.5 % ) , coital vaginal gel use for female sexual partners ( 46.4 % ) and monthly vaginal ring use for female sexual partners ( 39.4 % ) . Among men , the most important motivators for trial participation were social benefits , whereas personal risks ( most notably receiving injections and /or blood draws ) were deterrents ; this was not assessed in women . Other important lessons learnt are that male circumcision and antiretroviral drugs were not generally recognised as ways to prevent HIV , that having to use hormonal contraception during trial participation will likely reduce WTP , and that evening clinics are not likely to be popular . The barriers reported in this and other studies may be challenging but are not impossible to overcome |
11,817 | 30,591,664 | The oolong tea group also showed a significant decrease in FBG , but the quality of evidence was very low .
In conclusion , green tea consumption might decrease FBG levels , especially in < 55-year-olds or Asian-based population | Prospect i ve cohort studies have described an association between coffee or tea consumption and the risk of developing diabetes .
However , whether coffee or tea improves glucose metabolism remains uncertain . | BACKGROUND Green tea consumption has been associated with favorable changes in body weight and obesity-related hormones , although it is not known whether these changes result from green tea polyphenols or caffeine . OBJECTIVE We examined the impact of decaffeinated green tea extract ( GTE ) containing 843 mg of (-)-epigallocatechin-3-gallate on anthropometric variables , obesity-associated hormones , and glucose homeostasis . METHODS The Minnesota Green Tea Trial was a 12-mo r and omized , double-blind , placebo-controlled clinical trial of 937 healthy postmenopausal women assigned to either decaffeinated GTE ( 1315 mg total catechins/d ) or a placebo , stratified by catechol-O-methyltransferase ( COMT ) genotype . This study was conducted in a subset of 237 overweight and obese participants [ body mass index ( BMI ) ≥25 kg/m(2 ) ] . RESULTS No changes in energy intake , body weight , BMI , or waist circumference ( WC ) were observed over 12 mo in women taking GTE ( n = 117 ) or placebo ( n = 120 ) . No differences were seen in circulating leptin , ghrelin , adiponectin , or glucose concentrations at month 12 . Participants r and omly assigned to GTE with baseline insulin ≥10 μIU/mL ( n = 23 ) had a decrease in fasting serum insulin from baseline to month 12 ( -1.43 ± 0.59 μIU/mL ) , whereas those r and omly assigned to placebo with baseline insulin ≥10 μIU/mL ( n = 19 ) had an increase in insulin over 12 mo ( 0.55 ± 0.64 μIU/mL , P < 0.01 ) . Participants with the homozygous high-activity ( G/G ) form of COMT had significantly lower adiponectin ( 5.97 ± 0.50 compared with 7.58 ± 0.53 μg/mL , P = 0.03 ) and greater insulin concentrations ( 7.63 ± 0.53 compared with 6.18 ± 0.36 μIU/mL , P = 0.02 ) at month 12 compared with those with the low-activity ( A/A ) genotype , regardless of treatment group . CONCLUSIONS Decaffeinated GTE was not associated with reductions in body weight , BMI , or WC and did not alter energy intake or mean hormone concentrations in healthy postmenopausal women over 12 mo . GTE decreased fasting insulin concentrations in those with elevated baseline fasting concentrations . The high-activity form of the COMT enzyme may be associated with elevations in insulin and a reduction in adiponectin concentrations over time . This trial was registered at http://www . clinical trials.gov as NCT00917735 Background —Epidemiological studies suggest that tea consumption decreases cardiovascular risk , but the mechanisms of benefit remain undefined . Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress . Some antioxidants have been shown to reverse endothelial dysfunction , and tea contains antioxidant flavonoids . Methods and Results —To test the hypothesis that tea consumption will reverse endothelial dysfunction , we r and omized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design . Short-term effects were examined 2 hours after consumption of 450 mL tea or water . Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks . Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound . Fifty patients completed the protocol and had technically suitable ultrasound measurements . Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery , whereas consumption of water had no effect ( P < 0.001 by repeated- measures ANOVA ) . Tea consumption had no effect on endothelium-independent nitroglycerin-induced dilation . An equivalent oral dose of caffeine ( 200 mg ) had no short-term effect on flow-mediated dilation . Plasma flavonoids increased after short- and long-term tea consumption . Conclusions —Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease . This finding may partly explain the association between tea intake and decreased cardiovascular disease events BACKGROUND Green tea is one of the most popular beverages in the world . It is believed to have beneficial effects in the prevention and treatment of many diseases , one of which is type 2 diabetes . The aim of the study is to examine the effect of a decaffeinated green tea extract ( GTE ) providing a daily dose of 856 mg of epigallocatechin gallate ( EGCG ) on obese individuals with type 2 diabetes . MATERIAL S AND METHODS The clinical trial was a r and omized , double-blind , placebo-controlled clinical trial conducted from December 2007 through November 2008 . The subjects were r and omly assigned to either receive 1,500 mg of a decaffeinated GTE or placebo daily for 16 weeks . Sixty-eight of 80 subjects , ages 20 - 65 years with BMI > 25 kg/m2 and type 2 diabetes for more than one year , completed this study . Homeostasis model assessment for insulin resistance ( HOMA-IR ) was used as the major outcome measurement . At baseline and after 16 weeks of treatment , anthropometric measurements , fasting glucose , hemoglobin A1C percent ( HbA1C ) , hormone peptides , and plasma lipoproteins were measured from both groups . RESULTS No statistically significant differences were detected between the decaffeinated GTE and placebo groups in any measured variable . A statistically significant within-group 0.4-percent reduction in HbA1C ( from 8.4 to 8.0 % ) was observed after GTE treatment compared to baseline . Within-group comparison also revealed that the GTE group had significant reductions in waist circumference ( WC ) , HOMA-IR index , and insulin level , and a significant increase in the level of ghrelin . Within-group comparison of those in the placebo group showed a significant increase in the level of ghrelin . CONCLUSIONS This study found no statistical difference in any measured variable between the decaffeinated GTE and placebo groups ; however , there were some statistically significant within-group changes detected . More research is required to determine whether a decaffeinated GTE st and ardized for EGCG content will provide any clinical benefits in obese individuals with type 2 diabetes . Clinical Trial Registration NO : NCT00567905 AIMS Coffee consumption is associated with a reduced risk of Type 2 diabetes . Our aim was to investigate if coffee intake may also reduce the risk of latent autoimmune diabetes in adults , an autoimmune form of diabetes with features of Type 2 diabetes . METHODS We used data from a population -based case-control study with incident cases of adult onset ( ≥ 35 years ) diabetes , including 245 cases of latent autoimmune diabetes in adults ( glutamic acid decarboxylase antibody positive ) , 759 cases of Type 2 diabetes ( glutamic acid decarboxylase antibody negative ) , together with 990 control subjects without diabetes , r and omly selected from the population . Using question naire information on coffee consumption , we estimated the odds ratio of latent autoimmune diabetes in adults and Type 2 diabetes adjusted for age , sex , BMI , smoking , physical activity , alcohol , education and family history of diabetes . RESULTS Coffee intake was inversely associated with Type 2 diabetes ( odds ratio 0.92 , 95 % CI 0.87 - 0.98 per cup/day ) . With regard to latent autoimmune diabetes in adults , the general trend was weak ( odds ratio 1.04 , 95 % CI 0.96 - 1.13 ) , but stratification by degree of autoimmunity ( median glutamic acid decarboxylase antibody levels ) suggested that coffee intake may be associated with an increased risk of high glutamic acid decarboxylase antibody latent autoimmune diabetes in adults ( odds ratio 1.11 , 95 % CI 1.00 - 1.23 per cup/day ) . Furthermore , for every additional cup of coffee consumed per day , there was a 15.2 % ( P = 0.0268 ) increase in glutamic acid decarboxylase antibody levels . CONCLUSIONS Our findings confirm that coffee consumption is associated with a reduced risk of Type 2 diabetes . Interestingly , the findings suggest that coffee may be associated with development of autoimmunity and possibly an increased risk of more Type 1-like latent autoimmune diabetes in adults Purpose Coffee is known to contain phytochemicals with antioxidant potential . The aim of this study was to investigate possible antioxidant effects of coffee in healthy human volunteers . Methods A placebo-controlled intervention trial was carried out on 160 healthy human subjects , r and omised into three groups , receiving 3 or 5 cups of study coffee or water per day , for 8 weeks . Blood sample s were taken before , during , and after the intervention . Serum was used for analysis of blood lipids and st and ard clinical chemistry analytes . Peripheral blood mononuclear cells were isolated , and DNA damage ( str and breaks and oxidised bases ) was measured with the comet assay . The lipid oxidation product isoprostane 8-iso-PGF2α was assayed in urine sample s by LC – MS/MS . Results There was no significant effect of coffee consumption on the markers of oxidation of DNA and lipids . Creatinine ( in serum ) increased by a few per cent in all groups , and the liver enzyme γ-glutamyl transaminase was significantly elevated in serum in the 5 cups/day group . Other clinical markers ( including glucose and insulin ) , cholesterol , triacylglycerides , and inflammatory markers were unchanged . There was no effect of coffee on blood pressure . Conclusion In a carefully controlled clinical trial with healthy subjects , up to 5 cups of coffee per day had no detectable effect , either beneficial or harmful , on human health BACKGROUND Increasing coffee intake was inversely associated with risk of type 2 diabetes in population s of European descent ; however , data from high-risk Asian population s are lacking as are data on tea intake in general . OBJECTIVE We investigated the prospect i ve associations between intakes of coffee , black tea , and green tea with the risk of type 2 diabetes in Singaporean Chinese men and women . DESIGN We analyzed data from 36 908 female and male participants in the Singapore Chinese Health Study aged 45 - 74 y in 1993 - 1998 who had multiple diet and lifestyle measures assessed and then were followed up between 1999 and 2004 . We used Cox regression models to investigate the association of baseline coffee and tea intakes with incident type 2 diabetes during follow-up , with adjustment for a number of possible confounding or mediating variables . RESULTS In multivariate models participants reporting > or = 4 cups of coffee/d had a 30 % reduction in risk of diabetes [ relative risk ( RR ) : 0.70 ; 95 % CI : 0.53 , 0.93 ] compared with participants who reported nondaily consumption . Participants reporting > or = 1 cup of black tea/d had a suggestive 14 % reduction in risk of diabetes ( RR : 0.86 ; 95 % CI : 0.74 , 1.00 ) compared with participants who reported 0 cups/d , and we observed no association with green tea . CONCLUSION Regular consumption of coffee and potentially black tea , but not green tea , is associated with lower risk of type 2 diabetes in Asian men and women in Singapore The aim of this study is to investigate the effect of green tea extract on patients with type 2 diabetes mellitus and lipid abnormalities on glycemic and lipid profiles , and hormone peptides by a double-blinded , r and omized and placebo-controlled clinical trial . This trial enrolled 92 subjects with type 2 diabetes mellitus and lipid abnormalities r and omized into 2 arms , each arm comprising 46 participants . Of the participants , 39 in therapeutic arm took 500 mg green tea extract , three times a day , while 38 in control arm took cellulose with the same dose and frequency to complete the 16-week study . Anthropometrics measurements , glycemic and lipid profiles , safety parameters , and obesity-related hormone peptides were analyzed at screening and after 16-week course . Within-group comparisons showed that green tea extract caused a significant decrease in triglyceride and homeostasis model assessment of insulin resistance index after 16 weeks . Green tea extract also increased significantly high density lipoprotein cholesterol . The HOMA-IR index decreased from 5.4±3.9 to 3.5±2.0 in therapeutic arm only . Adiponectin , apolipoprotein A1 , and apolipoprotein B100 increased significantly in both arms , but only glucagon-like peptide 1 increased in the therapeutic arm . However , only decreasing trend in triglyceride was found in between-group comparison . Our study suggested that green tea extract significantly improved insulin resistance and increased glucagon-like peptide 1 only in within-group comparison . The potential effects of green tea extract on insulin resistance and glucagon-like peptide 1 warrant further investigation . Trial Registration Clinical Trials.gov The consumption of green tea has been associated with cardiovascular and metabolic diseases . There have been some studies on the influence of green tea on the mineral status of obese subjects , but they have not yielded conclusive results . The aim of the present study is to examine the effects of green tea extract on the mineral , body mass , lipid profile , glucose , and antioxidant status of obese patients . A r and omized , double-blind , placebo-controlled study was conducted . Forty-six obese patients were r and omly assigned to receive either 379 mg of green tea extract , or a placebo , daily for 3 months . At baseline , and after 3 months of treatment , the anthropometric parameters , blood pressure , and total antioxidant status were assessed , as were the levels of plasma lipids , glucose , calcium , magnesium , iron , zinc , and copper . We found that 3 months of green tea extract supplementation result ed in decreases in body mass index , waist circumference , and levels of total cholesterol , low-density cholesterol , and triglyceride . Increases in total antioxidant level and in zinc concentration in serum were also observed . Glucose and iron levels were lower in the green tea extract group than in the control , although HDL-cholesterol and magnesium were higher in the green tea extract group than in the placebo group . At baseline , a positive correlation was found between calcium and body mass index , as was a negative correlation between copper and triglycerides . After 3 months , a positive correlation between iron and body mass index and between magnesium and HDL-cholesterol , as well as a negative correlation between magnesium and glucose , were observed . The present findings demonstrate that green tea influences the body 's mineral status . Moreover , the results of this study confirm the beneficial effects of green tea extract supplementation on body mass index , lipid profile , and total antioxidant status in patients with obesity Context Caffeine intake from coffee has been associated with a lower incidence of diabetes . Research ers have not studied the relationship of green tea , a popular beverage in Japan , where the incidence of diabetes is increasing rapidly . Contributions The authors estimated the intake of caffeine-containing beverages in a community-based survey in Japan and measured the 5-year incidence of diabetes . Greater intake of green tea or coffee was associated with a reduced incidence of diabetes . The effect of green tea was largely observed in women , was dose-related , and reflected caffeine intake . Implication s Higher intake of caffeine , whether from coffee or green tea , is associated with a lower incidence of diabetes . The Editors The prevalence of type 2 diabetes has increased worldwide , particularly in Asian countries where it was previously low ( 1 ) . In Japan , population -based studies have shown a 2-fold increase in the prevalence of diabetes during the past 2 decades , from 5 % to 10 % to 10 % to 15 % ( 2 ) . Several cohort studies done in Europe and in the United States reported an association between coffee consumption , a major source of caffeine , and reduced risk for diabetes ( 3 - 7 ) . Although these studies did not show any association between consumption of black tea and the risk for diabetes , they did not examine the effect of green or oolong teas , major sources of caffeine in Asian countries . Consumption of green tea is common in Japan ; 80 % of the population drinks green tea , and the average consumption per capita is 2 cups per day ( 8) . We wanted to determine whether there is a relationship between consumption of green tea and the risk for type 2 diabetes and , if so , whether caffeine fully accounts for this relationship . To examine these questions , we analyzed data from a large cohort study of 19487 middle-aged men and women in 25 communities across Japan . We also examined the effect of age , sex , body mass index ( BMI ) , family history , smoking status , alcohol use , magnesium intake , and physical activity on the association between this mode of caffeine consumption and risk for diabetes . Methods The Japan Collaborative Cohort Study for Evaluation of Cancer Risk ( JACC Study ) started between 1988 and 1990 . A total of 110792 individuals ( 46465 men and 64327 women ) who were 40 to 79 years of age and living in 45 communities across Japan participated in municipal health screening examinations and completed self-administered question naires regarding lifestyle and medical history of cardiovascular disease and cancer ( 9 ) . Informed consent was obtained before the completion of the question naire . Participants from 25 of the 45 communities completed 5-year follow-up surveys . Among 35690 participants ( 15177 men and 20513 women ) who were 40 to 65 years of age at baseline without a history of type 2 diabetes , stroke , coronary heart disease , or cancer , 17413 individuals ( 49 % ; 6727 men and 10686 women ) completed the 5-year follow-up question naire and provided valid responses on tea or coffee consumption and history of type 2 diabetes . The data from these 17413 individuals were used for the analyses . The mean age of the nonrespondents was 1 year younger for men ( 52.3 vs. 53.3 years of age ) and did not differ for women ( 53.1 vs. 53.0 years of age ) compared with the respondents . The mean BMI and the prevalence of a BMI of 25.0 kg/m2 or greater did not differ between the respondents and nonrespondents . Mean BMI was 22.7 kg/m2 versus 22.8 kg/m2 for men and 22.8 kg/m2 versus 22.9 kg/m2 for women , respectively ; the prevalence of overweight was 18 % versus 19 % for men and 21 % versus 22 % for women , respectively . The ethical committees at Nagoya University and the University of Tsukuba approved the study . Assessment of Consumption of Tea and Coffee and Caffeine Intake At baseline , consumption of tea and coffee was assessed by using a self-administered dietary question naire . Participants were asked to state their average consumption of green tea , black tea , oolong tea , and coffee during the previous year . They could select any of 4 frequency responses : less than once a week , about 1 to 2 times a week , about 3 to 4 times a week , and almost every day . Participants who selected the response of almost every day were also asked to state their average consumption of these beverages in number of cups per day . We classified the categories of consumption as less than 1 cup per week , 1 to 6 cups per week , 1 to 2 cups per day , 3 to 5 cups per day , and 6 or more cups per day . The highest 2 or 3 consumption categories were combined for coffee , black tea , and oolong tea because of the small number of participants in these categories . The consumption of decaffeinated coffee or tea was not recorded because these products were not commercially available in Japan in the early 1990s . The total intake of caffeine was calculated by adding the caffeine content from each specific beverage ( 1 cup for coffee or tea ) and multiplying it by the participant 's weight proportional to the frequency of caffeine use . We estimated the size of the cup for each beverage from a validation study ( 10 ) and the caffeine content per 100 mL of each beverage from the Japan Food Tables ( 11 ) . The estimated caffeine content was 153 mg per cup ( 170 mL ) of coffee , 30 mg per cup ( 200 mL ) of green tea , 51 mg per cup ( 170 mL ) of black tea , and 38 mg per cup ( 190 mL ) of oolong tea . The mean caffeine intake was 229 mg/d for men and 215 mg/d for women . Relative proportions of caffeine intake by beverage were 46 % from green tea , 44 % to 47 % from coffee , 3 % from black tea , and 4 % to 5 % from oolong tea . For reproducibility , the Spearman correlation coefficients between the 2 question naires , administered 1 year apart for 85 participants ( 8 men and 77 women ) , were 0.79 for green tea , 0.87 for coffee , 0.77 for black tea , and 0.56 for oolong tea ( 10 ) . The validity of the data was confirmed for the 85 participants by comparing the data from the question naire with those from four 3-day dietary records collected approximately 3 to 4 months apart ( 10 ) . The mean frequency of consumption of green tea was 25.4 cups per week according to the question naire and 30.1 cups per week according to four 1-week dietary records ( Spearman correlation coefficient , 0.47 ) . The respective mean frequencies were 8.0 cups and 7.1 cups per week with a correlation coefficient of 0.79 for coffee , 1.4 cups and 1.6 cups per week with a correlation coefficient of 0.70 for black tea , and 1.8 cups and 1.2 cups per week with a correlation coefficient of 0.55 for oolong tea . When we restricted the data to the 77 women , the results were essentially the same . Assessment of Diabetes Cases Participants who reported having diabetes newly diagnosed by physicians on the 5-year follow-up question naire were considered to have incident diabetes . To examine the validity of self-reporting of diabetes , we compared self-report data with laboratory findings and treatment status in a sample of 1230 men and 1837 women . We considered elevated glucose concentrations ( fasting serum glucose concentration 7.8 mmol/L [ 140 mg/dL ] or a r and omly measured concentration of 11.1 mmol/L [ 200 mg/dL ] ) or treatment with oral hypoglycemic agents or insulin to indicate new cases of diabetes . Recent criteria from the American Diabetes Association ( 12 ) were not used because the cases in our study were diagnosed before 1995 . The sensitivity of self-reporting was 70 % for men and 75 % for women ; the specificity was 95 % for men and 98 % for women . Statistical Analysis To examine potential confounding variables reported from previous studies ( 3 - 7 ) , we presented baseline characteristics according to the frequency of consumption for each beverage . Tests for trends were conducted by using the median values of confounding variables in each category of beverage ; the linear regression model was used for continuous variables , and the logistic regression model was used for categorical variables . The odds ratios for incident type 2 diabetes were calculated in each category of beverage consumption and in each quartile of caffeine intake ; less than 1 cup per week or the lowest quartile was used as the reference category . We estimated age , sex , and BMI -adjusted odds ratios and multivariable odds ratios using the logistic regression model , adjusting for age ( in years ) , sex , sex-specific quintiles of BMI ( weight in kilograms divided by the square of height in meters ) , parental history of diabetes ( yes or no ) , smoking status ( never , former , or current [ 1 to 19 , 20 to 29 , or 30 cigarettes/d ] ) , alcohol intake ( never , former , or current [ 1 to 22 , 23 to 45 , 46 to 68 , or 69 g/d ] ) , sex-specific quintiles of magnesium intake , hours of walking ( < 0.5 , 0.5 , 0.6 to 0.9 , and 1.0 h/d ) , and hours of participation in sports ( < 1 , 1 to 2 , 3 to 4 , and 5 h/wk ) . Sex-specific quintiles of BMI and magnesium intake were used because of different distributions between the sexes . We adjusted for magnesium intake because previous cohort studies indicated an inverse association between magnesium intake and risk for diabetes ( 13 , 14 ) . We conducted a test for trend by treating median values of each category of beverage or caffeine intake as continuous variables . We examined the association between caffeine intake and the risk for diabetes stratified by age group ( 40 to 54 years and 55 to 65 years ) , sex , family history of diabetes ( yes or no ) , current smoking status ( yes or no ) , current alcohol intake ( yes or no ) , magnesium intake ( below and above the sex-specific median ) , BMI ( < 25.0 kg/m2 and 25.0 kg/m2 ) , hours of walking ( < 0.5 and 0.5 h/d ) , and hours of participation in sports ( < 5 and 5 h/wk ) . The interactions with these stratified variables were tested by using cross-product terms of caffeine intake and the stratified variables . All analyses were conducted by using the SAS statistical package , version 8.2 ( SAS Institute Inc. , Cary , North Carolina ) . P values for statistical tests were 2-tailed , and 95 % CIs were estimated . Role of Context A recently published study in a Dutch population identified an association between higher coffee consumption and lower risk for type 2 diabetes mellitus but did not distinguish between intake of regular and decaffeinated coffee . Contribution This large epidemiologic study in a U.S. sample confirmed the Dutch study findings . It also found a statistically significant protective association between total caffeine intake and type 2 diabetes mellitus and a modest inverse association with decaffeinated coffee consumption . Implication s Consumption of caffeinated coffee is associated with a reduced risk for type 2 diabetes mellitus . Further studies should explore the long-term effects of caffeine on glucose metabolism . The Editors The prevalence of type 2 diabetes mellitus has increased dramatically in the past decades , and the disease now affects approximately 8 % of U.S. adults ( 1 ) . Diet and lifestyle factors are primary determinants of risk for type 2 diabetes ( 2 ) . In addition to overweight and obesity , other independent behavioral and lifestyle factors include physical inactivity , smoking , and a diet higher in glycemic load and trans fatty acids and lower in fiber and polyunsaturated fatty acids . Coffee consumption may be related to diabetes because short-term metabolic studies have suggested that caffeine adversely affects insulin sensitivity and glucose metabolism ( 3 ) . Coffee consumption is widespread ; more than 50 % of Americans drink coffee , and average per capita intake is about 2 cups per day ( 4 ) . Coffee is the primary source of caffeine intake , providing approximately 210 mg/d per person in the United States . In humans , acute administration of caffeine decreases insulin sensitivity and impairs glucose tolerance ( 3 , 5 - 8 ) . On the other h and , caffeine stimulates thermogenesis and increases energy expenditure ( 9 - 11 ) , which may facilitate weight reduction and maintenance . Because of these complex physiologic effects of caffeine and because tolerance to the humoral and hemodynamic effects of caffeine typically develops with long-term use ( 12 ) , it is difficult to extrapolate findings from short-term metabolic studies to long-term use of coffee and other caffeinated beverages . A recent epidemiologic study has found a statistically significant inverse association between coffee consumption and risk for type 2 diabetes in a sample of Dutch participants ( 13 ) . After adjustment for potential confounders , the relative risk for type 2 diabetes among participants consuming at least 7 cups of coffee per day as compared with those consuming 2 cups or less per day was 0.50 ( 95 % CI , 0.35 to 0.72 ; P < 0.001 for trend ) . The study , however , could not distinguish regular coffee from decaffeinated coffee and did not evaluate the association with total caffeine intake . In our study , we examined long-term intake of coffee and other caffeinated beverages and decaffeinated coffee in relation to incidence of type 2 diabetes in 2 large prospect i ve cohorts of men and women . In particular , we examined whether the associations were modified by smoking and body mass index . Methods Study Sample The Health Professionals Follow-up Study The Health Professionals Follow-up Study ( HPFS ) was established in 1986 when 51 529 male health professionals , including dentists , optometrists , veterinarians , osteopathic physicians , podiatrists , and pharmacists , who were 40 to 75 years of age returned a mailed question naire providing detailed information about their medical history , lifestyle , and other risk factors ( 14 ) . Information on the cohort is up date d every 2 years to identify newly diagnosed diseases . For our analysis , we excluded men with a previous diagnosis of type 2 diabetes , coronary heart disease , or cancer at baseline . Participants who did not complete more than 70 of 131 food items in the 1986 dietary question naire or had extreme scores for total daily intake of energy ( < 800 kcal or > 4200 kcal ) were excluded . After exclusions , the analysis included 41 934 eligible men who were followed from 1986 to 1998 . The Nurses ' Health Study The Nurses ' Health Study ( NHS ) was established in 1976 when 121 700 female nurses 30 to 55 years of age living in 11 large states completed a mailed question naire providing detailed information about their medical history , lifestyles , and other risk factors ( 15 ) . The information is up date d every 2 years to identify newly diagnosed diseases . In 1980 , a semiquantitative food frequency question naire was added . For our analysis , we excluded women with a previous diagnosis of type 2 diabetes , coronary heart disease , or cancer at baseline . Participants who did not complete more than 10 items on the 1980 dietary question naire or had extreme scores for total daily intake of energy ( < 500 kcal or > 3500 kcal ) were also excluded , leaving 84 276 eligible women who were followed from 1980 to 1998 . Assessment of Coffee and Caffeine Intake Vali date d dietary question naires were sent to the HPFS participants in 1986 , 1990 , and 1994 and to the NHS participants in 1980 , 1984 , 1986 , 1990 , and 1994 . In all the question naires , participants were asked how often on average during the previous year they had consumed coffee and tea . Decaffeinated coffee and different types of caffeinated soft drinks were first assessed in 1986 in the HPFS and in 1984 in the NHS . We assessed the total intake of caffeine by summing the caffeine content for a specific amount of each food during the previous year ( 1 cup for coffee or tea , one 12-ounce bottle or can for carbonated beverages , and 1 ounce for chocolate ) multiplied by a weight proportional to the frequency of its use . The participants could choose from 9 frequency responses ( never , 1 to 3 per month , 1 per week , 2 to 4 per week , 5 to 6 per week , 1 per day , 2 to 3 per day , 4 to 5 per day , and 6 or more per day ) . Using the U.S. Department of Agriculture food composition sources , we estimated that the caffeine content was 137 mg per cup of coffee , 47 mg per cup of tea , 46 mg per bottle or can of cola beverage , and 7 mg per serving of chocolate c and y. In our validation studies , high correlations were recorded for coffee and other caffeinated beverage intake assessed by the food frequency question naire and several 1-week diet records ( coffee , r = 0.78 ; tea , r = 0.93 ; and caffeinated sodas , r = 0.85 ) ( 16 ) . For these analyses , coffee consumption was categorized into 5 groups : never , less than 1 cup per day , 1 to 3 cups per day , 4 to 5 cups per day , and 6 cups or more per day . Caffeine intake was categorized into quintiles . Assessment of Diabetes Cases Participants who reported having diabetes were sent a supplementary mailed question naire that asked about symptoms , diagnostic tests , and treatment . We considered any 1 of the following criteria to represent a new case of diabetes : classic symptoms and elevated glucose levels ( fasting plasma glucose concentration 7.8 mmol/L [ 140 mg/dL ] or r and omly measured concentration 11.1 mmol/L [ 200 mg/dL ] ) ; at least 2 elevated plasma glucose concentrations on different occasions in the absence of symptoms ( plasma glucose level 11.1 mmol/L [ 200 mg/dL ] 2 or more hours after oral glucose tolerance testing ) ; or treatment with oral hypoglycemic agents or insulin . Our criteria for diabetes classification are consistent with those proposed by the National Diabetes Data Group ( 17 ) because most cases were diagnosed before 1997 . The validity of this diagnostic procedure has been verified in a sub sample of this study sample ( 18 ) . The diagnosis of type 2 diabetes was confirmed by medical records in 98 % of the participants . In addition , another sub study assessing the prevalence of undiagnosed diabetes suggested a very low rate of false-negative results ( 19 ) . Statistical Analysis We calculated the follow-up period from the return of the baseline question naires ( in 1986 for men and in 1980 for women ) to the diagnosis of type 2 diabetes , death , or the end of follow-up ( January 1998 for men and June 1998 for women ) , whichever occurred first . Incidence rates for diabetes were calculated by dividing incident cases by person-years of follow-up in each category of coffee intake . Relative risks were calculated as the rate of occurrence of type 2 diabetes in each quintile of caffeine intake divided by the corresponding rate in the lowest quintile , and 95 % CIs were calculated . To inspect potential confounding variables for the analyses , we examined baseline characteristics ( directly st and ardized to the age distribution of each cohort ) according to coffee consumption levels . We used proportional hazards models ( 20 ) to adjust for several risk factors , including age in 5 categories ( < 50 , 50 to 54 , 55 to 59 , 60 to 64 , or 65 years of age ) ; body mass index ( weight divided by height [ kg/m2 ] ) in 8 categories ( < 23 , 23 to 24 , 25 to 28 , 29 to 30 , 31 to 32 , 33 to 34 , 35 to 39 , or 40 kg/m2 ) ; physical activity ( hours of moderate or vigorous exercise in NHS or quintiles of metabolic equivalents in HPFS ) ; family history of diabetes ( yes or no ) ; hormone use ( never , current , or past [ in NHS only ] ) ; smoking status ( never , past , or current smokers [ 1 to 14 , 15 to 24 , or 25 cigarettes per day ] ) ; alcohol consumption ( 0 , 0.1 to 4.9 , 5 to 9.9 , 10 to 14.9 , or 15 g/d ) ; total calorie intake ( continuous ) ; and quintiles of trans fat , glycemic load , and cereal fiber intake . We also adjusted for magnesium intake because our previous analyses have shown an inverse association between dietary magnesium and risk for diabetes ( 21 ) . Information on covariates was up date d periodically during follow-up . We performed a test for trend by treating median values of each category of caffeine and coffee intake as continuous variables . To represent long-term intake of coffee and caffeine and to reduce measurement error , we conducted analyses using cumulative up date d caffeine and coffee intake from all question naires ( 22 ) . For example , in the NHS , diabetes incidence between 1980 and 1984 was related to the coffee intake from the 1980 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 Green tea is believed to have beneficial effects in the prevention and treatment of acne . OBJECTIVE To examine the effects of a decaffeinated green tea extract ( GTE ) , providing a daily dose of 856 mg of epigallocatechin gallate ( EGCG ) upon women with post-adolescent acne . METHODS A r and omized , double-blind , placebo-controlled clinical trial was conducted from May 2012 through October 2013 . A final group of 80 subjects were r and omly assigned to receive either 1500 mg of decaffeinated GTE or placebo ( cellulose ) daily for 4 weeks . Inflammatory lesion counts were used as the major outcome measurement . At baseline and after 4 weeks of treatment , anthropometric measurements , fasting glucose levels and a lipid profile were measured from both groups . RESULTS Sixty-four of 80 women , from 25 to 45 years of age with moderate-to-severe acne completed the study . Statistically significant differences were noted in inflammatory lesion counts distributed on the nose , periorally and on the chin between the two groups . However , there were no significant differences between groups for total lesion counts . Within-group comparison revealed that the GTE group had significant reductions in inflammatory lesions distributed on the forehead and cheek , and significant reductions in total lesion counts . GTE result ed in significant reductions in total cholesterol levels within the GTE group . CONCLUSIONS GTE result ed in significant reductions in lesions located on the nose , perioral area and chin . More research is required to determine whether a decaffeinated GTE st and ardized for EGCG content will provide clinical benefits in women with post-adolescent acne Objectives : To study the effects of green tea on body weight , and biochemical and hormonal profiles in obese Chinese women with polycystic ovary syndrome ( PCOS ) . Methods : Thirty-four obese Chinese women with PCOS were r and omized into either treatment with green tea capsules or placebo for 3 months . The anthropomentric measurements , and biochemical and hormonal profiles before and after treatment in each group were compared . Results : The body weight of the green tea group decreased by a nonsignificant 2.4 % after treatment ; whereas the body weight , body mass index ( BMI ) , and body fat content of the control group were significantly higher after 3 months . There were no differences in any of the hormone levels measured in either group . The biochemical profiles of the two groups were also similar except that there was a small but significant rise in the triglyceride level in the green tea group . Fewer patients in the green tea group remained amenorrhoeic , but this was not significantly different from the control group . Conclusions : Green tea supplementation did not significantly reduce body weight in obese women with PCOS , nor did it alter the glucose or lipid metabolism Background Green tea was suggested as a therapeutic agent for the treatment of diabetes more than 70 years ago , but the mechanisms behind its antidiabetic effect remains elusive . In this work , we address this issue by feeding a green tea extract ( TEAVIGO ™ ) with a high content of epigallocatechin gallate ( EGCG ) or the thiazolidinedione PPAR-γ agonist rosiglitazone , as positive control , to db/db mice , an animal model for diabetes . Methods Young ( 7 week-old ) db/db mice were r and omized and assigned to receive diets supplemented with or without EGCG or rosiglitazone for 10 weeks . Fasting blood glucose , body weight and food intake was measured along the treatment . Glucose and insulin levels were determined during an oral glucose tolerance test after 10 weeks of treatment . Pancreata were sample d at the end of the study for blinded histomorphometric analysis . Islets were isolated and their mRNA expression analyzed by quantitative RT-PCR . Results The results show that , in db/db mice , EGCG improves glucose tolerance and increases glucose-stimulated insulin secretion . EGCG supplementation reduces the number of pathologically changed islets of Langerhans , increases the number and the size of islets , and heightens pancreatic endocrine area . These effects occurred in parallel with a reduction in islet endoplasmic reticulum stress markers , possibly linked to the antioxidative capacity of EGCG . Conclusions This study shows that the green tea extract EGCG markedly preserves islet structure and enhances glucose tolerance in genetically diabetic mice . Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes OBJECTIVE To determine the efficacy of oolong tea for lowering plasma glucose in type 2 diabetic patients in Miaoli , Taiwan . RESEARCH DESIGN AND METHODS A total of 20 free-living subjects who had type 2 diabetes and took hyperglycemic drugs as prescribed were enrolled in the present study . Subjects consumed oolong tea ( 1,500 ml ) or water for 30 days each in a r and omized crossover design . Tea was not consumed for 14 days prior to treatments . RESULTS Relative to initial concentrations , oolong tea markedly lowered concentrations of plasma glucose ( from 229 + /- 53.9 to 162.2 + /- 29.7 mg/dl , P < 0.001 ) and fructosamine ( from 409.9 + /- 96.1 to 323.3 + /- 56.4 micromol/l , P < 0.01 ) , whereas the water control group had not changed ( 208.7 + /- 61.0 vs. 232.3 + /- 63.1 mg/dl for glucose and from 368.4 + /- 85.0 to 340.0 + /- 76.1 micromol/l for fructosamine ) . CONCLUSIONS Oolong tea may be an effective adjunct to oral hypoglycemic agents in the treatment of type 2 diabetes Higher habitual coffee consumption was associated with higher insulin sensitivity ( 1 ) and a lower risk for type 2 diabetes ( 2–6 ) in diverse population s. In contrast , short-term metabolic studies showed that caffeine intake can acutely lower insulin sensitivity ( 7–9 ) and increase glucose concentrations ( 10–15 ) . R and omized intervention studies are needed to examine whether tolerance to these acute effects develops after longer-term consumption ( 16 ) . We therefore examined the effects of coffee and caffeine on fasting blood concentrations of glucose and insulin over 2–4 weeks in two crossover studies in healthy volunteers . The studies were approved by the TNO Nutrition and Food Research Medical Ethics Committee , and all participants gave informed consent . The trials were originally design ed to study the effects of coffee and caffeine on plasma concentrations of homocysteine , and the study design s have been reported in detail previously ( 17,18 ) . Participants were regular coffee consumers ( more than five cups/day ) and did not have known diabetes . The first study was a 4-week crossover study that compared the effects of regular paper-filtered coffee consumption with that of coffee abstinence . A total of 40 volunteers used 1 l of coffee ( 70 g coffee grounds ) for 4 weeks and abstained from coffee for 4 weeks in r and om order . Fourteen participants did not complete the trial because of nausea and restlessness ( n = Regular consumption of green tea may be cardioprotective . In the present study we investigated the health effects of dietary supplementation with green tea catechins and the potential modifying effect of the catechol-O-methyltransferase ( COMT ) Val/Met genotype . Subjects ( sedentary males , aged 40 - 69 years , with BMI ≥ 28 and ≤ 38 kg/m(2 ) ) were r and omly assigned to consume decaffeinated green tea extract ( DGT ; 530 mg containing about 400 mg total catechins/capsule , twice daily ) and placebo in a complete cross-over design . Ambulatory blood pressure and biomarkers of metabolic function ( cholesterol , TAG , glucose and insulin ) were measured at weeks 0 and 6 . Although a marked increase in the concentration of plasma epigallocatechin gallate ( EGCG ) , urinary epigallocatechin ( EGC ) and urinary 4'-O-methyl EGC was found after DGT treatment , no effect on blood pressure or biomarkers of metabolic function was observed . However , a period × treatment interaction ( P < 0·05 ) was detected for body-weight change . Despite a similar increase in estimated energy intake during intervention period 1 , body weight decreased by 0·64 ( sd 2·2 ) kg and increased by 0·53 ( sd 1·9 ) kg in the DGT and placebo groups , respectively ( P = 0·025 ) , suggesting a protective effect of green tea catechins on weight gain . Additionally , the COMT Val/Met genotype influenced urinary accumulation of EGC and 4'-O-methyl EGC ( P < 0·01 ) . Mean concentrations were lower in individuals homozygous for the high-activity G-allele , possibly reflecting increased metabolic flux and a more rapid conversion to downstream metabolic species , compared with individuals carrying at least one copy of the low-activity A-allele . Additional studies are needed to confirm these findings and further explore the modifying effect of genotype Background Coffee consumption has been associated with a lower risk of type 2 diabetes in prospect i ve cohort studies , but the underlying mechanisms remain unclear . The aim of this study was to evaluate the effects of regular and decaffeinated coffee on biological risk factors for type 2 diabetes . Methods R and omized parallel-arm intervention conducted in 45 healthy overweight volunteers who were nonsmokers and regular coffee consumers . Participants were assigned to consumption of 5 cups ( 177 mL each ) per day of instant caffeinated coffee , decaffeinated coffee , or no coffee ( i.e. , water ) for 8 weeks . Results Average age was 40 years and body mass index was 29.5 kg/m2 . Compared with consuming no coffee , consumption of caffeinated coffee increased adiponectin ( difference in change from baseline 1.4 μg/mL ; 95 % CI : 0.2 , 2.7 ) and interleukin-6 ( difference : 60 % ; 95 % CI : 8 , 138 ) concentrations and consumption of decaffeinated coffee decreased fetuin-A concentrations ( difference : -20 % ; 95 % CI : -35 , -1 ) . For measures of glucose tolerance , insulin sensitivity , and insulin secretion , no significant differences were found between treatment groups . Conclusions Although no changes in glycemia and /or insulin sensitivity were observed after 8 weeks of coffee consumption , improvements in adipocyte and liver function as indicated by changes in adiponectin and fetuin-A concentrations may contribute to beneficial metabolic effects of long-term coffee consumption . Trial Registration clinical trials.gov There have been no controlled intervention studies to investigate the effects of green tea on circulating hormone levels , an established breast cancer risk factor . We conducted a double-blind , r and omized , placebo-controlled intervention study to investigate the effect of the main green tea catechin , epigallocatechin gallate ( EGCG ) , taken in a green tea extract , polyphenon E ( PPE ) . Postmenopausal women ( n = 103 ) were r and omized into three arms : placebo , 400-mg EGCG as PPE , or 800-mg EGCG as PPE as capsules per day for 2 months . Urinary tea catechin and serum estrogen , and rogen , lipid , glucose-related markers , adiponectin , and growth factor levels were measured at baseline and at the end of months 1 and 2 of intervention . On the basis of urinary tea catechin concentrations , compliance was excellent . Supplementation with PPE did not produce consistent patterns of changes in estradiol ( E2 ) , estrone ( E1 ) , or testosterone ( T ) levels . Low-density lipoprotein (LDL)-cholesterol decreased significantly in both PPE groups but was unchanged in the placebo group ; the change in LDL-cholesterol differed between the placebo and PPE groups ( P = 0.02 ) . Glucose and insulin levels decreased nonsignificantly in the PPE groups but increased in the placebo group ; statistically significant differences in changes in glucose ( P = 0.008 ) and insulin ( P = 0.01 ) were found . In summary , green tea ( 400- and 800-mg EGCG as PPE ; ∼5–10 cups ) supplementation for 2 months had suggestive beneficial effects on LDL-cholesterol concentrations and glucose-related markers . Cancer Prev Res ; 5(3 ) ; 393–402 . © 2012 AACR OBJECTIVE High habitual coffee consumption has been associated with a lower risk of type 2 diabetes , but data on lower levels of consumption and on different types of coffee are sparse . RESEARCH DESIGN AND METHODS This is a prospect i ve cohort study including 88,259 U.S. women of the Nurses ' Health Study II aged 26 - 46 years without history of diabetes at baseline . Consumption of coffee and other caffeine-containing foods and drinks was assessed in 1991 , 1995 , and 1999 . We documented 1,263 incident cases of confirmed type 2 diabetes between 1991 and 2001 . RESULTS After adjustment for potential confounders , the relative risk of type 2 diabetes was 0.87 ( 95 % CI 0.73 - 1.03 ) for one cup per day , 0.58 ( 0.49 - 0.68 ) for two to three cups per day , and 0.53 ( 0.41 - 0.68 ) for four or more cups per day compared with nondrinkers ( P for trend < 0.0001 ) . Associations were similar for caffeinated ( 0.87 [ 0.83 - 0.91 ] for a one-cup increment per day ) and decaffeinated ( 0.81 [ 0.73 - 0.90 ] ) coffee and for filtered ( 0.86 [ 0.82 - 0.90 ] ) and instant ( 0.83 [ 0.74 - 0.93 ] ) coffee . Tea consumption was not substantially associated with risk of type 2 diabetes ( 0.88 [ 0.64 - 1.23 ] for four or more versus no cups per day ; P for trend = 0.81 ) . CONCLUSIONS These results suggest that moderate consumption of both caffeinated and decaffeinated coffee may lower risk of type 2 diabetes in younger and middle-aged women . Coffee constituents other than caffeine may affect the development of type 2 diabetes The objective of the U.K. Prospect i ve Diabetes Study is to determine whether improved blood glucose control in type II diabetes will prevent the complications of diabetes and whether any specific therapy is advantageous or disadvantageous . The study will report in 1998 , when the median duration from r and omization will be 11 years . This report is on the efficacy of therapy over 6 years of follow-up and the overall incidence of diabetic complications . Subjects comprised 4,209 newly diagnosed type II diabetic patients who after 3 months ' diet were asymptomatic and had fasting plasma glucose ( FPG ) 6.0–15.0 mmol/l . The study consists of a r and omized controlled trial with two main comparisons : 1 ) 3,867 patients with 1,138 allocated to conventional therapy , primarily with diet , and 2,729 allocated to intensive therapy with additional sulfonylurea or insulin , which increase insulin supply , aim ing for FPG < 6 mmol/l ; and 2 ) 753 obese patients with 411 allocated to conventional therapy and 342 allocated to intensive therapy with metformin , which enhances insulin sensitivity . In the first comparison , in 2,287 subjects studied for 6 years , intensive therapy with sulfonylurea and insulin similarly improved glucose control compared with conventional therapy , with median FPG at 1 year of 6.8 and 8.2 mmol/l , respectively ( P < 0.0001 ) . and median HbA1c of 6.1 and 6.8 % , respectively ( P < 0.0001 ) . During the next 5 years , the FPG increased progressively on all therapies ( P < 0.0001 ) with medians at 6 years in the conventional and intensive groups , FPG 9.5 and 7.8 mmol/l , and HbA1c 8.0 and 7.1 % , respectively . The glycemic deterioration was associated with progressive loss of β-cell function . In the second comparison , in 548 obese subjects studied for 6 years , metformin improved glucose control similarly to intensive therapy with sulfonylurea or insulin . Metformin did not increase body weight or increase the incidence of hypoglycemia to the same extent as therapy with sulfonylurea or insulin . A high incidence of clinical complications occurred by 6-year follow-up . Of all subjects , 18.0 % had suffered one or more diabetes-related clinical endpoints , with 12.1 % having a macrovascular and 5.7 % a microvascular endpoint . Sulfonylurea , metformin , and insulin therapies were similarly effective in improving glucose control compared with a policy of diet therapy . The study is examining whether the continued improved glucose control , obtained by intensive therapy compared with conventional therapy ( median over 6 years HbA1c 6.6 % compared with 7.4 % ) , will be clinical ly advantageous in maintaining health Interest in finding natural antioxidants for use in food or medical material s to prevent free radical imbalance has increased considerably over the past years . The aim of this research was to evaluate changes in glycemic control and psychological state of patients with type 2 diabetes mellitus ( T2DM ) after use of antioxidant plant preparations . Fifty-six patients with T2DM were r and omly allocated to receive st and ardized Ginkgo biloba L. leaves dry extract , green tea dry extract , or placebo capsules . Diabetes glycemic control measured as glycated hemoglobin ( HbA1c ) level , antioxidant state and psychological data were evaluated at baseline , after 9 and 18 months of using either antioxidant preparations or placebo . The level of perceived stress lowered significantly after 9 months ( p=0.038 ) and 18 months ( p=0.030 ) , and the psychological aspect of quality of life significantly improved after 18 months ( p=0.019 ) of use of G. biloba extract . No significant differences were detected after using green tea extract . In patients using placebo , significant lowering of HbA1c level was observed after 18 months ( p=0.017 ) . In conclusion , antioxidant G. biloba leaf extract exhibited a mild effect on psychological state and a trend of improving glycemic control in patients with type 2 diabetes mellitus BACKGROUND The effects of black tea consumption on cardiovascular risk factors have been inconsistent in previous r and omized trials , all of which have been limited to a few weeks duration . METHODS We conducted a pilot parallel- design r and omized controlled trial among 31 adults aged 55 years and older with either diabetes or 2 other cardiovascular risk factors but no established clinical cardiovascular disease . Participants were r and omized to drink 3 glasses daily of either a st and ardized black tea preparation or water for 6 months . Cardiovascular risk factors were measured at the beginning and conclusion of the study . RESULTS Three participants dropped out of the study , leaving 14 participants assigned to tea and 14 assigned to water eligible for analyses . We found no statistically significant effects of black tea on cardiovascular biomarkers , including lipids , inflammatory markers , hemoglobin , adhesion molecules , prothrombotic and fibrinolytic parameters , and lipoprotein oxidizability . Assignment to tea did not appreciably influence blood pressure , and heart rate among participants assigned to tea was marginally higher than among control participants at 3 months ( P = .07 ) but not 6 months . CONCLUSIONS In this r and omized trial of black tea intake over 6 months among older adults with known cardiovascular risk factors , black tea did not appreciably influence any traditional or novel biomarkers of cardiovascular risk . Longer r and omized trials are needed to verify the inverse association of tea with risk of cardiovascular disease seen in cohort studies and identify potential c and i date mechanisms for such an association OBJECTIVES A prospect i ve r and omized controlled clinical trial determined the effect of Mauritian black tea consumption on fasting blood plasma levels of glucose , lipid profiles and antioxidant status in a normal population . METHODS The study group ( 71 % ) consumed 3 x 200 ml of black tea infusate/day for 12 weeks without additives followed by a 3 week wash-out . The control group ( 29 % ) consumed equivalent volume of hot water for same intervention period . RESULTS The tea used had high levels of gallic acid derivatives ( 50 ± 0.4 mg/L ) , flavan-3-ols ( 42 ± 2 mg/L ) , flavonols ( 32 ± 1 mg/L ) and theaflavins ( 90 ± 1 mg/L ) . Daily 9 g supplementation of black tea infusate induced , in a normal population , a highly significant decrease of fasting serum glucose ( 18.4 % ; p<0.001 ) and triglyceride levels ( 35.8 % ; p<0.01 ) , a significant decrease in LDL/HDL plasma cholesterol ratio ( 16.6 % ; p<0.05 ) and a non significant increase in HDL plasma cholesterol levels ( 20.3 % ) , while a highly significant rise in plasma antioxidant propensity ( FRAP : 418 % ; p<0.001 ) was noted . CONCLUSION Black tea consumed within a normal diet contributes to a decrease of independent cardiovascular risk factors and improves the overall antioxidant status in humans BACKGROUND Oolong tea has been studied for its effect on cardiovascular disease and obesity . Plasma adiponectin levels are reduced in obesity , in patients with type 2 diabetes mellitus and in coronary artery disease ( CAD ) . OBJECTIVE To investigate prospect ively , whether intake of Oolong tea influences plasma adiponectin levels , low-density lipoprotein ( LDL ) particle size , total cholesterol , high-density lipoprotein ( HDL ) cholesterol , LDL cholesterol , serum triglyceride and plasma glucose levels in patients with CAD . METHODS Twenty two patients in our study consumed Oolong tea ( 1000 ml ) or water for 1 month in our r and omized cross-over study design . RESULTS There was a significant difference in plasma adiponectin levels before and after 1 month intake of Oolong tea ( 6.26 + /- 3.26 microg/ml versus 6.88 + /- 3.28 microg/ml , P < 0.05 ) , and in plasma level LDL particle size ( 25.02+/-0.67 nm versus 25.31+/-0.60 nm , P < 0.01 ) . The water-consuming control group showed no changes ( 6.28+/-3.28 microg/ml versus 6.23+/-3.21 microg/ml ) in adiponectin levels or LDL particle sizes ( 25.03+/-0.70 nm versus 25.02+/-0.72 nm ) . We also observed a significant difference in hemoglobin A1c levels ( 7.23 + /- 4.45 % versus 6.99 + /- 4.30 % , P < 0.05 ) before and after intake of Oolong tea . CONCLUSION Oolong tea may have beneficial effects on the progression of atherosclerosis in patients with CAD Abstract The efficacy of caffeine ingestion in enhancing aerobic performance is well established . However , despite suggestions that caffeine may enhance resistance exercise performance , research is equivocal on the effect of acute caffeine ingestion on resistance exercise performance . It has also been suggested that dampened perception of perceived exertion and pain perception might be an explanation for any possible enhancement of resistance exercise performance due to caffeine ingestion . Therefore , the aim of this study was to examine the acute effect of caffeine ingestion on repetitions to failure , rating of perceived exertion ( RPE ) and muscle pain perception during resistance exercise to failure . Eleven resistance trained individuals ( 9 males , 2 females , mean age±SD=26.4±6.4 years ) , took part in this double-blind , r and omised cross-over experimental study whereby they ingested a caffeinated ( 5 mg kg−1 ) or placebo solution 60 minutes before completing a bout of resistance exercise . Experimental conditions were separated by at least 48 hours . Resistance exercise sessions consisted of bench press , deadlift , prone row and back squat exercise to failure at an intensity of 60 % 1 repetition maximum . Results indicated that participants completed significantly greater repetitions to failure , irrespective of exercise , in the presence of caffeine ( p=0.0001 ) . Mean±S.D of repetitions to failure was 19.6±3.7 and 18.5±4.1 in caffeine and placebo conditions , respectively . There were no differences in peak heart rate or peak blood lactate values across conditions ( both p > 0.05 ) . RPE was significantly lower in the caffeine compared to the placebo condition ( p=0.03 ) and was significantly higher during lower body exercises compared to upper body exercises irrespective of substance ingested ( p=0.0001 ) . For muscle pain perception , a significant condition by exercise interaction ( p=0.027 ) revealed that muscle pain perception was lower in the caffeine condition , irrespective of exercise . With caffeine , pain perception was significantly higher in the deadlift and back squat compared to the bench press . However , with placebo , pain perception was significantly higher for the deadlift and back squat compared to the prone row only . Therefore , acute caffeine ingestion not only enhances resistance exercise performance to failure but also reduces perception of exertion and muscle pain |
11,818 | 22,786,518 | However , this combination also produced significantly more frequent side effect-related trial dropouts compared to gabapentin alone .
AUTHORS ' CONCLUSIONS Multiple , good- quality studies demonstrate superior efficacy of two-drug combinations .
However , the number of available studies for any one specific combination , as well as other study factors ( e.g. limited trial size and duration ) , preclude the recommendation of any one specific drug combination for neuropathic pain . | BACKGROUND Pharmacotherapy remains an important modality for the treatment of neuropathic pain .
However , as monotherapy current drugs are associated with limited efficacy and dose-related side effects .
Combining two or more different drugs may improve analgesic efficacy and , in some situations , reduce overall side effects ( e.g. if synergistic interactions allow for dose reductions of combined drugs ) .
OBJECTIVES This review evaluated the efficacy , tolerability and safety of various drug combinations for the treatment of neuropathic pain . | Abstract In a double blind , placebo controlled trial of 40 volunteers , the burning discomfort associated with application of capsaicin cream ( 0.025 % ) was compared to placebo , GTN cream ( 1.33 % ) and to the combination of capsaicin cream ( 0.025 % ) plus GTN cream 1.33 % . Median VAS for burning pain were 0 for the placebo , GTN and GTN+capsaicin groups and 3 for the capsaicin group after single application of each cream at daily intervals . This study demonstrates that after single application the addition of GTN to capsaicin significantly reduces the burning discomfort associated with application of capsaicin alone Experimental studies have indicated that N-methyl-D-aspartate ( NMDA ) receptor antagonists may be effective analgesics in a wide variety of chronic pain states . The mechanism is presumed to be related to decreased firing of dorsal horn neurons after constant repeated C-fiber stimulation . Dextromethorphan ( DM ) , a potent NMDA antagonist with a good safety profile , may be a promising agent for the treatment of persistent pain . An open-label r and omized trial was design ed to examine the effects of combining DM with NSAIDs , dextropropoxyphene , or morphine in cancer patients with pain . Patients who required a change in the step of the World Health Organization 's ( WHO ) analgesic ladder because of a pain level of 4 or more on a numerical pain scale were r and omly allocated to receive DM 30 mg three times a day ( 30 patients ) or conventional treatment ( 30 patients ) . There were 20 patients r and omized for each step of the analgesic ladder . Pain mechanisms , pain intensity ( numerical 0 - 10 scale ) , symptoms more frequently present in advanced cancer patients or associated with opioid therapy ( grade d on a 0 - 3 scale -- not at all , slight , a lot , awful ) , opioid escalation index , days on opioid treatment , and adverse effects were recorded . After 2 days 75 % , 80 % , and 100 % of patients treated with DM in steps 1 , 2 , and 3 , respectively , required conventional treatment , because adequate pain relief had not been achieved ( pain scale > 4 ) . Failure of this treatment was equally observed in neuropathic pain or nociceptive pain syndromes . Four patients treated with DM who did not require the conventional treatment immediately did require this change after some days , due to poor pain control . A highly significant reduction in pain was observed in patients directly treated with the conventional treatment in all the three steps of the analgesic ladder . No significant analgesic effects could be found when DM at this dose was combined with NSAIDs , dextropropoxyphene , or morphine Aims and Background Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain , even though no specific studies have demonstrated a benefit . A r and omized placebo-controlled , double-blind crossover study was design ed to evidence the effects of amitriptyline in patients with neuropathic cancer pain . Methods Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy , no longer receiving oncologic treatment , presenting moderate pain ( about 4 or more , but less than 7 , on a numerical scale of 0 - 10 ) in the last week , and given a stable morphine dose in the last 2 days were admitted to the study . During the first week of study , patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days . Doses for patients aged more than 65 years were 15 mg ( first 3 days ) and 30 mg ( 3 days after ) . After a week , a crossover took place for the second week , with the other treatment at an inverse sequence . Opioid consumption , pain intensity , symptoms and adverse effects , mood , sleep , patient 's preference , quality of life before starting the study , the first week after and the second week after were recorded . Results No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment , the least pain intensity or the pain evaluated just after a week of treatment , at the moment of the visit , when amitriptyline was compared with placebo . A significant difference was evidence d for the worst pain ( P < 0.035 ) . No differences in opioid doses during the period of study were found . Drowsiness , confusion and dry mouth were significantly more intense with amitriptyline than with placebo ( P < 0.036 , 0.003 , and 0.034 , respectively ) . There were no substantial differences between the two treatments in Spitzer 's quality of life score and for each item . No differences in patients ' preference for the two treatment periods were found . The analgesic effects of amitriptyline were slight and associated with adverse effects . Conclusions In light of the results obtained in the study , the extensive use of the drug for cancer pain should be question ed Neuropathic cancer pain represents a major challenge . Treatment often requires adjuvant analgesics , including gabapentin , to complement the effects of opioids . This study aim ed to compare the effectiveness and safety of gabapentin combined with an opioid versus opioid monotherapy for the management of neuropathic cancer pain . Seventy-five cancer patients who were receiving opioid therapy and reported sufficient pain relief of nociceptive , but not neuropathic , pain were enrolled . Sixty-three patients completed the study . Patients were r and omized to one of the following treatment protocol s : 1 ) gabapentin adjuvant to ongoing opioid treatment titrated according to pain response while opioid dose was kept constant ( group GO ) , and 2 ) continuation of opioid monotherapy according to the World Health Organization treatment ladder approach ( group OO ) . Changes in pain intensity , allodynia , and analgesic drug consumption were evaluated at Day 4 and Day 13 . Side effects were also recorded . Both treatments result ed in a significant reduction of pain intensity at Day 4 and Day 13 compared to baseline . However , mean pain intensity for burning and shooting pain was significantly higher in the OO group compared to the GO group at both the fourth ( P=0.0001 ) and 13th ( P=0.0001 ) days of the study . An earlier significant decrease ( at Day 4 , P=0.002 ) was observed for allodynia in the GO group compared to the OO group . The rate of side effects in the GO group was significantly lower than that in the OO group ( P=0.015 ) . These data suggest that gabapentin added to an opioid provides better relief of neuropathic pain in cancer patients than opioid monotherapy ; this combination of gabapentin and an opioid may represent a potential first-line regimen for the management of pain in these patients & NA ; Topical aspirin/diethyl ether ( ADE ) mixture was used to treat 45 consecutive patients with acute herpetic neuralgia ( AHN ) ( n = 28 ) and with post‐herpetic neuralgia ( PHN ) ( n = 17 ) in an open‐label study . Good‐to‐excellent results were achieved by 93 % of AHN patients and by 65 % of PHN patients . Earlier treatment yielded better results for the AHN but not the PHN group . The topical treatment seemed to accelerate the healing of acute herpetic skin lesions and possibly modulate the severity of the herpetic infection . Furthermore , a striking reduction in the percentage of AHN patients developing PHN was observed in the treated group , as compared with the disease natural history reported in the literature ( 4 vs. 50–70 % ) . Treatment tolerance was excellent with no adverse effect observed . In addition to the open trial , a pilot double‐blind crossover placebo‐controlled study ( n = 11 ) compared the analgesic efficacy of ADE with two other NSAID ( indomethacin and diclofenac ) drug/ether mixtures . Aspirin ( but not indomethacin and diclofenac ) was significantly superior to placebo as regards pain relief ( P < 0.05 ) Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Background We have recently reported successful treatment of patients with chronic pain syndromes using human pooled intravenous immunoglobulin ( IVIG ) in a prospect i ve , open-label cohort study . A r and omised , placebo controlled , double blinded study is needed to confirm these results . We chose to study patients with carbamazepine resistant primary Trigeminal Neuralgia ( rpTN ) , as these had responded particularly well to IVIG.A protocol involving the use of IVIG in rpTN is complex for three reasons : 1 . The effect of IVIG does not follow simple dose-response rules ; 2 . The response pattern of patients to IVIG was variable and ranged between no effect at all and pain free remission between two weeks and > 1 year ; 3 . TN is characterized by extremely severe pain , for which operative intervention is ( if temporarily ) helpful in most patients . Design A placebo controlled , parallel , add-on model was developed and the primary outcome variable defined as the length of time during which patients remain in the study . Study groups are compared using Kaplan-Maier survival analysis . Patients record their response to treatment ( " severe , moderate , slight , no pain " ) . The study coordinator monitors pain diaries . Severe or moderate pain of three days duration will result in termination of the study for that patient . Conclusions This study design utilizes a method of survival analysis and is novel in chronic pain research . It allows for both early departure from the study and voluntary crossover upon non-response . It may be applicable to the analysis of IVIG efficacy in other chronic pain syndromes & NA ; Levodopa has been used to treat some painful conditions and found to be effective in neuropathic pain due to herpes zoster in a double‐blind study . From our anecdotal observations about the efficacy of levodopa on diabetic neuropathic pain , we design ed a double‐blind placebo‐controlled study to test levodopa in painful diabetic neuropathy . Twenty‐five out‐ patients with painful symmetrical diabetic polyneuropathy were admitted to the study . Fourteen patients were given 100 mg levodopa plus 25 mg benserazide to be taken three times per day for 28 days . Eleven patients were given identical placebo capsules . A blinded neurologist evaluated the patients clinical ly and performed Visual Analogue Scale ( VAS ) measurement every week from day 0 to day 28 . The results seemed promising and levodopa may be a choice for the control of pain in neuropathy for which we do not have many alternative treatments This observational study examined the outcome of two different therapeutic strategies in the treatment of chronic neuropathic pain by including pregabalin ( PGB ) as mono- or add-on therapy in one of two treatment options . Patients with a pain score of ≥4 , refractory to usual care for neuropathic pain for at least 6 months , were allocated consecutively to one of two treatment strategies according to the decision of the physician : complete switch to a flexible-dosage , monotherapeutic or add-on therapy with pregabalin ( PGB group ) , or change established doses and combinations of pre-existing mono- or combination therapy without pregabalin ( non-PGB group ) . After 4 weeks ( primary endpoint ) a significant improvement in pain reduction was documented in both intention-to treat ( ITT ) analysis ( PGB group , n = 85 : mean pain score reduction of 3.53 , SD 2.03 , p < 0.001 ; non-PGB group , n = 102 ; mean pain score reduction of 2.83 , SD 2.23 , p < 0.001 ) and per- protocol ( PP ) analysis ( PGB group , n = 79 : mean pain score reduction 3.53 vs. 2.83 , p < 0.05 ; non-PGB group , n = 81 ; 3.5 vs. 2.9 , p < 0.05 ) compared to baseline . Comparison of the results observed in the two groups shows that patients in the PGB group achieved significantly greater pain reduction . These results demonstrate that PGB administered twice daily is superior to treatment regimes without PGB in reducing pain and pain-related interference in quality of life Pain can be a serious problem in patients with Guillain-Barré syndrome ( GBS ) . Different pain symptoms and the effect of methylprednisolone on pain are evaluated . Methods GBS patients were recruited from a r and omized placebo-controlled study comparing intravenous immunoglobulin ( IVIg ) + methylprednisolone ( 500 mg for 5 days ) versus IVIg + placebo . Presence and severity of pain were prospect ively scored at r and omization and after 4 weeks . Efficacy of methylprednisolone was evaluated using endpoints : percentage of patients with pain and percentage of patients improving in pain-severity level . Medical records of the subgroup of patients treated in the Erasmus MC were screened retrospectively for different pain symptoms and course . Pain was scored at different time intervals : within 4 weeks before r and omization and 0–2 , 2–4 , 4–24 , 24–52 weeks after r and omization . Results 123 ( 55 % ) of 223 patients had pain at r and omization . In 70 % , pain already started before onset of weakness . Methylprednisolone did not show a positive effect on the presence and reduction of pain . In the subgroup of 39 patients , backache ( 33 % ) , interscapular ( 28 % ) , muscle ( 24 % ) , radicular pain ( 18 % ) and painful par-/dysaesthesiae ( 18 % ) were most frequently present within the period of 4 weeks before r and omization . Twenty-six percent had extreme pain 0–2 weeks after r and omization . Most symptoms of pain decreased after this period , but painful par-/dysaesthesiae and muscle pain often remained present during at least 6 months . Conclusions Pain frequently occurs , often starts before onset of weakness and may cause severe complaints . Especially painful par-/dysaesthesiae and muscle pain may persist for months . Methylprednisolone seems to have no significant effect on the presence and intensity of pain BACKGROUND The available drugs to treat neuropathic pain have incomplete efficacy and dose-limiting adverse effects . We compared the efficacy of a combination of gabapentin and morphine with that of each as a single agent in patients with painful diabetic neuropathy or postherpetic neuralgia . METHODS In this r and omized , double-blind , active placebo-controlled , four-period crossover trial , patients received daily active placebo ( lorazepam ) , sustained-release morphine , gabapentin , and a combination of gabapentin and morphine -- each given orally for five weeks . The primary outcome measure was mean daily pain intensity in patients receiving a maximal tolerated dose ; secondary outcomes included pain ( rated according to the Short-Form McGill Pain Question naire ) , adverse effects , maximal tolerated doses , mood , and quality of life . RESULTS Of 57 patients who underwent r and omization ( 35 with diabetic neuropathy and 22 with postherpetic neuralgia ) , 41 completed the trial . Mean daily pain ( on a scale from 0 to 10 , with higher numbers indicating more severe pain ) at a maximal tolerated dose of the study drug was as follows : 5.72 at baseline , 4.49 with placebo , 4.15 with gabapentin , 3.70 with morphine , and 3.06 with the gabapentin-morphine combination ( P<0.05 for the combination vs. placebo , gabapentin , and morphine ) . Total scores on the Short-Form McGill Pain Question naire ( on a scale from 0 to 45 , with higher numbers indicating more severe pain ) at a maximal tolerated dose were 14.4 with placebo , 10.7 with gabapentin , 10.7 with morphine , and 7.5 with the gabapentin-morphine combination ( P<0.05 for the combination vs. placebo , gabapentin , and morphine ) . The maximal tolerated doses of morphine and gabapentin were lower ( P<0.05 ) with the combination than for each drug as single agent . At the maximal tolerated dose , the gabapentin-morphine combination result ed in a higher frequency of constipation than gabapentin alone ( P<0.05 ) and a higher frequency of dry mouth than morphine alone ( P<0.05 ) . CONCLUSIONS Gabapentin and morphine combined achieved better analgesia at lower doses of each drug than either as a single agent , with constipation , sedation , and dry mouth as the most frequent adverse effects OBJECTIVES Combination of drugs with different mechanisms of action helps in achieving synergistic analgesic effect in neuropathic pain . Keeping this point in view , the effect and safety aspects of sodium valproate and GTN were assessed alone as well as in combination in this study . DESIGN Prospect i ve double-blind r and omized placebo-controlled study . MATERIAL AND METHOD Eighty-seven type 2 diabetics with painful neuropathy were enrolled . Four were excluded : three with HbA1c>11 while one withdrew consent . The remaining 83 were given either sodium valproate and GTN spray ( group A ) or placebo drug and GTN spray ( group B ) or sodium valproate and placebo spray ( group C ) or placebo drug and placebo spray ( group D ) . Quantitative assessment of pain was done by McGill pain question naire , visual analogue score ( VAS ) and present pain intensity ( PPI ) at the beginning of the study and after 3 months along with motor and sensory nerve conduction velocities measurements . RESULTS All the three treatment groups experienced significant improvement in pain score in their drug phase of trial ( p<0.001/<0.05 ) along with some of the electrophysiological parameters . The assessment of the magnitude of therapeutic effect of sodium valproate , GTN and their combination gave numbers needed to treat ( NNT ) of 7 , 5 and 4 , respectively . CONCLUSION Sodium valproate and GTN are well tolerated and provide significant improvement in pain scores as well as in electrophysiological parameters & NA ; A prospect i ve double‐blind r and omized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone ( 50 mg q.i.d . ) or in combination with a weak opioid ( codeine 40 mg q.i.d . ) , or with an anti‐depressant ( imipramine , 10 or 25 mg t.i.d . ) . All demographic and clinical characteristics including cancer type , presence of bone metastases , baseline pain severity , neuropathic and nociceptive pain , and depressive state , were well balanced between the three treatment groups . The main analysis of the study was on the VAS scores at visit 2 ( day 4 ) . The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac . Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy , while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events . In conclusion , in a short‐term evaluation the addition of a tricyclic anti‐depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone The management of sciatica due to lumbar nerve root compromise remains controversial , probably because few well-controlled studies of conservative management have been performed . This preliminary study assesses the efficacy of epidural injections of 80 mg triamcinolone acetonide plus 0.5 % procaine hydrochloride in saline , administered via the caudal route , in a double-blind , placebo controlled trial with 1 year follow-up . Twenty-three patients were entered into the study : 12 received treatment and 11 placebo . The active group showed significant pain relief ( P=0.02 ) and a significant increase in mobility ( P=0.01 ) at 4 weeks , which result ed in improved quality of life ( P=0.02 ) . At 1 year , subjective and objective measures improved in both groups . The improvement was greater in the actively treated group , but only the objective assessment ( straight leg raise ) was statistically significant Objective Pain control in trigeminal neuralgia ( TN ) is achieved using anticonvulsivants , mainly carbamazepine . When this drug can not be used , other drugs like gabapentin ( GBP ) have been used to provide adequate pain control . To improve the therapeutic effect of GBP , we evaluated the clinical efficacy of associating GBP with ropivacain ( ROP ) analgesic block of facial trigger points in TN patients . Design Thirty-six TN patients were r and omly assigned during 4 weeks to 1 of the following protocol s : Protocol I — daily oral GBP administered in a titrated dose ; Protocol II — ROP applied as analgesic block to TN trigger points once a week ; Protocol III — daily oral GBP plus ROP once a week . Protocol II had to be discontinued in 7/12 patients owing to insufficient pain control . Pain intensity was evaluated by the Visual Analog Scale ( VAS ) and disability was assessed by Sickness Impact Profile . Results When compared with Protocol I , Protocol III ( GBP+ROP ) patients showed ( 1 ) a reduction of VAS score after 7 and 28 days of treatment , an effect that was still present 6 and 12 months later ; ( 2 ) a faster reduction of VAS score using a significantly lower dose of GBP ; ( 3 ) a smaller total and daily GBP dose at the end of the treatment , which result ed in a total absence of adverse side effects ; and ( 4 ) an improvement of the functional well-being measured by the Sickness Impact Profile . The number needed to treat ( NNT ) ( GBP+ROP vs. GBP protocol s ) to obtain 1 GBP+ROP-treated patient with at least 50 % pain relief was 1.71 ( day 7 ) and 2.40 ( day 28 ) . Conclusions The association of GBP and ROP is safe , without side effects and results in an important clinical benefit associated to an improvement of the functional health status of TN patients when compared with GBP alone . This may constitute a therapeutic alternative for pain control in TN patients who can not be treated with carbamazepine A double‐blind crossover study of the effects of baclofen was conducted on 10 patients with typical trigeminal neuralgia . Baclofen significantly decreased the number of painful paroxysms in 7 of the 10 patients . An open trial in another 50 patients with trigeminal neuralgia refractory to or unable to tolerate carbamazepine showed that 37 ( 74 % ) were relieved of their attacks by baclofen , either alone ( 12 patients ) or in combination with previously ineffective doses of carbamazepine or phenytoin ( 25 ) . On long‐term follow‐up of one to five years ( mean , 3.0 years ) , 18 of the 60 patients ( 30 % ) continued pain free while receiving baclofen ; 10 ( 17 % ) went into remission after 3 to 6 months ; 13 ( 22 % ) became refractory to baclofen after 1 to 18 months ; and 2 ( 3 % ) elected operation despite a good response to baclofen . The results indicate that baclofen is a useful drug in the treatment of trigeminal neuralgia BACKGROUND Treating sciatica with epidural steroid injection has been a common practice worldwide . N-methyl-D-aspartate ( NMDA ) receptors are an important component of pain pathways . OBJECTIVES The aim of this study was to evaluate the safety and efficacy of epidurally administered NMDA receptor antagonists ( ketamine ) for the treatment of chronic low back pain secondary to radiculopathy and its effect on patients ' quality of life . STUDY DESIGN R and omized , double blind controlled trial . SETTING Hospital outpatient setting . METHODS Two hundred participants aged 25 to 50 years old with a diagnosis of lumbar radiculopathic pain secondary to disc herniation were r and omized into 2 equal groups . Group I received 80 mg of triamcinolone ( 2 mL ) and 0.25 % bupivacaine ( 3 mL ) plus 30 mg ( 3 mL ) of preservative free ketamine . Group II received 80 mg of triamcinolone ( 2 mL ) and 0.25 % bupivacaine ( 3 mL ) plus 3 mL of 0.9 % saline . Pain scores were obtained before injection , immediately after injection , one week , one month , 3 months , 6 months , 9 months and one year post injection . The Oswestry Low Back Pain Disability Question naire was used at baseline and at one month , 3 , 6 , 9 , and 12 months after injection for assessment of quality of life . Patients were asked to report any side effects , particularly those related to ketamine , including nausea , vomiting , visual or auditory hallucinations , and delirium . RESULTS Immediately after injection there was no statistically significant difference between Group I and II regarding pain scale scores . After one week of injection , pain relief was significantly better in Group I compared to Group II and then at all evaluation times . The Oswestry Low Back Pain Disability Question naire score decreased significantly ( P < 0.05 ) from 72 ( range 62- 83 ) and 70 ( range 57- 82 ) to 8 ( range 2 - 12 ) and 17 ( range 9 - 27 ) at one month ; 6 ( range 4 - 12 ) and 18 ( range 14 - 22 ) at 3 months ; 12 ( range 9 - 16 ) and 28 ( range 22 - 34 ) at 6 months ; 17 ( range 9 - 24 ) and 31 ( range 21 - 35 ) at 9 months ; and 17 ( range 8 - 22 ) and 33 ( range 20 - 37 ) at 12 months in the groups , respectively . Six patients in the ketamine group showed short-lasting delusions lasting for 45 ± 12 minutes after injection . LIMITATIONS The limitations include a lack of placebo control . CONCLUSION Epidurally administrated ketamine seems to be a safe and useful adjunct to epidural corticosteroid therapy in chronic lumbar radicular pain Background The efficacy and safety of the association of celecoxib [ a selective cyclooxygenase-2 ( COX-2 ) inhibitor ] and pregabalin ( commonly used to control neuropathic pain ) , compared with monotherapy of each , were evaluated for the treatment of chronic low-back pain , a condition known to be due to neuropathic as well as nociceptive pain mechanisms . Material s and methods In this prospect i ve r and omized trial , 36 patients received three consecutive 4-week treatment regimes , r and omly assigned : celecoxib plus placebo , pregabalin plus placebo , and celecoxib plus pregabalin . All patients were assessed by using a visual analogue scale ( VAS , 0–100 mm ) and the Leeds Assessment of Neuropathic Symptoms and Signs ( LANSS ) pain scale by an investigator blinded to the administered pharmacological treatment . Results Celecoxib and pregabalin were effective in reducing low-back pain when patients were pooled according to LANSS score . The association of celecoxib and pregabalin was more effective than either monotherapy in a mixed population of patients with chronic low-back pain and when data were pooled according to LANSS score . Adverse effects of drug association and monotherapies were similar , with reduced drug consumption in the combined therapy . Conclusions Combination of celecoxib and pregabalin is more effective than monotherapy for chronic low-back pain , with similar adverse effects Objective The involvement of ongoing peripheral activity in the generation of nociceptive input in neuropathic pain suggests that topical drug delivery may be useful as a treatment strategy . This is a pilot study providing initial information regarding the use of novel topical preparations containing amitriptyline ( AMI ) , ketamine ( KET ) , and a combination of both in the treatment of neuropathic pain . Methods The study design included a 2 day r and omized , double blind , placebo controlled , 4 way cross-over trial of all treatments , followed by an open label treatment phase using the combination cream for 7 days . Twenty volunteers with chronic neuropathic pain were r and omly assigned to treatment order and applied 5 mls of each topical treatment ( 1 % AMI , 0.5 % KET , combination AMI 1%/KET 0.5 % , and placebo ) for 2 days . Measures of pain at the end of each block included the short form McGill Pain Question naire ( MPQ ) and visual analog scales ( VAS ) for present pain intensity and pain relief . Eleven subjects who judged subjective improvement from any treatment in the initial trial entered the open-label trial and used the combination cream for 7 days . Pain levels were recorded daily using the same measures . Blood levels for amitriptyline and ketamine were performed at 7 days to determine whether systemic absorption had occurred . Results There was no statistically significant difference from placebo after 2 days for any treatment during the double blind component of the trial . In the 11 subjects who used the combination cream , there was a statistically significant effect , with subjects reporting significantly greater analgesia by days 3 to 7 according to measures of pain and pain relief . Blood levels revealed that there was no significant systemic absorption of amitriptyline or ketamine . Only 2 subjects experienced side effects ; these were minor and did not lead to discontinuation of the cream . Conclusion This pilot study demonstrated a lack of effect for all treatments in the 2 day double blind placebo controlled trial , followed by analgesia in an open label trial in a subgroup of subjects who chose to use the combination cream for 7 days . Blood analysis revealed no significant systemic absorption of either agent after 7 days of treatment , and creams were well tolerated . A larger scale r and omized trial over a longer interval is warranted to examine further effects observed in the open label trial UNLABELLED The aim of this r and omized double-blind , placebo-controlled , parallel-group study was to evaluate the efficacy , safety , and tolerability of pregabalin in combination with oxycodone or placebo , in patients with either postherpetic neuralgia ( PHN ) or painful diabetic neuropathy ( PDN ) . After a 7-day washout period , 62 patients were r and omized to receive either oxycodone mixture 10 mg/day or placebo mixture for 1 week . Patients were then started on open-label pregabalin ( 75 , 150 , 300 and 600 mg/day ) according to a forced titration dosing regimen , while continuing the same dosage of oxycodone or placebo for 4 weeks . The primary efficacy measure was a decrease in the pain-intensity score of at least 2 cm and a pain score < 4 cm measured using a 10-cm visual analogue scale ( VAS ) following pregabalin dosage escalation and treatment for 4 weeks . Secondary efficacy measures included sleep interference and the Neuropathic Pain Scale . There were similar levels of overall efficacy between pregabalin/oxycodone and pregabalin/placebo groups in relieving PHN and PDN related pain . PERSPECTIVE Peripheral neuropathic pain presents commonly in clinical practice , and 2 of its most prevalent types are PHN and PDN . Currently available treatments provide some degree of pain relief in approximately 40 - 60 % of patients , leaving the remainder with unremitting pain . Although this study supports the effectiveness of pregabalin in the treatment of PHN or PDN , it also shows that the addition of a low dose of oxycodone at 10mg/day does not enhance the pain-relieving effects of pregabalin 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 CONTEXT Peripheral neuropathy is common in persons infected with the human immunodeficiency virus ( HIV ) but few data on symptomatic treatment are available . OBJECTIVE To evaluate the efficacy of a st and ardized acupuncture regimen ( SAR ) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients . DESIGN R and omized , placebo-controlled , multicenter clinical trial . Each site enrolled patients into 1 of the following 3 options : ( 1 ) a modified double-blind 2 x 2 factorial design of SAR , amitriptyline , or the combination compared with placebo , ( 2 ) a modified double-blind design of an SAR vs control points , or ( 3 ) a double-blind design of amitriptyline vs placebo . SETTING Terry Beirn Community Programs for Clinical Research on AIDS ( HIV primary care providers ) in 10 US cities . PATIENTS Patients with HIV-associated , symptomatic , lower-extremity peripheral neuropathy . Of 250 patients enrolled , 239 were in the acupuncture comparison ( 125 in the factorial option and 114 in the SAR option vs control points option ) , and 136 patients were in the amitriptyline comparison ( 125 in the factorial option and 11 in amitriptyline option vs placebo option ) . INTERVENTIONS St and ardized acupuncture regimen vs control points , amitriptyline ( 75 mg/d ) vs placebo , or both for 14 weeks . MAIN OUTCOME MEASURE Changes in mean pain scores at 6 and 14 weeks , using a pain scale ranging from 0.0 ( no pain ) to 1.75 ( extremely intense ) , recorded daily . RESULTS Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values . For both the acupuncture and amitriptyline comparisons , changes in pain score were not significantly different between the 2 groups . At 6 weeks , the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group ( a negative value indicates a greater reduction for the " active " treatment ) was 0.01 ( 95 % confidence interval [ CI ] , -0.11 to 0.12 ; P=.88 ) and for patients in the amitriptyline group vs those in the placebo group was -0.07 ( 95 % CI , -0.22 to 0.08 ; P=.38 ) . At 14 weeks , the difference for those in the SAR group compared with those in the control points group was -0.08 ( 95 % CI , -0.21 to 0.06 ; P=.26 ) and for amitriptyline compared with placebo was 0.00 ( 95 % CI , -0.18 to 0.19 ; P=.99 ) . CONCLUSIONS In this study , neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy Before implementing a new therapy , we should ascertain the benefits and risks of the therapy and assure ourselves that the re sources consumed during the intervention will not be exorbitant . In the hierarchy of research design s , the results of r and omized controlled trials , especially if systematic ally review ed , are considered the highest level of evidence . We suggest a three-step approach to using an article from the medical literature to guide your patient care . We recommend that readers ask whether the study can provide valid results , review the results , and consider how the results can be applied to patient care . Given the time constraints of busy surgical practice s and surgical training programs , applying this analysis to every relevant article will be challenging . However , the basis of this process is essentially what we all do many times each week when making decisions about whether and how to treat patients . Making this process explicit with guidelines to assess the strength of the available evidence can serve to improve patient care . It also allow us to defend therapeutic interventions based on available evidence and not anecdote OBJECTIVE To assess the efficacy of local infiltration of corticosteroid with lignocaine compared to lignocaine alone in the treatment of postherpetic neuralgia . DESIGN A r and omized clinical trial . PLACE AND DURATION OF STUDY The Skin Department , Military Hospital , Rawalpindi from September 2002 to March 2003 . PATIENTS AND METHODS Sixty patients were selected for the study . They were r and omly assigned to two groups . Group-I received injection triamcinolone acetonide with lignocaine and group-II was given injection lignocaine alone . Three injections were given to each patient at fortnightly interval and pain relief was assessed by visual analogue scale at 6 and 12 weeks following the first injection . RESULTS Follow-up at 6 weeks showed complete pain relief in 63.3 % ( n=19 ) patients of group-I in comparison to 16.6 % ( n=5 ) of group-II . Chi-square value was 13.3 ( p<0.001 ) . At 12 weeks follow-up group-I showed further improvement with complete pain relief in 83.3 % ( n=25 ) whereas group-II showed diminishing response with cure rates falling to 6.6 % ( n=2 ) . Chi-square value was 35.6 ( p<0.001 ) . CONCLUSION Locally infiltrated injection triamcinolone acetonide with lignocaine was significantly more effective than injection lignocaine alone in the treatment of postherpetic neuralgia both at 6 and 12 weeks follow-up The therapeutic effectiveness of a benfotiamine ( CAS 22457 - 89 - 2)-vitamin B combination ( Milgamma-N ) , administered in high ( 4 x 2 capsules/day , = 320 mg benfotiamine/day ) and medium doses ( 3 x 1 capsules/day ) , was compared to a monotherapy with benfotiamine ( Benfogamma ) ( 3 x 1 tablets/day , = 150 mg benfotiamine/day ) in diabetic patients suffering from painful peripheral diabetic neuropathy ( DNP ) . In a 6-week open clinical trial , 36 patients ( aged 40 to 70 yrs ) having acceptable metabolic control ( HbA1c < 8.0 % ) were r and omly assigned to three groups , each of them comprising 12 participants . Neuropathy was assessed by five parameters : the pain sensation ( evaluated by a modified analogue visual scale ) , the vibration sensation ( measured with a tuning fork using the Riedel-Seyfert method ) and the current perception threshold ( CPT ) on the peroneal nerve at 3 frequencies : 5 , 250 and 2000 Hz ) . Parameters were registered at the beginning of the study and at the end of the 3rd and 6th week of therapy . An overall bneneficial therapeutic effect on the neuropathy status was observed in all three groups during the study , and a significant improvement in most of the parameters studied appeared already at the 3rd week of therapy ( p < 0.01 ) . The greatest change occurred in the group of patients receiving the high dose of benfotiamine ( p < 0.01 and 0.05 , resp . , compared to the othr groups ) . Metabolic control did not change over the study . It is concluded that benfotiamine is most effective in large doses , although even in smaller daily dosages , either in combination or in monotherapy , it is effective & NA ; While many pre‐ clinical and clinical studies have suggested that the addition of N‐methyl‐D‐aspartate ( NMDA ) receptor antagonists , such as dextromethorphan ( DM ) , to opioid analgesics , such as morphine ( MS ) , may enhance the analgesic effects and prevent the tolerance that may result from chronic opioid administration , others have not . The potential for reduced doses , enhanced opioid analgesia , and decreased analgesic tolerance associated with the MS/DM combination were evaluated in a series of three large , r and omized , double‐blind , parallel group , phase 3 , multicenter trials each of 3 months duration in patients with chronic , non‐malignant , non‐neuropathic pain . To evaluate these unique endpoints , novel study design s were employed . In Study A , patients received fixed doses of MS or MS/DM , based on the stable dose of MS/DM attained during a Run‐in period ; changes from baseline in average daily pain intensity were compared . In Studies B and C , patients self‐titrated doses of MS or MS/DM , based on stable doses of MS or other opioids attained during Run‐in periods , to maintain pain relief ; percentage changes from baseline in MS ( or MS‐equivalent ) doses were compared . No statistically significant differences between treatment groups in any primary or secondary efficacy variables were demonstrated in any trial . These results suggest that adding the NMDA antagonist , dextromethorphan , to opioids does not add any clinical benefit BACKGROUND Severe , intractable , chronic pain is a significant management problem for those involved in the long-term care of spinal cord injury ( SCI ) patients . Gabapentin , an anticonvulsant , is widely used for treating chronic pain . Ketamine , an NMDA receptor antagonist , has been available in clinical practice for 35 years . Its usefulness in pathological pain states is known . Despite this , no formal research on its effectiveness in treating neuropathic SCI pain exists . OBJECTIVES This double-blind study sought to determine the safety and efficacy of adding a multi-day low dose ketamine infusion to oral gabapentin for treating chronic pain related to post spinal cord injury . STUDY DESIGN R and omized , controlled , double blind trial . SETTING Hospital , in-patient setting . METHODS Forty patients diagnosed with neuropathic pain secondary to spinal cord injury were r and omized into 2 equal groups . Group I received an 80 mg intravenous ketamine infusion diluted in 500 cc normal saline over a 5 hour period daily for one week and 300 mg of gabapentin 3 times daily . Group II received a placebo infusion and 300 mg of gabapentin 3 times daily ( continued ) after 300 mg of gabapentin 3 times daily . Using the visual analogue scale , pain was assessed prior to treatment , daily following ketamine or placebo infusions for 7 days , and then weekly for one month after infusion termination . Side effects , specifically those related to ketamine or gabapentin , were reported . RESULTS Both groups demonstrated significantly reduced pain scores compared with pre-treatment values ( P < 0.05 ) . Group I showed significant pain score improvements over Group II at all measurements ( P < 0.0001 ) during infusion and 2 weeks after infusion termination . There was no statistical difference between the groups at 3 weeks and 4 weeks after infusion termination ( P = 0.54 and P = 0.25 respectively ) . Both drugs were tolerated by all patients ; no side effects required intervention . CONCLUSION Multi-day low dose ketamine infusion as adjuvant to gabapentin in post-spinal cord injury related chronic pain is safe and efficacious in reducing pain , but the effect compared to placebo ceased 2 weeks after infusion termination . LIMITATIONS Study size limited to 40 patients & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies Ten adult insulin-dependent diabetics with symptomatic peripheral neuropathy were treated with amitriptyline alone or in combination with fluphenazine hydrochloride . Nine of the subjects had a good result within 48 to 72 hours . Two patients reacted adversely to the medication . These medications appear effective in treating the discomfort associated with diabetic peripheral neuropathy Abstract . The objective of this double-blind , r and omized , placebo-controlled study was to test the efficacy of high-dose prednisone , administered as early as possible , in modifying the natural progression of Bell 's palsy . Sixty-two consecutive patients , enrolled within 72 hours of facial palsy onset , were assigned to high dose intravenous prednisone in combination with intramuscular polyvitaminic therapy ( group A ) or polyvitaminic therapy alone ( group B ) . Clinical grading of facial muscle strength and length of absence from work were evaluated . An early worsening of facial muscle strength was observed in controls , leading to the divergence in the trends of the grading scores in the two groups ; this result was not confirmed in the long-term follow-up . Treated patients returned to work earlier than controls . In conclusion , early treatment based on high-dose corticosteroids slightly accelerates spontaneous improvement in Bell 's palsy A controlled clinical trial on the efficacy of a nortriptyline-fluphenazine combination was carried out in patients with painful diabetic polyneuropathy . A visual analog scale was used to evaluate the relief of pain or paresthesia . Significant relief of both pain and paresthesia was obtained with this combination . The differences were statistically significant . Side effects were frequent but not usually severe enough to lead to cessation of these medications UNLABELLED Burning Mouth Syndrome ( BMS ) is a disease that manifests as burning in the tongue or in any area of the oral mucosa , in the absence of clinical ly verifiable injuries . OBJECTIVES To verify the efficacy of alpha lipoic acid ( ALA ) and gabapentin ( GABA ) , used individually and jointly , to reduce the burning in patients with burning mouth and establish a drug therapy for the BMS . STUDY DESIGN During April and May 2008 , we conducted a r and omized , double-blind , placebo-controlled trial in the Department of Clinical Stomatology , Faculty of Dentistry , Rosario , Argentina . The gathering of patients was between those ones with BMS who were treated in our service between March 2003 and March 2008 without complying with the applied treatments . The 120 patients were r and omly divided into 4 groups and were provided , by lot and in a blinded fashion , with four different treatment cycles consisting of the following drugs : Group A ( n = 20 ) 600 mg / day of alpha lipoic acid for two months , Group B ( n = 20 ) 300 mg / day of gabapentin for two months , Group C ( n = 20 ) a combination of both drugs for two months and Group D ( n = 60 ) 100 mg / day of cellulose starch for two months ( control group ) . RESULTS AND CONCLUSIONS all 120 patients completed the treatment . The best response was obtained with the combination of ALA + GABA , with a 70 % of the cases with reduced burning in this group and a 13.2 times greater chance of presenting positive changes for these patients than those taking placebo . The combined use of drugs that act at different levels of the nociceptive system can be useful for the treatment of this syndrome ABSTRACT Objective : Neuropathic pain is often difficult to treat due to a complex pathophysiology . This study evaluated the efficacy , tolerability and safety of combination therapy with 5 % lidocaine medicated plaster and pregabalin for neuropathic pain in patients with post-herpetic neuralgia ( PHN ) or painful diabetic polyneuropathy ( DPN ) . Methods : Patients completing 4-week monotherapy with 5 % lidocaine medicated plaster or pregabalin were enrolled in an 8-week combination phase . Patients with adequate response to monotherapy ( recalled average pain intensity of 4 or less on 11-point numeric rating scale in the previous 3 days [ NRS-3 score ] ) continued their previous therapy , whereas those with insufficient response received combination therapy . Efficacy endpoints included change in NRS-3 from combination phase baseline , Patient and Clinical Global Impression of Change ( PGIC/CGIC ) , and patient 's satisfaction with treatment . Safety evaluation included adverse events ( AEs ) , drug-related AEs ( DRAEs ) , and withdrawal due to AEs . Clinical trial registration : EudraCT No. 2006 - 003132 - 29 . Results : Of 229 patients in the per- protocol set ( PPS : 68 PHN and 161 DPN ) , 71 received 5 % lidocaine medicated plaster monotherapy , 57 had pregabalin added to 5 % lidocaine medicated plaster , 57 pregabalin monotherapy and 44 received 5 % lidocaine medicated plaster in addition to continued pregabalin treatment . There were no meaningful differences in demographic data between the treatment groups . Patients continuing on monotherapy demonstrated additional decreases in NRS-3 scores . Patients receiving combination therapy achieved clinical ly relevant reduction in NRS-3 values in addition to improvement achieved during the 4 weeks of monotherapy . Improvement was similar between the two combination therapy groups . Considerable improvements in patients ’ treatment satisfaction were reported . Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well tolerated . Conclusions : In patients with PHN and painful DPN failing to respond to monotherapy , combination therapy with 5 % lidocaine medicated plaster and pregabalin provides additional clinical ly relevant pain relief and is safe and well-tolerated Although many therapies are used in the management of neuropathic pain ( NeP ) due to polyneuropathy ( PN ) , few comparison studies exist . We performed a prospect i ve , non-r and omized , unblended , efficacy comparison of the serotonin-norepinephrine reuptake inhibitor venlafaxine , as either monotherapy or adjuvant therapy , with a first-line medication for NeP , gabapentin , in patients with PN-related NeP. VAS pain scores were assessed after 3 and 6 months in intervention groups and in a cohort of patients receiving no pharmacotherapy . In a total of 223 patients , we analyzed pain quantity and quality ( visual analogue scale [ VAS ] score , Brief Pain Inventory [ BPI ] ) , quality of life and health status measures [ EuroQol 5 Domains , EQ-5D ] , Medical Outcomes Sleep Study Scale [ MOSSS ] , Hospital Anxiety and Depression Scale [ HADS ] and Short Form 36 Health Survey [ SF-36 ] ) after 6 months of therapy . Significant improvements in VAS pain scores occurred for all treatment groups after 6 months . Improvements in aspects of daily life and anxiety were identified in all treatment groups . Our data suggest that monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for NeP management . We advocate for head-to-head , r and omized , double-blinded studies of current NeP therapies Abstract Background and Objective : The management of diabetic neuropathy is still a challenge for physicians . The aim of this study was to assess the efficacy of a new combination of alpha lipoic acid and superoxide dismutase for the treatment of diabetic neuropathy . p ] Methods : The setting of this study was ambulatory ( outpatient ) care . A prospect i ve , non-r and omized , open-label study was conducted in 50 patients with diabetes mellitus and with a deficit in both motor and sensory nerve conduction . Treatment was with a new combination of alpha lipoic acid and superoxide dismutase ( ALA600SOD ® ) for 4 months . Electroneurographic parameters and perceived pain were assessed at baseline and after treatment . Results : After 4 months of treatment , patients significantly ( p < 0.001 ) improved their electroneurographic parameters and their perception of pain . Best improvements were observed in sensory nerve conduction . Conclusion : The combination of two powerful antioxidant agents leads to improvement in both subjective and objective parameters in patients with diabetic neuropathy . New profitable directions for investigations are opened for a non-invasive treatment of diabetic neuropathy in the future Background : A double-blind , r and omized , placebo-controlled 3-week study evaluated the efficacy of topical 2 % amitriptyline , 1 % ketamine , and a combination of both in treating patients with neuropathic pain . Methods : Ninety-two patients with diabetic neuropathy , postherpetic neuralgia , or postsurgical/posttraumatic neuropathic pain with allodynia , hyperalgesia , or pinprick hypesthesia were r and omly assigned to receive one of four creams ( placebo , 2 % amitriptyline , 1 % ketamine , or 2 % amitriptyline–1 % ketamine combined ) . The primary outcome measure was change in average daily pain intensity ( baseline week vs. final week ) using an 11-point numerical pain rating scale . Secondary outcomes included the McGill Pain Question naire , measures of allodynia and hyperalgesia , and patient satisfaction . Results : A reduction in pain scores of 1.1–1.5 units was observed in all groups , and there was no difference between groups . Blood concentrations revealed no significant systemic absorption . Minimal side effects were encountered . Conclusion : This r and omized , placebo-controlled trial examining topical 2 % amitriptyline , 1 % ketamine , and a combination in the treatment of neuropathic pain revealed no difference between groups . Optimization of doses may be required , because another study has revealed that higher concentrations of these agents combined do produce significant analgesia & NA ; A combination therapy of morphine with an NMDA‐receptor antagonist might be more effective than morphine without a NMDA‐receptor antagonist for the relief of neuropathic pain in patients with complex regional pain syndrome ( CRPS ) . In order to test the efficacy of this combination therapy we performed a double‐blind r and omized placebo‐controlled study on patients suffering from CRPS of the upper extremity . We used functional magnetic resonance imaging during movement of the affected and unaffected upper h and before and after a treatment regimen of 49 days that contrasted morphine and an NMDA‐receptor antagonist with morphine and placebo . We postulated superior pain relief for the combination therapy and concomitant changes in brain areas associated with nociceptive processing . Only the combination therapy reduced pain at rest and during movement , and disability . After treatment , activation in the contralateral primary somatosensory ( cS1 ) and anterior cingulate cortex was significantly reduced when the affected h and was moved . Pain relief during therapy was related to decreased activation in cS1 and secondary somatosensory cortex ( S2 ) . Our data suggest that the combination of morphine with an NMDA‐receptor antagonist significantly affects the cerebral processing of nociceptive information in CRPS . The correlation of pain relief and decrease in cortical activity in cS1 and S2 is in accordance with the expected impact of the NMDA‐receptor antagonist on cerebral pain processing with emphasis on sensory‐discriminative aspects of pain OBJECTIVE To determine whether oral prednisolone or aciclovir , used separately or in combination , early in the course of Bell 's palsy , improves the chances of recovery at 3 and 9 months . DESIGN A 2 x 2 factorial r and omised double-blind trial . Patients were r and omly assigned to treatment by an automated telephone service using a permuted block r and omisation technique with block sizes of four or eight , and no stratification . SETTING Mainl and Scotl and , with referrals mainly from general practice to 17 hospital trial sites . PARTICIPANTS Adults ( aged 16 years or older ) with unilateral facial nerve weakness of no identifiable cause presenting to primary care , the emergency department or NHS24 within 72 hours of symptom onset . INTERVENTIONS Patients were r and omised to receive active preparations or placebo for 10 days : ( 1 ) prednisolone ( 50 mg per day , 2 x 25-mg capsules ) and aciclovir ( 2000 mg per day , 5 x 400-mg capsules ) ; ( 2 ) prednisolone and placebo ( lactose , indistinguishable ) ; ( 3 ) aciclovir and placebo ; and ( 4 ) placebo and placebo . OUTCOME MEASURES The primary outcome was recovery of facial function assessed by the House-Brackmann scale . Secondary outcomes included health status , pain , self-perceived appearance and cost-effectiveness . RESULTS Final outcomes were available for 496 patients , balanced for gender ; mean age 44 years ; initial facial paralysis moderate to severe . One half of patients initiated treatment within 24 hours of onset of symptoms , one-third within 24 - 48 hours and the remainder within 48 - 72 hours . Of the completed patients , 357 had recovered by 3 months and 80 at 9 months , leaving 59 with a residual deficit . There were significant differences in complete recovery at 3 months between the prednisolone comparison groups ( 83.0 % for prednisolone , 63.6 % for no prednisolone , a difference of + 19.4 % ; 95 % confidence interval ( CI ) : + 11.7 % to + 27.1 % , p < 0.001 ) . The number needed to treat ( NNT ) in order to achieve one additional complete recovery was 6 ( 95 % CI : 4 to 9 ) . There was no significant difference between the aciclovir comparison groups ( 71.2 % for aciclovir and 75.7 % for no aciclovir ) . Nine-month assessment s of patients recovered were 94.4 % for prednisolone compared with 81.6 % for no prednisolone , a difference of + 12.8 % ( 95 % CI : + 7.2 % to + 18.4 % , p < 0.001 ) ; the NNT was 8 ( 95 % CI : 6 to 14 ) . Proportions recovered at 9 months were 85.4 % for aciclovir and 90.8 % for no aciclovir , a difference of -5.3 % . There was no significant prednisolone-aciclovir interaction at 3 months or at 9 months . Outcome differences by individual treatment ( the four-arm model ) showed significant differences . At 3 months the recovery rate was 86.3 % in the prednisolone treatment group , 79.7 % in the aciclovir-prednisolone group , 64.7 % in the placebo group and 62.5 % in the aciclovir group . At 9 months the recovery rates were respectively 96.1 % , 92.7 % , 85.3 % and 78.1 % . The increase in recovery rate conferred by the addition of prednisolone ( both for prednisolone over placebo and for aciclovir-prednisolone over aciclovir ) is highly statistically significant ( p < 0.001 ) . There were no significant differences in secondary measures apart from Health Utilities Index Mark 3 ( HUI3 ) at 9 months in those treated with prednisolone . CONCLUSIONS This study provided robust evidence to support the early use of oral prednisolone in Bell 's palsy as an effective treatment which may be considered cost-effective . Treatment with aciclovir , either alone or with steroids , had no effect on outcome Abstract Although lumbar radicular pain is the most common chronic neuropathic pain syndrome , there have been few r and omized studies of drug treatments . We compared the efficacy of morphine ( 15–90 mg ) , nortriptyline ( 25–100 mg ) , their combination , and a benztropine “ active placebo ” ( 0.25–1 mg ) in patients with chronic sciatica . Each period consisted of 5 weeks of dose escalation , 2 weeks of maintenance at the highest tolerated doses , and 2 weeks of dose tapering . The primary outcome was the mean daily leg pain score on a 0–10 scale during the maintenance period . Secondary outcomes included a 6‐point ordinal global pain relief scale , the Beck Depression Inventory ( BDI ) , the Oswestry Back Pain Disability Index ( ODI ) and the SF‐36 . In the 28 out of 61 patients who completed the study , none of the treatments produced significant reductions in average leg pain or other leg or back pain scores . Pain reduction , relative to placebo treatment was , 14 % for nortriptyline ( 95 % CI = [ −2 % , 30 % ] ) , 7 % for morphine ( 95 % CI = [ −8 % , 22 % ] ) , and 7 % for the combination treatment ( 95 % CI = [ −4 % , 18 % ] ) . Mean doses were : nortriptyline alone , 84 ± 24.44 ( SD ) mg/day ; morphine alone , 62 ± 29 mg/day ; and combination , morphine , 49 ± 27 mg/day plus nortriptyline , 55 mg ± 33.18 mg/day . Over half of the study completers reported some adverse effect with morphine , nortriptyline or their combination . Within the limitations of the modest sample size and high dropout rate , these results suggest that nortriptyline , morphine and their combination may have limited effectiveness in the treatment of chronic sciatica We performed a double-blinded , r and omized , controlled trial in 15 patients to determine the efficacy of intrathecal morphine or clonidine , alone or combined , in the treatment of neuropathic pain after spinal cord injury . The combination of morphine and clonidine produced significantly more pain relief than placebo 4 h after administration ; either morphine or clonidine alone did not produce as much pain relief . In addition , lumbar and cervical cerebrospinal fluid ( CSF ) concentrations , sample d at these levels at different times after administration were examined for a relationship between pain relief and CSF drug concentration . Lumbar CSF drug concentrations were initially several orders of magnitude larger than those in cervical CSF . After 1–2 h , the concentrations of morphine in cervical CSF markedly exceeded those of clonidine . The concentration of morphine in the cervical CSF and the degree of pain relief correlated significantly . We conclude that intrathecal administration of a mixture of clonidine and morphine is more effective than either drug administered alone and is related to the CSF-borne drug concentration above the level of spinal cord injury . If there is pathology that may restrict CSF flow , consideration should be given to intrathecal administration above the level of spinal cord damage to provide an adequate drug concentration in this region . Implication s Neuropathic pain after spinal cord injury is very difficult to control adequately by using currently available techniques . We have performed a placebo-controlled , double-blinded study demonstrating that administration of a combination of morphine and clonidine into the spinal fluid can provide substantial pain relief in some people with this type of pain Neuropathic pain ( NeP ) is prevalent in patients with peripheral neuropathy ( PN ) , regardless of etiology . We sought to compare the efficacy of the cannabinoid nabilone as either monotherapy or adjuvant therapy with a first-line medication for NeP , gabapentin , in a patient population with PN-NeP. Patients diagnosed with PN-NeP were permitted to initiate monotherapy ( nabilone or gabapentin ) or add one of these two medications ( adjuvant therapy ) to their existing NeP treatment regimen in a non-r and omized open-label nature . Baseline data collected included a primary outcome ( visual analog scores [ VAS ] of pain ) and secondary outcomes ( quality of life [ EuroQol 5 Domains and Short-Form 36 ] assessment s and assessment s of sleep [ Medical Outcomes Sleep Study Scale { MOSSS } ] , anxiety and depression [ Hospital Anxiety and Depression Scale ] , and pain [ Brief Pain Inventory ] ) . Re assessment and modulation of dosing and /or medications occurred at 3- and 6-month intervals . Medication adverse effects and drug efficacy , as well as question naires , were assessed at 6 months . Matched analysis of variance testing was performed to compare 3- and 6-month scores with baseline , as well as to compare therapies at equal time points . Significant improvements in pain VAS were seen in all treatment groups at 6 months . Numerous sleep parameters within MOSSS , Brief Pain Inventory , and Short-Form 36 improved in patients receiving nabilone or gabapentin either as monotherapy or adjuvant treatment . Hospital Anxiety and Depression Scale-A scores were significantly improved in all treatment groups . Sleep adequacy and the sleep problems index within the MOSSS improved in nabilone monotherapy patients in particular . The benefits of monotherapy or adjuvant therapy with nabilone appear comparable to gabapentin for management of NeP. We advocate for head-to-head r and omized , double-blind studies for current therapies for NeP in order to determine potential advantages beneficial in this patient population BACKGROUND Drugs for neuropathic pain have incomplete efficacy and dose-limiting side-effects when given as monotherapy . We assessed the efficacy and tolerability of combined nortriptyline and gabapentin compared with each drug given alone . METHODS In this double-blind , double-dummy , crossover trial , patients with diabetic polyneuropathy or postherpetic neuralgia , and who had a daily pain score of at least 4 ( scale 0 - 10 ) , were enrolled and treated at one study site in Canada between Nov 5 , 2004 , and Dec 13 , 2007 . 56 patients were r and omised in a 1:1:1 ratio with a balanced Latin square design to receive one of three sequences of daily oral gabapentin , nortriptyline , and their combination . In sequence , a different drug was given to each r and omised group in three treatment periods . During each 6-week treatment period , drug doses were titrated towards maximum tolerated dose . The primary outcome was mean daily pain at maximum tolerated dose . Analysis was by intention to treat . This trial is registered , number IS RCT N73178636 . FINDINGS 45 patients completed all three treatment periods ; 47 patients completed at least two treatment periods and were analysed for the primary outcome . Mean daily pain ( 0 - 10 ; numerical rating scale ) was 5.4 ( 95 % CI 5.0 to 5.8 ) at baseline , and at maximum tolerated dose , pain was 3.2 ( 2.5 to 3.8 ) for gabapentin , 2.9 ( 2.4 to 3.4 ) for nortriptyline , and 2.3 ( 1.8 to 2.8 ) for combination treatment . Pain with combination treatment was significantly lower than with gabapentin ( -0.9 , 95 % CI -1.4 to -0.3 , p=0.001 ) or nortriptyline alone ( -0.6 , 95 % CI -1.1 to -0.1 , p=0.02 ) . At maximum tolerated dose , the most common adverse event was dry mouth , which was significantly less frequent in patients on gabapentin than on nortriptyline ( p<0.0001 ) or combination treatment ( p<0.0001 ) . No serious adverse events were recorded for any patients during the trial . INTERPRETATION Combined gabapentin and nortriptyline seems to be more efficacious than either drug given alone for neuropathic pain , therefore we recommend use of this combination in patients who show a partial response to either drug given alone and seek additional pain relief . Future trials should compare other combinations to their respective monotherapies for treatment of such pain . FUNDING Canadian Institutes of Health Research Abstract Objective : To compare efficacy and safety of 5 % lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia ( PHN ) , and to assess the benefits of combining both drugs in patients not responding to either single agent . Study design and methods : This was a two-stage adaptive , r and omised , open-label , multicentre , non-inferiority study ( NCT 00414349 ) . The subset of patients with PHN is reported here . Patients with an absolute value of > 4 on the NRS-3 were r and omly assigned to 4-week treatment with 5 % lidocaine medicated plaster or twice-daily pregabalin capsules titrated to effect . Subsequently , patients sufficiently treated with monotherapy ( patients with NRS-3 ≤4 at 4 weeks or a reduction on the NRS-3 from baseline of ≥2 points ) continued with monotherapy ; patients insufficiently treated with monotherapy received both drugs in combination for 8 weeks . Outcome measures : Pain according to SF-MPQ and NPSI , onset of effect , reduction in worst pain on the NRS ; allodynia severity ; quality of life ( QoL ) based on EQ-5D , SF-36 ; PGIC ; rescue medication intake ; adverse events ( AEs ) monitoring . Results : At 4 weeks , SF-MPQ total scores improved by −7.6 ± 6.66 ( mean ± SD ) under 5 % lidocaine medicated plaster and by −5.3 ± 7.93 under pregabalin . NPSI total scores declined by −1.6 ± 1.73 under 5 % lidocaine medicated plaster and −1.4 ± 1.87 under pregabalin . Lidocaine plaster was also effective in reducing worst pain and showed a fast onset of effect . During combination treatment , SF-MPQ and NPSI scores , allodynia , EQ-5D and PGIC improved . Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well-tolerated . Conclusions : Although this open-label study is lacking a placebo control group , the results suggest that 5 % lidocaine medicated plaster is at least as effective as pregabalin for pain relief in PHN , with a favourable safety profile and a result ing positive benefit-risk ratio . In patients unresponsive to either monotherapy , combination therapy provides additional efficacy and is well-tolerated OBJECTIVE To evaluate dextromethorphan coadministered with quinidine as treatment of diabetic peripheral neuropathic pain . DESIGN In a 13-week , phase 3 , r and omized controlled trial , 379 adults with daily symmetric diabetic peripheral neuropathy ( DPN ) leg pain for ≥3 months received double-blind placebo , dextromethorphan/quinidine ( DMQ ) 45/30 mg , or DMQ 30/30 mg , administered once daily for 7 days and twice daily thereafter . Efficacy measures included four pain rating scales applied daily using patient diaries , and another two applied at five clinic visits . RESULTS On all six scales , DMQ 45/30 mg was significantly superior to placebo , including the primary efficacy analysis , which utilized mixed-effects modeling to test all scores on an 11-point numerical Pain Rating Scale ( P < 0.0001 ) . Sensitivity analyses gave consistent results . Efficacy vs placebo was also seen for diary ratings of present pain intensity , and pain interference with sleep and with activities ( all P < 0.0001 ) . Among clinic visit assessment s , DMQ 45/30 mg demonstrated greater leg pain relief ( P = 0.0002 ) and greater reduction of leg pain intensity ( P = 0.0286 ) vs placebo . The efficacy of DMQ 30/30 mg was numerically less than for 45/30 mg but for most outcomes remained significantly greater vs placebo . Adverse events were mostly mild or moderate and of expected types . Discontinuation for adverse events in the DMQ groups was at least twice as common as placebo . CONCLUSIONS Throughout a 13-week trial , DMQ was effective , with an acceptable safety profile , for treatment of DPN pain . Other fixed-dose combinations of DMQ should be studied to improve overall tolerability while maintaining significant efficacy UNLABELLED Progress in the underst and ing of chronic pain with neuropathic features has been hindered by a lack of epidemiologic research in the general population . The Leeds Assessment of Neuropathic Symptoms and Signs score ( S-LANSS ) was recently vali date d for use in postal surveys , making the identification of pain of predominantly neuropathic origin possible . Six family practice s in 3 UK cities ( Aberdeen , Leeds , and London ) generated a total r and om sample of 6,000 adults . The mailed question naire included demographic items , chronic pain identification , and intensity questions , the S-LANSS , the Level of Expressed Needs question naire , and the Neuropathic Pain Scale . With a corrected response rate of 52 % , the prevalence of any chronic pain was 48 % and the prevalence of pain of predominantly neuropathic origin was 8 % . Respondents with this chronic neuropathic pain were significantly more likely to be female , slightly older , no longer married , living in council rented accommodation , unable to work , have no educational qualifications , and be smokers than all other respondents . Multiple logistic regression modeling found that pain of predominantly neuropathic origin was independently associated with older age , gender , employment ( being unable to work ) , and lower educational attainment . Respondents with this pain type also reported significantly greater pain intensity , higher scores on the NPS , higher levels of expressed need , and longer duration of pain . This is the first estimate of the prevalence and distribution of pain of predominantly neuropathic origin in the general population , using a previously vali date d and reliable data collection instrument . PERSPECTIVE Chronic pain with neuropathic features appears to be more common in the general population than previously suggested . This type of pain is more severe than other chronic pain but distributed similarly throughout sociodemographic groups SUMMARY Objective : To determine the impact of the lidocaine patch 5 % on pain qualities associated with low-back pain ( LBP ) through use of the Neuropathic Pain Scale ( NPS ) . Patients and methods : Patients were enrolled in an open-label , non-r and omized , prospect i ve , 6-week study involving 8 clinical trial sites in the United States . Eligible patients had non-radicular LBP and reported moderate-to-severe pain on the NPS at study enrollment . Patients were stratified to 3 groups based on the duration of their LBP , defined as acute/sub-acute ( < 3 months ) , short-term chronic ( 3–12 months ) , or long-term chronic LBP ( > 12 months ) . The lidocaine patch 5 % was applied to the area of maximal pain , using no more than a total of 4 patches changed every 24 h. Effectiveness was measured by change from baseline to Week 2 and Week 6 in 4 composite measures of the NPS : NPS-10 , NPS-4 , NPS-8 , and NPS-non-allodynia . Safety was assessed by adverse events ( AEs ) , dermal assessment of application site(s ) , and skin sensory testing . Results : In the combined patient population ( n = 71 ) , 6 weeks of treatment with lidocaine patch 5 % significantly improved all 4 NPS composite measures at both Week 2 and Week 6 ( p < 0.001 ) . Separate analyses by subgroups revealed differential improvements in the 4 composite measures . Eleven patients ( 15.5 % ) experienced treatment-related AEs that were primarily mild-to-moderate and dermal in nature . Conclusions : In patients with moderate-to-severe LBP , 2 weeks and 6 weeks of treatment with the lidocaine patch 5 % significantly reduces the intensity of pain qualities as measured by all 4 NPS composite measures . Lidocaine patch 5 % is well tolerated with few systemic AEs and may provide beneficial pain relief for patients receiving multidisciplinary treatment without increasing risks for adverse drug interactions . Pain scales such as the NPS offer the ability to measure various pain qualities experienced by LBP patients and may allow clinicians to assess the treatment impact of different medications Study Design . A r and omized , double-blind trial was conducted . Objectives . To test the efficacy of periradicular corticosteroid injection for sciatica . Summary of Background Data . The efficacy of epidural corticosteroids for sciatica is controversial . Periradicular infiltration is a targeted technique , but there are no r and omized controlled trials of its efficacy . Methods . In this study 160 consecutive , eligible patients with sciatica who had unilateral symptoms of 1 to 6 months duration , and who never underwent surgery were r and omized for double-blind injection with methylprednisolone bupivacaine combination or saline . Objective and self-reported outcome parameters and costs were recorded at baseline , at 2 and 4 weeks , at 3 and 6 months , and at 1 year . Results . Recovery was better in the steroid group at 2 weeks for leg pain ( P = 0.02 ) , straight leg raising ( P = 0.03 ) , lumbar flexion ( P = 0.05 ) , and patient satisfaction ( P = 0.03 ) . Back pain was significantly lower in the saline group at 3 and 6 months ( P = 0.03 and 0.002 , respectively ) , and leg pain at 6 months ( 13.5 , P = 0.02 ) . Sick leaves and medical costs were similar for both treatments , except for cost of therapy visits and drugs at 4 weeks , which were in favor of the steroid injection ( P = 0.05 and 0.005 , respectively ) . By 1 year , 18 patients in the steroid group and 15 in the saline group underwent surgery . Conclusions . Improvement during the follow-up period was found in both the methylprednisolone and saline groups . The combination of methylprednisolone and bupivacaine seems to have a short-term effect , but at 3 and 6 months , the steroid group seems to experience a “ rebound ” phenomenon This r and omized , double-blind , placebo-controlled study was undertaken to evaluate the efficacy and tolerability of lamotrigine added to gabapentin , a tricyclic antidepressant , or a nonopioid analgesic in patients whose neuropathic pain was inadequately controlled with these medications . Patients with neuropathic pain from diabetic peripheral neuropathy , postherpetic neuralgia , traumatic/surgical nerve injury , incomplete spinal cord injury , trigeminal neuralgia , multiple sclerosis , or HIV-associated peripheral neuropathy , who had a mean weekly pain score > or = 4 on an 11-point numerical rating scale , were r and omized to receive a flexible dose of lamotrigine 200 , 300 , or 400 mg daily ( n=111 ) or placebo ( n=109 ) for up to 14 weeks ( including eight weeks of dose escalation ) in addition to their pre study regimen of gabapentin , a tricyclic antidepressant , or a nonopioid analgesic . No statistically significant difference in the mean change in pain-intensity score from baseline to Week 14 ( primary endpoint ) was detected between lamotrigine and placebo ( P=0.67 ) . Differences between lamotrigine and placebo were not statistically significant for secondary efficacy assessment s , including mean changes from baseline in the Short-Form McGill Pain Question naire , the Neuropathic Pain Scale , rescue medication use , and the percentages of patients rated as much improved or very much improved at the end of treatment on the Clinician Global Impression of Change scale and the Patient Global Impression of Change scale . Lamotrigine was generally well tolerated . Lamotrigine ( up to 400 mg/day ) added to gabapentin , a tricyclic antidepressant , or a nonopioid analgesic did not demonstrate efficacy as an adjunctive treatment of neuropathic pain but was generally safe and well tolerated Background Chemotherapy-induced peripheral neuropathy ( CIPN ) is a troublesome chronic symptom that has no proven pharmacologic treatment . The purpose of this double-blind r and omized placebo-controlled trial was to evaluate a novel compounded topical gel for this problem . Methods Patients with CIPN were r and omized to baclofen 10 mg , amitriptyline HCL 40 mg , and ketamine 20 mg in a pluronic lecithin organogel ( BAK-PLO ) versus placebo ( PLO ) to determine its effect on numbness , tingling , pain , and function . The primary endpoint was the baseline-adjusted sensory subscale of the EORTC QLQ-CIPN20 , at 4 weeks . Results Data in 208 patients reveal a trend for improvement that is greater in the BAK-PLO arm over placebo in both the sensory ( p = 0.053 ) and motor subscales ( p = 0.021 ) . The greatest improvements were related to the symptoms of tingling , cramping , and shooting/burning pain in the h and s as well as difficulty in holding a pen . There were no undesirable toxicities associated with the BAK-PLO and no evidence of systemic toxicity . Conclusion Topical treatment with BAK-PLO appears to somewhat improve symptoms of CIPN . This topical gel was well tolerated , without evident systemic toxicity . Further research is needed with increased doses to better clarify the clinical role of this treatment in CIPN The clinical response to therapeutic doses of two vitamins were determined in diabetic patients with symptomatic peripheral neuropathy . Of 200 consecutive patients , 100 were r and omly allocated to treatment with both thiamine ( 25 mg/day ) and pyridoxine ( 50 mg/day ) group A and the rest group B to treatment with an identical tablet containing 1 mg/day each of thiamine and pyridoxine . Pain , numbness , paraesthesia and impairment of sensation and ankle in the legs were grade d into none , mild , moderate or severe . Blood thiamine levels were measured using HPLC fluorimetry . Four weeks after starting treatment the grade was less than on the first visit in 88.9 % , 82.5 % and 89.7 % of those whose worst symptoms were pain , numbness and paraesthesia respectively for group A compared with 11.1 % , 40.5 % and 39.4 % respectively for group B. The severity of signs of peripheral neuropathy decreased in 48.9 % of patients in group A compared with 11.4 % in group B. The mean ( s.e . ) pre-treatment whole blood thiamine levels decreased with increasing severity of symptoms : 64.2 ( 2.81 ) , 57.7 ( 3.25 ) and 52.2 ( 2.14 ) micrograms/l for those with mild , moderate and severe symptoms respectively ( analysis of variance , p = 0.03 ) . Diabetic peripheral neuropathy in Dar es Salaam is associated with thiamine deficiency . Dietary guidelines for diabetic patients should emphasize a balanced diet PURPOSE To determine the analgesic effect of the addition of gabapentin to opioids in the management of neuropathic cancer pain . PATIENTS AND METHODS One hundred twenty-one consecutive patients with neuropathic pain due to cancer , partially controlled with systemic opioids , participated in a multicenter , r and omized , double-blind , placebo-controlled , parallel- design , 10-day trial from August 1999 to May 2002 . Gabapentin was titrated from 600 mg/d to 1,800 mg/d in addition to stable opioid dose . Extra opioid doses were available as needed . Zero to 10 numerical scale was used to rate average daily pain . The average pain score over the whole follow-up period was used as main outcome measure . Secondary outcome measures were : intensity of burning pain , shooting/lancinating pain , dysesthesias ( also scored on 0 to 10 numerical scale ) , number of daily episodes of lancinating pain , presence of allodynia , and daily extra doses of opioid analgesics . RESULTS Overall , 79 patients received gabapentin and 58 ( 73 % ) completed the study ; 41 patients received placebo and 31 ( 76 % ) completed the study . Analysis of covariance ( ANCOVA ) on the intent-to-treat population showed a significant difference of average pain intensity between gabapentin ( pain score , 4.6 ) and placebo group ( pain score , 5.4 ; P = .0250 ) . Among secondary outcome measures , dysesthesia score showed a statistically significant difference ( P = .0077 ; ANCOVA on modified intent-to-treat population = 115 patients with at least 3 days of pain assessment s ) . Reasons for withdrawing patients from the trial were adverse events in six patients ( 7.6 % ) receiving gabapentin and in three patients receiving placebo ( 7.3 % ) . CONCLUSION Gabapentin is effective in improving analgesia in patients with neuropathic cancer pain already treated with opioids OBJECTIVE To evaluate outcome in patients with failed back surgery syndrome treated with nerve root sleeve injections . DESIGN AND PATIENTS An open , nonblinded , r and omized study on 60 patients with documented fibrosis in fewer than three nerve roots . INTERVENTIONS After r and om selection , 20 patients were injected with 1 ml bupivacaine 0.5 % combined with 1500 units hyaluronidase and 1 ml saline per nerve root sleeve ( group A ) , another 20 were treated with 1 ml bupivacaine 0.5 % combined with 40 mg methylprednisolone solution ( Depo Medrol ) per nerve root ( group B ) , and a third group was treated with bupivacaine 0.5 % combined with 1500 units hyaluronidase and 40 mg methylprednisolone solution ( group C ) . The volume of each injection was 2 ml . The injections were given twice at an interval of 1 week . OUTCOME MEASURES The patients were evaluated on a verbal pain rating scale 1 , 3 , and 6 months after the second injection . The Kruskal-Wallis test was used to detect statistically significant differences among the three groups , and the analysis was refined with the Friedman test . RESULTS AND CONCLUSIONS Overall , although injections induced analgesia at 1 month , these effects were reduced at 3- and 6-month follow-ups . No statistical differences were found between the three treatment groups ( after 1 month , p = 0.71 ; after 3 months , p = 0.69 ; after 6 months , p = 0.66 . The Friedman test showed a significant decrease in treatment score as a function of time in groups B and C ( p = 0.015 ) but not in group A ( p = 0.074 ) . Corticosteroids seem responsible for the last phenomenon SUMMARY Objective : To determine the impact of the lidocaine patch 5 % on pain qualities associated with chronic pain from post-herpetic neuralgia ( PHN ) , painful diabetic neuropathy ( DN ) , and low-back pain ( LBP ) , using the Neuropathic Pain Scale ( NPS ) . Patients and methods : Patients with PHN , painful DN , and LBP were enrolled if they had partial response to gabapentin-containing analgesic regimens and if they reported moderate-to-severe pain on the NPS at study enrollment . Eligible patients were included in an open-label , non-r and omized , prospect i ve , 2-week study across 7 clinical trial sites in the United States . The lidocaine patch 5 % was applied to the area of maximal pain , using no more than a total of 4 patches changed every 24 h. Patients were maintained on their other analgesic regimens with no dose adjustment or additions allowed . Treatment effect was measured by change from baseline to Week 2 in 4 composite measures of the NPS : NPS-10 , NPS-4 , NPS-8 , and NPS-non-allodynia . Safety was assessed by adverse events ( AEs ) , dermal assessment of application site(s ) , and skin sensory testing . Results : In the combined patient population ( n = 77 ) , 2 weeks of treatment with the lidocaine patch 5 % significantly improved all 4 composite measures ( p < 0.01 ) . In the subgroup analyses , the lidocaine patch 5 % demonstrated numerical advantage for all 4 NPS composite measures for the PHN patients ( n = 8) , and significantly improved all 4 composite measures for the painful DN patients ( n = 41 ; p < 0.001 ) and LBP patients ( n = 28 ; p ≤ 0.005 ) . Overall , 8 patients ( 10 % ) experienced mild-to-moderate treatment-related AEs . Conclusions : The lidocaine patch 5 % effectively reduces the intensity of all common pain qualities in patients with moderate-to-severe chronic pain result ing from PHN , painful DN , or LBP . Treatment is well tolerated in combination with other analgesic regimens , with no reports of serious AEs or adverse drug interactions . Assessment scales such as the NPS may offer the possibility to differentiate between various pain states and to assess treatment outcomes for various pain qualities associated with a given pain state Objective To evaluate the safety and efficacy of gabapentin and venlafaxine in the treatment of painful diabetic neuropathy in patients whose pain did not improve with gabapentin monotherapy . Methods ( 1 ) A r and omized , double-blind , placebo-controlled , 8-week clinical trial comparing gabapentin versus placebo to define a patient population whose pain did not improve with monotherapy ; ( 2 ) a second 8-week trial comparing gabapentin plus venlafaxine with gabapentin plus placebo ; ( 3 ) a third uncontrolled 8-week trial of patients who did not improve on gabapentin monotherapy and then received venlafaxine in addition to gabapentin . Results ( 1 ) Gabapentin-treated patients showed statistically significant improvement in pain reduction as well as improvement in quality of life and mood disturbance when compared with placebo-treated patients ; ( 2 ) patients who received gabapentin plus venlafaxine showed significant improvement in pain reduction , mood disturbance , and quality of life when compared with patients treated with gabapentin plus placebo ; ( 3 ) patients who received gabapentin plus venlafaxine showed significant improvement in pain reduction , mood disturbance , and quality of life . Conclusions ( 1 ) Gabapentin is efficacious in the treatment of painful diabetic neuropathy ; ( 2 ) and ( 3 ) in patients who do not respond to gabapentin monotherapy , the addition of venlafaxine is also efficacious PURPOSE This study evaluated the effects of the multimodal therapy ( gabapentin-non steroidal anti inflammatory drug [NSAID]-morphine ) on intensity and relief of treatmentrelated neuropathic pain in patients with breast cancer . METHODS This study involved 75 breast cancer out patients who had previously undergone anti-neoplastic therapy ( surgery , chemotherapy , radiotherapy ) . The patients were r and omly divided into 3 groups , which were formed depending on the planned analgesic therapy ( gabapentin , gabapentin- NSAID , gabapentin-NSAID-morphine ) . Each group was a control group to itself . The pain intensity difference and scores of daily activities were collated and assessed by the modified Brief Pain Inventory ( BPI ) question naire ( VAS/Likert Scale ) . Monitoring the additional medication and side effects optimized the therapy efficiency evaluation . RESULTS During this 6-week study , the decrease of pain intensity was significant in all 3 groups ( p < 0.0001 ) . Although there was intergroup difference , it was statistically not significant ( p > 0.05 ) . The variant analysis of pain relief showed differences both among and within the groups in the first 3 weeks of the study ( F(1)=7.79 , p=0.000 ; F(2)=7.01 , p=0.001 ; F(3 ) = 5.49 , p=0.001 ) . The multimodal group needed the least of additional medication and the variant analysis showed a statistically significant difference ( p=0.001 ) from the 4th week of the trial period . The correlation between the increase trend of side effects and the frequency of additional medication was significant ( p < 0.05 ) . CONCLUSION The multimodal therapy ensures adequate cancer-related neuropathic pain control with minimal side effects Background Neuropathic pain is regarded as one of the main causes of cancer pain refractory to st and ard opioid therapy in palliative care . The use of adjuvant analgesics for neuropathic cancer pain is largely empirical and the true efficacy of these adjuvant analgesics has been unknown . Gabapentin is one of the new promising anticonvulsant drugs as an adjuvant analgesic for neuropathic cancer pain . Methods The clinical usefulness of gabapentin in combination with opioids for Japanese patients with neuropathic cancer pain was assessed in an open-label , single-center , prospect i ve study . Gabapentin was initiated in addition to the drugs currently being administered . The dose of gabapentin was titrated from 200 mg to a maximum dose of 2400 mg per day over 15 days , based on discussion with each patient . The primary endpoint variable was the numerical rating scale ( NRS ) of 0–10 measured using the brief pain inventory . Results From February 2007 to December 2007 , gabapentin was administered to 24 patients that were already receiving an opioid without sufficient analgesia . Administration of gabapentin statistically reduced the worst-NRS , the least-NRS , and the average-NRS ( 7.3 → 5.8 , 3.6 → 3.0 , 5.8 → 4.5 , respectively ) . Four patients ( 16.7 % ) were withdrawn from the study because of adverse events ( headache , myoclonus , heartburn , bronchial asthma ) . Conclusion Although gabapentin might be regarded as a promising new adjuvant analgesic for neuropathic cancer pain , our results indicated that the decrease in pain score was of minimal clinical benefit . Controlled trials with other adjuvant analgesics are needed AIMS This study compared the efficacy and safety of tramadol/acetaminophen ( T/A ) and gabapentin in the management of painful diabetic neuropathy . METHODS An open , r and omized , comparative study was conducted . Subjects with painful symmetric neuropathy in the lower limbs and mean pain-intensity score > or = 4 on a numeric rating scale were eligible . Subjects were r and omized to receive either tramadol ( 37.5 mg)/acetaminophen ( 325 mg ) or gabapentin ( 300 mg ) for 6 weeks . After 2 weeks of the titration period ( 1200 mg/day for gabapentin and three tablets/day for T/A ) , the doses were maintained if the pain was relieved . The primary efficacy outcome was a reduction in pain intensity . Secondary measures evaluated a pain relief scale , a Brief Pain Inventory , a 36-item Short Form Health Survey , average pain intensity and sleep disturbance . RESULTS One hundred and sixty-three subjects ( T/A 79 ; gabapentin 84 ) were included . At the final visit , the mean doses were 1575 mg/day for gabapentin and 4.22 tablets/day for T/A. Both groups were similar in terms of baseline pain intensity ( mean intensity : T/A 6.7 + /- 1.6 ; gabapentin 6.3 + /- 1.6 , P = 0.168 ) . At the final visit , the mean reductions in pain intensity were similar in both groups ( T/A -3.1 + /- 2.0 ; gabapentin -2.7 + /- 2.1 , P = 0.744 ) . Both groups had similar improvements in every Short Form Health Survey category and Brief Pain Inventory subcategory , and in the mean pain relief scores . CONCLUSION This study suggests that the T/A combination treatment is as effective as gabapentin in the treatment of painful diabetic neuropathy in patients with Type 2 diabetes We compared the efficacy and tolerance of the combination of nortriptyline-fluphenazine ( NF ) vs. carbamazepine ( CMZ ) in the symptomatic therapy of patients with severe , distal , symmetrical , predominantly sensitive diabetic polyneuropathy ( DPN ) . We followed a double blind , crossover , r and omized and double placebo design . Sixteen patients with severe DPN participated in the study . Patients received either NF ( 1 tablet three times a day ( tid ) ) , for 2 weeks and 2 tablets tid for the next 2 weeks or CMZ 1/2 tablet tid for 2 weeks and 1 tablet tid for the next 2 weeks . After this , patients received placebos of both drugs ( wash-out period ) , until symptoms returned to baseline levels ( 100 % ) , then they were crossed over to receive the other comparing drug schedule . A visual analogue scale was used to evaluate the percent changes in pain and paresthesia . HbA1 , fasting serum glucose , and safety tests were performed at 2- and 4-week intervals , respectively . Both therapies produced significant improvement of both pain and paresthesia . No statistically significant differences were observed between both therapies for either pain or paresthesia . No significant biochemical changes were observed with any of the two therapies . Side effects were mild and more frequent in the NF period . In this study no superiority of either drug schedule was demonstrated ; therefore , the decision to use any of them should be made according to the associated pathology and potential side effects of each drug BACKGROUND : Calcitonin was effective in a study of acute phantom limb pain , but it was not studied in the chronic phase . The overall literature on N-methyl-d-aspartate antagonists is equivocal . We tested the hypothesis that calcitonin , ketamine , and their combination are effective in treating chronic phantom limb pain . Our secondary aim was to improve our underst and ing of the mechanisms of action of the investigated drugs using quantitative sensory testing . METHODS : Twenty patients received , in a r and omized , double-blind , crossover manner , 4 IV infusions of : 200 IE calcitonin ; ketamine 0.4 mg/kg ( only 10 patients ) ; 200 IE of calcitonin combined with ketamine 0.4 mg/kg ; placebo , 0.9 % saline . Intensity of phantom pain ( visual analog scale ) was recorded before , during , at the end , and the 48 h after each infusion . Pain thresholds after electrical , thermal , and pressure stimulation were recorded before and during each infusion . RESULTS : Ketamine , but not calcitonin , reduced phantom limb pain . The combination was not superior to ketamine alone . There was no difference in basal pain thresholds between the amputated and contralateral side except for pressure pain . Pain thresholds were unaffected by calcitonin . The analgesic effect of the combination of calcitonin and ketamine was associated with a significant increase in electrical thresholds , but with no change in pressure and heat thresholds . CONCLUSIONS : Our results question the usefulness of calcitonin in chronic phantom limb pain and stress the potential interest of N-methyl-d-aspartate antagonists . Sensory assessment s indicated that peripheral mechanisms are unlikely important determinants of phantom limb pain . Ketamine , but not calcitonin , affects central sensitization processes that are probably involved in the pathophysiology of phantom limb pain & NA ; Twenty patients with chronic pain who previously had obtained analgesia from epidural clonidine and lignocaine agreed to participate in a double‐blind crossover study of lumbar epidural clonidine ( 150 & mgr;g ) , lignocaine ( 40 mg ) and the combination of clonidine ( 150 & mgr;g ) and lignocaine ( 40 mg ) , all drugs were given in a volume of 3 ml . There were 11 women and 9 men with a mean age 53 years ( range : 23–78 years ) ; 9 patients had low back and leg pain , 9 had neuropathic pain , 1 had pelvic pain and 1 Wegner 's granulomatosis . Pain intensity and pain relief , as well as sensory and motor blockade , were assessed for 3 h following each injection . The combination was reported as the best pain relief by 12 of the 17 patients who completed all three arms of the study ; 4 patients reported that clonidine was the best , 1 patient reported that none of the injections provided any analgesia and no patient reported that lignocaine was the best . SPID analysis revealed a significant difference between the combination and lignocaine ( P < 0.05 ) but no other significant difference . TOTPAR analysis revealed no significant difference between any of the injections . All 3 injections produced evidence of neurological blockade ; clonidine produced sensory blockade in 3 patients and motor blockade in 3 patients . Lignocaine produced sensory blockade in 6 patients and motor in 8 patients , while the combination produced evidence of neurological blockade in all 17 patients , sensory in 6 and motor in 11 patients . Overall there was no relationship between neurological blockade and analgesia . The reported side effects appeared to be related to clonidine . These data indicate that in these patients with chronic pain epidural clonidine had a supra‐additive effect and behaved more like a co‐analgesic than a pure analgesic Seventeen patients with long-lasting idiopathic trigeminal neuralgia ( ITN ) were treated with either five , weekly peripheral streptomycin/lidocaine ( S/L ) or lidocaine alone injections , in a double blind controlled study . Eight patients responded initially to the treatment in the S/L group and three patients in the lidocaine group . Pain recurred in four patients from the S/L group within two weeks and six months following the last injection . One patient from the lidocaine group remained pain-free for eight months . At the final assessment , three patients from the S/L group and two patients from the lidocaine group remained pain-free up to 30 months . Neither treatment affected sensory functions of the injected nerves . It is concluded that S/L injections are initially effective in the treatment of ITN . In the long term , however , their effects are similar to the effects of lidocaine alone OBJECTIVE Peripheral nerve blocks with methylprednisolone may provide effective pain therapy by decreasing ectopic neuronal discharge and the release of local inflammatory mediators at the site of nerve injury . In this study , we aim ed to compare the efficacy of lidocaine alone with a combination of depo-methylprednisolone plus lidocaine in the management of neuropathic pain due to peripheral nerve damage . DESIGN R and omized , double-blind comparator trial . SETTING Group control ( N = 44 ) received 0.5 % lidocaine and group methylprednisolone ( N = 44 ) received 80 mg depo-methylprednisolone + 0.5 % lidocaine proximal to the site of nerve injury with a total amount of 10 - 20 mL solution according to the type of peripheral nerve block with nerve stimulator . OUTCOME MEASURES Demographic data , preblock numerical rating scales ( NRSs ) , the Leeds assessment of neuropathic symptoms and signs ( LANSS(0 ) ) score , accompanying symptoms , and analgesic requirements were recorded . Postblock NRS scores were noted following peripheral nerve block and after 3 months . LANSS(1 ) , accompanying symptoms , and analgesic requirements were also reevaluated 3 months after the injection . RESULTS Demographic data , preblock NRS ( 8 ± 1.5 and 8.1 ± 1.2 , respectively ) , postblock NRS ( 2.1 ± 1.2 and 2.4 ± 1.4 , respectively ) , LANSS(0 ) ( 18.4 ± 2.2 and 18.2 ± 2.1 , respectively ) , and accompanying symptoms were comparable between groups . Scores for the methylprednisolone group were significantly improved at 3-month postblock for NRS ( 2 ± 1.4 vs 5.2 ± 1.7 ) and LANSS(1 ) scores ( 4.14 ± 2.7 vs 14.1 ± 2.8 ) , accompanying symptoms , and analgesic requirements ( P < 0.0001 ) . CONCLUSIONS Our results suggest that peripheral nerve block with 80 mg depo-methylprednisolone plus 0.5 % lidocaine provides effective management in the treatment of neuropathic pain due to peripheral nerve damage & NA ; R and omized , double‐blind , placebo‐controlled trials on neuropathic pain treatment are accumulating , so an up date d review of the available evidence is needed . Studies were identified using MEDLINE and EMBASE search es . Numbers needed to treat ( NNT ) and numbers needed to harm ( NNH ) values were used to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions . One hundred and seventy‐four studies were included , representing a 66 % increase in published r and omized , placebo‐controlled trials in the last 5 years . Painful poly‐neuropathy ( most often due to diabetes ) was examined in 69 studies , postherpetic neuralgia in 23 , while peripheral nerve injury , central pain , HIV neuropathy , and trigeminal neuralgia were less often studied . Tricyclic antidepressants , serotonin noradrenaline reuptake inhibitors , the anticonvulsants gabapentin and pregabalin , and opioids are the drug classes for which there is the best evidence for a clinical relevant effect . Despite a 66 % increase in published trials only a limited improvement of neuropathic pain treatment has been obtained . A large proportion of neuropathic pain patients are left with insufficient pain relief . This fact calls for other treatment options to target chronic neuropathic pain . Large‐scale drug trials that aim to identify possible subgroups of patients who are likely to respond to specific drugs are needed to test the hypothesis that a mechanism‐based classification may help improve treatment of the individual patients Pain associated with Herpes Zoster ( HZ ) and Post-herpetic Neuralgia ( PHN ) has been a challenging task to manage with ease . Topical aspirin dissolved in chloroform is an effective means of reducing pain due to HZ and PHN in most patients . The locus of pain origin and analgesia induced by topical aspirin is supposed to be at cutaneous free nerve ending pain receptors . The present study was conduced in fifty two patients of HZ and PHN . Pain intensity before and after the application of drug was measured with help of Sort Form McGill Pain Question naire ( SE-MPQ ) . Most of the patients experienced relief of pain within 1 - 5 minutes after the aspirin-chloroform application . Maximum relief was achieved in about 30 - 40 minutes and persisted for 5 - 6 hrs . In the beginning 3 - 4 applications were required but frequency decreased gradually as the pain abated The aim of this study was to establish if the cholecystokinin ( CCK ) 2 antagonist L-365,260 augments the analgesic effect of morphine in human subjects with chronic neuropathic pain . This is a r and omised , double blind , placebo controlled study of 40 adult subjects taking morphine for neuropathic pain . Each received placebo , L-365,260 30 mg and L-365,260 120 mg in three divided doses daily separated by a washout period in r and om order . Pain , activity , sedation , sleep and side effects were recorded along with 12 lead ECGs , renal and liver function tests and full blood pictures . L-365,260 failed to augment the analgesic effect of morphine at any of the dose levels used . Side effects were minor . There were no changes in ECGs and biochemical indices were unaltered with its use . The CCK 2 antagonist L-365,260 does not augment the analgesic effect of morphine in subjects with chronic neuropathic pain . L-365,260 was well tolerated and side effects from its use were minor Pain not responsive to morphine is often problematic . Animal and clinical studies have suggested that N-methyl-D-aspartate ( NMDA ) antagonists , such as ketamine , may be effective in improving opioid analgesia in difficult pain syndromes , such as neuropathic pain . A slow bolus of subhypnotic doses of ketamine ( 0.25 mg/kg or 0.50 mg/kg ) was given to 10 cancer patients whose pain was unrelieved by morphine in a r and omized , double-blind , crossover , double-dose study . Pain intensity on a 0 to 10 numerical scale ; nausea and vomiting , drowsiness , confusion , and dry mouth , using a scale from 0 to 3 ( not at all , slight , a lot , awful ) ; Mini-Mental State Examination ( MMSE ) ( 0 - 30 ) ; and arterial pressure were recorded before administration of drugs ( T0 ) and after 30 minutes ( T30 ) , 60 minutes ( T60 ) , 120 minutes ( T120 ) , and 180 minutes ( T180 ) . Ketamine , but not saline solution , significantly reduced the pain intensity in almost all the patients at both doses . This effect was more relevant in patients treated with higher doses . Hallucinations occurred in 4 patients , and an unpleasant sensation ( " empty head " ) was also reported by 2 patients . These episodes reversed after the administration of diazepam 1 mg intravenously . Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg . A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine . Ketamine can improve morphine analgesia in difficult pain syndromes , such as neuropathic pain . However , the occurrence of central adverse effects should be taken into account , especially when using higher doses . This observation should be tested in studies of prolonged ketamine administration OBJECTIVES pinal cord stimulation ( SCS ) is a well-established treatment for neuropathic pain ; nevertheless , 40 % of patients fail to obtain satisfactory pain relief and in many patients , the effect tends to diminish with time . Based on animal experiments , intrathecal baclofen was previously introduced clinical ly to enhance suboptimal SCS effects . Later animal experiments demonstrated similar data for clonidine . The aim of this study was to eluci date whether intrathecal clonidine or baclofen enhances the effect of SCS in neuropathic pain patients in whom the pain relieving-effect of SCS is inadequate . METHODS A r and omized , double-blind , placebo-controlled clinical trial was conducted with 10 patients experiencing neuropathic pain with insufficient pain relief with SCS alone . Clonidine , baclofen , and saline ( control ) were intrathecally administered by bolus injections in combination with SCS . RESULTS Seven of 10 patients reported significant pain reduction when SCS was combined with active drugs . The mean visual analog scale ratings were reduced by more than 50 % with either drug combined with SCS . Four patients previously treated with SCS alone later underwent implantation of a pump for long-term administration of clonidine or baclofen . In the 2 patients with clonidine pumps with a mean follow-up of 15 months , the combined therapy produced pain reduction of 55 % and 45 % , respectively . The corresponding effect with baclofen was 32 % and 82 % , respectively , at 7 months follow-up . CONCLUSION A trial with clonidine and baclofen combined with SCS may be warranted in patients who do not obtain satisfactory pain relief with SCS alone or experienced a decreasing therapeutic effect BACKGROUND Postherpetic neuralgia ( PHN ) is a vexing problem occurring in 10 to 20 percent of people with from herpes zoster ( shingles ) . Anecdotal reports show that fluphenazine enhances the effects of amitriptyline for the treatment of PHN . The aim of this study was to determine , in a controlled manner , whether this was the case . METHODS In a double-blind placebo-controlled study , 49 patients with PHN were r and omly assigned to four treatment groups : Group 1 , amitriptyline ; Group 2 , amitriptyline and fluphenazine ; Group 3 , fluphenazine ; Group 4 , a placebo . An active placebo was used to mimic the anticholinergic side effects of dry mouth . The study lasted 8 weeks , with weekly progress evaluations with use of visual analog scales ( VAS ) , the McGill Pain Question naire ( MPQ ) , and a side-effects scale . RESULTS A statistically significant decrease was seen in pain in Groups 1 and 2 , and no significant changes were seen in Groups 3 and 4 . There was no significant difference when fluphenazine was added to amitriptyline . CONCLUSION These data support the effectiveness of amitriptyline in treatment of PHN , but do not support the addition of fluphenazine Chronic post-thoracotomy pain ( CPP ) is associated with surgical intercostal nerve injury . Like other forms of neuropathic pain , there is no ideal treatment . Nitroglycerin ( NTG ) has been found efficacious in acute pain , but has not been tested for chronic pain with neuropathic characteristics . The present study investigated the efficacy of NTG combined with the nonsteroidal anti-inflammatory drug etodolac for the treatment of CPP . Thirty of 129 patients who underwent thoracotomy within an 18-month period had moderate to severe pain that did not respond to etodolac . NTG , 5 mg/day , was added to the treatment . A significant reduction in VAS was observed on day 14 of treatment ( from 66.7 + /- 11 to 42.1 + /- 5 , P < 0.05 ) . Similar changes were noted in breakthrough pain intensity and and sleep efficiency . The only side effect was mild headache , which was self-limited to the first few days of NTG administration . We conclude that NTG added to etodolac appears to be effective for the treatment of CPP , with minimal side effects . Further r and omized blinded studies are required OBJECTIVE The objective of this study was to compare the effectiveness of combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combination codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain . BACKGROUND Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen . METHODS In this r and omized , parallel-group , double-blind , repeated-dose , active-comparator , 4-week , multicenter study , 469 patients were r and omly assigned to receive a 1-tablet ( n = 156 ) or 2-tablet ( n = 153 ) dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg ( HI1 and HI2 , respectively ) or a 2-tablet dose of combination codeine 30 mg and acetaminophen 300 mg ( CA , n = 160 ) , the active comparator , every 6 to 8 hours as needed for pain . Efficacy was measured through pain relief scores , number of daily doses of study medication , number of daily doses of supplemental analgesics , number of patients who discontinued therapy due to an unsatisfactory analgesic response , and global assessment scores . RESULTS Of the 469 patients , 255 ( 54.4 % ) were female and 214 ( 45.6 % ) were male . The mean age was 51.1 years . Types of chronic pain included back ( 214 ; 45.6 % ) , arthritic ( 145 ; 30.9 % ) , other musculoskeletal ( 65 ; 13.9 % ) , cancer ( 6 ; 1.3 % ) , diabetic neuropathic ( 3 ; 0.6 % ) , postherpetic neuralgic ( 5 ; 1.1 % ) , other neurologic ( 21 ; 4.5 % ) , and other unclassified chronic pain ( 10 ; 2.1 % ) . During the 48 hours prior to the study , 351 ( 74.8 % ) patients had been treated with opioid or opioid-nonopioid combination analgesics . The overall mean daily pain relief score was significantly greater in the HI2 group ( 2.25+/-0.89 ) than in the HI1 group ( 1.98+/-0.87 ) ( P = 0.003 ) or the CA group ( 1.85+/-0.96 ) ( P < 0.001 ) . The overall mean number of daily doses of study medication was significantly less in the HI2 group ( 2.94+/-0.99 ) than in the HI1 group ( 3.23+/-0.76 ) ( P = 0.036 ) or the CA group ( 3.26+/-0.75 ) ( P = 0.014 ) . The overall mean number of daily doses of supplemental analgesics was significantly less in the HI2 group ( 0.24+/-0.49 ) than in the HI1 group ( 0.34+/-0.58 ) ( P = 0.021 ) or CA group ( 0.49+/-0.85 ) ( P = 0.010 ) . The number of patients who discontinued treatment due to an unsatisfactory analgesic response was significantly less in the HI2 group ( 2 ; 1.3 % ) than in the CA group ( 12 ; 7.5 % ) ( P = 0.008 ) . HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 ( P < 0.001 vs HI1 and CA ) , week 2 ( P < 0.001 vs HI1 and CA ) , and week 3 ( P = 0.008 vs HI1 and P < 0.001 vs CA ) ; daily doses of study medication for week 1 ( P = 0.019 vs HI1 and P = 0.011 vs CA ) ; daily doses of supplemental analgesics for week 1 ( P = 0.010 vs HI1 and CA ) ; and global assessment scores for week 1 ( P = 0.018 vs HI1 and P < 0.001 vs CA ) , week 2 ( P = 0.005 vs HI1 and P < 0.001 vs CA ) , and week 4 ( P = 0.013 vs HI1 and P = 0.023 vs CA ) . There were no significant differences between HI1 and CA in any efficacy variable . There were no significant differences in the number of patients experiencing adverse events in the HI2 ( 127 ; 83 % ) , HI1 ( 124 ; 79.5 % ) , and CA ( 129 ; 80.6 % ) groups . However , the mean number of patients who discontinued treatment due to adverse events was significantly greater in the HI2 group ( 40 ; 26.1 % ) than in the HI1 group ( 23 ; 14.7 % ) ( P = 0.013 ) . CONCLUSIONS The results of this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be more effective than either 1-tablet doses of this combination or 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg . Moreover , 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg Objective Postherpetic neuralgia ( PHN ) is responsible for one of the most common types of neuropathic pain , described as a burning pain that shakes , hits , and tightens and includes allodynia and paresthesia . Aim of the Study To evaluate the efficacy of Pregabalin when used during transcutaneous electric nerve stimulation ( TENS ) in patients with PHN and to analyze any changes in physical activity and sleep quality . Methods Patients aged 50 to 80 years were included in this r and omized study . We enrolled 15 male ( average age 65±8.6 y ) and 15 female patients ( average age 64±8.2 y ) . The male patients had a history of neuropathic pain lasting 15.6±8.8 months whereas the female patients had a history of neuropathic pain lasting about 14.9±8.6 months . We began with 1 week of patient screening followed by a week of Pregabalin titration . Then , we established the dose of Pregabalin for each patient to obtain visual analog scale ( VAS ) of less than 60 mm . The eligible patients were r and omly divided into 2 groups receiving Pregabalin + TENS or Pregabalin+TENS placebo for the following 4 weeks . Patients underwent 8 outpatient visits during which they completed VAS , SF-McGill Pain Question naire , and sleep interference question naire . Results The result ing data showed that Pregabalin administration associated with TENS reduced pain in patients with PHN . At the end of the treatment , all the observed groups presented a reduction of mean VAS . The group treated with Pregabalin 300 (P300)+TENS had a reduction of pain of 30 % and the group treated with Pregabalin 600 (P600)+TENS had a reduction of pain of 40 % . The comparison between group P300+TENS versus group P300+TENS placebo showed a statistically significant reduction of VAS ( P300+TENS 25±0.67 vs. P300+TENS placebo 39±1.19 P<0.02 ) . Moreover , the comparison between group P600+TENS versus group P600+TENS placebo has shown a statistically significant reduction of VAS ( P600+TENS 23±0.78 vs. P600+TENS placebo 32±0.81 P<0.02 ) . At the end of the study , all groups showed a statistically significant difference in terms of sleep interference , Short-Form McGill Pain Question naire total score , and Short-Form McGill Pain Question naire Present Pain Intensity . Conclusions These data support the conclusion that Pregabalin gives better results when combined with TENS therapy , which is an analgesic nonpharmacologic procedure . Therefore , a multidisciplinary treatment should be considered for this kind of pain We examined the role of N-methyl-D-aspartate ( NMDA ) receptors in chronic ( pathological ) pain in humans by using the NMDA receptor antagonist ketamine as a probe . Thirty patients with neuropathic pain in the trigeminal area were given an i.m . injection of ketamine 0.4 mg/kg combined with midazolam 0.05 mg/kg . Pethidine 1.0 mg/kg served as a control . Three different response patterns were observed . Ketamine caused a long-term ( 6 - 24 h ) analgesic effect partly dissociated from the mental side effects in 8 of the 26 patients who completed the study ; these patients also had a slight analgesic effect of pethidine . In nine patients , ketamine caused a short-lasting ( < 2 h ) analgesic effect closely associated with the mental side effects , whereas pethidine caused little or no analgesia . The remaining nine patients did not experience any reduction of pain after either drug in spite of characteristic side effects . One week after the i.m . challenge the patients received either 4.0 mg/kg ketamine hydrochloride or placebo capsules to be taken orally as a nightly dose for three consecutive nights . Five of the eight patients who had a long-term analgesic effect of the i.m . challenge reported decreased pain on days after ketamine . None of the others reported an analgesic effect . The phenomenon of long-term depression of pain in a subgroup of patients was thus confirmed when ketamine was given p.o . These findings indicate that NMDA receptors are involved in the perception and maintenance of pathological pain in some patients . In others , pain appears to be mediated by NMDA receptor-independent mechanisms . We suggest that NMDA receptor-independent transmission in central pain pathways may contribute to the reduced efficiency of analgesic drugs often seen in chronic pain states AIMS To assess the analgesic efficacy of topical administration of 3.3 % doxepin hydrochloride , 0.025 % capsaicin and a combination of 3 . 3 % doxepin and 0.025 % capsaicin in human chronic neuropathic pain . METHODS A r and omized , double-blind , placebo-controlled study of 200 consenting adult patients . Patients applied placebo , doxepin , capsaicin or doxepin/capsaicin cream daily for 4 weeks . Patients recorded on a daily basis overall pain , shooting , burning , paraesthesia and numbness using a 0 - 10 visual analogue scale during the week prior to cream application ( baseline levels ) and for the 4 week study period . Side-effects and desire to continue treatment were also recorded . RESULTS Overall pain was significantly reduced by doxepin , capsaicin and doxepin/capsaicin to a similar extent . The analgesia with doxepin/capsaicin was of more rapid onset . Capsaicin significantly reduced sensitivity and shooting pain . Burning pain was increased by doxepin and by capsaicin and to a lesser extent by doxepin/capsaicin . Side-effects were minor . One patient requested to continue placebo cream , 17 doxepin cream , 13 capsaicin and 9 the combination of doxepin and capsaicin . CONCLUSIONS Topical application of 3.3 % doxepin , 0.025 % capsaicin and 3.3 % doxepin/0 . 025 % capsaicin produces analgesia of similar magnitude . The combination produces more rapid analgesia BACKGROUND There is no effective treatment for intractable postherpetic neuralgia . Because there is evidence that postherpetic neuralgia has an inflammatory component , we assessed treatment with intrathecally administered methylprednisolone to reduce pain in patients with this disorder . METHODS We enrolled 277 patients who had had intractable postherpetic neuralgia for at least one year , 270 of whom were followed for two years . The patients were r and omly assigned to receive intrathecal methylprednisolone and lidocaine ( 3 ml of 3 percent lidocaine with 60 mg of methylprednisolone acetate , 89 patients ) , lidocaine alone ( 3 ml of 3 percent lidocaine , 91 patients ) , or no treatment ( 90 patients ) once per week for up to four weeks . Each weekly dose was injected into the lumbar intrathecal space . Pain was evaluated before r and omization , at the end of the treatment period , and then four weeks , one year , and two years later . Sample s of cerebrospinal fluid were obtained for measurement of interleukin-8 before and at the end of the treatment period . RESULTS There was minimal change in the degree of pain in the lidocaine-only and control groups during and after the treatment period . In the methylprednisolone-lidocaine group , the intensity and area of pain decreased , and the use of the nonsteroidal antiinflammatory drug diclofenac declined by more than 70 percent four weeks after the end of treatment . No complications related to intrathecal methylprednisolone were observed . Before treatment , the concentrations of interleukin-8 in the cerebrospinal fluid were inversely related to the duration of neuralgia in all the patients ( r=-0.49 , P<0.001 ) . In the patients who received methylprednisolone , interleukin-8 concentrations decreased by 50 percent , and this decrease correlated with the duration of neuralgia and with the extent of global pain relief ( P<0.001 for both comparisons ) . CONCLUSIONS The results of this trial indicate that the intrathecal administration of methylprednisolone is an effective treatment for postherpetic neuralgia Study Design . Prospect i ve comparison of periradicular infiltration with steroid versus saline on the spontaneous resorption of herniated nucleus pulposus in a r and omized controlled trial . Objectives . To evaluate whether periradicular steroid retards the resorption of herniated nucleus pulposus . Summary of Background Data : Rim enhancement around herniated nucleus pulposus is associated with spontaneous resorption of disc herniations . As rim enhancement consists of a macrophage infiltrate , periradicular steroid could theoretically interfere with the resorption process . Methods . Patients with disc herniation-induced sciatica were r and omized to receive either periradicular methylprednisolone ( in combination with bupivacaine ) or saline . Lumbar magnetic resonance imaging ( MRI ) was performed at baseline , at 2 months , and at 12 months . Disc herniation volume ( mm3 ) , coverage of rim enhancement ( % ) , and rim enhancement thickness ( mm ) were evaluated by a radiologist blinded to the allocation . Operated patients were excluded from the 1-year imaging . Changes in the parameters from baseline to 2 months , and from 2 to 12 months , were evaluated with the Mann-Whitney U test . Results . Change in herniation volume from baseline to 2 months was measurable in 34 patients of both groups , and from 2 to 12 months in 26 patients of the steroid group and 24 patients of the saline group . Significant spontaneous resorption of disc herniations occurred in both groups during the 1-year follow-up . In the subgroup analysis , there tended to be even faster resorption in the steroid group from baseline to 2 months for extrusions , and from 2 months to 12 months for contained herniations . No significant differences were observed in the enhancement parameters ( coverage and thickness ) between the two treatments . Conclusions . Periradicular corticosteroid does nothave a negative effect on the spontaneous resorption ofthe herniated nucleus pulposus BACKGROUND Post herpetic neuralgia is a chronic neuropathic pain syndrome which remains one of the most difficult pain disorders to treat . Epidural injection of methylprednisolone with or without local anesthetic provides relief for neuralgia for a short duration only . Recent studies have shown a promising anti nociceptive effect for intrathecal midazolam , a water soluble benzodiazepine , due to its interaction with benzodiazepine-GABA-A receptor complex within the spinal cord . STUDY DESIGN A r and omized , double blind study was conducted at 2 different centers in India . SETTING Two different interventional pain practice centers in India . OBJECTIVES To quantify the effectiveness of a single intrathecal injection of midazolam 2 mg with and without epidural methylprednisolone 60 mg for management of pain and allodynia in 150 adult patients with postherpetic neuralgia of 3 - 6 months duration involving lumbosacral dermatomes . METHODS Patients in Group M-0 ( n=50 ) received epidural methylprednisolone ( 60 mg ) , patients in group M-1 ( n=50 ) received midazolam 2 mg in the intrathecal space while patients in Group M-2 ( n=50 ) received methylprednisolone ( 60 mg ) in the epidural space plus midazolam 2 mg in the intrathecal space . RESULTS The administration of intrathecal midazolam ( 2 mg ) provided short term improvement in post herpetic neuralgia similar to epidural methylprednisolone . However , the combination of intrathecal midazolam with epidural methylprednisolone result ed in prolonged duration of analgesia in patients with post herpetic neuralgia . The need for analgesics was also significantly less in patients who received the combination compared to those who received either intrathecal midazolam or epidural methylprednisolone . No serious adverse effect was reported with the use of intrathecal midazolam except a mild degree of sedation . CONCLUSION The combination of intrathecal midazolam with epidural methylprednisolone result ed in prolonged duration of analgesia in patients with post herpetic neuralgia of lumbosacral dermatomes due to the complementary anti nociceptive action of intrathecal midazolam with epidural methylprednisolone on spinal nerve roots . LIMITATIONS The dose-response relationship of intrathecal midazolam was not evaluated in our study , so further study should be conducted with different doses of intrathecal midazolam for management of PHN OBJECTIVE To determine whether duloxetine is noninferior to ( as good as ) pregabalin in the treatment of pain associated with diabetic peripheral neuropathy . PATIENTS AND METHODS We performed a 12-week , open-label study of patients with diabetic peripheral neuropathic pain who had been treated with gabapentin ( ≥ 900 mg/d ) and had an inadequate response ( defined as a daily pain score of ≥ 4 on a numerical rating scale [ 0 - 10 points ] ) . The first patient was enrolled on September 28 , 2006 , and the last patient visit occurred on August 26 , 2009 . Patients were r and omized to duloxetine monotherapy ( n=138 ) , pregabalin monotherapy ( n=134 ) , or a combination of duloxetine and gabapentin ( n=135 ) . The primary objective was a noninferiority comparison between duloxetine and pregabalin on improvement in the weekly mean of the diary-based daily pain score ( 0- to 10-point scale ) at end point . Noninferiority would be declared if the mean improvement for duloxetine was no worse than the mean improvement for pregabalin , within statistical variability , by a margin of -0.8 unit . RESULTS The mean change in the pain rating at end point was -2.6 for duloxetine and -2.1 for pregabalin . The 97.5 % lower confidence limit was a -0.05 difference in means , establishing noninferiority . As to adverse effects , nausea , insomnia , hyperhidrosis , and decreased appetite were more frequent with duloxetine than pregabalin ; insomnia , more frequent with duloxetine than duloxetine plus gabapentin ; peripheral edema , more frequent with pregabalin than with duloxetine ; and nausea , hyperhidrosis , decreased appetite , and vomiting , more frequent with duloxetine plus gabapentin than with pregabalin . CONCLUSION Duloxetine was noninferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy who had an inadequate pain response to gabapentin . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00385671 We conducted a double-blind , placebo-controlled , crossover study of the effectiveness of amitriptyline and fluphenazine in alleviating the pain of diabetic peripheral neuropathy in six diabetic patients . Pain was evaluated by the patients with a graphic rating scale . A placebo response was found , but no additional effect of amitriptyline and fluphenazine was seen . Although the statistical power of this study was low , these data , when combined with a reevaluation of previous trials of amitriptyline and fluphenazine in the treatment of painful diabetic neuropathy , indicate that there is no justification for the use of these agents in the treatment of painful neuropathy outside of large , controlled clinical trials . Depression as a possible cause of this condition should not go unnoted or untreated 82 patients with chronic pain result ing from mononeuropathy were treated with psychotropic drugs in an open therapeutic study . In this study we found that treatment with a combination of clomipramine ( Anafranil ) and small doses of neuroleptics was significantly superior to therapy with neuroleptics alone . In a subsequent double-blind study , it was attempted for the first time to determine the efficacy of clomipramine compared to that of acetylsalicylic acid in 48 patients with painful mono- and polyneuropathies . The test was carried out in a cross-over trial with two sequence groups . We evaluated assessment s of pain by both patients and doctors , and were able to prove statistically that clomipramine possesses a significantly greater efficacy compared to that of acetylsalicylic acid . By taking into account recent anatomical , biochemical and pharmacological studies , it can be concluded that clomipramine probably has-in addition to the action on peripheral receptors-a direct effect upon pain modulation systems . It seems possible that clomipramine activates serotonin-containing neurons of the endorphin-mediated analgesia system that control pain transmission in the CNS Background : Neuropathic pain remains one of the most challenging pain syndromes ; under‐diagnosed , poorly managed and associated with significant co‐morbidity . With st and ard therapeutic treatments , responders rarely exceed 50 % pain relief and the majority suffer from residual pain . Titration to optimum dose is often limited by dose‐related adverse events |
11,819 | 31,679,970 | Enzalutamide appeared to have better OS compared with docetaxel in men with low-volume disease , but there was no difference in other comparisons .
Combination therapy with any of docetaxel , abiraterone acetate , enzalutamide , or apalutamide provides a significant OS benefit when compared with ADT alone .
We did not identify significant differences in OS between different combination therapies . | CONTEXT There have been substantial changes in the management of men with metastatic hormone-sensitive prostate cancer ( mHSPC ) over the past 5 yr , with upfront combination therapies replacing and rogen-deprivation therapy ( ADT ) alone .
A range of therapies have entered the space with no clear answer regarding their comparative efficacy .
OBJECTIVE To perform a systematic review and network meta- analysis to characterise the comparative efficacy of combination approaches in men with mHSPC . | Purpose Chemohormonal therapy with docetaxel and and rogen deprivation therapy ( ADT+D ) for metastatic hormone-sensitive prostate cancer improves overall survival as compared with and rogen deprivation therapy ( ADT ) alone . We compared the quality of life ( QOL ) between patients with metastatic hormone-sensitive prostate cancer who were treated with ADT+D and those who were treated with ADT alone . Methods Men were r and omly assigned to ADT+ D ( six cycles ) or to ADT alone . QOL was assessed by Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) , FACT-Taxane , Functional Assessment of Chronic Illness Therapy-Fatigue , and the Brief Pain Inventory at baseline and at 3 , 6 , 9 , and 12 months . The Wilcoxon signed rank test was used to examine changes over time . Mixed-effect models compared the QOL between arms at each time point . Results Seven hundred ninety men were r and omly assigned ( ADT+D [ n = 397 ] and ADT [ n = 393 ] ) and completed FACT-P ( 90 % at baseline , 86 % at 3 months , 83 % at 6 months , 78 % at 9 months , and 77 % at 12 months ) . ADT+D patients reported a statistically significant decline in FACT-P at 3 months ( P < .001 ) but FACT-P did not differ significantly between baseline and 12 months ( P = .38 ) . ADT+D FACT-P scores were significantly lower at 3 months ( P = .02 ) but significantly higher at 12 months ( P = .04 ) when compared with ADT FACT-P scores . Differences did not exceed the minimal clinical ly important difference at any time point . ADT+D patients reported significantly lower Functional Assessment of Chronic Illness Therapy-Fatigue scores at 3 months than did ADT patients ( P < .001 ) . Over time , both arms reported significantly poorer FACT-Taxane scores ( P < .001 ) when compared with baseline . Brief Pain Inventory scores were similar between arms . Conclusion Although ADT+D was associated with statistically worse QOL at 3 months , QOL was better at 12 months for ADT+D patients than for ADT patients . Both arms reported a similar minimally changed QOL over time , suggesting that ADT+D is not associated with a greater long-term negative impact on QOL Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Summary Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy . We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade 3–5 adverse events were reported for 399 ( 32 % ) patients receiving SOC , 197 ( 32 % ) receiving SOC + ZA , 288 ( 52 % ) receiving SOC + Doc , and 269 ( 52 % ) receiving SOC + ZA + Doc . Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of st and ard of care for this population . Docetaxel chemotherapy , given at the time of long-term hormone therapy initiation , showed evidence of improved survival accompanied by an increase in adverse events . Docetaxel treatment should become part of st and ard of care for adequately fit men commencing long-term hormone therapy . Funding Cancer Research UK , Medical Research Council , Novartis , Sanofi-Aventis , Pfizer , Janssen , Astellas , NIHR Clinical Research Network , Swiss Group for Clinical Cancer Research Background Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer . We assessed the effect of this combination in men starting long‐term and rogen‐deprivation therapy ( ADT ) , using a multigroup , multistage trial design . Methods We r and omly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate ( 1000 mg daily ) and prednisolone ( 5 mg daily ) ( combination therapy ) . Local radiotherapy was m and ated for patients with node‐negative , nonmetastatic disease and encouraged for those with positive nodes . For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease , treatment continued until radiologic , clinical , or prostate‐specific antigen ( PSA ) progression ; otherwise , treatment was to continue for 2 years or until any type of progression , whichever came first . The primary outcome measure was overall survival . The intermediate primary outcome was failure‐free survival ( treatment failure was defined as radiologic , clinical , or PSA progression or death from prostate cancer ) . Results A total of 1917 patients underwent r and omization from November 2011 through January 2014 . The median age was 67 years , and the median PSA level was 53 ng per milliliter . A total of 52 % of the patients had metastatic disease , 20 % had node‐positive or node‐indeterminate nonmetastatic disease , and 28 % had node‐negative , nonmetastatic disease ; 95 % had newly diagnosed disease . The median follow‐up was 40 months . There were 184 deaths in the combination group as compared with 262 in the ADT‐alone group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.52 to 0.76 ; P<0.001 ) ; the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease . There were 248 treatment‐failure events in the combination group as compared with 535 in the ADT‐alone group ( hazard ratio , 0.29 ; 95 % CI , 0.25 to 0.34 ; P<0.001 ) ; the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease . Grade 3 to 5 adverse events occurred in 47 % of the patients in the combination group ( with nine grade 5 events ) and in 33 % of the patients in the ADT‐alone group ( with three grade 5 events ) . Conclusions Among men with locally advanced or metastatic prostate cancer , ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure‐free survival than ADT alone . ( Funded by Cancer Research U.K. and others ; STAMPEDE Clinical Trials.gov number , NCT00268476 , and Current Controlled Trials number , IS RCT N78818544 . |
11,820 | 32,030,562 | CRP can be used as a biomarker to predict the development of HFpEF and long-term clinical outcomes in HFpEF patients , in turn justifying its use as a simple , accessible parameter to guide clinical management in this patient population . | Heart failure ( HF ) is a major epidemic with rising morbidity and mortality rates that encumber global healthcare systems .
While some studies have demonstrated the value of CRP in predicting ( i ) the development of HFpEF and ( ii ) long-term clinical outcomes in HFpEF patients , others have shown no such correlation .
As a result , we conducted the following systematic review and meta- analysis to assess both the diagnostic and prognostic role of CRP in HFpEF . | Background — Data supporting the prognostic significance of high-sensitivity C-reactive protein ( hs-CRP ) are derived largely from individuals with no overt coronary artery disease or from patients with acute coronary syndromes . In contrast , the ability of hs-CRP to predict outcomes in patients with stable coronary artery disease and the prognostic significance of the Centers for Disease Control/American Heart Association hs-CRP cut points in such a population remain relatively unexplored . Methods and Results — We measured hs-CRP in 3771 patients with stable coronary artery disease from the Prevention of Events With Angiotensin-Converting Enzyme Inhibition ( PEACE ) trial , a r and omized placebo-controlled trial of the angiotensin-converting enzyme inhibitor tr and olapril . Patients were followed up for a median of 4.8 years for cardiovascular death , myocardial infa rct ion , or stroke , as well as new heart failure and diabetes . After adjustment for baseline characteristics and treatments , higher hs-CRP levels , even > 1 mg/L , were associated with a significantly greater risk of cardiovascular death , myocardial infa rct ion , or stroke ( hs-CRP 1 to 3 mg/L : adjusted hazard ratio , 1.39 ; 95 % CI , 1.06 to 1.81 ; P=0.016 ; hs-CRP > 3 mg/L : adjusted hazard ratio , 1.52 ; 95 % CI , 1.15 to 2.02 ; P=0.003 ) . Similarly , elevated hs-CRP levels were an independent predictor of new heart failure ( adjusted P<0.001 for trend ) and new diabetes ( adjusted P<0.001 for trend ) . There were no significant interactions between hs-CRP levels and the effects of tr and olapril on any of the above outcomes . Conclusions — In stable coronary artery disease , an elevated hs-CRP level , even > 1 mg/L , is a significant predictor of adverse cardiovascular events independently of baseline characteristics and treatments . An elevated hs-CRP does not appear to identify patients with stable coronary artery disease and preserved ejection fraction who derive particular benefit from angiotensin-converting enzyme inhibition BACKGROUND C-reactive protein ( CRP ) is a sensitive marker of inflammation , and elevated levels have been associated with future risk of myocardial infa rct ion ( MI ) . However , whether measurement of CRP adds to the predictive value of total cholesterol ( TC ) and HDL cholesterol ( HDL-C ) in determining risk is uncertain . METHODS AND RESULTS Among 14916 apparently healthy men participating in the Physicians ' Health Study , baseline levels of CRP , TC , and HDL-C were measured among 245 study subjects who subsequently developed a first MI ( cases ) and among 372 subjects who remained free of cardiovascular disease during an average follow-up period of 9 years ( controls ) . In univariate analyses , high baseline levels of CRP , TC , and TC : HDL-C ratio were each associated with significantly increased risks of future MI ( all P values < 0.001 ) . In multivariate analyses , models incorporating CRP and lipid parameters provided a significantly better method to predict risk than did models using lipids alone ( all likelihood ratio test P values < 0.003 ) . For example , relative risks of future MI among those with high levels of both CRP and TC ( RR=5.0 , P=0.0001 ) were greater than the product of the individual risks associated with isolated elevations of either CRP ( RR=1.5 ) or TC ( RR=2.3 ) . In stratified analyses , baseline CRP level was predictive of risk for those with low as well as high levels of TC and the TC : HDL-C ratio . These findings were virtually identical in analyses limited to nonsmokers and after control for other cardiovascular risk factors . CONCLUSIONS In prospect i ve data from a large cohort of apparently healthy men , baseline CRP level added to the predictive value of lipid parameters in determining risk of first MI Background Pentraxin 3 ( PTX3 ) is a novel inflammatory marker produced by various cell types including those of the vasculature and the heart . The relationship between inflammatory markers and prognosis of patients with heart failure with normal ejection fraction ( HFNEF ) remains unknown . We investigated whether plasma PTX3 levels can predict future cardiovascular events in patients with HFNEF . Methods and Results Plasma PTX3 , high‐sensitivity C‐reactive protein , and B‐type natriuretic peptide levels were measured prospect ively in 360 stable patients with HFNEF . The subsequent incidence of cardiovascular events , including cardiovascular death , nonfatal myocardial infa rct ion ( MI ) , unstable angina pectoris , nonfatal ischemic stroke , hospitalization for heart failure decompensation , and coronary revascularization , was determined . During a mean 30‐month follow‐up , 106 patients experienced cardiovascular events . These events were more frequent in patients with high plasma PTX3 levels ( > 3.0 ng/mL ) than low levels ( ≤3.0 ng/mL ) . Multivariable Cox hazard analysis showed that PTX3 ( hazard ratio : 1.16 ; 95 % CI : 1.05 to 1.27 ; P<0.01 ) and B‐type natriuretic peptide ( hazard ratio : 1.08 ; 95 % CI : 1.03 to 1.14 ; P<0.001 ) , but not high‐sensitivity C‐reactive protein levels , were significant predictors of future cardiovascular events . Multivariable Cox analysis with the forced inclusion model , including 5 previously identified prognostic factors , found that PTX3 was a significant predictor of cardiovascular events ( hazard ratio : 1.16 ; 95 % CI : 1.06 to 1.27 ; P<0.01 ) . The C‐statistics for cardiovascular events substantially increased from 0.617 to 0.683 when PTX3 was added to the 5 previously identified prognostic factors . Conclusions High plasma PTX3 levels , but not other inflammatory markers , are correlated with future cardiovascular events in patients with HFNEF . PTX3 may be a useful biomarker for assessment of risk stratification in HFNEF . Clinical Trial Registration URL : http://www.umin.ac.jp ; Unique identifier : UMIN000002170 Sensitive cardiac troponin I ( cTnI ) predicts all-cause and cardiovascular mortality in various clinical setting s. However , its clinical significance in hemodialysis ( HD ) patients with preserved left ventricular ejection fraction ( LVEF ) has not been fully eluci date d. This study investigated the association of cTnI with LV morphology and function , and its long-term outcome in HD patients with preserved LVEF . This prospect i ve study consists of 96 HD patients with preserved LVEF ( 69 ± 8 years and 63 % male ) who underwent two-dimensional echocardiographic examination and biomarker tests including cTnI , brain natriuretic peptide , and high-sensitive C-reactive protein . The primary endpoint was all-cause death and secondary endpoint was cardiovascular death . Factors independently associated with cTnI were systolic blood pressure ( β = − 0.239 , p = 0.011 ) , heart rate ( β = 0.216 , p = 0.021 ) , LV mass index ( β = 0.231 , p = 0.020 ) , and E to e ’ ratio ( β = 0.237 , p = 0.016 ) . During a mean follow-up of 3.6 years , primary and secondary endpoints were observed in 23 ( 24 % ) and 18 ( 19 % ) patients , respectively . In the multivariate Cox proportional hazard analysis , the upper cTnI tertile has significantly increased risk of all-cause mortality [ hazard ratio ( HR ) , 2.69 ; 95 % confidence interval ( CI ) , 1.139–6.386 ; p = 0.024 ] and that of cardiovascular death ( HR , 4.56 ; 95 % CI 2.021–16.968 ; p = 0.006 ) independent of echocardiographic measures and other serum biomarkers . In HD patients with preserved LVEF , serum cTnI levels were significantly associated with diastolic function and risk of mortality independent of echocardiographic variables and other biomarkers Aims The prognostic role of high-sensitivity C-reactive protein ( hsCRP ) in acute heart failure is less well established than for chronic heart failure and the impact of its variation is unknown . We studied the impact of hsCRP variation in acute heart failure and whether it differed according to left ventricular function . Methods We analyzed patients prospect ively included in an acute heart failure registry . Admission and discharge hsCRP were evaluated as part of the registry 's protocol and its relative variation ( & Dgr;hsCRP ) was assessed . & Dgr;hsCRP during hospitalization = [ ( admission hsCRP – discharge hsCRP)/admission hsCRP ] × 100 . Endpoint : all-cause death ; follow-up : 3 years . A multivariate Cox-regression model was used to assess the prognostic value of & Dgr;hsCRP ( continuous and categorical variable : cut-off 40 % decrease ) ; analysis was stratified according to ventricular function . Results We studied 439 patients : mean age 75 years , 50.1 % men and 69.2 % had heart failure with reduced ejection fraction ( HFrEF ) . Median discharge hsCRP was 12.4 mg/l and median & Dgr;hsCRP was ∼40 % . During follow-up 247 patients ( 56.3 % ) died : 73 ( 54.1 % ) heart failure with preserved ejection fraction ( HFpEF ) patients and 174 ( 57.2 % ) HFrEF patients . The multivariate-adjusted hazard ratio of 3-year mortality in HFpEF patients with hsCRP decrease of at least 40 % during hospitalization was 0.56 ( 95 % CI 0.32–0.99 ) . A decrease of at least 40 % in hsCRP was not mortality-associated in HFrEF patients . There was interaction between & Dgr;hsCRP and left ventricular ejection fraction . Conclusion A decrease of at least 40 % in hsCRP in acute heart failure was associated with a 44 % decrease in 3-year death risk in HFpEF patients . No association between & Dgr;hsCRP and prognosis existed in HFrEF patients . Inflammation appears to play a different role according to left ventricular function BACKGROUND Soluble ST2 ( sST2 ) is a marker of inflammation and fibrosis , which is a significant predictor of prognosis of heart failure ( HF ) , independent of brain natriuretic peptide ( BNP ) . This study aim ed to clarify how sST2 associates with clinical outcome through investigations of clinical correlates and mode of death in patients with heart failure with preserved ejection fraction ( HFpEF ) . METHODS A total 191 patients with acute decompensated HF and EF ≥50 % were prospect ively enrolled . Echocardiographic and laboratory data including sST2 were obtained in pre-discharge stable condition . RESULTS Serum sST2 level showed significant positive correlations with C-reactive protein and pentraxin3 levels , and negative correlations with body mass index , albumin , and hemoglobin . Serum sST2 level was significantly higher in patients with all-cause death and non-cardiovascular ( CV ) death compared to those without events , whereas there was no significant difference in sST2 level between patients with and without CV death . On the other h and , BNP level was significantly higher in patients with all-cause death and CV death compared to those without events . Cox regression analyses adjusted for age and sex revealed that sST2 was a significant predictor of non-CV death , whereas BNP was a significant predictor of CV death . CONCLUSIONS Serum sST2 level was associated with non-CV death showing significant correlations with systemic factors including malnutrition and inflammation , while BNP was associated with CV death |
11,821 | 24,044,954 | RESULTS The current evidence provides moderate support for the inclusion of joint mobilizations in the treatment of lateral epicondylalgia ( LE ) .
Other described techniques include those known as Kaltenborn , Cyriax physical therapy , and Maitl and , but the evidence for these techniques is limited .
There is also limited evidence for the joint mobilizations in the treatment of wrist and h and conditions .
The current literature offers limited support for joint mobilizations of the wrist and h and , and moderate support for joint mobilizations of the elbow for LE .
There is moderate support for mobilization with movement .
| INTRODUCTION Joint mobilizations are used as an intervention for improving range of motion , decreasing pain and ultimately improving function in patients with a wide variety of upper extremity diagnoses .
However , there are only a limited number of studies describing this treatment for conditions affecting the elbow , wrist , and h and .
Furthermore , it is unclear as to the most effective joint mobilization technique utilized and the most beneficial functional outcomes gained .
PURPOSE Examine the current evidence describing joint mobilizations for treatment of conditions of the elbow , wrist and h and , and offer informative practical clinical guidance . | Clinical observations have suggested a relationship between shoulder range of movement ( ROM ) and lateral epicondylalgia . This study reports the effect of a single intervention of a mobilization with movement ( MWM ) applied to the elbow , on shoulder rotation ROM in subjects with lateral epicondylalgia . Twenty-three subjects with lateral epicondylalgia were included . In a one-group pretest-post-test design , ROM of shoulder internal and external rotation were measured by goniometer before and after the application of the MWM , of both the unaffected and the affected limbs . Significant differences in pre-intervention external rotation ROM were found between unaffected and affected shoulders of subjects with lateral epicondylalgia , but no significant difference remained post-intervention . It may be concluded that restriction of shoulder rotation ROM is present in patients with lateral epicondylalgia , probably due to a facilitated level of shoulder rotator muscle tone . Shoulder internal and external rotation ROM increases significantly following MWM to the elbow , in subjects with unilateral lateral epicondylalgia . Surprisingly , these ROM increases are also apparent on the ' unaffected ' limb . These findings suggest that the MWM causes a neurophysiologically mediated decrease in resting muscle tone The treatment of lateral epicondylalgia , a widely-used model of musculoskeletal pain in the evaluation of many physical therapy treatments , remains somewhat of an enigma . The protagonists of a new treatment technique for lateral epicondylalgia report that it produces substantial and rapid pain relief , despite a lack of experimental evidence . A r and omized , double blind , placebo-controlled repeated- measures study evaluated the initial effect of this new treatment in 24 patients with unilateral , chronic lateral epicondylalgia . Pain-free grip strength was assessed as an outcome measure before , during and after the application of the treatment , placebo and control conditions . Pressure-pain thresholds were also measured before and after the application of treatment , placebo and control conditions . The results demonstrated a significant and substantial increase in pain-free grip strength of 58 % ( of the order of 60 N ) during treatment but not during placebo and control . In contrast , the 10 % change in pressure-pain threshold after treatment , although significantly greater than placebo and control , was substantially smaller than the change demonstrated for pain-free grip strength . This effect was only present in the affected limb . The selective and specific effect of this treatment technique provides a valuable insight into the physical modulation of musculoskeletal pain and requires further investigation BACKGROUND AND PURPOSE Lateral epicondylitis ( " tennis elbow " ) is a common entity . Several nonoperative interventions , with varying success rates , have been described . The aim of this study was to compare the effectiveness of 2 protocol s for the management of lateral epicondylitis : ( 1 ) manipulation of the wrist and ( 2 ) ultrasound , friction massage , and muscle stretching and strengthening exercises . SUBJECTS AND METHODS Thirty-one subjects with a history and examination results consistent with lateral epicondylitis participated in the study . The subjects were r and omly assigned to either a group that received manipulation of the wrist ( group 1 ) or a group that received ultrasound , friction massage , and muscle stretching and strengthening exercises ( group 2 ) . Three subjects were lost to follow-up , leaving 28 subjects for analysis . Follow-up was at 3 and 6 weeks . The primary outcome measure was a global measure of improvement , as assessed on a 6-point scale . Analysis was performed using independent t tests , Mann-Whitney U tests , and Fisher exact tests . RESULTS Differences were found for 2 outcome measures : success rate at 3 weeks and decrease in pain at 6 weeks . Both findings indicated manipulation was more effective than the other protocol . After 3 weeks of intervention , the success rate in group 1 was 62 % , as compared with 20 % in group 2 . After 6 weeks of intervention , improvement in pain as measured on an 11-point numeric scale was 5.2 ( SD=2.4 ) in group 1 , as compared with 3.2 ( SD=2.1 ) in group 2 . DISCUSSION AND CONCLUSION Manipulation of the wrist appeared to be more effective than ultrasound , friction massage , and muscle stretching and strengthening exercises for the management of lateral epicondylitis when there was a short-term follow-up . However , replication of our results is needed in a large-scale r and omized clinical trial with a control group and a longer-term follow-up Abstract Objective To investigate the efficacy of physiotherapy compared with a wait and see approach or corticosteroid injections over 52 weeks in tennis elbow . Design Single blind r and omised controlled trial . Setting Community setting , Brisbane , Australia . Participants 198 participants aged 18 to 65 years with a clinical diagnosis of tennis elbow of a minimum six weeks ' duration , who had not received any other active treatment by a health practitioner in the previous six months . Interventions Eight sessions of physiotherapy ; corticosteroid injections ; or wait and see . Main outcome measures Global improvement , grip force , and assessor 's rating of severity measured at baseline , six weeks , and 52 weeks . Results Corticosteroid injection showed significantly better effects at six weeks but with high recurrence rates thereafter ( 47/65 of successes subsequently regressed ) and significantly poorer outcomes in the long term compared with physiotherapy . Physiotherapy was superior to wait and see in the short term ; no difference was seen at 52 weeks , when most participants in both groups reported a successful outcome . Participants who had physiotherapy sought less additional treatment , such as non-steroidal anti-inflammatory drugs , than did participants who had wait and see or injections . Conclusion Physiotherapy combining elbow manipulation and exercise has a superior benefit to wait and see in the first six weeks and to corticosteroid injections after six weeks , providing a reasonable alternative to injections in the mid to long term . The significant short term benefits of corticosteroid injection are paradoxically reversed after six weeks , with high recurrence rates , implying that this treatment should be used with caution in the management of tennis elbow Abstract Cyriax and Cyriax advocated the use of deep transverse friction massage in combination with Mill 's manipulation in treating lateral epicondylalgia . Evidence comparing this approach with other physical therapies is lacking . The purpose of this r and omized clinical trial was to compare the effectiveness of deep transverse friction massage with Mill 's manipulation versus phonophoresis with supervised exercise in managing lateral epicondylalgia . Sixty patients age 30 - 60 , presenting with the teno-periosteal variety of lateral epicondylalgia with symptom duration greater than one month , were r and omized into two groups . The control group received phonophoresis with diclofenac gel over the area of the lateral epicondyle for 5 minutes combined with supervised exercise . The experimental group received 10 minutes of deep transverse friction massage followed by a single application of Mill 's manipulation . Both groups received treatment 3 times per week for 4 weeks . Outcomes of interest included pain via visual analog scale ( VAS ) , pain-free grip strength , and functional status measured with the Tennis Elbow Function Scale . Data were analyzed using a one-way ANOVA . Whereas both groups improved significantly from the initiation of treatment , a between-group comparison revealed significantly greater ( p<0.05 ) improvements regarding pain , pain-free grip , and functional status for the experimental group compared to the control group . The results of this study demonstrate that Cyriax physiotherapy is a superior treatment approach compared to phonophoresis and exercise in managing lateral epicondylalgia Objective : To compare the effectiveness of Cyriax physiotherapy , a supervised exercise programme , and polarized polychromatic non-coherent light ( Bioptron light ) in the treatment of lateral epicondylitis . Design : Controlled clinical trial . Setting : Rheumatology and rehabilitation centre . Subjects : This study was carried out with 75 patients who had lateral epicondylitis . They were allocated to three groups by sequential allocation . Interventions : Group A ( n=25 ) was treated with Cyriax physiotherapy . A supervised exercise programme was given to group B ( n=25 ) . Group C ( n=25 ) received polarized polychromatic non-coherent light ( Bioptron light ) . All patients received three treatments per week for four weeks . Outcomes : Pain was evaluated using a visual analogue scale and function using a visual analogue scale and pain-free grip strength at the end of the four-week course of treatment ( week 4 ) , one month ( week 8) , three months ( week 16 ) and six months ( week 28 ) after the end of treatment . Results : The supervised exercise programme produced the largest effect in the reduction of pain and in the improvement of function at the end of the treatment ( P<0.05 ) and at any of the follow-up time points ( P<0.05 ) . Conclusion : The supervised exercise programme should be the first treatment option for therapists when they manage lateral epicondylitis patients . If this is not possible , Cyriax physiotherapy and polarized polychromatic non-coherent light ( Bioptron light ) may be suitable This preliminary study indicates the proportion of patients with lateral epicondylalgia that demonstrate a favourable initial response to a manual therapy technique - the mobilization with movement ( MWM ) for tennis elbow . Twenty-five subjects with lateral epicondylalgia participated . In a one-group pretest - post-test design , we measured ( 1 ) pain with active motion , ( 2 ) pain-free grip strength and , ( 3 ) maximum grip strength before and after a single intervention of MWM . Results of the study indicate that MWM was effective in allowing 92 % of subjects to perform previously painful movements pain-free , and improving grip strength immediately afterwards . Significant differences were found between the grip strength of the affected and unaffected limbs prior to the intervention . Both pain-free grip strength and maximum grip strength of the affected limb increased significantly following the intervention . Pain-free grip strength increased by a greater magnitude than maximum grip strength . It can be concluded that MWM is a promising intervention modality for the treatment of patients with Lateral Epicondylalgia . Pain-free grip strength is a more responsive measure of outcome than maximum grip strength for patients with Lateral Epicondylalgia . Further research is warranted to investigate the long-term effectiveness of MWM in the treatment of impairment and disability result ing from Lateral Epicondylalgia BACKGROUND AND PURPOSE Mulligan has proposed the use of mobilization with movement for lateral epicondylalgia . In this study , mobilization with movement for the elbow was examined to determine whether this intervention was capable of inducing physiological effects similar to those reported for some forms of spinal manipulation . PARTICIPANTS Seven women and 17 men ( mean age=48.5 years , SD=7.2 ) with chronic lateral epicondylalgia participated in the study . METHODS A placebo , control , repeated- measures study was conducted to evaluate whether mobilization with movement at the elbow produced concurrent hypoalgesia and sympathoexcitation . RESULTS The treatment demonstrated an initial hypoalgesic effect and concurrent sympathoexcitation . Improvements in pain result ed in increased pain-free grip force and pressure pain thresholds . Sympathoexcitation was indicated by changes in heart rate , blood pressure , and cutaneous sudomotor and vasomotor function . DISCUSSION AND CONCLUSION This study showed that a mobilization with movement treatment technique exerted a physiological effect similar to that reported for some spinal manipulations We performed a prospect i ve , r and omised trial on 106 patients to compare the effects of local corticosteroid injections with physiotherapy as advocated by Cyriax in the treatment of tennis elbow . The main outcome measures were the severity of pain , pain provoked by resisted dorsiflexion of the wrist , and patient satisfaction . At six weeks 22 of 53 patients in the injection group were free from pain compared with only three in the physiotherapy group . In the corticosteroid-treated group 26 patients had no pain on resisted dorsiflexion of the wrist compared with only three in the physiotherapy group . Thirty-five patients who had injections and 14 who had physiotherapy were satisfied with the outcome of treatment at six weeks . At the final assessment there were 18 excellent and 18 good results in the corticosteroid group and one excellent and 12 good results in the physiotherapy group . There was a significant increase in grip strength in both groups but those with injections had a significantly better result . After one year there were no significant differences between the two groups . Half of the patients , however , had received only the initial treatment , 20 % had had combined therapy and 30 % had had surgery . We conclude that at six weeks , treatment with corticosteroid injections was more effective than Cyriax physiotherapy and we recommend it because of its rapid action , reduction of pain and absence of side-effects Carpal tunnel syndrome is the most common peripheral entrapment neuropathy . There is little literature available that addresses the management of this condition , which may partly explain why physiotherapy is often overlooked as a treatment approach in its management . This study investigated the effects of two manual therapy techniques in the treatment of patients experiencing carpal tunnel syndrome . An experimental different subject design compared three groups of subjects in three different conditions ( two treatment interventions and one control group ) . Each group consisted of seven patients . The objectives of the study were : ( 1 ) to investigate differences between treated and untreated groups ; ( 2 ) to investigate differences in the effectiveness of treatment I ( median nerve mobilization ) compared with treatment II ( carpal bone mobilization ) . Measurements were taken applying several measurement tools , including active range of wrist movement ( ROM flexion and extension ) , upper limb tension test with a median nerve bias ( ULTT2a ) , three different scales to evaluate pain perception and function , and lastly numbers of patients continuing to surgery in each group were compared . In visual terms a clear trend was demonstrated between subjects who received treatment compared to those who were not treated , in particular the descriptive analysis of results for ULTT2a and numbers of patients continuing to surgery . When analysed statistically , less could be concluded . Only scores on a Pain Relief Scale ( P<0.01 ) demonstrated highly significant differences between the three groups when analyzed using Kruskal-Wallis Test . In exploring the results of the two intervention groups , no statistically significant difference in effectiveness of treatment was demonstrated between carpal bone mobilization and median nerve mobilization This study investigated whether passive mobilisation added to the effectiveness of an advice and exercise regimen for patients following distal radial fractures . Thirty-nine patients were r and omly allocated to one of two groups . Patients in the first group received advice and exercises ; patients in the second group also received a six-week course of passive mobilisation . Range of movement , function and pain were measured pre-treatment , and three and six weeks later . Significant improvements were found over time for all outcome measures . No significant differences were detected between groups for any outcomes except flexion , where the difference was not clinical ly important . Routine passive mobilisation does not appear to incur additional benefit over an advice and exercise regimen for this patient group BACKGROUND Recent research has shown that Mulligan 's Mobilization With Movement treatment technique for the elbow ( MWM ) , a peripheral joint mobilization technique , produces a substantial and immediate pain relief in chronic lateral epicondylalgia ( 48 % increase in pain-free grip strength).([1 ] ) This hypoalgesic effect is far greater than that previously reported with spinal manual therapy treatments , prompting speculation that peripheral manual therapy treatments may differ in mechanism of action to spinal manual therapy techniques . Naloxone antagonism and tolerance studies , which employ widely accepted tests for the identification of endogenous opioid-mediated pain control mechanisms , have shown that spinal manual therapy-induced hypoalgesia does not involve an opioid mechanism . OBJECTIVE The aim of this study was to evaluate the effect of naloxone administration on the hypoalgesic effect of MWM . METHODS A r and omized , controlled trial evaluated the effect of administering naloxone , saline , or no-substance control injection on the MWM-induced hypoalgesia in 18 participants with lateral epicondylalgia . Pain-free grip strength , pressure pain threshold , thermal pain threshold , and upper limb neural tissue provocation test 2b were the outcome measures . RESULTS The results demonstrated that the initial hypoalgesic effect of the MWM was not antagonized by naloxone , suggesting a nonopioid mechanism of action . CONCLUSIONS The studied peripheral mobilization treatment technique appears to have a similar effect profile to previously studied spinal manual therapy techniques , suggesting a nonopioid-mediated hypoalgesia following manual therapy Abstract Lateral epicondylalgia is a commonly encountered musculoskeletal complaint . Currently , there is no agreement regarding the exact underlying pathoanatomical cause or the most effective management strategy . Various forms of joint manipulation have been recommended as treatment . The purpose of this study was to systematic ally review available literature regarding the effectiveness of manipulation in treating lateral epicondylalgia . A comprehensive search of Medline , CINAHL , Health Source , SPORTD iscus , and the Physiotherapy Evidence Data base ending in November 2007 was conducted . Thirteen studies , both r and omized and non-r and omized clinical trials , met inclusion criteria . Articles were assessed for quality by one review er using the 10-point PEDro scale . Quality scores ranged from 1 - 8 with a mean score of 5.15 ± 1.85 . This score represented fair quality overall ; however , trends indicated the presence of consistent method ological flaws . Specifically , no study achieved successful blinding of the patient or treating therapist , and less than 50 % used a blinded outcome assessor . Additionally , studies varied significantly in terms of outcome measures , follow-up , and comparison treatments , thus making comparing results across studies difficult . Results of this review support the use of Mulligan 's mobilization with movement in providing immediate , short- , and long-term benefits . In addition , positive results were demonstrated with manipulative therapy directed at the cervical spine , although data regarding long-term effects were limited . Currently , limited evidence exists to support a synthesis of any particular technique whether directed at the elbow or cervical spine . Overall , this review identified the need for further high- quality studies using larger sample sizes , valid functional outcome measures , and longer follow-up periods |
11,822 | 28,983,792 | Overall , EOP individuals showed significant higher risk of poor outcome followed by AO individuals , CL individuals , and finally participants in the low group .
All conduct problems trajectories showed higher risk of poor psychosocial outcomes compared to the low group , but the magnitude of risk differed across trajectories , with a general trend for the EOP to perform significantly worse , followed by the AO and CL . | There is increasing evidence that youth who follow the early onset persistent ( EOP ) , adolescent-onset ( AO ) and childhood-limited ( CL ) trajectories of conduct problems show varying patterns of health , mental health , educational , and social outcomes in adulthood .
However , there has been no systematic review and meta- analysis on outcomes associated with different conduct problems trajectories . | Relationships among risky sexual behaviors , other problem behaviors , and the family and peer context were examined for two sample s of adolescents . Many adolescents reported behaviors ( e.g. , promiscuity or nonuse of condoms ) which risked HIV or other sexually transmitted disease infection . Such risky behaviors were significantly intercorrelated . Consistent condom use was rare among those whose behavior otherwise entailed the greatest risk of infection . In both sample s , an index of high-risk sexual behavior was significantly related to antisocial behavior , cigarette smoking , and illicit drug or alcohol use . Social context variables , including family structure , parenting practice s , and friends ' engagement in problem behaviors , were associated with high-risk sexual behavior . Finally , for sexually active adolescents , problem behaviors and social context variables were predictive of nonuse of condoms . Results were consistent across the two studies and regression weights held up well under cross-validation Little is known about early life diet as a risk factor for early-onset persistent conduct problems ( EOP CP ) . To investigate this , we used data from the Avon Longitudinal Study of Parents and Children , a UK-based prospect i ve epidemiological birth cohort . 5727 mother-child pairs ( 49.9 % boys ) monitored since pregnancy ( delivery date between 1 April , 1991 and 31 December , 1992 ) reported intake of fish and processed foods at 32 weeks gestation and , for the child , at 3 years ; EOP ( n = 666 ) and Low conduct problem ( Low CP , n = 5061 ) trajectories were measured from 4 to 13 years ; hyperactivity and emotional difficulties were assessed in childhood ( 4–10 years ) and early adolescence ( 12–13 years ) , in addition to potential confounding factors ( family adversity , birth complications , income ) . Compared to Low CP , mothers of EOP children consumed less fish ( p < 0.01 ) and more processed food ( p < 0.05 ) prenatally , while EOP children consumed more processed food at 3 years ( p < 0.05 ) . For EOP , but not Low CP children , consuming less than two servings/week of fish ( vs. two or more servings/week , p < 0.05 ) , and one or more servings/day of processed food ( vs. less than one serving/day , p < 0.01 ) , was associated with higher emotional difficulties in early adolescence . Conclusions : Findings suggest that prenatal and postnatal diets high in processed food , and low in fish , associate with an EOP CP trajectory and co-occurring difficulties in early adolescence . As small effect size differences were found , further studies are needed to investigate the long-term impact of early unhealthy diet Largely because of the influence of Moffitt 's useful distinction between adolescence-limited and life-course persistent antisocial behavior , it has become increasingly common to view problem behavior that makes its first appearance in adolescence as developmentally normative . This study prospect ively examined the lives of individuals in the NICHD Study of Early Child Care and Youth Development whose patterns of antisocial behavior varied with respect to age of onset and stability from kindergarten through age 15 . Consistent with past research , early-onset , persistently deviant youth experienced more context ual adversity and evinced higher levels of intraindividual disadvantages than their peers from infancy through midadolescence . However , relative to youth who never showed significantly elevated antisocial behavior through age 15 , children who showed antisocial behavior primarily in adolescence also were more disadvantaged from infancy forward , as were youth who only demonstrated significant externalizing problems in childhood . Findings generally replicated across sex and did not vary as a function of whether antisocial behavior groups were defined using T-scores normed within sex or identified using an empirically driven grouping method applied to raw data Moffitt 's theory regarding two types of adolescent antisocial behavior was investigated using a prospect i ve , longitudinal study of normal and abnormal development in a primarily low socioeconomic status , ethnically diverse sample . Results supported the presence of an early-onset/persistent ( EOP ) group and an adolescence-onset ( AO ) group . Groups were most reliably and significantly distinguished by indices of socioemotional history within the first 3 years , but no significant differences were found on early measures of temperament or neuropsychological functioning . EOPs scored significantly lower than other groups on measures of neuropsychological functioning only during late childhood and adolescence , suggesting that the declines in verbal functioning that have been so reliably found in this and other sample s of early-starting antisocial adolescents are progressive and consequent to adverse experience . In adolescence , AOs were significantly more likely to report high levels of internalizing symptoms and life stress , suggesting that AO antisocial behavior is not a benign phenomenon . Implication s of these findings for etiologic theories of adolescent antisocial behavior are discussed CONTEXT A cardinal feature of the DSM-IV diagnostic criteria for conduct disorder is the distinction between childhood- vs adolescent-onset subtypes . Whether such developmental subtypes exist in the population and have different prognoses should be rigorously tested to inform the DSM-V. OBJECTIVES To evaluate the epidemiological validity of childhood- vs adolescent-onset conduct problems in a prospect i ve birth cohort , and to assess whether life-course-persistent conduct problems are associated with a greater adult health burden . DESIGN , SETTING , AND PARTICIPANTS Our sample includes 526 male study members in the Dunedin Multidisciplinary Health and Development Study , a 1-year birth cohort ( April 1 , 1972 , through March 30 , 1973 ) . Developmental trajectories were defined using prospect i ve ratings of conduct problems at 7 , 9 , 11 , 13 , 15 , 18 , 21 , and 26 years of age . MAIN OUTCOME MEASURES Health burden was assessed as mental and physical health problems at 32 years of age measured via diagnostic interviews and physical examinations . RESULTS We identified the following 4 developmental subtypes of conduct problems through general growth mixture modeling : ( 1 ) childhood-onset/life-course-persistent , ( 2 ) adolescent onset , ( 3 ) childhood limited , and ( 4 ) low . At 32 years of age , study members with the life-course-persistent subtype experienced the worst health burden . To a lesser extent , those with the adolescent-onset subtype also experienced health problems . A childhood-limited subtype not specified by DSM-IV was revealed ; its adult health outcomes were within the range of the cohort norm . CONCLUSIONS Results support the epidemiological validity of the DSM-IV conduct disorder distinction based on age of onset but highlight the need to also consider long-term persistence to refine diagnosis . Preventing and treating conduct problems has the potential to reduce the adult health burden The prospect i ve relationships of conduct problems and peer coercion and deviancy training during kindergarten ( mean age = 5.3 years ) to overt and covert conduct problems in third-fourth grade were examined in a sample of 267 boys and girls . Coercion and deviancy training were distinct peer processes . Both were associated with earlier child conduct problems but were differentially associated with child impulsivity , verbal ability , anxiety , peer rejection , and deviant peer affiliation . Coercion by peers predicted overt conduct problems and peer deviancy training and the interaction of deviancy training and coercion predicted covert conduct problems in third-fourth grade . Peer deviancy training occurs in early childhood and may serve as an independent risk mechanism in addition to peer coercion for early-onset , persisting conduct problems 76 9 - 12 yr old aggressive males were assigned to anger-coping , goal - setting , anger-coping plus goal - setting , or no-treatment groups . Anger-coping interventions were school-based secondary prevention efforts that utilized social problem-solving and cognitive-behavioral techniques . At 1-mo followup , Ss who received anger-coping treatment had reduced their aggressive behavior in the classroom and at home and displayed improved self-esteem . ( 5 ref ) VioLit summary OBJECTIVE : The objective of this study by Lochman et al. was to observe the treatment and generalization effects of cognitive-behavioral and goal - setting interventions with aggressive boys . METHODOLOGY : An experimental design was used within a cognitive-behavioral framework , using a 2X2 factorial design to compare the separate and combined effects of a cognitive-behavioral condition , and a less intensive goal - setting condition . The 4 experimental cells were anger coping , goal setting , anger coping plus goal setting , and an untreated control cell . 76 boys , 9 - 12 years of age , from 8 elementary schools , were chosen via having the highest teacher ratings of aggression on the Missouri Children 's Behavior Checklist . These youth were assigned to cells on a rotating basis . FINDINGS / DISCUSSION : Children in the anger-coping cells displayed significant improvement over time versus subjects not in the anger-coping cells . Anger-coping plus goal - setting subjects significantly reduced their scores in comparison to subjects in the untreated control cell . The goal setting procedure tended to augment the treatment effects in the classroom . Despite indications in intervention , significant changes were not evident to teachers and peers , which may have been a result of limited treatment effects and rigid perceptions of the boys ' reputations . ( CSPV Abstract - Copyright © 1992 - 2007 by the Center for the Study and Prevention of Violence , Institute of Behavioral Science , Regents of the University of Colorado ) KW - Late Childhood KW - Child Anger KW - Child Aggression KW - Child Male KW - Child Treatment KW - Male Anger KW - Male Aggression KW - Aggression Treatment KW - Aggression Intervention KW - Cognitive Behavioral Treatment KW - Cognitive Behavioral Intervention KW - Anger Management KW - Goal Setting KW - Treatment Effectiveness Language : |
11,823 | 16,717,169 | The use of BNP tests to rule out CHF in primary care setting s could reduce dem and for echocardiography . | BACKGROUND Congestive heart failure ( CHF ) is a major public health problem .
The use of B-type natriuretic peptide ( BNP ) tests shows promising diagnostic accuracy .
Herein , we summarize the evidence on the accuracy of BNP tests in the diagnosis of CHF and compare the performance of rapid enzyme-linked immunosorbent assay ( ELISA ) and st and ard radioimmunosorbent assay ( RIA ) tests . | Abstract Objective : To investigate the performance of a novel assay for N-terminal pro-brain natriuretic peptide ( NT-proBNP ) in diagnosing heart failure in various r and omly selected general and high risk community population s. Design : Community cohort study ( sub study of the echocardiographic heart of Engl and screening study ) . Setting : Four r and omly selected general practice s in the West Midl and s of Engl and . Participants : 591 r and omly sample d patients over the age of 45 , stratified for age and socioeconomic status and falling into four cohorts ( general population , patients with an existing clinical label of heart failure , patients prescribed diuretics , and patients deemed at high risk of heart failure ) . Main outcome measure : Sensitivity , specificity , positive and negative predictive values , likelihood ratios , and area under receiver operating characteristic curve for NT-proBNP assay in the diagnosis of heart failure . Results : For NT-proBNP in the diagnosis of heart failure in the general population ( population screen ) , a level of > 36 pmol/l had a sensitivity of 100 % , a specificity of 70 % , a positive predictive value of 7 % , a negative predictive value of 100 % , and an area under the receiver operating characteristic curve of 0.92 ( 95 % confidence interval 0.82 to 1.0 ) . Similar negative predictive values were found for patients from the three other population s screened . Conclusions : This NT-proBNP assay seems to have value in the diagnosis of heart failure in the community . High negative predictive values indicate that the assay 's chief use would be to rule out heart failure in patients with suspected heart failure with normal concentrations of NT-proBNP . Positive results may identify patients who need cardiac imaging CONTEXT Several reports have suggested the usefulness of plasma brain natriuretic peptide ( BNP ) as a screening test for left ventricular hypertrophy ( LVH ) and systolic dysfunction ( LVSD ) . Prior studies were limited by small sample sizes and selection bias and none compared the diagnostic performance of these peptides in men and women . OBJECTIVES To examine the usefulness of natriuretic peptides for screening for elevated LV mass and LVSD in the community . DESIGN , SETTING , AND PARTICIPANTS Community-based prospect i ve cohort study of 3177 participants ( 1707 women ) from the Framingham Study who attended a routine examination in 1995 - 1998 . MAIN OUTCOME MEASURES Receiver operating characteristic ( ROC ) curves , test sensitivity , specificity , positive and negative predictive values , and likelihood ratios for identifying elevated LV mass ( sex-specific 90th percentile or higher of LV mass/[height](2 ) ) , LVSD ( ejection fraction < or = 50 % and /or fractional shortening < 29 % ) , and moderate to severe LVSD ( ejection fraction < or = 40 % and /or fractional shortening < 22 % ) at different discrimination limits of plasma BNP and N-terminal proatrial natriuretic peptide ( NT-ANP ) , with echocardiography as the criterion st and ard . RESULTS The areas under the ROC curves for elevated LV mass or LVSD were at or below 0.75 for both peptides , were higher for men compared with women , and were similar for BNP and NT-ANP . The diagnostic performance of natriuretic peptides for LVSD improved in women but not in men when select high-risk subgroups were targeted . Discrimination limits based on high specificity ( 0.95 ) yielded better positive predictive values and likelihood ratios compared with age- and sex-specific reference limits yet only identified less than one third of participants who had elevated LV mass or LVSD . CONCLUSION In our large community-based sample , the performance of BNP and NT-ANP for detection of elevated LV mass and LVSD was suboptimal , suggesting limited usefulness of natriuretic peptides as mass screening tools BACKGROUND The aim of the study was to prospect ively evaluate patients with suspected or known heart disease using plasma brain natriuretic peptide ( BNP ) measurement and radionuclide ventriculography to examine whether left ventricular dysfunction is associated with an abnormal rise of BNP concentration . METHODS Patients ( n=153 ) and controls ( n=14 ) underwent radionuclide ventriculography to determine Left ventricular Ejection Fraction ( LVEF ) and measurement of plasma BNP concentration using a commercial kit . RESULTS Plasma BNP concentration in controls was significantly lower than that in patients whatever the stage of the disease , significantly lower than that of patients with normal LVEF ( LVEF>55 % ) ; than that of patients with altered LVEF ( LVEF < or = 40 % ) ; and than that of patients with moderately reduced LVEF ( 40%<LVEF < or = 5 % ) . Comparisons between groups of patients showed that the more severe the disease , the higher the BNP level . From the ROC curve , a plasma BNP concentration of 52 pg/ml was attached to a 85 % sensitivity and 82 % specificity in identifying patients with LVEF < or = 40 % . CONCLUSIONS Plasma BNP concentration provides a reliable and sensitive marker of LV systolic dysfunction evaluated by a nuclear medicine technique , and could be a potential screening test to identify patients for additional investigations BACKGROUND B-type natriuretic peptide is released from the cardiac ventricles in response to increased wall tension . METHODS We conducted a prospect i ve study of 1586 patients who came to the emergency department with acute dyspnea and whose B-type natriuretic peptide was measured with a bedside assay . The clinical diagnosis of congestive heart failure was adjudicated by two independent cardiologists , who were blinded to the results of the B-type natriuretic peptide assay . RESULTS The final diagnosis was dyspnea due to congestive heart failure in 744 patients ( 47 percent ) , dyspnea due to noncardiac causes in 72 patients with a history of left ventricular dysfunction ( 5 percent ) , and no finding of congestive heart failure in 770 patients ( 49 percent ) . B-type natriuretic peptide levels by themselves were more accurate than any historical or physical findings or laboratory values in identifying congestive heart failure as the cause of dyspnea . The diagnostic accuracy of B-type natriuretic peptide at a cutoff of 100 pg per milliliter was 83.4 percent . The negative predictive value of B-type natriuretic peptide at levels of less than 50 pg per milliliter was 96 percent . In multiple logistic-regression analysis , measurements of B-type natriuretic peptide added significant independent predictive power to other clinical variables in models predicting which patients had congestive heart failure . CONCLUSIONS Used in conjunction with other clinical information , rapid measurement of B-type natriuretic peptide is useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea BACKGROUND In previous studies on the use of natriuretic peptides to detect left-ventricular systolic dysfunction , a higher rate of cardiac disorders in the control groups than in the study groups could have led to bias . We investigated the effectiveness of plasma N-terminal atrial natriuretic peptide ( NT-ANP ) and brain natriuretic peptide ( BNP ) concentrations to show left-ventricular systolic dysfunction in a r and om sample of the general population . METHODS We r and omly selected 2000 participants aged 25 - 74 years from family physicians ' lists in Glasgow , UK . We sent all participants question naires . 1653 respondents underwent echocardiography and electrocardiography . We took a left-ventricular ejection fraction of 30 % or less to show left-ventricular systolic dysfunction . NT-ANP and BNP were measured in plasma by RIAs . FINDINGS 1252 participants had analysable electrocardiograms and echocardiograms , completed question naires , and available blood sample s. Median concentrations of NT-ANP and BNP were significantly higher in participants with left-ventricular systolic dysfunction ( 2.8 ng/mL [ IQR 1.8 - 4.6 ] and 24.0 pg/mL [ 18.0 - 33.0 ] ) than in those without ( 1.3 ng/mL [ 0.9 - 1.8 ] and 7.7 pg/mL [ 3.4 - 13.0 ] ; each p < 0.001 ) . Among participants with left-ventricular systolic dysfunction , both symptomatic and asymptomatic subgroups had raised NT-ANP and BNP concentrations . A BNP concentration of 17.9 pg/mL or more gave a sensitivity of 77 % and specificity of 87 % in all participants , and 92 % and 72 % in participants aged 55 years or older . INTERPRETATION Measurement of BNP could be a cost-effective method of screening for left-ventricular systolic dysfunction in the general population , especially if its use were targeted to individuals at high risk BACKGROUND In the studies of left ventricular dysfunction ( SOLVD ) , enalapril reduced mortality in patients with symptomatic but not asymptomatic left ventricular systolic dysfunction during the trial . We did a 12-year follow-up of SOLVD to establish if the mortality reduction with enalapril among patients with heart failure was sustained , and whether a subsequent reduction in mortality would emerge among those with asymptomatic ventricular dysfunction . METHODS Of the 6797 patients previously enrolled in the SOLVD prevention and treatment trials , we ascertained the subsequent vital status of 5165 individuals who were alive when the trials had been completed . Follow-up was done through direct contacts in Belgium and linkages with national death registries and federal beneficiary or historic tax summary files in the USA and Canada . FINDINGS Follow-up was 99.8 % ( 6784/6797 ) complete . In the prevention trial , 50.9 % ( 1074/2111 ) of the enalapril group had died compared with 56.4 % ( 1195/2117 ) of the placebo group ( generalised Wilcoxon p=0.001 ) . In the treatment trial , 79.8 % ( 1025/1285 ) of the enalapril group had died compared with 80.8 % ( 1038/1284 ) of the placebo group ( generalised Wilcoxon p=0.01 ) . The reductions in cardiac deaths were significant and similar in both trials . When data for the prevention and treatment trials were combined , the hazard ratio for death was 0.90 for the enalapril group compared with the placebo group ( 95 % CI 0.84 - 0.95 , generalised Wilcoxon p=0.0003 ) . Enalapril extended median survival by 9.4 months in the combined trials ( 95 % CI 2.8 - 16.5 , p=0.004 ) . INTERPRETATION Treatment with enalapril for 3 - 4 years led to a sustained improvement in survival beyond the original trial period in patients with left ventricular systolic dysfunction , with an important increase in life expectancy BACKGROUND The reliability of a clinical diagnosis of heart failure in primary care is poor . Concentrations of natriuretic peptides are high in heart failure . This population -based study examined the predictive value of natriuretic peptides in patients with a new primary -care diagnosis of heart failure . METHODS Concentrations of plasma atrial ( ANP and N-terminal ANP ) and B-type ( BNP ) natriuretic peptides were measured by radioimmunoassay in 122 consecutive patients referred to a rapid-access heart-failure clinic with a new primary -care diagnosis of heart failure . On the basis of clinical assessment , chest radiography , and transthoracic echocardiography , a panel of three cardiologists decided that 35 ( 29 % ) patients met the case definition for new heart failure . ANP and NT-ANP results were available for 117 patients ( 34 with heart failure ) and BNP results for 106 ( 29 with heart failure ) . FINDINGS Geometric mean concentrations of natriuretic peptides were much higher in patients with heart failure than in those with other diagnoses ( 29.2 vs 12.4 pmol/L for ANP ; 63.9 vs 13.9 pmol/L for BNP ; 1187 vs 410.6 pmol/L for NT-ANP ; all p < 0.001 ) . At cut-off values chosen to give negative predictive values for heart failure of 98 % ( ANP > or = 18.1 pmol/L , NT-ANP > or = 537.6 pmol/L , BNP > or = 22.2 pmol/L ) , the sensitivity , specificity , and positive predictive value for ANP were 97 % , 72 % , and 55 % ; for NT-ANP 97 % , 66 % , and 54 % ; and for BNP 97 % , 84 % , and 70 % . Addition of ANP or NT-ANP concentration or both did not improve the predictive power of a logistic regression model containing BNP concentration alone . INTERPRETATION In patients with symptoms suspected by a general practitioner to be due to heart failure , plasma BNP concentration seems to be a useful indicator of which patients are likely to have heart failure and require further clinical assessment OBJECTIVES heart failure is primarily a disease of elderly people . Current guidelines suggest all patients with suspected heart failure should undergo objective assessment , usually by echocardiography . In the UK re sources are limited and not all patients have access to echocardiography . The electrocardiogram is widely used as a pre-screening investigation . Recently the natriuretic peptides have been shown to correlate well with left ventricular function , and evidence is accumulating which suggests that B-type natriuretic peptide may have a role in detecting cardiovascular disease . Elderly patients attending day hospital often have non-specific cardiovascular symptoms . B-type natriuretic peptide measurement in parallel with conventional electrocardiogram , may offer a novel method of identifying those with significant cardiac disease , which may warrant treatment . This study assessed the role of B-type natriuretic peptide and electrocardiogram in the detection of cardiac disease in patients attending Day Hospital . DESIGN prospect i ve cohort study of patients referred to Day Hospital with suspected cardiovascular disease . METHODS this study prospect ively evaluated 299 consecutive patients attending day hospital over a period of 13 months . Patients underwent clinical assessment , electrocardiography , echocardiography and natriuretic peptide measurement . Objective evidence of cardiac disease was based on electrocardiogram and echocardiographic findings . SETTING Medicine for the Elderly Day Hospital , Royal Victoria Hospital , Dundee . MAIN OUTCOME MEASURES sensitivity , specificity , positive and negative predictive values of screening tests for left ventricular systolic dysfunction . Receiver-Operating-Characteristic curves for ability of B-type natriuretic peptide to detect cardiac disease ( including left ventricular systolic dysfunction , valvular disease , atrial fibrillation and left ventricular hypertrophy ) . Mean B-type natriuretic peptide levels with ' incremental ' levels of cardiovascular disease . RESULTS 299 patients ( mean age 79 ; 65 % female ) completed the assessment . Ten percent of patients had left ventricular systolic dysfunction but 50 % had objective evidence of cardiac disease . B-type natriuretic peptide was significantly elevated in patients with left ventricular systolic dysfunction , atrial fibrillation , left ventricular hypertrophy and valvular disease . Both B-type natriuretic peptide and the electrocardiogram were sensitive in detecting left ventricular systolic dysfunction but lacked specificity . Combining B-type natriuretic peptide with the electrocardiogram improved detection of left ventricular systolic dysfunction . B-type natriuretic peptide levels increased progressively as the number of different cardiac abnormalities increased . CONCLUSIONS B-type natriuretic peptide may be a useful marker for cardiac disease in patients attending Day Hospital . Half of the patients assessed had cardiac disease detected . Both the electrocardiogram and B-type natriuretic peptide were sensitive in the detection of left ventricular systolic dysfunction but lacked specificity . B-type natriuretic peptide was superior to the electrocardiogram in the detection of valvular disease . If used to pre-screen cardiovascular disease in Day Hospital patients , B-type natriuretic peptide and the electrocardiogram could reduce the need for echocardiography in some patients before implementing evidence -based treatments . B-type natriuretic peptide increases progressively as the number of different cardiac abnormalities increases and this may explain why B-type natriuretic peptide is of such prognostic value in older patients BACKGROUND In most previous epidemiological studies on the prevalence of chronic heart failure ( CHF ) the disorder has been defined on clinical criteria . In a cross-sectional survey of 2000 men and women aged 25 - 74 , r and omly sample d from one geographical area , we assessed left-ventricular systolic function by echocardiography . METHODS 1640 ( 83 % ) of those invited took part . They completed a question naire on current medication , history , and symptoms of breathlessness . Blood pressure was measured and electrocardiography ( ECG ) and echocardiography were done . Left-ventricular ejection fraction was measurable in 1467 ( 89.5 % ) participants by the biplane Simpson 's rate method . FINDINGS The mean left-ventricular ejection fraction was 47.3 % . The prevalence of definite left-ventricular systolic dysfunction ( defined as a left-ventricular ejection fraction < or = 30 % ) was 2.9 % overall ( 43 participants ) ; it increased with age and was higher in men than in women ( 4.0 vs 2.0 % ) . The left-ventricular systolic dysfunction was symptomatic in 1.5 % of participants and asymptomatic in 1.4 % , 83 % of participants with left-ventricular systolic dysfunction had evidence of ischaemic heart disease ( IHD ) from history or ECG criteria compared with 21 % of those without this abnormality ( p < 0.001 ) . Hypertension was also more common in those with left-ventricular systolic dysfunction ( 72 vs 38 % , p < 0.001 ) , but there was no difference between those with and without left-ventricular systolic dysfunction in the rate of hypertension without IHD . INTERPRETATION Left-ventricular systolic dysfunction was at least twice as common as symptomatic heart failure defined by clinical criteria . The main risk factors are IHD and hypertension in the presence of IHD ; screening of such high-risk groups for left-ventricular systolic dysfunction should be considered BACKGROUND Left ventricular dilatation and dysfunction after myocardial infa rct ion are major predictors of death . In experimental and clinical studies , longterm therapy with the angiotensin-converting -- enzyme inhibitor captopril attenuated ventricular dilatation and remodeling . We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infa rct ion . METHODS Within 3 to 16 days after myocardial infa rct ion , 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were r and omly assigned to receive doubleblind treatment with either placebo ( 1116 patients ) or captopril ( 1115 patients ) and were followed for an average of 42 months . RESULTS Mortality from all causes was significantly reduced in the captopril group ( 228 deaths , or 20 percent ) as compared with the placebo group ( 275 deaths , or 25 percent ) ; the reduction in risk was 19 percent ( 95 percent confidence interval , 3 to 32 percent ; P = 0.019 ) . In addition , the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group . The reduction in risk was 21 percent ( 95 percent confidence interval , 5 to 35 percent ; P = 0.014 ) for death from cardiovascular causes , 37 percent ( 95 percent confidence interval , 20 to 50 percent ; P less than 0.001 ) for the development of severe heart failure , 22 percent ( 95 percent confidence interval , 4 to 37 percent ; P = 0.019 ) for congestive heart failure requiring hospitalization , and 25 percent ( 95 percent confidence interval , 5 to 40 percent ; P = 0.015 ) for recurrent myocardial infa rct ion . CONCLUSIONS In patients with asymptomatic left ventricular dysfunction after myocardial infa rct ion , long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events . These benefits were observed in patients who received thrombolytic therapy , aspirin , or beta-blockers , as well as those who did not , suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infa rct ion and the number of r and omised trials with diagnostic tests is rising . R and omised comparisons R and omised comparisons have several advantages over other methods of comparing medical interventions . R and om assignment of patients to the strategies under study should prevent any bias in the selection of patients : differences at baseline between groups of patients have to be attributed to chance . 4,5 This basic principle opens up the application of experimental statistical design , such as testing for significance and calculating confidence intervals . R and omised controlled trials are also attractive from a pragmatic point of view : if r and omisation coincides with a choice between two management strategies , trial design closely mimics existing clinical dilemmas . The precision of the estimates will mainly depend on the number of individuals included . One trial design is said to be more statistically efficient than another if it yields more precise estimates when applied in similarly sized groups . Recognition of heart failure ( HF ) may be difficult in patients presenting with acute dyspnoea , particularly in the presence of chronic airways obstruction . Since increased secretion of the cardiac hormones atrial natriuretic peptide ( ANP ) and brain natriuretic peptide ( BNP ) occurs early in the course of HF , we have assessed the value of measuring these hormones in plasma in the diagnosis of suspected HF in 52 elderly patients presenting with acute dyspnoea , and compared values with left-ventricular ejection fraction ( LVEF ) , a st and ard measure of left-ventricular function , by radionuclide angiography . Patients were enrolled prospect ively . On the basis of clinical findings , conventional tests , and response to specific treatment , 20 of the 52 patients were classified as having primary lung disorder ( PLD ) , 12 as HF alone , and 20 as HF with underlying PLD ( HF/PLD ) . Compared with findings in PLD patients , LVEF was significantly depressed in HF and HF/PLD patients ( p < 0.001 ) , whereas both plasma ANP and BNP were significantly increased ( p < 0.001 ) . Admission plasma BNP concentration more accurately reflected the final diagnosis of HF ( 93 % sensitivity and 90 % specificity when BNP > or = 22 pmol/L ) than LVEF or plasma ANP concentration . When all patients were considered together , there were strong negative correlations between LVEF and log BNP ( r = -0.7 , p < 0.001 ) and log ANP ( r = -0.59 , p < 0.001 ) . Our finding that plasma BNP is raised in dyspnoeic patients with HF but not in acutely breathless patients with PLD , suggests that rapid BNP assays may assist in the diagnosis of patients with acute dyspnoea |
11,824 | 25,305,289 | We conclude that the L : M test has many attributes , including reflecting 2 physiologic processes ( absorption and permeability ) and likely correlation with growth failure consequent to child gut dysfunction . | Childhood gut dysfunction ( enteropathy ) is common in re source -poor environments .
Stunting is its presumed major consequence .
Identification of biomarkers of gut dysfunction could identify the presence of , and , ideally , assess interventions for , enteropathy .
Classically , enteropathy has been identified histopathologically .
However , less invasive assays may be more sensitive for detecting earlier perturbations reflecting specific functional derangements .
The most commonly used test has been the urinary lactulose to mannitol ratio ( L : M ) , which primarily assesses gut leakiness , and which also measures absorption . | BACKGROUND Growth faltering during infancy is a characteristic of life in developing countries . Previous studies have shown that small-intestine mucosal enteropathy , accompanied by endotoxemia and a persistent systemic inflammatory response , accounts for up to 64 % of the growth faltering in Gambian infants . OBJECTIVE The objective was to test whether glutamine , with its putative trophic effects on enterocytes , immune cells , and intestinal integrity , can accelerate the repair of the intestine , lower immunostimulation , and reduce growth faltering . DESIGN Ninety-three infants aged 4 - 10 mo from the West Kiang region of The Gambia were studied in a double-blind , double-placebo , controlled trial . Glutamine ( 0.25 mg/kg body wt ) or a placebo that contained an isonitrogenous , isoenergetic mix of nonessential amino acids was orally administered twice daily throughout the 5-mo rainy season . Anthropometric measurements were made monthly during the supplementation period and for 6 mo after supplementation . Intestinal permeability was measured monthly ( by determining the ratio of lactulose to mannitol ) , and finger-prick blood sample s were collected for the analysis of plasma proteins on 3 occasions . RESULTS Gambian infants showed a seasonal deterioration in growth and persistently elevated acute phase protein concentrations and intestinal permeability . Oral supplementation with glutamine did not improve growth ( x + /- SE : weight gain , 60 + /- 19 and 69 + /- 20 g/mo ; length gain , 1.01 + /- 0.05 and 0.95 + /- 0.03 cm/mo ) or intestinal permeability [ lactulose : mannitol ratio : 0.29 ( 95 % CI : 0.23 , 0.35 ) and 0.26 ( 95 % CI : 0.21 , 0.32 ) ] in the glutamine and placebo groups , respectively . It also had no effect on infant morbidity or on plasma concentrations of immunoglobulins or acute phase proteins . CONCLUSION Glutamine supplementation failed to improve growth or intestinal status in malnourished Gambian infants BACKGROUND The effect of helminth infestation on the nutrition , growth , and physiology of the host is still poorly understood . Anthelmintic treatment of children in developing countries has had varying success in terms of growth improvements . OBJECTIVE The objective of this study was to assess the effect of regular deworming on child growth , physiology , and biochemical status . DESIGN The study was a 12-mo longitudinal intervention in 123 Bangladeshi children aged 2 - 5 y. Treatment ( mebendazole ) or placebo tablets were administered every 2 mo for 8 mo and again at 12 mo . Weight , height , midupper arm circumference , intestinal permeability , plasma albumin , alpha(1)-antichymotrypsin , and total protein concentration were assessed every 2 mo . RESULTS Treatment with mebendazole reduced the prevalence of Ascaris lumbricoides from 78 % to 8 % , of Trichuris trichiura from 65 % to 9 % , and of hookworm from 4 % to 0 % . There was no significant difference in the growth of treated children compared with those given placebo tablets . No changes in intestinal permeability or plasma albumin were observed after deworming . Significant decreases in total protein ( P<0.001 ) and alpha(1)-antichymotrypsin ( P<0.001 ) were observed in the treatment group , indicating possible reductions in inflammation and immunoglobulin concentration after deworming . A significant increase in the prevalence of Giardia intestinalis ( from 4 % to 49 % ) in the treatment group was associated with a short-term reduction in weight ( P = 0.02 ) and higher intestinal permeability ( P < 0.001 ) in infected subjects . No long-term effects of G. intestinalis on growth were observed . CONCLUSION Low-intensity helminth infections , predominantly of A. lumbricoides and T. trichiura , do not contribute significantly to the poor growth and biochemical status of rural Bangladeshi children BACKGROUND Tropical enteropathy is an asymptomatic villous atrophy of the small bowel that is prevalent in the developing world and is associated with altered intestinal function and integrity . The histology of tropical enteropathy resembles that seen in small-bowel bacterial overgrowth . OBJECTIVE This study tested the hypothesis that treatment of 3 - 5-y-old Malawian children with the probiotic Lactobacillus GG would improve their intestinal function and integrity . DESIGN Clinical ly healthy children ( n = 164 ) were enrolled in a placebo-controlled , r and omized , double-blind trial . Intestinal function and integrity were measured by using the site-specific sugar-absorption test before and after 30 d of treatment with Lactobacillus GG or placebo . The primary outcomes were the ratios of urinary lactulose to mannitol ( L : M ) and of urinary sucrose to lactulose ( S : L ) excretion . RESULTS Of the 161 children who completed the study , 119 ( 73 % ) had tropical enteropathy on enrollment ( L : M > 0.10 ) . Children receiving Lactobacillus GG did not differ significantly from the placebo group in the excretion ( in % of dose administered ) of mannitol ( mean + /- SD : 8.9 + /- 4.4 and 8.9 + /- 3.9 , respectively ) , lactulose ( 0.31 + /- 0.20 and 0.33 + /- 0.23 , respectively ) , or sucrose ( 0.078 + /- 0.058 and 0.082 + /- 0.075 , respectively ) . L : M and S : L also did not differ significantly between the Lactobacillus and placebo groups ( 0.19 + /- 0.13 and 0.20 + /- 0.12 , respectively , for L : M ; 0.58 + /- 0.46 and 0.65 + /- 0.57 , respectively , for S : L ) . CONCLUSION Administration of Lactobacillus GG for 30 d had no effect on the intestinal integrity of 3 - 5-y-old Malawian children The interrelationship between diarrhea , malnutrition , and small bowel integrity was investigated prospect ively in 68 Gambian infants aged 0 - 18 mo . Profiles of growth and morbidity were recorded for 8 mo . Each month intestinal permeability was measured by the differential uptake of orally administered lactulose ( L ) and mannitol ( M ) . In well infants the mean L : M ratio was 0.42 ( range 0.11 - 1.42 ) . This ratio was increased slightly for underweight ( 60 - 80 % wt for age ) infants ( mean 0.52 ) but considerably for those with marasmus ( less than 60 % wt for age ) ( mean 1.3 , p less than 0.001 ) , for those with acute or chronic diarrhea ( mean 1.0 and 2.85 , respectively ; p less than 0.001 ) , or with measles ( mean 1.4 , p less than 0.001 ) . Sequential studies of ward patients with malnutrition and diarrhea showed a rapid fall in L : M ratios with resolution of diarrhea . These studies suggest that damage to the small intestine may play an important part in the development of infant malnutrition in The Gambia Background : This study evaluates the effects of retinol on intestinal barrier function , growth , total parasites , and Giardia spp infections in children in northeastern Brazil . Subjects and Methods : The study was a double-blind , r and omized placebo-controlled trial ( http:// clinical trials.gov ; register no. # NCT00133406 ) involving 79 children who received vitamin A 100,000–200,000 IU ( n = 39 ) or placebo ( n = 40 ) at enrollment , 4 , and 8 months and were followed for 36 months . Intestinal barrier function was evaluated using the lactulose : mannitol ratio test . Stool lactoferrin was used as a marker for intestinal inflammation . Results : The groups were similar with regard to age , sex , nutritional parameters ( z scores ) , serum retinol concentrations , proportion of lactoferrin-positive stool sample s , and intestinal barrier function . The lactulose : mannitol ratio did not change during the same time of follow-up ( P > 0.05 ) . The proportion of lactoferrin-positive sample s evaluated at 1 month did not change between groups ( P > 0.05 ) . Total intestinal parasitic , specifically new , infections were significantly lower in the vitamin A treatment compared with control group ; these were accounted for entirely by significantly fewer new Giardia infections in the vitamin A treatment group . The cumulative z scores for weight-for-length or height , length or height-for-age z scores , and weight-for-age did not change significantly with vitamin A intervention for 36 months of follow-up . Conclusions : These data showed that total parasitic infection and Giardia spp infections were significantly lower in the vitamin A treatment group when compared with the placebo group , suggesting that vitamin A improves the host 's defenses against Giardia infections In order to test the impact of Giardia and geohelminthic infection on infant growth faltering in Bangladesh , a r and omised double-blind placebo controlled intervention of 36 weeks ' duration was conducted in a rural community located 40 km northwest of Dhaka . Infants aged between 3 and 15 months were r and omly assigned to either anti-Giardia and anthelminthic treatment , anti-Giardia treatment only , or a control . Weight and supine length were recorded every 4 weeks . Every 12 weeks intestinal permeability ( lactulose/mannitol ratio ) , haemoglobin , plasma albumin , alpha-1-acid glycoprotein , IgG and Giardia-specific IgM ( GSIgM ) and eggs of the three common geohelminths and G. intestinalis cysts were determined . Data on 222 fully compliant infants were analysed . No significant differences in intestinal permeability , biochemical or anthropometric variables were found between the intervention groups , although there were associations between improvement in small intestinal mucosal function and better weight-for-age and weight-for-height ( length ) Z-scores . GSIgM titres indicated high endemicity with rapid re-infection of Giardia among infants ; over 95 % of infants were positive throughout the study , whereas the stool examination showed very few infants with either geohelminth eggs or Giardia cysts Sub clinical mastitis , as diagnosed by an elevated sodium/potassium ratio in milk accompanied by an increased milk concentration of the inflammatory cytokine , interleukin-8 ( IL8 ) , was found to be common among breast feeding women in Bangladesh and Tanzania . Sub clinical mastitis results in leakage of plasma constituents into milk , active recruitment of leukocytes into milk , and possible infant gut damage from inflammatory cytokines . Therefore , we wished to investigate whether sub clinical mastitis was related to known risk factors for postnatal mother-to-child HIV transmission , that is , high milk viral load or increased infant gut permeability . HIV-infected South African women were recruited at the antenatal clinic of McCord 's Hospital , Durban . Risks and benefits of different feeding strategies were explained to them and , if they chose to breast feed , they were encouraged to do so exclusively . Women and infants returned to the clinic at 1 , 6 and 14 weeks postpartum for an interview about infant health and current feeding pattern , a lactulose/mannitol test of infant gut permeability , and milk sample collection from each breast separately for analysis of Na/K ratio , IL8 concentration and viral load in the cell-free aqueous phase . Only preliminary cross-sectional analyses from an incomplete data base are available at this point . Moderately ( 0.6 - 1.0 ) or greatly ( > 1.0 ) raised Na/K ratio was common and was often unilateral , although as a group right and left breasts did not differ . Considering both breasts together , normal , moderately raised or greatly raised Na/K was found , respectively , in 51 % , 28 % , 21 % of milk sample s at 1 week ( n=190 ) ; 69 % , 20 % , 11 % at 6 weeks ( n=167 ) ; and 72 % , 16 % , 12 % at 14 weeks ( n=122 ) . IL8 concentration significantly correlated with both Na/K and viral load at all times . Na/K correlated with viral load at 1 and 14 , but not 6 weeks . At 1 and 14 weeks , geometric mean viral loads in sample s with Na/K > 1.0 were approximately 4 times those in sample s with Na/K < 0.6 . At 1 week but not later times , exclusive breast feeding was associated with lower milk viral load than was mixed feeding . Gut permeability was unrelated to milk Na/K ratio or IL8 concentration and was not significantly increased by inclusion of other foods than breast milk in the infant 's diet . The results suggest that sub clinical mastitis among HIV-infected women may increase the risk of vertical transmission through breast feeding by increasing milk viral load . The importance of various causes of sub clinical mastitis , which likely differ at 1 week from at later times and may include local infection or sterile inflammation , systemic infection , micronutrient deficiencies , or poor lactation practice s , needs to be further clarified so that appropriate interventions can be implemented Gut integrity , which can be measured by the urinary lactulose : mannitol excretion test , deteriorates with the introduction of weaning foods . In The Gambia , gut integrity measured monthly over 15 months in 119 infants ( aged 2 - 15 months ) was least impaired from April to June . This coincides with the time of year of maximum vitamin A ( VA ) intake-the mango season . Subsequently , two VA intervention studies were done in infants in India . Eighty infants attending a community health center received 16,700 IU weekly or placebo . In another study , 94 hospitalized infants were given 200 , 000 IU VA or placebo : 31 received VA on admission , while the rest ( 32 VA , 31 placebo ) received treatment on discharge . All VA-treated groups had more rapid improvement in gut integrity than the placebo groups , but no group had gut integrity normalized by Western st and ards . The data suggest that VA status may influence gut integrity Background . Vitamin A has well‐recognized benefits for prevention of diarrhea , but the impact of therapeutic doses given during diarrhea on biochemical and clinical outcomes is less clear . We investigated these potential therapeutic benefits within a study of the optimum time for vitamin A supplementation to promote vitamin A status . Methods . Young children with severe diarrhea were r and omized to receive 60 mg of retinol as retinyl palmitate during acute diarrhea or once symptoms had resolved , usually after 5 to 8 days . Either during acute diarrhea or after its resolution , children not receiving vitamin A were given identical placebo . On Days 0 and 3 we measured urinary neopterin , plasma retinol and acute phase proteins and intestinal permeability by the lactulose/mannitol test . Eight weeks after discharge children returned to hospital for a modified dose response test of vitamin A stores . Results . Most children presented with watery diarrhea and grossly abnormal intestinal permeability and immune activation markers . At 8 weeks plasma retinol concentrations of children receiving vitamin A during acute diarrhea , compared with those receiving it in early convalescence [ 0.67 ( 95 % confidence interval , 0.58 to 0.76 ) & mgr;mol/l vs. 0.68 ( 95 % confidence interval , 0.59 to 0.79 ) & mgr;mol/l ] , and the proportion of children with deficient vitamin A stores ( 7 of 34 vs. 8 of 34 ) did not differ . Clinical features , lactulose/mannitol tests and urinary neopterin concentrations on Day 3 also did not differ significantly when vitamin A was given early or late . Conclusions . Even when it was given during severe diarrhea , a large dose of vitamin A improved vitamin A stores in a population in whom vitamin A deficiency is a public health problem . Vitamin A did not significantly improve early clinical or biochemical recovery from severe diarrhea BACKGROUND Most developing countries have adopted a st and ard WHO dosing schedule for vitamin A supplementation . However , in 2002 the International Vitamin A Consultative Group ( IVACG ) Annecy Accord recommended a new high-dose regimen for mothers and infants . Our aim was to test whether the new high-dose regimen of vitamin A supplementation would increase maternal and infant plasma vitamin A , reduce infant Helicobacter pylori infection and nasopharyngeal pneumococcal carriage , and improve infant gut epithelial integrity . METHODS In an area of moderate vitamin A deficiency in rural Gambia , 220 mother-infant pairs were enrolled in a r and omised double-blind trial between September , 2001 , and October , 2004 , that compared the IVACG high dose with the WHO dose . The primary endpoints were levels of maternal and infant plasma vitamin A , H pylori infection , pneumococcal carriage , and gut epithelial integrity . The trial is registered as IS RCT N 98554309 . FINDINGS 197 infants completed follow-up to 12 months ( 99 high dose and 98 WHO dose ) . There were no adverse events at dosing . No differences were found in the primary outcomes for high-dose versus WHO schedule : maternal vitamin A concentration at 2 months + 0.02 micromol/L ( 95 % CI -0.10 to 0.15 ) ; infant vitamin A at 5 months + 0.01 micromol/L ( -0.06 to 0.08 ) ; H pylori infection at 12 months -0.3 % ( -14.7 to 14.2 ) ; maternal pneumococcal carriage at 12 months -2.0 % ( -13.7 to 9.7 ) ; infant pneumococcal carriage at 12 months -4.1 % ( -15.8 to 7.6 ) ; infant gut mucosal damage at 12 months 5.2 % ( -8.7 to 19.2 ) . There were more clinic attendances by the high-dose group in the first 6 months of life ( p=0.018 ) . INTERPRETATION Our results do not lend support to the proposal to increase the existing WHO st and ard dosing schedule for vitamin A in areas of moderate vitamin A deficiency . Caution is urged for future studies because trials have shown possible adverse effects of higher doses of vitamin A , and potential negative interactions with the exp and ed programme on immunisation ( EPI ) vaccines To evaluate the effects of green banana and pectin ( nondigestible , dietary sources of colonic short-chain fatty acids [ SCFA ] ) on intestinal permeability , 57 boys ( 5–12 months ) with persistent diarrhea ( ≥14 days ) were given a week 's treatment with a rice-based diet containing either cooked green banana ( n=19 ) , pectin ( n=17 ) , or rice diet alone ( n=21 ) . Intestinal permeability was assessed before and after treatment by giving a lactulose – mannitol ( LM ) drink and measuring urinary recovery after 5 hr . Treatment with banana significantly ( P<0.05 ) reduced lactulose recovery , increased mannitol recovery , and decreased the LM ratio , indicating improvement of permeability . Pectin produced similar results . Permeability changes were associated with a 50 % reduction in stool weights which correlated strongly ( green banana , r2 = 0.84 , pectin , r2 = 0.86 ) with the LM ratio . Green banana-derived and SCFA-mediated stimulation of colonic as well as small bowel absorption is responsible for their antidiarrheal effects . The antidiarrheal effects of green banana and pectin are mediated by improvement of small intestinal permeability in addition to their known colonotrophic effects Summary Zinc has been shown to enhance intestinal mucosal repair in patients suffering from acrodermatitis enteropathica ; but the impact on mucosal integrity during acute ( AD ) or persistent ( PD ) diarrhoea is unknown . One hundred eleven children with AD and 190 with PD aged between 3 and 24 months received , r and omly and blind to the investigators , either an elemental zinc supplement of 5 mg/kg body wt/day or placebo in multivitamin syrup for 2 weeks while intestinal permeability and , biochemical and anthropometric markers were serially monitored . The permeability test was administered as an oral dose of 5 g lactulose/1 g mannitol in a 20-ml solution followed by a 5-h urine collection . The ratio of the urinary probe sugars was correlated to clinical , biochemical , and microbiological parameters . At presentation , lactulose excretion was increased and mannitol excretion decreased in both AD and PD as compared with age-matched asymptomatic children . The lactulose/mannitol ratio ( L/M ) was higher in subjects with mucosal invasive pathogens ( rotavirus and enteropathogenic Escherichia coli ) compared with children excreting Vibrio cholera and enterotoxigenic . coli . Two-week zinc supplementation significantly reduced lactulose excretion in both AD and PD , whereas the change in mannitol excretion and L/M was similar between study groups in both studies . Changes in lactulose excretion were significantly influenced by zinc supplementation in children with E. coli , Shigella sp. , and Campylobacter jejuni stool isolates . The greatest reduction in total lactulose excretion was seen in supplemented children who on presentation were lighter ( wt/age < 80 % ) , thinner ( wt/ht < 85 % ) , and undernourished [ middle upper arm circumference ( MUAC ) < 12.5 cm ] or with hypozincaemia ( < 14 μmlmol/L ) . The results suggest zinc supplementation improves intestinal permeability in certain groups of children with AD or PD syndrome and contributes to their recovery . This effect may indirectly reflect enhanced mucosal recovery . Further studies on the mechanisms of mucosal repair following zinc supplementation are recommended The lactulose breath test ( LBT ) and gastroenterocolonic scintigraphy ( GECS ) can both be usedto measure orocecal transit time ( OCTT ) . The aims ofthis study were ( 1 ) to measure OCTT by LBT and GECS and ( 2 ) to determine whether lactulose altersorocecal transit . Methods : Eight normal subjectsunderwent simultaneous breath hydrogen testing , GECS , and duodenal manometry while receiving either 10 glactulose or placebo with a radiolabeled solid/liquidtest meal during two studies . There was a goodcorrelation between OCTT by LBT and GECS when performedsimultaneously ( r = 0.95 ; P < 0.001 ) . OCTT by GECSwith lactulose was significantly faster ( P = 0.004 ) than byGECS without lactulose , despite no change in gastricemptying of liquids and slowing of gastric emptying ofsolids ( P = 0.02 ) . The postpr and ial duodenal motility index was greater with lactulose than withplacebo ( P = 0.031 ) . This study demonstrates that LBT and GECS ( without lactulose ) are not equivalent measures of OCTT . The st and ard LBT accelerates OCTT and slows gastric emptying . Therefore , lactulose has adirect accelerating effect on small intestinaltransit OBJECTIVES : Tropical enteropathy is characterized by an increased urinary lactulose-to-mannitol ( L : M ) ratio on a site-specific sugar absorption test and is associated with increased intestinal permeability and decreased nutrient absorptive capacity . The etiology of tropical enteropathy is postulated to be intestinal bacterial overgrowth . This study tested the hypothesis that treatment with a nonabsorbable , broad-spectrum antibiotic , rifaximin , reduces the L : M ratio in rural Malawian children , among whom tropical enteropathy is common . METHODS : All children aged 3–5 years from one village were enrolled in a r and omized , double-blind , placebo-controlled trial of treatment with rifaximin for 7 days . The L : M ratio was measured before and after treatment , and the change in the L : M ratio was the primary outcome . Secondary outcomes were changes in the urinary sucrose-to-lactulose ( SUC : L ) and sucralose-to-lactulose ( SCL : L ) ratios , as well as changes in the fractions of each test sugar recovered in the urine . RESULTS : A total of 144 children participated in this study , of whom 76 % had an elevated L : M ratio on enrollment ( L : M≥0.10 ) . Children who received rifaximin did not show an improvement in their L : M ratio compared with those who received placebo ( −0.01±0.12 vs. 0.02±0.16 , respectively , P=0.51 , mean±s.d . ) , nor were there significant differences between the two groups in excretion of lactulose , mannitol , sucralose , or sucrose , or in the SUC : L and SCL : L ratios . CONCLUSIONS : Rifaximin had no effect on the tropical enteropathy of 3–5-year-old Malawian children , suggesting that small-bowel bacterial overgrowth is not an important etiological factor in this condition Background Vitamin A is important for protection against diarrhea , and supplements may benefit gut function of infants of HIV-infected mothers . Methods We studied 238 infants of HIV-infected South African women participating in a r and omized , double-blind , placebo-controlled trial of vitamin A during pregnancy ( 1.5 mg retinyl palmitate and 30 mg & bgr;-carotene daily ) plus 60 mg retinyl palmitate at delivery . The placebo group received identical placebo capsules at the same times . When infants were 1 , 6 , and 14 weeks of age , lactulose/mannitol dual sugar intestinal permeability tests were performed . Results Maternal vitamin A supplementation did not significantly affect infant gut permeability in the group as a whole at any time . By multiple regression analysis , HIV infection of the infant by 14 weeks was significantly associated with increased gut permeability at both 6 and 14 weeks . After controlling for birth weight , gestational age , current weight , feeding mode and recent morbidity , there was a trend toward an interaction between vitamin A supplementation and HIV infection ( P = 0.086 ) at 14 weeks . Vitamin A made no difference to gut permeability of uninfected infants ( lactulose/mannitol ratio for vitamin A group : 0.11 , 95 % confidence interval [ CI ] 0.08 , 0.15 , n = 73 and for placebo group : 0.09 , 95 % CI 0.06 , 0.12 , n = 76 ) , but largely prevented the increase in the ratio of HIV-infected infants ( vitamin A group : 0.17 , 95 % CI 0.13 , 0.23 , n = 23 ; placebo group : 0.50 , 95 % CI 0.37 , 0.68 , n = 20 ) . The effects on the lactulose/mannitol ratio were related to changes in lactulose , not mannitol , excretion . Vitamin A supplementation was associated with significantly lower lactulose excretion at 1 and 14 weeks , suggesting the major effect of vitamin A was on maintaining the integrity of gut tight junctions . Conclusions Vitamin A supplementation of HIV-infected pregnant women may prevent the deterioration in gut integrity in the subgroup of their infants who themselves become infected . Improving vitamin A status of HIV-infected infants may decrease their gastrointestinal morbidity Objective : We examined the effect of st and ard formula and glutamine or glycine supplemented enteral formula on intestinal permeability and weight gain in children with malnutrition . Methods : 80 children aged 2 to 60 months with a weight-for-age z-score less than −2 were studied . From December 1996 to April 1999 , 27 study patients received nonsupplemented formula . From June 2001 to June 2002 an additional 53 patients were r and omly assigned to receive formula supplemented with glutamine or glycine ( isosmolar concentrations ) for 10 days . Lactulose/mannitol excretion ratio was used as a measure of intestinal permeability and was performed before and after 10 days of nutritional rehabilitation . Weight was measured before and after treatment . Results : Patients were similar on admission with regard to age , sex , nutritional status and lactulose/mannitol ratio . The lactulose/mannitol ratio significantly improved ( decreased ) in children receiving formula supplemented with glutamine for 10 days but not in those receiving glycine or nonsupplemented formula . Weight gain occurred during therapy in all groups and was not statistically different among groups . Conclusion : Formula supplemented with glutamine improves intestinal barrier function compared with nonsupplemented formula but does not augment weight gain Objective : We examined the effect of a diet supplemented with alanyl-glutamine ( AG ) or placebo glycine ( G ) on intestinal barrier function and growth in children in northeastern Brazil . Patients and Methods : One hundred seven children ages 7.9 to 82.2 months with a weight-for-age ( WAZ ) , height-for-age ( HAZ ) , or weight-for-height ( WHZ ) z-score less than −1 were studied . From July 2003 to November 2004 , 51 study patients received AG ( 24 g/d ) and 56 received G ( 25 g/d ; isonitrogenic concentration ) control for 10 days . Lactulose/mannitol excretion ratio was used as a measure of intestinal permeability and was performed on days 1 and 10 of nutritional supplementation . Weight and height were measured on days 1 , 10 , 30 , and 120 of the protocol . Results : The patients were similar on admission with regard to age , sex , birth weight , nutritional status , lactulose/mannitol ratio , and serum concentrations of glutamine and arginine . The percentage of lactulose urinary excretion significantly improved ( decreased ) in children receiving AG for 10 days but not in those receiving glycine controls . AG significantly increased cumulative change over 120 days in WHZ and WAZ scores but not HAZ scores after adjustment for age and season in comparison with the placebo glycine group . Conclusions : Children tolerated AG-supplemented enteral formula well , and it significantly improved cumulative WHZ and WAZ over 120 days in comparison with children in the placebo glycine group . The data also suggested a beneficial effect of AG in the barrier function paracellular pathway , albeit with reduced mannitol excretion . Thus , although the effect of AG on reduced mannitol concentration requires clarification , AG appears to improve nutrition and barrier function Summary : Exclusive breast feeding has been associated with a lower rate of mother‐to‐child HIV transmission than breast feeding plus other foods . To obtain further information on biologic outcomes of different feeding modes , we examined 272 infants of HIV‐infected South African women at ages 1 , 6 , and 14 weeks . At each visit information about infant diet and morbidity was collected and infants underwent a lactulose/mannitol dual sugar intestinal permeability test . In a subset of infants , urinary neopterin excretion was measured as an indicator of immune system activation . Infants who had themselves become HIV‐infected by 14 weeks had higher ( p < .01 ) intestinal permeability at 6 and 14 weeks and slightly ( .05 < p < .1 ) higher neopterin excretion at all times than uninfected infants . At 1 week infants given no breast milk had higher ( p < .05 ) intestinal permeability than infants given breast milk exclusively or with other foods . Intestinal permeability in infants fed breast milk plus other foods was never increased relative to that of exclusively breastfed infants . Feeding mode had no effect on neopterin excretion . Thus , infant HIV infection induces changes in gut permeability and possibly immune system activation before clinical symptoms become apparent . The effects of feeding mode on infant intestinal permeability or urinary neopterin excretion do not explain a possible protective effect of exclusive breast feeding on mother‐to‐child transmission of HIV |
11,825 | 28,553,154 | Skeletal effects were more marked in postmenopausal women .
There was no evidence of increased fracture risk , and only little data were available on hypoparathyroidism .
There was little difference in basic physiological parameters and limited literature regarding symptoms or significant events .
Impaired glucose metabolism and prothrombotic states were also found in DTC patients .
CONCLUSION There is limited literature regarding long-term DTC treatment-related morbidity , particularly regarding the effects of long-term hypocalcemia . | BACKGROUND Differentiated thyroid cancer ( DTC ) occurs in relatively young patients and is associated with a good prognosis and long survival .
The management of this disease involves thyroidectomy , radioiodine therapy , and long-term thyroid-stimulating hormone suppression therapy ( THST ) .
The long-term effects of the treatment and the interaction between sub clinical hyperthyroidism and long-term hypoparathyroidism are poorly understood .
This review sought to examine the available evidence . | Biondi , Fazio , and colleagues recently reported that long term T4 treatment to suppress serum TSH markedly affects cardiac function . T4-treated patients had more symptoms [ 12.2 + /- 3.9 ( + /-SD ) vs. 4.2 + /- 2.3 by quantitative question naire ] , higher mean heart rate , increased incidence of atrial extrasystoles , increased interventricular septal thickness and left ventricular mass index ( LVMi ) , and significant diastolic dysfunction . The severity of cardiac abnormalities was highly correlated with scores of a rating scale used for assessing symptoms of thyrotoxicosis . We have duplicated their studies in 17 athyreotic patients ( mean age , 45 + /- 10 yr ; range , 27 - 63 yr ) without heart disease or hypertension whose dose of T4 was titrated to suppress serum TSH to less than 0.01 microU/mL. The mean duration of T4 treatment was 9.2 + /- 5.4 yr . Controls were healthy volunteers matched for sex and age ( + /-3 yr ) . The mean T4 dose was 2.8 + /- 0.9 micrograms/kg ( 0.192 + /- 0.058 mg/day ) . By question naire , patients had minimal symptoms , although their symptom score was significantly greater than the control value ( 4 + /- 3 vs. 2 + /- 1 ; P < 0.05 ; maximum score , 36 ) . No differences in mean heart rate or in atrial or ventricular extrasystoles were noted . In patients , indexes of systolic and diastolic function and interventricular septal thickness were similar to control values . The mean LVMi was normal in both groups . However , the mean LVMi in patients ( 117 + /- 35 g/m2 ) was higher than that in controls ( 92 + /- 31 ; P < 0.05 ) . In conclusion , patients were minimally affected by TSH-suppressive doses of T4 . They had few symptoms and no increase in extrasystoles or basal heart rate . Based on current knowledge , the increase in LVMi observed in patients without associated significant systolic or diastolic abnormalities does not have clinical or prognostic importance . Therefore , in the absence of symptoms of thyrotoxicosis , patients treated with TSH-suppressive doses of L-T4 may be followed clinical ly without specific cardiac laboratory studies CONTEXT Previous studies of the effects of levothyroxine ( LT(4 ) ) therapy on bone and bone metabolism have provided conflicting results . OBJECTIVE This study evaluated the potential effects and dose-response relationship of LT(4 ) therapy on bone mineral density ( BMD ) as well as bone and muscle strength . DESIGN AND SETTING We conducted a prospect i ve , nonr and omized , controlled cohort study with 1.1 ± 0.2-yr follow-up at an academic outpatient clinic in Germany . PARTICIPANTS Ninety-seven men and premenopausal women were enrolled in the study after thyroidectomy and radioiodine remnant ablation for well-differentiated thyroid carcinoma ( DTC ) or strumectomy for nontoxic goiter . Patients were matched with 89 healthy controls . INTERVENTIONS Twenty-eight men and 46 women on TSH-suppressive doses of LT(4 ) had DTC , and 23 women were on LT(4 ) replacement therapy for nontoxic goiter . MAIN OUTCOME MEASURE This study assessed total and trabecular volumetric BMD ( vBMD ) as well as bone strength at the ultradistal radius , areal BMD at the lumbar spine and both hips , and the grip strength of the nondominant forearm . The dependent variables were annualized rates of change . RESULTS LT(4 ) therapy did not impair the areal BMD , bone strength , or grip strength of patients compared with controls . Women with DTC showed a significant loss of total vBMD , whereas men with DTC developed marginally less bone strength than women . Carboxy-terminal telopeptide indicated greater bone resorption in DTC patients compared with controls . CONCLUSIONS There was little evidence of adverse LT(4 ) effects on bone ; however , premenopausal women with DTC might be at risk for reduced vBMD in their ultradistal radii Data on co-morbidity in patients with postsurgical hypoparathyroidism ( HypoPT ) are sparse . We aim ed to assess risk of fractures , spinal stenosis , cataract , neuropsychiatric diseases , cancer , and infections within the historic cohort of patients with postsurgical HypoPT due to non-malignant causes that we previously have characterized . Patients were identified through the Danish National Patient Registry and regional prescription data bases , with subsequent validation of their individual hospital records . Identified cases were matched with three age- ( ± 2 yr ) and gender-matched controls from the general background population . Compared with controls , patients did not have an increased risk of cataract ( p = 0.52 ) , spinal stenosis ( p = 0.59 ) , or any fracture ( p = 0.98 ) . However , the risk of fractures at the upper extremities was significantly decreased in patients ( HR 0.69 , 95 % CI 0.49 - 0.97 ) . Compared with controls , patients had a significantly increased risk of hospitalization due to infections ( HR 1.42 , 95 % CI 1.20 - 1.67 ) and depression/bipolar affective disorders ( HR 1.99 , 95 % CI 1.14 - 3.46 ) . The risk of malignant diseases did not differ between groups although the risk of gastrointestinal cancers was significantly lower in patients compared with controls ( HR 0.63 , 95 % CI 0.44 - 0.93 ) . In conclusion , HypoPT is associated with an increased risk of depression and other types of neuropsychiatric diseases as well as infections , whereas patients seem to be protected against fractures at the upper extremities and gastrointestinal malignancies OBJECTIVE To evaluate if a supervised exercise training program improves the quality of life ( QoL ) of differentiated thyroid carcinoma ( DTC ) patients on TSH-suppressive therapy with levothyroxine ( L-T4 ) . SUBJECTS AND METHODS Initially , a cross-sectional study was performed to compare the QoL and the health-related quality of life ( HRQoL ) between sub clinical hyperthyroidism ( SCH ) patients ( n = 33 ) and euthyroid subjects ( EU ; n = 49 ) . In the prospect i ve phase of the study , SCH patients were r and omized in a non-blinded fashion to either participate ( SCH-Tr = trained patients ; n = 16 ) or not ( SCH-Sed = untrained patients ; n = 17 ) in a supervised exercise training program . The exercise program consisted of 60 minutes of aerobic and stretching exercises , twice a week , during twelve weeks . The QoL was assessed by the application of the WHOQOL-Bref , and the SF-36 was used to assess the HRQoL. RESULTS SCH patients had statistically lower scores than EU on the " physical " domain of WHOQOL-Bref , besides " physical function " , " role-physical " , " bodily pain " , " general health " , " vitality " , " role-emotional " , and " mental-health " domains of SF-36 . After three months , SCH-Tr patients showed improvement in the " physical " and " psychological " domains of WHOQOL-Bref ( p < 0.05 ) , and in the " physical function " , " role-physical " , " bodily pain " , " vitality " and " mental health " domains of SF-36 . CONCLUSION Patients on TSH-suppressive therapy with L-T4 for DTC had impaired QoL and HRQoL compared to EU , but it was improved after 3-months of an exercise training program . Exercise seems to play an important role in the follow-up of DTC patients , since it seems to minimize the adverse effects of the treatment on QoL and To determine the effect of suppressive doses of thyroxine ( T4 ) on bone mass , we studied 50 women on suppressive doses of T4 for 3 - 27 years ( mean of 11 years ) . Twenty-five had nontoxic goiter and 25 had well-differentiated thyroid carcinoma . Fifty controls were matched for age , menopausal status , and body mass index . Bone mineral density ( BMD ) was measured in the lumbar spine ( LS ) , femoral neck ( FN ) , trunk ( TK ) , and extremities ( EXT ) by dual-energy X-ray absorptiometry ( DXA ) . In addition , the trunk area was measured by neutron activation analysis and recorded as a calcium bone index ( CaBI ) . Twenty-one patients were restudied with DXA measurements at a mean of 1.5 + /- 0.5 ( 1 SD ) years . The total population of 50 patients showed no difference in bone mass from controls . In patients with nontoxic goiter , there was no evidence of any loss in bone mass . Cancer patients showed insignificant reductions of 2 - 5 % in BMD of LS , FN , and TK and a significant 5 % reduction in BMD of EXT , compared to controls , and a 12 % reduction in CaBI compared to goiter patients . Cancer patients had a slightly higher ( p < 0.001 ) mean daily dose of T4 than goiter patients ( 0.23 vs 0.15 mg/day ) but had a similar degree of TSH suppression . BMD and CaBI values did not correlate with free T4 index ) with the daily T4 dose , accumulative dose , or with duration of T4 therapy . There were no significant changes in bone mass in either goiter or cancer patients restudied after a mean of 1.5 years . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The influence of thyrotropin ( thyroid-stimulating hormone [ TSH ] ) suppressive therapy on bone mineral density ( BMD ) remains contentious . We have conducted a r and omized controlled trial evaluating the effects of postoperative TSH suppressive therapy on disease-free survival for papillary thyroid carcinoma ( PTC ) since 1996 , while prospect ively verifying the effects of TSH suppression on BMD . METHODS Lumbar spine BMD as expressed by T-score was examined annually in female patients r and omly assigned to receive TSH suppressive therapy ( group A ; n = 144 ) or no therapy ( group B ; n = 127 ) . RESULTS The mean TSH level was 0.07 ± 0.10 mU/L in group A and 3.14 ± 1.69 mU/L in group B. Group B did not show any significant decrease in T-score until 5 years postoperatively , whereas group A had a significant deterioration from 1 year postoperatively . Among group A patients , significant decreases in T-score within 1 year were seen in patients ≥ 50 years of age , but not in those < 50 years of age . After 5 years of TSH suppression , 20 patients had T-scores below -2.0 and 100 patients did not . These former patients were significantly older and had lower preoperative BMD measurements than the latter . CONCLUSION This prospect i ve controlled trial suggests that TSH suppression after surgery for PTC has adverse effects on BMD in women ≥ 50 years of age OBJECTIVE To address the influence of thyroid hormones on circulating markers of cell-mediated immune response in an in vivo human model . SUBJECTS AND DESIGN Twenty-two patients with stage I differentiated thyroid carcinoma were studied on the last day of thyroxine suppressive treatment , 4 - 7 days after withdrawal , and the day before whole body scanning . Three patients were excluded because of residual disease . Twenty euthyroid individuals served as controls . Serum thyrotrophin and thyroid hormones were measured by an immunometric assay , circulating cytokines by enzyme-linked immuno-sorbent assay and lymphoid population s by flow cytometry . RESULTS Thyroid function in patients changed from sub clinical or mild hyperthyroidism at the first visit , to a situation of normal circulating levels of free thyroxine and triiodothyronine at the second , ending in a state of overt hypothyroidism . Thyroxine suppressive treatment in patients increased serum interleukin-18 concentrations ( IL-18 , mean+/-s.d . , 280+/-122 vs 183+/-106 pg/ml , F = 3.192 , P = 0.029 ) , soluble interleukin-2 receptor levels ( sIL-2R , 4368+/-1480 vs 2564+/-846 pg/ml , F = 21.324 , P < 0.001 ) , and the percentage of natural killer ( NK ) cells in peripheral blood ( 15.9+/-8.6 vs 10.5+/-3.6 % , F = 4.977 , P = 0.004 ) compared with controls . After thyroxine withdrawal , serum levels of IL-18 , sIL-2R and the percentage of NK cells decreased progressively . CONCLUSION Our present results suggest that thyroid hormones modulate the cell-mediated immune response in humans Abstract . This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine ( l-T4 ) suppressive therapy in female patients who had undergone surgery for differentiated thyroid cancer ( DTC ) . Twenty female ( 14 premenopausal and 6 postmenopausal ) patients receiving l-T4 suppressive therapy for DTC were studied . The sample was selected in such a way as to avoid factors influencing bone metabolism other than l-T4 . All patients were monitored by sensitive thyroid-stimulating hormone , free triiodothyronine and free thyroxine assays throughout the follow-up . Nineteen healthy ( 12 premenopausal and 7 postmenopausal ) matched women served as controls . In all subjects bone turnover was evaluated by the measurement of global skeletal uptake of technetium-99 m methylene diphosphonate ( GSU ) ; bone mineral density ( BMD ) was measured by quantitative computed tomography at the lumbar spine ( LS ) and by dual-energy X-ray absorptiometry both at the LS and at three femoral sites : the femoral neck , Ward ’s triangle and the greater trochanter . No significant difference was found in either GSU or BMD between patients ( treated for an average period of 68 months ) and controls in the whole sample or in any subgroup . Furthermore , no correlations were found between either GSU or BMD and the duration of therapy , daily doses of l-T4 or results of thyroid function tests . Our data show that carefully monitored l-T4 therapy does not influence skeletal turnover ( directly reflected by GSU ) or the bone density of the spine and femur BACKGROUND Heart rate variability is a sensitive marker of cardiac sympathetic activity . OBJECTIVES To determine whether long-term hyperthyroidism induced by thyroxine suppressive therapy affects HRV . METHODS Nineteen patients treated with suppressive doses of thyroxin for thyroid cancer and 19 age-matched controls were enrolled . Thyroid function tests and 1 minute HRV were performed on all subjects and the results were compared between the groups . The 1 minute HRV was analyzed during deep breathing and defined as the difference in beats/minute between the shortest and the longest heart rate interval measured by eletrocardiographic recording during six cycles of deep breathing . RESULTS One minute HRV during deep breathing was significantly lower among thyroxine-treated patients compared to healthy controls ( 25.6 + /- 10.5 vs. 34.3 + /- 12.6 beats/min , P < 0.05 ) . There were no significant differences in mean , maximal and minimal heart rate between the groups . CONCLUSIONS Thyroxine therapy administered for epithelial thyroid cancer result ed in sub clinical hyperthyroidism and significantly decreased HRV due to autonomic dysfunction rather than basic elevated heart rate To examine whether suppressive doses of thyroxine have any adverse effects on bone , we evaluated various bone metabolic markers ( lectin-precipitated alkaline phosphatase , osteocalcin , carboxyl-terminal region of type I collagen propeptide , tartrate-resistant alkaline phosphatase , and urinary excretion of hydroxyproline and pyridinium crosslinks ) , incidence of vertebral deformity , total body and regional ( lumbar spine and radius ) bone mineral densities ( BMDs ) , and rates of bone loss in 24 late postmenopausal ( more than 5 years after menopause ) women who were treated with levothyroxine ( L-T4 ) after total thyroidectomy for differentiated carcinoma . Depending on the clinical records , including serum TSH levels measured by immunoradiometric assay , these patients were divided into two groups . One group of patients was given suppressive doses of L-T4 ( TSH < 0.1 mU/L , n = 12 ) and the other group was given nonsuppressive doses of L-T4 ( TSH > 0.1 mU/L , n = 12 ) . There was no difference in bone metabolic markers and incidence of vertebral deformity between the groups . In patients with TSH suppression , Z-scores of BMDs calculated from age-matched healthy women ( n = 179 , aged 55 to 80 ) were nearly in the zero range of values ( 0.077 at total body , 0.228 at lumbar spine , and -0.117 at trabecular region of lumbar spine ) . The rate of bone loss in TSH-suppressed patients ( -0.849 + /- 0.605%/year ) was not significantly different from that of nonsuppressed patients ( -0.669 + /- 0.659 ) . These prospect i ve and cross-sectional data suggest that long-term levothyroxine therapy using suppressive doses has no significant adverse effects on bone BACKGROUND Sub clinical thyrotoxicosis ( scTox ) may be associated with alterations in body composition and fatigue that can be possibly reversed with physical activity . The aim of the present study was to evaluate whether the systematic practice of physical activity improves lower extremity muscle mass and fatigue perception in patients with scTox . MATERIAL S AND METHODS We studied 36 patients ( 2 men ) with median age of 48.0 ( 43.0 - 51.0 ) years , body mass index of 27.4 ( 22.1 - 30.2 ) kg/m(2 ) , thyrotropin < 0.4 mU/L , and free thyroxine between 0.8 and 1.9 ng/dL and 48 control subjects ( C group ; 7 men ) . Patients were r and omly divided in two groups according to the adherence to the exercise training : scTox-Tr ( n = 19)- patients who adhered to the exercise intervention and scTox-Sed ( n = 17)-- patients who did not adhere to it . The C group did not participate in the r and omization . The exercise training was supervised by a physical education instructor , and it was composed of 60 minutes of aerobic activity and stretching exercises , twice a week , during 12 weeks . In both groups , body composition was assessed ( anthropometric method ) , and the Chalder Fatigue Scale was determined at baseline and after 3 months of intervention ( scTox-Tr group ) or observation ( scTox-Sed group ) . RESULTS At baseline , patients with scTox had lower muscle mass and mid-thigh girth and more fatigue on the Chalder Fatigue Scale than euthyroid control subjects . The scTox-Tr group had an increase in muscle mass , reduction in the variables reflecting whole body fat , and lesser perception of fatigue during the exercise training period ( p ≤ 0.05 for these parameters at the start and end of the exercise training period ) . CONCLUSIONS scTox is associated with lower muscle mass and mid-thigh girth and more fatigue . Physical activity training can partially ameliorate these characteristics . More studies are needed to determine what training program would be optimum , both in terms of beneficial effects and for avoiding potential adverse responses The effect of sub clinical hyperthyroidism on bone mineral density is controversial and could be significant in patients with differentiated thyroid carcinoma who receive suppressive doses of levothyroxine ( LT4 ) . To ascertain whether prolonged treatment with LT4 to suppress thyrotropin had a deleterious effect on bone mineral density and /or calcium metabolism in patients thyroidectomized for differentiated thyroid cancer we have performed a cross-sectional study in a group of 88 women ( mean + /- SD age : 51 + /- 12 years ) treated with LT4 after near-total thyroidectomy and in a control group of 88 healthy women ( 51 + /- 11 years ) matched for body mass index and menopausal status . We determined calcium metabolism parameters , bone turnover marker N-telopeptide and bone mass density by dual-energy X-ray absorptiometry . No differences were found between patients and controls in calcium metabolism parameters or N-telopeptide except for PTH , which was significantly increased in controls . No differences were found between groups in bone mineral density in femoral neck ( 0.971 + /- 0.148 gr/cm(2 ) vs 0.956 + /- 0.130 gr/cm(2 ) in patients and controls respectively , P = 0.5 ) . In lumbar spine , bone mineral density values were lower in controls than in patients ( 1.058 + /- 0.329 gr/cm(2 ) vs 1.155 + /- 0.224 gr/cm(2 ) respectively , P < 0.05 ) . When premenopausal ( n = 44 ) and postmenopausal ( n = 44 ) patients were compared with their respective controls , bone mineral density was similar both in femoral neck and lumbar spine . The proportion of women with normal bone mass density , osteopenia and osteoporosis in patient and control groups was similar in pre- and postmenopausal women . In conclusion , long-term suppressive LT4 treatment does not appear to affect skeletal integrity in women with differentiated thyroid carcinoma |
11,826 | 25,917,293 | Baseline severity was not associated with an antidepressant-placebo difference and placebo responses are large in the treatment of depressed elderly people . | BACKGROUND Baseline severity is a crucial moderator of trial outcomes in adult depression , with the advantage of antidepressants over placebo increasing as severity increases .
However , this relationship has not been examined in late-life depression . | Supportive social relationships , including a positive patient-practitioner relationship , have been associated with positive health outcomes . Using the data from a r and omized controlled trial ( RCT ) undertaken in the Boston area of the United States , this study sought to identify baseline factors predictive of patients ' response to an experimentally applied supportive patient-practitioner relationship . To sort through the hundreds of potential attributes affecting the patient-practitioner relationship , we applied a false discovery rate method borrowed from the field of genomics and bioinformatics . To our knowledge such a method has not previously been applied to generate hypotheses from clinical trial data . In a previous RCT , our team investigated the effect of the patient-practitioner relationship on symptom improvement in patients with irritable Bowel syndrome ( IBS ) . Data were collected on a sample of 289 individuals with IBS using a three-week , single blind , three arm , r and omized controlled design . We found that a supportive patient-practitioner relationship significantly improved symptomatology and quality of life . A complex , multi-level measurement package was used to prospect ively measure change and identify factors associated with improvement . Using a local false discovery rate procedure , we examined the association of 452 baseline subject variables with sensitivity to treatment . Out of 452 variables , only two baseline factors , reclusiveness , and previous trial experience increased sensitivity to the supportive patient-practitioner relationship . A third variable , additional opportunity during the study for subjects to discuss their illness through experiential interview , was associated with improved outcomes among subjects who did not receive the supportive patient-practitioner relationship . The few variables associated with differential benefit suggest that a patient-centered supportive patient-practitioner relationship may be beneficial for most patients . This may be especially important for reclusive individuals . Within the context of our study , additional study attention in the form of repeated experiential interviews compensated for a lack of positive patient-practitioner support . A supportive patient-practitioner relationship may also help overcome low provider expectations for subjects with previous trial experience . These results converge with the results of the parent trial , implicating the importance of the social world in healing Background It is an inherent assumption in r and omised controlled trials that the drug effect can be estimated by subtracting the response during placebo from the response during active drug treatment . Objective To test the assumption of additivity . The primary hypothesis was that the total treatment effect is smaller than the sum of the drug effect and the placebo effect . The secondary hypothesis was that non-additivity was most pronounced in participants with large placebo effects . Methods We used a within-subject r and omised blinded balanced placebo design and included 48 healthy volunteers ( 50 % males ) , mean ( SD ) age 23.4 ( 6.2 ) years . Experimental pain was induced by injections of hypertonic saline into the masseter muscle . Participants received four injections with hypertonic saline along with lidocaine or matching placebo in r and omised order : A : received hypertonic saline/told hypertonic saline ; B : received hypertonic saline+lidocaine/told hypertonic saline ; C : received hypertonic saline+placebo/told hypertonic saline+pain killer ; D : received hypertonic saline+lidocaine/told hypertonic saline+pain killer . The primary outcome measure was the area under the curve ( AUC , mm2 ) of pain intensity during injections . Results There was a significant difference between the sum of the drug effect and the placebo effect ( mean AUC 6279 mm2 ( 95 % CI , 4936–7622 ) ) and the total treatment effect ( mean AUC 5455 mm2 ( 95 % CI , 4585–6324 ) ) ( P = 0.049 ) . This difference was larger for participants with large versus small placebo effects ( P = 0.015 ) , and the difference correlated significantly with the size of the placebo effect ( r = 0.65 , P = 0.006 ) . Conclusion Although this study examined placebo effects and not the whole placebo response as in r and omised controlled trials , it does suggest that the additivity assumption may be incorrect , and that the estimated drug effects in r and omised controlled trials may be underestimated , particularly in studies reporting large placebo responses . The implication s for r and omised controlled trials and systematic review s need to be discussed BACKGROUND Depression is frequently found in patients with age-related macular degeneration ( AMD ) . The purpose of this study was to assess the effectiveness of escitalopram in treating major and minor depression in AMD patients . METHODS We conducted a crossover , r and omized , double-blind , placebo-controlled , 16-week study comparing escitalopram with placebo . Inclusion criteria included reduced vision from AMD and major or minor depression , with a 17-item Hamilton Rating Scale for Depression ( HAMD-17 ) score of ≥10 . Participants were r and omly assigned to receive either escitalopram or placebo for 8 weeks and then crossed over to the other treatment . The primary outcome was change on the total HAMD-17 score with escitalopram treatment compared with placebo . RESULTS We enrolled 16 AMD patients ( mean age 79.1 ) , 12 with major depression and 4 with minor depression . Mean HAMD-17 score at enrollment was 16.1 ± 4.2 , and mean visual acuity in the better eye was 20/70 . During escitalopram treatment , participants showed a significant reduction in HAMD-17 scores compared with placebo treatment ( P = .01 ) . CONCLUSIONS These findings suggest escitalopram may be an effective treatment for depressive symptoms associated with major or minor depression in AMD patients with vision loss OBJECTIVE The present study examined the efficacy and tolerability of acute escitalopram treatment in depressed patients aged 60 years or older . METHODS Patients aged > or = 60 years with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition major depressive disorder were r and omized to 12 weeks of double-blind , flexible-dose treatment with escitalopram ( 10 - 20 mg/day ; N = 130 ) or placebo ( N = 134 ) . The prospect ively defined primary efficacy end point was change from baseline to week 12 in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score using the last observation carried forward approach . RESULTS A total of 109 ( 81 % ) patients in the placebo group and 96 ( 74 % ) patients in the escitalopram group completed treatment . Mean age in both groups was approximately 68 years . Mean baseline MADRS scores were 28.4 and 29.4 for the placebo and escitalopram treatment groups , respectively . Escitalopram did not achieve statistical significance compared with placebo in change from baseline on the MADRS ( least square mean difference : -1.34 ; last observation carried forward ) . Discontinuation rates result ing from adverse events were 6 % for placebo and 11 % for escitalopram . Treatment-emergent adverse events reported by > 10 % of patients in the escitalopram group were headache , nausea , diarrhea , and dry mouth . CONCLUSIONS Escitalopram treatment was not significantly different from placebo treatment on the primary efficacy measure , change from baseline to week 12 in MADRS . In patients aged 60 years or older with major depression , acute escitalopram treatment appeared to be well tolerated The purpose of this study was to compare the effects of 16 weeks of a comprehensive exercise routine to supervised walking and social conversation on depression in nursing home residents with Alzheimer 's disease ( AD ) . Method : This study was a three-group , repeated- measures design with r and om assignment to treatment group . Forty-five nursing home residents with moderate to severe AD were r and omly assigned to a 16-week programme of comprehensive exercise , supervised walking or social conversation . Raters were blinded to treatment group assignment . Major outcome variables were depression measured by the Cornell Scale for Depression in Dementia , mood measured by the Dementia Mood Assessment Scale and the Alzheimer 's Mood Scale , and affect measured by the Observed Affect Scale . Depression was reduced in all three groups with some evidence of superior benefit from exercise . Depression is a common problem with serious and costly consequences for nursing home residents with AD . Exercise as a behavioural approach to treatment of depression in nursing home residents with severe AD evidence d a clear benefit to participants in this study . More research is needed to clarify the relative benefits of different types of exercise in conjunction with or without pharmacological intervention The logic of the r and omized double-blind placebo control group design is presented , and problems with using the design in psychotherapy are discussed . Placebo effects are estimated by examining clinical trials in medicine and psychotherapy . In medicine , a recent meta- analysis of clinical trials with treatment , placebo , and no treatment arms was conducted ( Hróbjartsson & Gøtzsche , 2001 ) , and it was concluded that placebos have small or no effects . A re- analysis of those studies , presented here , shows that when disorders are amenable to placebos and the design is adequate to detect the effects , the placebo effect is robust and approaches the treatment effect . For psychological disorders , particularly depression , it has been shown that pill placebos are nearly as effective as active medications whereas psychotherapies are more effective than psychological placebos . However , it is shown that when properly design ed , psychological placebos are as effective as accepted psychotherapies BACKGROUND Pill-taking , expectations and therapeutic alliance may account for much of the benefit of medication and placebo treatment for major depressive disorder ( MDD ) . Aims To examine the effects of medication , placebo and supportive care on treatment outcome , and the relationships of expectations and therapeutic alliance to improvement . METHOD A total of 88 participants were r and omised to 8 weeks of treatment with supportive care alone or combined with double-blind treatment with placebo or antidepressant medication . Expectations of medication effectiveness , general treatment effectiveness and therapeutic alliance were measured ( trial registration at Clinical Trials.gov : NCT00200902 ) . RESULTS Medication or placebo plus supportive care were not significantly different but had significantly better outcome than supportive care alone . Therapeutic alliance predicted response to medication and placebo ; expectations of medication effectiveness at enrolment predicted only placebo response . CONCLUSIONS Pill treatment yielded better outcome than supportive care alone . Medication expectations uniquely predicted placebo treatment outcome and were formed by time of enrolment , suggesting that they were shaped by prior experiences outside the clinical trial A previously tested theoretical model that specifies relationships among depression , activities of daily living ( ADL ) impairment , and social support components was vali date d with 307 patients aged 60 and older from a multisite effectiveness trial of 3 treatments ( antidepressant , placebo , Problem-Solving Treatment ) for dysthymia or minor depression in primary care . Participants completed interviews and self-reports at baseline and at 6 and 12 weeks . The short-term , longitudinal data were analyzed with covariance structure modeling techniques . Consistent with the previous model , impairment in ADLs was associated with subsequent increases in depression , a larger emotionally close network that made frequent visits was associated with subsequent increases in perceived support , and perceived support was associated with subsequent decreases in depression . This last effect was significant only among participants r and omly assigned to receive placebo with clinical management . The similar results in 2 different studies are a substantial validation of the theoretical model . The effect of perceived support primarily in the placebo group suggests that those with greater perceived social support and subsyndromal depression may be more likely to have a positive response to nonspecific clinical treatment components CONTEXT Insufficient evidence exists for recommendation of specific effective treatments for older primary care patients with minor depression or dysthymia . OBJECTIVE To compare the effectiveness of pharmacotherapy and psychotherapy in primary care setting s among older persons with minor depression or dysthymia . DESIGN R and omized , placebo-controlled trial ( November 1995-August 1998 ) . SETTING Four geographically and clinical ly diverse primary care practice s. PARTICIPANTS A total of 415 primary care patients ( mean age , 71 years ) with minor depression ( n = 204 ) or dysthymia ( n = 211 ) and a Hamilton Depression Rating Scale ( HDRS ) score of at least 10 were r and omized ; 311 ( 74.9 % ) completed all study visits . INTERVENTIONS Patients were r and omly assigned to receive paroxetine ( n = 137 ) or placebo ( n = 140 ) , starting at 10 mg/d and titrated to a maximum of 40 mg/d , or problem-solving treatment- primary care ( PST-PC ; n = 138 ) . For the paroxetine and placebo groups , the 6 visits over 11 weeks included general support and symptom and adverse effects monitoring ; for the PST-PC group , visits were for psychotherapy . MAIN OUTCOME MEASURES Depressive symptoms , by the 20-item Hopkins Symptom Checklist Depression Scale ( HSCL-D-20 ) and the HDRS ; and functional status , by the Medical Outcomes Study Short-Form 36 ( SF-36 ) physical and mental components . RESULTS Paroxetine patients showed greater ( difference in mean [ SE ] 11-week change in HSCL-D-20 scores , 0.21 [ 0 . 07 ] ; P = .004 ) symptom resolution than placebo patients . Patients treated with PST-PC did not show more improvement than placebo ( difference in mean [ SE ] change in HSCL-D-20 scores , 0.11 [ 0.13 ] ; P = .13 ) , but their symptoms improved more rapidly than those of placebo patients during the latter treatment weeks ( P = .01 ) . For dysthymia , paroxetine improved mental health functioning vs placebo among patients whose baseline functioning was high ( difference in mean [ SE ] change in SF-36 mental component scores , 5.8 [ 2.02 ] ; P = . 01 ) or intermediate ( difference in mean [ SE ] change in SF-36 mental component scores , 4.4 [ 1.74 ] ; P = .03 ) . Mental health functioning in dysthymia patients was not significantly improved by PST-PC compared with placebo ( P>/=.12 for low- , intermediate- , and high-functioning groups ) . For minor depression , both paroxetine and PST-PC improved mental health functioning in patients in the lowest tertile of baseline functioning ( difference vs placebo in mean [ SE ] change in SF-36 mental component scores , 4.7 [ 2.03 ] for those taking paroxetine ; 4.7 [ 1.96 ] for the PST-PC treatment ; P = .02 vs placebo ) . CONCLUSIONS Paroxetine showed moderate benefit for depressive symptoms and mental health function in elderly patients with dysthymia and more severely impaired elderly patients with minor depression . The benefits of PST-PC were smaller , had slower onset , and were more subject to site differences than those of paroxetine OBJECTIVE To compare the efficacy of duloxetine with placebo on depression in elderly patients with major depressive disorder . DESIGN Multicenter , 24-week ( 12-week short-term and 12-week continuation ) , r and omized , placebo-controlled , double-blind trial . SETTING United States , France , Mexico , Puerto Rico . PARTICIPANTS Age 65 years or more with major depressive disorder diagnosis ( one or more previous episode ) ; Mini-Mental State Examination score ≥20 ; Montgomery-Asberg Depression Rating Scale total score ≥20 . INTERVENTION Duloxetine 60 or 120 mg/day or placebo ; placebo rescue possible . MEASUREMENTS Primary -Maier subscale of the 17-item Hamilton Depression Rating Scale ( HAMD-17 ) at week 12 . Secondary -Geriatric Depression Scale , HAMD-17 total score , cognitive measures , Brief Pain Inventory ( BPI ) , Numeric Rating Scales ( NRS ) for pain , Clinical Global Impression-Severity scale , Patient Global Impression of Improvement in acute phase and acute plus continuation phase of treatment . RESULTS Compared with placebo , duloxetine did not show significantly greater improvement from baseline on Maier subscale at 12 weeks , but did show significantly greater improvement at weeks 4 , 8 , 16 , and 20 . Similar patterns for Geriatric Depression Scale and Clinical Global Impression-Severity scale emerged , with significance also seen at week 24 . There was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures in the acute phase , most BPI items and half of the NRS measures in the continuation phase . More duloxetine-treated patients completed the study ( 63 % versus 55 % ) . A significantly higher percentage of duloxetine-treated patients versus placebo discontinued due to adverse event ( 15.3 % versus 5.8 % ) . CONCLUSIONS Although the antidepressant efficacy of duloxetine was not confirmed by the primary outcome , several secondary measures at multiple time points suggested efficacy . Duloxetine had significant and meaningful beneficial effects on pain This study investigated the psychological characteristics and clinical features of 55 patients with geriatric depression , and evaluated the efficacy and safety of escitalopram in the treatment of geriatric depression , in a r and omized controlled trial . Fifty-five patients with geriatric depression were r and omly assigned to receive 8 weeks of escitalopram 10 mg , daily , orally ( n = 29 ) or placebo ( n = 26 ) . At baseline , these patients had significantly higher neuroticism and psychoticism scores on the Eysenck Personality Question naire - Adult scale than Chinese population norms . General Severity Index scores and the mean values of the nine subscales of the Symptom Checklist-90- Revised scale were also significantly higher in these patients than in Chinese population norms . The response rate to escitalopram after 8 weeks ' treatment was 74.1 % ( 20/27 patients ) . Adverse reactions included nausea , dry mouth and dizziness . In conclusion , depressed geriatric patients were found to have abnormal personality traits , and escitalopram was efficacious and had a good safety profile in the treatment of geriatric depression BACKGROUND Despite the high prevalence of depression in elderly patients , few well- design ed , placebo-controlled studies of antidepressants have been conducted in this population . This masked , placebo-controlled trial assessed the efficacy and safety of venlafaxine and fluoxetine in depressed patients older than 65 years . METHOD Three hundred patients were r and omly assigned to treatment with venlafaxine immediate release ( [ IR ] ; N = 104 ) , fluoxetine ( N = 100 ) , or placebo ( N = 96 ) in an eight-week trial . Venlafaxine doses were titrated from 37.5 to 225 mg per day and fluoxetine doses were titrated from 20 to 60 mg per day , as necessary , over 29 days . Efficacy variables included the 21-item Hamilton Depression Rating Scale ( HAM-D21 ) total score , HAM-D21 depressed mood item score , scores on the Montgomery Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impression-Severity of Illness ( CGI-S ) and Improvement ( CGI-I ) scales , and rates of response ( based on change from baseline HAM-D or MADRS score or CGI-I score ) and remission ( HAM-D17 < or = 7 ) . For the purpose s of this report , efficacy analyses are focused on the HAM-D21 total score . Safety assessment s included monitoring of adverse events ( AEs ) , physical examinations , vital signs assessment s , laboratory determinations , and electrocardiograms . RESULTS In all three of the treatment groups , there was a significant reduction at week 8 compared with the baseline HAM-D21 total score . However , there were no significant differences among the three treatment groups on the change in HAM-D21 , MADRS , or CGI scores from baseline to week 8 . There was no statistically significant difference in the proportion of remitters at the last on-therapy visit . The incidence of individual AEs was higher in the venlafaxine group ( 27 % ) compared with patients taking fluoxetine ( 19 % ) or placebo ( 9 % ) . CONCLUSION In this study , there was no significant difference in efficacy among placebo , venlafaxine , and fluoxetine for the treatment of depression BACKGROUND Depression is the second most common neuropsychiatric disorder in older Americans , with significant clinical and public health costs . Despite advances in treatment , late-life depression remains a clinical challenge . Although the selective serotonin reuptake inhibitors ( SSRIs ) are the most common pharmacologic intervention for late-life depression , few placebo-controlled trials have assessed the efficacy of SSRIs for this condition . METHOD In this 12-week , multicenter , placebo-controlled , flexible-dose , double-blind , r and omized trial , 319 elderly patients ( mean age = 70 years ) were treated with controlled-release paroxetine ( paroxetine CR ) up to 50 mg/day ( N = 104 ) , immediate-release paroxetine ( paroxetine IR ) up to 40 mg/day ( N = 106 ) , or placebo ( N = 109 ) . Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) . The primary efficacy measure was change from baseline to endpoint in HAM-D total score . RESULTS The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 ( 95 % confidence interval [ CI ] = -4.47 to -0.73 , p = .007 ) at the week 12 last-observation-carried-forward ( LOCF ) endpoint . The adjusted difference between paroxetine IR and placebo was -2.8 ( 95 % CI = -4.65 to -0.99 , p = .003 ) at week 12 . Paroxetine CR and IR were more effective than placebo , with mean + /- SD endpoint HAM-D total scores of 10.0 + /- 7.41 and 10.0 + /- 7.10 , respectively , for the active treatments compared with 12.6 + /- 7.34 for placebo . Response , defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale , was achieved by 72 % of paroxetine CR patients ( LOCF ; p < .002 vs. placebo ) , 65 % of paroxetine IR patients ( p = .06 vs. placebo ) , and 52 % of placebo patients . Remission , defined as a HAM-D total score < or = 7 , was achieved by 43 % of paroxetine CR patients ( LOCF ; p = .009 vs. placebo ) , 44 % of paroxetine IR patients ( p = .01 vs. placebo ) , and 26 % of placebo patients . In a post hoc analysis , mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients ( duration > 2 years ) and those with short-term ( < or = 2 years ) depression . Dropout rates due to adverse events were 12.5 % for paroxetine CR , 16.0 % for paroxetine IR , and 8.3 % for placebo . CONCLUSION Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients , including those with chronic depression OBJECTIVE To evaluate the efficacy and tolerability of low daily doses of controlled-release ( CR ) paroxetine in patients with late-life depression . METHOD This was a 10-week , multicenter , placebo-controlled , double-blind , fixed-dose trial r and omly assigning patients > or= 60 years old to daily doses of paroxetine CR 12.5 mg ( N = 168 ) , paroxetine CR 25 mg ( N = 177 ) , or placebo ( N = 180 ) . Patients had major depressive disorder ( DSM-IV criteria ) and 17-item Hamilton Rating Scale for Depression ( HAM-D ) total scores of > or= 18 . The primary efficacy variable was the change from baseline to study endpoint in total HAM-D scores . The study was conducted from June 2003 to October 2004 . RESULTS The drug/placebo difference in HAM-D change from baseline at study endpoint was -1.8 ( 95 % CI = -3.41 to -0.19 , p = .029 ) for paroxetine CR 12.5 mg , and -3.3 ( 95 % CI = -4.84 to -1.68 , p < .001 ) for paroxetine CR 25 mg . A significantly larger percentage of patients achieved remission ( HAM-D total score < or= 7 at endpoint ) with paroxetine CR 25 mg ( 41 % ) , but not with 12.5 mg ( 31 % ) , as compared with placebo ( 28 % ) ( p = .008 ) . Both doses of paroxetine CR also achieved statistical significance compared to placebo for the Clinical Global Impressions-Severity of Illness scale ( p < .01 ) and the patient-rated measures of depression severity ( p < .05 ) and quality of life ( p < or= .001 ) . Both active treatments were generally well tolerated , with adverse event withdrawal rates of 6 % , 8 % , and 7 % for paroxetine CR 12.5 mg , paroxetine CR 25 mg , and placebo , respectively . CONCLUSION These data demonstrate that paroxetine CR 12.5 mg and 25 mg daily are efficacious and well tolerated in the treatment of major depressive disorder in patients > or= 60 years of age , although effect sizes are relatively smaller with the 12.5 mg/day dose OBJECTIVE This study determined the efficacy of antidepressant medication for the treatment of depression in the " old-old . " METHOD This r and omized 8-week medication trial compared citalopram , 10 - 40 mg/day , to placebo in the treatment of patients 75 and older with unipolar depression . RESULTS A total of 174 patients who were 58 % women with a mean age of 79.6 years ( SD=4.4 ) and a mean baseline Hamilton Depression Rating Scale score of 24.3 ( SD=4.1 ) were r and omly assigned to treatment at 15 sites . There was a main effect for site but not for treatment condition . The remission rate , defined as a final Hamilton depression scale score < 10 , was 35 % for the citalopram and 33 % for the placebo groups . However , patients with severe depression ( baseline Hamilton depression scale score > 24 ) tended to have a higher remission rate with medication than with placebo ( 35 % versus 19 % ) . CONCLUSIONS In the oldest group of community-dwelling patients to be studied to date , medication was not more effective than placebo for the treatment of depression . However , given the considerable psychosocial support received by all patients , the placebo condition represents more than the ingestion of an inactive pill . Across sites , there was considerable range in response to medication , 18 % to 82 % , and to placebo , 16 % to 80 % OBJECTIVE There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients . This placebo-controlled study of sertraline was design ed to confirm the results of non-placebo-controlled trials . METHOD The subjects were out patients age 60 years or older who had a DSM-IV diagnosis of major depressive disorder and a total score on the 17-item Hamilton Depression Rating Scale of 18 or higher . The patients were r and omly assigned to 8 weeks of double-blind treatment with placebo or a flexible daily dose of 50 or 100 mg of sertraline . The primary outcome variables were the Hamilton scale and Clinical Global Impression ( CGI ) scales for severity and improvement . RESULTS A total of 371 patients assigned to sertraline and 376 assigned to placebo took at least one dose . At endpoint , the patients receiving sertraline evidence d significantly greater improvements than those receiving placebo on the Hamilton depression scale and CGI severity and improvement scales . The mean changes from baseline to endpoint in Hamilton score were -7.4 points ( SD=6.3 ) for sertraline and -6.6 points ( SD=6.4 ) for placebo . The rate of CGI-defined response at endpoint was significantly higher for sertraline ( 45 % ) than for placebo ( 35 % ) , and the time to sustained response was significantly shorter for sertraline ( median , 57 versus 61 days ) . There were few discontinuations due to treatment-related adverse events , 8 % for sertraline and 2 % for placebo . CONCLUSIONS Sertraline was effective and well tolerated by older adults with major depression , although the drug-placebo difference was not large in this 8-week trial The efficacy and tolerability of Lu AA21004 at 5 mg/day , a novel multimodal antidepressant , were assessed in elderly patients with recurrent major depressive disorder . Patients were r and omly assigned ( 1 : 1 : 1 ) to Lu AA21004 5 mg/day , duloxetine 60 mg/day ( reference ) or to placebo in an 8-week double-blind study . The primary efficacy measure was the 24-item Hamilton Depression Scale ( HAM-D24 ) total score ( analysis of covariance , last observation carried forward ) . Patients ( mean age 70.6 years ) had a mean baseline HAM-D24 score of 29.0 . Lu AA21004 showed significantly ( P=0.0011 ) greater improvement on the primary efficacy endpoint compared with placebo at week 8 ( 3.3 points ) . Duloxetine also showed superiority to placebo at week 8 , thereby validating the study . HAM-D24 response ( 53.2 vs. 35.2 % ) and HAM-D17 remission ( 29.2 vs. 19.3 % ) rates at endpoint were higher for Lu AA21004 than for placebo . Lu AA21004 showed superiority to placebo in cognition tests of speed of processing , verbal learning and memory . The withdrawal rate due to adverse events was 5.8 % ( Lu AA21004 ) , 9.9 % ( duloxetine ) and 2.8 % ( placebo ) . Whereas nausea was the only adverse event with a significantly higher incidence on treatment with Lu AA21004 ( 21.8 % ) compared with placebo ( 8.3 % ) , the incidence of nausea , constipation , dry mouth , hyperhidrosis and somnolence was higher for duloxetine . In conclusion , Lu AA21004 was efficacious and well tolerated in the treatment of elderly patients with recurrent major depressive disorder Abstract Expectation/placebo‐related mechanisms and specific effects of therapies show additive effects , such that a therapy is less effective if the placebo component is absent . So far , the placebo component has been disrupted experimentally by using covert administrations of treatments . Here , we show for the first time that disruption of expectation/placebo‐related analgesic mechanisms may occur in a clinical condition , Alzheimer ’s disease ( AD ) . In order to assess the placebo component of a therapy , we used the recently developed open – hidden paradigm . A local anesthetic was applied , either overtly or covertly , to the skin of AD patients to reduce burning pain after venipuncture . The placebo ( psychological ) component is represented by the difference between the analgesic effect after open ( expected ) and after hidden ( unexpected ) application . We correlated the placebo component with both cognitive status and functional connectivity among different brain regions . We found that AD patients with reduced Frontal Assessment Battery scores showed reduced placebo component of the analgesic treatment . We also found that the disruption of the placebo component occurred when reduced connectivity of the prefrontal lobes with the rest of the brain was present . Remarkably , the loss of these placebo‐related mechanisms reduced treatment efficacy , such that a dose increase was necessary to produce adequate analgesia . These findings highlight the active role of cognition and prefrontal lobes in the therapeutic outcome and underscore the need of considering a possible revision of the therapeutic approach in Alzheimer patients in order to compensate for the loss of the endogenous expectation and placebo mechanisms BACKGROUND Executive dysfunction is common in geriatric depression and persists after improvement of depressive symptoms . This study examined the relationship of executive impairment to the course of depressive symptoms among elderly patients with major depression . METHODS A total of 112 nondemented elderly patients with major depression participated in an 8-week citalopram trial at a target daily dose of 40 mg . Executive functions were assessed with the initiation/perseveration subscale of the Dementia Rating Scale and the Stroop Color-Word test . Medical burden was rated with the Cumulative Illness Rating Scale . RESULTS Both abnormal initiation/perseveration and abnormal Stroop Color-Word scores were associated with an unfavorable response of geriatric depression to citalopram . In particular , initiation/perseveration scores below the median ( < or = 35 ) and Stroop scores at the lowest quartile ( < or = 22 ) predicted limited change in depressive symptoms . Impairment in other Dementia Rating Scale cognitive domains did not significantly influence the outcome of depression . CONCLUSIONS Executive dysfunction increases the risk for poor response of geriatric depression to citalopram . Because executive functions require frontostriatal-limbic integrity , this observation provides the rationale for investigation of the role of specific frontostriatal-limbic pathways in perpetuating geriatric depression . Depressed elderly patients with executive dysfunction require vigilant clinical attention because they might be at risk to fail treatment with a selective serotonin reuptake inhibiting antidepressant OBJECTIVE Much of the response to an antidepressant is the result of placebo response . The placebo response embedded in drug response confounds studies seeking to identify brain mechanisms essential for pharmacologic response . Exclusion of patients who fail to meet entry criteria at the end of a placebo lead-in phase has been inadequate to reduce the effect of placebo during pharmacologic trials . This study focused on the placebo lead-in phase and examines whether change in severity of depression during placebo lead-in predicts change in depressive symptoms during antidepressant treatment . METHOD The subjects were patients aged 60 - 85 years with nonpsychotic unipolar major depression not attributed to dementing disorders , medical illnesses , or drugs causing depression and had a 24-item Hamilton Depression Rating Scale score of 18 or greater . After a two-week placebo lead-in , subjects with Hamilton Depression Rating Scale score of 18 or greater received 10 mg escitalopram for 12 weeks . RESULTS Worsening or limited change in depression during placebo treatment predicted improvement in depressive symptoms during escitalopram treatment . Limited change in anxiety , melancholia , helplessness , and paranoia during placebo treatment were the strongest predictors of improvement in depression while on escitalopram . CONCLUSIONS These findings , if replicated , may be used to characterize depressed older patients likely to respond to the pharmacologic action of antidepressants rather than the placebo response embedded in drug trials and thus improve the methodology of biomarker studies of antidepressant response . On a clinical level , depressed older patients who improve during a prolonged evaluation may be c and i date s for nonpharmacologic treatments because their drug response may be limited OBJECTIVE The authors compared the efficacy and side effects of fluoxetine and placebo in elderly out patients with dysthymic disorder . METHODS Patients were r and omly assigned to fluoxetine ( 20 mg-60 mg/day ) or placebo for 12 weeks in a double-blind trial . RESULTS Of 90 r and omized patients , 71 completed the trial . In the intent-to-treat sample , r and om regression analyses of the Hamilton Rating Scale for Depression ( Ham-D ; 24-item ) and Cornell Dysthymia Rating Scale ( CDRS ) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group . Analysis of percentage change in Ham-D scores yielded no effect for treatment group , but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group , favoring fluoxetine over placebo . In the intent-to-treat sample , response rates were 27.3 % for fluoxetine and 19.6 % for placebo . In the completer sample , response rates were 37.5 % for fluoxetine and 23.1 % for placebo . CONCLUSION Fluoxetine had limited efficacy in elderly dysthymic patients . The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults , and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients . Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder , and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance Sixty unipolar depressed geriatric out patients were subjects in a double-blind study of a new antidepressant , trazodone , versus imipramine and placebo . Over the four week study , patients in the two active medication groups improved significantly compared to placebo on both observer and self-ratings . Although imipramine and trazodone had similar therapeutic efficacy , trazodone was judged to have fewer side effects than imipramine , suggesting that trazodone may have particular clinical utility in the geriatric population which is especially vulnerable to cardiovascular and anticholinergic side effects |
11,827 | 25,851,268 | No differences were observed between antibiotics versus no treatment of asymptomatic bacteriuria for the development of symptomatic UTI , complications or death .
Antibiotics were superior to no treatment for the bacteriological cure but with significantly more adverse events .
There was no clinical benefit from treating asymptomatic bacteriuria in the studies included in this review | BACKGROUND Asymptomatic bacteriuria is commonly detected in women aged up to 60 years , patients with diabetes , and the elderly .
The benefit of antibiotic treatment for this condition is controversial .
OBJECTIVES To assess the effectiveness and safety of antibiotics treatment for asymptomatic bacteriuria in adults .
Specific objectives were to assess 1 ) the effectiveness of antibiotics for preventing development of symptomatic UTI , UTI-related complications , overall mortality , UTI-related mortality , and resolution of bacteriuria ; 2 ) the development of resistance to antibiotic treatment by comparing resistance of grown bacteria in urine before and after therapy ; and 3 ) the frequency of adverse events . | BACKGROUND Little is known about the role of asymptomatic bacteriuria ( AB ) treatment in young women affected by recurrent urinary tract infection ( UTI ) . We aim ed to evaluate the impact of AB treatment on the recurrence rate among young women affected by recurrent UTI . METHODS A total of 673 consecutive asymptomatic young women with demonstrated bacteriuria from January 2005 to December 2009 were prospect ively enrolled . Patients were split into 2 groups : not treated ( group A , n = 312 ) and treated ( group B , n = 361 ) . Microbiological and clinical evaluations were performed at 3 , 6 , and 12 months . Quality of life was also measured . Recurrence-free rate at the end of the entire study period was the main outcome measure . RESULTS At baseline , the 2 most commonly isolated pathogens were Escherichia coli ( group A , 38.4 % ; group B , 39.3 % ) and Enterococcus faecalis ( group A , 32.7 % ; group B , 33.2 % ) . At the first follow-up visit , there was no difference between the 2 groups ( relative risk [ RR ] , 1.05 ; 95 % confidence interval [ CI ] , 1.01 - 1.10 ) , whereas after 6 months , 23 ( 7.6 % ) in group A and 98 ( 29.7 % ) in group B showed recurrence with a statistically significant difference ( RR , 1.31 ; 95 % CI , 1.21 - 1.42 ; P < .0001 ) . At the last follow-up , 41 ( 13.1 % ) in group A and 169 ( 46.8 % ) in group B showed recurrence ( RR , 3.17 ; 95 % CI , 2.55 - 3.90 ; P < .0001 ) . One patient in group A and 2 patients in group B were found to have pyelonephritis . CONCLUSIONS This study shows that AB should not be treated in young women affected by UTI , suggesting it may play a protective role in preventing symptomatic recurrence BACKGROUND Persistent Escherichia coli asymptomatic bacteriuria ( ASB ) is common among persons with diabetes mellitus , but the duration of colonization and the rates of recolonization are unknown . We estimated the duration of colonization and the rate of recolonization among successively isolated E. coli from diabetic women with ASB and compared the virulence profiles with uropathogenic and commensal E. coli . METHODS A total of 105 women with diabetes were enrolled in a r and omized , controlled clinical trial for treatment of ASB in Manitoba , Canada , and were observed at least every 3 months for up to 3 years . We analyzed 517 isolates from 70 women with repeated E. coli ASB for genetic similarity using enterobacterial repetitive intergenic consensus polymerase chain reaction . Unique strains were screened for uropathogenic virulence characteristics using dot blot hybridization and compared with different collection s of E. coli isolates . RESULTS On average , differences were found among women assigned to treatment for ASB , those treated only for symptomatic infections , and untreated women in ( 1 ) follow-up time with bacteriuria ( 29 % , 31 % , and 66 % , respectively ; P<.001 ) , ( 2 ) duration of bacteriuria ( 2.2 , 2.5 , and 3.7 months , respectively ; P=.04 ) , and ( 3 ) carriage of unique isolates ( 2.4 , 2.8 , and 4 months , respectively ; P=.03 ) . Women assigned to antibiotic treatment usually had recurrent infection ( 76 % ) , 64 % of the time with a genetically new E. coli strain . Virulence characteristics of these isolates were comparable to those of fecal isolates from healthy women . CONCLUSIONS Treatment may reduce the overall proportion of time infected in the long term and carriage of a unique strain , but most treatment regimens were followed by subsequent recolonization . Infecting strains did not have virulence factors characteristic of uropathogenic E. coli This prospect i ve r and omized study was undertaken to determine the efficacy of antimicrobial therapy compared with no therapy for bacteriuria in elderly ambulatory nonhospitalized women . Sixty-one women ( mean age , 85.8 years ) with bacteriuria were in the no therapy control group and 63 women ( mean age , 85.8 years ) with bacteriuria were in the therapy group ; none had symptoms of urinary tract infection . One short course of antimicrobial therapy achieved a cure rate of 68.3 % ( 43 of 63 women cured ) two weeks after treatment . During the six-month follow-up period , ten ( 16.4 % ) of 61 women in the no therapy group and five ( 7.9 % ) of 63 women in the therapy group developed symptomatic urinary tract infection . At the time of six-month follow-up , 19 ( 34.5 % ) of 55 women in the no therapy group and 35 ( 63.6 % ) of 55 women in the therapy group did not have bacteriuria . We conclude that for asymptomatic bacteriuria in elderly ambulatory nonhospitalized women , short-course antimicrobial therapy is effective at two-week follow-up and that antimicrobial therapy can eliminate bacteriuria in most of these women for at least a six-month period OBJECTIVE To determine whether treatment of symptomatic bacteriuria in older ambulatory women affects the subsequent development of symptoms of urinary tract infection . DESIGN A controlled clinical trial . PARTICIPANTS Older women not having urinary catheters . MEASUREMENTS Urine cultures every 6 months ( the same organism at 10(5 ) colony-forming units or more per mL on two midstream urine specimens defined asymptomatic bacteriuria ) and question naire surveys for the new development of symptoms of urinary tract infection ( dysuria , frequency , urgency , low back pain with fever ) 1 , 3 , and 6 months after the initial survey . RESULTS Of the 23 initially culture-positive participants receiving antibiotic treatment for symptomatic bacteriuria , nine were culture positive at 6 months , which contrasts with 18 of 27 who received no treatment or placebo , P = .05 . However , symptoms of urinary tract infection were more common in the antibiotic-treated group . CONCLUSION Antibiotic therapy effectively reduced the subsequent occurrence of positive urine cultures , but symptoms were not reduced . Based on this study of morbidity , previous studies failing to show any relation to mortality , and the cost and complications of antibiotic therapy in the older population , treatment of asymptomatic bacteriuria in older women is contraindicated Fifty elderly ( mean age , 83.4 + /- 8.8 years ) institutionalized women with asymptomatic bacteriuria were r and omly assigned either to receive therapy for treatment of all episodes of bacteriuria identified on monthly culture or to receive no therapy unless symptoms developed . Subjects were followed for one year . The therapy group had a mean monthly prevalence of bacteriuria 31 + /- 15 percent lower than those in the no-therapy group , but periods free of bacteriuria lasting six months or longer were documented for only five ( 24 percent ) subjects . For residents receiving no therapy , 71 percent showed persistent infection with the same organism(s ) . Antimicrobial therapy was associated with an increased incidence of reinfection ( 1.67 versus 0.87 per patient-year ) and adverse antimicrobial drug effects ( 0.51 versus 0.046 per patient-year ) as well as isolation of increasingly resistant organisms in recurrent infection when compared with no therapy . No differences in genitourinary morbidity or mortality were observed between the groups . Thus , despite a lowered prevalence of bacteriuria , no short-term benefits were identified and some harmful effects were observed with treatment of asymptomatic bacteriuria . These data support current recommendations of no therapy for asymptomatic bacteriuria in this population Abstract . Background : The objective of this study was to examine the expression of Escherichia coli virulence-associated factors among the strains isolated from a group of women with a history of recurrent urinary tract infections ( UTIs ) , in whom asymptomatic bacteriuria ( ABU ) was detected at follow-up , and from a group of children without a history of previous UTI , in whom ABU was detected during the screening . Possible differences between the virulence potential of these strains were investigated . Material s and Methods : Hemolysin production , the ability to adhere to Buffalo green monkey cell line and hemagglutination ( HA ) ability of the ABU-associated E. coli strains were tested . E. coli strains isolated from patients with acute recurrent UTIs served as a comparison . Results : The well-known low virulence of strains isolated from patients with ABU was demonstrated . In contrast to strains isolated from recurrent uncomplicated UTIs , the ABU-associated strains were mostly nonhemolytic ( 75 % ) , nonadherent ( 70 % ) and lacked HA ability ( 61 % ) . HA ability was significantly more common among the strains isolated from children without a history of UTI than among the strains isolated from women with recurrent UTIs ( χ2 = 9.97 , p < 0.01 ) , whereas the adherence and hemolytic abilities did not differ between the two ABU groups . Conclusion : A further prospect i ve study is needed to determine whether the HA ability is the predictor of subsequent symptomatic UTI In a prospect i ve longitudinal study , ambulatory elderly men were followed from 1 to 4.5 years to gain insight into the prevalence rates , clinical characteristics , and patterns of clinical ly inapparent ( asymptomatic ) bacteriuria ( CIB ) . The prevalence of CIB was 12 % ( 29/238 ) and increases with age . Unlike the gram-negative organisms that cause overt urinary tract infection in this age group , gram-positive organisms dominated the CIB group . Both the CIB and abacteriuric patients have multiple chronic medical conditions and are indistinguishable on that basis . Twenty-nine elderly men with bacteriuria and 105 abacteriuric subjects were followed with serial urine cultures . During the study period the bacteriuric subjects exhibited spontaneous temporary or permanent resolution ( 76 % , 22/29 ) , intermittency ( 21 % , 6/29 ) , and probable bacterial persistence ( 38 % , 11/29 ) . No consistent pattern of bacteriuria was evident . Therefore , antimicrobial therapy is not warranted in the treatment of asymptomatic or clinical ly inapparent bacteriuria in ambulatory elderly men Asymptomatic bacteriuria , a common problem of the elderly , has been associated with increased mortality in the elderly [ 1 - 4 ] , although not all studies have confirmed this finding [ 5 - 9 ] . To reconcile these conflicting results , we did a longitudinal study of urinary tract infection in ambulatory elderly women to evaluate the putative relation between asymptomatic bacteriuria and mortality . We considered resolution of this issue to be important because of the implication s for clinical practice . If asymptomatic bacteriuria were shown to be an independent risk factor for mortality and if it could also be shown that eradication of the infection by antimicrobial therapy decreased the risk for death , then screening and antimicrobial treatment of elderly ambulatory women with asymptomatic bacteriuria might be warranted and the cost of identifying and treating such infections might be justified . Conversely , failure to confirm a relation would support the view that programs to screen for bacteriuria would not be justified if their goal was to enhance survival . This report summarizes the findings of our 9-year study to determine whether asymptomatic bacteriuria in elderly ambulatory women is a marker of increased mortality and , if so , whether it is because of an association with other determinants of mortality or because asymptomatic bacteriuria is itself an independent cause , the removal of which might improve longevity . The components of the study were a longitudinal study in elderly ambulatory women to compare mortality in those with and without asymptomatic bacteriuria and a double-blind , controlled clinical trial in which antimicrobial therapy was administered for asymptomatic bacteriuria to assess whether treatment decreases mortality . Methods Participant enrollment and the participating institutions have been described previously [ 10 , 11 ] . Elderly ambulatory residents of the Philadelphia Geriatric Center and of 21 continuing care retirement communities in the greater Philadelphia metropolitan area who gave informed consent were enrolled in this long-term study of urinary tract infection in the elderly . Enrollment continued throughout the course of the study . Philadelphia Geriatric Center houses about 1000 residents who primarily are Jewish ; incomes are higher than the maximum Social Security payment ; and congregate living is provided either in an apartment house or in a nursing home . In contrast , the continuing care retirement communities are smaller ( bed size range , 108 to 675 ) ; incomes are higher ; residents are primarily not Jewish ; and a higher proportion of residents are fully independent . All female residents were eligible to participate except those with indwelling catheters or those incapable of providing midstream clean-catch urine specimens for culture . Specimens were obtained on enrollment and every 6 months thereafter . The protocol was approved by the appropriate institutional review boards , and informed consent was obtained from the participants or their surrogates . Table 1 shows the study periods and chronology of important study events . Throughout the study , urine cultures were obtained at about 6-month intervals . An observational study to compare mortality of bacteriuric and nonbacteriuric volunteers regardless of treatment status was begun in January 1983 and ended in February 1992 . Initially , residents with asymptomatic bacteriuria were identified and followed , but treatment was not given . However , on 10 October 1983 , a controlled clinical trial was begun to evaluate whether antimicrobial therapy for asymptomatic bacteriuria decreased mortality ; every bacteriuric study participant identified after this date was enrolled in the trial . Mortality among residents who were treated with antimicrobial agents for asymptomatic bacteriuria each time it was present was compared with the mortality of those who received no therapy for their episodes of bacteriuria . At enrollment , participants were assigned to the treatment group or to the control group based on the last digit of an identification number unrelated to the conduct of the study . Urine cultures were read by personnel blinded to the study group assignment . When asymptomatic bacteriuria was identified , participants with even numbers were given antimicrobial therapy according to a defined protocol ( see below ) ; those with odd numbers served as controls . From 10 October 1983 to 10 December 1987 , controls were given no therapy . Thereafter , on the advice of external consultants , the protocol was changed so that participants not assigned to the active treatment group were given placebo pills in place of no treatment . The placebo pills were identical in appearance to each of the antimicrobial agents used . Thus , after 10 December 1987 , volunteers with asymptomatic bacteriuria were given therapy in either the form of antimicrobics or placebo after a new consent was obtained ; the volunteers and clinical personnel did not know study group assignments . Table 1 . Study Design and Enrollment The methods for collecting first-morning urine and for processing the specimens in our research microbiology laboratory have been previously described [ 10 , 11 ] . Participants were considered to have asymptomatic bacteriuria on a survey if two urine specimens were culture-positive ( 105 colony-forming units or more per mL of urine ) for the same organism within 2 weeks . From 10 October 1983 through 10 December 1987 , residents with asymptomatic bacteriuria who were assigned to receive antimicrobial treatment were given short-course therapy ( single dose or 3 days ) as follows : trimethoprim , 200 mg in one dose ; trimethoprim-sulfamethoxazole , 1 double-strength tablet ; cefaclor , 500 mg three times a day for 3 days ; amoxicillin , 250 mg three times a day for 3 days ; carbenicillin indanyl sodium , four times a day for 3 days ; or macrodantin , 100 mg twice a day for 3 days , depending on susceptibility of the infecting organism and history of drug allergy . Participants were considered cured if test-of-cure cultures contained less than 104 colony-forming units/mL of the infecting organism on cultures obtained 5 to 10 days after antimicrobial treatment or placebo or on cultures obtained on the next survey in those receiving no therapy . When positive for the same organism , patients were retreated for 14 days with test-of-cure culture afterward . If the organism differed , reinfection was diagnosed and a single dose or 3-day therapy was used ; treatment failures were treated as defined above . Test-of-cure cultures were obtained again after therapy and , if positive for the same organism , participants were treated for 14 days . No treatment was given after failure of a 14-day course or two reinfections after short courses . Controls received no therapy during this period . After 10 December 1987 , culture-positive patients were assigned to antimicrobial treatment or placebo . Single-dose therapy was given with trimethoprim , 200 mg , or norfloxacin , 400 mg , depending on the susceptibility of the organism ; the same drugs ( trimethoprim , 100 mg twice daily , and norfloxacin , 400 mg twice daily ) were used for 14 days of therapy in patients failing single-dose therapy . Single-dose therapy was used for reinfection . The placebo pills and regimen given to a placebo recipient matched the regimen administered to the participant in the active treatment group who was treated most recently ( for example , if the active treatment participant received short-course trimethoprim followed by 14 days of trimethoprim , the next placebo participant received short-course trimethoprim placebo followed by 14 days of trimethoprim placebo ) . Symptomatic infections were managed by the participant 's personal physician or by physicians associated with the facility in which the patient lived . Reports were received on an annual or semiannual basis from the participating institutions that detailed changes in their census . All deaths were noted , and registry coordinators review ed available documents to confirm each death . After 1 September 1987 , detailed functional and mental status assessment s were done when persons were newly enrolled into the study or were seen for an annual follow-up visit using techniques previously described [ 11 , 12 ] . Self-care activities of daily living were assessed by a modification of the Multilevel Assessment Instrument [ 13 ] , and mental status was assessed using a modified version of the Kahn and Goldfarb question naire [ 14 ] . A subjective measure of global health status ( scale , 1 to 4 ) was based on responses to the question : How do you rate your health : excellent ( score 1 ) , good , fair , and bad or poor ( score 4 ) ? Diagnoses recorded in the person 's medical record were extracted and provided a more objective measure of health status ; they were coded according to the ICD-9-CM three-digit codes [ 15 ] . The Geriatric Depression Scale [ 16 ] was used to assess depressive symptoms , and walking ability was assessed on a scale of 1 ( specialized help needed ) to 3 ( help not needed ) [ 11 ] . Statistical Analysis Observational Study These analyses compared residents with asymptomatic bacteriuria with residents who did not have asymptomatic bacteriuria on any of the urine culture surveys done during the period of their participation . For the purpose s of the survival analyses in the observational study , the results of urine cultures were considered a time-dependent covariate . Accordingly , participants were considered in the ever-positive group once asymptomatic bacteriuria was identified , and all subsequent time on study was contributed to the group with positive cultures regardless of urine culture results on subsequent surveys . Persons entering the study with a negative urine culture were considered in the never-positive group until asymptomatic bacteriuria was identified . Thus , a person who entered the study with negative cultures and who later became culture-positive would have contributed person-time to the follow-up of those in the BACKGROUND Asymptomatic bacteriuria is common in young women , but little is known about its pathogenesis , natural history , risk factors , and temporal association with symptomatic urinary tract infection . METHODS We prospect ively evaluated 796 sexually active , nonpregnant women from 18 through 40 years of age over a period of six months for the occurrence of asymptomatic bacteriuria ( defined as at least 10(5 ) colony-forming units of urinary tract pathogens per milliliter ) . The women were patients at either a university student health center or a health maintenance organization . Periodic urine cultures were taken , daily diaries were kept , and regularly scheduled interviews were performed . Escherichia coli strains were tested for hemolysin , the papG genotype , and the ribosomal RNA type . RESULTS The prevalence of asymptomatic bacteriuria ( the proportion of urine cultures with bacteriuria in asymptomatic women ) was 5 percent ( 95 percent confidence interval , 4 percent to 6 percent ) among women in the university group and 6 percent ( 95 percent confidence interval , 5 percent to 8 percent ) among women in the health-maintenance-organization group . Persistent asymptomatic bacteriuria with the same E. coli strain was rare . Symptomatic urinary tract infection developed within one week after 8 percent of occasions on which a culture showed asymptomatic bacteriuria , as compared with 1 percent of occasions when asymptomatic bacteriuria was not found ( P<0.001 ) . Asymptomatic bacteriuria was associated with the same risk factors as for symptomatic urinary tract infection , particularly the use of a diaphragm plus spermicide and sexual intercourse . CONCLUSIONS Asymptomatic bacteriuria in young women is common but rarely persists . It is a strong predictor of subsequent symptomatic urinary tract infection BACKGROUND Asymptomatic bacteriuria is common among women with diabetes , and the treatment of such infections has been recommended to prevent complications related to symptomatic urinary tract infection . METHODS We enrolled women ( > 16 years of age ) with diabetes , bacteriuria ( > or = 105 colony-forming units of an organism per milliliter in cultures of two consecutive urine specimens ) , and no urinary symptoms ; 50 were r and omly assigned to receive placebo and 55 to receive antimicrobial therapy . For the first six weeks , which included the initial course of treatment , the study was placebo-controlled and double-blind . Subsequently , the women were screened for bacteriuria every three months for up to three years ; antimicrobial therapy was provided to women in the antimicrobial-therapy group who had asymptomatic bacteriuria . RESULTS Four weeks after the end of the initial course of therapy , 78 percent of placebo recipients had bacteriuria , as compared with 20 percent of women who received antimicrobial agents ( P<0.001 ) . During a mean follow-up of 27 months , 20 of 50 women in the placebo group ( 40 percent ) and 23 of 55 women in the antimicrobial-therapy group ( 42 percent ) had at least one episode of symptomatic urinary tract infection . The time to a first symptomatic episode was similar in the placebo group and the antimicrobial-therapy group ( P=0.67 by the log-rank test ) , as were the ( + /-SD ) rates of any symptomatic urinary tract infection ( 1.10+/-0.17 and 0.93+/-0.14 per 1000 days of follow-up , respectively ; relative risk , 1.19 ; 95 percent confidence interval , 0.28 to 1.81 ) , pyelonephritis ( 0.28+/-0.08 and 0.13+/-0.05 per 1000 days of follow-up ; relative risk , 2.13 ; 95 percent confidence interval , 0.81 to 5.62 ) , and hospitalization for urinary tract infection ( 0.10+/-0.36 and 0.06+/-0.22 per 1000 days of follow-up ; relative risk , 1.93 ; 95 percent confidence interval , 0.47 to 7.89 ) . The women in the antimicrobial-therapy group had almost five times as many days of antibiotic use for urinary tract infection as did the women in the placebo group ( 158.2+/-1.7 vs. 33.7+/-0.91 per 1000 days of follow-up ; relative risk , 0.21 ; 95 percent confidence interval , 0.20 to 0.22 ) . CONCLUSIONS Treatment of asymptomatic bacteriuria in women with diabetes does not appear to reduce complications . Diabetes itself should not be an indication for screening for or treatment of asymptomatic bacteriuria Patients with diabetes mellitus ( DM ) have a higher prevalence of asymptomatic bacteriuria ( ASB ) and incidence of urinary tract infections ( UTIs ) compared with patients without DM . They also more often have bacteraemia , with the urinary tract as the most common focus for these infections , as well as a higher mortality outside the hospital compared with patients without DM . It appears that the increased prevalence of ASB in diabetic women is not the result of a difference in causative bacteria , as the same virulence factors and resistance to antimicrobials were found in Escherichia coli isolated from the urine of diabetic women with ASB compared with non-diabetic controls . Bacterial growth in vitro is increased after the addition of glucose , however glucosuria is not a risk factor for ASB or for the development of UTIs in vivo . No differences in granulocyte function tests were demonstrated among diabetic women with ASB , non-bacteriuric women and healthy control subjects , but women with both ASB and DM had lower urinary cytokine and leukocyte concentrations than women with ASB without DM . Finally , it was found that E. coli expressing type 1 fimbriae adhere better to uroepithelial cells of women with DM compared with those isolated from women without DM . There are no r and omised trials that answer the question as to the optimal duration of treatment for UTIs in diabetic patients . It has been recommended to consider these patients as having a complicated UTI and therefore to treat them for a period of 7 - 14 days In order to compare the incidence of symptomatic urinary tract infection ( UTI ) in diabetic patients with and without asymptomatic bacteriuria ( ASB ) , and to identify other risk factors for these infections , 289 females and 168 males were studied over a 12-month period . Symptomatic UTI occurred in 69.2 % of patients with ASB ( 67.6 % female and 76.5 % male ) versus 9.8 % without ASB ( 14.9 % female and 2.6 % male ) . ASB and urinary incontinence were associated with symptomatic UTI in both women and men . Other risk factors included previous antimicrobial treatment and macrovascular complications in women and obesity and prostatic syndrome in men . The presence of ASB was found to be the major risk factor for developing symptomatic urinary tract infection . Further prospect i ve r and omized clinical trials of diabetic patients with risk factors for UTI who are receiving or not receiving treatment may be considered Primary biliary cirrhosis ( PBC ) patients have an increased incidence of recurrent urinary tract infection compared with patients with other chronic liver diseases . The course of significant asymptomatic and symptomatic bacteriuria in women with PBC was evaluated : consecutive patients were screened for bacteriuria at their outpatient appointments . Bacteriuric patients who were asymptomatic ( n = 21 ) were r and omised to receive antimicrobial therapy ( n = 11 ) , or no therapy ( n = 10 ) . Bacteriuric patients who were symptomatic ( n = 13 ) were treated . All were followed up by weekly dipslide examination of urine . The course of bacteriuria in the 13 symptomatic and 11 asymptomatic treated patients was similar in terms of the medium interval between successive infective episodes ( three and four weeks respectively ) , the number of relapses ( six and seven ) and reinfections ( 14 and 18 ) . Most untreated asymptomatic patients became abacteriuric spontaneously but became reinfected with a different organism during the study period . A separate group of 24 PBC patients with no previous bacteriologically proved urinary tract infection was followed weekly in a similar fashion : seven ( 29 % ) became bacteriuric for two to four weeks during a three month period . This study suggests that treatment of recurrent bacteriuric episodes in PBC patients does not alter the natural history of their infection . The long term implication of periodically infected urine in these patients is currently unknown Response to therapy , renal function , and mortality were analyzed in a prospect i ve study of 249 men with bacteriuria followed for up to 10 years . All patients received initial organism-specific antibiotic therapy followed by 2 years of continuous treatment with sulfamethizole , nitrofurantoin , methenamine m and elate , or placebo . Continuous therapy with active drugs delayed recurrence of bacteriuria and reduced acute clinical exacerbations of infection . Patients with pure Escherichia coli bacteriuria , normal intravenous pyelogram , no previous therapy , and a normal prostate had a good prognosis with short-term antibiotic therapy alone . The presence of prostatic or upper urinary tract calculi , pyelonephritic scars , or mixed or enterococcal infections predicted a poor bacteriologic prognosis . In the absence of severe urologic disease or concomitant noninfectious renal disease no patients with persistent bacteriuria developed renal failure . Continuous antibiotic therapy is of value in selected male patients with bacteriuria in reducing recurrence and acute clinical exacerbations of urinary tract infection In 1963 , a r and om sample study was performed in Turku , including 405 subjects over 65 years of age . In this study , urinary tract infection was detected in 11 % of the men and in 33 % of the women . Recent reports have demonstrated an association between bacteriuria and excess mortality . Therefore , 40 in patients 60 or more years old with asymptomatic bacteriuria participated in a double-blind trial to assess the effect of 1-day treatment with trimethoprim . The patients were allocated r and omly to receive 100 mg . trimethoprim ( 20 patients ) or placebo ( 20 patients ) to be taken in the morning and evening for 1 day . All patients treated with trimethoprim obtained sterile urine , whereas all patients treated with placebo remained bacteriuric ( p less than 0.002 ) . No side effects were recorded . However , many of the cured patients suffered rapid reinfection . Of the 20 initially cured patients 14 ( 70 per cent , 95 per cent confidence limits 46 to 88 per cent ) had recurrent bacteriuria after 6 weeks , indicating that although this treatment is effective immediately it imparts no long-term effect Abstract This study aim ed to determine whether long-term oral fluoroquinolone administration exerts a significant positive effect on mobility and mortality in elderly subjects with asymptomatic bacteriuria . 132 institutionalized patients were divided into 4 groups : groups A and B were treated with ofloxacin while groups C and D were positive and negative control groups . At 3 months following treatment discontinuation 57 % , 53 % and 26 % of patients in groups A , B and C respectively had negative urine cultures and all subjects were alive . After 3 years , positive cultures were 41.7 % , 54.5 % and 42.9 % respectively for uncatheterized subjects per group vs. 13.3 % for group D. In groups A , B , and C 20 % , 15 % and 29 % of survivors respectively had permanent bladder catheters vs. 11.5 % of survivors of group D. Survival in groups A , B and C , combined or per group did not differ significantly from group D , although it was shorter . “ Pulse ” antibiotic administration tended to perform better , in terms of clearing infection and maintaining continence . At 3 years , bacteriuria recurred and the need for bladder catheterization was doubled . Mortality increased independently of treatment . More elderly bacteriuric subjects should be studied to evaluate mobility and mortality issues Over a two-year period we obtained monthly urine sample s from all noncatheterized male residents on two geriatric wards to determine the occurrence and optimal management of bacteriuria in this population . Among 88 men the prevalence of bacteriuria was 33 per cent , and the incidence was 45 infections per 100 patients per year . Outcomes after single-dose therapy for asymptomatic bacteriuria with 43 courses of trimethoprim/sulfamethoxazole and 23 of tobramycin included 15 cures , 40 relapses , and 11 treatment failures . Thirty-six residents who had a relapse or in whom single-dose therapy failed were r and omly assigned to receive therapy to eradicate bacteriuria or to receive no therapy . All 20 residents who received no therapy remained bacteriuric . The 16 residents who received therapy had fewer months of bacteriuria after r and omization , but at the end of the study only one remained free of bacteriuria . Mortality and infectious morbidity after r and omization were similar in the two groups . These data suggest that asymptomatic bacteriuria is common in elderly institutionalized men and that therapy is neither necessary nor effective |
11,828 | 23,672,779 | Despite heterogeneity in trial quality and design , we found GDT to be beneficial in all high-risk patients undergoing major surgery .
The mortality benefit of GDT was confined to the subgroup of patients at extremely high risk of death .
The reduction of complication rates was seen across all subgroups of GDT patients | Patients with limited cardiac reserve are less likely to survive and develop more complications following major surgery .
By augmenting oxygen delivery index ( DO2I ) with a combination of intravenous fluids and inotropes ( goal directed therapy ( GDT ) ) , postoperative mortality and morbidity of high-risk patients may be reduced .
However , although most studies suggest that GDT may improve outcome in high-risk surgical patients , it is still not widely practice d. We set out to test the hypothesis that GDT results in greatest benefit in terms of mortality and morbidity in patients with the highest risk of mortality and have undertaken a systematic review of the current literature to see if this is correct . | Introduction Acute hemodynamic instability increases morbidity and mortality . We investigated whether early non-invasive cardiac output monitoring enhances hemodynamic stabilization and improves outcome . Methods A multicenter , r and omized controlled trial was conducted in three European university hospital intensive care units in 2006 and 2007 . A total of 388 hemodynamically unstable patients identified during their first six hours in the intensive care unit ( ICU ) were r and omized to receive either non-invasive cardiac output monitoring for 24 hrs ( minimally invasive cardiac output/MICO group ; n = 201 ) or usual care ( control group ; n = 187 ) . The main outcome measure was the proportion of patients achieving hemodynamic stability within six hours of starting the study . Results The number of hemodynamic instability criteria at baseline ( MICO group mean 2.0 ( SD 1.0 ) , control group 1.8 ( 1.0 ) ; P = .06 ) and severity of illness ( SAPS II score ; MICO group 48 ( 18 ) , control group 48 ( 15 ) ; P = .86 ) ) were similar . At 6 hrs , 45 patients ( 22 % ) in the MICO group and 52 patients ( 28 % ) in the control group were hemodynamically stable ( mean difference 5 % ; 95 % confidence interval of the difference -3 to 14 % ; P = .24 ) . Hemodynamic support with fluids and vasoactive drugs , and pulmonary artery catheter use ( MICO group : 19 % , control group : 26 % ; P = .11 ) were similar in the two groups . The median length of ICU stay was 2.0 ( interquartile range 1.2 to 4.6 ) days in the MICO group and 2.5 ( 1.1 to 5.0 ) days in the control group ( P = .38 ) . The hospital mortality was 26 % in the MICO group and 21 % in the control group ( P = .34 ) . Conclusions Minimally-invasive cardiac output monitoring added to usual care does not facilitate early hemodynamic stabilization in the ICU , nor does it alter the hemodynamic support or outcome . Our results emphasize the need to evaluate technologies used to measure stroke volume and cardiac output -- especially their impact on the process of care -- before any large-scale outcome studies are attempted . Trial Registration The study was registered at Clinical Trials.gov ( Clinical Trials identifier NCT00354211 BACKGROUND Some observational studies suggest that the use of pulmonary-artery catheters to guide therapy is associated with increased mortality . METHODS We performed a r and omized trial comparing goal -directed therapy guided by a pulmonary-artery catheter with st and ard care without the use of a pulmonary-artery catheter . The subjects were high-risk patients 60 years of age or older , with American Society of Anesthesiologists ( ASA ) class III or IV risk , who were scheduled for urgent or elective major surgery , followed by a stay in an intensive care unit . Outcomes were adjudicated by observers who were unaware of the treatment-group assignments . The primary outcome was in-hospital mortality from any cause . RESULTS Of 3803 eligible patients , 1994 ( 52.4 percent ) underwent r and omization . The base-line characteristics of the two treatment groups were similar . A total of 77 of 997 patients who underwent surgery without the use of a pulmonary-artery catheter ( 7.7 percent ) died in the hospital , as compared with 78 of 997 patients in whom a pulmonary-artery catheter was used ( 7.8 percent)--a difference of 0.1 percentage point ( 95 percent confidence interval , -2.3 to 2.5 ) . There was a higher rate of pulmonary embolism in the catheter group than in the st and ard-care group ( 8 events vs. 0 events , P=0.004 ) . The survival rates at 6 months among patients in the st and ard-care and catheter groups were 88.1 and 87.4 percent , respectively ( difference , -0.7 percentage point [ 95 percent confidence interval , -3.6 to 2.2 ] ; negative survival differences favor st and ard care ) ; at 12 months , the rates were 83.9 and 83.0 percent , respectively ( difference , -0.9 percentage point [ 95 percent confidence interval , -4.3 to 2.4 ] ) . The median hospital stay was 10 days in each group . CONCLUSIONS We found no benefit to therapy directed by pulmonary-artery catheter over st and ard care in elderly , high-risk surgical patients requiring intensive care Background : An individualized fluid optimization strategy , based on maximization of cardiac stroke volume ( SV ) with colloid boluses ( goal ‐directed therapy ) , improves outcome after surgery . Oesophageal Doppler ( OD ) is used for SV maximization in most r and omized studies , but evidence ‐based guidelines for the SV maximization procedure are lacking and variation in SV may influence the indication for fluid administration . We measured beat‐to‐beat OD SV before and after fluid optimization in order to estimate the number of heartbeats for which SV needs to be averaged to provide an acceptable accuracy for goal ‐directed therapy with this technology Background Major colorectal surgery usually requires a hospital stay of more than 12 days . Inadequate pain management , intestinal dysfunction and immobilisation are the main factors associated with delay in recovery . The present work assesses the short and medium term results achieved by an enhanced recovery program based on previously published protocol s. Methods This prospect i ve study , performed at 12 Spanish hospitals in 2008 and 2009 , involved 300 patients . All patients underwent elective colorectal resection for cancer following an enhanced recovery program . The main elements of this program were : preoperative advice , no colon preparation , provision of carbohydrate-rich drinks one day prior and on the morning of surgery , goal directed fluid administration , body temperature control during surgery , avoiding drainages and nasogastric tubes , early mobilisation , and the taking of oral fluids in the early postoperative period . Perioperative morbidity and mortality data were collected and the length of hospital stay and protocol compliance recorded . Results The median age of the patients was 68 years . Fifty-two % of the patients were women . The distribution of patients by ASA class was : I 10 % , II 50 % and III 40 % . Sixty-four % of interventions were laparoscopic ; 15 % required conversion to laparotomy . The majority of patients underwent sigmoidectomy or right hemicolectomy . The overall compliance to protocol was approximately 65 % , but varied widely in its different components . The median length of postoperative hospital stay was 6 days . Some 3 % of patients were readmitted to hospital after discharge ; some 7 % required repeat surgery during their initial hospitalisation or after readmission . The most common complications were surgical ( 24 % ) , followed by septic ( 11 % ) or other medical complications ( 10 % ) . Three patients ( 1 % ) died during follow-up . Some 31 % of patients suffered symptoms that delayed their discharge , the most common being vomiting or nausea ( 12 % ) , dyspnoea ( 7 % ) and fever ( 5 % ) . Conclusion The following of this enhanced recovery program posed no risk to patients in terms of morbidity , mortality and shortened the length of their hospital stay . Overall compliance to protocol was 65 % . The following of this program was of benefit to patients and reduces costs by shortening the length of hospital stay . The implantation of such programmes is therefore highly recommended Introduction Perioperative hypovolemia arises frequently and contributes to intestinal hypoperfusion and subsequent postoperative complications . Goal -directed fluid therapy might reduce these complications . The aim of this study was to compare the effects of goal -directed administration of crystalloids and colloids on the distribution of systemic , hepatosplanchnic , and microcirculatory ( small intestine ) blood flow after major abdominal surgery in a clinical ly relevant pig model . Methods Twenty-seven pigs were anesthetized and mechanically ventilated and underwent open laparotomy . They were r and omly assigned to one of three treatment groups : the restricted Ringer lactate ( R-RL ) group ( n = 9 ) received 3 mL/kg per hour of RL , the goal -directed RL ( GD-RL ) group ( n = 9 ) received 3 mL/kg per hour of RL and intermittent boluses of 250 mL of RL , and the goal -directed colloid ( GD-C ) group ( n = 9 ) received 3 mL/kg per hour of RL and boluses of 250 mL of 6 % hydroxyethyl starch ( 130/0.4 ) . The latter two groups received a bolus infusion when mixed venous oxygen saturation was below 60 % ( ' lockout ' time of 30 minutes ) . Regional blood flow was measured in the superior mesenteric artery and the celiac trunk . In the small bowel , microcirculatory blood flow was measured using laser Doppler flowmetry . Intestinal tissue oxygen tension was measured with intramural Clark-type electrodes . Results After 4 hours of treatment , arterial blood pressure , cardiac output , mesenteric artery flow , and mixed oxygen saturation were significantly higher in the GD-C and GD-RL groups than in the R-RL group . Microcirculatory flow in the intestinal mucosa increased by 50 % in the GD-C group but remained unchanged in the other two groups . Likewise , tissue oxygen tension in the intestine increased by 30 % in the GD-C group but remained unchanged in the GD-RL group and decreased by 18 % in the R-RL group . Mesenteric venous glucose concentrations were higher and lactate levels were lower in the GD-C group compared with the two crystalloid groups . Conclusions Goal -directed colloid administration markedly increased microcirculatory blood flow in the small intestine and intestinal tissue oxygen tension after abdominal surgery . In contrast , goal -directed crystalloid and restricted crystalloid administrations had no such effects . Additionally , mesenteric venous glucose and lactate concentrations suggest that intestinal cellular substrate levels were higher in the colloid-treated than in the crystalloid-treated animals . These results support the notion that perioperative goal -directed therapy with colloids might be beneficial during major abdominal surgery Introduction Little is known about mortality rates following general surgical procedures in the United Kingdom . Deaths are most common in the ' high-risk ' surgical population consisting mainly of older patients , with coexisting medical disease , who undergo major surgery . Only limited data are presently available to describe this population . The aim of the present study was to estimate the size of the high-risk general surgical population and to describe the outcome and intensive care unit ( ICU ) re source use . Methods Data on inpatient general surgical procedures and ICU admissions in 94 National Health Service hospitals between January 1999 and October 2004 were extracted from the Intensive Care National Audit & Research Centre data base and the CHKS data base . High-risk surgical procedures were defined prospect ively as those for which the mortality rate was 5 % or greater . Results There were 4,117,727 surgical procedures ; 2,893,432 were elective ( 12,704 deaths ; 0.44 % ) and 1,224,295 were emergencies ( 65,674 deaths ; 5.4 % ) . A high-risk population of 513,924 patients was identified ( 63,340 deaths ; 12.3 % ) , which accounted for 83.8 % of deaths but for only 12.5 % of procedures . This population had a prolonged hospital stay ( median , 16 days ; interquartile range , 9–29 days ) . There were 59,424 ICU admissions ( 11,398 deaths ; 19 % ) . Among admissions directly to the ICU following surgery , there were 31,633 elective admissions with 3,199 deaths ( 10.1 % ) and 24,764 emergency admissions with 7,084 deaths ( 28.6 % ) . The ICU stays were short ( median , 1.6 days ; interquartile range , 0.8–3.7 days ) but hospital admissions for those admitted to the ICU were prolonged ( median , 16 days ; interquartile range , 10–30 days ) . Among the ICU population , 40.8 % of deaths occurred after the initial discharge from the ICU . The highest mortality rate ( 39 % ) occurred in the population admitted to the ICU following initial postoperative care on a st and ard ward . Conclusion A large high-risk surgical population accounts for 12.5 % of surgical procedures but for more than 80 % of deaths . Despite high mortality rates , fewer than 15 % of these patients are admitted to the ICU OBJECTIVE To determine the effect of a community hospital-wide program enabling nurses and prehospital personnel to mobilize institutional re sources for the treatment of patients with nontraumatic shock . DESIGN Historically controlled single-center study . SETTING A 180-bed community hospital . PATIENTS Patients in shock who were c and i date s for aggressive therapy . INTERVENTIONS From January 1998 to May 31 , 2000 , patients in shock received st and ard therapy ( control group ) . During the month of June 2000 , intensive education of all health-care providers ( ie , prehospital personnel , nurses , and physicians ) took place . From July 1 , 2000 , through June 30 , 2001 , patients in shock ( protocol group ) were managed with a hospital-wide shock program . The program included early recognition of shock and the initiation of therapy by nonphysicians . Frontline personnel mobilized a shock team , which used goal -directed resuscitation protocol s , early intensivist involvement , and rapid transfer to the ICU where protocol s specific to shock etiology were implemented . MEASUREMENTS AND MAIN RESULTS Eighty-six and 103 patients , respectively , were enrolled in the control and protocol groups . Baseline characteristics were similar . The protocol group had significant reductions in the median times to interventions , as follows : intensivist arrival , 2:00 h to 50 min ( p < 0.002 ) ; ICU/operating room admission , 2 h 47 min to 1 h 30 min ( p < 0.002 ) ; 2 L fluid infused , 3 h 52 min to 1 h 45 min ( p < 0.0001 ) ; and pulmonary artery catheter placement , 3 h 50 min to 2 h 10 min ( p 0.02 ) . Good outcomes ( ie , discharged to home or to a rehabilitation center ) were more likely in the protocol group than in the control group ( p = 0.02 ) . The hospital mortality rate was 40.7 % in the control group and 28.2 % in the protocol group ( p = 0.035 ) . CONCLUSION Similar to current practice in patients who have experienced trauma or cardiac arrest , the empowerment of nonphysician providers to mobilize hospital re sources for the care of patients with shock is effective . A community hospital program incorporating the education of providers , the activation of a coordinated team response , and early goal -directed therapy expedited appropriate treatment and was temporally associated with improved outcomes . R and omized multicenter trials are needed to further assess the impact of the shock program on outcomes Objectives : To determine whether a starch solution for volume resuscitation in a flow-based protocol improves circulatory status better than a crystalloid solution , as defined by the need for catecholamines in patients the morning after cardiac surgery , and whether this can be performed without increased morbidity . Design : Concealed , r and omized , double-blind , controlled trial . Participants : Two hundred sixty-two patients who underwent cardiac surgery at a tertiary care hospital . Interventions : Based on predefined criteria indicating a need for fluids , and a nurse-delivered algorithm that used central venous pressure and cardiac index obtained from a pulmonary artery catheter , patients were allocated to receive 250-mL boluses of 0.9 % saline or a 250-molecular weight 10 % solution of pentastarch . Results : Two hundred thirty-seven patients received volume boluses : 119 hydroxyethyl starches and 118 saline . Between 8:00 am and 9:00 am the morning after surgery , 13 ( 10.9 % ) of hydroxyethyl starch patients and 34 ( 28.8 % ) saline patients were using catecholamines ( p = .001 ) . Hydroxyethyl starch patients had less pneumonia and mediastinal infections ( p = .03 ) and less cardiac pacing ( p = .03 ) . There were two deaths in each group . There was no difference in the daily creatinine , development of RIFLE risk criteria during hospital stay , or new dialysis . The numbers and volumes of packed red blood cells were similar in the two groups , but more hydroxyethyl starch patients received plasma transfusions ( p = .05 ) . Conclusions : Use of a colloid solution for volume resuscitation in a nurse-delivered flow-based algorithm , which included a pulmonary artery catheter , significantly improved hemodynamic status , an important factor for readiness for discharge from the intensive care unit Introduction Total hip replacement is one of the most commonly performed major orthopaedic operations . Goal -directed therapy ( GDT ) using haemodynamic monitoring has previously demonstrated outcome benefits in high-risk surgical patients under general anaesthesia . GDT has never been formally assessed during regional anaesthesia . Methods Patients undergoing total hip replacement while under regional anaesthesia were r and omised to either the control group ( CTRL ) or the protocol group ( GDT ) . Patients in the GDT group , in addition to st and ard monitoring , were connected to the FloTrac sensor/Vigileo monitor haemodynamic monitoring system , and a GDT protocol was used to maximise the stroke volume and target the oxygen delivery index to > 600 mL/minute/m2 . Results Patients r and omised to the GDT group were given a greater volume of intravenous fluids during the intraoperative period ( means ± st and ard deviation ( SD ) : 6,032 ± 1,388 mL vs. 2,635 ± 346 mL ; P < 0.0001 ) , and more of the GDT patients received dobutamine ( 0 of 20 CTRL patients vs. 11 of 20 GDT patients ; P < 0.0003 ) . The GDT patients also received more blood transfused during the intraoperative period ( means ± SD : 595 ± 316 mL vs. 0 ± 0 mL ; P < 0.0001 ) , although the CTRL group received greater volumes of blood replacement postoperatively ( CTRL patients 658 ± 68 mL vs. GDT patients 198 ± 292 mL ; P < 0.001 ) . Overall blood consumption ( intraoperatively and postoperatively ) was not different between the two groups . There were an increased number of complications in the CTRL group ( 20 of 20 CTRL patients ( 100 % ) vs. 16 of 20 GDT patients ( 80 % ) ; P = 0.05 ) . These outcomes were predominantly due to a difference in minor complications ( 20 of 20 CTRL patients ( 100 % ) vs. 15 of 20 GDT patients ( 75 % ) ; P = 0.047 ) . Conclusions GDT applied during regional anaesthesia in patients undergoing elective total hip replacement changes intraoperative fluid management and may improve patient outcomes by decreasing postoperative complications . Larger trials are required to confirm our findings .Trial registration S RCT Organ dysfunction and multiple organ failure are the main causes of prolonged hospital stay after cardiac surgery , which increases re source use and health care costs . Increased levels of oxygen delivery and consumption are associated with improved outcome in different groups of postoperative patients . Cardiac surgical patients are at risk of inadequate perioperative oxygen delivery caused by extracorporeal circulation and limited cardiovascular reserves . The purpose of our study was to test whether increasing oxygen delivery immediately after cardiac surgery would shorten hospital and intensive care unit ( ICU ) stay . Four hundred three elective cardiac surgical patients were enrolled in the study and r and omly assigned to either the control or the protocol group . Goals of the protocol group were to maintain Svo2 > 70 % and lactate concentration ≤2.0 mmol/L from admission to the ICU and up to 8 h thereafter . Hemodynamics , oxygen transport data , and organ dysfunctions were recorded . The median hos-pital stay was shorter in the protocol group ( 6 vs 7 days , P < 0.05 ) , and patients were discharged faster from the hospital than those in the control group ( P < 0.05 ) . Discharge from the ICU was similar between groups ( P = 0.8 ) . Morbidity was less frequent at the time of hospital discharge in the protocol group ( 1.1 % vs 6.1 % , P < 0.01 ) . Increasing oxygen delivery to achieve normal Svo2 values and lactate concentration during the immediate postoperative period after cardiac surgery can shorten the length of hospital stay . Implication s Health care economics has challenged clinicians to reduce costs and improve re source use in cardiac surgery and anesthesia in a patient population increasing in age and in severity of disease . Optimizing cardiovascular function to maintain adequate oxygen delivery during the immediate postoperative period after cardiac surgery can decrease morbidity and reduce length of hospital stay Introduction Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and /or low dose inotropic therapy . The mechanisms underlying this benefit remain uncertain . The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery . Methods R and omised , controlled , single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery . For eight hours after surgery , intra-venous fluid therapy was guided by measurements of central venous pressure ( CVP group ) , or stroke volume ( SV group ) . In a third group stroke volume guided fluid therapy was combined with dopexamine ( 0.5 mcg/kg/min ) ( SV & DPX group ) . Results 135 patients were recruited ( n = 45 per group ) . In the SV & DPX group , increased global oxygen delivery was associated with improved sublingual ( P < 0.05 ) and cutaneous microvascular flow ( P < 0.005 ) ( sublingual microscopy and laser Doppler flowmetry ) . Microvascular flow remained constant in the SV group but deteriorated in the CVP group ( P < 0.05 ) . Cutaneous tissue oxygen partial pressure ( PtO2 ) ( Clark electrode ) improved only in the SV & DPX group ( P < 0.001 ) . There were no differences in serum inflammatory markers . There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group ( CVP group ten patients ( 22 % ) ; pooled SV and SV & DPX groups seven patients ( 8 % ) ; P = 0.03 ) ( post hoc analysis ) . Conclusions Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery , microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery . These observations may explain improved clinical outcomes associated with this treatment in previous trials . Trial registration numberIS RCT N CONTEXT Goal -directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department . OBJECTIVE To test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation ( ScvO2 ) as goals of early sepsis resuscitation . DESIGN , SETTING , AND PATIENTS Multicenter r and omized , noninferiority trial involving patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 at 1 of 3 participating US urban hospitals . INTERVENTIONS We r and omly assigned patients to 1 of 2 resuscitation protocol s. The ScvO2 group was resuscitated to normalize central venous pressure , mean arterial pressure , and ScvO2 of at least 70 % ; and the lactate clearance group was resuscitated to normalize central venous pressure , mean arterial pressure , and lactate clearance of at least 10 % . The study protocol was continued until all goals were achieved or for up to 6 hours . Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment . MAIN OUTCOME MEASURE The primary outcome was absolute in-hospital mortality rate ; the noninferiority threshold was set at Delta equal to -10 % . RESULTS Of the 300 patients enrolled , 150 were assigned to each group and patients were well matched by demographic , comorbidities , and physiological features . There were no differences in treatments administered during the initial 72 hours of hospitalization . Thirty-four patients ( 23 % ) in the ScvO2 group died while in the hospital ( 95 % confidence interval [ CI ] , 17%-30 % ) compared with 25 ( 17 % ; 95 % CI , 11%-24 % ) in the lactate clearance group . This observed difference between mortality rates did not reach the predefined -10 % threshold ( intent-to-treat analysis : 95 % CI for the 6 % difference , -3 % to 15 % ) . There were no differences in treatment-related adverse events between the groups . CONCLUSION Among patients with septic shock who were treated to normalize central venous and mean arterial pressure , additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00372502 BACKGROUND : There are few data describing the relationship between amount of perioperative fluid and organ function . In this study we investigated the effects of two levels of intravascular fluid administration ( “ liberal ” versus “ restrictive ” ) in knee arthroplasty on physiological recovery as the primary outcome variable . METHODS : In a double-blind study , 48 ASA I – III patients undergoing fast-track elective knee arthroplasty were r and omized to restrictive or liberal perioperative intravascular fluid administration . Patients received a fixed rate infusion of Ringer ’s lactate solution with a st and ardized volume of colloid . All other aspects of perioperative management ( including anesthesia , preoperative fluid status , and postoperative management ) were st and ardized . Primary outcome variables included pulmonary function ( spirometry ) , exercise capacity ( “ timed up and go ” test ) , coagulation ( Thrombelastograph ® ) , postoperative hypoxemia ( nocturnal pulse oximetry ) , postoperative ileus ( defecation ) , and subjective patient recovery ( visual analog scales ) . Hospital stay and complications were also noted . RESULTS : Fluid guidelines were followed strictly in all patients . Liberal ( median 4250 mL , range 3150–5200 mL ) compared with restrictive ( median 1740 mL , range 1100–2165 mL ) intravascular fluid administration led to improved pulmonary function 6 h postoperatively , significant hypercoagulability 24–48 h postoperatively , and reduced incidence of vomiting . There were no overall differences in the other assessed perioperative physiological recovery variables ( postoperative hypoxemia , exercise capacity or subjective patient recovery variables ) . No difference was found in hospital stay ( median 4 days in both groups , not significant ) . CONCLUSION : A liberal compared to a restrictive intravascular fluid regimen may lead to significant hypercoagulability and a reduction in vomiting , but without differences in other recovery variables or hospital stay after fast-track knee arthroplasty Abstract . Objective : To compare the cost and cost-effectiveness of a policy of pre-operative optimisation of oxygen delivery ( using either adrenaline or dopexamine ) to reduce the risk associated with major elective surgery , in high-risk patients . Methods : A cost-effectiveness analysis using data from a r and omised controlled trial ( RCT ) . In the RCT 138 patients undergoing major elective surgery were allocated to receive pre-operative optimisation employing either adrenaline or dopexamine ( assigned r and omly ) , or to receive routine peri-operative care . Differential health service costs were based on trial data on the number and cause of hospital in-patient days and the utilisation of health care re sources . These were costed using unit costs from a UK hospital . The cost-effectiveness analysis related differential costs to differential life-years during a 2year trial follow-up . Results : The mean number of in-patient days was 16 in the pre-optimised groups ( 19 adrenaline ; 13 dopexamine ) and 22 in the st and ard care group . The number ( % ) of deaths , over a 2year follow-up , was 24 ( 26 % ) in the pre-optimised groups and 15 ( 33 % ) in the st and ard care group . The mean total costs were EUR 11,310 in the pre-optimised groups and EUR 16,965 in the st and ard care group . Life-years were 1.68 in the pre-optimised groups and 1.46 in the st and ard care group . The probability that pre-operative optimisation is less costly than st and ard care is 98 % . The probability that it dominates st and ard care is 93 % . Conclusions : Based on re source use and effectiveness data collected in the trial , pre-operative optimisation of high-risk surgical patients undergoing major elective surgery is cost-effective compared with st and ard treatment Background Intraoperative hypovolemia is common and is a potential cause of organ dysfunction , increased postoperative morbidity , length of hospital stay , and death . The objective of this prospect i ve , r and omized study was to assess the effect of goal -directed intraoperative fluid administration on length of postoperative hospital stay . Methods One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were r and omly assigned to a control group ( n = 50 ) that received st and ard intraoperative care or to a protocol group ( n = 50 ) that , in addition , received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume . Length of postoperative hospital stay and postoperative surgical morbidity were assessed . Results Groups were similar with respect to demographics , surgical procedures , and baseline hemodynamic variables . The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group . Patients in the protocol group had a shorter duration of hospital stay compared with the control group : 5 ± 3 versus 7 ± 3 days ( mean ± SD ) , with a median of 6 versus 7 days , respectively ( P = 0.03 ) . These patients also tolerated oral intake of solid food earlier than the control group : 3 ± 0.5 versus 4.7 ± 0.5 days ( mean ± SD ) , with a median of 3 versus 5 days , respectively ( P = 0.01 ) . Conclusions Goal -directed intraoperative fluid administration results in earlier return to bowel function , lower incidence of postoperative nausea and vomiting , and decrease in length of postoperative hospital stay Introduction Optimal fluid management is crucial for patients who undergo major and prolonged surgery . Persistent hypovolemia is associated with complications , but fluid overload is also harmful . We evaluated the effects of a restrictive versus conventional strategy of crystalloid administration during goal -directed therapy in high-risk surgical patients . Methods We conducted a prospect i ve , r and omized , controlled study of high-risk patients undergoing major surgery . For fluid maintenance during surgery , the restrictive group received 4 ml/kg/hour and the conventional group received 12 ml/kg/hour of Ringer 's lactate solution . A minimally invasive technique ( the LiDCO monitoring system ) was used to continuously monitor stroke volume and oxygen delivery index ( DO2I ) in both groups . Dobutamine was administered as necessary , and fluid challenges were used to test fluid responsiveness to achieve the best possible DO2I during surgery and for 8 hours postoperatively . Results Eighty-eight patients were included . The patients ' median age was 69 years . The conventional treatment group received a significantly greater amount of lactated Ringer 's solution ( mean ± st and ard deviation ( SD ) : 4 , 335 ± 1 , 546 ml ) than the restrictive group ( mean ± SD : 2 , 301 ± 1 , 064 ml ) ( P < 0.001 ) . Temporal patterns of DO2I were similar between the two groups . The restrictive group had a 52 % lower rate of major postoperative complications than the conventional group ( 20.0 % vs 41.9 % , relative risk = 0.48 , 95 % confidence interval = 0.24 to 0.94 ; P = 0.046 ) . Conclusions A restrictive strategy of fluid maintenance during optimization of oxygen delivery reduces major complications in older patients with coexistent pathologies who undergo major surgery . Trial registration IS RCT N : IS RCT Purpose Goal -directed therapy in the perioperative setting has been shown to be associated with short-term improvements in outcome . This study assesses the longer-term survival of patients from a previous r and omized controlled trial of goal -directed therapy in high-risk surgical patients . Methods All patients from a previous r and omized controlled study were followed up for 15 years following r and omization to ascertain their length of survival following surgery . Factors that may be associated with increased survival were evaluated to determine what influenced long-term outcomes . Results Data from 106 of the original 107 patients ( 99 % ) were available for analysis . At 15 years , 11 ( 20.7 % ) of the goal -directed therapy patients versus 4 ( 7.5 % ) of the control group were alive ( p = 0.09 ) . Median survival for the goal -directed group was increased by 1,107 days ( 1,781 vs. 674 days , p = 0.005 ) . Long-term survival was associated with three independent factors : age [ hazard ratio ( HR ) 1.04 ( 1.02–1.07 ) , p < 0.0001 ] , r and omization to the goal -directed group of the study [ HR 0.61 ( 0.4–0.92 ) , p = 0.02 ] , and avoidance of a significant postoperative cardiac complication [ HR 3.78 ( 2.16–6.6 ) , p = 0.007 ] . Conclusions Long-term survival after major surgery is related to a number of factors , including patient age and avoidance of perioperative complications . Short-term goal -directed therapy in the perioperative period may improve long-term outcomes , in part due to its ability to reduce the number of perioperative complications Previously , we developed a protocol for shock resuscitation of severe trauma patients to reverse shock and regain hemodynamic stability during the first 24 intensive care unit ( ICU ) hours . Key hemodynamic measurements of cardiac output and preload were obtained using a pulmonary artery catheter ( PAC ) . As an alternative , we developed a protocol that used central venous pressure ( CVP ) to guide decision making for interventions to regain hemodynamic stability [ mean arterial pressure ( MAP ) ≥ 65 mmHg and heart rate ( HR ) ≤ 130 bpm ] . Either protocol was available and required for traumatic shock resuscitation using bedside computerized clinical decision support to st and ardize decision making , and PAC was available if CVP-directed resuscitation was inadequate . We hypothesized that patients would be appropriately assigned to either protocol by trauma surgeon assessment of hemodynamic stability upon ICU admission . High-risk patients admitted to a level-1 trauma center ICU underwent resuscitation . Criteria were 1 ) major torso trauma , 2 ) base deficit ( BD ) ≥ 6 mEq/L or systolic blood pressure < 90 mmHg , 3 ) transfusion of ≥ 1 unit packed red blood cells ( PRBC ) , or ≥ age 65 years with two of three criteria . Patients with brain injury were excluded . Data were recorded prospect ively . In 24 months ending July 31 , 2006 , of 193 patients , 114 ( 59 % ) were assigned CVP- directed resuscitation , and 79 ( 41 % ) were assigned PAC-directed resuscitation . A subgroup of 11 ( 10 % ) initially assigned CVP was reassigned PAC-directed resuscitation ( 7 ± 2 h after start ) due to hemodynamic instability . Crystalloid fluid and PRBC resuscitation volumes for PAC ( 8 ± 1 L lactated Ringer 's [ LR ] , 5 ± 0.4 units PRBC ) were > CVP ( 5 ± 0.4 L LR , 3 ± 0.3 units PRBC ) and similar to CVP - PAC protocol subgroup patients ( 9 ± 2 L LR , 5 ± 1 units PRBC ) . Intensive care unit ( ICU ) stay and survival rate for PAC ( 18 ± 2 days , 75 % ) were similar to CVP - PAC ( 17 ± 4 days , 73 % ) and worse than CVP protocol subgroup patients ( 9 ± 1 days , 98 % ) . Traumatic shock resuscitation is feasible using CVP as a primary hemodynamic monitor as part of a protocol that includes explicit definition of hemodynamic instability and where PAC monitoring is readily available . Computerized decision support provides a technique to implement complex protocol care processes and analyze patient response Abstract Objectives : To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery , and to determine whether the inotropes , adrenaline and dopexamine , used to enhance oxygen delivery influence outcome . Design : R and omised controlled trial with double blinding between inotrope groups . Setting : York District Hospital , Engl and . Subjects:138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions . Interventions : Patients were r and omised into three groups . Two groups received invasive haemodynamic monitoring , fluid and either adrenaline or dopexamine to increase oxygen delivery . Inotropic support was continued during surgery and for at least12 hours afterwards . The third group ( control ) received routine perioperative care . Main outcome measures : Hospital mortality and morbidity . Results : Overall , 3/92 ( 3 % ) preoptimised patients died compared with 8/46 controls ( 17 % ) ( P=0.007 ) . There were no differences in mortality between the treatment groups , but 14/46 ( 30 % ) patients in the dopexamine group developed complications compared with 24/46 ( 52 % ) patients in the adrenaline group ( difference 22 % , 95%confidence interval 2 % to 41 % ) and 28 patients ( 61 % ) in the control group ( 31 % , 11 % to 50 % ) . The use of dopexamine was associated with a decreased length of stay in hospital . Conclusion : Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care BACKGROUND Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements . Intraoperative gut hypoperfusion during major surgery is associated with increased morbidity and postoperative hospital stay . We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery . METHODS This single centre , blinded , prospect i ve controlled trial r and omized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based ( conventional ) intraoperative fluid management . The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aim ing for a CVP between 12 and 15 mm Hg . RESULTS The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P<0.05 . The median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P<0.001 . Doppler patients achieved significantly higher cardiac output , stroke volume , and oxygen delivery . Twenty-nine ( 45.3 % ) control patients suffered gastrointestinal morbidity compared with nine ( 14.1 % ) in the Doppler guided fluid group P<0.001 , overall morbidity was also significantly higher in the control group P=0.05 . CONCLUSIONS Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay . Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity BACKGROUND Dynamic variables , for example , systolic pressure variation ( SPV ) , are superior to filling pressures for assessing fluid responsiveness . We analysed the effects of SPV-guided intraoperative fluid management on organ function and perfusion when compared with routine care . METHODS Eighty patients ( 44 female and 36 male ) undergoing elective major abdominal surgery were r and omly assigned to a control group [ n=40 , mean age 66 ( sd 10 ) , range 40 - 84 yr ] or SPV group [ n=40 , age 61 ( 16 ) , range 26 - 100 yr ] in which intraoperative fluid management was guided by SPV ( trigger : SPV>10 % ) . Central venous O2 saturation ( ScvO2 ) , lactate and bilirubin , creatinine , indocyanine green plasma disappearance rate ( ICG-PDR ) , and gastric mucosal CO(2 ) tension were measured after induction of anaesthesia , after 3 , 6 , 12 , and 24 h. RESULTS Patient characteristics , duration of surgery [ 5.8 ( 2.5 ) vs 5.4 ( 2.5 ) h ] , and infusion volumes ( median 4865 vs 4330 ml ) were comparable between the groups . At 3 and 6 h , SPV ( P=0.04 , P=0.01 ) and Deltadown ( P=0.005 , P=0.01 ) were significantly higher in the control group . Oxygen transport and organ function were comparable : baseline and 24 h values for ICG-PDR : 28.5 ( 7.9 ) and 22.7 ( 7.8 ) vs 23.9 ( 6.9 ) and 26.1 (5.9)% min(-1 ) , 77.7 ( 6.6 ) and 72.6 ( 5.5 ) vs 79.3 ( 7.1 ) and 72.8 (6.7)% for ScvO2 and 1.0 ( 0.4 ) and 1.2 ( 0.6 ) vs 0.9 ( 0.2 ) and 1.3 ( 0.5 ) mmol litre(-1 ) for lactate . Length of mechanical ventilation , ICU stay , and mortality were comparable . CONCLUSIONS In comparison with routine care , intraoperative SPV-guided treatment was associated with slightly increased fluid adminstration whereas organ perfusion and function was similar BACKGROUND Elevation of systemic oxygen delivery and consumption has been associated with an improved outcome in critically ill patients . We conducted a r and omized trial to determine whether boosting oxygen delivery by infusing the inotropic agent dobutamine would improve the outcome in a diverse group of such patients . METHODS On the basis of previously published recommendations , we established the following goals : a cardiac index above 4.5 liters per minute per square meter of body-surface area , oxygen delivery above 600 ml per minute per square meter , and oxygen consumption above 170 ml per minute per square meter . If these goals were not achieved with volume expansion alone , patients were r and omly assigned to a treatment or control group . The treatment group received intravenous dobutamine ( 5 to 200 micrograms per kilogram of body weight per minute ) until all three goals had been achieved . Dobutamine was administered to the control group only if the cardiac index was below 2.8 liters per minute per square meter . RESULTS A total of 109 patients were studied . In nine patients the therapeutic goals were achieved with volume expansion alone ; all nine patients survived to leave the hospital . Fifty patients were r and omly assigned to the treatment group , and 50 to the control group . During treatment , there were no differences between the two groups in mean arterial pressure or oxygen consumption , despite a significantly higher cardiac index and level of oxygen delivery in the treatment group ( P < 0.05 ) . Although the predicted risk of death during hospitalization was 34 percent for both groups , the in-hospital mortality was lower in the control group ( 34 percent ) than in the treatment group ( 54 percent ) ( P = 0.04 ; 95 percent confidence interval , 0.9 to 39.1 percent ) . CONCLUSIONS The use of dobutamine to boost the cardiac index and systemic oxygen delivery failed to improve the outcome in this heterogeneous group of critically ill patients . Contrary to what might have been expected , our results suggest that in some cases aggressive efforts to increase oxygen consumption may have been detrimental BACKGROUND Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal may improve outcomes in critically ill patients . We studied whether increasing the cardiac index to a supranormal level ( cardiac-index group ) or increasing mixed venous oxygen saturation to a normal level ( oxygen-saturation group ) would decrease morbidity and mortality among critically ill patients , as compared with a control group in which the target was a normal cardiac index . METHODS A total of 10,726 patients in 56 intensive care units were screened , among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were r and omly assigned to the three groups ( 252 to the control group , 253 to the cardiac-index group , and 257 to the oxygen-saturation group ) . RESULTS The hemodynamic targets were reached by 94.3 percent of the control group , 44.9 percent of the cardiac-index group , and 66.7 percent of the oxygen-saturation group ( P < 0.001 ) . Mortality was 48.4 , 48.6 , and 52.1 percent , respectively ( P = 0.638 ) , up to the time of discharge from the intensive care unit and 62.3 , 61.7 , and 63.8 percent ( P = 0.875 ) at six months . Among patients who survived , the number of dysfunctional organs and the length of the stay in the intensive care unit were similar in the three groups . No differences in mortality among the three groups were found for any diagnostic category . A subgroup analysis of the patients in whom hemodynamic targets were reached revealed similar mortality rates : 44.8 , 40.4 , and 39.0 percent , respectively ( P = 0.478 ) . CONCLUSIONS Hemodynamic therapy aim ed at achieving supranormal values for the cardiac index or normal values for mixed venous oxygen saturation does not reduce morbidity or mortality among critically ill patients INTRODUCTION : No consensus exists regarding the optimal fluid ( crystalloid or colloid ) or strategy ( liberal , restricted , or goal directed ) for fluid management after colectomy . Prior assessment s have used normal saline . This is the first assessment of st and ard , goal -directed perioperative fluid management with either lactated Ringer ’s or hetastarch/lactated Ringer ’s , with use of esophageal Doppler for guidance , in laparoscopic colectomy with an enhanced recovery protocol . METHODS : A double-blinded , prospect i ve , r and omized , three-armed study with Institutional Review Board approval was used for patients undergoing laparoscopic segmental colectomy assigned to the st and ard , goal -directed/lactated Ringer ’s and goal -directed/hetastarch groups . A st and ard anesthesia and basal fluid administration protocol was used in addition to the goal -directed strategies guided by esophageal Doppler . RESULTS : Sixty-four patients undergoing laparoscopic colectomy ( 22 st and ard , 21 goal -directed/lactated Ringer ’s , 21 goal -directed/hetastarch ) had similar operative times ( st and ard , 2.3 hours ; goal -directed/lactated Ringer ’s , 2.5 hours ; goal -directed/hetastarch , 2.3 hours ) . The lactated Ringer ’s group received the greatest amount of total and milliliters per kilogram per hour of operative fluid ( st and ard , 2,850/18 ; goal -directed/lactated Ringer ’s , 3,800/23 ; and goal -directed/hetastarch , 3,300/17 ; P < 0.05 ) . The hetastarch group had the longest stay ( st and ard , 64.9 hours ; goal -directed/lactated Ringer ’s , 71.8 hours ; goal -directed/hetastarch , 75.5 hours ; P < 0.05 ) . The st and ard group received the greatest amount of fluid during hospitalization ( st and ard , 2.5 ml/kg/h ; goal -directed/lactated Ringer ’s , 1.9 ml/kg/h ; goal -directed/hetastarch , 2.1 ml/kg/h ; P < 0.05 ) . There was one instance of operative mortality in the goal -directed/hetastarch group . CONCLUSIONS : Goal -directed fluid management with a colloid/balanced salt solution offers no advantage and is more costly . However , goal -directed , individualized intraoperative fluid management with crystalloid should be evaluated further as a component of enhanced recovery protocol s following colectomy because of reduced overall fluid administration OBJECTIVE To investigate the effect of a restricted intravenous fluid regimen versus a st and ard regimen on complications after colorectal resection . SUMMARY BACKGROUND DATA Current fluid administration in major surgery causes a weight increase of 3 - 6 kg . Complications after colorectal surgery are reported in up to 68 % of patients . Associations between postoperative weight gain and poor survival as well as fluid overload and complications have been shown . METHODS We did a r and omized observer-blinded multicenter trial . After informed consent was obtained , 172 patients were allocated to either a restricted or a st and ard intraoperative and postoperative intravenous fluid regimen . The restricted regimen aim ed at maintaining preoperative body weight ; the st and ard regimen resembled everyday practice . The primary outcome measures were complications ; the secondary measures were death and adverse effects . RESULTS The restricted intravenous fluid regimen significantly reduced postoperative complications both by intention-to-treat ( 33 % versus 51 % , P = 0.013 ) and per- protocol ( 30 % versus 56 % , P = 0.003 ) analyses . The numbers of both cardiopulmonary ( 7 % versus 24 % , P = 0.007 ) and tissue-healing complications ( 16 % versus 31 % , P = 0.04 ) were significantly reduced . No patients died in the restricted group compared with 4 deaths in the st and ard group ( 0 % versus 4.7 % , P = 0.12 ) . No harmful adverse effects were observed . CONCLUSION The restricted perioperative intravenous fluid regimen aim ing at unchanged body weight reduces complications after elective colorectal resection BACKGROUND Improved postoperative outcome has been demonstrated by perioperative maximization of cardiac stroke volume ( SV ) with fluid challenges , so-called goal -directed therapy . Oesophageal Doppler ( OD ) has been the most common technique for goal -directed therapy , but other flow-related techniques and parameters are available and they are potentially easier to apply in clinical practice . The objective of this investigation was therefore to use OD for preoperative SV maximization and compare the findings with a Modelflow determined SV , with an OD estimated corrected flow time ( FTc ) , with central venous oxygenation ( Svo2 ) and with muscle and brain oxygenation assessed with near infrared spectroscopy ( NIRS ) . METHODS Twelve patients scheduled for radical prostatectomy were anaesthetized before optimization of SV estimated by OD . A fluid challenge of 200 ml colloid was provided and repeated if at least a 10 % increment in OD SV was obtained . Values were compared with simultaneously measured values of Modelflow SV , FTc , Svo2 and muscle and cerebral oxygenation estimated by NIRS . RESULTS Based upon OD assessment , optimization of SV was achieved after the administration of 400 - 800 ml ( mean 483 ml ) of colloid . The hypothetical volumes administered for optimization based upon Modelflow and Svo2 differed from OD in 10 and 11 patients , respectively . Changes in FTc and NIRS were inconsistent with OD guided optimization . CONCLUSION Preoperative SV optimization guided by OD for goal -directed therapy is preferable compared with Modelflow SV , FTc , NIRS and Svo2 until outcome studies for the latter are available OBJECTIVE To examine the association between the use of right heart catheterization ( RHC ) during the first 24 hours of care in the intensive care unit ( ICU ) and subsequent survival , length of stay , intensity of care , and cost of care . DESIGN Prospect i ve cohort study . SETTING Five US teaching hospitals between 1989 and 1994 . SUBJECTS A total of 5735 critically ill adult patients receiving care in an ICU for 1 of 9 prespecified disease categories . MAIN OUTCOME MEASURES Survival time , cost of care , intensity of care , and length of stay in the ICU and hospital , determined from the clinical record and from the National Death Index . A propensity score for RHC was constructed using multivariable logistic regression . Case-matching and multivariable regression modeling techniques were used to estimate the association of RHC with specific outcomes after adjusting for treatment selection using the propensity score . Sensitivity analysis was used to estimate the potential effect of an unidentified or missing covariate on the results . RESULTS By case-matching analysis , patients with RHC had an increased 30-day mortality ( odds ratio , 1.24 ; 95 % confidence interval , 1.03 - 1.49 ) . The mean cost ( 25th , 50th , 75th percentiles ) per hospital stay was $ 49 300 ( $ 17 000 , $ 30 500 , $ 56 600 ) with RHC and $ 35 700 ( $ 11 300 , $ 20 600 , $ 39 200 ) without RHC . Mean length of stay in the ICU was 14.8 ( 5 , 9 , 17 ) days with RHC and 13.0 ( 4 , 7 , 14 ) days without RHC . These findings were all confirmed by multivariable modeling techniques . Subgroup analysis did not reveal any patient group or site for which RHC was associated with improved outcomes . Patients with higher baseline probability of surviving 2 months had the highest relative risk of death following RHC . Sensitivity analysis suggested that a missing covariate would have to increase the risk of death 6-fold and the risk of RHC 6-fold for a true beneficial effect of RHC to be misrepresented as harmful . CONCLUSION In this observational study of critically ill patients , after adjustment for treatment selection bias , RHC was associated with increased mortality and increased utilization of re sources . The cause of this apparent lack of benefit is unclear . The results of this analysis should be confirmed in other observational studies . These findings justify reconsideration of a r and omized controlled trial of RHC and may guide patient selection for such a study Background and objective We hypothesized that , in vascular surgery patients , the application of a goal -directed strategy based on a pulse contour-derived cardiac index would be associated with a better haemodynamic status than the application of routine perioperative care and that the amount of fluid and /or inotropes required in such a goal -directed therapy depended on the general anaesthetic technique used . Methods Patients undergoing peripheral arterial bypass grafting were r and omly assigned to three groups . In group 1 , haemodynamic management was performed according to routine clinical practice . In the two other groups ( groups 2 and 3 ) a goal -directed therapy was applied aim ing to maintain the pulse contour-derived cardiac index above 2.5 l m−2 min−1 . Patients in groups 1 and 2 received sevoflurane-based anaesthesia and patients in group 3 propofol-based anaesthesia . Haemodynamic variables , amount of fluid and administration of inotropes were assessed at different time intervals . Results The amount of fluid administered was not significantly different between the groups . Two patients in group 1 , 13 patients in group 2 and 12 patients in group 3 were treated with dobutamine ( P < 0.001 ) . None of the patients anaesthetized with sevoflurane ( groups 1 and 2 ) experienced postoperative cardiovascular complications , whereas four patients in the total intravenous group ( group 3 ) experienced major postoperative cardiovascular complications ( P = 0.005 ) . Conclusion In the conditions of the present study , the application of a goal -directed therapy aim ing to maintain the cardiac index above 2.5 l min−1 m−2 did not result in a higher tissue oxygen delivery than when applying the st and ard haemodynamic strategy nor did it depend on the anaesthetic technique used OBJECTIVES To compare the influence of 2 volumes of fluid , integrated with goal -directed fluid therapy , on hypovolemia ( a key trigger of tissue hypoperfusion ) and central venous oxygen saturation ( Scvo₂ ) and to assess their relationships with postoperative morbidity . DESIGN , SETTING , AND PATIENTS A prospect i ve , r and omized trial of 70 consecutive patients undergoing major abdominal surgery . INTERVENTIONS Patients were r and omly assigned to 6 mL/kg/h of crystalloid ( a restrictive fluid strategy ) or 12 mL/kg/h of crystalloid ( a more conservative fluid strategy ) . In both groups , a fluid bolus was administered when respiratory variation in peak aortic flow velocity ( ΔPV ) was greater than 13 % . Data on hypovolemia ( ΔPV > 13 % ) , Scvo₂ , and postoperative complications were recorded for all patients . MAIN OUTCOME MEASURES Overall incidence of postoperative complications , especially anastomotic leak and sepsis . RESULTS Overall incidence of complications , including postoperative anastomotic leak and sepsis , was higher in the restrictive group than in the conservative group ( all P < .05 ) . The number of patients with hypovolemia increased significantly in the restrictive group compared with the conservative group ( P < .001 ) . The perioperative mean Scvo₂ ( P = .02 ) and mean minimum Scvo₂ ( P = .04 ) were significantly lower in the restrictive group than in the conservative group . Multivariate analysis showed that both hypovolemia and mean minimum Scvo₂ were independently associated with anastomotic leak and sepsis . CONCLUSIONS Excessive fluid restriction increased the level of hypovolemia , leading to reduced Scvo₂ and thereby increased incidence of postoperative complications . Excessive fluid restriction should be applied cautiously in surgical patients . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00852449 Early goal -directed therapy is a term used to describe the guidance of intravenous fluid and vasopressor/inotropic therapy by using cardiac output or similar parameters in the immediate post-cardiopulmonary bypass in cardiac surgery patients . Early recognition and therapy during this period may result in better outcome . In keeping with this aim in the cardiac surgery patients , we conducted the present study . The study included 30 patients of both sexes , with EuroSCORE > or=3 undergoing coronary artery bypass surgery under cardiopulmonary bypass . The patients were r and omly divided into two groups , namely , control and early goal -directed therapy ( EGDT ) groups . All the subjects received st and ardized care ; arterial pressure was monitored through radial artery , central venous pressure through a triple lumen in the right internal jugular vein , electrocardiogram , oxygen saturation , temperature , urine output per hour and frequent arterial blood gas analysis . In addition , cardiac index monitoring using FloTrac and continuous central venous oxygen saturation using PreSep was used in patients in the EGTD group . Our aim was to maintain the cardiac index at 2.5 - 4.2 l/min/m2 , stroke volume index 30 - 65 ml/beat/m2 , systemic vascular resistance index 1500 - 2500 dynes/s/cm5/m2 , oxygen delivery index 450 - 600 ml/min/m2 , continuous central venous oximetry more than 70 % , stroke volume variation less than 10 % ; in addition to the control group parameters such as central venous pressure 6 - 8 mmHg , mean arterial pressure 90 - 105 mmHg , normal arterial blood gas analysis values , pulse oximetry , hematocrit value above 30 % and urine output more than 1 ml/kg/h . The aims were achieved by altering the administration of intravenous fluids and doses of inotropic or vasodilator agents . Three patients were excluded from the study and the data of 27 patients analyzed . The extra volume used ( 330+/-160 v/s 80+/-80 ml , P=0.043 ) number of adjustments of inotropic agents ( 3.4+/-1.5 v/s 0.4+/-0.7 , P=0.026 ) in the EGDT group were significant . The average duration of ventilation ( 13.8+/-3.2 v/s 20.7+/-7.1 h ) , days of use of inotropic agents ( 1.6+/-0.9 v/s 3.8+/-1.6 d ) , ICU stay ( 2.6+/-0.9 v/s 4.9+/-1.8 d ) and hospital stay ( 5.6+/-1.2 v/s 8.9+/-2.1 d ) were less in the EGDT group , compared to those in the control group . This study is inconclusive with regard to the beneficial aspects of the early goal -directed therapy in cardiac surgery patients , although a few benefits were observed BACKGROUND Our objective was to compare the effect of a restricted intravenous fluid regimen adjusted by serum lactate level with a st and ard restricted regimen on complications after major elective surgery for gastrointestinal malignancy . METHODS This is a r and omized , observer-blinded , single-center trial conducted across a time span of 13 months . A total of 299 patients were allocated to either a restricted intravenous fluid regimen with supplementary intravenous fluids given based on serum lactate level ( group A ) or a st and ard restricted regimen ( group R ) . In group A , the serum lactate level was monitored closely postoperatively to maintain a normal pre-operative serum lactate level . Group R involved patients treated with a restricted fluid regimen in whom additional fluid and electrolytes were administered when deemed necessary based on the usual clinical criteria . The primary outcome measure was complications ; the secondary measures were death and adverse effects . RESULTS Additional fluid supplementation was needed in some patients in both groups ( group A [ 28 % ] vs group R [ 26 % ] ) . In group A , the time for additional fluid infusion occurred earlier in the postoperative period than group R. Patients in group A received their first supplementary fluid treatment within the first 12 h more commonly than those in group R ( 74 % vs 37 % , respectively ; P < .004 ) . The regimen adjusted by serum lactate decreased systemic postoperative complications in group A versus group R ( 10 % vs 22 % , respectively ; P = .023 ) but not overall total complications ( 23 % vs 33 % , respectively ; P = .090 ) . In contrast , in patients who required additional fluid infusion , the difference in complications between the 2 groups was greater ( overall complication , 45 % vs 85 % , respectively ; P = .023 ; major complication , 16 % vs 44 % , respectively ; P = .018 ; systemic complications , 19 % vs 63 % , respectively ; P = .001 ) . One patient died in group A and 4 died in group R ( 1 % vs 4 % , respectively ; P = .206 ) . CONCLUSION A fluid-restricted regimen after elective gastrointestinal operations for malignancy may lead to fluid insufficiency and low tissue perfusion in up to 28 % of patients . Close monitoring of serum lactate levels with adjustment of intravenous fluid administration intraoperatively and in the early postoperative period may improve the early detection and correction of inadequate tissue perfusion , thereby decreasing the rate of complications OBJECTIVE The authors determined whether the preoperative placement of a pulmonary artery catheter ( PAC ) with optimization of hemodynamics results in outcome improvement after elective vascular surgery . SUMMARY BACKGROUND DATA The PAC commonly is used not only in patients who are critically ill , but also perioperatively in major elective surgery . Few prospect i ve studies exist documenting its usefulness . METHODS One hundred four consecutive patients were r and omized to have a PAC placed the morning of operation ( group I ) or to have a PAC placed only if clinical ly indicated ( group II ) . Group I patients were resuscitated to preestablished endpoints before surgery and kept at these points both intraoperatively and postoperatively . Group II patients received st and ard care . RESULTS There was one death in each group . An intraoperative or postoperative complication developed in 13 patients in group I versus 7 patients in group II ( p = not significant ) . Group I patients received more fluid than did group II patients ( 5137 + /- 315 mL vs. 3789 + /- 306 mL ; p < 0.003 ) . There was no significant difference in either overall or surgical intensive care unit length of stay . Only one patient in group II required a postoperative PAC . CONCLUSIONS Routine PAC use in elective vascular surgery increases the volume of fluid given to patients without demonstrable improvement in morbidity or mortality Abstract . Objective : To compare the survival and clinical outcomes of critically ill patients treated with the use of a pulmonary artery catheter ( PAC ) to those treated without the use of a PAC . Design : Prospect i ve , r and omised , controlled , clinical trial from October 1997 to February 1999 . Setting : Adult intensive care unit at a large teaching hospital . Patients : Two hundred one critically ill patients were r and omised either to a PAC group ( n=95 ) or the control group ( n=106 ) . One patient in the control group was withdrawn from the study and five patients in the PAC group did not receive a PAC . All participants were available for follow-up . Interventions : Participants were assigned to be managed either with the use of a PAC ( PAC group ) or without the use of a PAC ( control group ) . Main outcome measures : Survival to 28 days , intensive care and hospital length of stay and organ dysfunction were compared on an intention-to-treat basis and also on a subgroup basis for those participants who successfully received a PAC . Results : There was no significant difference in mortality between the PAC group [ 46/95 ( 47.9 % ) ] and the control group [ 50/106 ( 47.6 ) ] ( 95 % confidence intervals for the difference –13 to 14 % , p>0.99 ) . The mortality for participants who had management decisions based on information derived from a PAC was 41/91 ( 45 % , 95 % confidence intervals –11 to 16 % , p=0.77 ) . The PAC group had significantly more fluids in the first 24 h ( 4953 ( 3140 , 7000 ) versus 4292 ( 2535 , 6049 ) ml ) and an increased incidence of renal failure ( 35 versus 20 % of patients at day 3 post r and omisation p<0.05 ) and thrombocytopenia ( p<0.03 ) . Conclusions : These results suggest that the PAC is not associated with an increased mortality Objective To evaluate the effect of early optimization in the survival of severely injured patients . Summary Background Data It is unclear whether supranormal ( “ optimal ” ) hemodynamic values should serve as endpoints of resuscitation or simply as markers of the physiologic reserve of critically injured patients . The failure of optimization to produce improved survival in some r and omized controlled trials may be associated with delays in starting the attempt to reach optimal goals . There are limited controlled data on trauma patients . Methods Seventy-five consecutive severely injured patients with shock result ing from bleeding and without major intracranial or spinal cord trauma were r and omized to resuscitation , starting immediately after admission , to either normal values of systolic blood pressure , urine output , base deficit , hemoglobin , and cardiac index ( control group , 35 patients ) or optimal values ( cardiac index > 4.5 L/min/m2 , ratio of transcutaneous oxygen tension to fractional inspired oxygen > 200 , oxygen delivery index > 600 mL/min/m2 , and oxygen consumption index > 170 mL/min/m2 ; optimal group , 40 patients ) . Initial cardiac output monitoring was done noninvasively by bioimpedance and , subsequently , invasively by thermodilution . Crystalloids , colloids , blood , inotropes , and vasopressors were used by predetermined algorithms . Results Optimal values were reached intentionally by 70 % of the optimal patients and spontaneously by 40 % of the control patients . There was no difference in rates of death ( 15 % optimal vs. 11 % control ) , organ failure , sepsis , or the length of intensive care unit or hospital stay between the two groups . Patients from both groups who achieved optimal values had better outcomes than patients who did not . The death rate was 0 % among patients who achieved optimal values compared with 30 % among patients who did not . Age younger than 40 years was the only independent predictive factor of the ability to reach optimal values . Conclusions Severely injured patients who can achieve optimal hemodynamic values are more likely to survive than those who can not , regardless of the resuscitation technique . In this study , attempts at early optimization did not improve the outcome of the examined subgroup of severely injured patients Our aim in this observational , prospect i ve , noncontrolled study was to detect , in 29 patients who underwent abdominal aortic aneurysm ( AAA ) surgery , correlations between the incidence of postoperative organ failure and intraoperative changes in arterial and portal blood lactate ; changes in intramucosal sigmoid pH ( pHi ) ; differences between sigmoid Pco2 and arterial Pco2 ( & Dgr;CO2 ) ; and hemoglobin ( Hb ) . Hb , arterial blood lactate concentrations , pHi , and & Dgr;CO2 ( air tonometry ) were recorded at the start of anesthesia ( T0 ) , before aorta clamping ( T1 ) , 30 minutes after clamping ( T2 ) , and at the end of surgery ( T3 ) . Portal venous lactate concentrations were recorded at T1 and T2 . Patients were stratified into two groups : group A patients had no postoperative organ failure , and group B patients had one or more organ failures . As compared with group A ( n = 16 ) , group B patients ( n = 13 ) had a lower pHi value at T2 and T3 and a higher & Dgr;CO2 at T3 . A pHi value of < 7.15 was a predictor of organ failure , with a sensitivity of 92.3 % , a specificity of 68.8 % , and positive and negative predictive values of 70.6 % and 91.7 % , respectively , whereas a & Dgr;CO2 value of > 28 mm Hg predicted later organ failure with a sensitivity of 92.3 % , a specificity of 62.5 % , and positive and negative predictive values of 66.6 % and 90.9 % , respectively . Portal venous lactate concentrations were larger in group B at T2 ( P < 0.001 ) , and an increase ≥5 g/dL predicted later postoperative organ failure with a sensitivity of 92.3 % , a specificity of 100 % , and positive and negative predictive values of 100 % and 94.1 % , respectively . The comparison of the receiving operator characteristic curves to test the discrimination of each variable and the logistic regression analysis revealed that the increase in portal lactate was the best predictor for the development of postoperative organ failure . Hb concentration was significantly smaller in group B at T0 ( 13.8 ± 1.0 g/dL versus 12.2 ± 2.2 g/dL ) and T2 ( 10.9 ± 1.2 g/dL versus 9.1 ± 1.9 g/dL ) . In conclusion , both pHi and & Dgr;CO2 are reasonably sensitive prognostic indices of organ failures after AAA surgery , but they are less specific and accurate than portal venous lactate BACKGROUND Ever since Charles Baxter 's recommendations the st and ard regime for burn shock resuscitation remains crystalloid infusion at a rate of 4 ml/kg/% burn in the first 24h following the thermal injury . A growing number of studies on invasive monitoring in burn shock , however , have raised a debate regarding the adequacy of this regime . The purpose of this prospect i ve , r and omised study was to compare goal -directed therapy guided by invasive monitoring with st and ard care ( Baxter formula ) in patients with burn shock . PATIENTS AND METHODS Fifty consecutive patients with burns involving more than 20 % body surface area were r and omly assigned to one of two treatment groups . The control group was resuscitated according to the Baxter formula ( 4 ml/kg BW/% BSA burn ) , the thermodilution ( TDD ) group was treated according to a volumetric preload endpoint ( intrathoracic blood volume ) obtained by invasive haemodynamic monitoring . RESULTS The baseline characteristics of the two treatment groups were similar . Fluid administration in the initial 24h after burn was significantly higher in the TDD treatment group than in the control group ( P = 0.0001 ) . The results of haemodynamic monitoring showed no significant difference in preload or cardiac output parameters . Signs of significant intravasal hypovolemia as indicated by subnormal values of intrathoracic and total blood volumes were present in both treatment groups . Mortality and morbidity were independent on r and omisation . CONCLUSION Burn shock resuscitation due to the Baxter formula leads to significant hypovolemia during the first 48 h following burn . Haemodynamic monitoring results in more aggressive therapeutic strategies and is associated with a significant increase in fluid administration . Increased crystalloid infusion does not improve preload or cardiac output parameters . This may be due to the fact that a pure crystalloid resuscitation is incapable of restoring cardiac preload during the period of burn shock Objective : To evaluate the length of the effects of long‐term ( 48 hrs ) , low‐dose dopamine infusion on both renal function and systemic hemodynamic variables in stable nonoliguric critically ill patients . Design : Prospect i ve , single‐blind , controlled clinical study . Setting : University hospital , 19‐bed multidisciplinary intensive care unit . Patients : Eight hemodynamically stable , critically ill patients with a mild nonoliguric renal impairment ( creatinine clearance between 30 and 80 mL/min ) . Interventions : Each patient consecutively received 4 hrs of placebo , followed by a 3 μg/kg/min dopamine infusion during 48 hrs , then a new 4‐hr placebo period . We measured cardiac output and other hemodynamic variables by using a pulmonary artery catheter . The bladder was emptied to determine urine volume and to collect urine sample s. Measurements were performed at six times : after the initial control of 4 hrs of placebo ( C1 ) ; after 4 hrs ( H4 ) , 8 hrs ( H8 ) , 24 hrs ( H24 ) , and 48 hrs ( H48 ) of dopamine infusion ; and after the second control of 4 hrs of placebo ( C2 ) . Measurements and Main Results : We saw no significant change in systemic hemodynamic variables with dopamine at all times of infusion . Diuresis , creatinine clearance , and the fractional excretion of sodium ( FeNa ) at C1 and C2 were not different . Urine flow , creatinine clearance , and FeNa increased significantly 4 hrs after starting dopamine ( for all these changes , p < .01 vs. C1 and C2 ) . The maximum changes were obtained at H8 , with an increase of 50 % for diuresis , 37 % for creatinine clearance , and 85 % for FeNa ( for all these changes , p < .01 vs. C1 and C2 ) . But these effects waned progressively from H24 , and both creatinine clearance and FeNa at H48 did not differ from control values . Conclusions : In stable critically ill patients , preventive low‐dose dopamine increased creatinine clearance , diuresis , and the fractional excretion of sodium without concomitant hemodynamic change . These effects reached a maximum during 8 hrs of dopamine infusion . But despite a slight persistent increase in diuresis , improvement in creatinine clearance and FeNa disappeared after 48 hrs . According to these data , it is likely that tolerance develops to dopamine‐receptor agonists in critically ill patients at risk of developing acute renal failure Purpose : To assess the effects of intraoperative infusion of dopexamine ( a DA-1 and B2 adrenoreceptor agonist ) on hemodynamic function , tissue oxygen delivery and consumption , splanchnic perfusion and gut permeability following aortic cross-clamp and release . Methods : In a r and omised double blind controlled trial 24 patients scheduled for elective infrarenal abdominal aortic aneurysm repair were studied in two centres and were assigned to one of two treatment groups . Group I received a dopexamine infusion starting at 0.5 µg·kg−1·min−1 increased to 2 µg·kg−1·min−1 maintaining a stable heart rate : Group II received a placebo infusion titrated in the same volumes following induction of anesthesia . Measured and derived hemodynamic data , tissue oxygen delivery and extraction and gut permeability were recorded at set time points throughout the procedure . Results : Dopexamine infusion ( 0.5–2 µg·kg−1·min−1 ) was associated with enhanced hemodynamic function ( MAP 65±5.5vs92±5.7 mm Hg , P=<0.05 ) only during the period of aortic cross clamping . However , during the most part of infrarenal abdominal aortic surgery , dopexamine did not reduce systemic vascular resistance index , mean arterial pressure nor oxygen extraction compared with the control group . The lactulose/ rhamnose permeation ratio was elevated above normal in both groups ( 0.22 and 0.29 in groups I and II respectively ) . Conclusions : Dopexamine infusion ( 0.5 −2 µg·kg−1 ) did not enhance hemodynamic function and tissue oxygenation values during elective infrarenal abdominal aortic aneurysm repair . RésuméObjectif : Évaluer les effets d’une perfusion peropératoire de dopexamine , un agonist edes adrénorécepteurs DA-1 et B2 , sur l’heémodynamie , l’apport et la consommation d’oxygène tissulaire , la perfusion splanchnique et la perméabilité intenstinale à la suite d’un clampage total de l’aorte et de son retrait . Méthode : Il s’agit d’un essai ranomisé , contrôlé et à double insu auprès de 24 patients , provenant de deux centres et répartis en deux groupes , qui ont subi la réparation d’un anévrysme aortique abdominal sous-rénal . Le groupe I a reçu une perfusion de dopexamine amorcée à 0,5 µg·kg−1·min−1 , augmentée à 2 µg·kg−1·min−1 , maintenant une fréquence cardiaque stable ; le groupe II a reçu une perfusion placebo de même volume après l’induction de l’anesthésie . Les données hémodynamiques mesurées et dérivées , l’apport et la consommation d’oxygène tissuulaire et la permeábilité intestinale ont été notés à des moments de mesure déterminés au cours de l’intervention . Résultats : La perfusion de dopexamine ( 0,5 –2µg·kg−1 ) a stimulé la fonction hémodynamique ( TAM 65±5,5vs 92±5,7 mm Hg , P=<0,05 ) pendant le clampage aortique seulement . Cependant , pendant la majeure partie de l’intervention aortique abdominale sous-rénale , la dopexamine n’a pas réduitl l’indice de résistance vasculaire générale , la tension artŕielle moyenne ou la consommation d’oxygène , ce sdonnées étant comparées avec celles du groupe témoin . Le ratio de dissémination de lactulose / rhamnose s’est élevé au-dessus de la normale dans les deux groupes ( 0,22 et 0,29 dans les groupes I et II respectivement ) . Conclusion : La perfusion de dopexamine ( 0,5 –µg·kg−1·min−1 ) n’a pas amélioré l’hémodynamie ni haussé les valeurs d’oxygénation tissulaire pendant la réparation d’un anévrysme aortique abdominal sous-rénal BACKGROUND Postoperative organ failures commonly occur after major abdominal surgery , increasing the utilization of re sources and costs of care . Tissue hypoxia is a key trigger of organ dysfunction . A therapeutic strategy design ed to detect and reverse tissue hypoxia , as diagnosed by an increase of oxygen extraction ( O2ER ) over a predefined threshold , could decrease the incidence of organ failures . The primary aim of this study was to compare the number of patients with postoperative organ failure and length of hospital stay between those r and omized to conventional vs a protocol ized strategy design ed to maintain O2ER < 27 % . METHODS A prospect i ve , r and omized , controlled trial was performed in nine hospitals in Italy . One hundred thirty-five high-risk patients scheduled for major abdominal surgery were r and omized in two groups . All patients were managed to achieve st and ard goals : mean arterial pressure > 80 mm Hg and urinary output > 0.5 mL/kg/h . The patients of the " protocol group " ( group A ) were also managed to keep O2ER < 27 % . MEASUREMENTS AND MAIN RESULTS In group A , fewer patients had at least one organ failure ( n = 8 , 11.8 % ) than in group B ( n = 20 , 29.8 % ) [ p < 0.05 ] , and the total number of organ failures was lower in group A than in group B ( 27 failures vs 9 failures , p < 0.001 ) . Length of hospital stay was significantly lower in the protocol group than in the control group ( 11.3 + /- 3.8 days vs 13.4 + /- 6.1 days , p < 0.05 ) . Hospital mortality was similar in both groups . CONCLUSIONS Early treatment directed to maintain O2ER at < 27 % reduces organ failures and hospital stay of high-risk surgical patients . Clinical trials.gov reference No. NCT00254150 The objective was to test prospect ively supranormal values of cardiac index ( CI ) , oxygen delivery index ( DO2I ) , and oxygen consumption index ( VO2I ) as resuscitation goals to improve outcome in severely traumatized patients . We included patients > or = 16 years of age who had either ( 1 ) an estimated blood loss > or = 2000 mL or ( 2 ) a pelvic fracture and /or two or more major long bone fractures with > or = four units of packed red cells given within six hours of admission . The protocol resuscitation goals were CI > or = 4.5 L/min/m2 , DO2I > or = 670 mL/min/m2 , and VO2I > or = 166 mL/min/m2 within 24 hours of admission . The control resuscitation goals were normal vital signs , urine output , and central venous pressure . The 50 protocol patients had a significantly lower mortality ( 9 of 50 , 18 % vs. 24 of 65 , 37 % ) and fewer organ failures per patient ( 0.74 + /- 0.28 vs. 1.62 + /- 0.45 ) than did the 75 control patients . We conclude that increased CI , DO2I , and VO2I seen in survivors of severe trauma are primary compensations that have survival value ; augmentation of these compensations compared to conventional therapy decreases mortality BACKGROUND Intraoperative fluid therapy regimens using oesophageal Doppler monitoring ( ODM ) to optimize stroke volume ( SV ) ( goal -directed fluid therapy , GDT ) have been associated with a reduction in length of stay ( LOS ) and complication rates after major surgery . We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge ( RfD ) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients . METHODS In this double-blinded controlled trial , 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically ' fit ' ( n=123 ) or ' unfit ' ( n=56 ) on the basis of their performance during a cardiopulmonary exercise test . Within these fitness strata , patients were r and omized to receive a st and ard fluid regimen with or without ODM-guided intraoperative GDT . RESULTS GDT patients received an average of 1360 ml of additional intraoperative colloid . The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls . Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance ( median 6.8 vs 4.9 days , P=0.09 , and median 8.8 vs 6.7 days , P=0.09 , respectively ) . Fit GDT patients had an increased RfD ( median 7.0 vs 4.7 days ; P=0.01 ) and LOS ( median 8.8 vs 6.0 days ; P=0.01 ) compared with controls . CONCLUSIONS Intraoperative SV optimization conferred no additional benefit over st and ard fluid therapy . In an aerobically fit subgroup of patients , GDT was associated with detrimental effects on the primary outcome . TRIAL REGISTRY UK NIHR CRN 7285 , IS RCT N 14680495 . http://public.ukcrn.org.uk/ Search / Study Detail.aspx ? Study ID=7285 Background : Previous studies found contradictory results regarding the question whether mixed venous oxygen saturation ( Svo2 ) and central venous oxygen saturation ( Scvo2 ) are equivalent . The inconsistency of study results may result from different study design s and different , partly question able , statistical approaches . Methods : The authors performed a prospect i ve clinical trial comparing individual oxygen saturation values as well as the trend of values in blood from the superior vena cava ( Scvo2 ) , the right atrium ( Srao2 ) , and the pulmonary artery ( Svo2 ) during varying hemodynamic situations . The subjects were 70 patients scheduled to undergo elective neurosurgical operations in the sitting position . Oxygen saturation was measured photospectrometrically in blood sample s simultaneously taken at four different time points during supine and sitting positions . Statistical analysis was performed following the recommendations of Bl and and Altman . Results : Five hundred two comparative sets of measurements were obtained . Ninety-five percent limits of agreement ranging from ±6.83 to ±9.30 % for single values were interpreted as clinical ly unacceptable . In contrast , correlations between changes of Svo2 and Scvo2 as well as of Svo2 and Srao2 were interpreted as clinical ly acceptable ( R ≥ 0.755 , Pearson correlation coefficient ; P ≤ 0.0001 ) . Conclusions : In this sample of patients , exact numerical values of Scvo2 and Srao2 are not equivalent to those of Svo2 in varying hemodynamic conditions . However , for clinical purpose s , the trend of Scvo2 may be substituted for the trend of Svo2 . In addition , previous studies investigating the agreement between Svo2 and Scvo2 were found to be lacking in their chosen statistical approaches The hypothesis that optimizing hemodynamics using pulmonary artery ( PA ) catheter ( preoperative ' tune-up ' ) would improve outcome in patients undergoing limb-salvage arterial surgery was tested . Eighty-nine patients were r and omized to preoperative tune-up either in the surgical intensive care unit ( SICU ) ( group 1 ) or the preinduction room ( group 2 ) or to control ( group 3 ) . The tune-up consisted of fluid loading , afterload reduction , and /or inotropic support to achieve predetermined endpoints . Patients with a PA catheter had significantly fewer adverse intraoperative events ( p less than 0.05 ) , less postoperative cardiac morbidity ( p less than 0.05 ) , and less early graft thrombosis ( p less than 0.05 ) than the control group . The overall study mortality rate was 3.4 % , with a mortality rate of 9.5 % in the control group and 1.5 % in the PA catheter groups . There were no differences in ICU length of stay ( LOS ) , hospital LOS , or total hospital costs , although the percentage of cost from complications was higher in group 3 ( p greater than 0.05 ) . In this group of patients , preoperative cardiac assessment and optimization is associated with improved outcome OBJECTIVE to evaluate whether perioperative haemodynamic optimisation influences outcome from infrarenal abdominal aortic aneurysm repair . METHODS a consecutive series of 100 eligible patients were r and omised to either haemodynamic optimisation through the use of a pulmonary artery catheter ( CI > 3.0 l/min/sqm , PWP > 10 and < 18 mmHg , SVR < 1450 dyne/sec/cm(-5 ) , DO(2 ) > 600 ml/min/sqm ) or conventional treatment . RESULTS there were no differences in terms of in-hospital mortality , cardiovascular morbidity , postoperative renal failure or duration of hospital stay between the groups . CONCLUSIONS in this study perioperative haemodynamic optimisation was not beneficial RATIONALE It is unknown whether lactate monitoring aim ed to decrease levels during initial treatment in critically ill patients improves outcome . OBJECTIVES To assess the effect of lactate monitoring and resuscitation directed at decreasing lactate levels in intensive care unit ( ICU ) patients admitted with a lactate level of greater than or equal to 3.0 mEq/L. METHODS Patients were r and omly allocated to two groups . In the lactate group , treatment was guided by lactate levels with the objective to decrease lactate by 20 % or more per 2 hours for the initial 8 hours of ICU stay . In the control group , the treatment team had no knowledge of lactate levels ( except for the admission value ) during this period . The primary outcome measure was hospital mortality . MEASUREMENTS AND MAIN RESULTS The lactate group received more fluids and vasodilators . However , there were no significant differences in lactate levels between the groups . In the intention-to-treat population ( 348 patients ) , hospital mortality in the control group was 43.5 % ( 77/177 ) compared with 33.9 % ( 58/171 ) in the lactate group ( P = 0.067 ) . When adjusted for predefined risk factors , hospital mortality was lower in the lactate group ( hazard ratio , 0.61 ; 95 % confidence interval , 0.43 - 0.87 ; P = 0.006 ) . In the lactate group , Sequential Organ Failure Assessment scores were lower between 9 and 72 hours , inotropes could be stopped earlier , and patients could be weaned from mechanical ventilation and discharged from the ICU earlier . CONCLUSIONS In patients with hyperlactatemia on ICU admission , lactate-guided therapy significantly reduced hospital mortality when adjusting for predefined risk factors . As this was consistent with important secondary endpoints , this study suggests that initial lactate monitoring has clinical benefit . Clinical trial registered with www . clinical trials.gov ( NCT00270673 ) OBJECTIVE To test the hypothesis that perioperative plasma volume expansion would preserve gut mucosal perfusion during elective cardiac surgery . DESIGN Prospect i ve r and omized open study . SETTING Teaching hospital . PATIENTS Sixty American Society of Anesthesiology grade III patients with a preoperative left ventricular ejection fraction of 50 % or greater undergoing elective cardiac surgery . INTERVENTIONS Patients were allocated r and omly to a control or protocol group . The control group was treated according to st and ard practice s. After induction of general anesthesia , the protocol group received , in addition , 200-mL boluses of a 6 % hydroxyethyl starch solution to obtain a maximum stroke volume . This procedure was repeated every 15 minutes until the end of surgery , except when the patient underwent cardiopulmonary bypass . MEASUREMENTS AND RESULTS Cardiac stroke volume was estimated by an esophageal Doppler system , and gastric mucosal perfusion was measured by tonometric assessment of gastric intramucosal pH in all patients . Patients were followed up postoperatively until discharge from the hospital or death . The incidence of gut mucosal hypoperfusion ( gastric intramucosal pH < 7.32 ) at the end of surgery was reduced in the protocol group ( 7 % vs 56 % ) ( P < .001 ) , as were the number of patients in whom major complications developed ( 0 vs 6 ) ( P = .01 ) , mean number of days spent in the hospital ( 6.4 [ range , 5 to 9 ] vs 10.1 [ range , 5 to 48 ] ) ( P = .011 ) , and mean number of days spent in the intensive care unit ( 1 [ range , 1 to 1 ] vs 1.7 [ range 1 to 11 ] days ) ( P = .023 ) . CONCLUSIONS Perioperative plasma volume expansion with colloid during cardiac surgery , guided by esophageal Doppler measurement of cardiac stroke volume , reduced the incidence of gut mucosal hypoperfusion . This group of patients also had an improved outcome when compared with controls BACKGROUND Gastric tonometry , as a method of organ-specific monitoring of the status of the splanchnic circulation , has demonstrated prognostic and therapeutic implication s in critically ill patients . The experience with this method in patients with trauma has been limited . STUDY DESIGN Fifty-seven patients were prospect ively r and omized into two groups : group 1 , n = 30 , normalization and maintenance of gastric mucosal pH ( pHi ) at or above 7.3 and group 2 , n = 27 , maintenance of oxygen delivery index of 600 or an oxygen consumption index of greater than 150 . The groups had statistically similar injury severity scores , lactate levels , and base deficits . RESULTS Of the 44 patients with pHi greater than 7.3 at 24 hours , three ( 6.8 percent ) died of multiple organ dysfunction syndrome as compared with seven ( 53.9 percent ) of 13 in whom pHi was not optimized , p = 0.006 . Optimization times for oxygen delivery index , oxygen consumption index , lactate levels , and base excess were similar between survivors and nonsurvivors . The time for pHi optimization was significantly longer in nonsurvivors . Multiple organ dysfunction syndrome points were significantly higher in patients who did not have pHi optimized within 24 hours ( 6.08 compared with 2.5 , p = 0.03 ) . Optimization time for pHi was predictive of mortality on multiple regression . Persistently low pHi was frequently associated with systemic or intra-abdominal complications . It was the first finding in all the nonsurvivors at least 48 to 72 hours before death . CONCLUSIONS Gastric mucosal pH may be an important marker to assess the adequacy of resuscitation . Monitoring of pHi may provide early warning for systemic complications in the postresuscitation period Background : The debate over the correct perioperative fluid management is unresolved . Methods : The impact of two intraoperative fluid regimes on postoperative outcome was prospect ively evaluated in 152 patients with an American Society of Anesthesiologists physical status of I – III who were undergoing elective intraabdominal surgery . Patients were r and omly assigned to receive intraoperatively either liberal ( liberal protocol group [ LPG ] , n = 75 ; bolus of 10 ml/kg followed by 12 ml · kg−1 · h−1 ) or restrictive ( restrictive protocol group [ RPG ] , n = 77 ; 4 ml · kg−1 · h−1 ) amounts of lactated Ringer 's solution . The primary endpoint was the number of patients who died or experienced complications . The secondary endpoints included time to initial passage of flatus and feces , duration of hospital stay , and changes in body weight , hematocrit , and albumin serum concentration in the first 3 postoperative days . Results : The number of patients with complications was lower in the RPG ( P = 0.046 ) . Patients in the LPG passed flatus and feces significantly later ( flatus , median [ range ] : 4 [ 3–7 ] days in the LPG vs. 3 [ 2–7 ] days in the RPG ; P < 0.001 ; feces : 6 [ 4–9 ] days in the LPG vs. 4 [ 3–9 ] days in the RPG ; P < 0.001 ) , and their postoperative hospital stay was significantly longer ( 9 [ 7–24 ] days in the LPG vs. 8 [ 6–21 ] days in the RPG ; P = 0.01 ) . Significantly larger increases in body weight were observed in the LPG compared with the RPG ( P < 0.01 ) . In the first 3 postoperative days , hematocrit and albumin concentrations were significantly higher in the RPG compared with the LPG . Conclusions : In patients undergoing elective intraabdominal surgery , intraoperative use of restrictive fluid management may be advantageous because it reduces postoperative morbidity and shortens hospital stay In the present study , we compared indices of respiratory-induced variation obtained from direct arterial blood pressure measurement with analogous indices obtained from the plethysmogram measured by the pulse oximeter to assess the value of these indices for predicting the cardiac output increase in response to a fluid challenge . Thirty-two fluid challenges were performed in 22 hypotensive patients who were also monitored with a pulmonary artery catheter . Hemodynamic and plethysmographic data were collected before and after intravascular volume expansion . Patients were classified as nonresponders if their cardiac index did not increase by 15 % from baseline . Nonresponding patients had both lower arterial pulse variation ( [ 10 ± 4]% vs [ 19 ± 13]% , P = 0.020 ) and lower plethysmographic pulse variation ( [ 12 ± 7]% vs [ 21 ± 14]% , P = 0.034 ) when compared with responders . Fluid responsiveness was similarly predicted by arterial and plethysmographic pulse variations ( area under ROC curve 0.74 vs 0.72 , respectively , P = 0.90 ) and by arterial and plethysmographic systolic variation ( area under ROC curve 0.64 vs 0.72 , respectively , P = 0.50 ) . Nonresponders were identified by changes in pulse variation both on arterial and plethysmographic waveform ( area under ROC curve 0.80 vs 0.87 , respectively , P = 0.40 ) and by changes in arterial and plethysmographic systolic variations ( area under ROC curve 0.84 vs 0.80 , respectively , P = 0.76 ) . In the population studied , plethysmographic dynamic indices of respiratory-induced variation were just as useful for predicting fluid responsiveness as the analogous indices derived from direct arterial blood pressure measurement . These plethysmographic indices could provide a noninvasive tool for predicting the cardiac output increase by administering fluid We prospect ively tested the effect of the early postinjury attainment of supranormal values of cardiac index ( > or = 4.52 L/min per square meter ) , oxygen delivery ( > or = 670 mL/min per square meter ) , and oxygen consumption ( > or = 166 mL/min per square meter ) on outcome in traumatized patients with an estimated blood loss of 2000 mL or more . The goals in control patients were to attain normal values for all hemodynamic measurements . During the 6-month period , 33 protocol patients and 34 control patients with similar vital signs , estimated blood losses , and severity of injuries were enrolled in the study . Eight ( 24 % ) protocol patients died , while 15 ( 44 % ) control patients died . The protocol patients had fewer mean ( + /- SEM ) organ failures per patient ( 0.76 + /- 1.21 vs 1.59 + /- 1.60 ) , shorter stays in the intensive care unit ( 5 + /- 3 vs 12 + /- 12 ) , and fewer mean days requiring ventilation ( 4 + /- 3 vs 11 + /- 10 ) than did the control patients ( P < .05 for each ) . We conclude that attaining supranormal circulatory values improves survival and decreases morbidity in the severely traumatized patient Objective : The objective of this study was to investigate the effects of 2 levels of intraoperative fluid administration on perioperative physiology and outcome after laparoscopic cholecystectomy . Summary Background Data : Intraoperative fluid administration is variable as a result of limited knowledge of physiological and clinical effects of different fluid substitution regimens . Methods : In a double-blind study , 48 ASA I – II patients undergoing laparoscopic cholecystectomy were r and omized to 15 mL/kg ( group 1 ) or 40 mL/kg ( group 2 ) intraoperative administration of lactated Ringer ’s solution ( LR ) . All other aspects of perioperative management as well as preoperative fluid status were st and ardized . Primary outcome parameters were assessed repeatedly for the first 24 postoperative hours and included pulmonary function ( spirometry ) , exercise capacity ( submaximal treadmill test ) , cardiovascular hormonal responses , balance function , pain , nausea and vomiting , recovery , and hospital stay . Results : Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR led to significant improvements in postoperative pulmonary function and exercise capacity and a reduced stress response ( aldosterone , antidiuretic hormone , and angiotensin II ) . Nausea , general well-being , thirst , dizziness , drowsiness , fatigue , and balance function were also significantly improved , as well as significantly more patients fulfilled discharge criteria and were discharged on the day of surgery with the high-volume fluid substitution . Conclusions : Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR improves postoperative organ functions and recovery and shortens hospital stay after laparoscopic cholecystectomy Objectives To describe temporal hemodynamic and oxygen transport patterns in a large series of high-risk surgical patients in order to document physiologic patterns , to develop therapeutic goals for a wide range of surgical conditions , and to propose a mechanistic model for acute postoperative circulatory failure . Design Prospect i ve , longitudinal study . Patients identified as high risk were studied prospect ively . The data were analyzed immediately after they were acquired , again on formal rounds twice daily , and at a formal data review after completion of monitoring . Setting A university-run county hospital . Patients The patient series consisted of 708 consecutively monitored high-risk surgical patients . Interventions Hemodynamic and oxygen transport values and their responses to surgical trauma are known to vary widely with age and prior medical conditions ; they may be used to predict outcome with a high degree of accuracy . Temporal hemodynamic and oxygen transport patterns in a large series of high-risk surgical operations were treated by one group , using a well-developed protocol . Measurements and Main Results Hemodynamic and oxygen transport monitored variables were analyzed before , during , and at frequent intervals after surgical operations . We stratified the temporal patterns of survivors and nonsurvivors in each of the following groups : a ) patients without evidence of cardiovascular disease whose preoperative baseline cardiac index values were normal ; and b ) patients with high or low preoperative baseline cardiac index values due to the presence of preoperatively identified medical conditions that affect the circulatory status . In addition , we stratified patients in various age ranges who were without known cardiovascular diseases . The present study analyzed over 20,000 data sets with up to 32 variables in each data set or > 500,000 values . The major findings were intraoperatively reduced circulatory functions , principally cardiac index values , oxygen delivery ( Do2 ) , and oxygen consumption ( Vo2 ) . These reductions in circulatory functions intraoperatively were followed , in the early postoperative period , by increases in these variables . The postoperative increases in cardiac index , Do2 , and Vo2 values were greater in survivors than in nonsurvivors ; these findings were more apparent when the postoperative patterns of each strata were related to their own preoperative control values . Conclusions The data indicate that there are increased metabolic requirements after surgical trauma and that the changes in cardiac index and Do2 represent compensatory increases in circulatory functions stimulated by increased metabolic needs . However , these metabolic needs change with age , gender , severity of illness , type of operation , associated medical conditions , duration of shock , complications , organ failure , and outcome BACKGROUND Emergency abdominal surgery carries a high risk of postoperative morbidity and mortality . Goal directed therapy has been advocated to improve outcome in high-risk surgery . The aim of the present pilot study was to examine the effect of goal directed therapy using fluid alone on postoperative renal function and organ failure score in patients undergoing emergency abdominal surgery . METHODS This prospect i ve r and omised pilot study included patients over the age of 50 undergoing emergency abdominal surgery . In the intervention group pulse pressure variation measurements were used to guide fluid boluses of 6 % Hydroxyethylstarch 130/0.4 . The control group received st and ard care . Serum urea , creatinine and cystatin C levels were measured prior to and at the end of surgery and postoperatively on day 1 , day 3 and day 5 . RESULTS Thirty patients were recruited . One patient died prior to surgery and was excluded from the analysis . The intervention group received a median of 750 ml of hydroxyethylstarch . The peak values of postoperative urea were 6.9 ( 2.7 - 31.8 ) vs. 6.4 (3.5 - 11.5)mmol/l ( p=0.425 ) , creatinine 100 ( 60 - 300 ) vs. 85 ( 65 - 150 ) micromol/l ( p=0.085 ) and cystatin C 1.09 ( 0.66 - 4.94 ) vs. 1.01 (0.33 - 2.29)mg/dl ( p=0.352 ) in the control and intervention group , respectively . CONCLUSIONS In the present pilot study replacing the identified fluid deficit was not associated with a change in renal function . These results do not preclude that goal directed therapy using fluid alone may have an effect on renal function but they would suggest that the effect size of fluid optimisation alone on renal function is small Summary Oesophageal Doppler monitoring allows non‐invasive estimation of stroke volume and cardiac output . We studied the impact of Doppler guided fluid optimisation on haemodynamic parameters , peri‐operative morbidity and hospital stay in patients undergoing major bowel surgery . Fifty‐seven patients were r and omly assigned to Doppler ( D ) or control ( C ) groups . All patients received intra‐operative fluid therapy at the discretion of the non‐investigating anaesthetist . In addition , Group D were given fluid challenges ( 3 ml.kg−1 ) guided by oesophageal Doppler . Group D received significantly more intra‐operative colloid than Group C ( mean 28 ( SD 16 ) vs. 19.4 ( SD 14.7 ) ml.kg−1 , p = 0.02 ) . Cardiac output increased significantly for Group D whilst that of controls remained unchanged . The mean difference between the groups in final cardiac output was 0.87 l.min−1 ( 95 % confidence interval 0.31–1.43 l.min−1 , p = 0.003 ) . Five control patients required postoperative critical care admission . Fluid titration using oesophageal Doppler during bowel surgery can improve haemodynamic parameters and may reduce critical care admissions postoperatively OBJECTIVE To evaluate the effects of maintaining increased levels of preload on cardiopulmonary function and visceral perfusion during resuscitation . METHODS R and omized , prospect i ve study of 39 consecutive trauma patients with a low right ventricular ejection fraction ( < 40 % ) admitted to a university Level I trauma center during a 10-month period . Patients were r and omized to one of two groups : increased preload ( PL ) , or normal preload with inotropes ( INO ) . The PL group received fluid administration to maintain a target right ventricular end-diastolic volume index ( RVEDVI ) > or = 120 mL/m2 during resuscitation . The INO group had inotropes added according to a prospect ively determined protocol and was maintained at a RVEDVI of 90 to 100 mL/m2 . Systemic perfusion was assessed using oxygen transport and acid-base parameters , and pulmonary function was evaluated with PaO2/FiO2 ratio , dynamic compliance , ventilator days , and incidence of adult respiratory distress syndrome . Gut perfusion was assessed by measuring gastric intramucosal pH ( pHi ) . Data are expressed as means + /- SD . RESULTS The mean RVEDVI was significantly higher in the PL group ( n = 19 ) than in the INO group ( n = 20 ) during resuscitation ( 119+/-18 vs. 103+/-22 mL/m2 , p = 0.01 ) . There was no difference in oxygen delivery , mixed venous oxygen saturation , lactate , PaO2/FiO2 ratio , dynamic compliance , or ventilator days between the groups . The incidence of adult respiratory distress syndrome was not significantly different ( PL 31 % vs. INO 50 % , p > 0.1 ) . In the patients who had pHi measured sequentially during resuscitation ( PL = 13 , INO = 17 ) , the final pHi was significantly higher in the PL group ( 7.31+/-0.1 vs. 7.16+/-0.2 , p = 0.03 ) . CONCLUSION Patients resuscitated at higher levels of preload have significantly better visceral perfusion than those resuscitated at normal preload with addition of inotropes . This higher preload does not adversely affect pulmonary function Abstract Objectives : To assess whether intraoperative intravascular volume optimisation improves outcome and shortens hospital stay after repair of proximal femoral fracture . Design : Prospect i ve , r and omised controlled trial comparing conventional intraoperative fluid management with repeated colloid fluid challenges monitored by oesophageal Doppler ultrasonography to maintain maximal stroke volume throughout the operative period . Setting : Teaching hospital , London . Subjects : 40 patients undergoing repair of proximal femoral fracture under general anaesthesia . Interventions : Patients were r and omly assigned to receive either conventional intraoperative fluid management ( control patients ) or additional repeated colloid fluid challenges with oesophageal Doppler ultrasonography used to maintain maximal stroke volume throughout the operative period ( protocol patients ) . Main outcome measures : Time declared medically fit for hospital discharge , duration of hospital stay ( in acute bed ; in acute plus long stay bed ) , mortality , perioperative haemodynamic changes . Results : Intraoperative intravascular fluid loading produced significantly greater changes in stroke volume ( median 15 ml ( 95 % confidence interval 10 to 21 ml ) ) and cardiac output ( 1.2 l/min ( 0.1 to 2.3 l/min ) ) than in the conventionally managed group ( −5 ml ( −10 to 1 ml ) and −0.4 l/min ( −1.0 to 0.2 l/min ) ) ( P<0.001 and P<0.05 , respectively ) . One protocol patient and two control patients died in hospital . In the survivors , postoperative recovery was significantly faster in the protocol patients , with shorter times to being declared medically fit for discharge ( median 10 ( 9 to 15 ) days v 15 ( 11 to 40 ) days , P<0.05 ) and a 39 % reduction in hospital stay ( 12 ( 8 to 13 ) days v 20 ( 10 to 61 ) days , P<0.05 ) . Conclusions : Proximal femoral fracture repair constitutes surgery in a high risk population . Intraoperative intravascular volume loading to optimal stroke volume result ed in a more rapid postoperative recovery and a significantly reduced hospital stay . Key messages Patients undergoing hip fracture repair constitute a high risk group with considerable mortality and morbidity and an often protracted postoperative hospital stay These patients often have depleted intravascular volume in the perioperative period and rarely receive either invasive haemodynamic monitoring or high dependency care Haemodynamic optimisation guided by pulmonary artery catheter in the perioperative period has been shown to improve outcome in high risk patients undergoing major surgery , but this is not considered routinely practicable for hip fracture repair Intravascular volume optimisation directed by minimally invasive oesophageal Doppler monitoring in the intraoperative period significantly reduces hospital |
11,829 | 29,865,900 | FGAs caused slightly less weight gain and more extrapyramidal symptoms than SGAs .
SGAs as a class caused adverse effects , including weight gain , high triglyceride levels , extrapyramidal symptoms , sedation , and somnolence .
They appeared to increase the risk for high cholesterol levels and type 2 diabetes .
Olanzapine caused more short-term gains in weight and body mass index than several other SGAs .
The dose of SGAs may not make a difference over the short term for some outcomes . | Objective : To up date and extend our previous systematic review on first- ( FGAs ) and second-generation antipsychotics ( SGAs ) for treatment of psychiatric and behavioral conditions in children , adolescents , and young adults ( aged ≤24 years ) .
This article focuses on the evidence for harms . | Atypical antipsychotics have been shown to improve disruptive and repetitive behaviors in pervasive developmental disorders ( PDDs ) , but they require assessment of potential side effects . This is the first placebo-controlled trial of olanzapine in the treatment of children and adolescents with PDD . Eleven patients with a diagnosis of either autism , Asperger 's syndrome , or PDD not otherwise specified ( PDD-NOS ) and aged 6 - 14 years were r and omized into an 8-week double-blind , placebo-controlled , parallel treatment study with olanzapine . There was a significant linear trend x group interaction on the Clinical Global Impressions- Improvement ( CGI-I ) and 50 % on olanzapine versus 20 % on placebo were responders . Olanzapine was associated with significant weight gain ( 7.5 + /- 4.8 lbs vs. 1.5 + /- 1.5 lbs on placebo ) . Olanzapine may be a promising treatment for improving global functioning of PDDs , but the risk of significant weight gain remains a concern . Additional studies are needed to determine the efficacy and safety of olanzapine in the treatment of children with PDD OBJECTIVE The authors studied weight gain mechanisms and energy balance in patients treated with olanzapine . METHOD The body mass index of male schizophrenic adolescent in patients treated with olanzapine ( N=10 ) and of 10 matched patients treated with haloperidol ( N=10 ) were measured at baseline and after 4 weeks of treatment . For the patients treated with olanzapine , caloric intake , resting energy expenditure , and physical activity ( determined through accelerometry and heart rate monitoring ) were assessed at baseline and after 4 weeks of treatment . RESULTS Body mass index significantly increased in those treated with olanzapine but not in those given haloperidol . The increase in body mass index was due to an increase in caloric intake without change in diet composition . Olanzapine had no significant effect on resting energy expenditure . Daily energy expenditure was very low before and after treatment . CONCLUSIONS Olanzapine-induced weight gain is associated with a general increase in caloric intake OBJECTIVE The purpose of this study was to evaluate the impact of prior antipsychotic exposure ( PAE ) on safety and tolerability outcomes in pediatric subjects receiving aripiprazole treatment . METHODS This study was a post-hoc analysis of pooled data from two 8-week , double-blind , r and omized , placebo-controlled studies evaluating aripiprazole for the treatment of irritability in pediatric subjects with autistic disorder , aged 6 - 17 years . Subjects were stratified by PAE ; adverse events ( AEs ) , and changes in weight , and metabolic measures were evaluated . For subjects receiving aripiprazole , regardless of PAE , baseline weight , age , gender , and symptom severity were evaluated in a regression model predicting body weight change . RESULTS Of 316 r and omized subjects , 259 ( 82.0 % ) were antipsychotic naïve ( AN ) and 57 ( 18.0 % ) had a PAE . Aripiprazole-treated AN subjects were more likely than PAE subjects to report somnolence ( 11.9 % vs. 2.8 % ) , sedation ( 22.7 % vs. 11.1 % ) , or fatigue ( 17.0 % vs. 13.9 % ) . Rates of extrapyramidal disorder and drooling , but not akathisia or tremor , were marginally higher in AN subjects . Overall , 10.8 % of aripiprazole-treated AN subjects had at least one AE leading to discontinuation compared with 8.3 % of aripiprazole-treated PAE subjects . AN subjects receiving aripiprazole had a larger change in weight from baseline to endpoint compared with those receiving placebo ( 1.9 vs. 0.7 kg ; treatment difference 1.2 kg , 95 % CI : 0.5 , 1.9 ) than PAE subjects receiving aripiprazole compared with subjects receiving placebo ( 0.4 vs. -0.4 kg ; treatment difference 0.9 kg , 95 % CI : -0.6 , 2.4 ) . Regression analysis identified that younger subjects with higher baseline weight z-score were at highest risk for weight gain . There were no significant changes in metabolic measures compared with placebo in either group . CONCLUSIONS Weight gain was more pronounced in AN subjects and more likely to occur in younger subjects with a higher baseline weight z-score . AN subjects were more likely to experience AEs related to somnolence . However , based on discontinuations rates from AEs , overall tolerability was good for both AN and PAE groups . CLINICAL TRIAL REGISTRATION Study of aripiprazole in the treatment of children and adolescents with autistic disorder . Registry : www . clinical trials.gov . Identifiers : NCT00332241 and NCT00337571 OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of acute quetiapine monotherapy in adolescents with schizophrenia . METHODS Patients ages 13 - 17 years with an American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . , Text Revision ( DSM-IV-TR ) diagnosis of schizophrenia and a Positive and Negative Syndrome Scale ( PANSS ) total score ≥60 were r and omized to 6 weeks of quetiapine ( 400 or 800 mg/day ) or placebo treatment . The primary efficacy measure was change in PANSS total score from baseline to day 42 . Safety endpoints included adverse events and assessment s of clinical chemistry values , suicidality , and extrapyramidal symptoms . RESULTS The intent-to-treat population included 220 patients . Least-squares mean change in PANSS total score from baseline to endpoint was -27.31 with quetiapine 400 mg/day , -28.44 with quetiapine 800 mg/day , and -19.15 with placebo ( p=0.043 and 0.009 for quetiapine 400 and 800 mg/day , respectively , vs. placebo ; mixed-model , repeated- measures analysis ) . Several secondary efficacy outcomes , including Clinical Global Impressions-Improvement score , supported the primary outcome measure in demonstrating significantly greater improvement in quetiapine groups than in the placebo group . Mean changes in body weight at day 42 were 2.2 kg and 1.8 kg for quetiapine 400 and 800 mg/day , respectively , and -0.4 kg for placebo . Mean changes in certain clinical chemistry parameters , including total cholesterol and triglycerides , were numerically greater in the quetiapine groups than in the placebo group . Adverse events associated with quetiapine were mostly mild to moderate in intensity and were consistent with its known profile in adults with schizophrenia . CONCLUSIONS In this 6-week study of adolescent patients , quetiapine at doses of 400 and 800 mg/day provided significant improvements in symptoms associated with schizophrenia in adolescent patients , including the primary efficacy measure of PANSS total score change . Quetiapine was generally well tolerated with a profile broadly similar to that reported in adult and adolescent population s. CLINICAL TRIAL REGISTRATION INFORMATION Quetiapine Fumarate ( SEROQUEL ( ™ ) ) Compared to Placebo in the Treatment of Adolescent Patients With Schizophrenia ( ANCHOR 112 ) . Available at : http://www . clinical trials.gov/ct2/show/NCT00090324?term=quetiapine+112&rank=1 BACKGROUND Paliperidone extended-release ( ER ) is approved for treatment of schizophrenia in adults but has not been evaluated in adolescents . METHODS In this 6-week , double-blind , parallel-group study , participants ( n = 201 ) aged 12 to 17 years , with a Positive and Negative Syndrome Scale ( PANSS ) total score of 60 to 120 were r and omly allocated ( 1:1:1:1 ) to receive either placebo or one of three weight-based , fixed doses of paliperidone ER , once-daily ( patients weighing 29 to < 51 kg at baseline : 1.5 mg [ Low ] , 3 mg [ Medium ] , or 6 mg [ High ] ; patients weighing ≥ 51 kg : 1.5 mg [ Low ] , 6 mg [ Medium ] , or 12 mg [ High ] ) . RESULTS The mean ( SD ) change in PANSS total score from baseline to endpoint ( primary efficacy variable ) was significant for the paliperidone ER Medium-treatment ( -17.3 [ 14.33 ] ; p < .05 ; n = 54 ) but not for Low- ( -9.8 [ 16.31 ] ; n = 48 ) or High-treatment groups ( -13.8 [ 15.74 ] ; n = 47 ) versus placebo ( -7.9 [ 20.15 ] ; n = 51 ) . By actual dose , the mean ( SD ) change in PANSS total score was significant for the 3- , 6- , and 12-mg doses ( 3 mg : -19.0 [ 15.45 ] ) , 6 mg : -13.8 [ 14.75 ] , and 12 mg : -16.3 [ 15.41 ; ] all ps < .05 ) , compared with placebo ( -7.9 [ 20.15 ] ) . The total percentages of treatment-emergent adverse events were dose-related for the three weight-based treatment groups . CONCLUSIONS With weight-based treatment , only paliperidone ER Medium-treatment ( 3 - 6 mg ) result ed in significant improvement in symptoms of schizophrenia in adolescents , as did 3 , 6 , and 12 mg by actual dose strengths . Weight-based dosing of paliperidone ER in adolescents with schizophrenia does not appear to be necessary . Paliperidone ER ( 1.5 - 12 mg , once daily ) was tolerable , and no new safety concerns were reported BACKGROUND This study evaluates the long-term efficacy of aripiprazole compared to placebo in children with bipolar disorders . METHOD Out patients aged 4 to 9 years meeting DSM-IV criteria for a bipolar disorder ( I , II , not otherwise specified , cyclothymia ) were eligible to receive up to 16 weeks of open-label treatment with aripiprazole ( phase 1 ) . Patients were r and omized into the 72-week double-blind phase of the study once they met a priori response criteria for stabilization ( phase 2 ) . During phase 2 , patients either remained on their current aripiprazole regimen or began a double-blind taper with aripiprazole discontinued and switched to placebo . The primary outcome measure for phase 2 was time to discontinuation due to a mood event . RESULTS Patients were recruited between May 2004 and November 2008 . Following phase 1 , in which 96 patients received aripiprazole , 30 patients ( mean age = 7.1 years ) were r and omly assigned to continue aripiprazole and 30 patients ( mean age = 6.7 years ) were r and omly assigned to placebo . The mean ( SD ) dose of aripiprazole prior to r and omization for these patients was 6.4 ( 2.1 ) mg/d . Patients r and omly assigned to aripiprazole were enrolled significantly longer until time to study discontinuation due to a mood event ( 6.14 median weeks , SE ± 11.88 weeks ; P = .005 ) and discontinuation for any reason ( including mood events ) ( 4.00 median weeks , SE ± 3.91 weeks ; P = .003 ) than those r and omly assigned to placebo ( mood event , 2.29 median weeks , SE ± 0.38 weeks ; any reason , 2.00 median weeks , SE ± 0.31 weeks ) . Regardless of r and om assignment , both the aripiprazole and placebo groups showed substantial rates of withdrawal from maintenance treatment over the initial 4 weeks ( 15/30 [ 50 % ] for aripiprazole ; 27/30 [ 90 % ] for placebo ) , suggesting a possible nocebo effect ( ie , knowledge of possibly switching from active medication to placebo increasing concern about relapse ) . The most frequently reported adverse events during double-blind aripiprazole therapy included stomach pain ( n = 10 , 33 % ) , increased appetite ( n = 9 , 30 % ) , and headaches ( n = 9 , 30 % ) . CONCLUSIONS Despite the possibility of a nocebo effect , these results suggest that aripiprazole may be superior to placebo in the long-term treatment of pediatric patients following stabilization with open-label aripiprazole . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00194077 BACKGROUND & AIMS Weight gain is an undesirable side effect of second-generation antipsychotics ( SGAs ) . We performed this study to examine the influence of SGAs on resting energy expenditure ( REE ) and the relationship of REE to weight gain in adolescent patients . METHODS Antipsychotic-naïve or quasi-naïve ( < 72 h of exposure to antipsychotics ) adolescent patients taking olanzapine , quetiapine , or risperidone in monotherapy were followed up for one year . We performed a prospect i ve study ( baseline , 1 , 3 , 6 , and 12 months after treatment ) based on anthropometric measurements , bioelectrical impedance analysis , and indirect calorimetry ( Deltatrac ™ II MBM-200 ) to measure REE . We also analyzed metabolic and hormonal data and adiponectin concentrations . RESULTS Forty-six out of the 54 patients that started treatment attended at least 2 visits , and 16 completed 1 year of follow-up . Patients gained 10.8 ± 6.2 kg ( 60 % in the form of fat mass ) and increased their waist circumference by 11.1 ± 5.0 cm after 1 year of treatment . The REE/kg body mass ratio decreased ( p = 0.027 ) , and the REE/percentage fat-free mass ( FFM ) ratio increased ( p = 0.007 ) following the fall in the percentage of FFM during treatment . Weight increase was significantly correlated with the REE/percentage FFM ratio at all the visits ( 1 - 3 - 6 - 12 months ) ( r = 0.69 , p = 0.004 at 12 months ) . CONCLUSIONS SGAs seem to induce a hypometabolic state ( reflected as decreased REE/kg body mass and increased REE/percentage FFM ) . This could explain , at least in part , the changes in weight and body composition observed in these patients The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder . In this multicenter trial , out patients age 6–17 years who met DSM-IV-TR criteria for autistic disorder , and who demonstrated irritability , agitation , and /or self-injurious behaviors were r and omized to 6 weeks of double-blind treatment with lurasidone 20 mg/day ( N = 50 ) , 60 mg/day ( N = 49 ) , or placebo ( N = 51 ) . Efficacy measures included the Aberrant Behavior Checklist Irritability subscale ( ABC-I , the primary endpoint ) and the Clinical Global Impressions , Improvement ( CGI-I ) scale , and were analyzed using a likelihood-based mixed model for repeated measures . Least squares ( LS ) mean ( st and ard error [ SE ] ) improvement from baseline to Week 6 in the ABC-I was not significantly different for lurasidone 20 mg/day ( −8.8 [ 1.5 ] ) and lurasidone 60 mg/day ( −9.4 [ 1.4 ] ) versus placebo ( −7.5 [ 1.5 ] ; p = 0.55 and 0.36 , respectively ) . CGI-I scores showed significantly greater LS mean [ SE ] improvement at Week 6 for lurasidone 20 mg/day versus placebo ( 2.8 [ 0.2 ] vs. 3.4 [ 0.2 ] ; p = 0.035 ) but not for lurasidone 60 mg/day ( 3.1 [ 0.2 ] ; p = 0.27 ) . Discontinuation rates due to adverse events were : lurasidone 20 mg/day , 4.1 % ; 60 mg/day , 3.9 % ; and placebo , 8.2 % . Adverse events with an incidence ≥10 % ( lurasidone combined , placebo ) included vomiting ( 18.0 , 4.1 % ) and somnolence ( 12.0 , 4.1 % ) . Modest changes were observed in weight and selected metabolic parameters . In this study , once-daily , fixed doses of 20 and 60 mg/day of lurasidone were not demonstrated to be efficacious compared to placebo for the short-term treatment of children and adolescents with moderate-to-severe irritability associated with autistic disorder OBJECTIVE To assess olanzapine 's efficacy and tolerability in adolescents with schizophrenia . METHOD One hundred seven inpatient and outpatient adolescents ( olanzapine , n = 72 , mean age 16.1 years ; placebo , n = 35 , mean age 16.3 years ) with schizophrenia participated in this r and omized ( 2:1 ) , international , multisite , industry-sponsored trial . All patients met DSM-IV-TR criteria for schizophrenia , and they were treated for up to 6 weeks with flexible doses of olanzapine ( 2.5 - 20.0 mg/day ) or placebo . Last-observation-carried-forward mean changes from baseline to endpoint on the anchored version of the Brief Psychiatric Rating Scale for Children , Clinical Global Impression Scale-Severity of Illness , and Positive and Negative Syndrome Scale ( PANSS ) were assessed . RESULTS More olanzapine-treated versus placebo-treated patients completed the trial ( 68.1 % versus 42.9 % , p = .020 ) . Compared with placebo-treated patients , olanzapine-treated adolescents had significantly greater improvement in Brief Psychiatric Rating Scale for Children total ( p = .003 ) , Clinical Global Impressions Scale-Severity of Illness ( p = .004 ) , PANSS total ( p = .005 ) , and PANSS positive scores ( p = .002 ) . Olanzapine-treated patients gained significantly more baseline-to-endpoint weight ( 4.3 kg versus 0.1 kg , p < .001 ) . Significantly more olanzapine-treated versus placebo-treated patients gained 7 % or greater of their body weight at any time during treatment ( 45.8 % versus 14.7 % , p = .002 ) . Prolactin and triglyceride mean baseline-to-endpoint changes were significantly higher in olanzapine-treated versus placebo-treated adolescents . The incidence of treatment-emergent significant changes in fasting glucose , cholesterol , or triglycerides did not differ between the groups at endpoint , but significantly more olanzapine-treated patients had high triglycerides at any time during treatment . CONCLUSIONS Olanzapine-treated adolescents with schizophrenia experienced significant symptom improvement . Significant increases in weight , triglycerides , uric acid , most liver function tests , and prolactin were observed during olanzapine treatment . Clinical trial registration information-Olanzapine Versus Placebo in the Treatment of Adolescents With Schizophrenia . URL : http://www . clinical trials.gov . Unique identifier : NCT00051298 BACKGROUND Treatment strategies for mental disorders may vary according to illness stage . However no data currently exist to guide treatment in first episode psychotic mania . The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine , as add-on to lithium , in patients with a first episode of psychotic mania , expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments . METHODS Data from 83 patients were collected in an 8-week r and omised controlled trial on clinical variables , side effects , vital signs , and weight . Analyses of treatment differences over time were based on intent-to-treat principles . Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures . RESULTS Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector . Contrary to our hypotheses , safety profile of both medications was similar . A signal for higher rate ( P=.032 ) and earlier occurrence ( P=.043 ) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons . CONCLUSIONS Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania . The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample This study investigated prolactin levels in two groups of children and adolescents receiving risperidone ( N=29 ) or olanzapine ( N=13 ) . It focused not only on significant differences but also on effect sizes ; took into account dose effects and gender differences ; used a longitudinal design ( months 1 , 3 , 6 and 12 ) that helped control for individual differences ; and took into account response differences due to the duration of antipsychotic treatment . Additionally , this study investigated tolerance development using statistical tests , and explored the effect of antipsychotic plasma concentrations at months 1 and 3 . After adjusting for gender , treatment duration and individual effects , mean prolactin levels on risperidone were 4.9 ng/mL higher than on olanzapine ( 10.3 times higher after controlling for dosing potency ) . On risperidone treatment , the adjusted mean prolactin level at the 3rd month of treatment was significantly higher than at the 1st month ; at the 12th month it was significantly lower than at the 1st month ; the 1st and 6th months were not significantly different . On olanzapine treatment , adjusted mean prolactin levels at the 3rd and 6th months of treatment were significantly higher than at the 1st month ; at the 12th month it was lower than at the 1st month , but the difference was not significant . In males , at the 3rd month , an increase of 1 ng/mL in plasma 9-hydroxyrisperidone concentrations raised prolactin levels significantly by 0.44 ng/mL. In females , independently of duration ( 1 or 3 months ) , an increase of 1 ng/mL in plasma olanzapine concentrations raised prolactin levels significantly by 2.1 ng/mL. After adjusting for dose and the greater potency of risperidone , the increase in prolactin levels during risperidone treatment appeared to be 10.3 times higher than that during olanzapine treatment . Our study showed a pattern consistent with the development of prolactin tolerance over time . Future prolactin studies in children and adolescents taking antipsychotics need to include larger sample s with more frequent prolactin measures and long-term plasma concentrations OBJECTIVE The purpose of this study was to evaluate the safety and efficacy of asenapine in adolescents with schizophrenia . METHODS In an 8 week , r and omized , double-blind placebo-controlled trial , subjects ( 12 - 17 years of age ) meeting Diagnostic and Statistical Manual of Mental Disorders , 4th ed . , Text Revision ( DSM-IV-TR ) criteria for schizophrenia were r and omized 1:1:1 to placebo , asenapine 2.5 mg b.i.d . , or asenapine 5 mg b.i.d . Subjects who completed the 8 week acute study could participate in a 26 week flexible-dose asenapine-only open-label extension ( OLE ) . RESULTS A similar percentage of subjects completed treatment on day 56 ( 2.5 mg b.i.d . ( n=98 ) : 83 % ; 5 mg b.i.d . [ n=106 ] : 79 % ; placebo [ n=102 ] : 79 % ) . In the mixed model for repeated measures analysis of the primary end-point ( with Hochberg correction for multiplicity ) , least squares ( LS ) mean differences between asenapine and placebo on the Positive and Negative Syndrome Scale ( PANSS ) total score at day 56 were not significant ( -4.8 for 2.5 mg b.i.d . , p=0.070 ; -5.6 for 5 mg b.i.d . , p=0.064 ) . Significant improvement in the Clinical Global Impressions-Severity score was observed in the 5 mg b.i.d . group versus placebo on day 56 ( LS mean -0.3 , p=0.024 ) . In the acute phase , ≥7 % weight gain and the composite event of somnolence , sedation , and hypersomnia were more common in both asenapine groups than in the placebo group . Akathisia , fasting glucose elevation , and extrapyramidal syndrome were more common in the 5 mg b.i.d . group than in the placebo group . There were no unexpected adverse events in the OLE , and PANSS total scores decreased by -16.1 points in the group previously treated with placebo ( n=62 ) and by -11.2 points in the continuous asenapine group ( n=131 ) from OLE baseline to week 26 . CONCLUSIONS Although improvements in PANSS total score at day 56 of the acute phase were numerically greater for both asenapine 2.5 and 5 mg b.i.d . than for placebo and were maintained in the OLE , the primary end-point did not achieve statistical significance in the acute phase . No new or unexpected safety concerns were detected during the acute phase or after an additional 26 weeks of asenapine treatment in the adolescent population with schizophrenia . CLINICAL TRIALS REGISTRY NCT01190254 and NCT1190267 at Clinical Trials.gov OBJECTIVE The Child and Adolescent First-Episode Psychosis Study ( CAFEPS ) is a naturalistic longitudinal study of early-onset first psychotic episodes . This report describes the antipsychotic treatment during the first year and compares the most frequently used agents after 6 months . METHODS Participants were 110 patients , aged 9 - 17 years , with a first psychotic episode attended consecutively at six different centers . The Positive and Negative Symptom Scale ( PANSS ) , Clinical Global Impressions ( CGI ) , Disability Assessment Schedule ( DAS ) , and Global Assessment of Function ( GAF ) scales were administered at baseline and at 6 months and the Udvalg for Kliniske Undersøgelser ( UKU ) Side Effects Rating Scale only at 6 months . RESULTS Diagnoses at baseline were 38.2 % psychotic disorder not otherwise specified , 39.1 % schizophrenia-type disorder , 11.8 % depressive disorder with psychotic symptoms , and 10.9 % bipolar disorder , manic episode with psychotic symptoms . The most frequently used antipsychotic agents were risperidone ( n = 50 ) , quetiapine ( n = 18 ) , and olanzapine ( n = 16 ) . Patients who were prescribed olanzapine or quetiapine had more negative and general symptoms . Using the baseline score as covariate , no significant differences were found in the reductions on any scale in patients treated with risperidone , quetiapine , or olanzapine for 6 months . Weight increase was greater with olanzapine than with risperidone ( p = 0.020 ) or quetiapine ( p = 0.040 ) . More neurological side effects appeared with risperidone than with olanzapine ( p = 0.022 ) . All side effects were mild or moderate . CONCLUSIONS Second-generation antipsychotics , especially risperidone , quetiapine , and olanzapine , are the most used in our context in first psychotic episodes in children and adolescents . These three obtain similar clinical improvement , but differ in their side effects OBJECTIVE The number of children and adolescents ( hereafter referred to as " children " ) who have been prescribed second-generation antipsychotics ( SGAs ) has increased over the last decade , but little is known about monitoring practice s in pediatric patients who are vulnerable to adverse effects . We examined factors associated with psychiatrists ' self-reported monitoring of children who were prescribed SGAs . METHODS A survey was mailed to a national , r and omly selected sample of 1600 child and adolescent psychiatrists from the American Medical Association mailing list . Using logistic regression , we tested whether psychiatrist characteristics , attitudes , and practice characteristics were associated with monitoring ( baseline and /or periodic ) the following : Patient history , height and weight , blood pressure , waist circumference , lipid and glucose levels , and electrocardiogram . RESULTS Among the analytic sample of 308 , at least two thirds reported monitoring patient history , height and weight , blood pressure , and fasting plasma lipids and glucose ; 23 % reported monitoring waist circumference ; and 12 % reported conducting an electrocardiogram . More than one third stated that they routinely monitored thyroid levels and more than half reported monitoring complete blood count and electrolytes/blood urea nitrogen . Psychiatrists reporting that they were able to measure vital signs on site were more likely to measure height and weight . Those who reported feeling comfortable conducting a physical examination were more likely to measure blood pressure . Those answering that the risk of metabolic syndrome was low were less likely to measure blood pressure and waist circumference . Being board certified and able to measure vital signs on site were associated with more monitoring of glucose and lipid levels . Conversely , years in practice and feeling that patients were nonadherent with blood work were associated with less monitoring of glucose and lipid levels . CONCLUSIONS In this sample , inconsistent monitoring patterns of children prescribed SGAs were found . Efforts to communicate guidelines ' evidence base and improve office capacity to measure and track adverse effects are needed to increase appropriate adverse effect monitoring in children who have been prescribed SGAs Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism . We aim ed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior ( aggressiveness , hyperactivity , irritability ) , social and emotional responsiveness , and communication skills . We conducted a r and omized , double-blind , placebo-controlled trial with 40 consecutive children with autism , whose ages ranged from 2 to 9 years , who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months . Autism symptoms were monitored periodically . The outcome variables were total scores on the Childhood Autism Rating Scale ( CARS ) and the Children 's Global Assessment Scale ( CGAS ) after 6 months . Of the 40 children enrolled , 39 completed the trial over a period of 18 months ; 19 received risperidone , and 20 received placebo . In the risperidone group , 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children 's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children 's Global Assessment Scale score in the placebo group ( P < .001 and P = .035 , respectively ) . Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression . Risperidone was associated with increased appetite and a mild weight gain , mild sedation in 20 % , and transient dyskinesias in three children . Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated . ( J Child Neurol 2006;21:450—455 ; DOI 10.2310/7010.2006.00099 ) BACKGROUND Childhood-onset schizophrenia is a rare but severe form of the disorder that is frequently treatment resistant . The psychiatrist has a limited evidence base to guide treatment , particularly as there are no trials in children comparing atypical antipsychotics , the mainstay of current treatment . OBJECTIVE To compare the efficacy and safety of olanzapine and clozapine , hypothesizing that clozapine would be more efficacious . DESIGN Double-blind r and omized 8-week controlled trial , with a 2-year open-label follow-up . SETTING National Institute of Mental Health study , January 1998 to June 2005 . Patients underwent re assessment 2 years after discharge . PATIENTS Children and adolescents recruited nationally , aged 7 to 16 years , meeting unmodified DSM-IV criteria for schizophrenia , and resistant to treatment with at least 2 antipsychotics . INTERVENTIONS After drug washout and a 1- to 3-week antipsychotic-free period , patients were r and omized to treatment with clozapine ( n = 12 ) or olanzapine ( n = 13 ) . MAIN OUTCOME MEASURES The Clinical Global Impression Severity of Symptoms Scale and Schedule for the Assessment of Negative/Positive Symptoms . RESULTS Clozapine was associated with a significant reduction in all outcome measures , whereas olanzapine showed a less consistent profile of clinical improvement . While there were moderate to large differential treatment effects in favor of clozapine , these reached significance only in the alleviation of negative symptoms from an antipsychotic-free baseline ( P = .04 ; effect size , 0.89 ) . Clozapine was associated with more overall adverse events . At 2-year follow-up , 15 patients were receiving clozapine with evidence of sustained clinical improvement , but additional adverse events emerged , including lipid anomalies ( n = 6 ) and seizures ( n = 1 ) . CONCLUSIONS While not demonstrating definitively the superiority of clozapine compared with olanzapine in treatment-refractory childhood-onset schizophrenia , the study suggests that clozapine has a more favorable profile of clinical response , which is balanced against more associated adverse events OBJECTIVES To evaluate the efficacy , safety , and tolerability of risperidone monotherapy for the treatment of an acute mixed or manic episode in children and adolescents with bipolar I disorder . METHODS This r and omized , placebo-controlled , double-blind , 3-arm study ( N = 169 ) included children and adolescents ( ages 10 - 17 years ) with a DSM-IV diagnosis of bipolar I disorder , experiencing a manic or mixed episode . Study participants were r and omized to placebo ( n = 58 ) , risperidone 0.5 - 2.5 mg/day ( n = 50 ) , or risperidone 3 - 6 mg/day ( n = 61 ) for 3 weeks . The primary efficacy measure was change in Young Mania Rating Scale ( YMRS ) total score from baseline to end point . Safety assessment s included adverse event ( AE ) monitoring and scores on extrapyramidal symptom rating scales . RESULTS Improvement in mean YMRS total score was significantly greater in risperidone-treated subjects than in placebo-treated subjects [ mean change ( SD ) -9.1 ( 11.0 ) for placebo ; -18.5 ( 9.7 ) for risperidone 0.5 - 2.5 mg ( p < 0.001 ) ; -16.5 ( 10.3 ) for risperidone 3 - 6 mg ( p < 0.001 ) ] . The most common risperidone-associated AEs were somnolence , headache , and fatigue . Mean ( SD ) weight gain was 0.7 ( 1.9 ) kg , 1.9 ( 1.7 ) kg , and 1.4 ( 2.4 ) kg in the placebo , risperidone 0.5 - 2.5 mg , and risperidone 3 - 6 mg groups , respectively , during this 3-week study . CONCLUSIONS At daily doses of 0.5 - 2.5 mg and 3 - 6 mg , risperidone was effective and well tolerated in children and adolescents experiencing acute manic or mixed episodes of bipolar I disorder . Results indicate that risperidone 0.5 - 2.5 mg has a better benefit-risk profile than risperidone 3 - 6 mg OBJECTIVE To assess weight and metabolic effects of 6 months of treatment with second-generation antipsychotics in naïve/quasi-naïve youths . METHOD This study looked at a nonr and omized , naturalistic , multicenter , inception cohort study of 279 patients aged 4 to 17 years ( mean = 14.6 ± 2.9 years ) . Of those , 248 ( 88.8 % ) received a single antipsychotic ( risperidone , olanzapine , or quetiapine ) and completed 2 visits , and 178 ( 63.8 % ) completed the 6-month follow-up . Patients had schizophrenia-spectrum disorders ( 44.5 % ) , mood-spectrum disorders ( 23.2 % ) , disruptive behavioral disorders ( 17.3 % ) , or other disorders ( 15.1 % ) . Fifteen age- and gender-matched , healthy , nonmedicated individuals served as a comparison group . RESULTS From baseline to 1 month , 3 months , and 6 months , all anthropometric measures increased significantly with each antipsychotic , that is , 6-month changes with risperidone ( n = 157 ; 7.1 kg and 0.66 body mass index [ BMI ] z score ) , olanzapine ( n = 44 ; 11.5 kg and 1.08 BMI z score ) , and quetiapine ( n = 47 ; 6.3 kg and 0.54 BMI z score ) , but not in healthy control participants ( -0.11 kg and 0.006 BMI z score ) . Fasting metabolic parameters increased significantly with risperidone ( glucose [ 3.8 ] mg/dL , insulin [ 4.9 ] mU/L , homeostasis model assessment of insulin resistance [ HOMA-IR : 1.2 ] , triglycerides [ 15.6 ] mg/dL ) , and olanzapine ( glucose [ 5.0 ] mg/dL , total cholesterol [ 21.2 ] mg/dL , and low-density lipoprotein cholesterol [ 44.6 ] mg/dL ) , but not with quetiapine or in healthy control participants . The percentage of research participants considered to be " at risk of adverse health outcome " increased during the 6 months from 8.9 % to 29.2 % for risperidone ( p < .0001 ) , 6.8 % to 38.1 % for olanzapine ( p < .0001 ) , and 6.3 % to 4.0 % for quetiapine ( p = .91 ) . CONCLUSION Olanzapine , quetiapine , and risperidone increase body weight but have different cardiometabolic side effect profiles and different temporal side effect patterns INTRODUCTION Early intervention in autism spectrum disorders ( ASDs ) appears promising and may represent a window of opportunity for more effective treatment . Whereas the safety and efficacy of risperidone have been established for children aged 5 and older , they has not been adequately tested in preschool children . METHODS A r and omized placebo-controlled study of risperidone in preschool children was conducted in a sample of young children , most of whom were also undergoing intensive behavioral treatment . RESULTS Preschool children tolerated low-dose risperidone well with no serious adverse effects observed over a 6-month treatment period . Weight gain and hypersalivation were the most common side effects reported , and hyperprolactinemia without lactation or related signs was observed . Significant differences between groups found at baseline complicated the analyses ; however , controlling for some of these differences revealed that preschoolers on risperidone demonstrated greater improvements in autism severity . The change in autism severity scores from baseline to 6-month follow up for the risperidone group was 8 % compared to 3 % for the placebo group . Notably , both groups significantly improved over the 6-month treatment period . CONCLUSIONS Study findings suggest that risperidone is well tolerated in preschoolers over a 6-month period , but that only minimally greater improvement in target symptoms was evident in the risperidone group , possibly due to the differences between groups at baseline or due to the small sample size . Although these findings are not sufficient to direct treatment , they suggest that larger-scale , double-blind , placebo-controlled investigations of risperidone in preschoolers with ASDs should now be conducted OBJECTIVE The objective of this study was to determine the efficacy and safety of valproic acid versus risperidone in children , 3 - 7 years of age , with bipolar I disorder ( BPD ) , during a mixed or manic episode . METHODS Forty-six children with Diagnostic and Statistical Manual of Mental Disorders . 4th ed . , Text Revision ( DSM-IV-TR ) diagnosis of bipolar disorder , manic , hypomanic , or mixed episode , were recruited over a 6 year period from two academic outpatient programs for a double-blinded , placebo-controlled trial in which subjects were r and omized in a 2:2:1 ratio to risperidone solution , valproic acid , or placebo . RESULTS After 6 weeks of treatment , the least-mean Young Mania Rating Scale ( YMRS ) total scores change , adjusted for baseline YMRS scores , from baseline by treatment group was : Valproic acid 10.0±2.46 ( p=0.50 ) ; risperidone 18.82±1.55 ( p=0.008 ) ; and placebo 4.29±3.56 ( F=3.93 , p=0.02 ) . The mixed models for repeated measure ( MMRM ) analysis found a significant difference for risperidone-treated subjects versus placebo treated subjects ( p=0.008 ) but not for valproic acid-treated subjects versus placebo-treated subjects ( p=0.50 ) . Treatment with risperidone over 6 weeks led to increased prolactin levels , liver functions , metabolic measures , and weight/body mass index ( BMI ) . Treatment with valproic acid led to increases in weight/ BMI and decreases in total red blood cells ( RBC ) , hemoglobin , and hematocrit . CONCLUSIONS In this small sample of preschool children with BPD , risperidone demonstrated clear efficacy versus placebo , whereas valproic acid did not . The laboratory and weight findings suggest that younger children with BPD are more sensitive to the effects of both of these psychotropics , and that , therefore , frequent laboratory and weight monitoring are warranted There are some uncontrolled studies about the efficacy and safety of both aripiprazole and risperidone for treating tic disorder . Moreover , the efficacy of these medications has never been compared . This is the first double blind r and omized clinical trial comparing the safety and efficacy of aripiprazole and risperidone for treating patients with tic disorder . Sixty children and adolescents with tic disorder were r and omly allocated into one of the two groups to receive either aripiprazole or risperidone for 2 months . The primary outcome measure was the score of Yale Global Tic Severity Scale . In addition , health related quality of life and adverse events were assessed . Both aripiprazole and risperidone decreased the Yale Global Tic Severity Scale score during this trial . Moreover , both medications increased the health related quality of life score . Both aripiprazole and risperidone were tolerated well . Aripiprazole [ 3.22 ( 1.9 ) mg/day ] decreased tic score as much as risperidone [ 0.6 ( 0.2 ) mg/day ] . Their adverse effects and their effects on health related quality of life were comparable . However , risperidone increased the patients ’ social functioning more than aripiprazole in short term BACKGROUND AND PURPOSE Childhood-onset schizophrenia ( COS ) is a clinical ly severe form of schizophrenia , which causes severe impairment to cognitive , linguistic , and social development . There are few prospect i ve and retrospective open clinical trials of risperidone and olanzapine in COS . In this open-label , r and omized , prospect i ve study , we compared the tolerability and effectiveness of risperidone versus olanzapine in the treatment of COS patients . METHODS The study population consisted of 25 children with COS ( mean age 11.09 + /- 1.55 years ) . After an evaluation , patients received risperidone ( 0.25 - 4.5 mg/day , mean dose 1.62 + /- 1.02 mg/day ) or olanzapine ( 2.5 - 20 mg/day , mean dose 8.18 + /- 4.41 mg/day ) for 12 weeks , with weekly evaluations . RESULTS Both groups showed comparable significant ( p < 0.001 ) within-group improvement from baseline to endpoint ( LOCF ) in Positive and Negative Symptoms Scale ( PANSS ) total and subscale scores . Of the olanzapine-treated children , 11 ( 91.7 % ) completed the 12 weeks of the study , whereas in the risperidone-treated children only 9 ( 69.2 % ) did . No significant differences between risperidone-treated children and olanzapine-treated children were observed on Barnes Akathisia Rating Scale ( BAS ) and Simpson-Angus Scale ( SAS ) rating scales . Both treatment groups showed significant ( p < 0.001 ) increase in weight from baseline to endpoint . CONCLUSION Our open-label , small-scale comparative study suggests that both risperidone and olanzapine appear to be efficacious antipsychotic medications in COS , with a slight nonsignificant advantage of olanzapine in the dropout rate 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 . To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders ( PDD ) . Methods . In this 8-week , r and omized , double-blind , placebo-controlled trial , risperidone/placebo solution ( 0.01–0.06 mg/kg/day ) was administered to 79 children who were aged 5 to 12 years and had PDD . Behavioral symptoms were assessed using the Aberrant Behavior Checklist ( ABC ) , Nisonger Child Behavior Rating Form , and Clinical Global Impression-Change . Safety assessment s included vital signs , electrocardiogram , extrapyramidal symptoms , adverse events , and laboratory tests . Results . Subjects who were taking risperidone ( mean dosage : 0.04 mg/kg/day ; 1.17 mg/day ) experienced a significantly greater mean decrease on the irritability subscale of the ABC ( primary endpoint ) compared with those who were taking placebo . By study endpoint , risperidone-treated subjects exhibited a 64 % improvement over baseline in the irritability score almost double that of placebo-treated subjects ( 31 % ) . Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC ; on the conduct problem , insecure/anxious , hyperactive , and overly sensitive subscales of the Nisonger Child Behavior Rating Form ( parent version ) ; and on the Visual Analog Scale of the most troublesome symptom . More risperidone-treated subjects ( 87 % ) showed global improvement in their condition compared with the placebo group ( 40 % ) . Somnolence , the most frequently reported adverse event , was noted in 72.5 % versus 7.7 % of subjects ( risperidone vs placebo ) and seemed manageable with dose/dose-schedule modification . Risperidone-treated subjects experienced statistically significantly greater increases in weight ( 2.7 vs 1.0 kg ) , pulse rate , and systolic blood pressure . Extrapyramidal symptoms scores were comparable between groups . Conclusions . Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children Objective : To evaluate the efficacy and safety of risperidone in children and adults with Tourette syndrome . Methods : This was an 8-week , r and omized , double-blind , placebo-controlled trial . The primary outcome measure was the Total Tic score of the Yale Global Tic Severity Scale ( YGTSS ) . Results : Thirty-four medication-free subjects ( 26 children and 8 adults ) ranging in age from 6 to 62 years ( mean = 19.7 ± 17.0 years ) participated . YGTSS Total Tic scores were similar at baseline ( 26.0 ± 5.1 for risperidone vs 27.4 ± 8.5 for placebo ) . After 8 weeks of treatment ( mean daily dose of 2.5 ± 0.85 ) , the 16 subjects on risperidone showed a 32 % reduction in tic severity from baseline , compared to a 7 % reduction for placebo patients ( n = 18 ) ( F[2,64 ] = 6.07 ; p = 0.004 ) . The 12 children r and omized to risperidone showed a 36 % reduction in tic symptoms compared to an 11 % decrease in the 14 children on placebo ( F[2,48 ] = 6.38 ; p = 0.004 ) . Two children on risperidone showed acute social phobia , which resolved with dose reduction in one subject but result ed in medication discontinuation in the other . A mean increase in body weight of 2.8 kg was observed in the risperidone group compared to no change in placebo ( F[2,64 ] = 10.68 ; p = 0.0001 ) . No extrapyramidal symptoms and no clinical ly significant alterations in cardiac conduction times or laboratory measures were observed . Conclusion : Risperidone appears to be safe and effective for short-term treatment of tics in children or adults with Tourette syndrome . Longer-term studies are needed to evaluate the durability of efficacy and safety over time OBJECTIVE The purpose of this study was to evaluate the short- and long-term efficacy , safety , and tolerability of ziprasidone in adolescents with schizophrenia . METHODS Subjects ages 13 - 17 years with schizophrenia ( American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . [ DSM-IV ] ) were enrolled in a 6 week , r and omized , double-blind , placebo-controlled multicenter trial ( RCT ) followed by a 26 week open-label extension study ( OLE ) . Subjects were r and omized in a 2:1 ratio to flexible-dose oral ziprasidone ( 40 - 160 mg/day , based on weight ) or placebo . Primary end-point was change from baseline in Brief Psychiatric Rating Scale-Anchored ( BPRS-A ) total score . Safety assessment s included adverse events , vital signs , laboratory measures , electrocardiograms , weight and body mass index , and movement disorder ratings . RESULTS Planned interim analysis for the primary end-point in the RCT result ed in early termination of both studies because of futility . In the RCT , 283 subjects received ziprasidone ( n=193 ) or placebo ( n=90 ) . In the intent-to-treat analysis population , the least squares mean ( SE ) BPRS-A score decrease from baseline at week 6 was not significantly different ( p=0.15 ; -14.16 [ 0.78 ] for ziprasidone and -12.35 [ 1.05 ] for placebo ) . Per- protocol analysis was significant ( p=0.02 ) . In the OLE , 221 subjects entered the OLE and received ziprasidone for a median of 99 days . The mean ( SD ) change in BPRS-A score from end of RCT to end of OLE ( last observation carried forward ) was -6.9 ( 8.9 ) . The most common treatment-emergent adverse events ( ≥ 10 % ) for all causalities during the RCT were somnolence and extrapyramidal disorders , and during OLE was somnolence only . No subjects had Fridericia 's corrected QT ( QTcF ) ≥ 500 ms in the RCT or OLE phases . One completed suicide occurred during the OLE phase . For RCT and OLE , no clinical ly significant changes were reported in metabolic indices and laboratory measures . CONCLUSIONS Ziprasidone failed to separate from placebo in treatment of schizophrenia in adolescents . Ziprasidone was generally well tolerated with an overall neutral weight and metabolic profile . CLINICAL TRIALS REGISTRY NCT00257192 and NCT00265382 at Clinical Trials.gov OBJECTIVES To review the evidence for efficacy and metabolic effects of atypical antipsychotics ( AAPs ) , and to propose a metabolic monitoring protocol for AAP use in children and adolescents . METHODS A PubMed search was performed to obtain all studies related to efficacy , metabolic side-effects , and monitoring in those less than 18 years of age . RESULTS There are no approved indications for AAP use in children and adolescents in Canada . Based on US Food and Drug Administration approvals and a review of r and omized controlled trials , we identified 7 indications for AAP use that target specific symptoms in youth including schizophrenia , bipolar I disorder , autism , pervasive developmental disorder , disruptive behaviour disorders ( including conduct disorder and ADHD ) , developmental disabilities and Tourette Syndrome . A wide range of metabolic effects including weight gain , increased waist circumference , dysglycemia , dyslipidemia , hypertension , elevated hepatic transaminases and prolactin levels have been reported . We have developed a proposal for metabolic monitoring that includes anthropometric measurements and laboratory testing at baseline and appropriate intervals thereafter . CONCLUSION There is an urgent need for national clinical practice guidelines that provide , not only appropriate treatment algorithms for AAP-use based on evidence , but also address metabolic monitoring and subsequent management of complications in this vulnerable population The symptom response and side-effects of olanzapine and risperidone were compared in patients with recent onset schizophrenia . Actively symptomatic patients ( n=44 ) r and omly received olanzapine 15 mg ( median dose ) or risperidone 4 mg ( median dose ) . Symptom response and side-effects were measured during a 6–10-week treatment study . No major differences were observed between the two treatment groups . Symptoms improved significantly on the Positive and Negative Syndrome Scale total score , positive subscale and general psychopathology subscale for both treatment groups . Using five symptom dimensions , both drugs were effective in treating positive symptoms and agitation/excitement symptoms , and neither olanzapine or risperidone influenced disorganization and depression symptoms . Results on the negative symptoms subscale and symptom dimension were inconclusive . No major differences were found in the frequency of the reported side-effects akathisia , parkinsonism and weight gain . These data indicate that the differences between olanzapine and risperidone in symptom response are small . In spite of the relatively low power of the study , we could exclude the presence of substantially different treatment effects between olanzapine and risperidone OBJECTIVE Quetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania . Large , placebo-controlled studies of interventions in pediatric bipolar depression are lacking . The current study investigated the efficacy and safety of quetiapine extended-release ( XR ) in patients 10 - 17 years of age , with acute bipolar depression . METHODS This multicenter , double-blind , r and omized , placebo-controlled study investigated quetiapine XR ( dose range , 150 - 300 mg/day ) in pediatric out patients with an American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . , Text Revision ( DSM-IV-TR ) diagnosis of bipolar I or bipolar II disorder ( current or most recent episode depressed ) treated for up to 8 weeks ( Clinical Trials.gov identifier : NCT00811473 ) . The primary study outcome was mean change in Children 's Depression Rating Scale-Revised ( CDRS-R ) total score . Secondary efficacy outcomes included CDRS-R-based response and remission rates . RESULTS Of 193 patients r and omized to treatment , 144 patients completed the study ( 75.3 % of quetiapine XR group [ n=70 ] ; 74.0 % of placebo group [ n=74 ] ) . Least squares mean changes in CDRS-R total score at week 8 were : -29.6 ( SE , 1.65 ) with quetiapine XR and -27.3 ( SE , 1.60 ) with placebo , a between-treatment group difference of -2.29 ( SE , 1.99 ; 95 % CI , -6.22 , 1.65 ; p=0.25 ; mixed-model for repeated measures analysis ) . Rates of response and remission did not differ significantly between treatment groups . The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release ( IR ) . Potentially clinical ly significant elevations in clinical chemistry values included triglycerides ( 9.3 % , quetiapine XR ; 1.4 % , placebo group ) and thyroid stimulating hormone ( 4.7 % , quetiapine XR ; 0 % , placebo group ) . An adverse event potentially related to diabetes mellitus occurred in 3.3 % of the quetiapine XR versus no adverse events in the placebo group . CONCLUSIONS Quetiapine XR did not demonstrate efficacy relative to placebo in this 8 week study of pediatric bipolar depression . Quetiapine XR was generally safe and well tolerated OBJECTIVE To determine whether risperidone is effective in reducing symptoms of disruptive behaviors ( such as aggression , impulsivity , defiance of authority figures , and property destruction ) associated with conduct disorder , oppositional defiant disorder , and disruptive behavior disorder-not otherwise specified in children with subaverage IQs . METHOD The trial consisted of a 1-week , single-blind , placebo run-in period and was followed by a 6-week , double-blind , placebo-controlled period . One hundred ten children ( aged 5 - 12 years inclusive ) with an IQ of 36 - 84 with a disruptive behavior disorder and a score of at least 24 on the Conduct Problem subscale of the Nisonger Child Behavior Rating Form ( NCBRF ) were enrolled . Eighty percent of subjects had comorbid attention-deficit/hyperactivity disorder ( ADHD ) . Risperidone doses ranged from 0.02 to 0.06 mg/kg per day . Subjects were rated on the NCBRF , Aberrant Behavior Checklist , Behavior Problems Inventory , Clinical Global Impressions ( CGI ) , modified California Verbal Learning Test ( CVLT ) , and a continuous performance task ( CPT ) . RESULTS The intention-to-treat analysis of risperidone-treated subjects showed a significant ( p < .001 ) reduction in mean scores ( from 33.4 at baseline to 17.6 at end point ; 47.3 % reduction ) versus placebo-treated subjects ( mean baseline of 32.6 to 25.8 at end point ; 20.9 % reduction ) on the Conduct Problem subscale of the NCBRF . Between-group differences in favor of risperidone were seen as early as week 1 and were significant at all post-baseline visits . Other subscales showed significant improvement with risperidone compared with placebo . CGI scale ratings of improvement showed highly significant gains for risperidone over placebo . A sub analysis demonstrated that the effect of risperidone was unaffected by diagnosis , presence/absence of ADHD , psychostimulant use , IQ status , and somnolence . Risperidone produced no changes on the cognitive variables ( CPT/modified CVLT ) . The most common side effects included somnolence , headache , appetite increase , and dyspepsia . Side effects related to extrapyramidal symptoms were reported in 7 ( 13.2 % ) and 3 ( 5.3 % ) of the subjects in the risperidone and placebo groups , respectively ( p = .245 ) . CONCLUSIONS Risperidone appears to be an adequately tolerated and effective treatment in children with subaverage IQs and severe disruptive behaviors such as aggression and destructive behavior This study was design ed to explore the placebo-controlled effects of risperidone on cognitive-motor processes , dyskinetic movements , and behavior in children receiving maintenance risperidone therapy . Sixteen children aged 4 - 14 years with disruptive behavior were r and omly assigned to drug order in a crossover study of risperidone and placebo for 2 weeks each . Dependent measures included tests of sustained attention , memory , visual matching , tremor , seat activity , abnormal movements , and parent behavior ratings . Results were compared by repeated measures ANOVA . Fourteen boys and 2 girls with disruptive behavior and IQ</=84 all completed the protocol . Risperidone was superior to placebo on response time ( p=0.01 , eta(P)(2)=0.43 ) and seat movement ( p<0.05 , eta(P)(2)=0.29 ) on a short-term memory task , and on a measure of static tremor ( p=0.05 , eta(P)(2)=0.28 ) . There was not a significant difference between treatment conditions on the Abnormal Involuntary Movement scale . Risperidone was superior to placebo on three subscales of the Nisonger Child Behavior Rating Form [ Overly Sensitive ( p<0.01 , eta(P)(2)=0.44 ) , Conduct Problem ( p=0.02 , eta(P)(2)=0.36 ) , Hyperactivity ( p=0.03 , eta(P)(2)=0.32 ) ] and on the Hyperactivity/Noncompliance subscale of the Aberrant Behavior Checklist ( p=0.01 , eta(P)(2)=0.41 ) . Significant increases in heart rate ( p=0.05 , eta(P)(2)=0.27 ) and weight ( p=0.02 , eta(P)(2)=0.36 ) occurred in the risperidone condition . The findings suggest a beneficial effect of risperidone after several months of treatment on efficiency of responding , activity level , static tremor , and aspects of behavior OBJECTIVE : The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these . METHODS : This 8-week , double-blind , r and omized , placebo-controlled , parallel-group study was conducted of children and adolescents ( aged 6–17 years ) with autistic disorder . Patients were r and omly assigned ( 1:1 ) to flexibly dosed aripiprazole ( target dosage : 5 , 10 , or 15 mg/day ) or placebo . Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression – Improvement score ( CGI-I ) . Safety and tolerability were also assessed . RESULTS : Ninety-eight patients were r and omly assigned to receive placebo ( n = 51 ) or aripiprazole ( n = 47 ) . Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8 . Aripiprazole demonstrated significantly greater global improvements than placebo , as assessed by the mean CGI-I score from week 1 through week 8 ; however , clinical ly significant residual symptoms may still persist for some patients . Discontinuation rates as a result of adverse events ( AEs ) were 10.6 % for aripiprazole and 5.9 % for placebo . Extrapyramidal symptom-related AE rates were 14.9 % for aripiprazole and 8.0 % for placebo . No serious AEs were reported . Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8 . CONCLUSIONS : Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated Forty-six patients ( 36 male , mean age 11.9 ± 2.6 ) with a variety of diagnoses and with significant aggressive behavior were treated in an open , non-r and omized fashion with Aripiprazole or Ziprasidone . Patients were diagnosed with the Mini International Neuropsychiatric Interview and the Child/Adolescent Symptom Inventory . The primary outcome measure was the Overt Aggression Scale ( OAS ) . After 2 months , 34 patients were still in treatment . The average improvement of the OAS in these 34 patients was 63 % . Clinical Global Impression-Improvement Scale was 2.1 ± 1.2 . Neither at baseline , nor at 2 months , were there any statistically significant differences between the Aripiprazole and Ziprasidone groups . Sedation was the most common side effect OBJECTIVE The purpose of this study was to evaluate the short- and long-term efficacy and safety of ziprasidone in children and adolescents with bipolar I disorder . METHODS Subjects 10 - 17 years of age with a manic or mixed episode associated with bipolar I disorder participated in a 4 week , r and omized , double-blind , placebo-controlled multicenter trial ( RCT ) followed by a 26 week open-label extension study ( OLE ) . Subjects were r and omized 2:1 to initially receive flexible-dose ziprasidone ( 40 - 160 mg/day , based on weight ) or placebo . Primary outcome was the change in Young Mania Rating Scale ( YMRS ) scores from baseline . Safety assessment s included weight and body mass index ( BMI ) , adverse events ( AEs ) , vital signs , laboratory measures , electrocardiograms , and movement disorder ratings . RESULTS In the RCT , 237 subjects were treated with ziprasidone ( n=149 ; mean age , 13.6 years ) or placebo ( n=88 ; mean age , 13.7 years ) . The estimated least squares mean changes in YMRS total ( intent-to-treat population ) were -13.83 ( ziprasidone ) and -8.61 ( placebo ; p=0.0005 ) at RCT endpoint . The most common AEs in the ziprasidone group were sedation ( 32.9 % ) , somnolence ( 24.8 % ) , headache ( 22.1 % ) , fatigue ( 15.4 % ) , and nausea ( 14.1 % ) . In the OLE , 162 subjects were enrolled , and the median duration of treatment was 98 days . The mean change in YMRS score from the end of the RCT to the end of the OLE ( last observation carried forward ) was -3.3 ( 95 % confidence interval , -5.0 to -1.6 ) . The most common AEs were sedation ( 26.5 % ) , somnolence ( 23.5 % ) , headache ( 22.2 % ) , and insomnia ( 13.6 % ) . For both the RCT and the OLE , no clinical ly significant mean changes in movement disorder scales , BMI z-scores , liver enzymes , or fasting lipids and glucose were observed . One subject on ziprasidone in the RCT and none during the OLE had Fridericia-corrected QT interval ( QTcF ) ≥ 460 ms . CONCLUSION These results demonstrate that ziprasidone is efficacious for treating children and adolescents with bipolar disorder . Ziprasidone was generally well tolerated with a neutral metabolic profile . CLINICAL TRIALS REGISTRY NCT00257166 and NCT00265330 at Clinical Trials.gov PURPOSE Side effects of pharmacological treatment in schizophrenia continue to be a major issue in spite of the development of new antipsychotics . The aim of this study is to explore the adverse effects of conventional and atypical antipsychotic drugs and their associated factors . METHODS Over 3 months , 41 patients with schizophrenia were r and omized to treatment with risperidone 1 - 12 mg ( n=21 ) or haloperidol 2 - 20 mg ( n=20 ) daily . Efficacy was assessed by improvement of psychotic symptoms , measured on the Positive and Negative Syndrome Scale ( PANSS ) . The safety and tolerability were assessed with the Extrapyramidal Symptom Rating Scale , the UKU Side-Effect Rating Scale and clinical laboratory assessment s. RESULTS Each treatment reduced psychotic symptoms . PANSS total scores , positive scores , and general psychopathology scores declined as trial went on without significant differences between the two groups . While PANSS negative scores improved better in the risperidone group than in the haloperidol group . The tolerability of antipsychotics was statistical significantly better in the risperidone than in the haloperidol-treated patients . The most frequent adverse effects for both groups were tremor and rigidity . Antipsychotics , their doses , and hyperprolactinemia predict short-term extrapyramidal side effects . Serum prolactin levels could predict parkinsonism and dyskinesia severity . However , dyskinesia was best predicted by the doses of neuroleptics . The predictive factor of dystonia was the antipsychotic drug itself . After adjusting drug doses and concomitant medications , side effects could be markedly improved . CONCLUSIONS This study suggested that risperidone was superior to haloperidol in improving negative symptoms and better tolerated during the 12 weeks ' treatment of schizophrenia . Serum prolactin levels could predict the severity of parkinsonism and dyskinesia Clomipramine , haloperidol , and placebo were compared with baseline in the treatment of autism , and overall outcome , specific symptoms , and side effects were examined . It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy . Individuals with a DSM-IV diagnosis of autistic disorder ( mean age , 16.3 years ; range , 10–36 years ) were r and omly assigned , by using a Latin square design , to the following 7-week trials : placebo , clomipramine ( mean daily dose , 128.4 mg ; range , 100–150 mg ) , or haloperidol ( mean daily dose , 1.3 mg ; range , 1–1.5 mg ) . Data on 36 subjects were analyzed and taken together ; the results favored haloperidol . In those patients who were able to complete a full therapeutic trial , clomipramine proved comparable to haloperidol in terms of improvement compared with baseline . However , significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial ( 37.5 % vs. 69.7 % , respectively ) for reasons related to both side effects and efficacy or behavior problems . In the intent-to-treat sample , which is perhaps more clinical ly relevant , only haloperidol proved superior to baseline on a global measure of autistic symptom severity , as well as specific measures for irritability and hyperactivity . Clomipramine did not seem more effective on a measure of stereotypy , nor was it better tolerated Objective The aim of the study was to compare safety , efficacy and tolerability of risperidone with haloperidol in the treatment of Autistic Disorder ( AD ) . Method This study was design ed as a double-blind , prospect i ve , for a 12-week period . A total of 30 subjects , between the ages of 8 and 18 with AD based on DSM IV criteria , were included in the study . Behavioral Rating Scales were performed by the investigators and the parents . Safety assessment included vital signs , electrocardiogram , electroencephalogram , adverse events , laboratory tests , extrapyramidal symptoms and the side effects . Both treatments were applied in a once daily dosage regimen of 0.01–0.08 mg/kg/day . Results The reduction from baseline in Ritvo – Freeman Real Life Rating Scale ( RF-RLRS ) , sensory motor ( subscale I ) and language ( subscale V ) scores were significant in risperidone group ( P < 0.05 ) . Compared to haloperidol , risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist ( ABC ) and Turgay DSM-IV Pervasive Developmental Disorder ( PDD ) scale scores ( P < 0.05 and P < 0.01 ) . There was a greater increase of prolactin in the risperidone group , while alanine amino transferase ( ALT ) had further increased in the haloperidol group . Sensory motor behaviors ( subscale I ) and language at the end of the 12th week , RF-RLRS sensory motor and language subscale scores decreased in the risperidone group further than the other group ( P < 0.05 ) . Conclusions Risperidone was found to be more effective than haloperidol in the treatment of behavioral symptoms , impulsivity , language skills , and impaired social relations in children with AD . These results demonstrated that both drugs were safe and well tolerated in the treatment of AD OBJECTIVE To evaluate the efficacy and safety of quetiapine monotherapy in children and adolescents with mania associated with bipolar I disorder . METHOD Patients aged 10 to 17 years , with a DSM-IV-TR diagnosis of a manic episode associated with bipolar I disorder and Young Mania Rating Scale ( YMRS ) total score ≥ 20 were r and omized to 3 weeks of quetiapine ( 400 or 600 mg/d ) or placebo . The primary efficacy measure was change in YMRS total score . The study was conducted at 34 centers in the United States between August 2004 and July 2006 . RESULTS The intent-to-treat population included 277 patients . Least squares mean change in YMRS score from baseline to end point by mixed-model , repeated- measures analysis was -14.25 , -15.60 , and -9.04 for quetiapine 400 mg/d , quetiapine 600 mg/d , and placebo , respectively ( P < .001 , each quetiapine dose vs placebo ) . Significant improvement in YMRS score versus placebo was first observed at day 4 ( P = .015 ) with quetiapine 400 mg/d and day 7 ( P < .001 ) with quetiapine 600 mg/d . Mean changes in body weight at day 21 ( observed cases ) were 1.7 kg for both quetiapine doses and 0.4 kg for placebo . Numerically larger mean increases in total cholesterol , low-density lipoprotein cholesterol , and triglycerides were observed with quetiapine than placebo . Adverse events associated with quetiapine were mostly mild to moderate in intensity . CONCLUSIONS In this 3-week study , quetiapine was significantly more effective than placebo in improving manic symptoms in youth with mania associated with bipolar disorder . Treatment was generally well tolerated and adverse events were broadly consistent with the known profile of quetiapine in adults with bipolar disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00090311 OBJECTIVE To assess dosing , efficacy , and tolerability of quetiapine fumarate in drug-naive first-episode psychosis . METHOD We present a prospect i ve , r and omized , controlled , single-center , double-blind , fixed-dose , 4-week comparison study of 200 mg/day versus 400 mg/day of quetiapine in 141 drug-naive acutely ill first-episode psychosis patients ( diagnosed according to DSM-IV ) aged 15 to 25 years . The double-blind 4-week trial ( Part 1 ) was followed by a single-blind , naturalistic , flexible-dose 8-week period ( Part 2 ) . The main outcome measures were symptomatic change , functioning , and tolerability . Data were collected from July 2003 until January 2006 . RESULTS The estimated time trends of the linear mixed-effects modeling indicated that efficacy between the 2 treatment groups in Part 1 was similar for most outcome measures except for 5 measures : the Scale for the Assessment of Negative Symptoms ( SANS ) anhedonia-asociality subscale ( p = .011 ) , the Social and Occupational Functioning Assessment Scale ( p = .020 ) , the Global Assessment of Functioning scale ( p = .070 ) , the SANS affective flattening or blunting subscale ( p = .051 ) , and the Udvalg for Kliniske Undersogelser total ( p = .056 ) , suggesting that the 200-mg group improved more for the SANS anhedonia-asociality subscale , whereas the 400-mg group showed a slight deterioration . Social and global functioning also improved more in the 200-mg group than in the 400-mg group . Part 2 of the study revealed that , independent of the initial target dose , when clinicians were able to adjust the dose flexibly , the dose at 12 weeks was similar between groups and averaged 268 mg/day . CONCLUSION Our study in acutely ill drug-naive first-episode psychosis patients suggests that quetiapine is a safe and well-tolerated antipsychotic medication . In contrast to multiepisode patients , dosing should be more conservative in untreated new-onset cases . An initial dose of 250 to 300 mg/day of quetiapine is proposed as a primary target dose in drug-naive first-episode psychosis patients . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00449397 OBJECTIVE There is a limited evidence base to guide treatment of children and adolescents with nonaffective psychoses because few comparative studies of first-line second-generation antipsychotics ( SGAs ) have been undertaken . To plan the design of a subsequent r and omized controlled trial ( RCT ) , the authors conducted this pilot study to demonstrate the feasibility of the treatment and measurement protocol s. METHOD Thirty children and adolescents ( 20 males , 10 females ) , ages 10 - 18 years , who met unmodified Diagnostic and Statistical Manual of Mental Disorders , 4th edition ( DSM-IV ) criteria for a schizophrenia-spectrum disorder ( schizophrenia , schizoaffective , schizophreniform , psychotic disorder not otherwise specified ) were r and omized to receive 12 weeks of open-label , flexibly dosed treatment with either risperidone ( mean [ st and ard deviation , SD ] dose = 3.4 mg [ 1.5 ] ) , olanzapine ( mean [ SD ] dose = 14.0 mg [ 4.6 ] ) or quetiapine ( mean [ SD ] dose = 611 mg [ 253.4 ] ) . RESULTS Twenty one ( 70 % ) of 30 subjects completed the study . There was no overall statistically significant difference with regard to reduction in Positive and Negative Syndrome Scale ( PANSS ) total scores in treatment efficacy observed ( F((2,24 ) ) = 3.13 , p = 0.06 ) . However , the possibility of a large differential treatment effect with regard to change in PANSS total scores favoring risperidone relative to quetiapine ( risperidone vs. quetiapine , d = 1.10 [ 95 % confidence interval , CI , 0.09 - 2.01 ] ) was suggested by the point estimate . CONCLUSIONS These preliminary data , viewed together with the extant literature , suggest that a future larger RCT with only two treatment arms may be warranted to establish whether there is a clinical ly significant differential treatment effect between risperidone and quetiapine for children and adolescents with nonaffective psychoses . Additional challenges and considerations for mounting a larger RCT are explored OBJECTIVE To examine the short-term efficacy and tolerability of aripiprazole for children and adolescents with Tourette 's disorder . METHOD This 10-week multicenter , double-blind , r and omized , placebo-controlled trial was conducted from August 2008 to April 2010 . Children and adolescents ( aged 6 - 18 years ) with a DSM-IV diagnosis of Tourette 's disorder and a Yale Global Tic Severity Scale total tic score of 22 or more were r and omly assigned ( 1:1 ratio ) to placebo or aripiprazole . The primary outcome measure was mean change from baseline in the total tic score on the Yale Global Tic Severity Scale ( last observation carried forward ) . Assessment s of safety and tolerability included spontaneously reported adverse events , extrapyramidal symptoms , serum prolactin level , metabolic variables , and other laboratory evaluations . RESULTS Of 61 subjects , 89 % completed the study . Patients who received aripiprazole demonstrated a significant reduction from baseline to end of study on the mean ( SD ) total tic score of the Yale Global Tic Severity Scale compared to those who received placebo ( -15.0 [ 8.4 ] and -9.6 [ 8.8 ] , respectively , P=.0196 ) . Response rate on the Tourette 's Syndrome Clinical Global Impression-Improvement was 66 % and 45 % in the aripiprazole and placebo groups , respectively . Mean decrease in the Tourette 's Syndrome Clinical Global Impression-Severity of Illness score was significantly different between the groups ( P=.0321 ) . In general , aripiprazole was well tolerated and there were no early discontinuations due to adverse events . The incidence of treatment-emergent adverse events between the groups was not significantly different ( P=.7550 ) . While aripiprazole decreased serum prolactin concentration ( P<.0001 ) , it increased mean body weight , body mass index , and waist circumference significantly ( P=.0055 , P=.0142 , and P=.0270 , respectively ) . CONCLUSIONS In comparison with placebo , aripiprazole was efficacious , generally tolerated and safe in the short-term treatment of children and adolescents with Tourette 's disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00706589 Atypical antipsychotics ( AP ) are increasingly being used in children and adolescents for the treatment of psychiatric disorders . Atypical AP may cause QT prolongation on the electrocardiogram ( ECG ) , which predisposes patients to an increased risk of developing threatening ventricular arrhythmias . Although this phenomenon has been exhaustively reported in adults , few studies investigated the safety of these drugs in pediatric patients . We performed an open-label , prospect i ve study to assess the arrhythmic risk of aripiprazole and risperidone in a pediatric population . A total of 60 patients ( 55 M/5F , mean age 10.2 + 2.6 years , range 4 - 15 years ) , receiving a new prescription of aripiprazole or risperidone in monotherapy underwent a st and ard ECG before and after two months from the beginning of antipsychotic treatment . Basal and post-treatment ECG parameters , including mean QT ( QTc ) and QT dispersion ( QTd ) , were compared within treatment groups . Twenty-nine patients were treated with aripiprazole ( mean dosage 7.4 + 3.1mg/day ) and 31 with risperidone ( mean dosage 1.5 + 1mg/day ) . In our series , no patient exhibited pathological values of QTc or QTd before and after treatment for both drugs . However , treatment with risperidone was associated with a slight increase of both mean QTc and QTd values ( 407.4 + 11.9 ms vs 411.2 + 13.0 ms , p<0.05 ; and 40.0 + 4.4 ms vs 44.7 + 5.5 ms , p<0.001 , respectively ) . Treatment with aripiprazole was associated with no changes of mean QTc , even if a small increase of QTd , ( 40.6 + 6.5 ms vs 46.3 + 7.2 ms , p<0.01 ) was observed . Although our data suggest a slight effect of aripiprazole and risperidone on ventricular repolarization , it is unlikely that such a change results in clinical ly relevant effects . The treatment with risperidone and aripiprazole in children with psychiatric disorders is not associated with clinical ly relevant modifications of QT interval . Caution in prescribing these drugs , however , is necessary in patients with family history of a genetic predisposition to arrhythmias in order to warrant a reliable assessment of drug-induced QT prolongation OBJECTIVE To examine whether risperidone is superior to placebo in the treatment of youths with conduct disorder . METHOD This was a 10-week , r and omized , double-blind , placebo-controlled study with 2 parallel arms . Ten youths were r and omly assigned to receive placebo and 10 youths were r and omly assigned to receive risperidone . Patients were seen weekly throughout the trial . Medications could be increased at weekly intervals during the first 6 weeks of the study from an initial dose of 0.25 mg or 0.50 mg each morning , depending on patient weight . Patients weighing less than 50 kg had a maximum total daily dose of risperidone of 1.5 mg . Patients weighing 50 kg or greater had a maximum total daily dose of risperidone of 3.0 mg . The primary outcome measure was the Rating of Aggression Against People and /or Property Scale . RESULTS Risperidone was superior to placebo in ameliorating aggression on most measures . Risperidone was reasonably well tolerated , with none of the risperidone-treated patients developing extrapyramidal side effects . CONCLUSIONS These data provide preliminary evidence that risperidone may have efficacy in the treatment of youths with conduct disorder . Because of the small sample size and the brief length of this study , further research is necessary to confirm these findings OBJECTIVE The aim of this study was to examine the safety and efficacy of risperidone , with or without concomitant psychostimulant use , in the treatment of children with conduct disorder ( CD ) or other disruptive behavior disorders [ oppositional defiant disorder ( ODD ) , disruptive behavior disorder-not otherwise specified ( DBD-NOS ) ] , and comorbid attention-deficit hyperactivity disorder ( ADHD ) . METHODS Data from two 6-week placebo-controlled trials assessing risperidone therapy in children with subaverage IQs and CD , ODD , DBD-NOS were combined , and patients with comorbid ADHD were selected for this post hoc analysis . Patients were grouped according to r and omized drug therapy ( risperidone or placebo ) , and then subgrouped according to their use of a concomitant psychostimulant . Safety outcomes included adverse events and weight change , while efficacy outcomes included changes in scores on disruptive behavior and hyperactivity-based subscales of two behavior-rating instruments ( Nisonger Child Behavior Rating Form and the Aberrant Behavior Checklist ) . RESULTS The analysis included 155 of 208 originally tested children divided into four sub-groups ( 35 - 43 patients each ) . There was no significant difference in the frequency of adverse events in patients who received risperidone alone and those who received risperidone plus a stimulant . The most common adverse events in risperidone-treated patients were somnolence , headache , dyspepsia , rhinitis , and vomiting . Within each r and omized treatment group , actual weight gain was comparable , regardless of concomitant stimulant use . Risperidone-treated patients had clinical ly and statistically significant reductions in both disruptive behavior and hyperactivity subscale scores , compared to placebo , regardless of concomitant stimulant use . The addition of risperidone to a psychostimulant result ed in significantly better control of hyperactivity ( p < 0.001 ) than was achieved with stimulant treatment alone , without causing an increase in adverse events . CONCLUSION Risperidone was a safe and effective treatment , with or without a combined psychostimulant , for both disruptive behavior disorders and comorbid ADHD in children OBJECTIVES To revise 2010 guidance on grading the strength of evidence ( SOE ) of the effectiveness of drugs , devices , and other preventive and therapeutic interventions in systematic review s produced by the Evidence -based Practice Center ( EPC ) program , established by the US Agency for Healthcare Research and Quality ( AHRQ ) . STUDY DESIGN AND SETTING A cross-EPC working group review ed authoritative systems for grading SOE [ primarily the approach from the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) working group ] and conducted extensive discussion s with GRADE and other experts . RESULTS Up date d guidance continues to be conceptually similar to GRADE . Review ers are to evaluate SOE separately for each major treatment comparison for each major outcome . We added reporting bias as a required domain and retained study limitations ( risk of bias ) , consistency , directness , and precision ( and three optional domains ) . Additional guidance covers scoring consistency , precision , and reporting bias , grading bodies of evidence with r and omized controlled trials and observational studies , evaluating single study bodies of evidence , using studies with high risk of bias , and presenting findings with greater clarity and transparency . SOE is grade d high , moderate , low , or insufficient , reflecting review ers ' confidence in the findings for a specific treatment comparison and outcome . CONCLUSION No single approach for grading SOE suits all review s , but a more consistent and transparent approach to reporting summary information will make review s more useful to the broad range of audiences that AHRQ 's work aims to reach . EPC working groups will consider ongoing challenges and modify guidance as needed , on issues such as combining trials and observational studies in bodies of evidence , weighting domains , and combining qualitative and quantitative syntheses BACKGROUND Effective treatments for adolescent schizophrenia are needed . AIMS To compare efficacy and safety of two dosing regimens of risperidone . METHOD Double-blind , 8-week study . Patients , 13 - 17 years , with an acute episode of schizophrenia , r and omised 1:1 to risperidone 1.5 - 6.0 mg/day ( regimen A ; n=125 ) or 0.15 - 0.6 mg/day ( regimen B ; n=132 ) . TRIAL REGISTRATION NUMBER NCT00034749 . RESULTS Mean total Positive and Negative Syndrome Scale ( PANSS ) score improved significantly ( P<0.001 ; effect size=0.49 ) from baseline to end-point for regimen A ( mean=96.4 ( s.d.=15.39 ) to mean=72.8 ( s.d.=22.52 ) ) compared with regimen B ( mean=93.3 ( s.d.=14.14 ) to mean=80.8 ( s.d.=24.33 ) ) . Treatment-emergent adverse events occurred in 74 % ( regimen A ) and 65 % ( regimen B ) of patients ; 4 % of patients overall discontinued for adverse events . Mean change in body weight was 3.2 kg ( s.d.=3.49 ) for regimen A and 1.7 kg ( s.d.=3.29 ) for regimen B. CONCLUSIONS Adolescent patients in the regimen A group showed greater improvement in total PANSS compared with the regimen B group . Treatment was well tolerated OBJECTIVE To evaluate the efficacy and tolerability of ziprasidone in children and adolescents with Tourette 's syndrome and chronic tic disorders . METHOD Twenty-eight patients aged 7 to 17 years were r and omly assigned to ziprasidone or placebo for 56 days . Ziprasidone was initiated at a dose of 5 mg/day and flexibly titrated to a maximum of 40 mg/day . RESULTS Ziprasidone was significantly more effective than placebo in reducing the Global Severity ( p = .016 ) and Total Tic ( p = .008 ) scores on the Yale Global Tic Severity Scale . Compared with placebo , ziprasidone significantly reduced tic frequencies as determined by blind videotape tic counts ( p = .039 ) . The mean ( + /- SD ) daily dose of ziprasidone during the last 4 weeks of the trial was 28.2 + /- 9.6 mg . Mild transient somnolence was the most common adverse event . No clinical ly significant effects were observed on specific ratings of extrapyramidal symptoms , akathisia , or tardive dyskinesia . CONCLUSIONS In this limited sample , ziprasidone ( 5 - 40 mg/day ) appears to be effective and well tolerated in the treatment of Tourette 's syndrome . Ziprasidone may be associated with a lower risk of extrapyramidal side effects in children . However , additional studies are necessary to evaluate more fully its safety and efficacy in children with tic disorders OBJECTIVE The purpose of this double-blind , placebo-controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa . METHOD Forty female subjects 12 to 21 years of age ( mean , 16 years ) with primary anorexia nervosa in an eating disorders program were r and omized to receive risperidone ( n = 18 ) or placebo ( n = 22 ) . Subjects completed the Eating Disorder Inventory 2 , Color-A-Person Test , Body Image Software , and Multidimensional Anxiety Scale for Children at baseline and regular intervals . Weight , laboratory values , and electrocardiograms were monitored . Study medication was started at 0.5 mg daily and titrated upward weekly in 0.5-mg increments to a maximum dose of 4 mg until the subject reached a study endpoint . RESULTS The mean dose for the risperidone group was 2.5 mg and for the placebo group was 3 mg for a mean duration of 9 weeks . Subjects taking risperidone had a significant decrease on the Eating Disorder Inventory 2 Drive for Thinness subscale over the first 7 weeks ( effect size , 0.88 ; p = .002 ) , but this difference was not sustained to the end of the study ( p = .13 ) . The Eating Disorder Inventory 2 Interpersonal Distrust subscale decreased significantly more in subjects taking risperidone ( effect size , 0.60 ; p = .03 ) . Subjects taking risperidone had increased prolactin levels ( week 7 ; p = .001 ) . There were no significant differences between groups at baseline or the end of the study for the other rating scales , change in weight , or laboratory measurements . CONCLUSIONS This study does not demonstrate a benefit for the addition of risperidone in adolescents with anorexia nervosa during the weight-restoration phase of care . Clinical trial registration information-A Double-Blind , Placebo-Controlled Study of Risperidone for the Treatment of Anorexia Nervosa , http://www . clinical trials.gov , NCT00140426 BACKGROUND Risperidone is an atypical antipsychotic drug that blocks dopamine as well as serotonin receptor systems . The present study was design ed to examine the efficacy and safety of risperidone in a 6-week double-blind , r and omized , parallel-group design in the treatment of aggression in adolescents with a primary diagnosis of DSM-IV disruptive behavior disorders and with subaverage intelligence . METHOD We r and omly assigned 38 adolescents ( 33 boys ; 10 subjects with slightly subaverage IQ , 14 with borderline IQ , and 14 with mild mental retardation ) , who were hospitalized for treatment of psychiatric disorders associated with severe aggression , to receive risperidone or placebo . The main efficacy measures were the Clinical Global Impressions-Severity of Illness scale ( CGI-S ) , the modified Overt Aggression Scale ( OAS-M ) , and the Aberrant Behavior Checklist ( ABC ) . Side effects were measured using the Extrapyramidal Symptom Rating Scale ( ESRS ) . RESULTS The mean daily dose of risperidone at the end of treatment was 2.9 mg ( range , 1.5 - 4 mg ) . Risperidone , compared with placebo , was associated with significant improvements on the CGI-S ( p < .001 ) and the at-school ABC overall and hyperactivity scales ( p < .05 ) . During a 2-week washout following the 6-week trial , a statistically significant worsening was found in the risperidone group on the CGI-S scale , the OAS-M. and the ABC . Extrapyramidal symptoms were absent or very mild during risperidone treatment . Transient tiredness was present in 11 ( 58 % ) of 19 drug-treated subjects . Other untoward effects included sialorrhea , nausea , and slight weight gain ( mean = 3.5 % of body weight in the risperidone group ) . No clinical ly relevant changes were found in laboratory parameters , electrocardiogram , heart rate , or blood pressure . CONCLUSION These results suggest that risperidone may be effective for severe aggression in adolescents with disruptive behavior disorders and subaverage intelligence , and these results are consistent with reports suggesting its effectiveness for treating severe aggression in adolescents in general OBJECTIVE To evaluate the effects of risperidone augmentation for treatment-resistant aggression in children with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD Twenty-five children ( ages 7 - 12 years ) with attention-deficit/hyperactivity disorder ( ADHD ) and significant aggressive behaviors were r and omized to risperidone or placebo for 4 weeks for this double-blind study . Subjects were already in treatment with a constant dose of psychostimulant medication . The primary efficacy measure was change from baseline in the Children 's Aggression Scale-Parent ( CAS-P ) and -Teacher ( CAS-T ) total scores . RESULTS The mean risperidone dose at endpoint was 1.08 mg/day . For the CAS-P total score , a significant difference was found ( chi(1)(2 ) = 4.30 , p < .05 ) with 100 % of risperidone subjects improving by more than 30 % from baseline to endpoint , whereas only 77 % of the placebo group reported a similar response . No differences were found on the CAS-T total score . For the CAS-P and CAS-T , no significant interaction was found between treatment group and time . Rates of adverse events did not differ significantly between groups . CONCLUSIONS Risperidone treatment appears to be well tolerated and modestly effective when used in combination with psychostimulants for treatment-resistant aggression in children with ADHD Thirty children with subaverage IQs and psychiatric diagnoses of attention deficit disorder and /or or conduct disorder took part in a double-blind study of placebo , methylpheni date , and thioridazine , which were given for 3 weeks each . The results showed a consistent and highly significant effect of methylpheni date in reducing teacher ratings of problem behavior . Parent ratings showed no behavioral effects for the group as a whole . An attentional model of stimulant drug response was used to divide subjects according to a cognitive maturity domain presumed to reflect selective attention . When divided according to breadth of attention , mental age , and IQ level , higher functioning subjects were found to show a generally favorable response to methylpheni date on both teacher and parent rating scales , whereas children of low functional level typically showed an adverse or indifferent response . The present data suggest that mental age and IQ may be important determinants of drug response ; below a given level , there was a greatly reduced likelihood of responding positively . Clinical response to thioridazine was substantially less than the response to methylpheni date , with significant improvements confined to conduct and hyperactivity problems on teacher ratings BACKGROUND The present study evaluated the effectiveness and safety of clozapine versus " high-dose " olanzapine in treatment-refractory adolescents with schizophrenia . METHODS Children , ages 10 - 18 years , who met DSM-IV criteria for schizophrenia and who were resistant or intolerant to at least two antipsychotic drugs were r and omized to receive 12 weeks of double-blind flexibly dosed treatment with clozapine ( n = 18 ) or " high-dose " olanzapine ( up to 30 mg/day ) ( n = 21 ) . The primary efficacy measure was response ( improvement ) , defined as a decrease of 30 % or more in total Brief Psychiatric Rating Scale score from baseline and a Clinical Global Impression Scale improvement rating of " 1 " ( very much improved ) or " 2 " ( much improved ) . RESULTS Significantly more clozapine-treated adolescents met response criteria ( 66 % ) compared with olanzapine-treated subjects ( 33 % ) . Clozapine was superior to olanzapine in terms of reduction of the psychosis cluster scores and negative symptoms from baseline to end point . However , both treatments were associated with significant weight-gain and related metabolic abnormalities . CONCLUSIONS This double-blind r and omized comparison of two second-generation antipsychotic drugs for treatment-refractory adolescents with schizophrenia supports clozapine as the agent of choice . The development of interventions to limit weight gain and metabolic side effects are needed to enhance the risk-benefit profile for both study treatments This pilot study was undertaken to estimate the acute antipsychotic effect size and side effect propensity of risperidone and olanzapine in the pediatric population , in comparison to haloperidol , a conventional antipsychotic with established efficacy . Risperidone and olanzapine are widely used as first-line treatments to ameliorate psychotic symptoms in youth , but their abilities to specifically treat children and adolescents presenting due to psychotic symptoms have not been rigorously studied . Subjects , selected because of prominent positive psychotic symptoms , were r and omly assigned to double-blind , parallel treatment with risperidone , olanzapine , or haloperidol for 8 weeks . The primary outcome was reduction in the Brief Psychiatric Rating Scale for Children total score from baseline to termination . An exploratory , descriptive analysis was done to compare the three treatments . A total of 50 patients , 8–19 years , participated . All treatments reduced symptoms significantly with p-values ( corrected for multiple comparisons ) of 0.0018 for each of the atypical agents and 0.012 for haloperidol . In all , 88 % of subjects treated with olanzapine , 74 % treated with risperidone , and 53 % treated with haloperidol met response criteria . The primary side effects observed in all patients were mild to moderate sedation , extrapyramidal symptoms , and weight gain . Risperidone and olanzapine acutely reduced psychotic symptoms in this pediatric sample . Exploratory comparisons indicate the magnitude of the antipsychotic response with these atypical agents is comparable to that observed with haloperidol . However , youth treated with risperidone and olanzapine experienced weight gain and extrapyramidal effects that appear more prevalent and severe than reported in adults OBJECTIVE The authors compared the effects of maintenance versus withdrawal of risperidone treatment in children and adolescents with symptoms of disruptive behavior disorder . METHOD Patients with disruptive behavior disorder ( 5 - 17 years of age and a range of intellect ) who had responded to risperidone treatment over 12 weeks were r and omly assigned to 6 months of double-blind treatment with either risperidone or placebo . The primary efficacy measure was time to symptom recurrence , defined as sustained deterioration on either the Clinical Global Impression severity rating ( /2 points ) or the conduct problem subscale of the Nisonger Child Behavior Rating Form ( /7 points ) . Secondary efficacy measures included rates of discontinuation due to symptom recurrence , disruptive behavior disorder symptoms , and general function . Safety and tolerability were also assessed . Risperidone dosage was based on weight ( patients < 50 kg : 0.25 - 0.75 mg/day ; patients /50 kg : 0.5 - 1.5 mg/day ) . RESULTS Treatment was initiated in 527 patients , with 335 r and omly assigned to a double-blind maintenance condition . Time to symptom recurrence was significantly longer in patients who continued risperidone treatment than in those switched to placebo . Symptom recurrence in 25 % of patients occurred after 119 days with risperidone and 37 days with placebo . Secondary efficacy measures also favored risperidone over placebo . Weight increased over the initial 12 weeks of treatment ( mean weight z score change=0.2 , SD=2.7 , N=511 ) , after which it plateaued . CONCLUSIONS This study is the first placebo-controlled maintenance versus withdrawal trial of its kind in disruptive behavior disorder and provides evidence that patients who respond to initial treatment with risperidone would benefit from continuous treatment over the longer term OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of olanzapine for the treatment of acute manic or mixed episodes associated with bipolar disorder in adolescents . METHOD A 3-week multicenter , parallel , double-blind , r and omized placebo-controlled trial was conducted at 24 sites in the United States and two sites in Puerto Rico . The participants were outpatient and inpatient male and female adolescents 13 - 17 years of age with an acute manic or mixed episode . Subjects received either olanzapine ( 2.5 - 20 mg/day [ N=107 ] ) or placebo ( N=54 ) . The mean change from baseline to endpoint in the Young Mania Rating Scale total score was the primary outcome measure . RESULTS The mean baseline-to-endpoint change in the Young Mania Rating Scale total score was significantly greater for patients receiving olanzapine relative to patients receiving placebo , and a greater proportion of olanzapine-treated patients met response and remission criteria ( 44.8 % versus 18.5 % and 35.2 % versus 11.1 % , respectively ) . The mean baseline-to-endpoint weight change was significantly greater for patients receiving olanzapine relative to patients receiving placebo ( 3.7 kg versus 0.3 kg ) , and the incidence of treatment-emergent weight gain > or = 7 % of baseline was higher for olanzapine-treated patients ( 41.9 % versus 1.9 % ) . The mean baseline-to-endpoint changes in prolactin , fasting glucose , fasting total cholesterol , uric acid , and the hepatic enzymes aspartate transaminase and alanine transaminase were significantly greater in patients treated with olanzapine relative to patients receiving placebo . CONCLUSIONS Olanzapine was effective in the treatment of bipolar mania in adolescent patients . Patients treated with olanzapine , however , had significantly greater weight gain and increases in the levels of hepatic enzymes , prolactin , fasting glucose , fasting total cholesterol , and uric acid BACKGROUND Childhood-onset schizophrenia is a rare but severe form of the disorder that is often treatment-refractory . In this study , the efficacy and adverse effects of clozapine and haloperidol were compared for children and adolescents with early-onset schizophrenia . METHODS Twenty-one patients ( mean [ + /-SD ] age , 14.0 + /- 2.3 years ) with onset of Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition-defined schizophrenia that began by age 12 years and who had been nonresponsive to typical neuroleptics participated in the study . Patients were r and omized to a 6-week double-blind parallel comparison of clozapine ( mean [ + /-SD ] final dose , 176 + /- 149 mg/d ) , or haloperidol , ( 16 + /- 8 mg/d ) . RESULTS Clozapine was superior to haloperidol on all measures of psychosis ( P = .04-.002 ) . Positive and negative symptoms of schizophrenia improved . However , neutropenia and seizures were major concerns . To date , one third of the group has discontinued using clozapine . CONCLUSIONS Clozapine has striking superiority for positive and negative symptoms in treatment-refractory childhood-onset schizophrenia . However , due to possibly increased toxic effects in this pediatric population , close monitoring for adverse events is essential BACKGROUND The use of antipsychotics , especially second-generation antipsychotics ( SGAs ) , for children with mental health disorders in Canada has increased dramatically over the past five years . These medications have the potential to cause major metabolic and neurological complications with chronic use . OBJECTIVE To synthesize the evidence for specific metabolic and neurological side effects associated with the use of SGAs in children , and provide evidence -based recommendations for the monitoring of these side effects . METHODS A systematic review of controlled clinical trials of SGAs involving children was performed . Recommendations for monitoring SGA safety were made according to a classification scheme based on the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) system . When there was inadequate evidence , recommendations were based on consensus and expert opinion . A multidisciplinary consensus group review ed all relevant evidence and reached consensus on the recommendations . RESULTS The present guidelines provide evidence -based recommendations for monitoring SGA safety . The strength of recommendations for specific physical examination manoeuvres and laboratory tests are provided for each SGA medication at specific time points . CONCLUSION Multiple r and omized controlled trials evaluated the efficacy of many of the SGAs in paediatric mental health disorders . These benefits , however , are not without risks - both metabolic and neurological side effects occur in children treated with SGAs . The risk of weight gain , increased body mass index and abnormal lipid levels is greatest with olanzapine , followed by clozapine and quetiapine . The risk of neurological side effects of the treatment is greatest with risperidone , olanzapine and aripiprazole . Appropriate monitoring procedures for adverse effects will improve the quality of care of children treated with these medications OBJECTIVE The short-term efficacy and safety of risperidone in the treatment of disruptive behaviors was examined in a well-characterized cohort of children with subaverage intelligence . METHOD In this 6-week , multicenter , double-blind , parallel-group study of 118 children ( aged 5 - 12 years ) with severely disruptive behaviors and subaverage intelligence ( IQ between 36 and 84 , inclusive ) , the subjects received 0.02 - 0.06 mg/kg per day of risperidone oral solution or placebo . The a priori primary efficacy measure was the change in score from baseline to endpoint on the conduct problem subscale of the Nisonger Child Behavior Rating Form . RESULTS The risperidone group showed significantly greater improvement than did the placebo group on the conduct problem subscale of the Nisonger Child Behavior Rating Form from week 1 through endpoint ( change in score of -15.2 and -6.2 , respectively ) . Risperidone was also associated with significantly greater improvement than placebo on all other Nisonger Child Behavior Rating Form subscales at endpoint , as well as on the Aberrant Behavior Checklist subscales for irritability , lethargy/social withdrawal , and hyperactivity ; the Behavior Problems Inventory aggressive/destructive behavior subscale ; a visual analogue scale of the most troublesome symptom ; and the Clinical Global Impression change score . The most common adverse effects reported during risperidone treatment were headache and somnolence . The extrapyramidal symptom profile of risperidone was comparable to that of placebo . Mean weight increases of 2.2 kg . and 0.9 kg occurred in the risperidone and placebo groups , respectively . CONCLUSIONS Risperidone was effective and well tolerated for the treatment of severely disruptive behaviors in children with subaverage IQ OBJECTIVE To evaluate safety and tolerability of four doses of immediate-release molindone hydrochloride in children with attention-deficit/hyperactivity disorder ( ADHD ) and serious conduct problems . METHODS This open-label , parallel-group , dose-ranging , multicenter trial r and omized children , aged 6 - 12 years , with ADHD and persistent , serious conduct problems to receive oral molindone thrice daily for 9 - 12 weeks in four treatment groups : Group 1 - 10 mg ( 5 mg if weight < 30 kg ) , group 2 - 20 mg ( 10 mg if < 30 kg ) , group 3 - 30 mg ( 15 mg if < 30 kg ) , and group 4 - 40 mg ( 20 mg if < 30 kg ) . The primary outcome measure was to evaluate safety and tolerability of molindone in children with ADHD and serious conduct problems . Secondary outcome measures included change in Nisonger Child Behavior Rating Form-Typical Intelligence Quotient ( NCBRF-TIQ ) Conduct Problem subscale scores , change in Clinical Global Impressions-Severity ( CGI-S ) and -Improvement ( CGI-I ) subscale scores from baseline to end point , and Swanson , Nolan , and Pelham rating scale-revised ( SNAP-IV ) ADHD-related subscale scores . RESULTS The study r and omized 78 children ; 55 completed the study . Treatment with molindone was generally well tolerated , with no clinical ly meaningful changes in laboratory or physical examination findings . The most common treatment-related adverse events ( AEs ) included somnolence ( n=9 ) , weight increase ( n=8 ) , akathisia ( n=4 ) , sedation ( n=4 ) , and abdominal pain ( n=4 ) . Mean weight increased by 0.54 kg , and mean body mass index by 0.24 kg/m(2 ) . The incidence of AEs and treatment-related AEs increased with increasing dose . NCBRF-TIQ subscale scores improved in all four treatment groups , with 34 % , 34 % , 32 % , and 55 % decreases from baseline in groups 1 , 2 , 3 , and 4 , respectively . CGI-S and SNAP-IV scores improved over time in all treatment groups , and CGI-I scores improved to the greatest degree in group 4 . CONCLUSIONS Molindone at doses of 5 - 20 mg/day ( children weighing < 30 kg ) and 20 - 40 mg ( ≥ 30 kg ) was well tolerated , and preliminary efficacy results suggest that molindone produces dose-related behavioral improvements over 9 - 12 weeks . Additional double-blind , placebo-controlled trials are needed to further investigate molindone in this pediatric population OBJECTIVE To compare the tic suppression , electrocardiogram ( ECG ) changes , weight gain , and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders . METHOD This was a r and omized , double-blind , crossover ( evaluable patient analysis ) study . Nineteen children aged 7 to 17 years with Tourette 's or chronic motor tic disorder were r and omized to 4 weeks of treatment with pimozide or risperidone , followed by the alternate treatment after a 2-week placebo washout . The primary efficacy outcome measure was change in tic severity assessed by the Yale Global Tic Severity Scale ( YGTSS ) . ECG results , weight gain , and side effects were also compared . RESULTS Compared to pimozide treatment , risperidone treatment was associated with significantly lower tic severity scores ( YGTSS : baseline 43.3 + /- 17.5 , pimozide 34.2 + /- 14.2 , risperidone 25.2 + /- 13.6 ; p = .05 ) . Weight gain during the 4-week treatment periods was greater for risperidone ( mean 1.9 kg ) than pimozide ( 1.0 kg ) . No patient suffered a serious adverse event , but 6 of 19 subjects failed to complete the protocol . Neither medication was associated with ECG changes . CONCLUSIONS In this study , risperidone appeared superior to pimozide for tic suppression but was associated with greater weight gain OBJECTIVE To conduct a pilot study comparing the effects of quetiapine and placebo for the treatment of depressive episodes in adolescents with bipolar I disorder . METHOD Thirty-two adolescents ( ages 12 - 18 years ) with a depressive episode associated with bipolar I disorder were r and omized to eight weeks of double-blind treatment with quetiapine , 300 - 600 mg/day , or placebo . This two-site study was conducted from March 2006 through August 2007 . The primary efficacy measure was change in Children 's Depression Rating Scale-Revised Version ( CDRS-R ) scores from baseline to endpoint . Secondary efficacy measures included change in CDRS-R scores over the eight-week study period ( PROC MIXED ) , changes from baseline to endpoint in Hamilton Anxiety Rating Scale ( HAM-A ) , Young Mania Rating Scale ( YMRS ) , and Clinical Global Impression-Bipolar Version Severity ( CGI-BP-S ) scores , as well as response and remission rates . Safety and tolerability were assessed weekly . RESULTS There was no statistically significant treatment group difference in change in CDRS-R scores from baseline to endpoint ( p = 0.89 , effect size = -0.05 , 95 % confidence interval : -0.77 - 0.68 ) , nor in the average rate of change over the eight weeks of the study ( p = 0.95 ) . Additionally , there were no statistically significant differences in response ( placebo = 67 % versus quetiapine = 71 % ) or remission ( placebo = 40 % versus quetiapine = 35 % ) rates , or change in HAM-A , YMRS , or CGI-BP-S scores ( all p > 0.7 ) between treatment groups . Dizziness was more commonly reported in the quetiapine ( 41 % ) than in the placebo ( 7 % ) group ( Fisher 's exact test , p = 0.04 ) . CONCLUSIONS The results suggest that quetiapine monotherapy is no more effective than placebo for the treatment of depression in adolescents with bipolar disorder . However , limitations of the study , including the high placebo response rate , may have contributed to our findings and should be considered in the design of future investigations of pharmacological interventions for this population OBJECTIVES This r and omized , double-blind , placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with divalproex ( DVP ) for acute mania in adolescents with bipolar disorder . It was hypothesized that DVP in combination with quetiapine would be more effective than DVP alone for treating mania associated with adolescent bipolar disorder . Furthermore , it was hypothesized that quetiapine would be well tolerated . METHOD Thirty manic or mixed bipolar I adolescents ( 12 - 18 years ) received an initial DVP dose of 20 mg/kg and were r and omly assigned to 6 weeks of combination therapy with quetiapine , which was titrated to 450 mg/day ( n = 15 ) or placebo ( n = 15 ) . Primary efficacy measures were change from baseline to endpoint in Young Mania Rating Scale ( YMRS ) score and YMRS response rate . Safety and tolerability were assessed weekly . RESULTS The DVP + quetiapine group demonstrated a statistically significantly greater reduction in YMRS scores from baseline to endpoint than the DVP + placebo group ( F(1,27 ) = 5.04 , p = .03 ) . Moreover , YMRS response rate was significantly greater in the DVP + quetiapine group than in the DVP + placebo group ( 87 % versus 53 % ; Fisher exact test , p = .05 ) . No significant group differences from baseline to endpoint in safety measures were noted . Sedation , rated as mild or moderate , was significantly more common in the DVP + quetiapine group than in the DVP + placebo group . CONCLUSIONS The findings of this study indicate that quetiapine in combination with DVP is more effective for the treatment of adolescent bipolar mania than DVP alone . In addition , the results suggest that quetiapine is well tolerated when used in combination with DVP for the treatment of mania OBJECTIVE This study characterizes the tolerability of ziprasidone in children and adolescents with bipolar mania , schizophrenia , or schizoaffective disorder . METHOD Sixty-three subjects ( aged 10 - 17 years ) entered an open-label study consisting of a 3-week fixed-dose period ( Period 1 ) and a subsequent 24-week flexible-dose period ( Period 2 ) . In Period 1 , subjects received ziprasidone 80 or 160 mg/d in two divided doses , titrated over 10 days . In Period 2 , subjects received flexible doses ( 20 - 160 mg/d ) . Tolerability was evaluated using movement rating scales , laboratory tests , and electrocardiograms . Clinical response was assessed using the Young Mania Rating Scale , the Brief Psychiatric Rating Scale-Anchored Version , and the Clinical Global Impressions-Severity scale . RESULTS Adverse events ( AEs ) occurred mostly during dose titration and in the high-dose ( 160 mg/d ) group . The most common AEs during Period 1 were sedation ( 32 % ) , somnolence ( 30 % ) , and nausea ( 25 % ) and during Period 2 were sedation ( 30 % ) , somnolence ( 30 % ) , and headache ( 25 % ) . The incidence of movement disorder AEs was 22 % and 16 % during Periods 1 and 2 , respectively . Six percent of study participants discontinued study participation due to AEs during Period 1 and 20 % discontinued in Period 2 . Thirty-three percent of subjects gained > or=7 % of their baseline weight . No Fridericia-corrected QT ( QTcF ) intervals of > 450 ms were observed during Period 1 and only one occurred during Period 2 . No QTcF increase > or=60 ms from baseline was observed . Symptom reductions were observed in all patient groups . CONCLUSIONS No unexpected tolerability findings were observed in this prospect i ve trial of ziprasidone in children and adolescents with bipolar mania , schizophrenia , or schizoaffective disorder . On the basis of the results , a starting dose of 20 mg/d titrated to between 80 and 160 mg/d over 1 - 2 weeks appears optimal for most patients OBJECTIVE To evaluate asenapine versus placebo in 403 patients aged 10 to 17 years with bipolar I disorder currently in manic or mixed episodes . METHOD In this double-blind , placebo-controlled , international trial , patients were r and omized 1:1:1:1 to placebo , asenapine 2.5 , 5 , or 10 mg b.i.d . ( twice daily ) . Primary efficacy measure was change from baseline in Young-Mania Rating Scale ( YMRS ) total score at day 21 . Analyses of patients with/without attention-deficit/hyperactivity disorder ( ADHD ) and with/without stimulant use were performed . RESULTS The mean difference in asenapine versus placebo in YMRS was -3.2 ( p = .0008 ) , -5.3 ( p < .001 ) , and -6.2 ( p < .001 ) for asenapine 2.5 , 5 , and 10 mg b.i.d . , respectively . Treatment-emergent adverse events with an incidence ≥5 % and at least twice placebo were somnolence , sedation , hypoesthesia oral , paresthesia oral , and increased appetite . The asenapine groups had a higher incidence of ≥7 % weight gain ( range , 8.0%-12.0 % ) versus placebo ( 1.1 % ; p < .05 ) . The mean change from baseline in fasting insulin was larger for patients treated with asenapine than those with placebo ( asenapine 2.5 mg b.i.d . : 73.375 pmol/L ; asenapine 5 mg b.i.d . : 114.042 pmol/L ; asenapine 10 mg b.i.d . : 59.846 pmol/L ; placebo : 3.690 pmol/L ) . The mean changes from baseline for lipid parameters and glucose were also larger in asenapine groups than in the placebo group . No safety differences were observed with respect to ADHD and stimulant use . CONCLUSION All asenapine doses versus placebo were superior based on change in YMRS at day 21 . Asenapine was generally well tolerated in patients aged 10 to 17 years with bipolar I disorder in manic or mixed states . Increases in weight and fasting insulin were associated with asenapine . Clinical trial registration information-Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder ; http:// clinical trials.gov ; NCT01244815 The pharmacotherapy for tic management in Tourette syndrome ( TS ) relies on neuroleptics , which have been associated with electrocardiographic abnormalities , including QTc interval prolongation . This study assessed the cardiovascular safety of the newer antipsychotic aripiprazole in comparison with the neuroleptic pimozide among young patients affected by TS . Fifty patients aged 6–18 years were assigned to either pimozide ( n = 25 ; mean daily dose 4.4 mg/die ) or aripiprazole ( n = 25 ; 5.3 mg/die ) treatment for up to 24 months . All patients underwent five serial cardiovascular assessment s ( baseline , 6 , 12 , 18 and 24 months ) . The group treated with pimozide showed significant changes in blood pressure ( decreased ) , QT and QTc ( both prolonged ) . The aripiprazole group showed changes from baseline to peak values in blood pressure ( increased ) , whilst modifications in QT and QTc were not statistically significant . At equivalent doses , aripiprazole is characterised by a safer cardiovascular profile than pimozide , being associated with a lower frequency of QTc prolongation OBJECTIVE To evaluate weight gain associated with olanzapine , risperidone , and haloperidol treatment and its clinical risk factors in adolescent patients . METHOD The study was conducted at three adolescent psychiatric departments in two mental health centers in the Tel Aviv area . All patients were Jewish Israelis . Weight and body mass index ( BMI ) of hospitalized adolescents treated with olanzapine ( n = 21 ) , risperidone ( n = 21 ) , or haloperidol ( n = 8) were prospect ively monitored on a weekly basis for the first 12 weeks of treatment . Various clinical risk factors were tested for association with weight gain . RESULTS The olanzapine and risperidone groups experienced significant weight gain between baseline and endpoint ( p < .01 ) , whereas the average weight of the haloperidol group did not change . Average weight gain was significantly higher for the olanzapine group ( 7.2 + /- 6.3 kg , 11.1 % + /- 7.8 % ) than for the risperidone ( 3.9 + /- 4.8 kg , 6.6 % + /- 8.6 % ) and haloperidol ( 1.1 + /- 3.3 kg , 1.5 % + /- 6.0 % ) groups . Extreme weight gain ( > 7 % ) was recorded in 19 patients ( 90.5 % ) , 9 patients ( 42.9 % ) , and 1 ( 12.5 % ) patient , respectively Gender ( males ) , low concern about gaining weight ( females ) , low baseline BMI , and paternal BMI were positively correlated with weight gain , whereas previous neuroleptic history , neuroleptic dosage , response to treatment , and illness duration were not . CONCLUSIONS Olanzapine and risperidone are associated with extreme weight gain in adolescents , much higher than that reported in adults . This side effect should be taken into consideration before prescribing these medications , especially in patients at high risk Article abstract The authors r and omized 10 patients ( age range , 7 to 13 years ) with Tourette ’s syndrome who had achieved a stable level of tic control on open-label pimozide to continue on pimozide ( n = 6 ) or be withdrawn from therapy ( n = 4 ) in a double-blind study . The median time to end point ( the time when an increased dose of study medication was required to control tics ) was 231 days ( continued ) versus 37 days ( withdrawn ) , and the survival curves were significantly different ( p = 0.02 ) . Chronic , longer term treatment with pimozide appears to be more effective in controlling the course of tics than using the drug acutely to treat an exacerbation BACKGROUND To evaluate short-term safety and efficacy of atypical antipsychotics in a single-site , prospect i ve , open-label , 8-week study of risperidone and olanzapine monotherapy in preschoolers with bipolar disorder ( BPD ) . METHODS Risperidone was initiated at an open-label dose of .25 mg/day , increased weekly according to response and tolerability to a maximum does of 2.0 mg/day . Olanzapine was initiated at 1.25 mg/day and increased to no more than 10 mg/day . RESULTS Thirty-one children aged 4 - 6 years were treated with olanzapine ( n = 15 , 6.3 + /- 2.3 mg/day ) or risperidone ( n = 16 , 1.4 + /- .5 mg/day ) . At study end point ( week 8 or last observation carried forward ) , there was a 18.3 + /- 11.9 point ( t = -5.6 , p < .001 ) reduction in risperidone-treated subjects and a 12.1 + /- 10.4 point ( t = -4.4 , p < .001 ) reduction in Young Mania Rating Scale ( YMRS ) scores in olanzapine-treated subjects that did not differ between groups ( t = 1.4 , p = .2 ) . Response criteria ( Clinical Global Impression improvement of " Much " or " Very Much " improved or a YMRS change of > or= 30 % or more ) indicated no difference in rate of response with risperidone and olanzapine ( 69 % vs. 53 % , chi(2)((1 ) ) = .8 , p = .4 ) . CONCLUSIONS This prospect i ve open study suggests that treatment with risperidone or olanzapine may result in a rapid reduction of symptoms of mania in preschool children with BPD . Because of substantial residual symptomatology and adverse effects , however , a pressing need exists to identify additional safe and effective treatments for the management of BPD in this high-risk population OBJECTIVES Conventional neuroleptics ameliorate symptoms in children with autistic disorder ; however , they are known to cause dyskinesias . Atypical neuroleptics , including olanzapine , may have less risk for dyskinesia , but their efficacy in autistic disorder is not established . This study was design ed to investigate the safety and effectiveness of open-label olanzapine as a treatment for children with autistic disorder by using haloperidol as a st and ard comparator treatment . METHOD In a parallel groups design , 12 children with DSM-IV autistic disorder ( mean age 7.8+/-2.1 years ) were r and omized to 6 weeks of open treatment with olanzapine or haloperidol . Mean final dosages were 7.9+/-2.5 mg/day for olanzapine and 1.4+/-0.7 mg/day for haloperidol . Outcome measures included the Clinical Global Impressions ( CGI ) and the Children 's Psychiatric Rating Scale ( CPRS ) . RESULTS Both groups had symptom reduction . Five of six in the olanzapine group and three of six in the haloperidol group were rated as responders according to the CGI Improvement item . Subjects showed improvement on the CPRS Autism Factor ( F1,9 = 24.4 , p = .0008 ) . Side effects included drowsiness and weight gain . CONCLUSIONS The findings suggest that olanzapine is a promising treatment for children with autistic disorder . Further placebo-controlled and long-term studies of olanzapine in autistic disorder are required OBJECTIVE To assess response to treatment with aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD Children and adolescents were extensively assessed according to DSM-IV criteria for bipolar disorder comorbid with ADHD ( n = 710 ) . Those with this comorbidity who were acutely manic or in mixed states were r and omly assigned in a 6-week double-blind , placebo-controlled trial to aripiprazole ( n = 18 ) or placebo ( n = 25 ) . Primary outcome measures were assessed weekly and included the Young Mania Rating Scale ; the Swanson , Nolan , and Pelham Scale-Version IV ; and weight . Secondary outcome measures were the Clinical Global Impressions-Severity of Illness scale , the Child Mania Rating Scale-Parental Version ( CMRS-P ) , the Children 's Depression Rating Scale-Revised , the Kutcher Adolescent Depression Scale , and adverse events . The trial was conducted at the Hospital de Clínicas de Porto Alegre , Rio Gr and e do Sul , Brazil , from January 2005 to November 2007 . RESULTS The group receiving aripiprazole showed a significantly greater reduction in YMRS scores ( P = .02 , effect size [ ES ] = 0.80 ) , CMRS-P scores ( P = .02 ; ES = 0.54 ) , and CGI-S scores ( P = .04 ; ES = 0.28 ) from baseline to endpoint than the placebo group . In addition , higher rates of response ( P = .02 ) and remission ( P = .01 ) were found for the aripiprazole group . No significant between-group differences were found in weight , ADHD symptoms , and depressive symptoms . Adverse events significantly more frequent in the aripiprazole group were somnolence and sialorrhea . CONCLUSION Aripiprazole was effective in reducing manic symptoms and improving global functioning without promoting severe adverse events or weight gain . No significant treatment effect in ADHD symptoms was observed . Studies are needed to assess psychopharmacologic interventions for improving ADHD symptoms in juvenile bipolar disorder comorbid with ADHD . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116259 BACKGROUND The treatment of Tourette 's disorder with classical neuroleptics is limited by their side effects . Risperidone is a new efficacious antipsychotic with a low propensity for extrapyramidal side effects . To establish risperidone 's therapeutic potential in Tourette 's disorder , we studied the safety and efficacy of risperidone in comparison with pimozide in patients with Tourette 's disorder diagnosed according to DSM-III-R. METHOD In a 12-week , multicenter , double-blind , parallel-group study , 26 patients were treated with risperidone ( mean daily dose = 3.8 mg ) , and 24 patients were treated with pimozide ( mean daily dose = 2.9 mg ) . RESULTS There was significant improvement of tics with respect to the Tourette 's Symptom Severity Scale ( TSSS ) for both groups . Forty-one patients completed the study . At endpoint , 54 % ( 14/26 ) of the risperidone patients and 38 % ( 9/24 ) of the pimozide patients had only very mild or no symptoms on the global severity rating of the TSSS . Both treatment groups had improved significantly at endpoint in regard to Global Assessment of Functioning and Clinical Global Impressions scale outcomes . Symptoms of anxiety and depressive mood improved significantly from baseline in both groups . Obsessive-compulsive behavior improvement reached significance only in the risperidone group . Although the severity of extrapyramidal side effects was low in both groups , fewer patients in the risperidone group reported extrapyramidal side effects ( N = 4 ) compared with the pimozide group ( N = 8) . Depression , fatigue , and somnolence were reported as the most prominent side effects in both treatment groups . CONCLUSION Both drugs were efficacious and well tolerated in patients with Tourette 's disorder . Risperidone may become the first-line drug in the treatment of Tourette 's disorder owing to a more favorable efficacy and tolerability profile OBJECTIVES To determine the efficacy and safety of aripiprazole for the treatment of pediatric bipolar I disorder , manic or mixed episode , with or without psychotic features . METHOD Subjects were enrolled between March 2005 and February 2007 in a r and omized , multicenter , double-blind 4-week study of aripiprazole 10 mg/d , aripiprazole 30 mg/d , and placebo . Subjects ( n = 296 ) were 10 to 17 years old with a DSM-IV diagnosis of bipolar I disorder with current manic or mixed episodes , with or without psychotic features , and a Young Mania Rating Scale ( YMRS ) score > or = 20 . The primary efficacy variable was change from baseline in the YMRS total score . RESULTS Both doses of aripiprazole were superior to placebo on the YMRS total score beginning at week 1 and continuing through week 4 . Aripiprazole 10 mg and 30 mg were more effective than placebo on global improvement , mania , and overall bipolar illness outcome measures . Response ( > or = 50 % reduction in YMRS total score ) at week 4 was achieved by 44.8 % , 63.6 % , and 26.1 % of subjects in the aripiprazole 10 mg , aripiprazole 30 mg , and placebo groups , respectively ( P < .01 both doses vs placebo ) . Both doses were generally well tolerated . The most common adverse events were extrapyramidal disorder and somnolence ; rates were higher for aripiprazole 30 mg compared with aripiprazole 10 mg . Average weight gain was not significantly different between the aripiprazole 10 mg ( + 0.82 kg ) or 30 mg ( + 1.08 kg ) groups compared with the placebo group ( + 0.56 kg ) ( P = .35 and P = .13 , respectively ) . CONCLUSIONS Aripiprazole in daily doses of 10 mg or 30 mg is an effective and generally well-tolerated acute treatment for pediatric subjects with bipolar I mania or mixed episodes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00110461 OBJECTIVE The authors evaluated the relative efficacy and safety of pimozide and haloperidol in the treatment of Gilles de la Tourette 's syndrome in children and adolescents . METHOD A double-blind , 24-week , placebo-controlled double crossover study of equivalent dose formulations of haloperidol and pimozide was conducted with 22 subjects , aged 7 - 16 years , with Tourette 's disorder who were r and omly assigned to first one active drug treatment and then the other . Biweekly assessment and flexible dose titration mimicked clinical practice . The primary outcome variable was total score on the Tourette Syndrome Global Scale . Final outcome was determined after 6 weeks of each treatment ( placebo , pimozide , haloperidol ) , with a 2-week placebo baseline period and intervening 2-week placebo washout periods between treatments . RESULTS Pimozide proved significantly different from placebo in affecting the primary outcome variable , whereas haloperidol failed to have a significant effect . Haloperidol exhibited a threefold higher frequency of serious side effects and significantly greater extrapyramidal symptoms relative to pimozide . Haloperidol-associated treatment-limiting adverse events were experienced by 41 % of the patients . The therapeutic doses of pimozide and haloperidol were equivalent ( mean = 3.4 mg/day , SD = 1.6 , and mean = 3.5 mg/day , SD = 2.2 , respectively ) . CONCLUSIONS At equivalent doses , pimozide is superior to haloperidol for controlling symptoms of Tourette 's disorder in children and adolescents Objective To compare the efficacy , safety , and tolerability of olanzapine and quetiapine in adolescents with first episode psychosis . Method Fifty adolescents ( age 16 ± 1.25 ) with a first episode of psychosis were r and omized to quetiapine or olanzapine in a 6-month open label study . Efficacy and side effect scales , as well as vital signs and laboratory data were recorded at baseline , 7 , 15 , 30 , 90 , and 180 days ( end of study ) . Results Out of the total sample included in the study , 32 patients completed the trial ( quetiapine n = 16 , olanzapine n = 16 ) . Patients in both treatment groups had a significant reduction in all clinical scales with the exception of the negative scale of the Positive and Negative Symptom Scale ( PANSS ) for olanzapine and the general psychopathology scale of the PANSS for quetiapine . The only difference between treatment arms on the clinical scales was observed on the patients ’ strength and difficulties question naire ( SDQ ) scale , with greater improvement for olanzapine . Patients on olanzapine gained 15.5 kg and patients on quetiapine gained 5.5 kg . Conclusion Olanzapine and quetiapine reduced psychotic symptoms in this adolescent sample . Patients on olanzapine gained significantly more weight . Side effects with both drugs seemed to be more prevalent than those reported in adult studies BACKGROUND The prodromal phase of schizophrenic disorders has been described prospect ively . The present study aim ed to determine the short-term efficacy and safety of olanzapine treatment of prodromal symptoms compared with placebo . METHODS This was a double-blind , r and omized , parallel-groups , placebo-controlled trial with fixed-flexible dosing conducted at four sites . Sixty patients met prodromal diagnostic criteria , including attenuated psychotic symptoms , as determined by structured interviews . Olanzapine 5 - 15 mg daily or placebo was prescribed for 8 weeks . RESULTS In the mixed-effects , repeated- measures analysis , the treatment x time interaction for the change from baseline on the Scale of Prodromal Symptoms total score was statistically significant , and post hoc analyses revealed that the olanzapine-placebo difference reached p<.10 by week 6 and p<.05 at week 8 . Ratings of extrapyramidal symptoms remained low in each group and were not significantly different . Olanzapine patients gained 9.9 lb versus.7 lb for placebo patients ( p<.001 ) . CONCLUSIONS This short-term analysis suggests olanzapine is associated with significantly greater symptomatic improvement but significantly greater weight gain than is placebo in prodromal patients . Extrapyramidal symptoms with olanzapine were minimal and similar to those with placebo . Future research over the longer term with more patients will be needed before recommendations can be made regarding routine treatment OBJECTIVE To evaluate the efficacy and safety of aripiprazole versus placebo in preventing relapse of irritability symptoms associated with autistic disorder in pediatric patients . METHOD This multicenter , double-blind , r and omized , placebo-controlled , relapse-prevention trial enrolled patients ( 6 - 17 years ) who met the current Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision ( DMS-IV-TR ) criteria for autistic disorder and who also had serious behavioral problems ( ie , tantrums , aggression , self-injurious behavior , or a combination of these behavioral problems ) between March 2011 and June 2012 . In phase 1 , single-blind aripiprazole was flexibly dosed ( 2 - 15 mg/d ) for 13 - 26 weeks . Patients with a stable response ( ≥ 25 % decrease in Aberrant Behavior Checklist-irritability subscale score and a rating of " much improved " or " very much improved " on the Clinical Global Impressions-Improvement scale ) for 12 consecutive weeks were r and omized into phase 2 to continue aripiprazole or switch to placebo . Treatment was continued until relapse or up to 16 weeks . The primary end point was time from r and omization to relapse . RESULTS Eighty-five patients were r and omized in phase 2 . The difference in time to relapse between aripiprazole and placebo was not statistically significant ( P = .097 ) . Kaplan-Meier relapse rates at week 16 were 35 % for aripiprazole and 52 % for placebo ( hazard ratio [ HR ] = 0.57 ; number needed to treat [ NNT ] = 6 ) . The most common adverse events during phase 1 were weight increase ( 25.2 % ) , somnolence ( 14.8 % ) , and vomiting ( 14.2 % ) ; and , during phase 2 ( aripiprazole vs placebo ) , they were upper respiratory tract infection ( 10.3 % vs 2.3 % ) , constipation ( 5.1 % vs 0 % ) , and movement disorder ( 5.1 % vs 0 % ) . CONCLUSIONS In this study , there was no statistically significant difference between aripiprazole and placebo in time to relapse during maintenance therapy . However , the HR and NNT suggest some patients will benefit from maintenance treatment . Patients receiving aripiprazole should be periodically reassessed to determine the continued need for treatment . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01227668 Abstract Aripiprazole and risperidone are the only FDA approved medications for treating irritability in autistic disorder , however there are no head-to-head data comparing these agents . This is the first prospect i ve r and omized clinical trial comparing the safety and efficacy of these two medications in patients with autism spectrum disorders . Fifty nine children and adolescents with autism spectrum disorders were r and omized to receive either aripiprazole or risperidone for 2 months . The primary outcome measure was change in Aberrant Behavior Checklist ( ABC ) scores . Adverse events were assessed . Aripiprazole as well as risperidone lowered ABC scores during 2 months . The rates of adverse effects were not significantly different between the two groups . The safety and efficacy of aripiprazole ( mean dose 5.5 mg/day ) and risperidone ( mean dose 1.12 mg/day ) were comparable . The choice between these two medications should be on the basis of clinical equipoise considering the patient ’s preference and clinical profile OBJECTIVE The aim of this study was to improve and evaluate the practibility of a method for the assessment of drug-associated side effects , and we implemented a clinical drug monitoring for atypical neuroleptics . METHODS Side effects of initially hospitalized patients treated with clozapine ( n = 16 ) , olanzapine ( n = 16 ) , and risperidone ( n = 19 ) were prospect ively monitored on a weekly basis for the first 3 weeks . In the case of stable medication , measurements of all variables were made every 4 weeks or upon discharge . We used the Dosage Record Treatment Emergent Symptom Scale ( DOTES ) in a supplemented version to measure the presence and severity of side effects . RESULTS Drowsiness and decreased motor activity were common , especially in the first 2 weeks . Orthostatic hypotension , increased salivation , constipation , and nasal congestion were seen in more than 30 % to 60 % of patients treated with clozapine and were less common in adolescents treated with olanzapine and risperidone . Rigidity , tremor , and dystonia were seen in 5 % to 15 % of patients treated with risperidone and olanzapine . The average weight gain after 6 weeks of treatment with the atypical neuroleptics was significantly higher for the olanzapine group ( 4.6 + /- 1.9 kg ) than for the risperidone ( 2.8 + /- 1.3 kg ) and clozapine ( 2.5 + /- 2.9 kg ) groups . CONCLUSIONS The authors ' supplemented DOTES version is generally applicable to clinical use in mental health centers . The differences among the side effects of these three agents may affect compliance with medication and medical risks of metabolic syndrome , diabetes , and cardiovascular disease . More research on the short- and long-term safety of psychotropic drugs in children and adolescents , using st and ardized methods , should be considered OBJECTIVE To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder . METHOD Two hundred eighteen children and adolescents ( aged 6 - 17 years ) with a diagnosis of autistic disorder , and with behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these symptoms , were r and omized 1:1:1:1 to aripiprazole ( 5 , 10 , or 15 mg/day ) or placebo in this 8-week double-blind , r and omized , placebo-controlled , parallel-group study . Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale ( primary efficacy measure ) and the clinician-rated Clinical Global Impressions-Improvement score . Safety and tolerability were also assessed . RESULTS At week 8 , all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores ( 5 mg/day , -12.4 ; 10 mg/day , -13.2 ; 15 mg/day , -14.4 ; versus placebo , -8.4 ; all p < .05 ) . All aripiprazole doses demonstrated significantly greater improvements in mean Clinical Global Impressions-Improvement score than placebo at week 8 . Discontinuation rates due to adverse events were as follows : placebo 7.7 % , aripiprazole 5 mg/day 9.4 % , 10 mg/day 13.6 % , and 15 mg/day 7.4 % . The most common adverse event leading to discontinuation was sedation . There were two serious adverse events : presyncope ( 5 mg/day ) and aggression ( 10 mg/day ) . At week 8 , mean weight change ( last observation carried forward ) was as follows : placebo + 0.3 kg , aripiprazole 5 mg/day + 1.3 kg , 10 mg/day + 1.3 kg , and 15 mg/day + 1.5 kg ; all p < .05 versus placebo . CONCLUSIONS Aripiprazole was efficacious and generally safe and well tolerated in the treatment of children and adolescents with irritability associated with autistic disorder OBJECTIVE The authors tested the hypothesis that a dopamine D(2 ) receptor occupancy level between 60 % and 70 % in patients with recent-onset schizophrenia would result in optimal subjective experience . In addition , they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol . METHOD Subjects ( N=24 ) who met DSM-IV criteria for schizophrenia were r and omly assigned to 6 weeks of double-blind treatment with either olanzapine , 7.5 mg/day , or haloperidol , 2.5 mg/day . Subjective experience , psychopathology , and extrapyramidal symptoms were assessed at baseline and at endpoint . After 6 weeks , D(2 ) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography . RESULTS The two study groups were similar at baseline . After 6 weeks , patients receiving olanzapine had a significantly lower mean dopamine D(2 ) receptor occupancy ( 51.0 % , range=36%-67 % ) than those given haloperidol ( 65.5 % , range=45%-75 % ) . Receptor occupancy between 60 % and 70 % was associated with optimal subjective experience , and subjective experience improved significantly in the haloperidol group . CONCLUSIONS A level of D(2 ) receptor occupancy between 60 % and 70 % is optimal for subjective experience of patients with recent-onset schizophrenia . Substantial interindividual variation in D(2 ) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol . Olanzapine , 7.5 mg/day , showed no superior subjective response over haloperidol , 2.5 mg/day . Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia , and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy As part of systematic treatment trials of haloperidol , clozapine , and olanzapine with a total of 35 children and adolescents with early onset psychosis , prolactin was measured at baseline and week 6 of treatment . The National Institute of Mental Health patients --13 females , 22 males ( mean age , 14.1+/-2.3 years ; range , 9.1 - 19 years ) with childhood onset schizophrenia ( n = 32 ) , or Psychotic Disorder not otherwise specified ( NOS ) ( n = 3 ) with onset of psychosis before age 13 - -were recruited for open or double-blind trials of haloperidol , clozapine , or olanzapine . Baseline serum prolactin was measured after a 3-week washout period and after 6 weeks of treatment . Mean prolactin concentration after 6 weeks of treatment was significantly elevated on all three drugs ; however , on clozapine , mean prolactin remained within the normal range . Prolactin was increased above the upper limit of normal for 100 % of 10 patients on haloperidol , 70 % of 10 patients on olanzapine , and 0 % of 15 patients on clozapine ( chi2 analyses : H > C , p = 0.004 ; O > C , p = 0.001 ) . Given the potential endocrine and possible cardiac correlates of hyperprolactinemia , these more robust prolactin elevations in pediatric patients after short-term exposure to olanzapine than those reported for adults justify longer observation intervals with bigger sample s to establish treatment safety of atypical antipsychotics in adolescents OBJECTIVE Aripiprazole is a dopamine partial agonist approved for use in adults for short- and long-term treatment of schizophrenia and bipolar disorder . This study was design ed to examine the acute efficacy , safety , and tolerability of aripiprazole for adolescents with schizophrenia . METHOD This was a 6-week multicenter , double-blind , r and omized , placebo-controlled trial . Subjects 13 to 17 years old with a DSM-IV diagnosis of schizophrenia and a Positive and Negative Syndrome Scale ( PANSS ) total score of 70 or more were r and omly assigned ( 1:1:1 ratio ) to placebo or 10 or 30 mg/day of aripiprazole . The primary endpoint was mean change from baseline to endpoint ( last observation carried forward ) in PANSS total score . Assessment s of safety and tolerability included spontaneously reported adverse events , extrapyramidal symptom scores , serum prolactin concentration , body weight , and metabolic measures . RESULTS Of 302 patients , 85 % completed the 6-week study . The mean baseline PANSS score was 94.1 . At the end of the study , both aripiprazole doses showed statistically significant differences from placebo in reduction in PANSS total score . Adverse events occurring in more than 5 % of either aripiprazole group and with a combined incidence at least twice the rate for placebo were extrapyramidal disorder , somnolence , and tremor . Mean changes in prolactin were -8.45 , -11.93 , and -15.14 ng/ml for placebo and 10 mg and 30 mg of aripirazole , respectively . Mean body weight changes were -0.8 , 0.0 , and 0.2 kg for placebo and 10 mg and 30 mg of aripiprazole , respectively . CONCLUSION Both 10- and 30-mg/day doses of aripiprazole were superior to placebo in the acute treatment of adolescents with schizophrenia . Aripiprazole was generally well tolerated This double-blind and placebo-controlled clinical trial in autistic children had three objectives : ( a ) to replicate earlier findings that haloperidol administration is associated with a significant reduction of behavioral symptoms ; ( b ) to further assess its safety when given on a short-term basis : and ( c ) to assess whether it has an effect on discrimination learning . Forty-five children , 2.02 to 7.58 years old ( M=4.49 ) , completed this crossover design , with r and om assignment to treatment sequences . Haloperidol was shown to be a powerful therapeutic agent when administered for 4 weeks and free of side effects ; at doses ranging from 0.25 to 4.0 mg/day ( M=0.844 ) , there was a clinical ly and statistically significant reduction of a variety of symptoms . Under the given conditions , the children failed to learn on either haloperidol or placebo OBJECTIVE Although combination pharmacotherapy is common in child and adolescent psychiatry , there has been little research evaluating it . The value of adding risperidone to concurrent psychostimulant and parent training ( PT ) in behavior management for children with severe aggression was tested . METHOD One hundred sixty-eight children 6 to 12 years old ( mean age 8.89 ± 2.01 years ) with severe physical aggression were r and omized to a 9-week trial of PT , stimulant ( STIM ) , and placebo ( Basic treatment ; n = 84 ) or PT , STIM , and risperidone ( Augmented treatment ; n = 84 ) . All had diagnoses of attention-deficit/hyperactivity disorder and oppositional-defiant disorder ( n = 124 ) or conduct disorder ( n = 44 ) . Children received psychostimulant ( usually Osmotic Release Oral System methylpheni date ) for 3 weeks , titrated for optimal effect , while parents received PT . If there was room for improvement at the end of week 3 , placebo or risperidone was added . Assessment s included parent ratings on the Nisonger Child Behavior Rating Form ( Disruptive-Total subscale was the primary outcome ) and Antisocial Behavior Scale ; blinded clinicians rated change on the Clinical Global Impressions scale . RESULTS Compared with Basic treatment ( PT + STIM [ 44.8 ± 14.6 mg/day ] + placebo [ 1.88 mg/day ± 0.72 ] ) , Augmented treatment ( PT + STIM [ 46.1 ± 16.8 mg/day ] + risperidone [ 1.65 mg/day ± 0.75 ] ) showed statistically significant improvement on the Nisonger Child Behavior Rating Form Disruptive-Total subscale ( treatment-by-time interaction , p = .0016 ) , the Nisonger Child Behavior Rating Form Social Competence subscale ( p = .0049 ) , and Antisocial Behavior Scale Reactive Aggression subscale ( p = .01 ) . Clinical Global Impressions scores were substantially improved for the 2 groups but did not discriminate between treatments ( Clinical Global Impressions-Improvement score ≤2 , 70 % for Basic treatment versus 79 % for Augmented treatment ) . Prolactin elevations and gastrointestinal upset occurred more with Augmented treatment ; other adverse events differed modestly from Basic treatment ; weight gain in the Augmented treatment group was minor . CONCLUSIONS Risperidone provided moderate but variable improvement in aggressive and other seriously disruptive child behaviors when added to PT and optimized stimulant treatment . Clinical trial registration information-Treatment of Severe Childhood Aggression ( The TOSCA Study ) , URL : http:// clinical trials.gov , unique identifier : NCT00796302 OBJECTIVE To evaluate the efficacy , safety , and tolerability of paliperidone extended release ( ER ) relative to aripiprazole in adolescent schizophrenia . METHOD In this multicenter , double-blind , phase 3 study ( screening [ ≤3 weeks ] , with an acute treatment period [ 8 weeks ] and a maintenance period [ 18 weeks ] ) , adolescents ( 12 - 17 years old ) with schizophrenia ( DSM-IV diagnosis ; Positive and Negative Symptom Score [ PANSS ] total score 60 - 120 ) were r and omized ( 1:1 ) to once-daily paliperidone ER ( 6 mg per day [ days 1 - 7 ] , flexibly dosed 3 , 6 , or 9 mg per day from week 2 to end of study [ EOS ] ) , or to aripiprazole ( 2 mg per day [ days 1 and 2 ] , 5 mg per day [ days 3 and 4 ] , 10 mg per day [ days 5 - 7 ] , flexibly dosed 5 , 10 , or 15 mg per day [ week 2 to EOS ] ) . RESULTS Overall , 76 % of enrolled patients ( 174/228 ) completed the study ( paliperidone ER , 75 % [ 85/113 ] ; aripiprazole , 77 % [ 89/115 ] ) . There was no significant difference in change in PANSS total scores from baseline to day 56 ( primary endpoint ) ( paliperidone ER versus aripiprazole , -19.3 [ 13.80 ] versus -19.8 [ 14.56 ] , p = .935 ) ; responders , 67.9 % versus 76.3 % , p = .119 ) and day 182 ( -25.6 [ 16.88 ] versus -26.8 [ 18.82 ] , p = .877 ; responders , 76.8 % versus 81.6 % , p = .444 ) . All secondary endpoints ( maintenance of clinical stability , change in PANSS-negative symptoms , Clinical Global Impression-Severity , and Personal and Social Performance scores ) were similar in both treatment groups . The most common ( > 10 % patients ) treatment-emergent adverse events for paliperidone ER were akathisia , headache , somnolence , tremor , and weight gain , and for aripiprazole were worsening of schizophrenia and somnolence . Extrapyramidal symptoms including dystonia and hyperkinesia occurred in > 2 % in paliperidone ER-treated versus aripiprazole-treated patients . CONCLUSION Paliperidone ER did not demonstrate superior efficacy to aripiprazole in treating adolescent schizophrenia . Both drugs showed clinical ly meaningful improvements in symptom and functional measurements and were generally tolerable . Clinical Trial Registration Information-An Efficacy and Safety Study of Extended-Release ( ER ) Paliperidone in Adolescent Participants With Schizophrenia ; http:// clinical trials.gov ; NCT01009047 Abstract Although a frequent co-occurrence between bipolar disorder ( BD ) and conduct disorder ( CD ) in youth has been frequently reported , data about pharmacological management are scarce and focused on BD type I. Second generation antipsychotics are frequently used in clinical practice , but no comparative studies are available . The aim of this exploratory study was to compare efficacy and safety of risperidone and quetiapine in a sample of adolescents presenting a BD type II comorbid with CD . Twenty-two patients diagnosed with a structured interview according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , ( male/female ratio , 12/10 ; mean ( SD ) age 15.0 ( 1.4 ) years ) were r and omized in 2 treatment groups ( quetiapine [ n = 12 ] vs risperidone [ n = 10 ] ) , treated with flexible doses , and followed up for 12 weeks . Efficacy measures assessed manic symptoms , aggression , anxiety , depression , global clinical severity , and impairment . Safety measures included body mass index , serum prolactin , extrapyramidal adverse effects , and electrocardiogram . At the end of the study , all patients improved in all efficacy measures . Both treatments showed similar efficacy in reducing manic symptoms and aggression . Quetiapine was more effective in improving anxiety and depressive symptoms . A change in body mass index was found , and in a post hoc analysis , it was significant only in the risperidone group . Prolactin significantly increased only in the risperidone group . In BD type II , CD comorbidity , quetiapine , or risperidone monotherapy may be effective and relatively safe , although the small sample size , the limited duration of the study , and the design ( lack of a blind assessment s and of a placebo group ) make it difficult to draw definitive conclusions OBJECTIVE The aim of this study was to examine whether quetiapine is superior to placebo in the treatment of adolescents with conduct disorder . METHODS This was a 7-week , r and omized , double-blind , placebo-controlled pilot study with two parallel arms . Nine youths were r and omly assigned to receive quetiapine , and 10 youths were r and omly assigned to receive placebo . Patients were assessed weekly throughout the trial . Quetiapine was dosed twice daily , and medications could be titrated flexibly through the end of study week 5 . The dose was fixed for the final 2 weeks of the study . The primary outcome measures were the clinician-assessed Clinical Global Impressions-Severity ( CGI-S ) and -Improvement ( CGI-I ) scales . Secondary outcome measures included parent-assessed quality of life , the overt aggression scale ( OAS ) , and the conduct problems subscale of the Conners ' Parent Rating Scale ( CPRS-CP ) . RESULTS The final mean dose of quetiapine was 294 + /- 78 mg/day ( range 200 - 600 mg/day ) . Quetiapine was superior to placebo on all clinician-assessed measures and on the parent-assessed quality of life rating scale . No differences were found on the parent-completed OAS and CPRS-CP . Quetiapine was well tolerated . One patient r and omized to quetiapine developed akathisia , requiring medication discontinuation . No other extrapyramidal side effects occurred in patients receiving active drug . CONCLUSIONS This method ologically controlled pilot study provides data that quetiapine may have efficacy in the treatment of adolescents with conduct disorder . Because of the preliminary nature of the study , further research with larger sample s is needed to confirm these findings OBJECTIVE The aim of this study was to evaluate the efficacy and safety of two dose ranges of risperidone in adolescents with schizophrenia . METHODS In a 6-week , r and omized , double-blind , placebo-controlled study , adolescents aged 13 - 17 years with acute exacerbation of schizophrenia were r and omized to placebo , flexible doses of risperidone 1 - 3 mg/day , or risperidone 4 - 6 mg/day . Assessment s included the Positive and Negative Syndrome Scale ( PANSS ) , clinical response ( > or = 20 % reduction in PANSS total score ) , adverse event ( AE ) monitoring , and extrapyramidal symptom ( EPS ) scale ratings . RESULTS A total of 160 subjects received placebo ( n = 54 ) , risperidone 1 - 3 mg/day ( n = 55 ) , or risperidone 4 - 6 mg/day ( n = 51 ) . Significant improvements occurred in both risperidone groups versus placebo ( p < 0.001 ) in PANSS total change scores ( placebo , -8.9 [ 16.1 ] ; risperidone 1 - 3 mg , -21.3 [ 19.6 ] ; risperidone 4 - 6 mg , -21.2 [ 18.3 ] ) and clinical response rates ( 35 % , 65 % , 72 % , respectively ) . Overall AE rates were more common in risperidone groups ( 75 % and 76 % ) versus placebo ( 54 % ) . Risperidone 4 - 6 mg/day had a higher incidence of extrapyramidal disorder , dizziness , and hypertonia than risperidone 1 - 3 mg . No prolactin-related AEs occurred . Overall EPS severity was low . CONCLUSIONS Risperidone 1 - 3 mg/day and 4 - 6 mg/day were well tolerated and effective in adolescents experiencing acute episodes of schizophrenia . The benefit-risk profile suggests that a dose of 1 - 3 mg/day might be optimal for this population The objective of this study was to evaluate the efficacy and tolerability of quetiapine in the treatment of first onset psychosis in older adolescents using risperidone as a comparator . Twenty-two patients with first onset psychosis were r and omized to receive quetiapine ( up to 800 mg/day ) or risperidone ( up to 6 mg/day ) for 6 weeks . Raters blind to treatment assignment performed outcome symptom ratings . No statistical differences emerged in terms of efficacy or tolerability between the two drugs . However , there were some clinical ly notable differences that seem to favour the efficacy of risperidone over quetiapine . Patients taking quetiapine , although improved , showed less clinical improvement on scores for total positive and negative symptoms , clinical global severity and depression at 6 weeks than patients taking risperidone . Although both treatments were associated with weight gain and sedation , more patients on quetiapine experienced over 10 % weight gain . However , fewer patients who were taking quetiapine required anticholinergic medication or experienced extrapyramidal side effects than patients taking risperidone . Risperidone was significantly more likely to be associated with elevation in serum prolactin levels in this population . In conclusion , the results in this small trial show that adolescent patients may benefit more from treatment with risperidone than quetiapine . However , those susceptible to side effects , particularly hyperprolactinaemia , may be more suitable for treatment with quetiapine OBJECTIVE Atypical ( second-generation ) antipsychotics are considered st and ard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder . However , the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated . This study compared the efficacy and safety of two second-generation antipsychotics ( olanzapine and risperidone ) with a first-generation antipsychotic ( molindone ) in the treatment of early-onset schizophrenia and schizoaffective disorder . METHOD This double-blind multisite trial r and omly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine ( 2.5 - 20 mg/day ) , risperidone ( 0.5 - 6 mg/day ) , or molindone ( 10 - 140 mg/day , plus 1 mg/day of benztropine ) for 8 weeks . The primary outcome was response to treatment , defined as a Clinical Global Impression ( CGI ) improvement score of 1 or 2 and > or=20 % reduction in Positive and Negative Syndrome Scale ( PANSS ) total score after 8 weeks of treatment . RESULTS In total , 119 youth were r and omly assigned to treatment . Of these subjects , 116 received at least one dose of treatment and thus were available for analysis . No significant differences were found among treatment groups in response rates ( molindone : 50 % ; olanzapine : 34 % ; risperidone : 46 % ) or magnitude of symptom reduction . Olanzapine and risperidone were associated with significantly greater weight gain . Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol , low density lipoprotein , insulin , and liver transaminase levels . Molindone led to more self-reports of akathisia . CONCLUSIONS Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder . Adverse effects were frequent but differed among medications . The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia and schizoaffective disorder . The safety findings related to weight gain and metabolic problems raise important public health concerns , given the widespread use of second-generation antipsychotics in youth for nonpsychotic disorders |
11,830 | 30,776,855 | We were therefore unable to conclude with any confidence that , in people with chronic pain , TENS is harmful , or beneficial for pain control , disability , health-related quality of life , use of pain relieving medicines , or global impression of change . | BACKGROUND Chronic pain , considered to be pain lasting more than three months , is a common and often difficult to treat condition that can significantly impact upon function and quality of life .
Treatment typically includes pharmacological and non-pharmacological approaches .
Transcutaneous electrical nerve stimulation ( TENS ) is an adjunct non-pharmacological treatment commonly recommended by clinicians and often used by people with pain .
OBJECTIVES To provide an overview of evidence from Cochrane Review s of the effectiveness of TENS to reduce pain in adults with chronic pain ( excluding headache or migraine).To provide an overview of evidence from Cochrane Review s of the safety of TENS when used to reduce pain in adults with chronic pain ( excluding headache or migraine).To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain ( excluding headache or migraine ) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting .
To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain ( excluding headache or migraine ) with a view to recommending strategies to reduce any uncertainty . | & NA ; Transcutaneous electrical nerve stimulation ( TENS ) is a frequently applied therapy in chronic pain although evidence for effectiveness is inconclusive . Several types of TENS , based on different combinations of frequency , pulse duration and intensity , exist . The precise mechanism of action and the relevance of combinations of stimulus parameters are still unclear . To compare the effectiveness of three types of TENS we conducted a r and omized , single blinded crossover trial . Patients received two times a 2‐week period of daily TENS treatment , separated by a washout period of 2 weeks . In total , 180 chronic pain patients were r and omized into three groups . In group 1 , high frequency , low intensity TENS ( HFT ) was compared with high frequency , high intensity TENS ( HIT ) . In groups 2 and 3 , HFT and HIT were compared with a control TENS ( COT ) . The order of applying the different modalities of TENS in each group was also r and omized . Primary outcome was the patient 's overall assessment of effectiveness and pain reduction ( VAS ) . No differences were found in patient 's assessment or pain reducing effect between the three groups , indicating no superiority of one type of TENS . In total , 56 % continued TENS after the 2‐week treatment period . At 6 months , 42 % of all patients still used TENS . We concluded that there were no differences in effectiveness for the three types of TENS used in this study . Because no placebo group was included , no definite conclusions on effectiveness of TENS in general in the treatment of chronic pain could be made Objective : To investigate the hypoalgesic effects of transcutaneous electrical nerve stimulation ( TENS ) upon low back pain ( LBP ) in people with multiple sclerosis ( MS ) . Design : A r and omized double-blind placebo controlled clinical pilot study . Subjects and setting : Fifteen people with MS were recruited and r and omly allocated to one of the following groups under double blind conditions ( n = 5 per group ) : TENS 1 ( 4 Hz , 200 µs ) , TENS 2 ( 110 Hz , 200 µs ) , placebo TENS . Interventions : Treatment was applied for 45 minutes three times a week for six weeks with a four-week follow-up . Outcome measures : The following outcome measures were taken at weeks 1 , 6 , and 10 : visual analogue scale ( VAS ) ( for current LBP , right leg pain , left leg pain ) ; Leeds Multiple Sclerosis Quality of Life Question naire ; Rol and Morris Disability Question naire ; Short Form-36 ( SF-36 ) Version 1 ; and the McGill Pain Question naire ( MPQ ) . VAS for current LBP , right and left leg pain were also taken before and after treatment , and once a week during the follow-up period . Results : Analysis showed no statistically significant effects for any of the data . However , both active treatment groups showed a trend of improvement in the majority of the outcome measures . Conclusion : Active TENS was more effective than placebo TENS in decreasing VAS scores following each treatment although results were not statistically significant . Further work in this area is warranted and should include a larger number of participants in the form of a r and omized controlled clinical trial to determine the efficacy of this modality OBJECTIVES A preliminary examination of NMES and combined NMES/TENS for the management of chronic back pain . DESIGN Double-blind , placebo-controlled , r and omized repeated measures . SUBJECTS AND SETTING Consecutive sample of 24 chronic back pain patients ( 16 women and 8 men ) attending an outpatient pain clinic ( mean age 51.67 years , mean pain duration 3.83 years ) . All treatments were administered at home . INTERVENTIONS Subjects self-administered NMES , combined NMES/TENS , TENS , and placebo treatments . Each treatment had a duration of 5 consecutive hours per day over 2 consecutive days , with a 2-day hiatus between treatments to minimize carryover effects . MAIN OUTCOME MEASURES Pain reduction was assessed through pretreatment to posttreatment differences on the Present Pain Intensity ( PPI ) scale , and a visual analogue scale of Pain Intensity ( VAS-I ) . Posttreatment pain relief was assessed using a visual analogue scale of Pain Relief ( VAS-R ) . RESULTS Combined treatment , NMES , and TENS each produced significant pretreatment to posttreatment reductions in pain intensity as measured by both the PPI and VAS-I ( p < .05 ) . Combined treatment was superior to placebo on pain reduction ( p = .001 , p = .016 ) as well as pain relief ( p < .001 ) . Combined treatment was also superior to both TENS and NMES for pain reduction and pain relief ( p < .01 ) . NMES and TENS were superior only to placebo for pain relief ( p < .001 ) . CONCLUSIONS Combined NMES/TENS treatment consistently produced greater pain reduction and pain relief than placebo , TENS , or NMES . NMES alone , although less effective , did produce as much pain relief as TENS . Although preliminary , this pattern of results suggests that combined NMES/TENS may be a valuable adjunct in the management of chronic back pain . Further research investigating the effectiveness of both NMES and combined NMES/TENS seems warranted Objective This study was design ed to investigate the hypoalgesic effects of self-applied transcutaneous electrical nerve stimulation ( TENS ) on chronic low-back pain ( LBP ) in a multiple sclerosis ( MS ) population . Methods Ninety participants with probable or definite MS ( aged 21 to 78 y ) presenting with chronic LBP were recruited and r and omized into 3 groups ( n=30 per group ) : ( 1 ) low-frequency TENS group ( 4 Hz , 200 μs ) ; ( 2 ) high-frequency TENS group ( 110 Hz , 200 μs ) ; and ( 3 ) placebo TENS . Participants self-applied TENS for 45 minutes , a minimum of twice daily , for 6 weeks . Outcome measures were recorded at weeks 1 , 6 , 10 , and 32 . Primary outcome measures included : Visual Analog Scale for average LBP and the McGill Pain Question naire . Secondary outcome measures included : Visual Analog Scale for worst and weekly LBP , back and leg spasm ; Rol and Morris Disability Question naire ; Barthel Index ; Rivermead Mobility Index ; Multiple Sclerosis Quality of Life-54 Instrument , and a daily logbook . Data were analyzed blind using parametric and nonparametric tests , as appropriate . Results Results indicated a statistically significant interactive effect between groups for average LBP ( P=0.008 ) ; 1-way analysis of covariance did not show any significant effects at any time point once a Bonferonni correction was applied ( P>0.05 ) . However , clinical ly important differences were observed in some of the outcome measures in both active treatment groups during the treatment and follow-up periods . Discussion Although not statistically significant , the observed effects may have implication s for the clinical prescription and the use of TENS within this population In 23 patients with pancreatitis , daily pain for at least 3 months , and no abuse of alcohol , the pain-relieving effect of electroacupuncture ( 13 patients ) or transcutaneous electric nerve stimulation ( TENS ) ( 16 patients ) was studied . In two prospect i ve studies with a cross-over design , active acupuncture was compared with sham acupuncture , and TENS of the segmental points of the pancreas with sham treatment . Neither electroacupuncture nor TENS brought about pain relief that could substitute for or supplement medical treatment |
11,831 | 22,258,960 | The risk of developing new active brain lesions decreased over time but this data was obtained from single studies on Magnetic Resonance Imaging ( MRI ) , performed in subgroups of patients ; in spite of no effect on progression , the radiological data supported an effect on MRI parameters .
The safety profile reflects what is commonly reported in MS IFN-treated patients .
Recombinant IFN beta does not prevent the development of permanent physical disability in SPMS .
We were unable to verify the effect on cognitive function for the lack of comparable data .
This treatment significantly reduces the risk of relapse and of short -term relapse-related disability .
Overall , these results show that IFNs ' anti-inflammatory effect is unable to retard progression , when established .
We believe that this review gives conclusive evidence on the clinical efficacy of IFNs versus placebo in SPMS | BACKGROUND Therapy with either recombinant beta-1a or beta-1b interferons ( IFNs ) is worldwide approved for Relapsing Remitting Multiple Sclerosis ( RRMS ) .
A major unanswered question is whether this treatment is able to safely reverse or retard the progressive phase of the disease .
OBJECTIVES The main objective was to verify whether IFNs treatment in Secondary Progressive Multiple Sclerosis ( SPMS ) is more effective than placebo in reducing the number of patients who experience disability progression . | Objective : Interferon ( IFN ) beta has repeatedly shown benefit in multiple sclerosis ( MS ) in reducing the rate of relapse , the disease activity as shown with magnetic resonance imaging and , to some degree , the progression of disability ; however , it is unknown how much the therapeutic response depends on the dose , the subgroup involved , and the disease stage . This multicentre , double blind , placebo controlled study explored the dose−response curve by examining the clinical benefit of low dose IFN beta-1a ( Rebif ® ) , 22 μg subcutaneously once weekly , in patients with secondary progressive MS . Methods : A total of 371 patients with clinical ly definite SPMS were r and omised to receive either placebo or subcutaneous IFN beta-1a , 22 μg once weekly , for 3 years . Clinical assessment s were performed every 6 months . The primary outcome was time to sustained disability , as defined by time to first confirmed 1.0 point increase on the Exp and ed Disability Status Scale ( EDSS ) . Secondary outcomes included a sensitive disability measure and relapse rate . Results : Treatment had no beneficial effect on time to confirmed progression on either the EDSS ( hazard ratio ( HR ) = 1.13 ; 95 % confidence interval ( CI ) 0.82 to 1.57 ; p = 0.45 for 22 μg v placebo ) or the Regional Functional Status Scale ( HR = 0.93 ; 95 % CI 0.68 to 1.28 ; p = 0.67 ) . Other disability measures were also not significantly affected by treatment . Annual relapse rate was 0.27 with placebo and 0.25 with IFN ( rate ratio = 0.90 ; 95 % CI 0.64 to 1.27 ; p = 0.55 ) . The drug was well tolerated with no new safety concerns identified . No significant gender differences were noted . Conclusions : This patient population was less clinical ly active than SPMS population s studied in other trials . Treatment with low dose , IFN beta-1a ( Rebif ® ) once weekly did not show any benefit in this study for either disability or relapse outcomes , including a subgroup with preceding relapses . These results add a point at one extreme of the dose−response spectrum of IFN beta therapy in MS , indicating that relapses in this phase may need treatment with higher doses than in the initial phases Background : The recently completed placebo-controlled multicenter r and omized trial of interferon beta-1b ( Betaferon ) in 718 patients with secondary progressive MS shows significant delay of disease progression and reduction of relapse rate . This study provides an opportunity to assess the level of relationship between clinical and MRI outcomes in this cohort of patients with secondary progressive MS . Methods : Brain T2-weighted lesion volume was measured annually in all available patients , with visual analysis to identify any new or enlarging ( active ) T2 lesions at each annual time point . A subgroup of 125 patients had monthly gadolinium-enhanced , T1-weighted imaging at months 0 to 6 and 18 to 24 . Relapses were documented and exp and ed disability status scale ( EDSS ) was measured every 3 months . Results : For the annual MRI outcomes , a significant but modest correlation was identified between the change in T2 lesion volume from baseline to the final scan and the corresponding change from baseline in EDSS ( r = 0.17 , p < 0.0001 ) . There were significant correlations between the cumulative number of active T2 lesions and 1 ) change in EDSS ( r = 0.18 , p < 0.0001 ) and 2 ) relapse rate ( r = 0.24 , p < 0.0001 ) . In the subgroup of 125 patients undergoing monthly imaging , MRI lesion activity was correlated with relapse rate over months 0 to 24 ( r = 0.24 , p = 0.006 ) but not with change in EDSS . Conclusions : These results confirm that the clinical –MRI relationships previously identified in relapsing-remitting MS still are apparent in the secondary progressive phase of the disease and support the use of MRI as a relevant outcome measure . In view of the relatively modest nature of the correlations , it seems unwise to rely on such MRI measures alone as primary efficacy variables in secondary progressive MS trials Recently , the clinical efficacy of interferon beta-1b ( IFNbeta-1b ) was demonstrated for secondary progressive ( SP ) multiple sclerosis in a European multicentre study . We evaluated the effect of IFNbeta-1b treatment on the rate of development of hypointense T(1 ) MRI lesions , a putative marker of axonal damage . Unenhanced T(1)-weighted images were obtained in a subgroup of 95 multiple sclerosis patients from five centres at 6-month intervals ; this subgroup was similar to the total study population for all demographic , clinical and MRI parameters . An experienced observer blinded to the clinical data and treatment allocation measured volumes . The median baseline lesion load for hypointense T(1 ) lesions was 5.1 cm(3 ) for placebo-treated and 4.9 cm(3 ) for IFNbeta-1b-treated patients ( P = 0.56 ) . Placebo-treated patients showed an increase in T(1 ) lesion load by a median of 14 % per year ( P = 0.0002 compared with baseline ) ; this was reduced to 7.7 % per year in the IFNbeta-1b-treated patients ( P = 0.003 versus placebo ) . In the IFNbeta-1b arm there was a statistically significant correlation between absolute change in Exp and ed Disability Status Scale scores and T(1 ) lesion load by month 36 ( r = 0.38 , P = 0.0015 ) . In patients with SP multiple sclerosis , IFNbeta-1b treatment reduces the development of hypointense T(1 ) lesions , suggesting that reduced axonal damage in lesions may play a part in the beneficial effect that is observed clinical ly Several phase III studies have proven that the beta-interferons have positive effects on the number and severity of acute exacerbations of relapsing remitting multiple sclerosis . Recently the first study on the effectiveness of interferon beta-1b in secondary progressive multiple sclerosis was published . In a multicenter , double-blind , r and omized , Placebo-controlled study 718 patients with secondary progressive multiple sclerosis and an exp and ed disability status scale ( EDSS ) value between 3.0 and 6.5 were treated with either 8 Mio.interferon beta-1b or Placebo subcutaneously every second day for two to three years . The primary study end-point was the time until confirmed progression of the disease as signified by a one point increase of the EDSS value ( for initial EDSS values between 3.0 and 5.5 ) or 0.5 point increase when the initial EDSS value was between 6.0 and 6.5 . After two years an interim analysis showed a highly significant difference in delay of disease progression by nine to twelve months for the treatment group ( p = 0.0008 ) . This means that interferon beta-1b is the first recombinant beta-interferon to be shown effective in the treatment of secondary progressive multiple sclerosis Abstract Combination therapy may benefit the subgroup of patients with secondary progressive multiple sclerosis ( SPMS ) who do not respond to interferon beta ( IFNB ) . We performed a two-year study of azathioprine ( AZA ) combined with IFNB-1b in SPMS patients who had not responded well to IFNB-1b alone . Patients with SPMS were eligible for this non-controlled prospect i ve study if they had two or more relapses requiring corticosteroid treatment or deteriorated by at least 0.5 points on the Exp and ed Disability Status Scale ( EDSS ) while on IFNB-1b in the year preceeding the study . Patients were to continue treatment with IFNB-1b ( 8 MIU qod , subcutaneous ) and received AZA ( 50 mg tid , oral ) . Safety was assessed in terms of adverse reactions and laboratory measures grade d according to the WHO toxicity scale . Efficacy was explored by changes in relapse rate , EDSS , 9-hole peg test ( 9-HPT ) , neuropsychological scores , and magnetic resonance imaging ( MRI ) results . Neutralizing antibodies ( NAB ) were measured . Ten SPMS patients ( 6 females ) with a median EDSS score of 4.5 were enrolled . One patient withdrew because of gastrointestinal complaints , one was withdrawn owing to poor compliance , and 8 patients completed therapy . The only frequent side effect was lymphopenia , reported at least once in all patients . Annual relapse rate was reduced by approximately 50 % in the second year . There was a significant trend for EDSS increase . Total lesion load measured by MRI decreased at 12 and 24 months ; only one patient had active lesions . No changes were seen in the 9-HPT . There was a significant improvement in neuropsychological tests after 24 months ( p = 0.045 ) . One patient tested positive for NAB throughout the study , and transient NAB were detected in 4 patients . In conclusion , combination therapy with IFNB-1b and AZA was safe and generally well tolerated in patients with SPMS . Strict clinical and laboratory monitoring is recommended during this combination therapy Background Evidence for efficacy of disease-modifying drugs in multiple sclerosis ( MS ) comes from trials of short duration . We report results from a 16 y , retrospective follow-up of the pivotal interferon β-1b ( IFNB-1b ) study . Methods The 372 trial patients were r and omly assigned to placebo ( n=123 ) , IFNB-1b 50 μg ( n=125 ) or IFNB-1b 250 μg ( n=124 ) subcutaneously every other day for at least 2 y. Some remained r and omised for up to 5 y but , subsequently , patients received treatment according to physicians ' discretion . Patients were re-contacted and asked to participate . Efficacy related measures included MRI parameters , relapse rate , the Exp and ed Disability Status Scale , the Multiple Sclerosis Functional Composite Measure and conversion to secondary progressive MS . Results Of the 88.2 % ( 328/372 ) of patients who were identified , 69.9 % ( 260/372 ) had available case report forms . No differences in outcome between original r and omisation groups could be discerned using st and ard disability and MRI measures . However , mortality rates among patients originally treated with IFNB-1b were lower than in the original placebo group ( 18.3 % ( 20/109 ) for placebo versus 8.3 % ( 9/108 ) for IFNB-1b 50 μg and 5.4 % ( 6/111 ) for IFNB-1b 250 μg ) . Conclusions The original treatment assignment could not be shown to influence st and ard assessment s of long-term efficacy . On- study behaviour of patients was influenced by factors that could not be controlled with the sacrifice of r and omisation and blinding . Mortality was higher in patients originally assigned to placebo than those who had received IFNB-1b 50 μg or 250 μg . The data set provides important re sources to explore early predictors of long-term outcome This manuscript describes the outline of a double-blind , placebo-controlled , ( European ) , multicentre phase III study to evaluate the safety and efficacy of 8 MIU of interferon beta-Ib given subcutaneously every other day for 3 years in patients with secondary progressive multiple sclerosis . The primary efficacy variable of this trial is the time to confirmed neurological deterioration as documented by the Exp and ed Disability Status Scale . The essentials of the study design are presented , including the rationale for the performance of the study and the selection of both clinical and magnetic resonance imaging outcome parameters Objective : To investigate the relationship between neutralizing antibodies ( NAB ) and disease progression , relapses , and MR measures of MS . Methods : Sequential serum sample s from all 718 patients of the European Study Group in Interferon β-1b in Secondary Progressive MS were analyzed to investigate relations between NAB and disease progression , relapses , and MR measures . Results : This study showed no attenuating effect of NAB development on progression in disability . The effects of NAB on relapse rate showed substantial variation , depending on the statistical approach and definition of positivity , though analyses comparing low- and high-NAB+ periods with NAB− periods suggested a titer-related effect . MR T2 lesion volume changes from baseline were significantly higher for NAB+ patients but remained lower than for placebo patients . A substantial proportion of NAB+ patients became NAB−. No untoward effect of NAB development on safety was observed . Conclusion : These results support the conclusion that even though high NAB titers appear to have impact on treatment efficacy with respect to relapses , treatment decisions should be based primarily on clinical grounds Objective : To determine the percentage of patients with residual deficits following multiple sclerosis ( MS ) exacerbations and the magnitude of those deficits using a data base of pooled placebo patients from clinical trials . Methods : A data base of patients assigned to the placebo group in several r and omized clinical trials was queried to determine those patients with Exp and ed Disability Status Scale ( EDSS ) and Scripps Neurologic Rating Scale assessment s prior to , at the time of , and after an acute exacerbation of MS . The extent of deficit present at these time points was compared to determine the acute effect of exacerbations and the degree of persistent disability . Results : Forty-two percent of patients had residual deficit of at least 0.5 and 28 % had residual of ≥1.0 EDSS units , at an average of 64 days after an exacerbation . The results were reproduced across subsequent exacerbations and were sustained over time . The subgroup of patients with measurable change in EDSS during the exacerbation had more extensive residual impairment on the follow-up visits . Similar results were seen when the Scripps score was examined . Conclusion : MS exacerbations produce a measurable and sustained effect on disability BACKGROUND The Multiple Sclerosis Functional Composite ( MSFC ) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation ( Timed 25-Foot Walk ) , arm function ( 9-Hole Peg Test ) , and cognitive function ( Paced Auditory Serial Addition Test ) . The MSFC is the primary outcome measure in the ongoing multinational phase 3 trial of interferon beta-1a ( Avonex ) in patients with secondary progressive MS . OBJECTIVE To assess the practice effects , reliability , and validity of the MSFC clinical outcome measure . DESIGN Examining technicians underwent formal training using st and ardized material s. The MSFC was performed according to a st and ardized protocol . The 436 patients enrolled in the International Multiple Sclerosis Secondary Progressive Avonex Controlled Trial underwent 3 prebaseline MSFC testing sessions before r and omization . RESULTS Practice effects were evident initially for the MSFC but stabilized by the fourth administration . The Paced Auditory Serial Addition Test demonstrated the most prominent practice effects . The reliability of the MSFC was excellent , with an intraclass correlation coefficient for session 3 ( final prebaseline session ) vs session 4 ( baseline ) of 0.90 . The MSFC at baseline correlated moderately strongly with the Kurtzke Exp and ed Disability Status Scale . Among the MSFC components , the Timed 25-Foot Walk correlated most closely . Correlations among the 3 MSFC components were weak , suggesting they assess distinct aspects of neurologic function in patients with MS . CONCLUSIONS The MSFC demonstrated excellent intrarater reliability in this multinational phase 3 trial . Three prebaseline testing sessions were sufficient to compensate for practice effects . The pattern of correlations among the MSFC , its components , and the Kurtzke Exp and ed Disability Status Scale supported the validity of the MSFC OBJECTIVE This article describes the design of and difficulties inherent in the execution of a long-term , observational trial that sought to assess the validity of short-term measures of multiple sclerosis ( MS ) ( eg , relapse rate , inflammatory lesions ) for long-term disease outcomes . METHODS In the original double-blind , placebo-controlled interferon (IFN)-p1b study , 372 patients with relapsing-remitting MS ( Exp and ed Disability Status Scale score 0.0 - 5.5 ) were r and omly assigned to IFN-beta1b 50 ug ( n = 125 ) , IFN-beta1b 250 microg ( n = 124 ) , or placebo ( n = 123 ) for 2 years . These patients were recruited 16 years later for participation in this long-term follow-up ( LTF ) study , which had no exclusion criteria or drug interventions . RESULTS The 11 centers identified 88.2 % ( 328/372 ) of the original study patients at LTF ; however , 10.8 % ( n = 40 ) refused to participate and 9.4 % ( n = 35 ) were deceased . Detailed evaluations were available for 260 patients , which included 7 deceased patients . No differences in demographic or baseline disease characteristics were found between individuals who did and did not participate in the LTF . More patients r and omly assigned to placebo in the original trial were deceased ( 20/123 [ 16.3 % ] ) than those assigned to IFN-beta1b 50 microg ( 9/125 [ 7.2 % ] ; uncorrected P = 0.044 ) or IFN-beta1b 250 microg ( 6/124 [ 4.8 % ] ; uncorrected P = 0.003 ) . CONCLUSIONS Although most patients ( 88.2 % ) were identified at LTF , ascertainment was incomplete . This was attributable to patients ' refusal to participate , loss to follow-up , or death . Delays in the registration of death data and recent privacy legislation provided further barriers . Mortality was lower for patients originally r and omized to receive IFN-beta1b rather than placebo . We recommend that all short-term trials on chronic diseases include provisions for LTF Background The natural history of cognitive impairment in multiple sclerosis ( MS ) and its relationship with disease activity is not well known . In this study , we evaluate a prospect i ve cohort of 44 MS patients who were followed every 3 months for 2 years . Cognitive evaluation was done at baseline and by the end of the study using the Brief Repeatable Battery-Neuropsychology . Clinical evaluation included assessment of new relapses and changes in disability ( Extended Disability Status Scale ( EDSS ) ) confirmed at 6 months . Results We found that verbal memory performance deteriorates after 2 years in patients with MS . These changes were observed in stable and active patients both in terms of relapses and disability progression , even at the beginning of the disease , and in patients with or without cognitive impairment at study entry . Attention and executive functions measured with the symbol digit modality test ( SDMT ) declined after 2 years in patients with confirmed disability progression . Furthermore , SDMT performance correlated with the EDSS change . Conclusions Our findings indicate that verbal memory steadily declines in patients with MS from the beginning of the disease and independently of other parameters of disease activity Objective : To assess the safety , tolerability , and biologic and clinical activity of a solubilized complex comprised of human leukocyte antigen — DR2 with myelin basic protein84 - 102 (AG284)in patients with secondary progressive MS . Background : Soluble species-specific major histocompatibility complex myelin basic protein91 - 103 complexes ameliorate disease in a dose-dependent manner when administered to SJL/J mice with chronic relapsing experimental allergic encephalomyelitis . Preincubation with AG284 reduces the proliferative response of a DR2-restricted , myelin basic protein84 - 102–reactive T cell clone , derived from a MS patient , to myelin basic protein84 - 102 in the presence of autologous antigen-presenting cells . Methods : Thirty-three patients with secondary progressive MS were r and omly assigned to receive three alternate day IV doses of AG284 or placebo in a double-masked dose escalation study . The primary outcome was safety and tolerability . Secondary outcomes included a comparison of pre- and post-treatment gadolinium-enhanced brain MRI activity , Kurtzke Exp and ed Disability Status Scale , and Nine Hole Peg Test scores . Results : The frequency of adverse events was similar in the AG284 and placebo recipients . No significant treatment effect was detected by Exp and ed Disability Status Scale , Nine Hole Peg Test , or number of new gadolinium-enhancing MRI lesions . Conclusions : AG284 as administered during this study was safe and well tolerated . Further studies are warranted to determine the biologic activity and clinical efficacy of this potential treatment for MS Inflammation and neurodegeneration may have differential impacts on disease evolution in the different forms of multiple sclerosis . However , a beneficial effect of immunomodulatory drugs should not be ruled out in primary progressive multiple sclerosis . Our aim is to investigate the safety and efficacy of interferon beta-1b in primary progressive multiple sclerosis . We conducted a double-blind , stratified , r and omized , parallel group , phase II pilot study where patients with primary progressive multiple sclerosis or ‘ transitional ’ forms of multiple sclerosis received interferon beta-1b at doses of 8 MIU or placebo for 24 months . The main objective of the study was to investigate the safety and tolerability of interferon beta-1b . The primary efficacy variable was the time to neurological deterioration ( Exp and ed Disability Status Scale ) confirmed at 3 months . Seventy-three patients were included and three dropped out the study . More patients in the treatment arm had at least one related adverse event ( 94.4 % versus 45.9 % ; p < 0.001 ) ; no other significant differences in safety endpoints were observed . Time to neurological deterioration was not different between trial arms ( log-rank test , p = 0.3135 ) . Statistically significant differences favoring treatment were observed for the Multiple Sclerosis Functional Composite score at several timepoints , T1 and T2 lesion volume changes at 12 and 24 months , mean number of active lesions and proportion of patients with active lesions at 24 months . We conclude that interferon beta-1b is safe and well tolerated in patients with primary progressive multiple sclerosis and transitional multiple sclerosis . Positive effects of interferon beta on secondary clinical and magnetic resonance imaging outcomes were observed , but a beneficial effect on Exp and ed Disability Status Scale progression was not demonstrated OBJECTIVE To assess safety and immune modulation by BHT-3009 , a tolerizing DNA vaccine encoding full-length human myelin basic protein , in patients with multiple sclerosis ( MS ) . DESIGN The study was a r and omized , double-blind , placebo-controlled trial . Subjects receiving placebo were crossed over into an active arm after treatment unblinding . SETTING The trial was conducted at 4 academic institutions within North America . Patients Thirty patients with relapsing-remitting or secondary progressive MS who were not taking any other disease-modifying drugs were enrolled in the trial . Further , the patients were required to have either 1 to 5 gadolinium-enhancing lesions on screening brain magnetic resonance imaging ( MRI ) , a relapse in the previous 2 years , or disease worsening in the previous 2 years . INTERVENTIONS BHT-3009 was administered as intramuscular injections at weeks 1 , 3 , 5 , and 9 after r and omization into the trial , with or without 80 mg of daily oral atorvastatin calcium in combination . Three dose levels of BHT-3009 were tested ( 0.5 mg , 1.5 mg , and 3 mg ) . MAIN OUTCOME MEASURES The primary outcome measures were safety and tolerability of BHT-3009 . Secondary outcome measures included the number and volume of gadolinium-enhanced lesions on MRI , relapses , and analysis of antigen-specific immune responses . RESULTS BHT-3009 was safe and well tolerated , provided favorable trends on brain MRI , and produced beneficial antigen-specific immune changes . These immune changes consisted of a marked decrease in proliferation of interferon-gamma-producing , myelin-reactive CD4 + T cells from peripheral blood and a reduction in titers of myelin-specific autoantibodies from cerebral spinal fluid as assessed by protein microarrays . We did not observe a substantial benefit of the atorvastatin combination compared with BHT-3009 alone . CONCLUSION In patients with MS , BHT-3009 is safe and induces antigen-specific immune tolerance with concordant reduction of inflammatory lesions on brain MRI Background : Visual dysfunction is one of the most common causes of disability in multiple sclerosis ( MS ) . The Multiple Sclerosis Functional Composite ( MSFC ) , a new clinical trial outcome measure , does not currently include a test of visual function . Objective : To examine contrast letter acuity as a c and i date visual function test for the MSFC . Methods : Binocular contrast letter acuity testing ( Sloan charts ) was performed in a subgroup of participants from the International Multiple Sclerosis Secondary Progressive Avonex Controlled Trial ( IMPACT Sub study ) and in MS patients and disease-free control subjects from a cross-sectional study of visual outcome measures ( Multiple Sclerosis Vision Prospect i ve cohort [ MVP cohort ] ) . High-contrast visual acuity was measured in both studies ; MVP cohort participants underwent additional binocular testing for contrast sensitivity ( Pelli – Robson chart ) , color vision ( D-15 desaturated test ) , and visual field ( Esterman test , Humphrey Field Analyzer II ) . Results : Contrast letter acuity ( Sloan charts , p < 0.0001 , receiver operating characteristic curve analysis ) and contrast sensitivity ( Pelli – Robson chart , p = 0.003 ) best distinguished MS patients from disease-free control subjects in the MVP cohort . Correlations of Sloan chart scores with MSFC and Exp and ed Disability Statue Scale ( EDSS ) scores in both studies were significant and moderate in magnitude , demonstrating that Sloan chart scores reflect visual and neurologic dysfunction not entirely captured by the EDSS or MSFC . Conclusions : Among clinical measures , contrast letter acuity ( Sloan charts ) and contrast sensitivity ( Pelli – Robson chart ) demonstrate the greatest capacity to identify binocular visual dysfunction in MS . Sloan chart testing also captures unique aspects of neurologic dysfunction not captured by current EDSS or MSFC components , making it a strong c and i date visual function test for the MSFC The recently completed European trial of interferon beta-1b ( IFNbeta-1b ) in patients with secondary progressive multiple sclerosis ( SP multiple sclerosis ) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI . Unenhanced T(1)-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres ; imaging was performed at 6-month intervals from month 0 to month 36 . A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point , using an algorithm with a high level of reproducibility and automation . There was a significant and progressive reduction in cerebral volume in both placebo and treated groups , with a mean reduction of 3.9 and 2.9 % , respectively , by month 36 ( P = 0.34 between groups ) . Exploratory subgroup analyses indicated that patients without gadolinium ( Gd ) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group ( mean reduction at month 36 : placebo 5.1 % , IFNbeta-1b 1.8 % , P < 0.05 ) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNbeta-1b ( placebo 2.6 % , IFNbeta-1b 3.7 % ; P > 0.05 ) . These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis . This finding is concordant with previous observations that disease progression , although delayed , is not halted by IFNbeta . The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNbeta-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug . Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease Objective : To evaluate the efficacy and safety of interferon beta-1b ( IFNβ-1b ) in subjects with secondary progressive multiple sclerosis ( SPMS ) . Methods : This 3-year , multicenter , double-blind , placebo-controlled , r and omized trial of IFNβ-1b included 939 subjects from the United States and Canada with SPMS and Exp and ed Disability Status Scale ( EDSS ) scores ranging from 3.0 to 6.5 . Subjects were r and omly assigned to receive either placebo or IFNβ-1b ( 250 μg or 160 μg/m2 body surface area ) , administered subcutaneously every other day . The primary outcome was time to progression by ≥1.0 EDSS point ( 0.5 point if EDSS score was 6.0 to 6.5 at entry ) confirmed at 6 months . Secondary outcomes included mean change in EDSS score from baseline , relapse-related measures , MRI activity , and a st and ardized neuropsychological function test . Results : There was no significant difference in time to confirmed progression of EDSS scores between placebo-treated patients and either of the IFNβ-1b treatment groups . However , IFNβ-1b treatment result ed in improvement on secondary outcome measures involving clinical relapses , newly active MRI lesions , and accumulated burden of disease on T2-weighted MRI . Effects were similar for both IFNβ-1b treatment groups . Neutralizing antibodies to IFNβ-1b were detected in 23 % of 250-μg and 32 % of 160-μg/m2 recipients , but their presence did not consistently affect clinical or MRI outcomes . IFNβ-1b was also well tolerated at both doses . Conclusions : Although no treatment benefit was seen on the time to confirmed progression of disability , relapse- and MRI-related outcomes showed significant benefit with both dosing regimens tested , a result consistent with the outcomes of earlier clinical trials Acetylcholinesterase inhibitors are used to treat dementia associated with Alzheimer 's disease , but their cognitive benefits may extend to additional disorders such as multiple sclerosis ( MS ) . A single-center double-blind placebo-controlled r and omized clinical trial evaluated the effectiveness of donepezil in a sample of 69 MS persons selected for initial memory difficulties . Subjects received neuropsychological assessment at baseline and after 24 weeks of treatment . The primary outcome was change in total recall on the Selective Reminding Test , a measure of verbal learning and memory . Secondary outcomes included other neuropsychological tests from the Brief Repeatable Battery , patient-reported change in memory , and physician-reported impression of cognitive change . Donepezil improved memory performance on the SRT compared to placebo . This benefit remained significant after controlling for various covariates including Exp and ed Disability Status Scale ( EDSS ) , MS subtype , interferon beta use , treatment group beliefs , gender , baseline selected reminding test ( SRT ) score , and reading ability . Subjects on donepezil were more likely to report memory improvement ( 65.7 % ) than those on placebo ( 32.4 % ) . The clinician also reported cognitive improvement in more donepezil ( 54.3 % ) than placebo ( 29.4 % ) subjects . No serious adverse events related to study medication occurred . However , more donepezil ( 34.3 % ) than placebo ( 8.8 % ) subjects reported unusual/abnormal dreams . Donepezil improved learning and memory in MS patients with initial cognitive difficulties in a single-center clinical trial . Replication of results in a larger multi-center investigation is warranted in order to more definitively assess the efficacy of this intervention Objective : To evaluate the efficacy and safety of combination therapy with pulse cyclophosphamide given with methylprednisolone ( MP ) and interferon beta (IFNβ)-1a in multiple sclerosis ( MS ) patients with active disease during IFNβ monotherapy . Methods : This was a r and omized , single-blind , parallel-group , multicenter trial in MS patients with a history of active disease during IFNβ treatment . Patients were r and omized to either cyclophosphamide 800 mg/m2 plus methylprednisolone 1 g IV ( CY/MP ) or methylprednisolone once a month for six months and then followed for an additional 18 months . All patients received three days of methylprednisolone 1 g IV at screening and 30 mcg IFNβ-1a IM weekly for the entire 24 months . The primary endpoint was change from baseline in the mean number of gadolinium-enhancing ( Gd+ ) lesions . Secondary clinical endpoints included time to treatment failure . Results : Fifty-nine patients were r and omized to treatment : 30 to CY/MP and 29 to MP . Change from baseline in the number of Gd+ lesions was significantly different between treatment groups at three ( P=0.01 ) , six ( P=0.04 ) and 12 months ( P=0.02 ) , with fewer lesions in the CY/MP group . The cumulative rate of treatment failure was significantly lower in the CY/MP group compared with the MP group ( rate ratio = 0.30 ; 95 % confidence interval , 0.12 - 0.75 ; P=0.011 ) . CY/MP treatment was well tolerated . Conclusion : Combination therapy with CY/MP and IFNβ-1a decreased the number of Gd+ lesions and slowed clinical activity in patients with previously active disease on IFNβ alone Background : Inferences about long-term effects of therapies in multiple sclerosis ( MS ) have been based on surrogate markers studied in short-term trials . Preventing progressive disability is the key therapeutic goal but there remains no vali date d definition for its measurement in a trial context . Meanwhile , MS trials continue to shorten and to depend on unvali date d surrogates . Since there have been no treatment cl aims for improving unremitting disability , worsening of disability in the placebo/control arm must occur for effectiveness on this outcome to be shown . Methods : We examined widely-used clinical surrogates of long-term disability progression in individual patients with MS within a unique data base from the placebo arms of 31 r and omized clinical trials . Results : Detection of treatment effects in secondary progressive MS trials is undermined by noise in disability measurement . Whereas existing measures can be partially vali date d in secondary progressive MS , this is not the case in relapsing-remitting MS . Here , examination of widely used definitions of treatment failure demonstrated that disability progression was no more likely than similarly defined improvement . Existing definitions of disease progression in short-term intervention trials in relapsing-remitting patients reflect r and om variation , measurement error , and remitting relapses . Conclusion : Clinical surrogates of unremitting disability used in trials of relapsing-remitting multiple sclerosis can not be vali date d. Trials have been too short or degrees of disability change too small to measure the key outcomes . These analyses highlight the difficulty in determining effectiveness of therapy in chronic diseases Background Interferon & bgr;-1a ( IFN&bgr;-1a , Avonex ) is efficacious in relapsing forms of MS . Studies of other IFN&bgr ; preparations in secondary progressive MS ( SPMS ) yielded conflicting results . This study was undertaken to determine whether IFN&bgr;-1a slowed disease progression in SP-MS . Methods A total of 436 subjects with SPMS and Exp and ed Disability Status Scale ( EDSS ) score 3.5 to 6.5 were r and omized to receive IFN&bgr;-1a ( 60 & mgr;g ) or placebo by weekly intramuscular injection for 2 years . The primary outcome measure , used for the first time in a large-scale MS trial , was baseline to month 24 change in the MS Functional Composite ( MSFC ) , comprising quantitative tests of ambulation ( Timed 25-Foot Walk ) , arm function ( Nine-Hole Peg Test [ 9HPT ] ) , and cognition ( Paced Auditory Serial Addition Test [ PASAT ] ) . Results Median MSFC Z-score change was reduced 40.4 % in IFN&bgr;-1a subjects ( −0.096 vs −0.161 in placebo subjects , p = 0.033 ) , an effect driven mainly by the 9HPT and PASAT . There was no discernible benefit on the EDSS , which in this range principally reflects walking ability . IFN&bgr;-1a subjects had 33 % fewer relapses ( p = 0.008 ) . There was significant benefit on eight of 11 MS Quality of Life Inventory subscales . New or enlarging T2-hyperintense brain MRI lesions and gadolinium-enhancing lesions were reduced at months 12 and 24 ( both p < 0.001 ) . IFN&bgr;-1a was well tolerated by the majority of subjects . Neutralizing antibodies developed in 3.3 % of IFN&bgr;-1a – treated subjects . Conclusions IFN&bgr;-1a demonstrated benefit on MSFC progression , relapses , quality of life , and MRI activity in SPMS Background : Based on a prospect ively planned interim analysis , the European study of interferon β-1b ( IFNβ-1b ) provided evidence that the treatment delays neurologic deterioration in patients with secondary progressive MS ( SPMS ) . The authors analyzed all data collected until closure of the double-blind study to further scrutinize the consistency of the findings . Methods : The multicenter , double-blind , r and omized , placebo-controlled trial treated patients for up to 36 months . The primary and all secondary endpoints of this study were evaluated using the data set at study termination , with a mean follow-up under double-blind conditions of 1054 ± 199 and 1068 ± 176 days for the placebo and IFNβ-1b group . Alternative and more dem and ing definitions of disease progression were explored . Confirmed progression was analyzed in subgroups according to baseline demographics and baseline indicators of disease activity . Results : Forty-eight of 358 placebo and 40 of 360 IFNβ-1b – allocated patients were lost to follow-up . Time to confirmed 1.0-point Exp and ed Disability Status Scale ( EDSS ) progression for patients receiving IFNβ-1b was delayed ( p = 0.007 ) . The proportion of patients with a confirmed 2.0-point EDSS progression was approximately 27 % lower for the group treated with IFNβ-1b , both including and excluding EDSS data collected during relapses . The proportion of patients with either progression or relapses decreased by nearly 30 % in patients treated with IFNβ-1b compared with placebo . Analysis of subgroups suggests that patients with higher pre study disease activity ( more than two relapses or EDSS progression by more than 1.0 point or both ) seem to have a more pronounced treatment effect . Conclusion : Analysis of the data set at study termination including additional post hoc outcome measures is consistent with the original findings , thus supporting the conclusion that treatment with IFNβ-1b is effective in patients with SPMS fulfilling the inclusion criteria of this study Background : Magnetization transfer ( MT ) MRI can provide in vivo markers reflecting the severity of irreversible , MS-related brain damage occurring within and outside T2-visible lesions . Objective : To assess the effect of interferon ( IFN ) β-1b treatment on the accumulation of brain damage in patients with secondary progressive ( SP ) MS , measured using MT MRI . Methods : Eighty-two patients with SPMS from five centers participating in a European , multicenter , double-blind , placebo-controlled trial of IFNβ-1b in SPMS underwent brain T2-weighted and MT MRI at baseline . Evaluable follow-up data were available for 75 patients at 12 months , 54 at 24 months , and 47 at 36 months . MT MRI scans were postprocessed and analyzed to obtain histograms of MT ratio ( MTR ) values from the whole brain . A region of interest – based analysis of MTR values from the normal-appearing white matter ( NAWM ) was also performed . Results : In both the treatment arms , there was a decrease of average brain MTR values from baseline to month 24 ( mean change −4.9 % ) and month 36 ( mean change −4.3 % ) . These changes were significant for the placebo group at both timepoints and for the IFNβ-1b group at month 24 only , with no significant treatment effect . A decrease of NAWM MTR was also observed , with no significant difference between the two treatment arms . Conclusion : In this cohort of patients with secondary progressive MS , interferon β-1b did not show an overall effect on the worsening of magnetization transfer MRI measures , when compared with placebo . The data show that change in magnetization transfer ratio is a promising tool for monitoring disease evolution in secondary progressive MS and that the information obtained from magnetization transfer MRI complements that obtained from MRI measures of lesion load and inflammation Objective : To investigate disease progression and risk factors in a large geographically based population with multiple sclerosis ( MS ) , using two different inception points— clinical onset and date of birth . Methods : The authors review ed a data base of subjects with definite MS and symptom onset prior to July 1988 . The main outcome was sustained progression to Exp and ed Disability Status Scale ( EDSS ) 6 ( requires a cane ) , using the date of birth and date of MS onset as inception points in separate analyses . Risk factors examined were sex , relapsing vs primary progressive course , onset age , and onset symptoms . Results : The study included 2,837 patients , followed prospect ively for 22,723 patient years . The median time to EDSS 6 was 27.9 years , 15 years after onset ; only 21 % reached EDSS 6 , and by age 50 , 28 % required a cane . Men progressed 38 % more quickly than women from onset ( p < 0.0005 ) , yet both required canes at similar ages : 58.8 years for men and 60.1 for women ( p = 0.082 ) . A younger onset age predicted a slower progression , but those older at onset were consistently older when reaching EDSS 6 . A primary progressive course predicted a more rapid progression from both onset ( p < 0.0005 ) and birth ( hazard ratio = 2.7 [ 95 % CI : 2.2 to 3.3 ] ) . No onset symptom consistently predicted progression . Conclusion : Disability progression in multiple sclerosis ( MS ) accrued more slowly than found in earlier longitudinal studies . The authors also challenged two fundamental concepts in MS , demonstrating that neither male sex nor older onset age was associated with worse disease outcome Background The IMPACT study demonstrated the benefit of interferon beta-1a ( IFNβ-1a , Avonex ® ) two-year change in disability measured by the Multiple Sclerosis Functional Composite ( MSFC ) in secondary progressive multiple sclerosis ( SP-MS ) and health-related quality of life ( HRQoL ) measured by the Multiple Sclerosis Quality of Life Inventory ( MSQLI ) . The IMPACT data permit a detailed assessment of the relation between clinical and self-reported measures . Methods IMPACT was an international r and omized , double-blind , placebo-controlled trial of SP-MS patients . As the MSQLI is only in English , this report includes US and Canadian subjects . Subjects were r and omized to weekly intramuscular ( i m ) injections of INb-1a ( 60 mg ) or placebo for 24 months . Results At baseline and follow-up , MSQLI correlations were generally stronger with the EDSS than with the MSQLI , MSFC but comparable with MSFC components . Combining the two groups , MSQLI changes for those in the best and worst MSFC change quartiles demonstrated a statistical difference for six of the 11 MSQLI scales . Linear regression demonstrated that EDSS change from baseline to month-24 scores was correlated with change in two MSQLI components . Conclusion These data support the appropriateness of using the MSQLI with individuals who have SP-MS Objective : A double-blind , placebo-controlled phase II study was conducted in 168 patients , most with relapsing-remitting MS , to evaluate whether lenercept would reduce new lesions on MRI . Background : Tumor necrosis factor ( TNF ) has been implicated in MS pathogenesis , has been identified in active MS lesions , is toxic to oligodendrocytes in vitro , and worsens the severity of experimental allergic encephalomyelitis ( EAE ) in animals . Lenercept , a recombinant TNF receptor p55 immunoglobulin fusion protein ( sTNFR-IgG p55 ) , protects against EAE . Methods : Patients received 10 , 50 , or 100 mg of lenercept or placebo IV every 4 weeks for up to 48 weeks . MRI scans and clinical evaluations were performed at screening , at baseline , and then every 4 weeks ( immediately before dosing ) through study week 24 . Results : There were no significant differences between groups on any MRI study measure , but the number of lenercept-treated patients experiencing exacerbations was significantly increased compared with patients receiving placebo ( p = 0.007 ) and their exacerbations occurred earlier ( p = 0.006 ) . Neurologic deficits tended to be more severe in the lenercept treatment groups , although this did not affect Exp and ed Disability Status Scale scores . Anti-lenercept antibodies were present in a substantial number of treated patients ; serum lenercept trough concentrations were detectable in only a third . Adverse events that increased in frequency in treated patients included headache , nausea , abdominal pain , and hot flushes . Conclusions : Lenercept failed to be beneficial , but insight into the role of TNF in MS exacerbations was gained Two multicenter , r and omized , double-blind , placebo-controlled phase III studies to evaluate the safety and efficacy of 6 and 12 MIU of recombinant human interferon beta ( r-hIFN-beta ) ( Rebif ) given subcutaneously three times per week , in patients with MS , are described . In one study , patients with relapsing-remitting multiple sclerosis are treated for 24 months ; the primary efficacy end point is the number of exacerbations . In the other study patients with secondary progressive multiple sclerosis are treated for 36 months ; the primary efficacy end point is time to sustained progression in disability as determined by the Exp and ed Disability Status Scale ( EDSS ) . Both studies are conducted in centers in Europe , Australia and Canada Fear of pain from injections may affect adherence to needed drug therapy . A single-blind , placebo-controlled crossover study was conducted to evaluate the efficacy of EMLA cream in reducing the fear and pain associated with intramuscular ( IM ) injection during administration of interferon beta-1a to patients with multiple sclerosis . Patients rated fear of injection on a visual analog scale before the injection and rated injection pain following the injection . With the application of EMLA cream , the mean pain-of-injection score was found to be significantly lower than the mean fear-of-injection score . The 18 patients who completed the study experienced a statistically significant decrease in both scores . This study suggests that the use of EMLA cream may reduce the pain and fear associated with IM injections The results of multicenter study of Rebif 22 micrograms in Russia have been reported . 167 multiple sclerosis patients have received Rebif 22 micrograms three times a week for 1 year . This study provides evidence for reduction of the relapse rate in patients with relapsing/remitting and secondary progressive multiple sclerosis . The tendency to the decrease of the severity of relapses , less need for steroid use and the decrease of EDSS score in patients with relapsing/remitting multiple sclerosis have been shown . In general Rebif 22 micrograms was tolerated well Abstract —Depression is a suspected side effect of treatment with interferon & bgr;1a in MS . However , an association with depression has not been confirmed by rigorous studies . During the SPECTRIMS clinical trial of interferon & bgr;1a ( Rebif ) in secondary progressive MS , depression ratings were obtained from 365 subjects treated either with interferon & bgr;1a or with placebo . No significant differences between groups emerged during 36 months of follow-up . These data suggest that depression is not a side effect of interferon & bgr;1a BACKGROUND The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment ( BENEFIT ) trial investigated the effect of treatment with interferon beta-1b after a clinical ly isolated syndrome . The 5-year active treatment extension compares the effects of early and delayed treatment with interferon beta-1b on time to clinical ly definite multiple sclerosis ( CDMS ) and other disease outcomes , including disability progression . METHODS Patients with a first event suggestive of multiple sclerosis and a minimum of two clinical ly silent lesions in MRI were r and omly assigned to receive interferon beta-1b 250 microg ( n=292 ; early treatment ) or placebo ( n=176 ; delayed treatment ) subcutaneously every other day for 2 years , or until diagnosis of CDMS . All patients were then eligible to enter a prospect ively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after r and omisation . Patients and study personnel remained unaware of initial treatment allocation throughout the study . Primary endpoints were time to CDMS , time to confirmed disability progression measured with the exp and ed disability status scale , and the functional assessment of multiple sclerosis trial outcomes index ( FAMS-TOI ) at 5 years . Analysis of the primary endpoints was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00185211 . FINDINGS 235 ( 80 % ) patients from the early treatment and 123 ( 70 % ) from the delayed treatment group completed the 5-year study . Early treatment reduced the risk of CDMS by 37 % ( hazard ratio [ HR ] 0.63 , 95 % CI 0.48 - 0.83 ; p=0.003 ) compared with delayed treatment . The risk for confirmed disability progression was not significantly lower in the early treatment group ( 0.76 , 0.52 - 1.11 ; p=0.177 ) . At 5 years , median FAMS-TOI scores were 125 in both groups . No significant differences in other disability related outcomes were recorded . Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b . INTERPRETATION Effects on the rate of conversion to CDMS and the favourable long-term safety and tolerability profile support early initiation of treatment with interferon beta-1b , although a delay in treatment by up to 2 years did not affect long-term disability outcomes . FUNDING Bayer Schering Pharma A r and omized placebo-controlled trial of interferon-beta1b was performed on 718 patients with secondary progressive multiple sclerosis with follow-up of up to 3 years . In addition to clinical variables , serial magnetic resonance imaging ( MRI ) studies were performed to determine the effect of treatment on the pathological evolution of the disease . All patients eligible for MRI had annual proton density/T2-weighted brain scans from which total lesion volume was measured and the number of new and enlarging lesions noted . A subgroup of 125 patients also underwent monthly gadolinium-enhanced and proton density/T2-weighted brain MRI from months 0 to 6 and 18 to 24 to determine the effect of treatment on the frequency of new lesion activity , defined as new enhancing lesions and new/enlarging T2 lesions not enhancing with gadolinium . The difference in total lesion volume between treatment groups was highly significant . In the placebo group , there was an increase of 15 % from baseline to last scan , whereas in the interferon-beta1b group , a reduction of 2 % was seen . Within the placebo group , there was a significant year-on-year increase in total lesion volume , with a mean increase of 16 % at year 3 compared with baseline . In the treated group , there was a significant reduction at year 1 ( 4 % ) and year 2 ( 5 % ) compared with baseline ; the 2 % decrease at year 3 was not significant . The number of new or enlarging proton density/T2 lesions was also significantly reduced by treatment . In the frequent MRI subgroup , treatment was associated with a significant 65 % reduction in new lesion activity between months 1 and 6 , and 78 % reduction from months 19 to 24 . Interferon-beta1b has a substantial and sustained effect on reducing the accumulation of new inflammatory disease foci in secondary progressive MS . This therapeutic mechanism may contribute to the positive clinical benefits of treatment on the progression of sustained neurological disability and relapse activity that were also identified in this trial Background : After the resolution of contrast enhancement , the majority of new MS lesions become isointense with surrounding white matter on T1-weighted MRI . Less commonly , a hypointense T1 lesion develops , representing the development of more severe focal tissue damage . Interferon beta ( IFNβ ) reduces both the number of new enhancing lesions and the duration of contrast enhancement . Objective : To determine if IFNβ affects the degree of tissue damage within new lesions and if its effects are related to lesion size . Methods : One hundred twenty-five patients with secondary progressive MS from seven European sites were r and omized to receive either IFNβ-1b or placebo . Monthly , contrast-enhanced T1-weighted MR images were acquired at baseline , at months 1 to 6 , and at months 19 to 24 . The size of all new enhancing lesions developing between months 1 and 6 was recorded and their appearance at follow-up documented . Results : In the first 6 months , fewer new enhancing lesions occurred in the IFNβ-1b arm . This difference was greater for small ( 70 % decrease ) than for large ( 46 % decrease ) lesions . Hypointense T1 lesions were more likely to form from large ( 25 % ) than from small ( 9 % ) enhancing lesions in both treatment arms . Patients taking IFNβ-1b developed fewer hypointense T1 lesions ; however , the proportion of enhancing lesions developing into hypointense T1 lesions was similar in both arms . Conclusion : IFNβ-1b reduced the number of new enhancing lesions , with a greater effect on small lesions . However , when a new enhancing lesion did become established , treatment with IFNβ-1b did not alter its subsequent course Objective : To examine MRI changes result ing from treatment of secondary progressive MS ( SPMS ) with two doses of interferon-beta-1a ( Rebif ) . Background : Interferon-beta ( IFN-β ) reduces relapses and delays progression in relapsing-remitting MS , but there are conflicting results on its clinical benefit in SPMS . Methods : In a double-blind , r and omized , multicenter , placebo-controlled study ( SPECTRIMS ) , 618 patients received IFN-β-1a 22 μg , 44 μg , or placebo subcutaneously three times weekly for 3 years . T2 activity and burden of disease ( BOD ) were measured in 617 patients by using semiannual proton density/T2-weighted ( PD/T2 ) MRI scans . A cohort of 283 patients also had 11 monthly PD/T2 and T1-weighted gadolinium-enhanced ( T1-Gd ) scans at study start . Results : Treatment reduced median numbers of active lesions per patient per scan ( semiannual T2 activity : 0.17 , 0.20 and 0.67 for the high dose , low dose , and placebo , p < 0.0001 ; monthly combined unique activity [ T1+T2 ] : 0.11 , 0.22 , and 1.00 , p < 0.0001 ) and accumulation of BOD ( percent change from baseline to month 36 : −1.3 , −0.5 , and 10.0 for the high dose , low dose , and placebo , respectively ; p = 0.0001 ) . MRI benefit was most evident in the subgroup of patients who reported relapses in the 2 years before the study . Neutralizing antibody development was associated with reduction in treatment effect : antibody-positive patients did not show significant differences from placebo at either dose . Conclusions : Interferon-β-1a used in SPMS showed significant effects on all MRI measures , particularly in patients with relapses in the 2 years before the study Background : Mitoxantrone ( MTX ) is an immunosuppressive drug approved for multiple sclerosis ( MS ) treatment . Objective : The aim of this study is to evaluate and to compare the clinical and neuroradiological responses to MTX in relapsing — remitting ( RR ) and secondary progressive ( SP ) MS patients . Methods : We conducted a retrospective , non-r and omized , open-label , observational study to evaluate the clinical and neuroradiological response to the drug in 79 patients with RR MS and 210 patients with SP MS . Results : A statistically significant reduction ( p < 0.001 ) in the number of relapses was observed during MTX treatment and in the year after in both RR and SP MS patients . On the contrary , an opposite behavior in terms of disease progression was found in RR compared with SP MS patients , result ing in a statistically significant improvement of the Exp and ed Disability Status Scale score during the MTX treatment ( p < 0.001 ) and in the year after ( p < 0.001 ) for RR MS patients compared with a continuous , although mild , worsening of the disability in SP MS patients ( p < 0.001 ) . Finally , a significant reduction ( p < 0.001 ) of new Gd-enhanced lesions in both RR and SP MS patients was observed in a subgroup of 224 individuals who underwent a brain MRI evaluation before and after MTX treatment . Conclusions : MTX should be considered as an effective therapeutic option in RR MS patients with evidence of relevant disease activity , but the potential life-threatening adverse events and the overall benefit — risk ratio must be carefully evaluated at individual patient level Objective – To examine neurological and magnetic resonance imaging ( MRI ) changes following discontinuation of interferon (IFN)‐β‐1a treatment in secondary progressive multiple sclerosis ( SPMS ) The original glucose-based formulation of Betaferon ® /Betaseron ® ( interferon beta-1b ) requires refrigerated storage . A refrigeration-free formulation of interferon beta-1b , based on mannitol , is stable at room temperature for up to 2 years , and offers a greater degree of flexibility for patients with multiple sclerosis ( MS ) . We compared the safety and tolerability of the two formulations in a 24-week , r and omized , double-blind , parallel group , Phase IV clinical study conducted in 303 patients with MS . Patients received the glucose formulation ( IFNβ-1b-G ) for 8 weeks , and were then r and omized to receive either IFNβ-1b-G or the refrigeration-free formulation ( IFNβ-1b-M ) for a further 8 weeks . On completion of the double-blind phase , all patients received IFNβ-1b-M for an 8-week follow-up period . The primary outcome measure was the proportion of injection sites that developed reactions per patient during the double-blind period . In addition , a range of secondary outcomes relating to these reactions was also assessed . The difference in the proportion of injection-site reactions between the two groups was not statistically significant ( 59 % IFNβ-1b-G versus 60 % IFNβ-1b-M ) . There were no statistically significant differences observed between the two treatment groups in any of the secondary tolerability endpoints . The results from this study demonstrate that the tolerability and safety profiles of both formulations are extremely good , and that the refrigeration-free formulation of interferon beta-1b is comparable with that of the original glucose formulation Objective : A recent cross-sectional study has shown a plateauing relationship between T2 lesion volume ( T2LV ) and disability in patients with multiple sclerosis ( MS ) . In this analysis , which also included longitudinal observations , we investigated whether such a relationship is a consequence of the decreased frequency of “ inflammatory ” events occurring in more disabled patients , rather than reflecting their disability status . Methods : The placebo arms of 2 clinical trials were analyzed . One cohort consisted of 548 patients with relapsing-remitting ( RR ) MS enrolled in a 14-month , r and omized , double-blind , placebo-controlled trial of oral glatiramer acetate . The second cohort consisted of 358 patients with secondary progressive ( SP ) MS still experiencing relapses enrolled in a 3-year , r and omized , double-blind , placebo-controlled trial of interferon beta-1b . Results : At baseline , T2LV was associated with disease duration ( p < 0.001 ) , age at MS onset ( p < 0.001 ) , and disability ( p < 0.001 ) . The relationship between baseline T2LV and Exp and ed Disability Status Scale ( EDSS ) was not significantly different between patients with RRMS and SPMS . At a multivariate analysis , T2LV change was associated with the number of on-trial relapses ( p < 0.001 ) and age at MS onset ( p = 0.02 ) . The correlations of T2LV change with baseline EDSS and EDSS changes were not significant . Conclusions : We showed that the plateauing relationship between T2 lesion volume and disability in multiple sclerosis is not always present and is likely due to the reduced frequency of “ inflammatory ” events in the most common form of secondary progressive multiple sclerosis |
11,832 | 27,432,490 | There is uncertainty about the effect of adding targeted therapy to chemotherapy on survival outcomes in people with advanced gastric cancer , with very little information on its impact on quality of life .
There is more certain evidence of increased risk of adverse events and serious adverse events . | BACKGROUND Gastric cancer is the fifth most common cancer and third leading cause of cancer-related deaths worldwide .
Complete resection of the whole tumor remains the only approach to treat this malignant disease .
Since gastric cancer is usually asymptomatic in its early stages , many people are diagnosed at an advanced stage when the tumor is inoperable .
In addition , because other conventional treatments ( radiotherapy and chemotherapy ) have only modest efficacy for those with advanced/metastatic gastric cancer , the prognosis in such cases is poor .
Recently , trials have provided some promising results regarding molecular-targeted therapy , raising the possibility that the development of these agents could be a fruitful approach .
However , the benefit of molecular-targeted therapy for advanced gastric cancer remains inconclusive .
OBJECTIVES To evaluate the efficacy and safety of molecular-targeted therapy , either alone or in combination with chemotherapy , in people with advanced gastric cancer .
The eligible trials should aim to evaluate the effects of molecular-targeted agents on participants ' prognosis . | Background : This study aim ed to determine whether combination S-1 plus cisplatin ( CDDP ) therapy , the most widely used therapy for Japanese patients with advanced gastric cancer , and the novel oral antiangiogenic agent TSU-68 could contribute to gastric cancer treatment . Methods : Ninety-three patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers were r and omised into two groups : TSU-68 plus S-1/CDDP ( group A ) and S-1/CDDP ( group B ) groups . Both patient groups received identical S-1 and CDDP dosages . TSU-68 was orally administered for 35 consecutive days . Group B patients received S-1 orally twice daily for three consecutive weeks , followed by intravenous CDDP on day 8 . The primary endpoint was progression-free survival ( PFS ) . Results : Median PFS periods were 208 and 213 days in groups A and B , respectively ( P=0.427 ) . Median survival periods for groups A and B were 497.0 and 463.5 days , respectively ( P=0.219 ) . No statistically significant differences were noted for PFS , survival or the adverse event ( AE ) incidence rate . All AEs were expected according to previous reports for TSU-68 , TS-1 , and CDDP . Conclusion : Combination therapy involving TSU-68 , S-1 , and CDDP was safe and well tolerated in patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers . However , factors related to therapeutic efficacy should be investigated further PURPOSE The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer . This international , double-blind , phase III study compared everolimus efficacy and safety with that of best supportive care ( BSC ) in previously treated advanced gastric cancer . PATIENTS AND METHODS Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were r and omly assigned to everolimus 10 mg/d ( assignment schedule : 2:1 ) or matching placebo , both given with BSC . R and omization was stratified by previous chemotherapy lines ( one v two ) and region ( Asia v rest of the world [ ROW ] ) . Treatment continued until disease progression or intolerable toxicity . Primary end point was overall survival ( OS ) . Secondary end points included progression-free survival ( PFS ) , overall response rate , and safety . RESULTS Six hundred fifty-six patients ( median age , 62.0 years ; 73.6 % male ) were enrolled . Median OS was 5.4 months with everolimus and 4.3 months with placebo ( hazard ratio , 0.90 ; 95 % CI , 0.75 to 1.08 ; P = .124 ) . Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms , respectively ( hazard ratio , 0.66 ; 95 % CI , 0.56 to 0.78 ) . Common grade 3/4 adverse events included anemia , decreased appetite , and fatigue . The safety profile was similar in patients enrolled in Asia versus ROW . CONCLUSION Compared with BSC , everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy . The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers BACKGROUND Clinical data showed promising antitumour activity with feasible tolerability for matuzumab plus epirubicin , cisplatin and capecitabine ( ECX ) chemotherapy in untreated advanced oesophago-gastric ( OG ) cancer . The aim was to evaluate the efficacy of matuzumab plus ECX versus ECX alone . PATIENTS AND METHODS In this multicentre , r and omised open-label phase II study , 72 patients with metastatic OG cancer were r and omly assigned to either 800 mg matuzumab weekly plus epirubicin 50 mg/m² , cisplatin 60 mg/m² on day 1 and capecitabine 1250 mg/m² daily in a 21-day cycle ( ECX ) or the same ECX regimen alone . The primary end point was objective response . Secondary end points included progression-free survival ( PFS ) , overall survival ( OS ) , quality of life , safety and tolerability . RESULTS Following r and om assignment , 35 patients ( median age 59 years ) received ECX/matuzumab and 36 patients ( median age 64 years ) ECX . The addition of matuzumab to ECX did not improve objective response : 31 % for ECX/matuzumab [ 95 % confidence interval ( CI ) 17 - 49 ] compared with 58 % for the ECX arm ( 95 % CI 41 - 74 ) P = 0.994 ( one sided ) . There was no significant difference in median PFS : 4.8 months ( 95 % CI 2.9 - 8.1 ) for ECX/matuzumab versus 7.1 months ( 95 % CI 4.4 - 8.5 ) for ECX , or in median OS : 9.4 months ( 95 % CI 7.5 - 16.2 ) , compared with 12.2 months ( 95 % CI 9.8 - 13.8 months ) . Grade 3/4 treatment-related toxicity was observed in 27 and 25 patients in the ECX/matuzumab and ECX groups , respectively . CONCLUSION Matuzumab 800 mg weekly combined with ECX chemotherapy does not increase response or survival for patients with advanced OG cancer . Therefore , ECX/matuzumab should not be examined further in phase III trials BACKGROUND Dysregulation of the hepatocyte growth factor (HGF)/MET pathway promotes tumour growth and metastasis . Rilotumumab is a fully human , monoclonal antibody that neutralises HGF . We aim ed to assess the safety , efficacy , biomarkers , and pharmacokinetics of rilotumumab combined with epirubicin , cisplatin , and capecitabine ( ECX ) in patients with advanced gastric or oesophagogastric junction cancer . METHODS We recruited patients ( ≥18 years old ) with unresectable locally advanced or metastatic gastric or oesophagogastric junction adenocarcinoma , an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 , who had not received previous systemic therapy , from 43 sites worldwide . Phase 1b was an open-label , dose de-escalation study to identify a safe dose of rilotumumab ( initial dose 15 mg/kg intravenously on day 1 ) plus ECX ( epirubicin 50 mg/m(2 ) intravenously on day 1 , cisplatin 60 mg/m(2 ) intravenously on day 1 , capecitabine 625 mg/m(2 ) twice a day orally on days 1 - 21 , respectively ) , administered every 3 weeks . The phase 1b primary endpoint was the incidence of dose-limiting toxicities in all phase 1b patients who received at least one dose of rilotumumab and completed the dose-limiting toxicity assessment window ( first cycle of therapy ) . Phase 2 was a double-blind study that r and omly assigned patients ( 1:1:1 ) using an interactive voice response system to receive rilotumumab 15 mg/kg , rilotumumab 7·5 mg/kg , or placebo , plus ECX ( doses as above ) , stratified by ECOG performance status and disease extent . The phase 2 primary endpoint was progression-free survival ( PFS ) , analysed by intention to treat . The study is registered with Clinical Trials.gov , number NCT00719550 . FINDINGS Seven of the nine patients enrolled in the phase 1b study received at least one dose of rilotumumab 15 mg/kg , only two of whom had three dose-limiting toxicities : palmar-plantar erythrodysesthesia , cerebral ischaemia , and deep-vein thrombosis . In phase 2 , 121 patients were r and omly assigned ( 40 to rilotumumab 15 mg/kg ; 42 to rilotumumab 7·5 mg/kg ; 39 to placebo ) . Median PFS was 5·1 months ( 95 % CI 2·9 - 7·0 ) in the rilotumumab 15 mg/kg group , 6·8 months ( 4·5 - 7·5 ) in the rilotumumab 7·5 mg/kg group , 5·7 months ( 4·5 - 7·0 ) in both rilotumumab groups combined , and 4·2 months ( 2·9 - 4·9 ) in the placebo group . The hazard ratio for PFS events compared with placebo was 0·69 ( 80 % CI 0·49 - 0·97 ; p=0·164 ) for rilotumumab 15 mg/kg , 0·53 ( 80 % CI 0·38 - 0·73 ; p=0·009 ) for rilotumumab 7·5 mg/kg , and 0·60 ( 80 % CI 0·45 - 0·79 ; p=0·016 ) for combined rilotumumab . Any grade adverse events more common in the combined rilotumumab group than in the placebo group included haematological adverse events ( neutropenia in 44 [ 54 % ] of 81 patients vs 13 [ 33 % ] of 39 patients ; anaemia in 32 [ 40 % ] vs 11 [ 28 % ] ; and thrombocytopenia in nine [ 11 % ] vs none ) , peripheral oedema ( 22 [ 27 % ] vs three [ 8 % ] ) , and venous thromboembolism ( 16 [ 20 % ] vs five [ 13 % ] ) . Grade 3 - 4 adverse events more common with rilotumumab included neutropenia ( 36 [ 44 % ] vs 11 [ 28 % ] ) and venous thromboembolism ( 16 [ 20 % ] vs four [ 10 % ] ) . Serious adverse events were balanced between groups except for anaemia , which occurred more frequently in the combined rilotumumab group ( ten [ 12 % ] vs none ) . INTERPRETATION Rilotumumab plus ECX had no unexpected safety signals and showed greater activity than placebo plus ECX . A phase 3 study of the combination in MET-positive gastric and oesophagogastric junction cancer is in progress . FUNDING Amgen BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche Background In the United Kingdom ( UK ) , there is an extensive market for the class ' A ' drug heroin . Many heroin users spend time in prison . People addicted to heroin often require prescribed medication when attempting to cease their drug use . The most commonly used detoxification agents in UK prisons are buprenorphine , dihydrocodeine and methadone . However , national guidelines do not state a detoxification drug of choice . Indeed , there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons . This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons . Methods / Design The Leeds Evaluation of Efficacy of Detoxification Study ( LEEDS ) Prisons Pilot Study will use r and omised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification , given in the context of routine care , within HMP Leeds . Prisoners who are eligible and give informed consent will be entered into the trial . The primary outcome measure will be abstinence status at five days post detoxification , as determined by a urine test . Secondary outcomes during the detoxification and then at one , three and six months post detoxification will be recorded Objectives We aim ed to evaluate the efficacy and safety of combination therapy of Endostar ( recombinant human endostatin ) and S-1 combined with oxaliplatin ( SOX ) in patients with advanced gastric cancer . Methods In this r and omized , controlled trial , 165 late-stage gastric cancer patients were assigned to the experimental arm with Endostar in combination with SOX ( 80 patients ) and the control arm with SOX alone ( 85 patients ) . The end points of this study included progression-free survival , response rate , and disease-control rate . Results There was no statistically significant difference in response rate between the experimental arm and the control arm ( 53.8 % vs 42.4 % , P=0.188 ) . The difference in disease-control rate was also statistically insignificant between the two arms ( 85.0 % vs 72.9 % , P=0.188 ) . Progression-free survival in the experimental arm was significantly higher than that in the control arm ( 15.0 months vs 12.0 months , P=0.0001 ) . Common adverse events included immunosuppression , gastrointestinal distress , and neuropathy . There was no statistical difference in the incidences of adverse events . Conclusion Combination therapy of Endostar and SOX provides therapeutic benefits to advanced gastric cancer patients , with tolerable adverse effects e21021 Background : Nimotuzumab , a humanized IgG1 anti-EGFR monoclonal antibody , has demonstrated efficacy associated with an absence of severe skin toxicity in many phase I/II cancer trials . METHODS This is a single-center , r and omized , parallel assignment and open-label study of nimotuzumab ( N : 200 mg iv on day 1 , 8 and 15 , repeat every 3 weeks ) + cisplatin ( C : 30mg/m2/day , on day 1 and day 2 , repeat every 3 weeks ) + S-1 ( S : 80mg/m2/day , twice daily on day 1 - 14 , followed 7 days off ) , vs cisplatin ( C : 30mg/m2/day , on day 1 and day 2 , repeat every 3 weeks ) + S-1 ( S : 80mg/m2/day , twice daily on day 1 - 14 , followed 7 days off ) as first line in patients with advanced or metastatic gastric cancer . If tumor control was achieved , NCS and CS were continued until unacceptable toxicity or disease progression . The primary endpoint was ORR and the secondary endpoints included TTP , PFS , 1-year survival rates and safety . RESULTS 40 patients , 27 men and 13 women , median age 54 years ( 21 - 74 years ) ECOG PS 0 - 2 were treated with NCS ( n = 20 ) or CS ( n = 20 ) . Up to 2011 - 01 - 14 , 36 patients ( NCS 19 cases compared with CS 17 ) have undergone efficacy assessment . The objective response rate ( ORR ) was 63.2 % ( 12/19 ) in NCS group compared with 64.7 % ( 11/17 ) in CS group . Until the same day , 18 patients have achieved progression in both groups ( NCS 10 vs. FCS 8) , median TTP was 5.5 months in NCS group compared with 3 months in CS group , and average TTP was 5.3 months in NCS group compared with 3.1 months in CS group . The incidence of adverse events was similar between both groups . No adverse events of grade 3 skin rash or grade 3 infusion-related reactions were observed . CONCLUSIONS Initial results have demonstrated benefit in TTP improvement and showed a potential improvement of OS . This study supports that nimotuzumab combine with cisplatin and S-1 has better outcomes compare to cisplatin and S-1 . The further study is ongoing Tyrosine kinase inhibitors ( TKIs ) of the epidermal growth factor receptor ( EGFR ) have activity in solid tumors . The authors evaluated an oral EGFR TKI , erlotinib , in patients with previously treated esophageal cancer PURPOSE In Asian countries , paclitaxel once per week is used as second-line treatment in advanced gastric cancer , including human epidermal growth factor receptor 2 ( HER2 ) -positive tumors . The role of anti-HER2 agents , including lapatinib , in this setting and population is unclear . PATIENTS AND METHODS TyTAN was a two-part , parallel-group , phase III study in Asian patients . An open-label , dose-optimization phase ( n = 12 ) was followed by a r and omized phase ( n = 261 ) , in which patients who were HER2 positive by fluorescence in situ hybridization ( FISH ) received lapatinib 1,500 mg once per day plus once-per-week paclitaxel 80 mg/m(2 ) or paclitaxel alone . The primary end point was overall survival ( OS ) . Secondary end points included progression-free survival ( PFS ) , time to progression ( TTP ) , overall response rate ( ORR ) , time to response , response duration , and safety . Analyses were based on immunohistochemistry ( IHC ) and gastrectomy status , prior trastuzumab therapy , and regional sub population s. RESULTS Median OS was 11.0 months with lapatinib plus paclitaxel versus 8.9 months with paclitaxel alone ( P = .1044 ) , with no significant difference in median PFS ( 5.4 v 4.4 months ) or TTP ( 5.5 v 4.4 months ) . ORR was higher with lapatinib plus paclitaxel versus paclitaxel alone ( odds ratio , 3.85 ; P < .001 ) . Better efficacy with lapatinib plus paclitaxel was demonstrated in IHC3 + compared with IHC0/1 + and 2 + patients and in Chinese compared with Japanese patients . A similar proportion of patients experienced adverse events with each treatment ( lapatinib plus paclitaxel , 100 % v paclitaxel alone , 98 % ) . CONCLUSION Lapatinib plus paclitaxel demonstrated activity in the second-line treatment of patients with HER2 FISH-positive IHC3 + advanced gastric cancer but did not significantly improve OS in the intent-to-treat population BACKGROUND Patients with advanced gastric cancer have a poor prognosis and few efficacious treatment options . We aim ed to assess the addition of cetuximab to capecitabine-cisplatin chemotherapy in patients with advanced gastric or gastro-oesophageal junction cancer . METHODS In our open-label , r and omised phase 3 trial ( EXP AND ) , we enrolled adults aged 18 years or older with histologically confirmed locally advanced unresectable ( M0 ) or metastatic ( M1 ) adenocarcinoma of the stomach or gastro-oesophageal junction . We enrolled patients at 164 sites ( teaching hospitals and clinics ) in 25 countries , and r and omly assigned eligible participants ( 1:1 ) to receive first-line chemotherapy with or without cetuximab . R and omisation was done with a permuted block r and omisation procedure ( variable block size ) , stratified by disease stage ( M0 vs M1 ) , previous oesophagectomy or gastrectomy ( yes vs no ) , and previous (neo)adjuvant (radio)chemotherapy ( yes vs no ) . Treatment consisted of 3-week cycles of twice-daily capecitabine 1000 mg/m(2 ) ( on days 1 - 14 ) and intravenous cisplatin 80 mg/m(2 ) ( on day 1 ) , with or without weekly cetuximab ( 400 mg/m(2 ) initial infusion on day 1 followed by 250 mg/m(2 ) per week thereafter ) . The primary endpoint was progression-free survival ( PFS ) , assessed by a masked independent review committee in the intention-to-treat population . We assessed safety in all patients who received at least one dose of study drug . This study is registered at EudraCT , number 2007 - 004219 - 75 . FINDINGS Between June 30 , 2008 , and Dec 15 , 2010 , we enrolled 904 patients . Median PFS for 455 patients allocated capecitabine-cisplatin plus cetuximab was 4.4 months ( 95 % CI 4.2 - 5.5 ) compared with 5.6 months ( 5.1 - 5.7 ) for 449 patients who were allocated to receive capecitabine-cisplatin alone ( hazard ratio 1.09 , 95 % CI 0.92 - 1.29 ; p=0.32 ) . 369 ( 83 % ) of 446 patients in the chemotherapy plus cetuximab group and 337 ( 77 % ) of 436 patients in the chemotherapy group had grade 3 - 4 adverse events , including grade 3 - 4 diarrhoea , hypokalaemia , hypomagnesaemia , rash , and h and -foot syndrome . Grade 3 - 4 neutropenia was more common in controls than in patients who received cetuximab . Incidence of grade 3 - 4 skin reactions and acne-like rash was substantially higher in the cetuximab-containing regimen than in the control regimen . 239 ( 54 % ) of 446 in the cetuximab group and 194 ( 44 % ) of 436 in the control group had any grade of serious adverse event . INTERPRETATION Addition of cetuximab to capecitabine-cisplatin provided no additional benefit to chemotherapy alone in the first-line treatment of advanced gastric cancer in our trial . FUNDING Merck BACKGROUND & AIMS Atrophic corpus gastritis ( ACG ) is believed to be an early precursor of gastric adenocarcinoma . We aim ed to investigate trends of ACG in Northern Sweden , from 1990 through 2009 , and to identify possible risk factors . METHODS We r and omly selected serum sample s collected from 5284 participants in 1990 , 1994 , 1999 , 2004 , and 2009 , as part of the population -based , cross-sectional Northern Sweden Multinational Monitoring of Trends and Determinants in Cardiovascular Disease study ( ages , 35 - 64 y ) . Information was collected on sociodemographic , anthropometric , lifestyle , and medical factors using question naires . Serum sample s were analyzed for levels of pepsinogen I to identify participants with functional ACG ; data from participants with ACG were compared with those from frequency-matched individuals without ACG ( controls ) . Blood sample s were analyzed for antibodies against Helicobacter pylori and Cag pathogenicity isl and protein A. Associations were estimated with unconditional logistic regression models . RESULTS Overall , 305 subjects tested positive for functional ACG , based on their level of pepsinogen I. The prevalence of ACG in participants age 55 to 64 years old decreased from 124 per 1000 to 49 per 1000 individuals between 1990 and 2009 . However , the prevalence of ACG increased from 22 per 1000 to 64 per 1000 individuals among participants age 35 to 44 years old during this time period . Cag pathogenicity isl and protein A seropositivity was associated with risk for ACG ( odds ratio , 2.29 ; 95 % confidence interval , 1.69 - 3.12 ) . Other risk factors included diabetes , low level of education , and high body mass index . The association between body mass index and ACG was confined to individuals age 35 to 44 years old ; in this group , overweight and obesity were associated with a 2.8-fold and a 4.7-fold increased risk of ACG , respectively . CONCLUSIONS Among residents of Northern Sweden , the prevalence of ACG increased from 1990 through 2009 , specifically among adults age 35 to 44 years old . The stabilizing seroprevalence of H pylori and the increasing prevalence of overweight and obesity might contribute to this unexpected trend . Studies are needed to determine whether these changes have affected the incidence of gastric cancer Summary Background EGFR overexpression occurs in 27–55 % of oesophagogastric adenocarcinomas , and correlates with poor prognosis . We aim ed to assess addition of the anti-EGFR antibody panitumumab to epirubicin , oxaliplatin , and capecitabine ( EOC ) in patients with advanced oesophagogastric adenocarcinoma . Methods In this r and omised , open-label phase 3 trial ( REAL3 ) , we enrolled patients with untreated , metastatic , or locally advanced oesophagogastric adenocarcinoma at 63 centres ( tertiary referral centres , teaching hospitals , and district general hospitals ) in the UK . Eligible patients were r and omly allocated ( 1:1 ) to receive up to eight 21-day cycles of open-label EOC ( epirubicin 50 mg/m2 and oxaliplatin 130 mg/m2 on day 1 and capecitabine 1250 mg/m2 per day on days 1–21 ) or modified-dose EOC plus panitumumab ( mEOC+P ; epirubicin 50 mg/m2 and oxaliplatin 100 mg/m2 on day 1 , capecitabine 1000 mg/m2 per day on days 1–21 , and panitumumab 9 mg/kg on day 1 ) . R and omisation was blocked and stratified for centre region , extent of disease , and performance status . The primary endpoint was overall survival in the intention-to-treat population . We assessed safety in all patients who received at least one dose of study drug . After a preplanned independent data monitoring committee review in October , 2011 , trial recruitment was halted and panitumumab withdrawn . Data for patients on treatment were censored at this timepoint . This study is registered with Clinical Trials.gov , number NCT00824785 . Findings Between June 2 , 2008 , and Oct 17 , 2011 , we enrolled 553 eligible patients . Median overall survival in 275 patients allocated EOC was 11·3 months ( 95 % CI 9·6–13·0 ) compared with 8·8 months ( 7·7–9·8 ) in 278 patients allocated mEOC+P ( hazard ratio [ HR ] 1·37 , 95 % CI 1·07–1·76 ; p=0·013 ) . mEOC+P was associated with increased incidence of grade 3–4 diarrhoea ( 48 [ 17 % ] of 276 patients allocated mEOC+P vs 29 [ 11 % ] of 266 patients allocated EOC ) , rash ( 29 [ 11 % ] vs two [ 1 % ] ) , mucositis ( 14 [ 5 % ] vs none ) , and hypomagnesaemia ( 13 [ 5 % ] vs none ) but reduced incidence of haematological toxicity ( grade ≥3 neutropenia 35 [ 13 % ] vs 74 [ 28 % ] ) . Interpretation Addition of panitumumab to EOC chemotherapy does not increase overall survival and can not be recommended for use in an unselected population with advanced oesophagogastric adenocarcinoma . Funding Amgen , UK National Institute for Health Research Biomedical Research Centre PURPOSE A phase II trial of the oral epidermal growth factor receptor ( EGFR ) inhibitor erlotinib in patients with gastroesophageal adenocarcinomas stratified according to primary tumor location into two groups : gastroesophageal junction (GEJ)/cardia and distal gastric adenocarcinomas . PATIENTS AND METHODS Patients with a histologically proven diagnosis of adenocarcinoma of the GEJ or stomach ( ST ) that was unresectable or metastatic ; presence of measurable disease ; no prior chemotherapy for advanced or metastatic cancer ; Zubrod performance status ( PS ) of 0 to 1 ; and adequate renal , hepatic , and hematologic function were treated with erlotinib 150 mg/d orally . Patient characteristics were median age , GEJ-63 years , ST-64 years ; sex , GEJ-84 % male and 16 % female , ST-60 male and 40 female ; Zubrod PS , GEJ-25 had a PS of 0 and 18 had a PS 1 , ST-13 had a PS of 0 and 12 had a PS of 1 . RESULTS Percentage of common toxicities were skin rash , 86 % and 72 % ; fatigue , 51 % and 44 % ; and AST/ALT elevation , 28 % and 28 % , respectively for GEJ and ST . There has been one confirmed complete response , three confirmed partial responses ( PRs ) and one unconfirmed PR for an overall response probability of 9 % confirmed ( 95 % CI , 3 % to 22 % ) , all occurring in GEJ stratum . No responses were observed in ST stratum . The median survival was 6.7 months in GEJ and 3.5 months in ST stratum . Neither intratumoral EGFR , transforming growth factor-alpha or phosphorylated Akt kinase expression nor plasma proteomic analyses were predictive of clinical outcome . No somatic mutations of the EGFR exons 18 , 19 , or 21 were detected and there was no gross amplification of EGFR by fluorescence in situ hybridization . CONCLUSION Erlotinib is active in patients with GEJ adenocarcinomas , but appears inactive in gastric cancers . The molecular correlates examined were not predictive of the patient therapeutic response TPS178 Background : Advanced gastroesophageal cancers ( AGEC ) harbour a dismal prognosis ( overall survival [ OS ] < 1 year ) . EGFR inhibitors showed promising activity in patients ( pts ) with AGEC . Dysregulation of the HGF/c-Met pathway is a rational therapeutic target in AGEC . This r and omised phase II study aims to assess the efficacy and safety of fluorouracil ( FU ) , folinic acid ( FA ) and oxaliplatin-based chemotherapy ( modified FOLFOX6 regimen ) alone or combined to either panitumumab , an anti-EGFR monoclonal antibody , or to AMG 102 , an anti-HGF monoclonal antibody , as first-line treatment for pts with AGEC . METHODS This multicentre , open-label , r and omised phase II trial is ongoing in 30 centres in France . Main eligibility criteria include : histologically proven adenocarcinoma of the stomach , esophagus or gastroesophageal junction ; locally advanced or metastatic disease ; measurable disease ( RECIST 1.1 ) ; no known HER2 overexpression ; no prior palliative chemotherapy ; age > 18 years ; ECOG performance status 0 or 1 ; adequate bone marrow , liver and renal function . Patients are r and omised to modified FOLFOX6 ( oxaliplatin 85 mg/m² , FA 400 mg/m² , FU 400 mg/m² bolus then 2400 mg/m² over 46 hr ) alone or combined to either panitumumab ( 6 mg/kg ) or AMG 102 ( 10 mg/kg ) every two weeks until unacceptable toxicity or disease progression . Judgment criteria include 4-month progression-free survival rate ( primary endpoint ) , OS , objective response rate , and safety . Ancillary studies aim to identify c and i date predictive and prognostic biomarkers among functional of molecular alterations of the EGFR/RAS/RAF and HGF/c-Met pathways , and to monitor circulating tumour cells and circulating immune cells ( myeloid derived suppressor cells , NK cells ) in sequential blood sample s taken at baseline and through the study treatment . A total of 165 pts will be enrolled ( Fleming 's one-step design ) . The first patient enrolled in January 2011 PURPOSE To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain ( CNG ) or an activating truncation within a deoxyadenosine tract element ( DATE ) in the promoter region of the MET lig and HGF . PATIENTS AND METHODS A single-institution cohort of 230 patients with stage II/III gastric cancer was studied . Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction . Quantitative polymerase chain reaction ( qPCR ) for MET CNG and sequencing for HGF DATE truncation ( < 25 deoxyadenosines instead of 30 ) were used . Results were analyzed for association with disease-free survival ( DFS ) and overall survival ( OS ) . To assess the reliability of the qPCR measurement , a r and om sample of cases was reanalyzed using an alternative assay ( fluorescent in situ hybridization [ FISH ] ) with calculation of the intracorrelation coefficient ( ICC ) . RESULTS In 216 assessable patients , MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients ( 10 % ) and 30 patients ( 13 % ) , respectively . Patients with MET CNG five or more copies ( MET-positive ) showed significantly worse prognosis with multivariate hazard ratio ( HR ) of 3.02 ( 95 % CI , 1.71 to 5.33 ; P < .001 ) for DFS and multivariate HR of 2.91 ( 95 % CI , 1.65 to 5.11 ; P < .001 ) for OS . The agreement between qPCR and FISH was high , with ICC = 0.9 % ( 95 % CI , 0.81 % to 0.95 % ; the closer the ICC is to 1 , the greater is the agreement ) . HGF-truncated DATE did not show relevant prognostic effect . CONCLUSION In this study , qPCR revealed approximately 10 % of white patients with gastric cancer harboring MET CNG of five or more copies . This marker was significantly associated with unfavorable prognosis . This information is relevant to the current clinical development of anti-MET compounds BACKGROUND Advanced gastric cancer can respond to S-1 , an oral fluoropyrimidine . We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer . METHODS Patients in Japan with stage II or III gastric cancer who underwent gastrectomy with extended ( D2 ) lymph-node dissection were r and omly assigned to undergo surgery followed by adjuvant therapy with S-1 or to undergo surgery only . In the S-1 group , administration of S-1 was started within 6 weeks after surgery and continued for 1 year . The treatment regimen consisted of 6-week cycles in which , in principle , 80 mg of oral S-1 per square meter of body-surface area per day was given for 4 weeks and no chemotherapy was given for the following 2 weeks . The primary end point was overall survival . RESULTS We r and omly assigned 529 patients to the S-1 group and 530 patients to the surgery-only group between October 2001 and December 2004 . The trial was stopped on the recommendation of the independent data and safety monitoring committee , because the first interim analysis , performed 1 year after enrollment was completed , showed that the S-1 group had a higher rate of overall survival than the surgery-only group ( P=0.002 ) . Analysis of follow-up data showed that the 3-year overall survival rate was 80.1 % in the S-1 group and 70.1 % in the surgery-only group . The hazard ratio for death in the S-1 group , as compared with the surgery-only group , was 0.68 ( 95 % confidence interval , 0.52 to 0.87 ; P=0.003 ) . Adverse events of grade 3 or grade 4 ( defined according to the Common Toxicity Criteria of the National Cancer Institute ) that were relatively common in the S-1 group were anorexia ( 6.0 % ) , nausea ( 3.7 % ) , and diarrhea ( 3.1 % ) . CONCLUSIONS S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer . ( Clinical Trials.gov number , NCT00152217 [ Clinical Trials.gov ] . ) PURPOSE The Avastin in Gastric Cancer ( AVAGAST ) trial was a multinational , r and omized , placebo-controlled trial design ed to evaluate the efficacy of adding bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced gastric cancer . PATIENTS AND METHODS Patients received bevacizumab 7.5 mg/kg or placebo followed by cisplatin 80 mg/m(2 ) on day 1 plus capecitabine 1,000 mg/m(2 ) twice daily for 14 days every 3 weeks . Fluorouracil was permitted in patients unable to take oral medications . Cisplatin was given for six cycles ; capecitabine and bevacizumab were administered until disease progression or unacceptable toxicity . The primary end point was overall survival ( OS ) . Log-rank test was used to test the OS difference . RESULTS In all , 774 patients were enrolled ; 387 were assigned to each treatment group ( intention-to-treat population ) , and 517 deaths were observed . Median OS was 12.1 months with bevacizumab plus fluoropyrimidine-cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin ( hazard ratio 0.87 ; 95 % CI , 0.73 to 1.03 ; P = .1002 ) . Both median progression-free survival ( 6.7 v 5.3 months ; hazard ratio , 0.80 ; 95 % CI , 0.68 to 0.93 ; P = .0037 ) and overall response rate ( 46.0 % v 37.4 % ; P = .0315 ) were significantly improved with bevacizumab versus placebo . Preplanned subgroup analyses revealed regional differences in efficacy outcomes . The most common grade 3 to 5 adverse events were neutropenia ( 35 % , bevacizumab plus fluoropyrimidine-cisplatin ; 37 % , placebo plus fluoropyrimidine-cisplatin ) , anemia ( 10 % v 14 % ) , and decreased appetite ( 8 % v 11 % ) . No new bevacizumab-related safety signals were identified . CONCLUSION Although AVAGAST did not reach its primary objective , adding bevacizumab to chemotherapy was associated with significant increases in progression-free survival and overall response rate in the first-line treatment of advanced gastric cancer |
11,833 | 24,798,864 | The combination of low sodium and low fructose did increase mtDNA but it did not increase it more than the low sodium diet alone without fructose restriction .
This suggests that the eff ect appears dependent on sodium but not fructose .
Conversely , in isocaloric comparisons where energy intake is matched , these eff ects are not observed .
That is , fructose behaves no worse than any other carbohydrate [ 4 – 8 ] , although there may be a dosethreshold for some fasting lipid eff ects [ 4 , 10 – 12 ] .
This lack of eff ect remains true even under conditions of fructose overfeeding ( positive energy balance ) , as long as the comparison is matched for the excess calories .
Taken together , the main driver mediating any harm attributable to fructose appears to be excess energy .
In conclusion , there is insuffi cient evidence to conclude that fructose restriction has a signifi ca nt eff ect on mtDNA and oxidative stress when holding energy equal .
Energy imbalance appears to be a prerequisite for eliciting an eff ect . | Dear Editor , We read with interest the pilot study by Hern and ez-Rios et al. comparing the eff ect of a low sodium diet with or without fructose restriction under isocaloric conditions on mitochondrial DNA ( mtDNA ) and oxidative stress [ 1 ] .
In line with this fi nding , our research group through a series of systematic review s and meta-analyses of controlled feeding trials has shown that supplementing background diets with excess energy from fructose consistently leads to adverse eff ects on cardiometabolic risk factors associated with infl ammation , including body weight [ 4 ] , fasting and postpr and ial blood lipids [ 5 , 6 ] , fasting glucose and insulin [ 7 ] , uric acid [ 8 ] , and markers of non-alcoholic fatty liver disease ( NAFLD ) [ 9 ] . | OBJECTIVE To evaluate the effect of sodium and fructose restriction on mitochondrial DNA ( mtDNA ) content and systemic oxidative stress in a sample of overweight and pre hypertensive subjects . MATERIAL / METHODS Data and blood sample s were collected from 36 overweight and pre hypertensive patients r and omly assigned to either an isocaloric ( with respect to baseline ) low sodium-fructose diet or an isocaloric low sodium diet . Patients were followed for 8 weeks . We measured mitochondrial DNA ( mtDNA ) content from peripheral blood white cells by Real-time PCR and plasma malondialdehyde ( MDA ) and 2,4-dinitrophenylhydrazine ( DNPH ) as markers of reactive oxygen species ( ROS ) . RESULTS Compared to baseline , at week 8 there was a continued and significant increase in mtDNA in both the low sodium diet group [ 2.4 vs. 13.1 ( relative copy number ) , p<0.05 ] and the low sodium diet-fructose group ( 1.9 vs. 147.2 , p<0.05 ) . By week 8 there was a continued decrease in plasma DNPH levels in the low sodium diet group ( 4.6 vs. 2.6 , p<0.05 ) and in the low sodium diet-fructose group ( 5.8 vs. 2.2 , p<0.05 ) . No significant differences were found with MDA . CONCLUSION Our studies suggest that simple dietary measures such as reducing salt with or without restricting fructose can increase mtDNA and improve markers of oxidative stress |
11,834 | 21,309,711 | Most of the studies indicated positive effects to quell anxiety .
It is recommended that aromatherapy could be applied as a complementary therapy for people with anxiety symptoms . | PURPOSE We review ed studies from 1990 to 2010 on using aromatherapy for people with anxiety or anxiety symptoms and examined their clinical effects . | Research suggests that patients with cancer , particularly in the palliative care setting , are increasingly using aromatherapy and massage . There is good evidence that these therapies may be helpful for anxiety reduction for short periods , but few studies have looked at the longer term effects . This study was design ed to compare the effects of four-week courses of aromatherapy massage and massage alone on physical and psychological symptoms in patients with advanced cancer . Forty-two patients were r and omly allocated to receive weekly massages with lavender essential oil and an inert carrier oil ( aromatherapy group ) , an inert carrier oil only ( massage group ) or no intervention . Outcome measures included a Visual Analogue Scale ( VAS ) of pain intensity , the Verran and Snyder-Halpern ( VSH ) sleep scale , the Hospital Anxiety and Depression ( HAD ) scale and the Rotterdam Symptom Checklist ( RSCL ) . We were unable to demonstrate any significant long-term benefits of aromatherapy or massage in terms of improving pain control , anxiety or quality of life . However , sleep scores improved significantly in both the massage and the combined massage ( aromatherapy and massage ) groups . There were also statistically significant reductions in depression scores in the massage group . In this study of patients with advanced cancer , the addition of lavender essential oil did not appear to increase the beneficial effects of massage . Our results do suggest , however , that patients with high levels of psychological distress respond best to these therapies Results of the pilot study of the four counties r and omised controlled trial to evaluate the effectiveness of aromatherapy massage with 1 % Santalum album ( S and alwood ) ( group A ) when compared with massage with Sweet Almond Carrier oil , ( group B ) or S and alwood oil via an aromastone ( group C ) , in reducing levels of anxiety in palliative care . The aims of the pilot study were to evaluate the effectiveness of aromatherapy in reducing anxiety in patients receiving palliative care in four counties . The primary end points of the research were to report a statistically significant difference in anxiety scores between experimental group ( B ) and comparison groups ( A and C ) and to influence the integration of aromatherapy into all aspects of palliative care . The limited data of the pilot study ( N=34 ) tested the logistics of the research , particularly the 25 % attrition rate and the robustness of the data collection tools . The results were not substantial enough to generate coherent statistics . Therefore no assumptions could be drawn from these results due to the inconsistencies that were bound to occur in such a small sample . However , the results do seem to support the notion that S and alwood oil is effective in reducing anxiety The goal of this study was to investigate the impact of the essential oils of orange and lavender on anxiety , mood , alertness and calmness in dental patients . Two hundred patients between the ages of 18 and 77 years ( half women , half men ) were assigned to one of four independent groups . While waiting for dental procedures patients were either stimulated with ambient odor of orange or ambient odor of lavender . These conditions were compared to a music condition and a control condition ( no odor , no music ) . Anxiety , mood , alertness and calmness were assessed while patients waited for dental treatment . Statistical analyses revealed that compared to control condition both ambient odors of orange and lavender reduced anxiety and improved mood in patients waiting for dental treatment . These findings support the previous opinion that odors are capable of altering emotional states and may indicate that the use of odors is helpful in reducing anxiety in dental patients CONTEXT Interest in the use of alternative therapies to reduce anxiety in patients undergoing medical interventions is increasing . We sought to assess the effectiveness of aromatherapy involving essential oils in reducing preoperative anxiety in women undergoing abortions . SETTING An urban , free-st and ing abortion clinic in Vancouver , BC . PATIENTS 66 women waiting for surgical abortions . DESIGN A double blind , r and omized trial . INTERVENTION Ten minutes spent sniffing a numbered container with either a mixture of the essential oils vetivert , bergamot , and geranium ( treatment arm ) or a hair conditioner ( placebo ) . OUTCOME MEASURES Anxiety was measured before and after the intervention by using a verbal anxiety scale from 0 to 10 . RESULTS The anxiety score was reduced by 1.0 point ( 5.0 to 4.0 ) in the aromatherapy group and by 1.1 points ( 6.1 to 5.0 ) in the placebo group ( P = 0.71 ) . The 95 % CI on the 0.1 greater decrease in anxiety for the placebo group extends from 0.55 less ( favors aromatherapy ) to 0.75 greater ( favors placebo ) . CONCLUSION Aromatherapy involving essential oils is no more effective than having patients sniff other pleasant odors in reducing preprocedure anxiety OBJECTIVE Melissa officinalis ( lemon balm ) and Valeriana officinalis ( valerian ) have been used both traditionally and contemporaneously as mild sedatives , anxiolytics and hypnotics . Recent research has suggested that both may attenuate laboratory induced stress . As the two herbs are most often sold in combination with each other the current study assessed the anxiolytic properties of such a combination during laboratory-induced stress . METHODS In this double-blind , placebo-controlled , r and omized , balanced cross-over experiment , 24 healthy volunteers received three separate single doses ( 600 mg , 1200 mg , 1800 mg ) of a st and ardized product containing M. officinalis and V. officinalis extracts , plus a placebo , on separate days separated by a 7 day wash out period . Modulation of mood and anxiety were assessed during pre-dose and 1 h , 3 h and 6 h post-dose completions of a 20 min version of the Defined Intensity Stressor Simulation ( DISS ) battery . Cognitive performance on the four concurrent tasks of the battery was also assessed . RESULTS The results showed that the 600 mg dose of the combination ameliorated the negative effects of the DISS on ratings of anxiety . However , the highest dose ( 1800 mg ) showed an increase in anxiety that was less marked but which reached significance during one testing session . In addition , all three doses led to decrements in performance on the Stroop task module within the battery , and the two lower doses led to decrements on the overall score generated on the DISS battery . CONCLUSIONS These results suggest that a combination of Melissa officinalis and Valeriana officinalis possesses anxiolytic properties that deserve further investigation This study examined the effect of aromatherapy-massage in healthy postpartum mothers . A quasi-experimental between-groups design was used . Mothers who received aromatherapy-massage were compared with a control group who received st and ard postpartum care . Thirty-six healthy , first-time mothers with vaginal delivery of a full-term , healthy infant participated in this study . Sixteen mothers received a 30-minute aromatherapy-massage on the second postpartum day ; 20 mothers were in the control group . All mothers completed the following four st and ardized question naires before and after the intervention : 1 ) Maternity Blues Scale ; 2 ) State-Trait Anxiety Inventory ; 3 ) Profile of Mood States ( POMS ) ; and 4 ) Feeling toward Baby Scale . In the aromatherapy-massage group , posttreatment scores significantly decreased for the Maternity Blues Scale , the State-Anxiety Inventory , and all but one of the Profile of Mood States subscales . Posttreatment scores in the intervention group significantly increased in Profile of Mood States-Vigor subscale and the Approach Feeling toward Baby subscale . Scores in the intervention group significantly decreased in Conflict Index of Avoidance/Approach Feeling toward Baby subscale . Our results suggest that aromatherapy-massage might be an effective intervention for postpartum mothers to improve physical and mental status and to facilitate mother-infant interaction PURPOSE To test the effectiveness of supplementing usual supportive care with aromatherapy massage in the management of anxiety and depression in cancer patients through a pragmatic two-arm r and omized controlled trial in four United Kingdom cancer centers and a hospice . PATIENTS AND METHODS Two hundred eighty-eight cancer patients , referred to complementary therapy services with clinical anxiety and /or depression , were allocated r and omly to a course of aromatherapy massage or usual supportive care alone . RESULTS Patients who received aromatherapy massage had no significant improvement in clinical anxiety and /or depression compared with those receiving usual care at 10 weeks postr and omization ( odds ratio [ OR ] , 1.3 ; 95 % CI , 0.9 to 1.7 ; P = .1 ) , but did at 6 weeks postr and omization ( OR , 1.4 ; 95 % CI , 1.1 to 1.9 ; P = .01 ) . Patients receiving aromatherapy massage also described greater improvement in self-reported anxiety at both 6 and 10 weeks postr and omization ( OR , 3.4 ; 95 % CI , 0.2 to 6.7 ; P = .04 and OR , 3.4 ; 95 % CI , 0.2 to 6.6 ; P = .04 ) , respectively . CONCLUSION Aromatherapy massage does not appear to confer benefit on cancer patients ' anxiety and /or depression in the long-term , but is associated with clinical ly important benefit up to 2 weeks after the intervention The purpose of this study was to assess the effects of water , lavender , or rosemary scent on physiology and mood state following an anxiety-provoking task . The nonsmoking participants , ages 18–30 years , included 42 women and 31 men who reported demographic information and measures of external temperature and heart rate were taken prior to introduction of an anxiety-eliciting task and exposure to lavender , rosemary , or water scents . Following the task , participants completed the Profile of Mood States to assess mood , and temperature and heart rate were reassessed . Participants rated the pleasantness of the scent received . When pleasantness ratings of scent were covaried , physiological changes in temperature and heart rate did not differ based on scent exposure , but mood ratings differed by scent condition . Participants in the rosemary condition scored higher on measures of tension – anxiety and confusion – bewilderment relative to the lavender and control conditions . The lavender and control conditions showed higher mean vigor – activity ratings relative to the rosemary group , while both rosemary and lavender scents were associated with lower mean ratings on the fatigue – inertia subscale , relative to the control group . These results suggest that , when individual perception of scent pleasantness is controlled , scent has the potential to moderate different aspects of mood following an anxiety-provoking task OBJECTIVE The objective is to identify whether single 20 min massage sessions were safe and effective in reducing stress levels of isolated haematological oncology patients . DESIGN Based on a r and omised controlled trial , 39 patients were r and omised to aromatherapy , massage or rest ( control ) arm . MEASURES The measures were serum cortisol and prolactin levels , quality of life ( EORTC QLQ-C30 ) and semi-structured interviews . Primary outcome measure was the fall in serum cortisol levels . RESULTS A significant difference was seen between arms in cortisol ( P=0.002 ) and prolactin ( p=0.031 ) levels from baseline to 30 min post-session . Aromatherapy and massage arms showed a significantly greater drop in cortisol than the rest arm . Only the massage arm had a significantly greater reduction in prolactin then the rest arm . The EORTC QLQ-C30 showed a significant reduction in ' need for rest ' for patients in both experimental arms compared with the control arm , whereas the semi-structured interviews identified a universal feeling of relaxation in patients in the experimental arms . CONCLUSION This pilot study demonstrated that in isolated haematological oncology patients , a significant reduction in cortisol could be safely achieved through massage , with associated improvement in psychological well-being . The implication s are discussed The purpose of this study was to evaluate the use of aromatherapy to reduce anxiety prior to a scheduled colonoscopy or esophagogastroduodenoscopy . A controlled , prospect i ve study was done on a convenience sample of 118 patients . The “ state ” component of the State Trait Anxiety Inventory ( STAI ) was used to evaluate patients ' anxiety levels pre- and postaromatherapy . The control group was given an inert oil ( placebo ) for inhalation , and the experimental group was given the essential oil , lavender , for inhalation . The STAI state anxiety raw score revealed that patients were at the 99th ( women ) and 96th ( men ) percentiles for anxiety . The intervention group and the control group had similar levels of state anxiety prior to the beginning of the study ( t[116 ] = .47 , p = .64 ) . There was no difference in state anxiety levels between pre- and postplacebo inhalation in the control group ( t[112 ] = .48 , p = .63 ) . There was no statistical difference in state anxiety levels between pre- and postlavender inhalation in the experimental group ( t[120 ] = .73 , p = .47 ) . Although this study did not show aromatherapy to be effective based on statistical analysis , patients did generally report the lavender scent to be pleasant . Lavender is an inexpensive and popular technique for relaxation that can be offered to patients as an opportunity to promote preprocedural stress reduction in a hospital setting Benzodiazepines remain widely used for the treatment of anxiety disorders despite prominent , often limiting side effects including sedation , muscle relaxation , and ataxia . A compound producing a robust anxiolytic action comparable to benzodiazepines , but lacking these limiting side effects at therapeutic doses ( an anxioselective agent ) , would represent an important advance in the treatment of generalized anxiety disorder , and perhaps other anxiety disorders . Here we report that the pyrazolo[1,5-a]-pyrimidine , ocinaplon , exhibits an anxioselective profile in both pre clinical procedures and in patients with generalized anxiety disorder , the most common of the anxiety disorders . In rats , ocinaplon produces significant muscle relaxation , ataxia , and sedation only at doses > 25-fold higher than the minimum effective dose ( 3.1 mg/kg ) in the Vogel " conflict " test . This anticonflict effect is blocked by flumazenil ( Ro 15 - 1788 ) , indicating that like benzodiazepines , ocinaplon produces an anxiolytic action through allosteric modulation of GABA(A ) receptors . Nonetheless , in eight recombinant GABA(A ) receptor isoforms expressed in Xenopus oocytes , the potency and efficacy of ocinaplon to potentiate GABA responses varied with subunit composition not only in an absolute sense , but also relative to the prototypical benzodiazepine , diazepam . In a double blind , placebo controlled clinical trial , a 2-week regimen of ocinaplon ( total daily dose of 180 - 240 mg ) produced statistically significant reductions in the Hamilton rating scale for anxiety scores . In this study , the incidence of benzodiazepine-like side effects ( e.g. , sedation , dizziness ) in ocinaplon-treated patients did not differ from placebo . These findings indicate that ocinaplon represents a unique approach both for the treatment and underst and ing of anxiety disorders The use of complementary therapies , such as massage and aromatherapy massage , is rising in popularity among patients and healthcare professionals . They are increasingly being used to improve the quality of life of patients , but there is little evidence of their efficacy . This study assessed the effects of massage and aromatherapy massage on cancer patients in a palliative care setting . We studied 103 patients , who were r and omly allocated to receive massage using a carrier oil ( massage ) or massage using a carrier oil plus the Roman chamomile essential oil ( aromatherapy massage ) . Outcome measurements included the Rotterdam Symptom Checklist ( RSCL ) , the State – Trait Anxiety Inventory ( STAI ) and a semi-structured question naire , administered 2 weeks postmassage , to explore patients ' perceptions of massage . There was a statistically significant reduction in anxiety after each massage on the STAI ( P < 0.001 ) , and improved scores on the RSCL : psychological ( P < 0.001 ) , quality of life ( P < 0.01 ) , severe physical ( P < 0.05 ) , and severe psychological ( P < 0.05 ) subscales for the combined aromatherapy and massage group . The aromatherapy group 's scores improved on all RSCL subscales at the 1 % level of significance or better , except for severely restricted activities . The massage group 's scores improved on four RSCL subscales but these improvements did not reach statistical significance . Massage with or without essential oils appears to reduce levels of anxiety . The addition of an essential oil seems to enhance the effect of massage and to improve physical and psychological symptoms , as well as overall quality of life PURPOSE To determine whether the inhalation of aromatherapy during radiotherapy reduces anxiety . PATIENTS AND METHODS Three hundred thirteen patients undergoing radiotherapy were r and omly assigned to receive either carrier oil with fractionated oils , carrier oil only , or pure essential oils of lavender , bergamot , and cedarwood administered by inhalation concurrently with radiation treatment . Patients underwent assessment by the Hospital Anxiety and Depression Scale ( HADS ) and the Somatic and Psychological Health Report ( SPHERE ) at baseline and at treatment completion . RESULTS There were no significant differences in HADS depression or SPHERE scores between the r and omly assigned groups . However , HADS anxiety scores were significantly lower at treatment completion in the carrier oil only group compared with either of the fragrant arms ( P = .04 ) . CONCLUSION Aromatherapy , as administered in this study , is not beneficial |
11,835 | 28,843,576 | Interpretation We found evidence that HSV-2 infection increases the risk of HIV acquisition .
Interventions targeting HSV-2 , such as new HSV vaccines , have the potential for additional benefit against HIV , which could be particularly powerful in regions with a high incidence of co-infection . | Summary Background HIV and herpes simplex virus type 2 ( HSV-2 ) infections cause a substantial global disease burden and are epidemiologically correlated .
Two previous systematic review s of the association between HSV-2 and HIV found evidence that HSV-2 infection increases the risk of HIV acquisition , but these review s are now more than a decade old . | Background : In the And ean Region , HIV and sexually transmitted infections ( STI ) are most prevalent among men who have sex with men ( MSM ) , but incidence estimates and associated factors have never been prospect ively assessed . Methods : A cohort of 1056 high-risk HIV-negative MSM in Lima , Peru , were recruited during 1998 - 2000 ( the ALASKA Cohort ) , and a nested case-control analysis was conducted between seroconverters and nonseroconverters , matched 1:3 by age and duration of follow-up for comparison of risk behaviors , acute retroviral symptoms , circumcision , and STI . Results : During average follow-up of 335 days , 34 men seroconverted , providing a HIV incidence estimate of 3.5 per 100 person-years [ 95 % confidence interval ( CI ) : 2.3 to 4.7 ] . High syphilis ( 8.4 per 100 person-years , 95 % CI : 6.7 to 10.1 ) and herpes simplex virus type 2 ( HSV-2 ) infection ( 10.4 per 100 person-years , 95 % CI : 8.6 to 11.9 ) incidence estimates were obtained . HIV seroconverters were more likely than men who remained seronegative to report fever ≥3 days ( 46 % vs. 7 % ) , to seek medical care ( 62 % vs. 27 % ) , and to have ≥1 casual partner ( 86.2 % vs. 74.1 % ) since their last visit . HIV seroconverters also were more likely to have acquired syphilis or HSV-2 infection ( 31 % vs. 8 % among initially HSV-2-seronegative men ) although they were less likely to be circumcised ( 4.2 % vs. 20.6 % , a nonsignificant difference ) . In multivariate analysis , incident syphilis or HSV-2 infection ( odds ratio [ OR ] : 5.9 , 95 % CI : 1.5 to 22.7 ) and sex with any casual partner ( OR : 4.8 , 95 % CI : 0.9 to 26.2 ) were associated with HIV seroconversion . Conclusions : STI that may cause anogenital ulcers are important risk factors for HIV acquisition among high-risk MSM in Lima , a population with a very high HIV incidence estimate . Synergistic interventions focusing in preventing both HIV and HSV-2 , like male circumcision , are warranted to be assessed , especially in MSM population s with low levels of circumcision and high incidence estimates of ulcerative STI Background Although HIV treatment as prevention ( TasP ) via early antiretroviral therapy ( ART ) has proven to reduce transmissions among HIV-serodiscordant couples , its full implementation in developing countries remains a challenge . In this study , we determine whether China 's current HIV treatment program prevents new HIV infections among discordant couples in rural China . Methods A prospect i ve , longitudinal cohort study was conducted from June 2009 to March 2011 , in rural Yunnan . A total of 1,618 HIV-discordant couples were eligible , 1,101 were enrolled , and 813 were followed for an average of 1.4 person-years ( PY ) . Routine ART was prescribed to HIV-positive spouses according to eligibility ( CD4<350 cells/µl ) . Seroconversion was used to determine HIV incidence . Results A total of 17 seroconversions were documented within 1,127 PY of follow-up , for an overall incidence of 1.5 per 100 PY . Epidemiological and genetic evidence confirmed that all 17 seroconverters were infected via marital secondary sexual transmission . Having an ART-experienced HIV-positive partner was associated with a lower rate of seroconvertion compared with having an ART-naïve HIV-positive partner ( 0.8 per 100 PY vs. 2.4 per 100 PY , HR = 0.34 , 95%CI = 0.12–0.97 , p = 0.0436 ) . While we found that ART successfully suppressed plasma viral load to < 400 copies/ml in the majority of cases ( 85.0 % vs. 19.5 % , p<0.0001 at baseline ) , we did document five seroconversions among ART-experienced subgroup . Conclusions ART is associated with a 66 % reduction in HIV incidence among discordant couples in our sample , demonstrating the effectiveness of China 's HIV treatment program at preventing new infections , and providing support for earlier ART initiation and TasP implementation in this region Introduction : We explored factors associated with differential HIV incidence among women participating in a HIV prevention trial in Harare , Durban , and Johannesburg . The trial had shown no effect of the intervention ( diaphragm and lubricant gel ) on HIV incidence . Methods : A prospect i ve cohort analysis was conducted of trial participants followed for 12 - 24 months . Sociodemographic , biological , and behavioral data were collected at baseline and at quarterly visits . Factors associated with HIV incidence were estimated using multivariable Cox regression models , stratified by study location . Attributable risk was calculated from the adjusted hazard ratios ( AHR ) . Results : There were 309 incident HIV infections among the 4948 women in the analysis . HIV incidence was highest in Durban [ 6.75/100 person-years ; 95 % confidence interval ( CI ) : 5.74 to 7.93 ] , lower in Johannesburg ( 3.33/100 person-years ; 95 % CI : 2.51 to 4.44 ) , and lowest in Harare ( 2.72/100 person-years ; 95 % CI : 2.26 to 3.26 ) . Sexually transmitted infections were important risk factors in Harare [ prevalent herpes simplex virus type 2 ( HSV2 ) AHR = 2.56 , 95 % CI : 1.61 to 4.06 ; incident HSV2 AHR = 12.60 , 95 % CI : 2.13 to 21.87 ; Neisseria gonorrhoeae AHR = 6.82 , 95 % CI : 2.13 to 21.87 ] and in Durban ( prevalent HSV2 AHR = 1.64 , 95 % CI : 1.07 to 2.51 ; N. gonorrhoeae AHR = 4.40 , 95 % CI : 2.07 to 9.39 ) . In Durban , having multiple partners ( adjusted odds ratio ( AOR ) = 1.78 95 % CI : 1.11 to 2.85 ) and sex although a partner was under the influence of alcohol/drugs ( AOR = 1.51 95 % CI : 1.05 to 2.16 ) significantly increased risk , whereas in Johannesburg , sexual debut < 16 years ( AOR = 2.60 95 % CI : 1.30 to 5.17 ) was a strong predictor of HIV acquisition . Discussion : Important differences were seen in drivers of HIV incidence at the 3 study locations . Results from this analysis imply that targeted HIV programing could have a large impact on incident HIV infection in women , and that the most effective approach will likely vary based on knowledge of the local situation/epidemiology Objective : We assessed the protective effect of medical male circumcision ( MMC ) against HIV , herpes simplex virus type 2 ( HSV-2 ) , and genital ulcer disease ( GUD ) incidence . Design : Two thous and , seven hundred and eighty-seven men aged 18–24 years living in Kisumu , Kenya were r and omly assigned to circumcision ( n=1391 ) or delayed circumcision ( n = 1393 ) and assessed by HIV and HSV-2 testing and medical examinations during follow-ups at 1 , 3 , 6 , 12 , 18 , and 24 months . Methods : Cox regression estimated the risk ratio of each outcome ( incident HIV , GUD , HSV-2 ) for circumcision status and multivariable models estimated HIV risk associated with HSV-2 , GUD , and circumcision status as time-varying covariates . Results : HIV incidence was 1.42 per 100 person-years . Circumcision was 62 % protective against HIV [ risk ratio = 0.38 ; 95 % confidence interval ( CI ) 0.22–0.67 ] and did not change when controlling for HSV-2 and GUD ( risk ratio = 0.39 ; 95 % CI 0.23–0.69 ) . GUD incidence was halved among circumcised men ( risk ratio = 0.52 ; 95 % CI 0.37–0.73 ) . HSV-2 incidence did not differ by circumcision status ( risk ratio = 0.94 ; 95 % CI 0.70–1.25 ) . In the multivariable model , HIV seroconversions were tripled ( risk ratio = 3.44 ; 95 % CI 1.52–7.80 ) among men with incident HSV-2 and seven times greater ( risk ratio = 6.98 ; 95 % CI 3.50–13.9 ) for men with GUD . Conclusion : Contrary to findings from the South African and Ug and an trials , the protective effect of MMC against HIV was independent of GUD and HSV-2 , and MMC had no effect on HSV-2 incidence . Determining the causes of GUD is necessary to reduce associated HIV risk and to underst and how circumcision confers protection against GUD and HIV BACKGROUND Male circumcision could provide substantial protection against acquisition of HIV-1 infection . Our aim was to determine whether male circumcision had a protective effect against HIV infection , and to assess safety and changes in sexual behaviour related to this intervention . METHODS We did a r and omised controlled trial of 2784 men aged 18 - 24 years in Kisumu , Kenya . Men were r and omly assigned to an intervention group ( circumcision ; n=1391 ) or a control group ( delayed circumcision , 1393 ) , and assessed by HIV testing , medical examinations , and behavioural interviews during follow-ups at 1 , 3 , 6 , 12 , 18 , and 24 months . HIV seroincidence was estimated in an intention-to-treat analysis . This trial is registered with Clinical Trials.gov , with the number NCT00059371 . FINDINGS The trial was stopped early on December 12 , 2006 , after a third interim analysis review ed by the data and safety monitoring board . The median length of follow-up was 24 months . Follow-up for HIV status was incomplete for 240 ( 8.6 % ) participants . 22 men in the intervention group and 47 in the control group had tested positive for HIV when the study was stopped . The 2-year HIV incidence was 2.1 % ( 95 % CI 1.2 - 3.0 ) in the circumcision group and 4.2 % ( 3.0 - 5.4 ) in the control group ( p=0.0065 ) ; the relative risk of HIV infection in circumcised men was 0.47 ( 0.28 - 0.78 ) , which corresponds to a reduction in the risk of acquiring an HIV infection of 53 % ( 22 - 72 ) . Adjusting for non-adherence to treatment and excluding four men found to be seropositive at enrollment , the protective effect of circumcision was 60 % ( 32 - 77 ) . Adverse events related to the intervention ( 21 events in 1.5 % of those circumcised ) resolved quickly . No behavioural risk compensation after circumcision was observed . INTERPRETATION Male circumcision significantly reduces the risk of HIV acquisition in young men in Africa . Where appropriate , voluntary , safe , and affordable circumcision services should be integrated with other HIV preventive interventions and provided as expeditiously as possible Vaginal Gel Versus HIV HIV prevention technologies for women are urgently needed , especially in sub-Saharan Africa where young women bear the greatest burden of the HIV epidemic . Abdool Karim et al. ( p. 1168 ; published online 19 July ) present the results of the CAPRISA 004 r and omized control trial . The nearly 3-year-long trial , conducted in urban and rural South African women , tested the efficacy of a vaginal gel containing the antiretroviral drug tenofovir in preventing HIV infection . The dosing strategy required application of the gel both before and after coitus , and with this regime HIV infection was reduced by approximately 39 % overall , by 54 % in women with high adherence to the protocol , and with no increase in overall adverse event rates . Tenofovir in a vaginal gel formulation shows significant protection against HIV infection in a r and omized control trial . The Centre for the AIDS Program of Research in South Africa ( CAPRISA ) 004 trial assessed the effectiveness and safety of a 1 % vaginal gel formulation of tenofovir , a nucleotide reverse transcriptase inhibitor , for the prevention of HIV acquisition in women . A double-blind , r and omized controlled trial was conducted comparing tenofovir gel ( n = 445 women ) with placebo gel ( n = 444 women ) in sexually active , HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal , South Africa . HIV serostatus , safety , sexual behavior , and gel and condom use were assessed at monthly follow-up visits for 30 months . HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years ( person time of study observation ) ( 38 out of 680.6 women-years ) compared with 9.1 per 100 women-years ( 60 out of 660.7 women-years ) in the placebo gel arm ( incidence rate ratio = 0.61 ; P = 0.017 ) . In high adherers ( gel adherence > 80 % ) , HIV incidence was 54 % lower ( P = 0.025 ) in the tenofovir gel arm . In intermediate adherers ( gel adherence 50 to 80 % ) and low adherers ( gel adherence < 50 % ) , the HIV incidence reduction was 38 and 28 % , respectively . Tenofovir gel reduced HIV acquisition by an estimated 39 % overall , and by 54 % in women with high gel adherence . No increase in the overall adverse event rates was observed . There were no changes in viral load and no tenofovir resistance in HIV seroconverters . Tenofovir gel could potentially fill an important HIV prevention gap , especially for women unable to successfully negotiate mutual monogamy or condom use Background : The epidemiologic utility of STARHS hinges not only on producing accurate estimates of HIV incidence , but also on identifying risk factors for recent HIV infection . Methods : As part of an HIV seroincidence study , 800 Rw and an female sex workers ( FSW ) were HIV tested , with those testing positive further tested by BED-CEIA ( BED ) and AxSYM Avidity Index ( Ax-AI ) assays . A sample of HIV-negative ( N=397 ) FSW were followed prospect ively for HIV seroconversion . We compared estimates of risk factors for : 1 ) prevalent HIV infection ; 2 ) recently acquired HIV infection ( RI ) based on three different STARHS classifications ( BED alone , Ax-AI alone , BED/Ax-AI combined ) ; and 3 ) prospect ively observed seroconversion . Results : There was mixed agreement in risk factors between methods . HSV-2 coinfection and recent STI treatment were associated with both prevalent HIV infection and all three measures of recent infection . A number of risk factors were associated only with prevalent infection , including widowhood , history of forced sex , regular alcohol consumption , prior imprisonment , and current breastfeeding . Number of sex partners in the last 3 months was associated with recent infection based on BED/Ax-AI combined , but not other STARHS-based recent infection outcomes or prevalent infection . Risk factor estimates for prospect ively observed seroconversion differed in magnitude and direction from those for recent infection via STARHS . Conclusions : Differences in risk factor estimates by each method could reflect true differences in risk factors between the prevalent , recently , or newly infected population s , the effect of study interventions ( among those followed prospect ively ) , or assay misclassification . Similar investigations in other population s/ setting s are needed to further establish the epidemiologic utility of STARHS for identifying risk factors , in addition to incidence rate estimation BACKGROUND Knowledge of factors that affect per-act infectivity of human immunodeficiency virus type 1 ( HIV-1 ) is important for design ing HIV-1 prevention interventions and for the mathematical modeling of the spread of HIV-1 . METHODS We analyzed data from a prospect i ve study of African HIV-1-serodiscordant couples . We assessed transmissions for linkage within the study partnership , based on HIV-1 sequencing . The primary exposure measure was the HIV-1-seropositive partners ' reports of number of sex acts and condom use with their study partner . RESULTS Of 3297 couples experiencing 86 linked HIV-1 transmissions , the unadjusted per-act risks of unprotected male-to-female ( MTF ) and female-to-male ( FTM ) transmission were 0.0019 ( 95 % confidence interval [ CI ] , .0010-.0037 ) and 0.0010 ( 95 % CI , .00060-.0017 ) , respectively . After adjusting for plasma HIV-1 RNA of the HIV-1-infected partner and herpes simplex virus type 2 serostatus and age of the HIV-1-uninfected partner , we calculated the relative risk ( RR ) for MTF versus FTM transmission to be 1.03 ( P = .93 ) . Each log(10 ) increase in plasma HIV-1 RNA increased the per-act risk of transmission by 2.9-fold ( 95 % CI , 2.2 - 3.8 ) . Self-reported condom use reduced the per-act risk by 78 % ( RR = 0.22 [ 95 % CI , .11-.42 ] ) . CONCLUSIONS Modifiable risk factors for HIV-1 transmission were plasma HIV-1 RNA level and condom use , and , in HIV-1-uninfected partners , herpes simplex virus 2 infection , genital ulcers , Trichomonas vaginalis , vaginitis or cervicitis , and male circumcision BACKGROUND The MRKAd5 HIV-1 gag/pol/nef subtype B vaccine was design ed to elicit T-cell-mediated immune responses capable of providing complete or partial protection from HIV-1 infection or a decrease in viral load after acquisition . We aim to assess the safety and efficacy of the vaccine in South Africa , where the major circulating clade is subtype C. METHODS We did a phase 2b double-blind , r and omised test-of-concept study in sexually active HIV-1 seronegative participants at five sites in South Africa . R and omisation was by a computer-generated r and om number sequence . The vaccine and placebo were given by intramuscular injection on a 0 , 1 , 6 month schedule . Our co primary endpoints were a vaccine-induced reduction in HIV-1 acquisition and viral-load setpoint . These endpoints were assessed independently in the modified intention-to-treat ( MITT ) cohort with two-tailed significance tests stratified by sex . We assessed immunogenicity by interferon-γ ELISPOT in peripheral-blood mononuclear cells . After the lack of efficacy of the MRKAd5 HIV-1 vaccine in the Step study , enrolment and vaccination in our study was halted , treatment allocations were unmasked , and follow-up continued . This study is registered with the South Africa National Health Research Data base , number DOH-27 - 0207 - 1539 , and Clinical Trials.gov , number NCT00413725 . FINDINGS 801 of a scheduled 3000 participants , of whom 360 ( 45 % ) were women , were r and omly assigned to receive either vaccine or placebo . 445 participants ( 56 % ) had adenovirus serotype 5 ( Ad5 ) titres greater than 200 , and 129 men ( 29 % ) were circumcised . 34 MITT participants in the vaccine group were diagnosed with HIV-1 ( incidence rate 4·54 per 100 person-years ) and 28 in the placebo group ( 3·70 per 100 person-years ) . There was no evidence of vaccine efficacy ; the hazard ratio adjusted for sex was 1·25 ( 95 % CI 0·76 - 2·05 ) . Vaccine efficacy did not differ by Ad5 titre , sex , age , herpes simplex virus type 2 status , or circumcision . The geometric mean viral-load setpoint was 20,483 copies per mL ( n=33 ) in the vaccine group and 34,032 copies per mL ( n=28 ) in the placebo group ( p=0·39 ) . The vaccine elicited interferon-γ-secreting T cells that recognised both clade B ( 89 % ) and C ( 77 % ) antigens . INTERPRETATION The MRKAd5 HIV-1 vaccine did not prevent HIV-1 infection or lower viral-load setpoint ; however , stopping our trial early probably compromised our ability to draw conclusions . The high incidence rates noted in South Africa highlight the crucial need for intensified efforts to develop an efficacious vaccine . FUNDING The US National Institute of Allergy and Infectious Disease and Merck and Co Introduction Adolescents having unprotected heterosexual intercourse are at risk of HIV infection and unwanted pregnancy . However , there is little evidence to indicate whether pregnancy in early adolescence increases the risk of subsequent HIV infection . In this paper , we tested the hypothesis that adolescent pregnancy ( aged 15 or younger ) increases the risk of incident HIV infection in young South African women . Methods We assessed 1099 HIV-negative women , aged 15–26 years , who were volunteer participants in a cluster-r and omized , controlled HIV prevention trial in the predominantly rural Eastern Cape province of South Africa . All of these young women had at least one additional HIV test over two years of follow-up . Outcomes were HIV incidence rates per 100 person years and HIV incidence rate ratios ( IRRs ) estimated by Poisson multivariate models . Three pregnancy categories were created for the Poisson model : early adolescent pregnancy ( a first pregnancy at age 15 years or younger ) ; later adolescent pregnancy ( a first pregnancy at age 16 to 19 years ) ; and women who did not report an adolescent pregnancy . Models were adjusted for study design , age , education , time since first sexual experience , socio-economic status , childhood trauma and herpes simplex virus type 2 infection . Results HIV incidence rates were 6.0 per 100 person years over two years of follow-up . The adjusted IRR was 3.02 ( 95 % CI 1.50–6.09 ) for a pregnancy occurring at age 15 or younger . Women with pregnancies occurring between 16 and 19 years of age did not have a higher incidence of HIV ( IRR 1.08 ; 95 % CI 0.64–1.84 ) . Early adolescent pregnancies were associated with higher partner numbers and a greater age difference with partners . Conclusions Early adolescent pregnancies increase the incidence of HIV among South African women . The higher risk is associated with sexual risk behaviours such as higher partner numbers and a greater age difference with partners rather than a biological explanation of hormonal changes during pregnancy Background : An association has been demonstrated between herpes simplex type 2 ( HSV-2 ) and HIV infection among men , but prospect i ve studies in women have yielded mixed results . Objective : To estimate the effects of prevalent and incident HSV-2 infection on subsequent HIV acquisition among women in two African countries . Design : Prospect i ve cohort study . Methods : HSV-2 and HIV serostatus were evaluated at enrollment and quarterly for 15–24 months among 4531 sexually active , HIV-uninfected women aged 18–35 years from Ug and a and Zimbabwe . The association between prior HSV-2 infection and HIV acquisition was estimated using a marginal structural discrete survival model , adjusted for covariates . Results : HSV-2 seroprevalence at enrollment was 52 % in Ug and a and 53 % in Zimbabwe ; seroincidence during follow-up was 9.6 and 8.8/100 person-years in Ug and a and Zimbabwe , respectively . In Ug and a , the hazard ratio ( HR ) for HIV was 2.8 [ 95 % confidence interval ( CI ) , 1.5–5.3 ] among women with seroprevalent HSV-2 and 4.6 ( 95 % CI , 1.6–13.1 ) among women with seroincident HSV-2 , adjusted for confounding . In Zimbabwe , the HR for HIV was 4.4 ( 95 % CI , 2.7–7.2 ) among women with seroprevalent HSV-2 , and 8.6 ( 95 % CI , 4.3–17.1 ) among women with seroincident HSV-2 , adjusted for confounding . The population attributable risk percent for HIV due to prevalent and incident HSV-2 infection was 42 % in Ug and a and 65 % in Zimbabwe . Conclusions : HSV-2 plays an important role in the acquisition of HIV among women . Efforts to implement known HSV-2 control measures , as well as identify additional measures to control HSV-2 , are urgently needed to curb the spread of HIV BACKGROUND Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus ( HIV ) acquisition . METHODS We r and omly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs , emtricitabine and tenofovir disoproxil fumarate ( FTC-TDF ) , or placebo once daily . All subjects received HIV testing , risk-reduction counseling , condoms , and management of sexually transmitted infections . RESULTS The study subjects were followed for 3324 person-years ( median , 1.2 years ; maximum , 2.8 years ) . Of these subjects , 10 were found to have been infected with HIV at enrollment , and 100 became infected during follow-up ( 36 in the FTC-TDF group and 64 in the placebo group ) , indicating a 44 % reduction in the incidence of HIV ( 95 % confidence interval , 15 to 63 ; P=0.005 ) . In the FTC-TDF group , the study drug was detected in 22 of 43 of seronegative subjects ( 51 % ) and in 3 of 34 HIV-infected subjects ( 9 % ) ( P<0.001 ) . Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group ( P<0.001 ) . The two groups had similar rates of serious adverse events ( P=0.57 ) . CONCLUSIONS Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects . Detectable blood levels strongly correlated with the prophylactic effect . ( Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation ; Clinical Trials.gov number , NCT00458393 . ) BACKGROUND Cross-sectional studies have shown that intimate partner violence and gender inequity in relationships are associated with increased prevalence of HIV in women . Yet temporal sequence and causality have been question ed , and few HIV prevention programmes address these issues . We assessed whether intimate partner violence and relationship power inequity increase risk of incident HIV infection in South African women . METHODS We did a longitudinal analysis of data from a previously published cluster-r and omised controlled trial undertaken in the Eastern Cape province of South Africa in 2002 - 06 . 1099 women aged 15 - 26 years who were HIV negative at baseline and had at least one additional HIV test over 2 years of follow-up were included in the analysis . Gender power equity and intimate partner violence were measured by a sexual relationship power scale and the WHO violence against women instrument , respectively . Incidence rate ratios ( IRRs ) of HIV acquisition at 2 years were derived from Poisson models , adjusted for study design and herpes simplex virus type 2 infection , and used to calculate population attributable fractions . FINDINGS 128 women acquired HIV during 2076 person-years of follow-up ( incidence 6.2 per 100 person-years ) . 51 of 325 women with low relationship power equity at baseline acquired HIV ( 8.5 per 100 person-years ) compared with 73 of 704 women with medium or high relationship power equity ( 5.5 per 100 person-years ) ; adjusted multivariable Poisson model IRR 1.51 , 95 % CI 1.05 - 2.17 , p=0.027 . 45 of 253 women who reported more than one episode of intimate partner violence at baseline acquired HIV ( 9.6 per 100 person-years ) compared with 83 of 846 who reported one or no episodes ( 5.2 per 100 person-years ) ; adjusted multivariable Poisson model IRR 1.51 , 1.04 - 2.21 , p=0.032 . The population attributable fractions were 13.9 % ( 95 % CI 2.0 - 22.2 ) for relationship power equity and 11.9 % ( 1.4 - 19.3 ) for intimate partner violence . INTERPRETATION Relationship power inequity and intimate partner violence increase risk of incident HIV infection in young South African women . Policy , interventions , and programmes for HIV prevention must address both of these risk factors and allocate appropriate re sources . FUNDING National Institute of Mental Health and South African Medical Research Council The first estimates of the seroincidence of human immunodeficiency virus type 1 ( HIV-1 ) and of the risk factors for seroconversion in a cohort of high-risk patients attending sexually transmitted disease ( STD ) clinics in India are reported . Between 1993 and 1995 , 851 HIV-1-seronegative persons were evaluated prospect ively every 3 months for HIV infection and biologic and behavioral characteristics . The overall incidence of HIV-1 was 10.2/100 person-years ( 95 % confidence interval , 7.9 - 13.1 ) . The incidence among commercial sex workers ( CSWs ) was 26.1/100 person-years , compared with 8.4 among non-CSWs . Recurrent genital ulcer disease and urethritis or cervicitis during the follow-up period were independently associated with a 7- ( P < .001 ) and 3-fold ( P = .06 ) increased risk of HIV-1 seroconversion , respectively . Because of the association of recurrent ulcerative and nonulcerative STDs with HIV-1 seroconversion in this setting , behavioral and biologic measures directed at the prevention and control of STDs would be expected to greatly reduce the transmission of HIV-1 infection in similar high-risk groups BACKGROUND Male circumcision significantly reduced the incidence of human immunodeficiency virus ( HIV ) infection among men in three clinical trials . We assessed the efficacy of male circumcision for the prevention of herpes simplex virus type 2 ( HSV-2 ) and human papillomavirus ( HPV ) infections and syphilis in HIV-negative adolescent boys and men . METHODS We enrolled 5534 HIV-negative , uncircumcised male subjects between the ages of 15 and 49 years in two trials of male circumcision for the prevention of HIV and other sexually transmitted infections . Of these subjects , 3393 ( 61.3 % ) were HSV-2-seronegative at enrollment . Of the seronegative subjects , 1684 had been r and omly assigned to undergo immediate circumcision ( intervention group ) and 1709 to undergo circumcision after 24 months ( control group ) . At baseline and at 6 , 12 , and 24 months , we tested subjects for HSV-2 and HIV infection and syphilis , along with performing physical examinations and conducting interviews . In addition , we evaluated a subgroup of subjects for HPV infection at baseline and at 24 months . RESULTS At 24 months , the cumulative probability of HSV-2 seroconversion was 7.8 % in the intervention group and 10.3 % in the control group ( adjusted hazard ratio in the intervention group , 0.72 ; 95 % confidence interval [ CI ] , 0.56 to 0.92 ; P=0.008 ) . The prevalence of high-risk HPV genotypes was 18.0 % in the intervention group and 27.9 % in the control group ( adjusted risk ratio , 0.65 ; 95 % CI , 0.46 to 0.90 ; P=0.009 ) . However , no significant difference between the two study groups was observed in the incidence of syphilis ( adjusted hazard ratio , 1.10 ; 95 % CI , 0.75 to 1.65 ; P=0.44 ) . CONCLUSIONS In addition to decreasing the incidence of HIV infection , male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection , findings that underscore the potential public health benefits of the procedure . ( Clinical Trials.gov numbers , NCT00425984 and NCT00124878 . Background More insight is needed regarding risk factors for prevalent and incident HIV-1 infection among male farm workers in Sub-Saharan Africa to control the HIV-1 epidemic . Methods Male farm workers were recruited from a sugar estate in Zambia to participate in a prospect i ve cohort study . Question naire data were collected via interview , and testing was conducted for HIV-1 , herpes simplex virus type 2 ( HSV-2 ) , and syphilis infection at baseline and follow-up between May 2006 and September 2007 . Results Among 1062 workers enrolled , HIV-1 prevalence at baseline was 20.7 % . Testing HSV-2 seropositive ( adjusted odds ratio ( AOR ) 5.4 , 95 % CI 3.6 to 8.1 ) , self-reported genital ulcers in the past year ( AOR 2.8 , 95 % CI 1.9 to 4.2 ) , and being widowed ( AOR 3.7 , 95 % CI 2.0 to 6.9 ) were significantly associated with prevalent HIV-1 infection . The HIV-1 incidence among 731 initially negative participants with at least one follow-up visit was 4.1 per 1000 person-months ( 95 % CI 2.6 to 5.7 ) ; seroconversion was independently associated with prevalent HSV-2 infection ( adjusted hazard ratio ( AHR ) 2.4 , 95 % CI 1.0 to 5.8 ) and incident HSV-2 infection ( AHR 18.0 , 95 % CI 4.2 to 76.3 ) . HIV-1 prevalence and incidence rates were similar among migrant and non-migrant workers . Conclusions HIV-1 prevalence and incidence were high , and HSV-2 infection was a risk factor for HIV-1 acquisition . There is an urgent need to exp and HIV-1 prevention programmes tailored to farm workers and their communities We studied the role of genital ulcerative infections for acquisition of human immunodeficiency virus type 1 ( HIV-1 ) infection in a cohort of 989 homosexual men in Amsterdam between October 1984 and December 1988 . Among 53 HIV-1 seroconverters serological and anamnestic data were gathered regarding herpes simplex virus type 2 ( HSV-2 ) and syphilis in the 6 months before seroconversion . For statistical analysis a control who remained seronegative during the same interval was selected at r and om for each HIV-1 seroconverter . A significant difference between the prevalence of HSV-2 antibodies among HIV-1 seroconverters and controls was found ( 72 % vs 38 % ) . HSV-2 seroconversions among men initially seronegative for HSV-2 were found among three of 18 HIV-1 seroconverters and among three of 36 controls . ( O.R. = 2.2 , 95 % C.I. 0.4 - 12.1 ) . Self-reported cases of anogenital herpes were found more frequently among HIV-1 seroconverters ( 8) than among controls ( 4 ) . One case of syphilis was diagnosed among HIV-1 seroconverters , and one among controls . Summing up these cases we assessed the total number of genital ulcerative infections : 12 among HIV-1 seroconverters and eight among controls ( 23 vs 15 % , O.R. 1.7 , C.I. 0.6 - 4.62 ) . These data suggest little evidence for genital ulcerative infections being an important independent risk factor for HIV-1 acquisition among homosexual men in Amsterdam during the time period studied Objectives To prepare for future HIV prevention trials , we conducted prospect i ve cohort studies among women working in food and recreational facilities in northern Tanzania . We examined the prevalence and incidence of HIV and HSV-2 , and associated risk factors . Methods Women aged 18–44 years working in food and recreational facilities were screened to determine their eligibility for the studies . Between 2008–2010 , HIV-negative women were enrolled and followed for 12 months . At enrolment and 3-monthly , we collected socio-demographic and behavioural data , and performed clinical examinations for collection of biological specimens that were tested for reproductive tract infections . Risk factors for HIV and HSV-2 incidence were investigated using Poisson regression models . Results We screened 2,229 and enrolled 1,378 women . The median age was 27 years ( interquartile range , IQR 22 , 33 ) , and median duration working at current facility was 2 years . The prevalences of HIV at screening and HSV-2 at enrolment were 16 % and 67 % , respectively . Attendance at the 12-month visit was 86 % . HIV and HSV-2 incidence rates were 3.7 ( 95 % confidence interval , CI : 2.8,5.1 ) and 28.6 ( 95 % CI : 23.5,35.0)/100 person-years , respectively . Women who were separated , divorced , or widowed were at increased risk of HIV ( adjusted incidence rate ratio , aRR = 6.63 ; 95 % CI : 1.97,22.2 ) and HSV-2 ( aRR = 2.00 ; 95 % CI : 1.15,3.47 ) compared with married women . Women reporting ≥3 partners in the past 3 months were at higher HIV risk compared with women with 0–1 partner ( aRR = 4.75 ; 95 % CI : 2.10,10.8 ) , while those who had reached secondary education or above were at lower risk of HSV-2 compared with women with incomplete primary education ( aRR = 0.42 ; 95 % CI : 0.22,0.82 ) . Conclusions HIV and HSV-2 rates remain substantially higher in this cohort than in the general population , indicating urgent need for effective interventions . These studies demonstrate the feasibility of conducting trials to test new interventions in this highly-mobile population BACKGROUND The association between human papillomavirus ( HPV ) infection and the risk of human immunodeficiency virus ( HIV ) seroconversion is unclear , and the genital cellular immunology has not been evaluated . METHODS A case-control analysis nested within a male circumcision trial was conducted . Cases consisted of 44 male HIV seroconverters , and controls were 787 males who were persistently negative for HIV . The Roche HPV Linear Array Genotype Test detected high-risk HPV ( HR-HPV ) and low-risk HPV ( LR-HPV ) genotypes . Generalized estimating equations logistic regression was used to estimate adjusted odds ratios ( aORs ) of HIV seroconversion . In addition , densities of CD1a(+ ) dendritic cells , CD4(+ ) T cells , and CD8(+ ) T cells were measured using immunohistochemistry analysis in foreskins of 79 males r and omly selected from participants in the circumcision trial . RESULTS HR-HPV or LR-HPV acquisition was not significantly associated with HIV seroconversion , after adjustment for sexual behaviors . However , HR-HPV and LR-HPV clearance was significantly associated with HIV seroconversion ( aOR , 3.25 [ 95 % confidence interval { CI } , 1.11 - 9.55 ] and 3.18 [ 95 % CI , 1.14 - 8.90 ] , respectively ) . The odds of HIV seroconversion increased with increasing number of HPV genotypes cleared ( P < .001 , by the test for trend ) . The median CD1a(+ ) dendritic cell density in the foreskin epidermis was significantly higher among males who cleared HPV ( 72.0 cells/mm(2 ) [ interquartile range { IQR } , 29.4 - 138.3 cells/mm(2 ) ] ) , compared with males who were persistently negative for HPV ( 32.1 cells/mm(2 ) [ IQR , 3.1 - 96.2 cells/mm(2 ) ] ; P = .047 ) , and increased progressively with the number of HPV genotypes cleared ( P = .05 ) . CONCLUSIONS HPV clearance was associated with subsequent HIV seroconversion and also with increased epidermal dendritic cell density , which potentially mediates HIV seroconversion Background The Phase 2b double-blinded , r and omized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa . Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas , Caribbean , and Australia was unblinded for non-efficacy . Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients , impelling the HVTN 503-S recall study . Methods HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants , provide HIV testing , risk reduction counseling , physical examination , risk behavior assessment and treatment assignment recall . After adding HVTN 503-S data , HIV-1 infection hazard ratios ( HR vaccine vs. placebo ) were estimated by Cox models . Results Of the 695 eligible , 465 ( 67 % ) enrolled with 230 from the vaccine group and 235 from the placebo group . 38 % of the 184 Phambili dropouts were enrolled . Enrollment did not differ by treatment group , gender , or baseline HSV-2 . With the additional 1286 person years of 503-S follow-up , the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 ( 95 % CI 1.08–2.15 , p = 0.02 , 82 vaccine/54 placebo infections ) . The HR was significant for men ( HR = 2.75 , 95 % CI 1.49 , 5.06 , p = 0.001 ) but not for women ( HR = 1.12 , 95 % CI 0.73 , 1.72 , p = 0.62 ) . Conclusion The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women . Trial Registration clinical trials.gov NCT00413725 SA National Health Research Data base DOH-27 - 0207 - BACKGROUND Prevalent herpes simplex virus type 2 ( HSV-2 ) infection increases human immunodeficiency virus acquisition . We hypothesized that HSV-2 infection might also predispose individuals to acquire other common sexually transmitted infections ( STIs ) . METHODS We studied the association between prevalent HSV-2 infection and STI incidence in a prospect i ve , r and omized trial of periodic STI therapy among Kenyan female sex workers . Participants were screened monthly for infection with Neisseria gonorrhoeae and Chlamydia trachomatis , and at least every 6 months for bacterial vaginosis ( BV ) and infection with Treponema pallidum , Trichomonas vaginalis , and /or HSV-2 . RESULTS Increased prevalence of HSV-2 infection and increased prevalence of BV were each associated with the other ; the direction of causality could not be determined . After stratifying for sexual risk-taking , BV status , and antibiotic use , prevalent HSV-2 infection remained associated with an increased incidence of infection with N. gonorrhoeae ( incidence rate ratio [ IRR ] , 4.3 [ 95 % confidence interval { CI } , 1.5 - 12.2 ] ) , T. vaginalis ( IRR , 2.3 [ 95 % CI , 1.3 - 4.2 ] ) , and syphilis ( IRR , 4.7 [ 95 % CI , 1.1 - 19.9 ] ) . BV was associated with increased rates of infection with C. trachomatis ( IRR , 2.1 [ 95 % CI , 1.1 - 3.8 ] ) and T. vaginalis ( IRR , 8.0 [ 95 % CI , 3.2 - 19.8 ] ) . CONCLUSION ; Increased prevalences of HSV-2 infection and BV were associated with each other and also associated with enhanced susceptibility to an overlapping spectrum of other STIs . Demonstration of causality will require clinical trials that suppress HSV-2 infection , BV , or both Objectives ( 1 ) To assess the HIV incidence rate among men who have sex with men ( MSM ) in a large cohort study in Beijing , China and ( 2 ) to identify sociodemographic and behavioural risk factors of HIV seroconversion among MSM in Beijing , China . Design A prospect i ve cohort study . Setting Baseline and follow-up visits were conducted among MSM in Beijing , China . Participants A cohort of 797 HIV-seronegative MSM was recruited from August to December 2009 , with follow-up occurring after 6 and 12 months . Primary and secondary outcome measures At baseline and follow-up visits , participants reported sociodemographic and sexual behaviour information , and were tested for HIV , herpes simplex virus-2 ( HSV-2 ) and syphilis with whole blood specimens . Cox regression analysis was used to identify factors associated with HIV seroconversion . Results Most study participants ( 86.8 % ) were retained by the 12-month follow-up . The HIV , HSV-2 and syphilis incidence rates were 8.09 ( 95 % CI 6.92 to 9.26 ) , 5.92 ( 95 % CI 5.44 to 6.40 ) and 8.06 ( 95 % CI 7.56 to 8.56 ) cases per 100 person-years , respectively . HIV seroconversion was significantly associated with being < 25 years old , having < 12 years of education , having > 1 male sex partner in the past 6 months , and being syphilis positive or HSV-2 positive . Conclusions The HIV incidence among MSM in Beijing is serious . Interventions and treatment of sexually transmitted diseases ( STD ) should be combined with HIV control and prevention measures among MSM Objective To assess the impact of Stepping Stones , a HIV prevention programme , on incidence of HIV and herpes simplex type 2 ( HSV-2 ) and sexual behaviour . Design Cluster r and omised controlled trial . Setting 70 villages ( clusters ) in the Eastern Cape province of South Africa . Participants 1360 men and 1416 women aged 15 - 26 years , who were mostly attending schools . Intervention Stepping Stones , a 50 hour programme , aims to improve sexual health by using participatory learning approaches to build knowledge , risk awareness , and communication skills and to stimulate critical reflection . Villages were r and omised to receive either this or a three hour intervention on HIV and safer sex . Interviewers administered question naires at baseline and 12 and 24 months and blood was tested for HIV and HSV-2 . Main outcome measures Primary outcome measure : incidence of HIV . Other outcomes : incidence of HSV-2 , unwanted pregnancy , reported sexual practice s , depression , and substance misuse . Results There was no evidence that Stepping Stones lowered the incidence of HIV ( adjusted incidence rate ratio 0.95 , 95 % confidence interval 0.67 to 1.35 ) . The programme was associated with a reduction of about 33 % in the incidence of HSV-2 ( 0.67 , 0.46 to 0.97 ; P=0.036)—that is , Stepping Stones reduced the number of new HSV-2 infections over a two year period by 34.9 ( 1.6 to 68.2 ) per 1000 people exposed . Stepping Stones significantly improved a number of reported risk behaviours in men , with a lower proportion of men reporting perpetration of intimate partner violence across two years of follow-up and less transactional sex and problem drinking at 12 months . In women desired behaviour changes were not reported and those in the Stepping Stones programme reported more transactional sex at 12 months . Conclusion Stepping Stones did not reduce incidence of HIV but had an impact on several risk factors for HIV — notably , HSV-2 and perpetration of intimate partner violence . Trial Registration Clinical Trials NCT00332878 Objective Conventional survival estimates may be biased if loss to follow-up ( LTF ) is associated with the outcome of interest . Our goal was to assess whether the association between sexual risk behavior and HIV-1 acquisition changed after accounting for LTF with competing risks regression . Methods HIV-1-seronegative women who enrolled in a Kenyan sex worker cohort from 1993–2007 were followed prospect ively and tested for HIV at monthly clinic visits . Our primary predictor was self-reported sexual risk behavior in the past week , analyzed as a time-dependent covariate . Outcomes included HIV-1 acquisition and LTF . We analyzed the data using Cox proportional hazards regression and competing risks regression , in which LTF was treated as a competing event . Results A total of 1,513 women contributed 4,150 person-years ( py ) , during which 198 ( 13.1 % ) acquired HIV-1 infection ( incidence , 4.5 per 100 py ) and 969 ( 64.0 % ) were LTF ( incidence , 23.4 per 100 py ) . After adjusting for potential confounders , women reporting unprotected sex with multiple partners were less likely to be lost to follow-up ( adjusted sub-hazard ratio ( aSHR ) 0.50 , 95 % confidence interval ( CI ) 0.32–0.76 , relative to no sexual activity ) . The risk of HIV-1 acquisition after reporting unprotected sex with multiple partners was similar with Cox regression ( adjusted hazard ratio ( aHR ) 2.41 , 95 % CI 1.36–4.27 ) and competing risks regression ( aSHR 2.47 , 95 % CI 1.33–4.58 ) . Conclusions Unprotected sex with multiple partners was associated with higher HIV-1 acquisition risk , but lower attrition . This differential attrition did not substantially bias Cox regression estimates when compared to competing risks regression results BACKGROUND The probability of HIV-1 transmission per coital act in representative African population s is unknown . We aim ed to calculate this probability overall , and to estimate how it is affected by various factors thought to influence infectivity . METHODS 174 monogamous couples , in which one partner was HIV-1 positive , were retrospectively identified from a population cohort in Rakai , Ug and a. Frequency of intercourse and reliability of reporting within couples was assessed prospect ively . HIV-1 seroconversion was determined in the uninfected partners , and HIV-1 viral load was measured in the infected partners . Adjusted rate ratios of transmission per coital act were estimated by Poisson regression . Probabilities of transmission per act were estimated by log-log binomial regression for quartiles of age and HIV-1 viral load , and for symptoms or diagnoses of sexually transmitted diseases ( STDs ) in the HIV-1-infected partners . RESULTS The mean frequency of intercourse was 8.9 per month , which declined with age and HIV-1 viral load . Members of couples reported similar frequencies of intercourse . The overall unadjusted probability of HIV-1 transmission per coital act was 0.0011 ( 95 % CI 0.0008 - 0.0015 ) . Transmission probabilities increased from 0.0001 per act at viral loads of less than 1700 copies/mL to 0.0023 per act at 38 500 copies/mL or more ( p=0.002 ) , and were 0.0041 with genital ulceration versus 0.0011 without ( p=0.02 ) . Transmission probabilities per act did not differ significantly by HIV-1 subtypes A and D , sex , STDs , or symptoms of discharge or dysuria in the HIV-1-positive partner . INTERPRETATION Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act in this Ug and an population BACKGROUND Few data on the effect of human papillomavirus ( HPV ) infection on human immunodeficiency virus ( HIV ) acquisition are available . METHODS HIV-seronegative , sexually active , 18 - 24-year-old Kenyan men participating in a r and omized trial of male circumcision provided exfoliated penile cells from 2 anatomical sites ( glans/coronal sulcus and shaft ) at baseline . The GP5+/6 + polymerase chain reaction assay ascertained a wide range of HPV DNA types at the baseline visit . The risk of HIV infection was estimated using Kaplan-Meier methods and hazard ratios from proportional hazards models . RESULTS Of 2168 uncircumcised men with baseline HPV data , 1089 ( 50 % ) were positive for HPV DNA . The cumulative incidence of HIV infection by 42 months was 5.8 % ( 95 % confidence interval [ CI ] , 3.6%-7.9 % ) among men with HPV-positive glans/coronal sulcus specimens , versus 3.7 % [ 95 % CI , 1.8%-5.6 % ] among men with HPV-negative glans/coronal sulcus specimens ( P = .01 ) . Controlling for subsequent circumcision status , baseline herpes simplex virus type 2 serostatus , and sexual and sociodemographic risk factors , the hazard ratio for HIV infection among men with HPV-positive glans/coronal sulcus specimens was 1.8 ( 95 % CI , 1.1 - 2.9 ) , compared with men with HPV-negative glans/coronal sulcus specimens . CONCLUSION The results suggest an independent increased risk of HIV seroconversion among HPV-positive men . If this finding is confirmed in other studies , HPV prevention could be another tool for HIV prevention The clustering of human papillomavirus ( HPV ) infections in some individuals is often interpreted as the result of common risk factors rather than biological interactions between different types of HPV . The intraindividual correlation between times-at-risk for all HPV infections is not generally considered in the analysis of epidemiologic studies . We used a deterministic transmission model to simulate cross-sectional and prospect i ve epidemiologic studies measuring associations between 2 HPV types . When we assumed no interactions , the model predicted that studies would estimate odds ratios and incidence rate ratios greater than 1 between HPV types even after complete adjustment for sexual behavior . We demonstrated that this residual association is due to correlation between the times-at-risk for different HPV types , where individuals become concurrently at risk for all of their partners ' HPV types when they enter a partnership and are not at risk when they are single . This correlation can be controlled in prospect i ve studies by restricting analyses to susceptible individuals with an infected sexual partner . The bias in the measured associations was largest in low-sexual-activity population s , cross-sectional studies , and studies which evaluated infection with a first HPV type as the exposure . These results suggest that current epidemiologic evidence does not preclude the existence of competitive biological interactions between HPV types Background : Trichomonas vaginalis ( T. vaginalis ) is the most common nonviral sexually transmitted infection in the world . Despite the coexisting global epidemics of T. vaginalis and HIV , little attention has focused on the emerging evidence that T. vaginalis increases susceptibility to , and potentially transmission of , HIV . Methods : We evaluated T. vaginalis infection in the context of a multisite , r and omized controlled trial amongst women in South Africa and Zimbabwe , to determine first , if risk of HIV acquisition was increased among women recently infected with T. vaginalis , and second , if risk of T. vaginalis acquisition was increased among women infected with HIV . Results : After controlling for potential confounders , participants infected with T. vaginalis were more likely to test positive for HIV at their following visit , compared to participants uninfected with T. vaginalis ( adjusted hazard ratio = 2.05 ; 95 % CI , 1.05–4.02 ) . Similarly , HIV-positive participants were twice as likely to have acquired T. vaginalis infection at the following visit , compared to HIV-negative participants ( adjusted hazard ratio = 2.12 ; 95 % CI , 1.35–3.32 ) . Conclusions : We found an increased risk of both HIV acquisition associated with T. vaginalis infection and risk of T. vaginalis acquisition associated with HIV infection . This bidirectional relationship represents a potentially important factor in sustaining the HIV epidemic in population s where T. vaginalis is endemic BACKGROUND Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate ( DMPA ) than in those who do not use hormonal contraception . We aim ed to assess whether two injectable progestin-only contraceptives , DMPA and norethisterone enanthate ( NET-EN ) , confer different risks of HIV-1 acquisition . METHODS We included data from South African women who used injectable contraception while participating in theVOICE study , a multisite , r and omised , placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9 , 2009 , and Aug 13 , 2012 . Women were assessed monthly for contraceptive use and incident infection . We estimated the difference in incident HIV-1infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospect i ve cohort . The VOICE trial is registered with Clinical Trials.gov , NCT00705679 . FINDINGS 3141 South African women using injectable contraception were included in the present analysis : 1788 (56·9%)solely used DMPA , 1097 ( 34·9 % ) solely used NET-EN , and 256 ( 8·2 % ) used both injectable types at different times during follow-up . During 2733·7 person-years of follow-up , 207 incident HIV-1 infections occurred ( incidence7·57 per 100 person-years , 95 % CI 6·61–8·68 ) . Risk of HIV-1 acquisition was higher among DMPA users ( incidence 8·62 per 100 person-years , 95 % CI 7·35–10·11 ) than among NET-EN users ( 5·67 per 100 person-years , 4·35–7·38;hazard ratio 1·53 , 95 % CI 1·12–2·08 ; p=0·007 ) . This association persisted when adjusted for potential confoundingvariables ( adjusted hazard ratio [ aHR ] 1·41 , 95 % CI 1·06–1·89 ; p=0·02 ) . Among women seropositive for herpes simplex virus type 2 ( HSV-2 ) at enrolment , the aHR was 2·02 ( 95 % CI 1·26–3·24 ) compared with 1·09 (0·78–1·52)for HSV-2-seronegative women ( pinteraction=0·07 ) . INTERPRETATION Although moderate associations in observational analyses should be interpreted with caution , thesefi ndings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence setting s where NET-EN is available . FUNDING National Institutes of Health , Mary Meyer Scholars Fund , and the Ruth Freeman Memorial Fund To evaluate the association between sexually transmitted diseases that commonly may cause genital ulceration and prevalent and incident HIV infections , we conducted three case control studies in a cohort of 21-year-old male military conscripts in northern Thail and . The men were evaluated at baseline in 1991 and semiannually until their discharge 2 years later . Serologic evidence of infection with herpes simplex virus type 2 ( HSV-2 ) , Haemophilus ducreyi , and HIV were more frequent at baseline in 83 men with a history of genital ulcer than in 97 men without such a history . Seropositivity to H. ducreyi ( odds ratio [ OR ] = 3.46 ) , HSV-2 ( OR = 3.83 ) , and syphilis ( OR = 1.53 ) were more common in HIV-positive than HIV-negative men . Men ( N = 45 ) who seroconverted to HIV while in the military were more often seropositive for H. ducreyi and HSV-2 before HIV seroconversion and also were more likely to seroconvert to HSV-2 and H. ducreyi during the same interval as their HIV seroconversion compared with men who remained HIV-negative . These data suggest that HSV-2 and H. ducreyi may be both markers for high-risk sexual behavior and risk factors for HIV infection among young men in Thail and BACKGROUND Daily oral preexposure prophylaxis ( PrEP ) using the antiretroviral tenofovir disoproxil fumarate ( TDF ) alone or in combination with emtricitabine ( FTC-TDF ) reduces the risk for HIV-1 acquisition . Tenofovir has in vitro activity against herpes simplex virus type 2 ( HSV-2 ) . OBJECTIVE To assess the efficacy of daily oral PrEP with tenofovir and FTC-TDF in the prevention of HSV-2 acquisition . DESIGN Subgroup analysis of data from a r and omized , placebo-controlled trial with concealed allocation . ( Clinical Trials.gov : NCT00557245 ) . SETTING Multiple sites in Kenya and Ug and a. PARTICIPANTS Heterosexual men and women who were seronegative for HIV-1 and HSV-2 and at high risk for HIV-1 acquisition due to having an HIV-1-infected partner . INTERVENTION Once-daily oral tenofovir disoproxil fumarate ( TDF ) , alone or combined with emtricitabine ( FTC-TDF ) , compared with placebo . MEASUREMENTS HSV-2 seroconversion . RESULTS A total of 131 participants seroconverted to HSV-2 ( 79 of 1041 assigned to tenofovir or FTC-TDF PrEP [ HSV-2 incidence , 5.6 per 100 person-years ] and 52 of 481 assigned to placebo [ HSV-2 incidence , 7.7 per 100 person-years ] ) . The hazard ratio ( HR ) for HSV-2 acquisition with daily oral PrEP was 0.70 ( 95 % CI , 0.49 to 0.99 ; P = 0.047 ) compared with placebo , and the absolute risk reduction was 2.1 per 100 person-years . Among the 1044 participants with HSV-2-infected partners , the HR for PrEP was 0.67 ( CI , 0.46 to 0.98 ; P = 0.038 ) compared with placebo , and the absolute risk reduction was 3.1 per 100 person-years . LIMITATION R and omization was not stratified by HSV-2 status , and diagnostic tests to exclude participants with acute HSV-2 at baseline are not available . CONCLUSION Daily oral tenofovir-based PrEP significantly reduced the risk for HSV-2 acquisition among heterosexual men and women . Modest protection against HSV-2 is an added benefit of HIV-1 prevention with oral tenofovir-based PrEP . PRIMARY FUNDING SOURCE Bill & Melinda Gates Foundation BACKGROUND Risk factors influencing the incidence of human immunodeficiency virus ( HIV ) infection were investigated in a case-control study nested within a community-r and omized trial of treatment of syndromic sexually transmitted infections ( STIs ) in rural Tanzania . METHODS Case patients were persons who became HIV positive , and control subjects were r and omly selected from among persons who remained HIV negative . For each sex , we obtained adjusted odds ratios ( ORs ) and population -attributable fractions ( PAFs ) for biomedical and behavioral factors . RESULTS We analyzed 92 case patients and 903 control subjects . In both sexes , the incidence of HIV infection was significantly higher in subjects with an HIV-positive spouse than in those with HIV-negative spouse ( men : OR , 25.1 ; women : OR , 34.0 ) . The incidence of HIV infection was significantly higher in those who became positive for herpes simplex virus type 2 ( HSV-2 ) ( men : OR , 5.60 ; women : OR , 4.76 ) and those who were HSV-2-positive at baseline ( men : OR , 3.66 ; women : OR , 2.88 ) than in subjects who were HSV-2 negative . In women , living elsewhere ( OR , 3.22 ) and never having given birth ( OR , 4.27 ) were significant risk factors . After adjustment , the incidence of HIV infection was not significantly associated with a history of injections or STIs in either sex . CONCLUSION HSV-2 infection was the most important risk factor for HIV infection , which highlights the need for HSV-2 interventions in HIV infection control , and there were particularly strong associations with recent HSV-2 seroconversion . The PAF associated with having an HIV-positive spouse was low , but this is likely to increase during the epidemic Summary : This study investigated the impact of prevalent and incident HSV-2 infection on the incidence of HIV-1 infection in a cohort of female commercial sex workers in KwaZulu-Natal , South Africa . Prior to a vaginal microbicide trial , 416 women were screened for antibodies to HIV-1 and herpes simplex virus-2 ( HSV-2 ) infections and a question naire was used to establish behavioral , social , and demographic characteristics . A total of 187 HIV-1-seronegative women were followed up at monthly intervals when blood was drawn and used to detect HIV-1 and HSV-2 antibodies . The median duration of follow-up was 2.2 years . At screening 50 % of the women were HIV-1 seropositive and 84 % were HSV-2 seropositive . The hazards of HIV-1 among women who were HSV-2 seropositive or seronegative throughout , or among those who seroconverted during the study , were not significantly different . When HSV-2 seroconversion was analyzed as a time-dependent covariate , the hazard ratio for HIV-1 seroconversion was 6.0 ( 95 % CI : 2.6 - 14.0 ) times greater among women with incident than among women with prevalent HSV-2 infections . Drawing on other recent studies these data suggest that incident HSV-2 infection increases the risk of HIV-1 infection ; the effect wanes with time since infection ; and the effect is significantly greater for men than it is for women BACKGROUND Infection with herpes simplex virus type 2 ( HSV-2 ) is associated with an increased risk of acquiring infection with the human immunodeficiency virus ( HIV ) . This study tested the hypothesis that HSV-2 suppressive therapy reduces the risk of HIV acquisition . METHODS Female workers at recreational facilities in northwestern Tanzania who were 16 to 35 years of age were interviewed and underwent serologic testing for HIV and HSV-2 . We enrolled female workers who were HIV-seronegative and HSV-2-seropositive in a r and omized , double-blind , placebo-controlled trial of suppressive treatment with acyclovir ( 400 mg twice daily ) . Participants attended mobile clinics every 3 months for a follow-up period of 12 to 30 months , depending on enrollment date . The primary outcome was the incidence of infection with HIV . We used a modified intention-to-treat analysis ; data for participants who became pregnant were censored . Adherence to treatment was estimated by a tablet count at each visit . RESULTS A total of 821 participants were r and omly assigned to receive acyclovir ( 400 participants ) or placebo ( 421 participants ) ; 679 ( 83 % ) completed follow-up . Mean follow-up for the acyclovir and placebo groups was 1.52 and 1.62 years , respectively . The incidence of HIV infection was 4.27 per 100 person-years ( 27 participants in the acyclovir group and 28 in the placebo group ) , and there was no overall effect of acyclovir on the incidence of HIV ( rate ratio for the acyclovir group , 1.08 ; 95 % confidence interval , 0.64 to 1.83 ) . The estimated median adherence was 90 % . Genital HSV was detected in a similar proportion of participants in the two study groups at 6 , 12 , and 24 months . No serious adverse events were attributable to treatment with acyclovir . CONCLUSIONS These data show no evidence that acyclovir ( 400 mg twice daily ) as HSV suppressive therapy decreases the incidence of infection with HIV . ( Current Controlled Trials number , IS RCT N35385041 [ controlled-trials.com ] . ) Objectives To quantify the association between prevalent or incident Herpes simplex virus type-2 ( HSV2 ) infection and the incidence of HIV seroconversion among adults in the general population in rural Tanzania . Study population Adults aged 15–54 years sample d r and omly from 12 rural communities in Mwanza Region , Tanzania and recruited to a r and omized trial of improved treatment of sexually transmitted diseases . Study design Unmatched case – control study nested within trial cohort . Methods Participants included 127 cases who seroconverted to HIV during the 2-year follow-up period and 636 r and omly selected controls who remained HIV negative . Subjects were tested for HSV2 serology at baseline and follow-up , and associations between HIV and HSV2 were analysed with adjustment for socio-demographic and behavioural factors . Results After adjusting for confounding factors , a strong association between HSV2 infection and HIV seroconversion was observed in men ( test for trend : P < 0.001 ) , with adjusted odds ratios ( OR ) of 6.12 [ 95 % confidence interval ( CI ) , 2.52–14.9 ] in those HSV2 positive at baseline , and 16.8 ( 95 % CI , 6.06–46.3 ) in those acquiring HSV2 infection during follow-up . A weaker association was observed in women ( tests for trend : P = 0.14 ) , with adjusted OR of 1.32 ( 95 % CI , 0.62–2.78 ) and 2.36 ( 95 % CI , 0.81–6.84 ) , respectively . Population attributable fractions of incident HIV infection due to HSV2 were estimated as 74 % in men and 22 % in women . Conclusions The results suggest that HSV2 plays an important role in the transmission of HIV infection in this population . There is an urgent need to identify effective HSV2 control measures in order to reduce HIV incidence in Africa Objectives : There are very few data from men on the risk of HIV acquisition associated with penile human papillomavirus ( HPV ) infection and no data on the potential modifying effect of male circumcision . Therefore , this study evaluated whether HPV is independently associated with risk of HIV . Design : A cohort study of HPV natural history nested within a r and omized control trial of male circumcision to reduce HIV incidence in Kisumu , Kenya . Methods : Prospect i ve data from 2519 men were analyzed using 6-month discrete-time Cox models to determine if HIV acquisition was higher among circumcised or uncircumcised men with HPV compared to HPV-uninfected men . Results : Risk of HIV acquisition was nonsignificantly increased among men with any HPV [ adjusted hazard ratio ( aHR ) 1.72 ; 95 % confidence interval ( CI ) 0.94–3.15 ] and high-risk HPV ( aHR 1.92 ; 95 % CI 0.96–3.87 ) compared to HPV-uninfected men , and estimates did not differ by circumcision status . Risk of HIV increased 27 % with each additional HPV genotype infection ( aHR 1.27 ; 95 % CI 1.09–1.48 ) . Men with persistent ( aHR 3.27 ; 95 % CI 1.59–6.72 ) or recently cleared ( aHR 3.05 ; 95 % CI 1.34–6.97 ) HPV had a higher risk of HIV acquisition than HPV-uninfected men . Conclusions : Consistent with the findings in women , HPV infection , clearance , and persistence were associated with an increased risk of HIV acquisition in men . Given the high prevalence of HPV in population s at risk of HIV , consideration of HPV in future HIV-prevention studies and investigation into mechanisms through which HPV might facilitate HIV acquisition are needed OBJECTIVES To determine the rate of and risk factors for HIV-1 seroconversion and describe sexually transmitted disease ( STD ) prevalence rates for young men in northern Thail and . METHODS Data were collected from self-administered question naires and serologic testing at enrollment in a prospect i ve study in 1991 and at follow-up after 6 , 17 , and 23 months on a cohort of 1115 men selected by lottery for military conscription . RESULTS A total of 14 men seroconverted to HIV-1 envelope subtype E. The overall HIV-1 incidence rate was 1.1 ( 95 % confidence interval [ CI ] , 0.6 - 1.8 ) per 100 person-years ( PY ) of follow-up . However , the rate was 2.0/100 PY for conscripts from the upper northern subregion of Thail and compared with 0.5/100 PY from other regions ( adjusted rate ratio [ RR ] = 2.69 ; 95 % CI , 0.8 - 12.2 ) . On multivariate analyses , the behavioral factors associated with HIV-1 seroconversion were frequency of sex with female sex workers ( FSWs ; p = .04 ) , receptive anal sex ( adjusted RR = 6.73 ; 95 % CI , 1.8 - 21.7 ) , and large amount of alcohol consumption ( adjusted RR = 3.12 ; 95 % CI , 1.0 - 10.9 ) . Genital ulceration was the STD most strongly associated with seroconversion . The prevalence of serologic reactivity to syphilis , Haemophilus ducreyi , and herpes simplex virus type 2 increased with greater frequency of sex with FSWs and was generally higher for men from the upper north . CONCLUSION Young men in northern Thail and are at high risk for HIV-1 , primarily through sex with FSWs ; and other STDs are highly associated with HIV-1 incidence . As HIV-1 infection extends into the general population , intervention programs are needed to address the problem of sexual transmission apart from commercial sex venues BACKGROUND Treatment of sexually-transmitted infections ( STIs ) and behavioural interventions are the main methods to prevent HIV in developing countries . We aim ed to assess the effect of these interventions on incidence of HIV-1 and other sexually-transmitted infections . METHODS We r and omly allocated all adults living in 18 communities in rural Ug and a to receive behavioural interventions alone ( group A ) , behavioural and STI interventions ( group B ) , or routine government health services and community development activities ( group C ) . The primary outcome was HIV-1 incidence . Secondary outcomes were incidence of herpes simplex virus type 2 ( HSV2 ) and active syphilis and prevalence of gonorrhoea , chlamydia , reported genital ulcers , reported genital discharge , and markers of behavioural change . Analysis was per protocol . FINDINGS Compared with group C , the incidence rate ratio of HIV-1 was 0.94 ( 0.60 - 1.45 , p=0.72 ) in group A and 1.00 ( 0.63 - 1.58 , p=0.98 ) in group B , and the prevalence ratio of use of condoms with last casual partner was 1.12 ( 95 % CI 0.99 - 1.25 ) in group A and 1.27 ( 1.02 - 1.56 ) in group B. Incidence of HSV2 was lower in group A than in group C ( incidence rate ratio 0.65 , 0.53 - 0.80 ) and incidence of active syphilis for high rapid plasma reagent test titre and prevalence of gonorrhoea were both lower in group B than in group C ( active syphilis incidence rate ratio , 0.52 , 0.27 - 0.98 ; gonorrhoea prevalence ratio , 0.25 , 0.10 - 0.64 ) . INTERPRETATION The interventions we used were insufficient to reduce HIV-1 incidence in rural Ug and a , where secular changes are occurring . More effective STI and behavioural interventions need to be developed for HIV control in mature epidemics Background : Studies of the effect of hormonal contraceptive use on the risk of HIV-1 acquisition have generated conflicting results . A recent study from Ug and a and Zimbabwe found that women using hormonal contraception were at increased risk for HIV-1 if they were seronegative for herpes simplex virus type 2 ( HSV-2 ) , but not if they were HSV-2 seropositive . Objective : To explore the effect of HSV-2 infection on the relationship between hormonal contraception and HIV-1 in a high-risk population . Hormonal contraception has previously been associated with increased HIV-1 risk in this population . Methods : Data were from a prospect i ve cohort study of 1206 HIV-1 seronegative sex workers from Mombasa , Kenya who were followed monthly . Multivariate Cox proportional hazards analyses were used to adjust for demographic and behavioral measures and incident sexually transmitted diseases . Results : Two hundred and thirty-three women acquired HIV-1 ( 8.7/100 person-years ) . HSV-2 prevalence ( 81 % ) and incidence ( 25.4/100 person-years ) were high . In multivariate analysis , including adjustment for HSV-2 , HIV-1 acquisition was associated with use of oral contraceptive pills [ adjusted hazard ratio ( HR ) , 1.46 ; 95 % confidence interval ( CI ) , 1.00–2.13 ] and depot medroxyprogesterone acetate ( adjusted HR , 1.73 ; 95 % CI , 1.28–2.34 ) . The effect of contraception on HIV-1 susceptibility did not differ significantly between HSV-2 seronegative versus seropositive women . HSV-2 infection was associated with elevated HIV-1 risk ( adjusted HR , 3.58 ; 95 % CI , 1.64–7.82 ) . Conclusions : In this group of high-risk African women , hormonal contraception and HSV-2 infection were both associated with increased risk for HIV-1 acquisition . HIV-1 risk associated with hormonal contraceptive use was not related to HSV-2 serostatus Objective : Mycoplasma genitalium is an emerging sexually transmitted infection ( STI ) and has been associated with reproductive tract infections and HIV in cross-sectional studies . In this longitudinal study , we assess whether M. genitalium is associated with risk of acquiring HIV-1 infection . Design : Nested case – control study within a large prospect i ve study in Zimbabwe and Ug and a Methods : A total of 190 women who seroconverted to HIV-1 during follow-up ( cases ) were matched with up to two HIV-negative controls . Mycoplasma genitalium testing was performed by PCR-ELISA , using archived cervical sample s from the HIV-1 detection visit and the last HIV-negative visit for cases , and equivalent visits in follow-up time for controls . Risk factors for HIV-1 acquisition were analyzed using conditional logistic regression , with M. genitalium as the primary exposure . Results : Mycoplasma genitalium was a common infection in these population s ( 14.8 and 6.5 % prevalence among cases and controls , respectively , at the visit prior to HIV-1 detection ) , and more prevalent than other nonviral STIs . We found a greater than two-fold independent increased risk of HIV-1 acquisition among women infected with M. genitalium at the visit prior to HIV-1 acquisition [ adjusted odds ratio ( AOR ) = 2.42 ; 95 % confidence interval ( CI ) 1.01–5.80 ) , and at time of HIV-1 acquisition ( AOR = 2.18 ; 95 % CI 0.98–4.85 ) . An estimated 8.7 % ( 95 % CI 0.1–12.2 % ) of incident HIV-1 infections were attributable to M. genitalium . Conclusion : This is the first longitudinal study to assess the relationship between M. genitalium and HIV-1 acquisition . If findings from this research are confirmed , M. genitalium screening and treatment among women at high risk for HIV-1 infection may be warranted as part of an HIV-1 prevention strategy Objectives : To determine the incidence of HIV-1 infection , temporal trends in incidence , and risk factors for seroconversion in a cohort of female commercial sex workers ( CSW ) in upper northern Thail and , the region of Thail and with the highest rates of HIV-1 infection . Methods : CSW were enrolled from 1991 through 1994 and evaluated prospect ively with interviews , physical examination , testing for sexually transmitted diseases ( STD ) , and serologic testing for HIV-1 infection . Results : The incidence of HIV-1 seroconversion in the first year of follow-up was 20.3 per 100 person-years among 126 brothel-based CSW and 0.7 per 100 person-years among 159 other CSW who worked in other venues such as bars or massage parlors . Incidence remained elevated among brothel-based CSW who were enrolled later in the study compared with those who enrolled earlier . Through 1996 , 30 women seroconverted . In a multivariable proportional hazards model , seroconversion was significantly associated ( P < 0.05 ) with brothel-based sex work ( adjusted risk ratio , 7.3 ) and Chlamydia trachomatis cervical infection ( adjusted risk ratio , 3.3 ) . Conclusion : Despite national HIV control efforts and declining rates of infection among young men in Thail and , brothel-based CSW may continue to be at high risk for HIV-1 infection . Additional efforts are needed to provide alternative economic choices for young women , to ensure universal condom use during commercial sex , and to develop new prevention technologies CONTEXT Sexually transmitted infections ( STIs ) are common in female sex workers ( FSWs ) and may enhance susceptibility to infection with human immunodeficiency virus type 1 ( HIV-1 ) . OBJECTIVE To examine regular antibiotic prophylaxis in FSWs as a strategy for reducing the incidence of bacterial STIs and HIV-1 . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial conducted between 1998 - 2002 among FSWs in an urban slum area of Nairobi , Kenya . Of 890 FSWs screened , 466 who were seronegative for HIV-1 infection were enrolled and r and omly assigned to receive azithromycin ( n = 230 ) or placebo ( n = 236 ) . Groups were well matched at baseline for sexual risk taking and STI rates . INTERVENTION Monthly oral administration of 1 g of azithromycin or identical placebo , as directly observed therapy . All participants were provided with free condoms , risk-reduction counseling , and STI case management . MAIN OUTCOME MEASURES The primary study end point was incidence of HIV-1 infection . Secondary end points were the incidence of STIs due to Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis , Treponema pallidum , and Haemophilus ducreyi , as well as bacterial vaginosis . Analysis of herpes simplex virus type 2 ( HSV-2 ) infection was performed post hoc . RESULTS Seventy-three percent of participants ( n = 341 ) were followed up for 2 or more years or until they reached an administrative trial end point . Incidence of HIV-1 did not differ between treatment and placebo groups ( 4 % [ 19 cases per 473 person-years of follow-up ] vs 3.2 % [ 16 cases per 495 person-years of follow-up ] rate ratio [ RR ] , 1.2 ; 95 % CI , 0.6 - 2.5 ) . Incident HIV-1 infection was associated with preceding infection with N gonorrhoeae ( rate ratio [ RR ] , 4.9 ; 95 % CI , 1.7 - 14.3 ) or C trachomatis ( RR , 3.0 ; 95 % CI , 1.1 - 8.9 ) . There was a reduced incidence in the treatment group of infection with N gonorrhoeae ( RR , 0.46 ; 95 % CI , 0.31 - 0.68 ) , C trachomatis ( RR , 0.38 ; 95 % CI , 0.26 - 0.57 ) , and T vaginalis ( RR , 0.56 ; 95 % CI , 0.40 - 0.78 ) . The seroprevalence of HSV-2 infection at enrollment was 72.7 % , and HSV-2 infection at baseline was independently associated with HIV-1 acquisition ( RR , 6.3 ; 95 % CI , 1.5 - 27.1 ) . CONCLUSIONS Despite an association between bacterial STIs and acquisition of HIV-1 infection , the addition of monthly azithromycin prophylaxis to established HIV-1 risk reduction strategies substantially reduced the incidence of STIs but did not reduce the incidence of HIV-1 . Prevalent HSV-2 infection may have been an important cofactor in acquisition of HIV-1 Objective : To estimate the effects of reproductive tract infections ( RTIs ) on HIV acquisition among Zimbabwean and Ug and an women . Methods : A multicenter prospect i ve observational cohort study enrolled 4439 HIV-uninfected women aged 18 to 35 attending family planning clinics in Zimbabwe and Ug and a. Participants were interviewed , and tested for HIV and RTIs every 3 months for 15 to 24 months . They received HIV risk reduction counseling , male condoms , and treatment for curable RTIs . Results : Despite HIV risk reduction counseling and regular screening and treatment for RTIs , the HIV incidence did not decline during the study . Positive HSV-2 serostatus at baseline ( hazard ratio [ HR ] = 3.69 , 95 % confidence interval = 2.45–5.55 ) , incident HSV-2 ( HR = 5.35 , 3.06–9.36 ) , incident Neisseria gonorrhoeae ( HR = 5.46 , 3.41–8.75 ) , and altered vaginal flora during the study ( bacterial vaginosis [ BV ] : HR = 2.12 , 1.50–3.01 ; and intermediate flora : HR = 2.02 , 1.39–2.95 ) were independently associated with HIV acquisition after controlling for demographic and behavioral covariates and other RTIs ( Treponema pallidum , Chlamydia trachomatis , Trichomonas vaginalis , and vaginal yeasts ) . For N. gonorrhoeae , C. trachomatis , T. vaginalis , and vaginal yeasts , the risk of HIV acquisition increased when the infection was identified at the visit before the HIV-detection visit or with the duration of infection . Population attributable risk percent ( PAR% ) calculations show that HSV-2 contributes most to acquisition of new HIV infections ( 50.4 % for baseline HSV-2 and 7.9 % for incident HSV-2 ) , followed by altered vaginal flora ( 17.2 % for bacterial vaginosis and 11.8 % for intermediate flora ) . Conclusions : A substantial proportion of new HIV infections in Zimbabwean and Ug and an women are attributable to RTIs , particularly HSV-2 and altered vaginal flora BACKGROUND Female-controlled methods of HIV prevention are urgently needed . We assessed the effect of provision of latex diaphragm , lubricant gel , and condoms ( intervention ) , compared with condoms alone ( control ) on HIV seroincidence in women in South Africa and Zimbabwe . METHODS We did an open-label , r and omised controlled trial in HIV-negative , sexually active women recruited from clinics and community-based organisations , who were followed up quarterly for 12 - 24 months ( median 21 months ) . All participants received an HIV prevention package consisting of pre-test and post-test counselling about HIV and sexually transmitted infections , testing , treatment of curable sexually transmitted infections , and intensive risk-reduction counselling . The primary outcome was incident HIV infection . This study is registered with Clinical Trials.gov , number NCT00121459 . FINDINGS Overall HIV incidence was 4.0 % per 100 woman-years : 4.1 % in the intervention group ( n=2472 ) and 3.9 % in the control group ( n=2476 ) , corresponding to a relative hazard of 1.05 ( 95 % CI 0.84 - 1.32 , intention-to-treat analysis ) . The proportion of women using condoms was significantly lower in the intervention than in the control group ( 54%vs 85 % of visits , p<0.0001 ) . The proportions of participants who reported adverse events ( 60 % [ 1523 ] vs 61 % [ 1529 ] ) and serious adverse events ( 5 % [ 130 ] vs 4 % [ 101 ] ) were similar between the two groups . INTERPRETATION We observed no added protective benefit against HIV infection when the diaphragm and lubricant gel were provided in addition to condoms and a comprehensive HIV prevention package . Our observation that lower condom use in women provided with diaphragms did not result in increased infection merits further research . Although the intervention seemed safe , our findings do not support addition of the diaphragm to current HIV prevention strategies We assess the relative contribution of viral and bacterial sexually transmitted infections ( STIs ) on HIV acquisition among southern African women in a nested case-control study within the Methods for Improving Reproductive Health in Africa ( MIRA ) trial . Cases were women with incident HIV infection ; controls were HIV-uninfected at the time of case seroconversion selected in a 1 to 3 case to control ratio ( risk-set sampling ) , matched on study site and time of follow-up . Conditional logistic regression models were used to calculate adjusted odds ratios ( AORs ) and population -attributable fractions ( PAF ) . Among 4948 enrolled women , we analysed 309 cases and 927 controls . The overall HIV incidence rate was 4.0 per 100 women-years . The incidence of HIV infection was markedly higher in women who had prevalent Herpes simplex virus type 2 ( HSV-2 ) ( AOR : 2.14 ; 95 % confidence interval [ CI ] : 1.55–2.96 ) , incident HSV-2 ( AOR : 4.43 ; 95 % CI : 1.77–11.05 ) and incident Neisseria gonorrhoeae ( AOR : 6.92 ; 95 % CI : 3.01–15.90 ) . The adjusted PAF of HIV incidence for prevalent HSV-2 was 29.0 % ( 95 % CI : 16.8–39.3 ) , for incident HSV-2 2.1 % ( 95 % CI : 0.6–3.6 ) and for incident N. gonorrhoeae 4.1 % ( 95 % CI : 2.5–5.8 ) . Women 's greatest risk factors for HIV acquisition were incident bacterial and viral STIs . Women-centred interventions aim ed at decreasing HIV incidence in young African women need to address these common co-morbid conditions Objective : To test the hypothesis that increasing community antiretroviral therapy ( ART ) coverage would be associated with lower HIV incidence in female sex workers ( FSWs ) in Mombasa District , Kenya . Design : Prospect i ve cohort study . Methods : From 1998 to 2012 , HIV-negative FSWs were asked to return monthly for an interview regarding risk behavior and testing for sexually transmitted infections including HIV . We evaluated the association between community ART coverage and FSW 's risk of becoming HIV infected using Cox proportional hazards models adjusted for potential confounding factors . Results : One thous and , four hundred and four FSWs contributed 4335 woman-years of follow-up , with 145 acquiring HIV infection ( incidence 3.35/100 woman-years ) . The ART rollout began in 2003 . By 2012 , an estimated 52 % of HIV-positive individuals were receiving treatment . Community ART coverage was inversely associated with HIV incidence ( adjusted hazard ratio 0.77 ; 95 % confidence interval 0.61–0.98 ; P = 0.03 ) , suggesting that each 10 % increase in coverage was associated with a 23 % reduction in FSWs ’ risk of HIV acquisition . Community ART coverage had no impact on herpes simplex virus type-2 incidence ( adjusted hazard ratio 0.97 ; 95 % confidence interval 0.79–1.20 ; P = 0.8 ) . Conclusion : Increasing general population ART coverage was associated with lower HIV incidence in FSWs . The association with HIV incidence , but not herpes simplex virus type-2 incidence , suggests that the effect of community ART coverage may be specific to HIV . Interventions such as preexposure prophylaxis and antiretroviral-containing microbicides have produced disappointing results in HIV prevention trials with FSWs . These results suggest that FSWs ’ risk of acquiring HIV infection might be reduced through the indirect approach of increasing ART coverage in the community Herpes simplex virus ( HSV ) infection is common in persons coinfected with human immunodeficiency virus ( HIV ) . In a prospect i ve study , daily viral cultures of the mouth , genitals , and rectum were collected from 68 HIV-positive and 13 HIV-negative men who have sex with men . Subjects completed a median of 57 days of follow-up . Anogenital HSV-2 cultures were positive on 405 ( 9.7 % ) of 4167 days for HIV-positive men and on 24 ( 3.1 % ) of 766 days for HIV-negative men . Most reactivations were perirectal and sub clinical . Risk factors for increased HSV-2 shedding among HIV-positive men were low CD4 cell count ( odds ratio , 2.5 ; 95 % confidence interval , 1.2 - 5.4 ) and antibodies to both HSV-1 and HSV-2 versus HSV-2 only ( odds ratio , 1.9 ; 95 % confidence interval , 1.0 - 3.7 ) . Three isolates obtained from 3 separate subjects were resistant to acyclovir . Thus , sub clinical HSV-2 reactivation is an important opportunistic infection in persons with HIV infection . Further studies are necessaryto determine the impact of sub clinical HSV-2 reactivation on the natural history of HIV infection Objective : To determine the association between female genital Schistosoma haematobium infection and HIV . Design and methods : A cross-sectional study with a 1-year follow-up . Gynecological and laboratory investigations were performed for S. haematobium and HIV . Sexually transmitted infections , demographic and urogenital history were analysed as confounders . The participants were 527 sexually active , non-pregnant , non-menopausal women between the ages of 20 and 49 years . The setting was a rural Zimbabwean community where S. haematobium related lesions were found in 46 % of the women , HIV in 29 % and herpes simplex type- 2 ( HSV-2 ) in 65 % . Results : In permanent residents ( > 3 years residency ) , HIV was found in 41 % ( 29/70 ) of women with laboratory proven genital schistosomiasis as opposed to 26 % HIV positive ( 96/375 ) in the schistosomal ova negative group [ odds ratio ( OR ) , 2.1 ; 95 % confidence interval ( CI ) , 1.2–3.5 ; P = 0.008 . In multivariate analysis S. haematobium infection of the genital mucosa was significantly associated with HIV seropositivity ( adjusted OR , 2.9 ; 95 % CI , 1.11–7.5 ; P = 0.030 ) . All seven women who became HIV positive during the study period ( seroincidence 3.1 % ) had signs of S. haematobium at baseline . In accordance with other studies HIV was significantly associated with HSV-2 ( OR , 3.0 ; 95 % CI , 1.7–5.3 ; P < 0.001 ) , syphilis and human papillomavirus . The highest HIV prevalence ( 45 % ) was found in the 25–29 years age group . Conclusion : Women with genital schistosomiasis had an almost three-fold risk of having HIV in this rural Zimbabwean community . Prospect i ve studies are needed to confirm the association Seroepidemiologic studies have shown that herpes simplex virus ( HSV ) genital infection may be the most common sexually transmitted disease in the United States . Studies using both viral culture and gene amplification techniques have shown frequent viral shedding from the mucosa and epidermis of otherwise asymptomatic patients [ 1 - 3 ] . Human immunodeficiency virus ( HIV ) infection is associated with dramatically severe and chronic genital HSV infections that may occasionally respond poorly to conventional therapy [ 4 - 6 ] . However , data on the effect of HIV infection on the overall frequency of HSV shedding are sparse . If HSV shedding , particularly asymptomatic shedding , is increased in the setting of HIV infection , the risk for transmission of HSV may in turn be increased . We sought to determine the prevalence of HSV genital shedding in a sample of women who were HIV-seropositive and HSV-2-seropositive and to compare it with that found in a control group of HIV-seronegative and HSV-2-seropositive women , as well as to assess the relation between immune status and shedding rates . Methods From September 1991 to May 1994 , 106 HIV-seropositive and HSV-2-seropositive women were enrolled as part of the Women 's AIDS Cohort Study , a prospect i ve study of the natural history of HIV infection in women . Women were recruited from two HIV primary care clinics at a large inner-city public hospital . Women who had a history of AIDS-defining illness [ 7 ] or who were pregnant were not eligible for enrollment . All women eligible for enrollment were asked to participate , and approximately 90 % agreed . Seventy sexually active HIV-seronegative and HSV-2-seropositive controls from the same community were enrolled as part of the Heterosexual AIDS Transmission Study , a prospect i ve evaluation of the behavioral and biologic risk factors for HIV acquisition [ 8 ] . Serum sample s from both groups were screened for the presence of antibodies to HIV-1 using the Recombigen enzyme immunoassay ( Cambridge Biotech Corporation , Worcester , Massachusetts ) . Sample s positive by enzyme immunoassay were tested by Western blot analysis ( Dupont Company , Wilmington , Delaware ) . A specimen was considered positive if any two of three ( p24 , gp41 , gp120/160 ) b and s were detected . Information pertaining to basic demographics , socioeconomic status , history of alcohol or drug use , and sexual practice s was obtained with a st and ard question naire . A medical history and a physical examination were done . Lymphocyte phenotyping was done for HIV-seropositive women by flow cytometry using monoclonal antibodies ( Becton-Dickinson , San Jose , California ) . For all HIV-seropositive and HIV-seronegative women , serologic evidence of previous infection with HSV-2 was determined by Western blot . Herpes simplex virus type 2 lysate from st and ard HSV-2 strains was separated using gel electrophoresis and transferred to nitrocellulose strips . Strips were incubated with the patients ' serum and then developed using a biotinylated horseradish peroxidase system . We assayed positive and negative controls for HSV-1 , HSV-2 , and combined HSV-1 and HSV-2 infection on each run . Serologic diagnosis of HSV-2 was made by the identification of the 92-kd gG glycoprotein b and pattern , which previously has been shown to be specific for HSV-2 [ 9 ] . All women had gynecologic examinations . At enrollment , we collected cervical and vulvar specimens for HSV culture from all of the HIV-seropositive women , regardless of HSV-2 serostatus or the presence of symptoms consistent with HSV genital infection . Dacron and plastic swabs ( S/P Sterile Swab , Baxter Healthcare Corporation , McGaw Park , Illinois ) from both sites were placed together into a single vial of viral transport medium ( 2.0 mL of Hanks balanced salt solution , 0.5 % bovine serum albumin , 20 mM HEPES , gentamicin , vancomycin , and nystatin ) . After specimens were vortexed for 15 seconds , 0.2 mL of material was inoculated into two tubes each of A549 and human neonatal kidney cells ( BioWhittaker Incorporated , Walkersville , Maryl and ) . We observed monolayers for 2 weeks for the development of cytopathic effect . We identified isolates by immunofluorescence using type-specific monoclonal antibodies ( Syva Corporation , Palo Alto , California ) . If a genital ulcer was noted during the examination , a separate specimen for viral culture was obtained from that site . All cultures were done on the day of collection . We obtained genital specimens for HSV-2 culture from 56 ( 80 % ) of the 70 HIV-seronegative and HSV-2-seropositive women during a follow-up visit . At the time of culture , none of these women was noted to have a genital lesion or symptoms consistent with HSV infection , and none of the women in either group was receiving therapy with agents active against HSV . Differences in categorical variables were tested for statistical significance using the generalized Fisher exact test . Associations by CD4 grouping were evaluated by the exact trend test and two-sided mid-P values ( StatXact , Cytel Software Corporation , Cambridge , Massachusetts ) . Results Demographic characteristics of study participants are shown in Table 1 . There was a greater proportion of black women among the HIV-seronegative controls than among the HIV-seropositive women . Although race differed between HIV-seropositive and HIV-seronegative patients , the prevalence of recovery of HSV-2 infection by race did not differ ( P = 0.75 ) , making it unnecessary to control for race when comparing HSV prevalence by HIV serostatus . Table 1 . Characteristics of Patients with Herpes Simplex Virus Type 2 Infection by HIV Serostatus Fourteen ( 13.2 % ) of the HIV-seropositive and HSV-2-seropositive women were positive for HSV-2 infection by culture from genital specimens , compared with 2 of 56 HIV-seronegative and HSV-2-seropositive women ( P = 0.04 ; odds ratio , 4.1 [ 95 % CI , 1.0 to 27.4 ] ) . Three of these HIV-seropositive women ( 21.4 % ) had lesions consistent with HSV genital infection at the time of their evaluation . Eleven ( 78.6 % ) were asymptomatic . All of the isolates recovered were HSV-2 . The rate of HSV-2 genital shedding increased as the CD4 cell count decreased ( P < 0.025 ; Table 2 ) . This trend persisted when only asymptomatic shedding was considered , but the finding did not reach statistical significance ( P < 0.086 ) . Table 2 . Herpes Simplex Virus Type 2 Shedding by Level of Immunosuppression Discussion The prevalence of combined symptomatic and asymptomatic genital HSV-2 shedding was significantly greater in HIV-seropositive women than in HIV-seronegative controls drawn from the same community and was associated with declining CD4 cell counts . The rate of asymptomatic HSV-2 shedding by CD4 cell count did not reach statistical significance . Asymptomatic shedding of HSV-2 in women is common . Almost all women who are seropositive for HSV-2 antibody will shed the virus asymptomatically at one time or another [ 1 ] . The isolation rate of virus varies in proportion to the frequency of sampling [ 1 - 310 , 11 ] . Studies conducted with women who are presumably not infected with HIV and using traditional culture methods have shown an isolation rate of virus of approximately 1 % of all specimens taken . In our study , the rate of isolation of HSV-2 from asymptomatic HIV-seropositive women ( 11 % ) was 11 times greater than that of these historical controls , but it was only three times greater than that of our own HIV-seronegative controls ( 11 % compared with 3.6 % ) . The most conspicuous shortcoming of our analysis is its reliance on cross-sectional data . Shedding of HSV-2 is a dynamic process , which may transiently occur and abate . Measuring its occurrence at a single point in time does not necessarily reflect overall shedding rates . Many more patients may have shed the virus on days preceding or following their clinical evaluation . These findings are important . Sexual transmission of HSV-2 occurs during periods of symptomatic and asymptomatic shedding [ 12 - 15 ] . Although viral shedding is quantitatively lower in asymptomatic periods , the attributable risk for transmission of HSV-2 is probably much higher because sexual activity is less likely to be restricted in asymptomatic women . Concomitant HIV and HSV infection may substantially increase the risk for HSV transmission through increased instances of symptomatic , and more importantly , asymptomatic shedding . The risk for neonatal acquisition of HSV infection from pregnant HIV-seropositive women may likewise be higher than that from HIV-seronegative women [ 16 - 18 ] . Given these concerns , the incidence of these phenomena should be examined further . Presented in part at the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy , New Orleans , Louisiana , October 1993 . Dr. Feldman : Box 43 , Clarkson Avenue , Brooklyn , NY 11203 . Dr. Chirgwin : Box 77 , 450 Clarkson Avenue , Brooklyn , NY 11203 . Dr. Zenilman : Johns Hopkins University School of Medicine , Ross 1159 , 720 Rutl and Avenue , Baltimore , MD 21205 . Dr. Clarke : Box 37 , 450 Clarkson Avenue , Brooklyn , NY 11203 . Dr. DeHovitz : Box 43 , 450 Clarkson Avenue , Brooklyn , NY 11203 . Dr. L and esman : Box 122 , 450 Clarkson Avenue , Brooklyn , NY 11203 . Dr. Minkoff : Box 24 , 450 Clarkson Avenue , Brooklyn , NY 11203 OBJECTIVE To determine the prevalence , incidence , and correlates of HIV-1 infection in a cohort of east African trucking company employees . METHODS HIV-1-seronegative trucking company employees were enrolled in a prospect i ve cohort study and evaluated at 3 monthly intervals for HIV-1 seroconversion , sexually transmitted diseases , and sexual behavior . RESULTS The baseline seroprevalence of HIV-1 among 1500 trucking company employees was 17.8 % . Among 752 HIV-1-seronegative men who were followed , the HIV-1 annual seroincidence was 3.1 % . In univariate analysis , HIV-1 acquisition was associated with age under 25 years , 10 years or less of sexual activity , occupation as a driver/driver 's assistant , occupational travel for more than 14 days per month , religion other than Christian or Muslim , uncircumcised status , sex with a prostitute , sex with a girlfriend/casual partner , extramarital sex , and enrollment seropositivity to Treponema pallidum , Haemophilus ducreyi , and Herpes simplex virus type 2 ( all P values < or = 0.05 ) . Using multivariate analysis , HIV-1 acquisition was independently associated with 10 years or less of sexual activity ( hazard rate ratio ( HRR ) 2.0 , 95 % confidence interval ( CI ) 1.0 - 4.3 ) , occupation as a driver/driver 's assistant ( HRR 3.9 , 95 % CI 1.7 - 9.0 ) , religion other than Christian or Muslim ( HRR 6.1 , 95 % CI 1.4 - 25.7 ) , uncircumcised status ( HRR 2.3 , 95 % CI 1.0 - 5.0 ) , and unprotected sex with a prostitute ( HRR 2.8 , 95 % CI 1.1 - 7.0 ) . CONCLUSIONS Trucking company employees had a high HIV-1 seroprevalence rate at enrollment and a high HIV-1 seroincidence during follow-up . Risk factors for HIV-1 seroconversion included years of sexual activity , occupation , religion , uncircumcised status , and unprotected sex with a prostitute . This population is an appropriate target for HIV-1 prevention trials and behavioral interventions BACKGROUND Across many observational studies , herpes simplex virus type 2 ( HSV-2 ) infection is associated with two-fold to three-fold increased risk for HIV-1 infection . We investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition . METHODS We undertook a double-blind , r and omised , placebo-controlled phase III trial in HIV-negative , HSV-2 seropositive women in Africa and men who have sex with men ( MSM ) from sites in Peru and the USA . Participants were r and omly assigned by block r and omisation to twice daily aciclovir 400 mg ( n=1637 ) or matching placebo ( n=1640 ) for 12 - 18 months , and were seen monthly for dispensation of study drug , adherence counselling and measurement by pill count and self-reporting , and risk reduction counselling , and every 3 months for genital examination and HIV testing . The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00076232 . FINDINGS 3172 participants ( 1358 women , 1814 MSM ) were included in the primary data set ( 1581 in aciclovir group , 1591 in control group ) . The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group ( 75 events in 1935 person-years of follow-up ) and 3.3 per 100 person-years in the placebo group ( 64 events in 1969 person-years of follow-up ; hazard ratio 1.16 [ 95 % CI 0.83 - 1.62 ] ) . Incidence of genital ulcers on examination was reduced by 47 % ( relative risk 0.53 [ 0.46 - 0.62 ] ) and HSV-2 positive genital ulcers by 63 % ( 0.37 [ 0.31 - 0.45 ] ) in the aciclovir group . Adherence to dispensed study drug was 94 % in the aciclovir group and 94 % in the placebo group , and 85 % of expected doses in the aciclovir group and 86 % in the placebo group . Retention was 85 % at 18 months in both groups ( 1028 of 1212 in aciclovir group , 1030 of 1208 in placebo group ) . We recorded no serious events related to the study drug . INTERPRETATION Our results show that suppressive therapy with st and ard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM . Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1 OBJECTIVE To assess the effect of oral and injectable contraceptive use compared to nonhormonal contraceptive use on HIV acquisition among Southern African women enrolled in a microbicide trial . STUDY DESIGN This is a prospect i ve cohort study using data from women enrolled in HIV Prevention Trials Network protocol 035 . At each quarterly visit , participants were interviewed about self-reported contraceptive use and sexual behaviors and underwent HIV testing . Cox proportional hazards regression was used to assess the effect of injectable and oral hormonal contraceptive use on HIV acquisition . RESULTS The analysis included 2830 participants , of whom 106 became HIV infected ( 4.07 per 100 person-years ) . At baseline , 1546 ( 51 % ) participants reported using injectable contraceptives and 595 ( 21 % ) reported using oral contraceptives . HIV incidence among injectable , oral and nonhormonal contraceptive method users was 4.72 , 2.68 and 3.83 per 100 person-years , respectively . Injectable contraceptive use was associated with a nonstatistically significant increased risk of HIV acquisition [ adjusted hazard ratio (aHR)=1.17 ; 95 % confidence interval ( CI ) 0.70 , 1.96 ] , while oral contraceptive use was associated with a nonstatistically significant decreased risk of HIV acquisition ( aHR=0.76 ; 95 % CI 0.37,1.55 ) . CONCLUSION In this secondary analysis of r and omized trial data , a marginal , but nonstatistically significant , increase in HIV risk among women using injectable hormonal contraceptives was observed . No increased HIV risk was observed among women using oral contraceptives . Our findings support the World Health Organization 's recommendation that women at high risk for acquiring HIV , including those using progestogen-only injectable contraception , should be strongly advised to always use condoms and other HIV prevention measures . IMPLICATION S Among Southern African women participating in an HIV prevention trial , women using injectable hormonal contraceptives had a modest increased risk of HIV acquisition ; however , this association was not statistically significant . Continued research on the relationship between widely used hormonal contraceptive methods and HIV acquisition is essential Objectives Identification of risk factors is essential for developing herpes simplex virus type 2 ( HSV-2 ) prevention interventions that could also reduce HIV-1 transmission , particularly among HIV-1-discordant couples . Methods A prospect i ve cohort study was conducted among HIV-1-discordant couples from June 2009 to March 2011 in Yunnan province , China . 413 HIV-1-infected partners and 517 HIV-1-uninfected partners who were HSV-2 seronegative or equivocal at enrolment and who had a study partner completing the baseline survey and HSV-2 testing were included in the analysis . Results HSV-2 incidence was 2.9 per 100 person-years ( PY ) for HIV-1-infected partners and 4.5 per 100 PY for HIV-1-uninfected partners . At least 36 % of incident HSV-2 infections were from outside sexual partner . Among HIV-1-infected partners , multivariate analysis indicated that HSV-2 incidence was significantly higher among those with baseline equivocal HSV-2 result , having an initially HSV-2 seropositive or equivocal partner , reporting no sex with study partner and initiating antiretroviral therapy ( ART ) during follow-up . Among HIV-1-uninfected partners , multivariate analysis indicated that HSV-2 incidence was significantly higher among those having an initially HSV-2 seropositive partner and reporting sex with study partner ≥5 times/month , but was lower among those having a partner with baseline CD4 + count ≥350 cells/μL. Conclusions Our findings underscore the importance of developing prevention and intervention programmes to reduce HSV-2 transmission among this population . The relationship between ART initiation and HSV-2 seroconversion requires further investigation Objective : The objective of this study was to underst and temporal trends in the contribution of different genital tract infections to HIV incidence over 20 years of follow-up in a cohort of high-risk women . Design : A prospect i ve cohort study . Methods : We performed monthly evaluations for HIV , vaginal yeast , bacterial vaginosis , Trichomonas vaginalis , Neisseria gonorrhoeae , nonspecific cervicitis , herpes simplex virus type two ( HSV-2 ) , genital ulcer disease ( GUD ) and genital warts . We used Cox regression to evaluate the association between sexually transmitted infections ( STIs ) and HIV acquisition over four time periods ( 1993–1997 , 1998–2002 , 2003–2007 , 2008–2012 ) . Models were adjusted for age , workplace , sexual risk behaviour , hormonal contraceptive use and other STIs . The result ing hazard ratios were used to calculate population attributable risk percentage ( PAR% ) . Results : Between 1993 and 2012 , 1964 women contributed 6135 person-years of follow-up . The overall PAR% for each infection was prevalent HSV-2 ( 48.3 % ) , incident HSV-2 ( 4.5 % ) , bacterial vaginosis ( 15.1 % ) , intermediate microbiota ( 7.5 % ) , vaginal yeast ( 6.4 % ) , T. vaginalis ( 1.1 % ) , N. gonorrhoeae ( 0.9 % ) , nonspecific cervicitis ( 0.7 % ) , GUD ( 0.8 % ) and genital warts ( −0.2 % ) . Across the four time periods , the PAR% for prevalent HSV-2 ( 40.4 % , 61.8 % , 58.4 % , 48.3 % ) and bacterial vaginosis ( 17.1 % , 19.5 % , 14.7 % , 17.1 % ) remained relatively high and had no significant trend for change over time . The PAR% for trichomoniasis , gonorrhoea , GUD and genital warts remained less than 3 % across the four periods . Conclusion : Bacterial vaginosis and HSV-2 have consistently been the largest contributors to HIV acquisition risk in the Mombasa Cohort over the past 20 years . Interventions that prevent these conditions would benefit women 's health and could reduce their risk of becoming infected with HIV Objectives : HIV-neutralizing immunoglobulin A ( IgA ) and HIV-specific cellular immunity have been described in highly exposed , persistently seronegative ( HEPS ) individuals , but well controlled studies have not been performed . We performed a prospect i ve , nested case – control study to examine the association of genital IgA and systemic cellular immune responses with subsequent HIV acquisition in high-risk Kenyan female sex workers ( FSWs ) . Design and methods : A r and omized trial of monthly antibiotic prophylaxis to prevent sexually transmitted disease/HIV infection was performed from 1998 to 2002 in HIV-uninfected Kenyan FSWs . After the completion of trial , FSWs who had acquired HIV ( cases ) were matched 1 : 4 with persistently uninfected controls based on study arm , duration of HIV-seronegative follow-up , and time of cohort enrolment . Blinded investigators assayed the ability at enrolment of genital IgA to neutralize primary HIV isolates as well as systemic HIV-specific cellular IFNγ-modified enzyme-linked immunospot and proliferative responses . Results : The study cohort comprised 113 FSWs : 24 cases who acquired HIV and 89 matched controls . Genital HIV-neutralizing IgA was associated with reduced HIV acquisition ( P = 0.003 ) , as was HIV-specific proliferation ( P = 0.002 ) , and these associations were additive . HIV-specific IFNγ production did not differ between case and control groups . In multivariable analysis , HIV-neutralizing IgA and HIV-specific proliferation each remained independently associated with lack of HIV acquisition . Genital herpes ( HSV2 ) was associated with increased HIV risk and with reduced detection of HIV-neutralizing IgA. Conclusion : Genital HIV-neutralizing IgA and systemic HIV-specific proliferative responses , assayed by blinded investigators , were prospect ively associated with HIV nonacquisition . The induction of these immune responses may be an important goal for HIV vaccines Background : Combined oral contraceptives ( COC ) and depot-medroxyprogesterone acetate ( DMPA ) are among the most widely used family planning methods ; their effect on HIV acquisition is not known . Objective : To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections . Methods : This multicenter prospect i ve cohort study enroled 6109 HIV-uninfected women , aged 18–35 years , from family planning clinics in Ug and a , Zimbabwe and Thail and . Participants received HIV testing quarterly for 15–24 months . The risk of HIV acquisition with different contraceptive methods was assessed ( excluding Thail and , where there were few HIV cases ) . Results : HIV infection occurred in 213 African participants ( 2.8/100 woman-years ) . Use of neither COC [ hazard ratio ( HR ) , 0.99 ; 95 % confidence interval ( CI ) , 0.69–1.42 ] nor DMPA ( HR , 1.25 ; 95 % CI , 0.89–1.78 ) was associated with risk of HIV acquisition overall , including among participants with cervical or vaginal infections . While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 ( HSV-2 ) than in those seronegative at enrolment , among the HSV-2-seronegative participants , both COC ( HR , 2.85 ; 95 % CI , 1.39–5.82 ) and DMPA ( HR , 3.97 ; 95 % CI , 1.98–8.00 ) users had an increased risk of HIV acquisition compared with the non-hormonal group . Conclusions : No association was found between hormonal contraceptive use and HIV acquisition overall . This is reassuring for women needing effective contraception in setting s of high HIV prevalence . However , hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition . Additional research is needed to confirm and explain this finding BACKGROUND Globally , herpes simplex virus type 2 ( HSV-2 ) infection is the most common cause of genital ulcer disease . Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections . METHODS We assessed the effectiveness of pericoital tenofovir gel , an antiviral microbicide , in preventing HSV-2 acquisition in a subgroup of 422 HSV-2-negative women enrolled in the Centre for the AIDS Programme of Research in South Africa ( CAPRISA ) 004 study , a double-blind , r and omized , placebo-controlled trial . Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit . A confirmatory analysis was performed by Western blot testing . RESULTS The HSV-2 incidence rate was 10.2 cases per 100 person-years ( 95 % confidence interval [ CI ] , 6.8 to 14.7 ) among 202 women assigned to tenofovir gel , as compared with 21.0 cases per 100 person-years ( 95 % CI , 16.0 to 27.2 ) among 222 women assigned to placebo gel ( incidence rate ratio , 0.49 ; 95 % CI , 0.30 to 0.77 ; P=0.003 ) . The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years , as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir ( incidence rate ratio , 0.37 ; 95 % CI , 0.04 to 1.51 ; P=0.14 ) . As confirmed by Western blot testing , there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel ( incidence rate ratio , 0.45 ; 95 % CI , 0.23 to 0.82 ; P=0.005 ) . CONCLUSIONS In this study in South Africa , pericoital application of tenofovir gel reduced HSV-2 acquisition in women . ( Funded by the U.S. Agency for International Development and others ; Clinical Trials.gov number , NCT00441298 . ) |
11,836 | 24,448,991 | The relationship of blood pressure ( BP ) with stroke is direct and progressive throughout the range of usual BP , starting at a level of ≈115/75 mm Hg.4 It has been estimated that elevated BP accounts for 54 % of stroke and 47 % of coronary heart disease events.5 It is noteworthy that about half of these events occur in persons without hypertension . | The burden of stroke is enormous and increasing .
According to the Global Burden of Disease Study , stroke is the second leading cause of mortality and the third leading cause of disability-adjusted life-years worldwide.1 In the United States , stroke is the second leading cause of mortality and the seventh leading cause of disability-adjusted life-years.2 Although st and ardized rates of stroke seem to be decreasing somewhat , the absolute number of strokes , both ischemic and hemorrhagic , have increased during the past 2 decades.3 Importantly , most strokes occur in low- and middle-income countries , which are poorly equipped to deal with the vast medical , economic , and societal consequences of strokes .
To date , > 50 clinical trials have evaluated the effects of sodium reduction on BP in adults . | Objectives To evaluate salt sensitivity in elderly subjects with different forms of hypertension and controls and to investigate any modulation by genotype Design R and omized , double-blinded , placebo-controlled latin-square Setting Tertiary referral hospital Participants Community subjects ( n = 46 ) aged ⩾ 60 years classified as isolated systolic hypertension [ ISH ; systolic blood pressure ( SBP ) ⩾ 160 , diastolic blood pressure ( DBP ) < 90 mmHg , n = 19 ] , diastolic ± systolic hypertension ( SDH ; DBP ⩾ 90 mmHg , n = 10 ) and normotension ( SBP < 160 , DBP < 90 mmHg , n = 17 ) . Intervention Four 14 day treatments , 50 , 100 , 200 and 300 mmol/day of sodium chloride supplementation interspersed with 14 day washout periods on a salt-restricted diet . Main outcome measures The 24 h blood pressure , heart rate , weight , urinary sodium and creatinine clearance measured during baseline , treatment and washout periods and angiotensinogen ( AGT ) and angiotensin converting enzyme ( ACE ) genotypes . Results For the entire cohort , the mean ± st and ard error ( SE ) of change from baseline in SBP for 50 , 100 , 200 and 300 mmol/day salt was 7.7 ± 2.4 , 12.1 ± 2.4 , 16.6 ± 3.0 , 18.5 ± 2.6 mmHg , respectively . For DBP , the respective changes were:− 0.1 ± 1.5 , 2.4 ± 1.6 , 3.0 ± 1.5 , 5.8 ± 1.7 mmHg . The increase in SBP among ISH subjects was significantly higher than among subjects in the SDH and normotensive groups ( P < 0.05 ) . AGT genotype influenced the effect of salt dose on the change in DBP ( P = 0.006 ) but not SBP ( P = 0.7 ) . Conclusions In healthy , older subjects , a linear increase in BP occurred with increasing salt dose , it appeared most pronounced in ISH subjects and could be modulated by AGT genotype The aim of the present study was to evaluate the effects of a normal-sodium ( 120 mmol sodium ) diet compared with a low-sodium diet ( 80 mmol sodium ) on readmissions for CHF ( congestive heart failure ) during 180 days of follow-up in compensated patients with CHF . A total of 232 compensated CHF patients ( 88 female and 144 male ; New York Heart Association class II-IV ; 55 - 83 years of age , ejection fraction < 35 % and serum creatinine < 2 mg/dl ) were r and omized into two groups : group 1 contained 118 patients ( 45 females and 73 males ) receiving a normal-sodium diet plus oral furosemide [ 250 - 500 mg , b.i.d . ( twice a day ) ] ; and group 2 contained 114 patients ( 43 females and 71 males ) receiving a low-sodium diet plus oral furosemide ( 250 - 500 mg , b.i.d . ) . The treatment was given at 30 days after discharge and for 180 days , in association with a fluid intake of 1000 ml per day . Signs of CHF , body weight , blood pressure , heart rate , laboratory parameters , ECG , echocardiogram , levels of BNP ( brain natriuretic peptide ) and aldosterone levels , and PRA ( plasma renin activity ) were examined at baseline ( 30 days after discharge ) and after 180 days . The normal-sodium group had a significant reduction ( P<0.05 ) in readmissions . BNP values were lower in the normal-sodium group compared with the low sodium group ( 685+/-255 compared with 425+/-125 pg/ml respectively ; P<0.0001 ) . Significant ( P<0.0001 ) increases in aldosterone and PRA were observed in the low-sodium group during follow-up , whereas the normal-sodium group had a small significant reduction ( P=0.039 ) in aldosterone levels and no significant difference in PRA . After 180 days of follow-up , aldosterone levels and PRA were significantly ( P<0.0001 ) higher in the low-sodium group . The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels , and PRA . The results of the present study show that a normal-sodium diet improves outcome , and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients . Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet BACKGROUND Few trials have evaluated the effects of reduced sodium intake in older individuals , and no trial has examined the effects in relevant subgroups such as African Americans . PATIENTS AND METHODS The effects of sodium reduction on blood pressure ( BP ) and hypertension control were evaluated in 681 patients with hypertension , aged 60 to 80 years , r and omly assigned to a reduced sodium intervention or control group . Participants ( 47 % women , 23 % African Americans ) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication . Three months after the start of intervention , medication was withdrawn . The primary end point was occurrence of an average systolic BP of 150 mm Hg or more , an average diastolic BP of 90 mm Hg or more , the resumption of medication , or a cardiovascular event during follow-up ( mean , 27.8 months ) . RESULTS Compared with control , mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group ( P<.001 ) ; significant reductions in sodium excretion occurred in subgroups defined by sex , race , age , and obesity . Prior to medication withdrawal , mean reductions in systolic and diastolic BPs from the reduced sodium intervention , net of control , were 4.3 mm Hg ( P<.001 ) and 2.0 mm Hg ( P = .001 ) . During follow-up , an end point occurred in 59 % of reduced sodium and 73 % of control group participants ( relative hazard ratio = 0.68 , P<.001 ) . In African Americans , the corresponding relative hazard ratio was 0.56 ( P = .005 ) ; results were similar in other subgroups . In dose-response analyses , end points were progressively less frequent with greater sodium reduction ( P for trend = .002 ) . CONCLUSION A reduced sodium intake is a broadly effective , nonpharmacologic therapy that can lower BP and control hypertension in older individuals This study presents an extensive analysis of the effects on blood pressure ( BP ) of changes in sodium intake over a wide array of subgroups , including joint subgroups defined by age and hypertension status , race or ethnicity and hypertension status , and gender and race or ethnicity . Participants were given 3 levels of sodium ( 50 , 100 , and 150 mmol/2,100 kcal ) for 30 days while consuming the Dietary Approaches to Stop Hypertension ( DASH ) diet ( rich in fruits , vegetables , and low-fat dairy ) or a more typical American diet . Within each diet and subgroup , there was a general pattern such that the lower the sodium level , the greater the mean reduction in BP . Sodium reduction from 100 to 50 mmol/2,100 kcal generally had twice the effect on BP as reduction from 150 to 100 mmol/2,100 kcal . Age had a strong and grade d influence on the effect of sodium within the typical and DASH diets , respectively : -4.8 and -1.0 mm Hg systolic for 23 to 41 years , -5.9 and -1.8 mm Hg for 42 to 47 years , -7.5 and -4.3 mm Hg for 48 to 54 years , and -8.1 and -6.0 mm Hg for 55 to 76 years . The influence of age on the effect of sodium reduction was particularly strong in nonhypertensive patients : -3.7 mm Hg systolic for < 45 years and -7.0 mm Hg for > 45 years with the typical diet and -0.7 and -2.8 mm Hg with the DASH diet . Reduced sodium intake and the DASH diet should be advocated for the prevention and treatment of high BP , particularly because the benefits to BP strengthen as subjects enter middle age , when the rate of cardiovascular disease increases sharply Computer simulations have been used to estimate the mortality benefits from population -wide reductions in dietary sodium , although comparisons of these estimates have not been rigorously evaluated . We used 3 different approaches to model the effect of sodium reduction in the US population over the next 10 years , incorporating evidence for direct effects on cardiovascular disease mortality ( method 1 ) , indirect effects mediated by blood pressure changes as observed in r and omized controlled trials of antihypertension medications ( method 2 ) , or epidemiological studies ( method 3).The 3 different modeling approaches were used to model the same scenarios : scenario A , gradual uniform reduction totaling 40 % over 10 years ; scenario B , instantaneous 40 % reduction in sodium consumption sustained for 10 years to achieve a population -wide mean of 2200 mg/d ; and scenario C , instantaneous reduction to 1500 mg sodium per day sustained for 10 years . All 3 methods consistently show a substantial health benefit for reductions in dietary sodium under each of the 3 scenarios tested . A gradual reduction in dietary sodium over the next decade ( scenario A ) as might be achieved with a range of proposed public health interventions would yield considerable health benefits over the next decade , with mean effects across the 3 models ranging from 280 000 to 500 000 deaths averted . Projections of instantaneous reductions illustrate the maximum benefits that could be achieved ( 0.7–1.2 million deaths averted in 10 years ) . Under 3 different modeling assumptions , the projected health benefits from reductions in dietary sodium are substantial BACKGROUND The effect of dietary composition on blood pressure is a subject of public health importance . We studied the effect of different levels of dietary sodium , in conjunction with the Dietary Approaches to Stop Hypertension ( DASH ) diet , which is rich in vegetables , fruits , and low-fat dairy products , in persons with and in those without hypertension . METHODS A total of 412 participants were r and omly assigned to eat either a control diet typical of intake in the United States or the DASH diet . Within the assigned diet , participants ate foods with high , intermediate , and low levels of sodium for 30 consecutive days each , in r and om order . RESULTS Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg ( P<0.001 ) during the control diet and by 1.3 mm Hg ( P=0.03 ) during the DASH diet . Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet ( P<0.001 ) and 1.7 mm Hg during the DASH diet ( P<0.01 ) . The effects of sodium were observed in participants with and in those without hypertension , blacks and those of other races , and women and men . The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level ; and the difference was greater with high sodium levels than with low ones . As compared with the control diet with a high sodium level , the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension , and 11.5 mm Hg lower in participants with hypertension . CONCLUSIONS The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially , with greater effects in combination than singly . Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods 31 patients with a diastolic blood-pressure between 95 and 109 mm Hg have been treated for two years with a regimen involving a moderate restriction of salt in the diet . The results are compared with those in a control group and in a drug-treated group . Salt restriction has reduced the diastolic blood-pressure by 7.3+/-1.6 mm Hg , a result similar to that in patients treated with antihypertensive drugs . In the untreated group the diastolic blood-pressure rose by 1.8+/-1.1 mm Hg . Most patients did not achieve the desired amount of salt restriction and a stricter adherence to the diet might have caused further falls in blood-pressure . Excessive salt intake is probably a major cause of the epidemic of hypertension in " civilised " countries and a reduction in salt intake may help to control the epidemic . In persons with a diastolic blood-pressure between 90 and 105 mm Hg salt restriction should be tried before drugs Studies have shown that patients with compensated heart failure ( HF ) receiving high diuretic doses associated with normal sodium diet and fluid intake restrictions demonstrated significant reductions in readmissions and mortality compared with those who received low-sodium diets , and over a 6-month observation period , a reduction in neurohormonal activation was also observed . The aim of this study was to evaluate the effects of different sodium diets associated with different diuretic doses and different levels of fluid intake on hospital readmissions and neurohormonal changes after 6-month follow-up in patients with compensated HF . Four hundred ten consecutive patients with compensated HF ( New York Heart Association class II to IV ) aged 53 to 86 years , with ejection fractions < 35 % and serum creatinine < 2 mg/dl , were r and omized into 8 groups : group A ( n = 52 ) : 1,000 ml/day of fluid intake , 120 mmol/day , and 250 mg furosemide twice daily ; group B ( n = 51 ) : 1,000 ml/day of fluid intake , 120 mmol/day , and 125 mg furosemide twice daily ; group C ( n = 51 ) : 1,000 ml/day fluid intake , 80 mmol/day , and 250 mg furosemide twice daily ; group D ( n = 51 ) : 1,000 ml/day fluid intake , 80 mmol/day , and 125 mg furosemide twice daily ; group E ( n = 52 ) : 2,000 ml/day fluid intake , 120 mmol/day , and 250 mg furosemide twice daily ; group F ( n = 50 ) : 2,000 ml/day fluid intake , 120 mmol/day , and 125 mg furosemide twice daily ; group G ( n = 52 ) : 2,000 ml/day fluid intake , 80 mmol/day , and 250 mg furosemide twice daily ; and group H ( n = 51 ) : 2,000 ml/day fluid intake , 80 mmol/day , and 125 mg furosemide twice daily . All patients received the treatments > or=30 days after discharge and for 180 days afterward . Signs of HF , body weight , blood pressure , heart rate , laboratory parameters , electrocardiograms , echocardiograms , brain natriuretic peptide , aldosterone , and plasma renin activity were examined at baseline and 180 days later . Group A showed the best results , with a significant reduction ( p < 0.001 ) in readmissions , brain natriuretic peptide , aldosterone , and plasma renin activity compared with the other groups during follow-up ( p < 0.001 ) . In conclusion , these data suggest that the combination of a normal-sodium diet with high diuretic doses and fluid intake restriction , compared with different combinations of sodium diets with more modest fluid intake restrictions and conventional diuretic doses , leads to reductions in readmissions , neurohormonal activation , and renal dysfunction OBJECTIVE To provide a firmer basis for preventing high blood pressure ( BP ) , we tested interventions to promote weight loss , dietary sodium reduction , and their combination for lowering diastolic BP , systolic BP , and the incidence of hypertension during a 3- to 4-year period . METHODS We conducted a r and omized , 2 x 2 factorial , clinical trial , with BP levels measured by blinded observers . Nine academic medical centers recruited 2382 men and women ( age range , 30 - 54 years ) not taking antihypertensive drugs , with a diastolic BP of 83 to 89 mm Hg , a systolic BP lower than 140 mm Hg , and a body mass index ( the weight in kilograms divided by the square of the height in meters ) representing 110 % to 165 % of desirable body weight . Counseling aim ed at helping participants achieve their desirable weight or a 4.5-kg or more weight reduction ( in the weight loss and combined groups ) and /or sodium intake of 80 mmol/d ( in the sodium reduction and combined groups ) was provided . RESULTS From baseline , participants ' weight decreased by 4.3 to 4.5 kg at 6 months and by approximately 2 kg at 36 months in the weight loss and combined groups compared with weight changes in the usual care group ( all groups , P < .001 ) . Sodium excretion decreased 50 and 40 mmol/d at 6 and 36 months , respectively , in the sodium reduction group and about 15 mmol/d less at each time point in the combined group compared with the usual care group ( all groups , P < .01 ) . Compared with the usual care group , BP decreased 3.7/2.7 mm Hg in the weight loss group , 2.9/1.6 mm Hg in the sodium reduction group , and 4.0/2.8 mm Hg in the combined group at 6 months ( all groups , P < .001 ) . At 36 months , BP decreases remained greater in the active intervention groups than in the usual care group ( weight loss group , 1.3/0.9 mm Hg ; sodium reduction group , 1.2/0.7 mm Hg ; combined group , 1.1/0.6 mm Hg ) . Differences were statistically significant for systolic and diastolic BP in the weight loss group and for systolic BP in the sodium reduction group . Through 48 months , the incidence of hypertension ( BP > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic or the use of antihypertensive drugs ) was significantly less in each active intervention group than the usual care group ( average relative risks , 0.78 - 0.82 ) . CONCLUSIONS In overweight adults with high-normal BP , weight loss and reduction in sodium intake , individually and in combination , were effective in lowering systolic and diastolic BP , especially in the short-term ( 6 months ) . Although the effects on average BP declined over time , reductions in hypertension incidence were achieved CONTEXT Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly , but there is a paucity of evidence from r and omized controlled trials in support of this recommendation . OBJECTIVE To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension . DESIGN R and omized controlled trial . PARTICIPANTS A total of 975 [ corrected ] men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication . SETTING Four academic health centers . INTERVENTION The 585 obese participants were r and omized to reduced sodium intake , weight loss , both , or usual care , and the 390 nonobese participants were r and omized to reduced sodium intake or usual care . Withdrawal of antihypertensive medication was attempted after 3 months of intervention . MAIN OUTCOME MEASURE Diagnosis of high blood pressure at 1 or more follow-up visits , or treatment with antihypertensive medication , or a cardiovascular event during follow-up ( range , 15 - 36 months ; median , 29 months ) . RESULTS The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake ( relative hazard ratio , 0.69 ; 95 % confidence interval [ CI ] , 0.59 - 0.81 ; P<.001 ) and , in obese participants , among those assigned vs not assigned to weight loss ( relative hazard ratio , 0.70 ; 95 % CI , 0.57 - 0.87 ; P<.001 ) . Relative to usual care , hazard ratios among the obese participants were 0.60 ( 95 % CI , 0.45 - 0.80 ; P<.001 ) for reduced sodium intake alone , 0.64 ( 95 % CI , 0.49 - 0.85 ; P=.002 ) for weight loss alone , and 0.47 ( 95 % CI , 0.35 - 0.64 ; P<.001 ) for reduced sodium intake and weight loss combined . The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups . CONCLUSION Reduced sodium intake and weight loss constitute a feasible , effective , and safe nonpharmacologic therapy of hypertension in older persons 20 patients with mild hypertension ( average supine blood pressure without treatment , 164/101 mm Hg ) reduced their salt intake to 50 mmol ( 3 g ) per day for a month . They then entered a 3 month double-blind r and omised crossover study of three levels of sodium intake : 200 , 100 , and 50 mmol per day . Blood pressure was significantly reduced on the middle and lowest sodium intakes . The average fall in blood pressure from the highest to the lowest sodium intake was 16/9 mm Hg . Patients continued to restrict their sodium intake for a further year . In 16 of the 20 patients blood pressure remained well controlled with salt restriction alone . Supine blood pressure at 1 year was 142/87 ( SE 3/2 ) mm Hg with a 24 h urinary sodium excretion of 54 ( 7 ) mmol . These results show a progressive blood pressure fall as salt intake is reduced and that , in many patients with mild essential hypertension , blood pressure can be controlled without the need for drug therapy OBJECTIVE To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure . DESIGN R and omized control multicenter trials . SETTING Volunteers recruited from the community , treated and followed up at special clinics . PARTICIPANTS Of 16,821 screenees , 2182 men and women , aged 30 through 54 years , with diastolic blood pressure from 80 through 89 mm Hg were selected . Of these , 50 did not return for follow-up blood pressure measurements . INTERVENTIONS Three life-style change groups ( weight reduction , sodium reduction , and stress management ) were each compared with unmasked nonintervention controls over 18 months . Four nutritional supplement groups ( calcium , magnesium , potassium , and fish oil ) were each compared singly , in double-blind fashion , with placebo controls over 6 months . MAIN OUTCOME MEASURES Primary : change in diastolic blood pressure from baseline to final follow-up , measured by blinded observers . Secondary : changes in systolic blood pressure and intervention compliance measures . RESULTS Weight reduction intervention produced weight loss of 3.9 kg ( P less than .01 ) , diastolic blood pressure change of -2.3 mm Hg ( P less than .01 ) , and systolic blood pressure change of -2.9 mm Hg ( P less than .01 ) . Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h ( P less than .01 ) , diastolic blood pressure by 0.9 mm Hg ( P less than .05 ) , and systolic blood pressure by 1.7 mm Hg ( P less than .01 ) . Despite good compliance , neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly ( P greater than .05 ) . CONCLUSIONS Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons . Sodium reduction is also effective . The long-term effects of weight reduction and sodium reduction , alone and in combination , require further evaluation |
11,837 | 23,171,675 | Conclusions No apps for people with asthma combined reliable , comprehensive information about the condition with supportive tools for self-management .
There remains much to be done if apps are to find broad use in clinical practice ; clinicians can not recommend tools that are inaccurate , unsafe or lack an evidence base | Background Apps have been enthusiastically adopted by the general public .
They are increasingly recognized by policy-makers as a potential medium for supporting self-management of long-term conditions .
We assessed the degree to which current smartphone and tablet apps for people with asthma offer content and tools of appropriate quality to support asthma self-management . | Objective To determine whether mobile phone based monitoring improves asthma control compared with st and ard paper based monitoring strategies . Design Multicentre r and omised controlled trial with cost effectiveness analysis . Setting UK primary care . Participants 288 adolescents and adults with poorly controlled asthma ( asthma control question naire ( ACQ ) score ≥1.5 ) from 32 practice s. Intervention Participants were central ly r and omised to twice daily recording and mobile phone based transmission of symptoms , drug use , and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring . Main outcome measures Changes in scores on asthma control question naire and self efficacy ( knowledge , attitude , and self efficacy asthma question naire ( KASE-AQ ) ) at six months after r and omisation . Assessment of outcomes was blinded . Analysis was on an intention to treat basis . Results There was no significant difference in the change in asthma control or self efficacy between the two groups ( ACQ : mean change 0.75 in mobile group v 0.73 in paper group , mean difference in change −0.02 ( 95 % confidence interval −0.23 to 0.19 ) ; KASE-AQ score : mean change −4.4 v −2.4 , mean difference 2.0 ( −0.3 to 4.2 ) ) . The numbers of patients who had acute exacerbations , steroid courses , and unscheduled consultations were similar in both groups , with similar healthcare costs . Overall , the mobile phone service was more expensive because of the expenses of telemonitoring . Conclusions Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines st and ards . The mobile technology was not cost effective . Trial registration Clinical Trials NCT00512837 The self-management of asthma can improve clinical outcomes . Recently , mobile telephones have been widely used as an efficient , instant personal communication tool . This study investigated whether a self-care system will achieve better asthma control through a mobile telephone-based interactive programme . This was a prospect i ve , controlled study in outpatient clinics . From 120 consecutive patients with moderate-to-severe persistent asthma , 89 were eventually recruited for the study , with 43 in the mobile telephone group ( with a mobile telephone-based interactive asthma self-care system ) . In the mobile telephone group , mean±sem peak expiratory flow rate significantly increased at 4 ( 378.2±9.3 L·min−1 ; n = 43 ; p = 0.020 ) , 5 ( 378.2±9.2 L·min−1 ; n = 43 ; p = 0.008 ) and 6 months ( 382.7±8.6 L·min−1 ; n = 43 ; p = 0.001 ) compared to the control group . Mean±sem forced expiratory volume in 1 s significantly increased at 6 months ( 65.2±3.2 % predicted ; n = 43 ; p<0.05 ) . Patients in the mobile telephone group had better quality of life after 3 months , as determined using the Short Form-12 ® physical component score , and fewer episodes of exacerbation and unscheduled visits than the control group . Patients in the mobile telephone group significantly increased their mean daily dose of either systemic or inhaled corticosteroids compared with the control group . The mobile telephone-based interactive self-care system provides a convenient and practical self-monitoring and -management of asthma , and improves asthma control BACKGROUND For children younger than 12 years old with asthma , there are several quality -of-life instruments , clinical diaries , and question naires assessing symptoms ; however , a vali date d tool for assessing asthma control is currently lacking . OBJECTIVE To develop and vali date the Childhood Asthma Control Test ( C-ACT ) , a self-administered tool for identifying children aged 4 - 11 years whose asthma is inadequately controlled . METHODS A 21-item question naire was administered to 343 patients with asthma and their caregivers , r and omly assigning 75 % ( n = 257 ) for development and cross-sectional validation of the tool and 25 % ( n = 86 ) to a confirmatory sample . Stepwise logistic regression was used to reduce the 21 items to those best able to discriminate control as defined by the specialist 's rating of asthma control . RESULTS Seven items were selected from regression analyses of the development sample to comprise the C-ACT . The scores of each item were summed for a total score ( 0 - 27 ) , with lower scores indicating poorer control . Summed scores discriminated between groups of patients differing in the specialists ' rating of asthma control ( F = 36.89 ; P < .0001 ) , the need for change in patients ' therapy ( F = 20.07 ; P < .0001 ) , and % predicted FEV(1 ) ( F = 2.66 ; P = .0494 ) . A score of 19 indicated inadequately controlled asthma ( specificity 74 % , sensitivity 68 % ) . These analyses were confirmed in the confirmatory sample . CONCLUSION The C-ACT is a vali date d tool to assess asthma control and identify children with inadequately controlled asthma . CLINICAL IMPLICATION S The C-ACT can be valuable in clinical practice and research based on its validation , ease of use , input from the child and caregiver , and alignment with asthma guidelines |
11,838 | 23,723,992 | CONCLUSIONS The efficacy of pharmacologic treatments did not significantly differ , on average , between RCTs including older adults only and RCTs of all adults . | CONTEXT Older adults are underrepresented in clinical research .
To assess therapeutic efficacy in older patients , some r and omized controlled trials ( RCTs ) include older adults only .
OBJECTIVE To compare treatment effects between RCTs including older adults only ( elderly RCTs ) and RCTs including all adults ( adult RCTs ) by a meta-epidemiological approach . | Background : Information on major harms of medical interventions comes primarily from epidemiologic studies performed after licensing and marketing . Comparison with data from large-scale r and omized trials is occasionally feasible . We compared evidence from r and omized trials with that from epidemiologic studies to determine whether they give different estimates of risk for important harms of medical interventions . Methods : We targeted well-defined , specific harms of various medical interventions for which data were already available from large-scale r and omized trials ( > 4000 subjects ) . Nonr and omized studies involving at least 4000 subjects addressing these same harms were retrieved through a search of MEDLINE . We compared the relative risks and absolute risk differences for specific harms in the r and omized and nonr and omized studies . Results : Eligible nonr and omized studies were found for 15 harms for which data were available from r and omized trials addressing the same harms . Comparisons of relative risks between the study types were feasible for 13 of the 15 topics , and of absolute risk differences for 8 topics . The estimated increase in relative risk differed more than 2-fold between the r and omized and nonr and omized studies for 7 ( 54 % ) of the 13 topics ; the estimated increase in absolute risk differed more than 2-fold for 5 ( 62 % ) of the 8 topics . There was no clear predilection for r and omized or nonr and omized studies to estimate greater relative risks , but usually ( 75 % [ 6/8 ] ) the r and omized trials estimated larger absolute excess risks of harm than the nonr and omized studies did . Interpretation : Nonr and omized studies are often conservative in estimating absolute risks of harms . It would be useful to compare and scrutinize the evidence on harms obtained from both r and omized and nonr and omized studies Background We aim ed to determine the representation of elderly people in published reports of r and omized controlled trials ( RCTs ) . We focused on trials of 4 medications — pioglitazone , rosuvastatin , risedronate , and valsartan — frequently used by elderly patients with chronic medical conditions . Methods and Findings We selected all reports of RCTs indexed in PubMed from 1966 to April 2008 evaluating one of the 4 medications of interest . Estimates of the community-based “ on-treatment ” population were from a national health insurance data base ( SNIIR-AM ) covering approximately 86 % of the population in France . From this data base , we evaluated data cl aims from January 2006 to December 2007 for 1,958,716 patients who received one of the medications of interest for more than 6 months . Of the 155 RCT reports selected , only 3 studies were exclusively of elderly patients ( 2 assessing valsartan ; 1 risedronate ) . In only 4 of 37 reports ( 10.8 % ) for pioglitazone , 4 of 22 ( 18.2 % ) for risedronate , 3 of 29 ( 10.3 % ) for rosuvastatine and 9 of 67 ( 13.4 % ) for valsartan , the proportion of patients aged 65 or older was within or above that treated in clinical practice . In 62.2 % of the reports for pioglitazone , 40.9 % for risedronate , 37.9 % for rosuvastatine , and 70.2 % for valsartan , the proportion of patients aged 65 or older was lower than half that in the treated population . The representation of elderly people did not differ by publication date or sample size . Conclusions Elderly patients are poorly represented in RCTs of drugs they are likely to receive Context Prescription and management of medications are important issues for older adults . Contribution Among elders enrolled in two managed care organizations , most quality problems were related to failure to prescribe indicated medications ; failure to monitor medications ; and failure to provide medication along with proper documentation and education in concert with other physicians . Implication s Prescribing inappropriate medications for older adults is less of an issue than other aspects of drug therapy . Quality improvement efforts should focus on avoiding errors of omission in prescribing indicated medications , monitoring , patient education , and follow-up . The Editors Pharmacotherapy is an essential component of medical treatment for older patients , but medications are also responsible for many adverse events in this group . Ninety percent of people 65 years of age or older take at least one medication ( 1 ) . This age group , which represents only 13 % of the population , accounts for one third of all prescription drug expenditures in the United States ( 2 ) . Many older persons take multiple drugs for the treatment of several conditions , which increases the chance of adverse drug reactions , drugdrug interactions , and drugdisease interactions . The frequency of adverse drug events in elderly out patients ranges from 10 % to 35 % , depending on the setting ( 3 - 5 ) . Recognizing the magnitude of medication-related issues , panels of geriatric experts rate medication problems among the most important quality -of-care problems for older patients ( 6 - 8 ) . Reflecting the severity and frequency of adverse drug events in older patients , many investigations have focused on the appropriateness of medication prescribing to elderly persons . Implicit review mechanisms include the Medication Appropriateness Index , which consists of 10 medication characteristics ( including indication , effectiveness , and dosage ) that a trained pharmacist review er can judge as appropriate , marginally appropriate , or inappropriate . An application of the Medication Appropriateness Index to elderly veterans taking 5 or more prescription medications found that 74 % had at least 1 inappropriate aspect to their prescriptions ( 9 , 10 ) . Review s using explicit criteria usually focus on medications that should be avoided in the care of older patients . The list of medications to avoid , which was developed by Beers and colleagues on the basis of a formal consensus of geriatric experts ( 11 - 13 ) , has been applied to various groups of patients , revealing a high prevalence of inappropriate drug use ( 14 - 20 ) . In addition , explicit criteria about drugdrug interactions , treatment duration , and drug contraindications were created by Tamblyn and colleagues and applied to medications prescribed to older patients in Canada ( 21 ) . They found that more than half of older patients took at least one high-risk medication . Health policy efforts , on the other h and , have focused predominantly on finding ways to pay for the medication needed by older patients . Proposals aim to improve access to pharmacologic care but do not strive to develop mechanisms to evaluate or improve the quality of medication management for older patients . Improvement in access to medications without quality assurance may result in a mere increase in care without change in outcomes . To provide a more comprehensive evaluation of the quality of pharmacologic care for older patients , we systematic ally evaluated medication management for a sample of older patients by taking advantage of a set of explicit process of care quality indicators developed and implemented in the Assessing Care of Vulnerable Elders ( ACOVE ) project ( 22 ) . Whereas the earlier ACOVE analysis described overall quality of care and compared care quality for geriatric and medical conditions , this study focuses on pharmacologic care and identifies improvement needs in medication management . Our quality evaluation covered the continuum of pharmacologic care , from recognizing the indications for medications to choosing medication , prescribing appropriately , educating and documenting , and monitoring after prescribing . Methods The ACOVE project developed a set of explicit quality indicators to evaluate the care provided to vulnerable older persons ( 22 - 24 ) . The system focuses on processes of care within the domains of prevention , diagnosis , treatment , and follow-up and covers the spectrum of care contained in 22 conditions that are important in the care of older patients ( 7 ) . The methods for selecting conditions and developing the quality indicators are described in detail elsewhere ( 7 , 23 ) . Methods included systematic literature review s and multiple layers of expert judgment ( 23 ) . The literature review result ed in proposal of c and i date quality indicators , which were review ed by an expert panel that rated each of the proposed quality indicators for validity and feasibility . This set was modified and approved by a clinical committee of national geriatric experts and by the American College of Physicians Task Force on Aging ( 24 ) . From the final ACOVE set of quality indicators , 43 quality indicators ( Table 1 and Appendix Table ) that pertained to pharmacologic care and had more than 5 eligible patients are included in this analysis . Table 1 . Medication Quality Indicators , Number of Eligible Patients , and Pass Rates Patients and Data Collection We assessed care provided to older persons who were enrolled in 2 managed care organizations . Each managed care organization , one in the U.S. Northeast and the other in the Southwest , had more than 20 000 senior enrollees and contracted with a network of providers to deliver care . A r and om sample of community-dwelling persons 65 years of age or older was drawn from enrollees in each managed care organization . Eligibility criteria included continuous enrollment in the managed care organization for at least 13 months , no out-of-plan care , and no active treatment for malignant conditions ( excluding nonmelanoma skin cancer ) during the period . In addition , persons who did not speak English were excluded because our interview instruments were not available in other language s. Among the enrollees , we targeted vulnerable elders , defined as persons 65 years of age and older who are at increased risk for death or functional decline . Vulnerable elders were identified on the basis of self-report ( or proxy report ) by using a brief screening survey ( the Vulnerable Elders-13 [ VE-13 ] Survey [ 25 ] ) administered by telephone . The R AND Institutional Review Board approved the study protocol . Data were derived mainly from abstract ing medical records . For participating patients , we identified all inpatient and outpatient medical records during the 13-month period of 1 July 1998 to 31 July 1999 . These medical records were abstract ed by trained nurses with experience in quality assessment . The abstract or considered all of a patient 's medical records when assessing whether a patient was eligible for and received the indicated care processes . Information on eligibility for a quality indicator could be derived from one medical record ( such as a primary care physician starting an appropriate antidepressant ) and the care process delivered and documented from records in another setting ( such as a psychiatric consultant escalating the antidepressant dosage in response to lack of improvement ) . A senior nurse- review er assessed each completed medical record abstract , and physician overreaders review ed quality indicators that required a clinical assessment , such as whether there was follow-up to newly started long-term therapy with a medication or whether newly started therapy with a highly anticholinergic drug had acceptable alternatives . We evaluated inter-rater reliability by re- abstract ing a r and om sample of 10 % of the medical records . These records contained 698 quality indicators ; 97 % had identical eligibility and 95 % demonstrated identical eligibility and score . Details of study enrollment and data collection can be found elsewhere ( 22 ) . Because some aspects of care might not be adequately captured in the medical record ( for example , patient education about medications ) , these data were supplemented by a quality -of-care interview with study participants ( or , if necessary , their proxies ) . During the interview , patients were asked to list all of their medications . On the basis of conditions and medications reported during the interview , patients were asked about specific processes of care they had received . The interview was conducted by telephone between August and October 2000 . To minimize recall bias , we asked about most recent care when implementing quality indicators that may include multiple events ( for example , education about newly started therapy with a medication ) . Information was obtained from medical records for 37 quality indicators and from the patient interview for 6 quality indicators . For 4 quality indicators reported previously by using medical record data ( 22 ) , we used interview data in this analysis because subsequent evaluation revealed that interview data on information transfer quality indicators yielded higher pass rates that were aligned with a priori hypotheses and provided more conservative estimates of quality of care . Statistical Analysis A quality indicator was scored for a patient if he or she met the eligibility criteria to receive the specified care process . The quality indicator was passed if the care process was implemented for the patient . If the medical record indicated that the patient declined the care process , the quality indicator was considered to be passed . On the other h and , if the patient had a prespecified contraindication to the care process ( such as a patient with asthma who otherwise was eligible to receive a -blocker after a myocardial infa rct ion ) , the patient was considered ineligible for the quality indicator . Quality scores were calculated as the proportion of eligible patients who received indicated care . 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 Frail older people have been systematic ally excluded from r and omised controlled trials ( RCT ) . We aim to recruit older , frail hospitalised patients in an RCT and evaluate the frailty index ( FI ) as a measure to describe the types of people included in the study . We recruited 315 hospitalised patients aged 65 years ; age ranged from 60 to 102 years . Baseline assessment scores ranged as follow : Mini‐Mental Status Examination from 7 to 30 , Barthel index from 5 to 100 and FI from 2 to 24 . Total deaths were 20 ( 6 % ) . We demonstrated that it is feasible to recruit frail older people into RCTs . The FI does not show any ‘ floor ’ or ‘ ceiling ’ effects . We can measure frailty in an RCT cohort , and we believe that clinical trials should include more frail older people and that the use of an FI can facilitate such trials and generate reliable data to guide future medical practice in a rapidly ageing society CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , generalizable data on drug safety reporting are sparse . OBJECTIVE To scrutinize the completeness of safety reporting in r and omized trials . DESIGN , SETTING , AND PATIENTS Survey of safety reporting in 192 r and omized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm ( N = 130074 patients ) . Trial reports were identified from comprehensive meta-analyses in 7 medical areas . MAIN OUTCOME MEASURES Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects ; article space allocated to safety reporting and predictors of such reporting . RESULTS Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39 % and 29 % of trial reports , respectively . Only 46 % of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity . For these 3 parameters , there was significant heterogeneity in rates of adequate reporting across topics ( P = .003 , P<.001 , and P = .02 , respectively ) . Overall , the median space allocated to safety results was 0.3 page . A similar amount of space was devoted to contributor names and affiliations ( P = .16 ) . On average , the percentage of space devoted to safety in the results section was 9.3 % larger in trials involving dose comparisons than in those that did not ( P<.001 ) and 3.8 % smaller in trials reporting statistically significant results for efficacy outcomes ( P = .047 ) . CONCLUSIONS The quality and quantity of safety reporting vary across medical areas , study design s , and setting s but they are largely inadequate . Current st and ards for safety reporting in r and omized trials should be revised to address this inadequacy OBJECTIVE To determine the extent to which the elderly have been excluded from trials of drug therapies used in the treatment of acute myocardial infa rct ion , to identify factors associated with such exclusions , and to explore the relationship between the exclusion of elderly and the representation of women . DATA SOURCES We conducted a systematic search of the English- language literature from January 1960 through September 1991 to identify all relevant studies of specific pharmacotherapies employed in the treatment of acute myocardial infa rct ion . To accomplish this , we search ed MEDLINE , major cardiology textbooks , meta-analyses , review s , editorials , and the bibliographies of all identified articles . STUDY SELECTION Only trials in which patients were r and omly allocated to receive a specific therapeutic regimen or a placebo or nonplacebo control regimen were included for review . DATA EXTRACTION Studies were abstract ed for year of publication , source of support , performance location , drug therapies to which patients were r and omized , use of invasive diagnostic tests or therapeutic procedures , exclusion criteria , size and demographic characteristics of the r and omized study population , and principal outcome measures . DATA SYNTHESIS A total of 214 trials met inclusion criteria , involving 150,920 study subjects . Over 60 % of trials excluded persons over the age of 75 years . Studies published after 1980 were more likely to have age-based exclusions compared with studies published before 1980 ( adjusted odds ratio , 4.92 ; 95 % confidence interval , 2.33 to 10.54 ) . Trials of thrombolytic therapy involving an invasive procedure were more likely to exclude elderly patients compared with other studies ( adjusted odds ratio , 2.45 ; 95 % confidence interval , 1.10 to 5.47 ) . Studies with age-based exclusions had a smaller percentage of women compared with those without such exclusions ( 18 % vs 23 % ; P = .0002 ) , with the mean age of the study population significantly associated with the proportion of women participants ( P = .0001 , R2 = .29 ) . CONCLUSIONS Age-based exclusions are frequently used in clinical trials of medications used in the treatment of acute myocardial infa rct ion . Such exclusions limit the ability to generalize study findings to the patient population that experiences the most morbidity and mortality from acute myocardial infa rct ion BACKGROUND Reports of clinical trials usually emphasize efficacy results , especially when results are statistically significant . Poor safety reporting can lead to misinterpretation and inadequate conclusions about the interventions assessed . Our aim was to describe the reporting of harm-related results from r and omized controlled trials ( RCTs ) . METHODS We search ed the MEDLINE data base for reports of RCTs published from January 1 , 2006 , through January 1 , 2007 , in 6 general medical journals with a high impact factor . Data were extracted by use of a st and ardized form to appraise the presentation of safety results in text and tables . RESULTS Adverse events were mentioned in 88.7 % of the 133 reports . No information on severe adverse events and withdrawal of patients owing to an adverse event was given in 27.1 % and 47.4 % of articles , respectively . Restrictions in the reporting of harm-related data were noted in 43 articles ( 32.3 % ) with a description of the most common adverse events only ( n = 17 ) , severe adverse events only ( n = 16 ) , statistically significant events only ( n = 5 ) , and a combination of restrictions ( n = 5 ) . The population considered for safety analysis was clearly reported in 65.6 % of articles . CONCLUSION Our review reveals important heterogeneity and variability in the reporting of harm-related results in publications of RCTs BACKGROUND AND METHODS Aldosterone is important in the pathophysiology of heart failure . In a doubleblind study , we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor , a loop diuretic , and in most cases digoxin . A total of 822 patients were r and omly assigned to receive 25 mg of spironolactone daily , and 841 to receive placebo . The primary end point was death from all causes . RESULTS The trial was discontinued early , after a mean follow-up period of 24 months , because an interim analysis determined that spironolactone was efficacious . There were 386 deaths in the placebo group ( 46 percent ) and 284 in the spironolactone group ( 35 percent ; relative risk of death , 0.70 ; 95 percent confidence interval , 0.60 to 0.82 ; P<0.001 ) . This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes . The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group ( relative risk of hospitalization , 0.65 ; 95 percent confidence interval , 0.54 to 0.77 ; P<0.001 ) . In addition , patients who received spironolactone had a significant improvement in the symptoms of heart failure , as assessed on the basis of the New York Heart Association functional class ( P<0.001 ) . Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone , as compared with 1 percent of men in the placebo group ( P<0.001 ) . The incidence of serious hyperkalemia was minimal in both groups of patients . CONCLUSIONS Blockade of aldosterone receptors by spironolactone , in addition to st and ard therapy , substantially reduces the risk of both morbidity and death among patients with severe heart failure |
11,839 | 20,117,566 | Evidence in this review of studies published from 1986 through 2004 indicates that reminder/recall systems can effectively increase screening with mammography , Pap , fecal occult blood tests , and flexible sigmoidoscopy . | Most major medical organizations recommend routine screening for breast , cervical , and colorectal cancers .
Screening can lead to early detection of these cancers , result ing in reduced mortality .
Yet , not all people who should be screened are screened regularly or , in some cases , ever .
This report presents results of systematic review s of effectiveness , applicability , economic efficiency , barriers to implementation , and other harms or benefits of provider reminder/recall interventions to increase screening for breast , cervical , and colorectal cancers .
These interventions involve using systems to inform healthcare providers when individual clients are due ( reminder ) or overdue ( recall ) for specific cancer screening tests . | Recent re-evaluation of preventive health care has result ed in more limited and directed guidelines ; nonetheless , physician compliance has remained poor . This study assessed whether an inexpensive reminder system of preventive care checklists would improve physician implementation of periodic health measures . Residents in internal medicine were r and omly placed into two groups : one received a copy of the appropriate checklist with each patient 's medical record ; the other did not . After one year , 200 r and omly selected records were audited to determine the proportion of recommendations implemented for each patient . Residents who received checklists performed appropriate preventive health measures at a significantly higher rate than those who did not ( 0.56 + /- 0.26 versus 0.39 + /- 0.22 , p less than 0.002 ) . The actual use of the checklist to record the results was associated with an even higher rate of compliance compared with instances in which the checklists were provided but not used and instances in which checklists were not received ( 0.70 + /- 0.21 versus 0.44 + /- 0.24 and 0.39 + /- 0.22 , respectively , p less than 0.002 ) . These data suggest that a physician 's use of simple checklists can provide an inexpensive and effective means of improving implementation of periodic health maintenance We developed a computer-stored medical record system containing a limited set of the total clinical data base -- primarily diagnostic studies and treatments . This system responds to its own content according to physician-authored reminder rules . To determine the effect of the reminder messages generated by 1490 rules on physician behavior , we r and omly assigned practitioners in a general medicine clinic to study or control groups . The computer found indications for six different actions per patient in 12 467 patients during a 2-year study : 61 study group residents who received computer reminders responded to 49 % of these indications ; 54 control group residents , to only 29 % ( p less than 0.0001 ) . Preventive care ( occult blood testing , mammographic screening , weight reduction diets , influenza and pneumococcal vaccines ) was affected . The intentions of the study group to use a given action for an indication predicted their response to the indications ( p less than 0.03 , r2 = 0.33 ) . The intentions of the control residents did not In an academic general medicine clinic , we performed a r and omized , controlled trial to compare ( 1 ) the effects of supplying monthly feedback reports of compliance with preventive care protocol s by 135 internal medicine house staff with ( 2 ) the effects of specific reminders given to them at the time of patient visits . The protocol s were r and omly divided into two groups , A and B , and half the house staff were given feedback for Group A and half for Group B. Thus , each group served as a control for the other . Each feedback group was also r and omly assigned to receive reminders for either Group A or B protocol s. House staff receiving feedback more often complied with fecal occult blood testing , mammography , pneumococcal vaccination , use of metronidazole , and combined Group A and B protocol s than did controls ( P < 0.01 ) . There was also significantly more compliance with the same protocol s by house staff receiving reminders , but the increase for fecal occult blood testing , pneumococcal vaccination , and combined Group A protocol s was twice that seen in physicians given feedback alone . In addition , reminders alone increased compliance with oral calcium supplementation . Overall compliance with the preventive care protocol s was low : 10 - 15 % in physicians receiving neither feedback nor reminders , increasing to 15 - 30 % in those receiving reminders . Physician compliance with suggested preventive care protocol s can be increased by both delayed feedback and immediate reminders , but reminders have a greater effect OBJECTIVE --To discover whether systematic methods of call and recall are more effective than a non- systematic method and to see which of the two systematic methods was more effective . DESIGN -- Prospect i ve r and omised controlled trial over a year . SETTING --One group general practice . PATIENTS --416 Women over 35 eligible for a smear test who had never had a cervical smear test or in whom a smear test was overdue ( previous test more than five years before ) . INTERVENTIONS --One group received written invitations to have a smear taken . The second group had their notes tagged so that the doctor would remind them ( when they attended for another reason ) to have a smear test . No special intervention was made in the third group . MAIN OUTCOME MEASURE -- Performance of a cervical smear test during the year of the study . RESULTS --32 % ( 45/140 ) of the screened group , 27 % ( 39/142 ) of the tagged group , and 15 % ( 20/134 ) of the control group had a smear test during the year . The percentage of women having a smear test in the screened group was not significantly different from that in the tagged group , but the percentages in the two groups were significantly different from that in the control group . Whether a woman had had a previous smear test significantly affected the uptake of the invitation to have a smear test independently of the method of invitation . CONCLUSIONS --The systematic methods of call and recall were more effective than a non- systematic method . There was no significant difference between the two systematic methods ( sending letters or tagging the notes ) at one year Objective : To improve the delivery of preventive care in a medical clinic , a controlled trial was conducted of two interventions that were expected to influence delivery of preventive services differently , depending on level of initiative required of the physician or patient to complete a service . Design : A prospect i ve , controlled trial of five-months ’ duration . Setting : A university hospital-based , general medical clinic . Participants : Thirty-nine junior and senior medical residents who saw patients in stable clinic teams throughout the study .Intervention : A computerized reminder system for physicians and a patient question naire and educational h and out on preventive care . Measurements and main results : Delivery of five of six audited preventive services improved significantly after the interventions were introduced . The computerized reminder alone increased completion rates of services that relied primarily on physician initiative ; the question naire alone increased completion rate of the service that depended more on patient compliance as well as on some physician-dependent services . Both interventions used together were slightly less effective in improving performance of physician-dependent services than the computerized reminder used alone . Conclusions : These interventions can improve the delivery of preventive care but they differ in their impacts on physician and patient behaviors . Overall , the computer reminder was the more effective intervention BACKGROUND We compared the efficacy of a computer-generated prompt sheet placed on the front of patients ' charts with a patient-carried prompt card to remind physicians to perform selected health maintenance items . METHODS A r and omized prospect i ve single-blind study was performed in private practice offices in rural eastern North Carolina , with 28 family practitioners and nine general internists participating . Twenty-two physicians were r and omized to the computer prompt group and 22 to the card prompt group . Four physicians in the computer group did not complete the study because of computer software problems , and three physicians did not complete the study because their limited staff was unable to enter patient data into the computer . Before the intervention , 20 patient charts ( 10 males and 10 females ) from each physician were audited for the performance of influenza vaccinations , stool for occult blood , pap smears , breast examinations performed by the physicians , and mammograms . One year after the intervention was instituted , chart audits for the above five items were done again on 20 different patient charts for each physician . RESULTS There was a 7 % increase in the performance of influenza vaccinations in the card group ( 17 % vs 24 % ) compared with a 6 % increase in the computer group ( 20 % vs 26 % ) . There was a 5 % decrease in the performance of stool for occult blood in the card group ( 28 % vs 23 % ) compared with a 1 % increase in the computer group ( 30 % vs 31 % ) . There was an 11 % decrease in the performance of pap smears in the card group ( 26 % vs 15 % ) compared with a 3 % increase in the computer group ( 23 % vs 26 % ) . There was a 2 % decrease in the performance of breast examinations by the physician in the card group ( 35 % vs 33 % ) compared with a 3 % increase in the computer group ( 30 % vs 33 % ) . Finally , there was a 3 % increase in the performance of mammograms in the card group ( 22 % vs 25 % ) compared with an 11 % increase in the computer group ( 15 % vs 26 % ) . CONCLUSIONS Our data show a greater increase in performance of health maintenance items in the computer-prompted group . The performance of stool for occult blood , pap smears , breast examinations performed by the physician , and mammograms were increased more in the computer-prompted group than in the card group . However , there was not a statistically significant difference after intervention for any of the audited health maintenance items for either the computer group or the card group . Overall , health maintenance measures were performed in only a minority of appropriate patients To determine effective methods of promoting routine cancer screening , we r and omly assigned 62 internal medicine residents to receive cancer screening reminders ( computer-generated lists of overdue tests at patients ' visits ) , audit with feedback ( monthly seminars about screening , with feedback about their performance rates ) , or no intervention ( controls ) . Half of the residents in each group also were r and omized to receive patient education ( patients received literature and notices of overdue tests ) . We review ed a sample of each physician 's medical records to assess performance of seven tests during 9-month periods before and after initiating the interventions . Cancer screening reminders increased performance of six of seven tests ; audit with feedback , four of seven tests ; and patient education , one of two targeted breast cancer screening tests . The results indicate that the cancer screening reminders strategy was the most effective in promoting the performance of routine cancer screening tests In a r and omized trial three ways of increasing rates of cervical screening were compared for women attending a family medicine center . Working from computerized medical records , 1,587 women aged 18 to 35 years who were overdue for a screening test were included in the study . In a control group , no formal method was used to encourage patients to attend for screening , and 13.7 percent obtained a test within the trial year . In one intervention group the physician was issued a message identifying those women visiting the center for a routine appointment who were due for screening ; 16.1 percent were screened . Sending a letter to patients in a second group yielded a 25.9 percent compliance rate . In a third group the practice nurse called patients on the telephone to advise them to obtain the test , and 20.0 percent complied . Reminders issued to the physician provide a low-cost , opportunistic approach to reach women who happen to visit the practice , but this approach should be supplemented by telephoning or sending a letter to those women who do not attend regularly Despite its demonstrated efficacy in reducing breast carcinoma mortality , screening mammography remains underutilized and its promotion in the primary care setting provides an important opportunity for intervention BACKGROUND Colorectal cancer is the second leading cause of cancer mortality in israel . Unfortunately , compliance with annual fecal occult blood testing is very low . OBJECTIVE To assess the effectiveness of interventions to increase FOBT screening in primary care clinics in Israel . METHODS A prospect i ve , r and omized study included all 50 - 75 year old enrollees of six family physicians in two primary care clinics . The register of two physicians , one from each clinic , was allocated to one of three groups . Two FOBT reminder strategies were tested : a physician reminder ( 753 patients ) , and a patient reminder that was either a phone call ( 312 patients ) or a letter ( 337 patients ) . The control group ( 913 patients ) of physicians continued administering their regular level of care . The main outcome measure was the percentage of patients undergoing FOBT screening in each study arm at the conclusion of the one year study period . RESULTS In the intervention groups 14.3 % ( 201/1,402 ) were screened using the FOBT over the course of the study year . Using an intent-to-screen analysis , the screening rate in the physician and patient reminder groups was significantly higher than in the control group ( 16.5 and 11.9 % , vs. 1.2 % respectively , P < 0.0001 ) . Phone reminders were significantly more effective than letters ( 14.7 vs. 9.2 % , P = 0.01 ) . CONCLUSIONS Various reminder systems for FOBT are beneficial , especially those centered around the family physician . Further research should focus on this area , in conjunction with other novel approaches Performance of health maintenance procedures by internal medicine house staff is inadequate , yet little has been published outlining means to improve performance rates . We prospect ively studied the effectiveness of a reminder system to improve screening by Pap smear , rectal examination with stool guaiac test , breast examination , and pneumococcal vaccine administration in two resident outpatient clinics . Performance of these preventive health measures was determined during a six-week baseline period and again after five months of chart reminders to residents in one clinic , and after six months without reminders . For the intervention , a physician 's assistant screened each chart and attached a reminder to the front indicating which procedures were overdue based on published recommendations . Health screening behavior was not significantly different between the two resident clinics during baseline . After the five-month reminder intervention , residents in both groups moderately increased their preventive health activities over baseline ; however , only the reminded group showed significant improvement ( chi 2 = 11.60 , P less than .001 ) . Six months after remainders were discontinued there was no difference in overall performance between the two clinics ( chi 2 = 2.79 , NS ) . The reminded group did preserve its significant improvement over the baseline phase ( chi 2 = 6.12 , P less than .01 ) . This simple reminder system had a modest but statistically significant positive impact on health screening behavior . Despite this improvement , absolute rates of screening remained below 50 % in both clinics Objective : To improve compliance with computer-generated reminders to perform fecal occult blood testing ( FOBT ) , mammography , and cervical Papanicolaou ( Pap ) testing . Design : Six-month prospect i ve , r and omized , controlled trial . Setting : Academic primary care general internal medicine practice .Subjects : Thirty-one general internal medicine faculty , 145 residents , and 5,407 patients with scheduled visits who were eligible for any of the three cancer screening protocol s . Intervention : Primary care teams of internal medicine residents and faculty received either routine computer reminders ( control ) or the same reminders to which they were required to circle one of four responses : 1 ) “ done/order today , ” 2 ) “ not applicable to this patient , ” 3 ) “ patient refused , ” or 4 ) “ next visit . ” Results : Intervention physicians complied more frequently than control physicians with all reminders combined ( 46 % vs 38 % , respectively , p=0.002 ) and separately with reminders for FOBT ( 61 % vs 49 % , p=0.0007 ) and mammography ( 54 % vs 47 % , p=0.036 ) but not cervical Pap testing ( 21 % vs 18 % , p=0.2 ) . Intervention residents responded significantly more often than control residents to all reminders together and separately to reminders for FOBT and mammography but not Pap testing . There was no significant difference between intervention and control faculty , but the compliance rate for control faculty was significantly higher than the rate for control residents for all reminders together and separately for FOBT but not mammography or Pap testing . The intervention ’s effect was greatest for patients ≥70 years old , with significant results for all tests , together and singly , for residents but not faculty . Intervention physicians felt that the reminders were not applicable 21 % of the time ( due to inadequate data in patients ’ electronic medical records ) and stated that their patients refused 10 % of the time . Conclusions : Requiring physicians to respond to computer-generated reminders improved their compliance with preventive care protocol s , especially for elderly patients for whom control physicians ’ compliance was the lowest . However , 100 % compliance with cancer screening reminders will be unattainable due to incomplete data and patient refusal Although cure of many diseases depends on early detection , screening schemes have been difficult to implement in busy clinic environments . We describe the testing of a nurse-initiated prompting system for six health promotion and disease prevention procedures in an internal medicine residents ' clinic at a university-affiliated community program . Maneuvers investigated were breast examination , pelvic examination and Pap smear , rectal examination in men , mammogram , stool guaiac test , and blood glucose determination . A nurse review ed the charts and used a list in the front of each chart to prompt residents in the experimental group . Residents in the control group were not prompted . A significant improvement ( P < .05 ) in performance was seen in the prompted group . Performance of rectal examination and mammograms improved most , increasing from 41 % to 93 % and 18 % to 64 % , respectively . There were no significant changes in the control group . This simple nurse-initiated prompting system improved the performance of health promotion and disease prevention maneuvers Objectives To examine the effectiveness and cost-effectiveness of two primary care based interventions aim ed at increasing breast screening uptake for women who had recently failed to attend . Setting 13 General practice s with low uptake in the second round of breast screening ( below 60 % ) in north west London and the West Midl and s , United Kingdom . Participants were women in these practice s who were recent non-attenders for breast screening in the third round . Methods Pragmatic factorial r and omised controlled trial , with people r and omised to a systematic intervention ( general practitioner letter ) , an opportunistic intervention ( flag in women 's notes prompting discussion by health professionals ) , neither intervention , or both . Outcome measures were attendance for screening 6 months after r and omisation and cost-effectiveness of the interventions . Results 1158 Women were individually r and omised as follows : 289 control ; 291 letter ; 290 flag ; 288 both interventions . Attendance was ascertained for 1148 ( 99 % ) of the 1158 women . Logistic regression adjusting for the other intervention and practice produced an odds ratio ( OR ) for attendance of 1.51 ( 95 % confidence interval ( 95 % CI 1.02 to 2.26 ; p=0.04 ) for the letter , and 1.39 ( 95 % CI 0.93 to 2.07 ; p=0.10 ) for the flag . Health service costs/additional attendance were £ 35 ( letter ) and £ 65 ( flag ) . Conclusions Among recent non-attenders , the letter was effective in increasing breast screening attendance . The flag was of equivocal effectiveness and was considerably less cost-effective than the letter Similar general medical outpatient clinics with r and omly assigned patients were used to evaluate the effectiveness of a program that was to increase house staff compliance with preventive medicine guidelines . Two clinics were design ated experimental and two served as controls . In the experimental clinics , age-specific checklists of all recommended preventive procedures ( drawn from the Canadian Task Force report on The Periodic Health Examination and American Cancer Society guidelines ) were appended to each patient 's chart . In addition , house officers were presented with a series of weekly seminars dealing with issues in screening , as well as the specific recommendations included in the checklist . House officers in all four clinics were tested for their knowledge and attitudes toward the preventive program before and after the intervention . Counts of immunizations and mammograms performed and the total population s eligible for these procedures were determined for all four clinics . As predicted , test scores as well as mammography and immunization rates increased significantly ( from 2 - 40 per cent ) in the intervention clinics as compared with controls . We conclude that this intervention was clearly effective in the short run . However , follow-up studies will be necessary to determine whether the desired long-term effect has been achieved Despite its effectiveness as a method of controlling cervical carcinoma , the use of Pap smear testing remains incomplete , and its promotion in the primary care setting provides an important opportunity for intervention Despite an emerging consensus on appropriate preventive services , a minority of patients receive them . A study was undertaken to assess the impact of computer-generated reminders to adult patients , their physicians , or both patients and physicians on adherence to five recommended preventive services : cholesterol measurements , fecal occult blood testing , mammography , Papanicolaou smears , and tetanus immunization . During the academic year 1988 - 1989 , all 7397 adult patients and their 49 physicians in a university family medicine clinical practice were r and omized by practice group into one of four study groups : control , physician reminders , patient reminders , and both physician and patient reminders . Adherence was defined in community-oriented terms : the percentage of patients within each group who had received the preventive service in the recommended interval . During the study period , adherence to four of the five preventive services increased significantly , with the largest increases in the physician and patient reminder group : cholesterol measurements increased from 19.5 % to 38.1 % , fecal occult blood testing 9.3 % to 27.0 % , mammography 11.4 % to 27.1 % , and tetanus immunization 23.4 % to 35.4 % ( for each increase , P less than .0001 , McNemar 's chi-square test ) . In general , increases were greater in blacks and in patients with any form of insurance coverage . Computer-based physician and patient reminder systems have great promise of improving adherence to preventive services in primary care setting Abstract : A cost‐effectiveness study of three different interventions to promote the uptake of screening for cervical cancer in general practice was carried out in Perth in 1991 . Women eligible for a Pap smear were r and omly allocated to one of four groups : one receiving letters with specific appointments to attend a screening clinic staffed by female doctors , one receiving letters informing them of the availability of the clinic and suggesting they make an appointment , one whose files were tagged to remind a doctor to offer a smear during a consultation , and a comparison control group that received opportunistic screening only . Variable and fixed costs for each group were itemised and summarised to give an average cost per smear taken . The cost and effectiveness of each intervention were then compared with those of the control group . Sensitivity analysis was performed on the major component of the costs , the doctor 's time . Opportunistic screening cost $ 14.60 per smear and attained 16 per cent recruitment . Tagging files was the cheapest intervention ( $ 14.75 per smear ) although it was the least effective in recruiting women ( 20 per cent ) . This result held true for different scenarios of doctor 's time allocated . Intervention by invitation letter with no appointment cost $ 45.35 per smear and attained 26 per cent recruitment , and intervention with a specific appointment cost $ 48.21 per smear and attained 30 per cent recruitment . Compared with the control group , the incremental cost‐effectiveness for the tagged group was $ 15.40 , for the letter‐without‐appointment group $ 97.75 and for the letter‐with‐appointment group $ 86.50 BACKGROUND This 1-year r and omized trial tested the efficacy of behavioral techniques for increasing mammography referrals by primary care physicians in small , community practice s. METHODS Sixty-one practice s were r and omly assigned to one of three conditions : ( 1 ) education-only control , ( 2 ) education plus cue enhancement using mammography chart stickers , and ( 3 ) education plus cue enhancement plus feedback and token rewards . Quarterly chart audits of a defined sample ( N = 11,716 ) of women patients 50 years of age or older were conducted to document mammography referrals , completions , and compliance . RESULTS Referral and completion rates increased from baseline to first quarter and gradually declined thereafter . Overall , these rates were higher in the cuing conditions than in the control condition . In contrast , compliance rates in both experimental conditions increased over the year while remaining static in the control condition , demonstrating a strong and continuing effect for cue enhancement . Compliance increases were greatest for physicians who were older , nonwhite , with a second speciality , in solo practice , not members of the AMA , not residency trained , and not board certified . CONCLUSIONS Chart stickers can significantly increase mammography utilization in small , community practice s. These practice s are an efficient route to reaching large numbers of older women in need of mammography screening Physicians ' performance of the periodic health examination is often incomplete . Performance rates may be low because physicians forget recommendations for specific periodic health examination components at the time of the patient encounter . We studied the effect of providing information about seven periodic health examination actions ( cervical Pap smear , mammography , fecal occult blood testing , serum cholesterol level , and influenza , pneumococcal , and diphtheria-tetanus immunizations ) on first-year medical residents ' performance of these actions over a three-month period . We r and omly selected 16 residents to receive periodic health examination recommendations , plus data supporting each recommendation , on their outpatient charts at the patient encounter . Thirteen residents who did not receive this information served as controls . Experimental and control groups achieved similar knowledge scores ( 0.53 versus 0.47 , P = .48 ) and attitude scores ( 0.73 versus .078 , P = .19 ) for preventive care measures on pre study testing . The experimental group performed 10.5 % of indicated periodic health examination actions , whereas the control group performed 5.8 % of indicated actions ( P = NS ) . These results suggest no clinical ly meaningful improvement in performance of periodic health examination actions , even when periodic health examination guidelines were available at the time of the physician-patient encounter A protocol for adult health maintenance was design ed for display on a desk-top microcomputer in the general practitioner 's office . Two hundred and twenty-two patients were entered into a r and omized study comparing the outcome of the computerized protocol with manual records . The doctor had the option of displaying the single-screen protocol for the experimental group and acting on its prompts in the course of his normal clinical consultations . At the end of 30 months , significantly more preventive medicine items -- smoking , height , blood group , tetanus and rubella immunization status and family planning -- had been recorded for patients in the computerized group . For other items , requiring more frequent measurements , computerization produced an advantage only for blood pressure and breast examination , but not for weight , occult blood and serum cholesterol . Recording rates increased significantly for patients in both the control and the computerized groups for all the items . Using the computer lengthened the average consultation time from 8.5 minutes to 10 minutes . Such systems are a valuable aid to encouraging doctors to increase the amount of preventive medicine they incorporate into their routine practice Objectives To examine the effectiveness and cost-effectiveness of two interventions based in primary care aim ed at increasing uptake of breast screening . Setting 24 General practice s with low uptake in the second round of screening ( below 60 % ) in north west London and the West Midl and s , UK . Participants were all women registered with these practice s and eligible for screening in the third round . Methods Pragmatic factorial cluster r and omised controlled trial , with practice s r and omised to a systematic intervention ( general practitioner letter ) , an opportunistic intervention ( flag in women 's notes prompting discussion by health professionals ) , neither intervention , or both . Outcome measures were attendance for screening 6 months after the practice s had been screened and cost-effectiveness of the interventions . Results 6133 Women were included : 1721 control ; 1818 letter ; 1232 flag ; 1362 both interventions . Attendance data were obtained for 5732 ( 93 % ) women . The two interventions independently increased breast screening uptake in a logistic regression model adjusted for clustering , with the flag ( odds ratio ( OR ) 1.43 , 95 % confidence interval ( 95 % CI ) 1.14 to 1.79 ; p=0.0019 ) marginally more effective than the letter ( OR 1.31 , 95 % CI 1.05 to 1.64 ; p=0.015 ) . Health service costs per additional attendance were £ 26 ( letter ) and £ 41 ( flag ) . Conclusions Although both interventions increased attendance for breast screening , the letter was the more cost-effective . Any decision to implement both interventions rather than just the letter will depend on whether the additional ( £ 41 ) costs are judged worthwhile in terms of the gains in breast screening uptake Recent studies have documented that physician compliance with recommended periodic health screening improves with reminders to physicians . These reminders , however , are often costly to maintain and modify . This study investigates the influence of a microcomputer tickler system on the ordering of mammograms . All women ( N = 1262 ) aged 40 years and older who made visits to an outpatient office during a 6-month period were r and omly assigned to one of two groups . For the experimental group , the date of the last mammogram ordered and recorded in the clinical data base was printed on the encounter form generated for each patient visit . No information regarding previous mammograms was printed for patients in the control group . Women in the experimental group were more likely to have a mammogram ordered during the study period ( 19 % compared with 12 % , P = .001 ) and , as a result , were more likely to be in compliance with mammography guidelines at the study 's completion ( 27 % compared with 21 % , P = .011 ) . Microcomputerized data storage and retrieval systems may help increase physicians ' attention to preventive health screening recommendations |
11,840 | 28,244,794 | Conclusions : GGPH is useful in the management of enteral nutrition associated diarrhea . | Introduction : Dietary fiber is an important component of human diet .
Since each fiber type has specific metabolic and gastrointestinal function effects , in each specific pathology we will have to choose the optimum type of fiber , considering its chemical , physical and physiological properties .
Objective : to put partially hydrolyzed guar gum in its place in the complex framework of dietary fiber , to review its physicochemical properties and possible mechanisms of action ; as well as its potential usefulness in different clinical situations in adult patients .
Results : Partially hydrolyzed guar gum ( PHGG ) is obtained from a partial enzymatic hydrolysis of guar gum by the enzyme β-endo-mannanase .
It is a soluble , highly fermentable fiber with low viscosity .
The fermentation of GGPH in colon produces short chain fatty acids , implicated in the main pathophysiological mechanisms responsible for their clinical effects .
The usefulness of GGPH has been studied in many other clinical situations , such as diabetes , hypercholesterolemia , bacterial overgrowth , etc .
with promising results . | Background . Germinated barley foodstuff ( GBF ) is a prebiotic foodstuff that effectively increases luminal butyrate production by stimulating the growth of protective bacteria . In the first pilot study , GBF has been shown to reduce both clinical activity and mucosal inflammation in ulcerative colitis ( UC ) . The aim of this study was to investigate the efficacy of GBF in the treatment of UC in a multicenter open control trial . Methods . Eighteen patients with mildly to moderately active UC were divided into two groups using a r and om allocation protocol . The control group ( n = 7 ) were given a baseline anti-inflammatory therapy for 4 weeks . In the GBF-treated group ( n = 11 ) , patients received 20–30 g GBF daily , together with the baseline treatment , for 4 weeks . The response to the treatments was evaluated clinical ly and endoscopically . Fecal micro-flora were also analyzed . Results . After 4 weeks of observation , the GBF-treated group showed a significant decrease in clinical activity index scores compared with the control group ( P < 0.05 ) . No side effects related to GBF were observed . GBF therapy increased fecal concentrations of Bifidobacterium and Eubacterium limosum . Conclusions . Oral GBF therapy may have the potency to reduce clinical activity of UC . We believe that these results support the use of GBF administration as a new adjunct therapy for UC This document represents the first collaboration between 2 organizations — the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine — to describe best practice s in nutrition therapy in critically ill children . The target of these guidelines is intended to be the pediatric critically ill patient ( > 1 month and 2–3 days in a PICU admitting medical , surgical , and cardiac patients . In total , 2032 citations were scanned for relevance . The PubMed / MEDLINE search result ed in 960 citations for clinical trials and 925 citations for cohort studies . The EMBASE search for clinical trials culled 1661 citations . In total , the search for clinical trials yielded 1107 citations , whereas the cohort search yielded 925 . After careful review , 16 r and omized controlled trials and 37 cohort studies appeared to answer 1 of the 8 preidentified question groups for this guideline . We used the GRADE criteria ( Grading of Recommendations , Assessment , Objective To determine the effectiveness of increasing the dietary content of soluble fibre ( psyllium ) or insoluble fibre ( bran ) in patients with irritable bowel syndrome . Design R and omised controlled trial . Setting General practice . Participants 275 patients aged 18 - 65 years with irritable bowel syndrome . Interventions 12 weeks of treatment with 10 g psyllium ( n=85 ) , 10 g bran ( n=97 ) , or 10 g placebo ( rice flour ) ( n=93 ) . Main outcome measures The primary end point was adequate symptom relief during at least two weeks in the previous month , analysed after one , two , and three months of treatment to assess both short term and sustained effectiveness . Secondary end points included irritable bowel syndrome symptom severity score , severity of abdominal pain , and irritable bowel syndrome quality of life scale . Results The proportion of responders was significantly greater in the psyllium group than in the placebo group during the first month ( 57 % v 35 % ; relative risk 1.60 , 95 % confidence interval 1.13 to 2.26 ) and the second month of treatment ( 59 % v 41 % ; 1.44 , 1.02 to 2.06 ) . Bran was more effective than placebo during the third month of treatment only ( 57 % v 32 % ; 1.70 , 1.12 to 2.57 ) , but this was not statistically significant in the worst case analysis ( 1.45 , 0.97 to 2.16 ) . After three months of treatment , symptom severity in the psyllium group was reduced by 90 points , compared with 49 points in the placebo group ( P=0.03 ) and 58 points in the bran group ( P=0.61 versus placebo ) . No differences were found with respect to quality of life . Fifty four ( 64 % ) of the patients allocated to psyllium , 54 ( 56 % ) in the bran group , and 56 ( 60 % ) in the placebo group completed the three month treatment period . Early dropout was most common in the bran group ; the main reason was that the symptoms of irritable bowel syndrome worsened . Conclusions Psyllium offers benefits in patients with irritable bowel syndrome in primary care . Trial registration Clinical trials NCT00189033 Background and Aim Partially hydrolyzed guar gum ( PHGG ) is a water-soluble , non-gelling dietary fiber with a wide range of uses in clinical nutrition . The aim of this prospect i ve study was to investigate the effect of guar gum on colonic transit time ( CTT ) and symptoms of chronic constipation . Methods We enrolled patients fulfilling Rome III criteria for chronic constipation . CTT was measured before and at the end of treatment . After a 2-week run-in period , patients received 5 mg PHGG daily for 4 weeks . During study period , patients kept daily symptoms , stool and laxative usage diaries . They also recorded their symptom-related satisfaction weekly and treatment adverse events . Results Forty-nine patients received treatment ; 39 ( 80 % ) completed the study . Treatment significantly reduced colon transit time , from 57.28 ± 39.25 to 45.63 ± 37.27 h ( p = 0.026 ) , a reduction more prominent in slow transit patients ( from 85.50 ± 27.75 to 63.65 ± 38.11 h , p = 0.016 ) . Overall , the weekly number of complete spontaneous and spontaneous bowel movements increased significantly ( p < 0.001 ) ; the latter correlated significantly with the acceleration of CTT in the overall population and in slow transit patients ( B = 0.382 ; p = 0.016 and B = 0.483 ; p = 0.023 , respectively ) . In addition , the number of bowel movements with straining decreased ( p < 0.001 ) and stool form improved ( p < 0.001 ) , while days with laxative intake and days with abdominal pain decreased ( p = 0.001 and p = 0.027 , respectively ) . Conclusion Four-week PHGG use accelerates colon transit time in patients with chronic constipation , especially in those with slow transit , and improves many of their symptoms including frequency of bowel movements BACKGROUND AND AIMS Enteral fiber-free diets alter intestinal transit and produce diarrhea or constipation . This prospect i ve double blind , controlled study evaluates the use of guar gum , a soluble fiber and a c and i date prebiotic in enteral feeds , to prevent diarrhea and potential health benefits in intensive care unit patients . METHODS Twenty patients on enteral nutrition with persistent diarrhea were r and omized to receive a new enteral feed either enriched with 2 % soluble guar gum ( study group , n = 10 ) or fiber-free ( control group , n = 10 ) for 4 successive days . RESULTS The number of liquid stools in response to a soluble fiber-enriched diet was 2.0+/-0.9 ( first day ) vs. 1.0+/-0.7 ( fourth day ) ( P < 0.01 ) , and in the control group 1.2+/-0.7 ( first day ) vs. 2.1+/-0.8 ( fourth day ) ( P < 0.05 ) . In the fiber-enriched feed group , plasma glucose and cholesterol levels at termination of the study , respectively , reached 126+/-81 and 164+/-71 mg dl(-1 ) , as compared to 333+/-108 and 378+/-26 mg dl(-1 ) on Day first ( P < 0.01 ) . In the control group , these values on the fourth day were , respectively , 267+/-94 and 263+/-79 vs. 247+/-115 and 315+/-78 on Day first ( P > 0.05 ) . CONCLUSIONS Guar gum-enriched enteral nutrition was related to a decrease of diarrheal episodes in ICU patients with preexisting diarrhea ; and to a trend for lower plasma glucose and cholesterol levels Abstract PURPOSE : Inflammation is a constant finding in the ileal reservoir of patients with an ileal pouch-anal anastomosis and is associated with decreased fecal concentrations of the short chain fatty acid butyrate , increased fecal pH , changes in fecal flora , and increased concentrations of secondary bile acids . In healthy subjects , inulin , a dietary fiber , is fermented to short chain fatty acids and leads to a lower pH and potentially beneficial changes in fecal flora . The aim of the present study was to investigate the effect of enteral supplementation of inulin on inflammation of the ileal reservoir . METHODS : Twenty patients received 24 g of inulin or placebo daily during three weeks in a r and omized , double-blind , crossover design . Stools were analyzed after each test period for pH , short chain fatty acids , microflora , and bile acids . Inflammation was assessed endoscopically , histologically , and clinical ly . RESULTS : Compared with placebo , three weeks of dietary supplementation with 24 g of inulin increased butyrate concentrations , lowered pH , decreased numbers of Bacteroides fragilis , and diminished concentrations of secondary bile acids in feces . This was endoscopically and histologically accompanied by a reduction of inflammation of the mucosa of the ileal reservoir . CONCLUSION : Enteral inulin supplementation leads to a decrease of inflammation-associated factors and to a reduction of inflammation of pouch mucosa The effect of hydrolyzed partially guar-gum was evaluated in the treatment of functional constipation among hospitalized patients . Following a r and omized blind controlled-trial 64 adults were allocated to two groups : one received daily high-fiber diet ( approximately 30 g ) and the other similar diet plus 10 g of hydrolyzed partially guar-gum , during 15 days . Dietary fiber reduced functional constipation by 78.0 % . Hydrolyzed partially guar-gum did not show any additional effect in defecation frequency , fecal consistence , need of laxative drug use , although a reduction in bowel complaints . Dietary fiber may be used in the treatment of functional constipation . However the therapeutic role of hydrolyzed partially guar-gum should be further investigated BACKGROUND AND AIMS Attempts to control enteral nutrition associated diarrhea in the critically ill tube-fed patient by implementing feeding formulas enriched with fiber were mostly unsuccessful . Recently , it was shown that enteral feeding containing soluble partially hydrolyzed guar decreased the incidence of diarrhea in a cohort of non-critically ill medicosurgical patients . We investigated whether this type of enteral feed could also influence stool production in patients with severe sepsis , a population at risk for developing diarrhea . METHODS The study was double-blind . Patients with severe sepsis and septic shock were consecutively enrolled and at r and om received either an enteral formula supplemented with 22 g/l partially hydrolyzed guar or an isocaloric isonitrogenous control feed without fiber . All patients were mechanically ventilated and treated with catecholamines and antibiotics . Enteral feeding was provided through a nasogastric tube for a minimum of 6 days . A semiquantitative score based on stool volume and consistency was used for daily assessment of diarrhea . RESULTS 25 patients fulfilled the criteria for data analysis . Soluble fiber was administered in 13 of them . The two groups were well-matched for gender , age , disease severity , cause of sepsis , laboratory parameters , total feeding days and time to reach nutritional goals . The mean frequency of diarrhea days was significantly lower in patients receiving fiber than in those on st and ard alimentation ( 8.8+/-10.0 % vs 32.0+/-15.3 % ; P=0.001 ) . The whole group of fiber-fed patients had less days with diarrhea per total feeding days ( 16/148 days ( 10.8 % ) vs 46/146 days ( 31.5 % ) ; P<0.001 ) and a lower mean diarrhea score ( 4.8+/-6.4 vs 9.4+/-10.2 ; P<0.001 ) . The type of enteral diet did not influence sepsis-related mortality and duration of stay in the intensive care unit . CONCLUSION Total enteral nutrition supplemented with soluble fiber is beneficial in reducing the incidence of diarrhea in tube-fed full-resuscitated and mechanically ventilated septic patients OBJECTIVE Butyrate enemas may be effective in the treatment of active distal ulcerative colitis . Because colonic fermentation of Plantago ovata seeds ( dietary fiber ) yields butyrate , the aim of this study was to assess the efficacy and safety of Plantago ovata seeds as compared with mesalamine in maintaining remission in ulcerative colitis . METHODS An open label , parallel-group , multicenter , r and omized clinical trial was conducted . A total of 105 patients with ulcerative colitis who were in remission were r and omized into groups to receive oral treatment with Plantago ovata seeds ( 10 g b.i.d . ) , mesalamine ( 500 mg t.i.d . ) , and Plantago ovata seeds plus mesalamine at the same doses . The primary efficacy outcome was maintenance of remission for 12 months . RESULTS Of the 105 patients , 102 were included in the final analysis . After 12 months , treatment failure rate was 40 % ( 14 of 35 patients ) in the Plantago ovata seed group , 35 % ( 13 of 37 ) in the mesalamine group , and 30 % ( nine of 30 ) in the Plantago ovata plus mesalamine group . Probability of continued remission was similar ( Mantel-Cox test , p = 0.67 ; intent-to-treat analysis ) . Therapy effects remained unchanged after adjusting for potential confounding variables with a Cox 's proportional hazards survival analysis . Three patients were withdrawn because of the development of adverse events consisting of constipation and /or flatulence ( Plantago ovata seed group = 1 and Plantago ovata seed plus mesalamine group = 2 ) . A significant increase in fecal butyrate levels ( p = 0.018 ) was observed after Plantago ovata seed administration . CONCLUSIONS Plantago ovata seeds ( dietary fiber ) might be as effective as mesalamine to maintain remission in ulcerative colitis Psyllium is a bulk-forming laxative and is high in both fiber and mucilage . The beneficial effect of dietary fiber in the management of type II diabetes , has not been totally demonstrated . The purpose of this study was to determine the plasma-lowering effects of 5.1 g b.i.d . of psyllium husk fiber , as an adjunct to dietary and drug therapy on lipid and glucose levels , in patients with type II diabetes . Patients were r and omly selected from an outpatient clinic of primary care to participate in a double-blind placebo-controlled study in which Plantago ovata Forsk . , or placebo was given in combination with their anti-diabetic drugs . Forty-nine subjects were included in the study that were given diet counseling before the study and then followed for 8 weeks in the treatment period . Fasting plasma glucose ( FBS ) was measured every 2 weeks , and total plasma cholesterol ( TC ) , LDL-cholesterol ( LDL-C ) , HDL-cholesterol ( HDL-C ) , triglyceride ( TG ) , and insulin levels were measured every 4 weeks . Glycosylated hemoglobin ( HbA1c ) was also measured at the beginning and ending of the study . The test products ( psyllium or placebo ) were supplied to subjects in identically labeled foil packets containing a 5.1 g dose of product , to consume two doses per day , half an hour before breakfast and dinner . Both products were well tolerated , with no serious adverse events related to treatment was reported in either . Better gastric tolerance to metformin was recorded in the psyllium group . FBS , and HbA1c , showed a significant reduction ( p<0.05 ) , whereas HDL-C increased significantly ( p<0.05 ) following psyllium treatment . LDL/HDL ratio was significantly decreased ( p<0.05 ) . Our results show that 5.1 g b.i.d . of psyllium for persons with type II diabetes is safe , well tolerated , and improves glycemic control BACKGROUND Gastrointestinal side effects , particularly diarrhea , are still the main reasons for discontinuation of enteral nutrition . Although the causes of diarrhea are diverse , the enteral nutrition solution is frequently suspected of playing a leading role in causing diarrhea . METHODS Our r and omized , prospect i ve , double-blind trial with 100 patients assessed the effects of feeding a st and ard diet ( Nutrodrip St and ard ) vs the same diet supplemented with 20 g of soluble fiber , containing partially hydrolyzed guar gum ( Sunfiber ) , per 1000 mL. Thirty patients received total enteral nutrition postoperatively , and 70 patients received enteral supplementation . RESULTS The patients receiving total enteral nutrition with soluble fiber had decreased diarrhea but increased flatulence . In none of these patients did enteral feeding have to be discontinued because of gastrointestinal side effects , whereas in four patients who were on a st and ard diet , enteral feeding had to be interrupted because of diarrhea ( p < .05 ) . Similar observations were made in patients receiving enteral supplementation . In both groups , the incidence of diarrhea decreased significantly with the soluble fiber diet compared with the st and ard diet ( 6 vs 15 , p < .05 ) . CONCLUSIONS Enteral feeding with a formula supplemented with partially hydrolyzed guar gum reduces the incidence of diarrhea in patients receiving total enteral nutrition as well as in those receiving enteral supplementation , regardless of the cause of diarrhea . The increased hydrogen production and the significantly higher rate of flatulence are likely to result from fermentation of the soluble fiber in the colon , with concomitant production of short-chain fatty acids , which leads to increased absorption of short-chain fatty acids , sodium , and water by the colonocytes . This effect , together with the observed cholecystokinin-mediated decrease in colonic transit time with partially hydrolyzed guar gum , may explain the reduction in the incidence of diarrhea in this study Objective The purpose of this study was to initially determine if growth hormone or nutrients , given alone or together , could enhance absorption from the remnant small bowel after massive intestinal resection . If clinical improvement were observed , this therapy would then be used to treat patients with the short-bowel syndrome over the long term . Summary Background Data Patients who undergo extensive resection of the gastrointestinal tract frequently develop malabsorption and require long-term parenteral nutrition . The authors hypothesized that the administration of growth factors and /or nutrients could enhance further compensation of the remnant intestine and thereby improve absorption . Specifically , animal studies have shown that there is enhanced cellularity with the administration of growth hormone ( GH ) or glutamine ( GLN ) , or a fiber-containing diet . Methods Initially , 17 studies were performed in 15 total parenteral nutrition (TPN)-dependent short-bowel patients over 3 to 4 weeks in the clinical research center ; the first week served as a control period , and during the next 1 to 3 weeks , the specific treatment was administered and evaluated . Throughout the study , food of known composition was provided and all stool was collected and analyzed to determine absorption across the remaining bowel . The effect of a high-carbohydrate , low-fat diet ( DIET ) , the amino acid glutamine ( GLN ) and growth hormone ( GH ) administered alone or in combination with the other therapies ( GH + GLN + DIET ) was evaluated . The treatment was exp and ed to 47 adults ( 25 men , 22 women ) with the short-bowel syndrome , dependent on TPN for 6 ± 1 years . The average age was 46 ± 2 years , and the average jejunal-ileal length was 50 ± 7 cm ( median 35 cm ) in those with all or a portion of colon and 102 ± 24 cm ( median 102 cm ) in those with no colon . After 28 days of therapy , the patients were discharged on only GLN + DIET . Results The initial balance studies indicated improvement in absorption of protein by 39 % accompanied by a 33 % decrease in stool output with the GH + GLN + DIET . In the long-term study , 40 % of the group remain off TPN and an additional 40 % have reduced their TPN requirements , with follow-up averaging a year and the longest being over 5 years Background : Partially hydrolyzed guar gum ( PHGG ) is a water-soluble fiber if added to oral rehydration solution ( ORS ) and undergoes fermentation in the colon liberating short chain fatty acids ( SCFAs ) . SCFAs potentiate the effect of ORS , reducing the severity of diarrhea . Aim : To examine the effect of PHGG-added ORS in reducing the stool output and duration of diarrhea in adult cholera . Methods : 195 male patients were studied in a r and omized controlled trial : ( a ) 65 received ORS + 25 g PHGG ; ( b ) 65 received ORS + 50 g PHGG , and ( c ) 65 received ORS alone ( control ) . Major outcomes were stool weight and duration of diarrhea . Results : No significant differences were found in mean ± SD stool weight ( g/kg b.w . ) during the first and second 24 h. In the subgroup analysis ( excluding very high purging patients , stool weight in the first 24 h was > 10 kg ) , the stool weight ( g/kg b.w . ) was significantly reduced in the first 24 h in both groups receiving PHGG ( PHGG 25 g , 136 ± 68 vs. PHGG 50 g , 144 ± 49 vs. control , 176 ± 43 , p = 0.01 ) . Conclusion : PHGG-added ORS might have a beneficial effect in moderately purging adult cholera . However , further studies are warranted to confirm the preliminary findings |
11,841 | 22,606,679 | There is sufficient evidence to support recommendations for some of these interventions for selected neuropathic pain conditions . | BACKGROUND The Special Interest Group of the Canadian Pain Society has produced consensus-based guidelines for the pharmacological management of neuropathic pain .
The society aim ed to generate an additional guideline for other forms of neuropathic pain treatments .
OBJECTIVE To develop evidence -based recommendations for neuropathic pain interventional treatments . | Background : Pain following spinal cord injury ( SCI ) is a therapeutic challenge . Only a few treatments have been assessed in r and omized , controlled trials . The primary objective of the present study was to examine the analgesic effect of ketamine and lidocaine in a group of patients with neuropathic pain below the level of spinal cord injury . We also wanted to assess sensory abnormalities to see if this could help us to identify responders and if treatments result ed in changes of sensibility OBJECTIVES Complex regional pain syndrome ( CRPS ) , formerly known as reflex sympathetic dystrophy ( RSD ) , is a painful , disabling disorder for which treatment is difficult . The aim of this study was to determine the efficacy of pamidronate in a double-blind r and omized placebo-controlled trial . METHODS Patients referred to our regional multidisciplinary pain management center who fulfilled the International Association for the Study of Pain criteria for CRPS Type I were enrolled in the study over a 2-year period . Patients were administered , intravenously , either pamidronate , 60 mg as a single dose , or normal saline . Patients ' pain scores , global assessment of disease severity scores , and functional assessment ( SF-36 ) scores were documented at baseline and at 1 and 3 months . RESULTS Twenty-seven patients ( 18 female , 9 male ; average age 45 years ) were recruited , of whom 14 received pamidronate and 13 received placebo . Overall improvements in pain score , patient 's global assessment of disease severity score , and physical function ( SF-36 ) score were noted in the pamidronate group at 3 months , and improvements in role physical ( SF-36 ) score were noted at 1 and 3 months . There was variability in pamidronate response among individuals . CONCLUSIONS Pamidronate may be a useful treatment option in the management of patients with CRPS Type I. Although treatment response was variable , the majority of patients improved . Early administration in t and em with other treatment measures is recommended Background : The mechanisms underlying neuropathic pain are incompletely understood . Targeting specific molecular mechanisms in the pain signaling system may assist in underst and ing key features in neuropathic pains such as allodynia . This study examined the effect of systemically administered ketamine , an N-methyl-d-aspartate receptor antagonist and lidocaine , a sodium channel blocker , on spontaneous pain , brush-evoked pain , and pinprick-evoked pain in patients with nerve injury pain . Methods : Twenty patients participated in two r and omized , double-blinded , placebo-controlled , crossover experiments in which they , on four different days , received a 30-minute intravenous infusion of ketamine ( 0.24 mg/kg ) , lidocaine ( 5 mg/kg ) , or saline . Ongoing pain , pain evoked by brush and repetitive pinprick stimuli , and acetone was measured before , during , and after infusion . Results : Ketamine significantly reduced ongoing pain and evoked pain to brush and pinprick , whereas lidocaine only reduced evoked pain to repetitive pinprick stimuli . In individual patients , there was no correlation between the pain-relieving effect of lidocaine and ketamine on ongoing or mechanically evoked pains . Conclusions : N-methyl-d-aspartate receptor-linked systems and sodium channels are involved in generation and maintenance of pain in patients with peripheral nerve injury . It is likely that ongoing pain as well as mechanical hyperalgesia in individual patients is dependent on several separate molecular mechanisms Study Design . A r and omized , controlled , double-blind trial . Objective . To assess the effectiveness of fluoroscopically directed caudal epidural injections in managing chronic low back and lower extremity pain in patients with disc herniation and radiculitis with local anesthetic with or without steroids . Summary of Background Data . The available literature on the effectiveness of epidural injections in managing chronic low back pain secondary to disc herniation is highly variable . Methods . One hundred twenty patients suffering with low back and lower extremity pain with disc herniation and radiculitis were r and omized to one of the two groups : group I received caudal epidural injections with an injection of local anesthetic , lidocaine 0.5 % , 10 mL ; group II patients received caudal epidural injections with 0.5 % lidocaine , 9 mL , mixed with 1 mL of steroid . The Numeric Rating Scale ( NRS ) , the Oswestry Disability Index 2.0 ( ODI ) , employment status , and opioid intake were utilized with assessment at 3 , 6 , and 12 months posttreatment . Results . The percentage of patients with significant pain relief of 50 % or greater and /or improvement in functional status with 50 % or more reduction in ODI scores was seen in 70 % and 67 % in group I and 77 % and 75 % in group II with average procedures per year of 3.8 ± 1.4 in group I and 3.6 + 1.1 in group II . However , the relief with first and second procedures was significantly higher in the steroid group . The number of injections performed was also higher in local anesthetic group even though overall relief was without any significant difference among the groups . There was no difference among the patients receiving steroids . Conclusion . Caudal epidural injection with local anesthetic with or without steroids might be effective in patients with disc herniation or radiculitis . The present evidence illustrates potential superiority of steroids compared with local anesthetic at 1-year follow-up Background and objective To investigate the effect of intravenous regional anesthesia ( Bier block ) with methylprednisolone and lidocaine in complex regional pain syndrome ( CRPS ) type I in a r and omized , double-blinded , and placebo-controlled study . Methods Twenty-two patients with the diagnosis of CRPS of their upper limb were divided r and omly into 2 groups . The mean age was 22.3 ±1.6 years . Average pain duration was 3.1 ± 1.4 months . In the placebo group ( 10 patients ) , patients received only 100 mL of saline . In the study group ( 12 patients ) , 40 mg of methylprednisolone and 10 mL of 2 % lidocaine were added to the saline . Treatments were applied once a week . Unless significant adverse effects occurred , 3 sessions of blockade were completed . Pain severity , range of motion ( ROM ) , and volumetric edema measurements were obtained before treatment . Pain severity and satisfaction ( resolved , better , no change , or worse ) were recorded after each session . The final assessment was performed 1.5 months later . ROM and volumetric measurements were repeated the day after the block and at the final assessment . Results Differences in pretreatment features of the patients were not statistically significant ( P > .05 ) . In all assessment periods during the study , improvement in pain severity was statistically significant ( P < .05 ) in both groups . This statistically significant difference disappeared at the final assessment ( P > .05 ) . No statistically significant difference was obtained in ROM and volumetric measures in any assessment period before and after the block . Satisfaction scores between the groups were also not different in any assessment period . Conclusions Bier block with methylprednisolone and lidocaine in CRPS type I does not provide long-term benefit in CRPS , and its short-term benefit is not superior to placebo Background Efficacy of epidural local anesthetics plus steroids for the treatment of cervicobrachial pain is uncertain . Methods A prospect i ve study r and omized 160 patients with cervicobrachial pain resistant to conventional therapy . Patients were divided into 4 groups on the basis of the time between pain onset and treatment initiation : group A , 40 patients with pain onset 15 to 30 days ; group B , 40 patients with pain from 31 to 60 days ; group C , 40 patients , 61 to 180 days ; and group D , 40 patients with pain > 180 days . Patients of each group were r and omized to receive an epidural block with bupivacaine and methylprednisolone at intervals of 4 to 5 days ( Single injection ) or continuous epidural bupivacaine every 6 , 12 , or 24 hours plus methylprednisolone every 4 to 5 days ( Continuos epidural ) . The maximum duration of treatment ( 9 blocks in Single injection , and 30 days in Continuos epidural ) was dependent on achieving Pain Control ( PC ) ≥80 % [ PC is defined by this formulae : ( 100 ) (VASinitial−VASfinal)/VASinitial ] . Follow-up at 1 month and 6 months compared PC and the number of pain-free hours of sleep . Results One hundred forty-one patients completed the study . The 4 groups had similar characteristics . At the 1-month and 6-month follow-up analysis based on the time between pain onset and treatment initiation showed that patients of group D , who received the Continuous epidural treatment , had significantly greater PC and significantly more pain-free hours of sleep compared with similar patients in Single injection . Conclusions Therapy with continuous epidural local anesthetic and methylprednisolone provides better control of chronic cervicobrachial pain compared with Single injection . These results are discussed with respect to the possible mechanism of action of the drugs and may relate to the physiopathologic mechanisms associated with neuronal plasticity that result in chronic pain Background : Neuropathic pain in spinal cord injury is a common challenging therapeutic condition . The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine . Methods : Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were r and omized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min . Twelve patients reported evoked pain , and 12 patients had no evoked pain . Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing . Results : Lidocaine significantly reduced spontaneous pain in all patients ( P < 0.01 ) and in each of the two groups with ( P < 0.01 ) and without ( P = 0.048 ) evoked pain , with no difference in number of responders ( pain reduction ≥ 33 % ) between the patients with ( n = 6 ) and without ( n = 5 ) evoked pain . Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia , pinprick hyperalgesia , or pain evoked by repetitive pinprick . Conclusions : Lidocaine reduced neuropathic pain at and below the level of injury irrespective of the presence or absence of evoked pain . Results are consistent with a central -acting effect of sodium channel blockers acting on neuronal hyperexcitability . Agents ( such as anticonvulsants or antiarrhythmics ) with sodium channel – blocking properties may be a treatment option for spinal cord injury pain Study Design . Clinical practice guideline . Objective . To develop evidence -based recommendations on use of interventional diagnostic tests and therapies , surgeries , and interdisciplinary rehabilitation for low back pain of any duration , with or without leg pain . Summary of Background Data . Management of patients with persistent and disabling low back pain remains a clinical challenge . A number of interventional diagnostic tests and therapies and surgery are available and their use is increasing , but in some cases their utility remains uncertain or controversial . Interdisciplinary rehabilitation has also been proposed as a potentially effective noninvasive intervention for persistent and disabling low back pain . Methods . A multidisciplinary panel was convened by the American Pain Society . Its recommendations were based on a systematic review that focused on evidence from r and omized controlled trials . Recommendations were grade d using methods adapted from the US Preventive Services Task Force and the Grading of Recommendations , Assessment , Development , and Evaluation Working Group . Results . Investigators review ed 3348 abstract s. A total of 161 r and omized trials were deemed relevant to the recommendations in this guideline . The panel developed a total of 8 recommendations . Conclusion . Recommendations on use of interventional diagnostic tests and therapies , surgery , and interdisciplinary rehabilitation are presented . Due to important trade-offs between potential benefits , harms , costs , and burdens of alternative therapies , shared decision-making is an important component of a number of the recommendations A total of 57 patients , aged between 23 and 86 years , with complex regional pain syndrome ( CRPS ) type 1 nine weeks after an isolated closed fracture of the distal radius , was r and omised to receive either serial intravenous regional blockade ( IVRB ) with 15 mg of guanethidine in 30 ml of 0.5 % prilocaine or serial IVRB with 30 ml of normal saline at weekly intervals until the tenderness in their fingers had resolved or they had received a maximum of four IVRBs . The analgesic efficacy was assessed at 24 hours , 48 hours and one week after each procedure by the dolorimetry ratio and verbal pain scores , and at intervals up to six months after the fracture . There was no significant difference in the number of IVRBs administered or in finger tenderness , stiffness or grip strength between the two groups . The guanethidine group experienced more pain in the affected h and ( p = 0.025 ) and at six months had more vasomotor instability ( p < 0.0001 ) compared with the control group . IVRB using guanethidine offers no significant analgesic advantage over a normal saline placebo block in the treatment of early CRPS type 1 of the h and after fracture of the distal radius . It does not improve the outcome of this condition and may delay the resolution of vasomotor instability when compared with the placebo Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials . This EFNS Task Force aim ed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain . Studies were identified using first the Cochrane Data base then Medline . Trials were classified according to the aetiological condition . All class I and II controlled trials ( according to EFNS classification of evidence ) were assessed , but lower‐class studies were considered in conditions that had no top level studies . Only treatments feasible in an outpatient setting were evaluated . Effects on pain symptoms/signs , quality of life and comorbidities were particularly search ed for . Most of the r and omized controlled trials included patients with postherpetic neuralgia ( PHN ) and painful polyneuropathies ( PPN ) mainly caused by diabetes . These trials provide level A evidence for the efficacy of tricyclic antidepressants , gabapentin , pregabalin and opioids , with a large number of class I trials , followed by topical lidocaine ( in PHN ) and the newer antidepressants venlafaxine and duloxetine ( in PPN ) . A small number of controlled trials were performed in central pain , trigeminal neuralgia , other peripheral neuropathic pain states and multiple‐aetiology neuropathic pains . The main peripheral pain conditions respond similarly well to tricyclic antidepressants , gabapentin , and pregabalin , but some conditions , such as HIV‐associated polyneuropathy , are more refractory . There are too few studies on central pain , combination therapy , and head‐to‐head comparison . For future trials , we recommend to assess quality of life and pain symptoms or signs with st and ardized tools Neuropathic pain ( NeP ) , generated by disorders of the peripheral and central nervous system , can be particularly severe and disabling . Prevalence estimates indicate that 2 % to 3 % of the population in the developed world suffer from NeP , which suggests that up to one million Canadians have this disabling condition . Evidence -based guidelines for the pharmacological management of NeP are therefore urgently needed . R and omized , controlled trials , systematic review s and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting . Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one method ologically sound , r and omized , controlled trial showing significant benefit relative to placebo or another relevant control group . Recommendations for treatment are based on degree of evidence of analgesic efficacy , safety , ease of use and cost-effectiveness . Analgesic agents recommended for first-line treatments are certain antidepressants ( tricyclics ) and anticonvulsants ( gabapentin and pregabalin ) . Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine . Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain . Recommended fourth-line treatments include cannabinoids , methadone and anticonvulsants with lesser evidence of efficacy , such as lamotrigine , topiramate and valproic acid . Treatment must be individualized for each patient based on efficacy , side-effect profile and drug accessibility , including cost . Further studies are required to examine head-to-head comparisons among analgesics , combinations of analgesics , long-term outcomes , and treatment of pediatric and central OBJECTIVE Low back pain is a highly common problem and causes much morbidity and socioeconomic loss in the community . Although the use of caudal epidural injections in the management of the low back pain with radicular signs is commonplace , it has not been well investigated . We compare the effectiveness of caudal epidural injection versus non-steroidal anti-inflammatory drugs ( NSAIDs ) in the treatment of low back pain accompanied with radicular pain . METHODS The study was a controlled prospect i ve unblinded trial . A total of consecutive 64 patients with subacute or chronic low back pain accompanied with radicular pain were included . The patients were r and omly allocated to two groups . First group was caudal epidural injection plus therapeutic exercise group , and the second group was NSAIDs plus therapeutic exercise group . Patients were assessed with 10 cm visual analogue scale for pain , straight leg raising test and Oswestry low back pain disability question naire at the beginning and at 15th day , 1st and 3rd month . RESULTS It was seen that both groups ' improvement were good and statistically significant . On the other h and , caudal epidural injection group 's improvement was better and faster than the NSAID group 's , and the differences between assessment scores of the groups were statistically significant , except the 3rd month Oswestry scores . CONCLUSION Finally , caudal epidural injection in the management of the subacute/chronic low back and radicular pain is a preferable choice , if applied by experienced specialists Study Design . Prospect i ve , double-blind , reference-controlled , investigator-initiated , single center . Objective . To evaluate the efficacy of Autologous Conditioned Serum ( ACS ; Orthokine ) for the treatment of lumbar radicular compression in comparison to triamcinolone . Summary of Background Data . Evidence from animal studies indicates that cytokines such as interleukin-1 play a decisive role in the pathophysiology of lumbar radiculopathy . ACS is enriched in the interleukin-1 receptor antagonist and other anti-inflammatory cytokines . Methods . Thirty-two patients were treated by epidural perineural injections with ACS ; 27 patients were treated with 5 mg triamcinolone and 25 patients with 10 mg triamcinolone . Treatment was applied once per week for 3 consecutive weeks and followed for 6 months . The Visual Analogue Scale ( VAS ) of low back pain was the primary outcome measure . The Oswestry Disability Index ( ODI ) was the secondary endpoint of the study . All statistical analyses were performed in an exploratory manner using SAS for Windows , version 8.2 , on a personal computer . Descriptive statistics were calculated for the VAS and ODI by treatment group and time point . The data were su bmi tted to a repeated- measurements analysis of variance with effects on treatment group , time , and treatment group-by-time interaction . Results . Patients with lumbar back pain who were treated with ACS or the 2 triamcinolone concentrations showed a clinical ly remarkable and statistically significant reduction in pain and disability , as measured by patient administered outcome measurements . From Week 12 to the final evaluation at Week 22 , injections with ACS showed a consistent pattern of superiority over both triamcinolone groups with regard to the VAS score for pain , but statistical significance was observed only at Week 22 in direct comparison to the triamcinolone 5 group . However , there was no statistically significant difference between the 2 triamcinolone dosages during the 6 months of the study . Conclusion . ACS is an encouraging treatment option for patients with unilateral lumbar radicular compression . The decrease in pain was pronounced , clinical ly remarkable , and potentially superior to steroid injection Study Design . A r and omized , double-blind controlled trial . Objectives . To determine the treatment effect of corticosteroids in periradicular infiltration for chronic radicular pain . We also examined prognostic factors in relation to the outcome of the procedure . Summary of Background Data . Various studies have examined the therapeutic value of periradicular infiltration using treatment agents consisting of local anesthetic and corticosteroids for radicular pain , secondary to lumbar disc herniation and spinal stenosis . There is currently no r and omized trial to determine the efficacy of a single injection of corticosteroids for chronic radicular pain . Methods . Eligible patients with radicular pain who had unilateral symptoms who failed conservative management were r and omized for a single injection with bupivacaine and methylprednisolone or bupivacaine only . Outcome measures included the Oswestry Disability Index , visual analogue score for back pain and leg pain , claudication walking distance , and the patient 's subjective level of satisfaction of the outcome . Results . We recruited 43 patients in the bupivacaine and methylprednisolone group and 43 patients in the bupivacaine only group . The follow-up rate is 100 % . Five patients had early termination of the trial for discectomy and further root block . There is no statistically significant difference in the outcome measures between the groups at 3 months ( change of the Oswestry Disability Index [ P = 0.68 ] , change in visual analogue score [ back pain , P = 0.68 ; leg pain , P = 0.94 ] , change in walking distance [ P = 0.7 ] ) . Duration of symptoms has a statistically significant negative association with the change in Oswestry Disability Index ( P = 0.03 ) . Conclusion . Clinical improvement occurred in both groups of patients . Corticosteroids did not provide additional benefit 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 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 Lignocaine is a cardiac antiarrhythmic agent occasionally used to treat neuropathic pain . This study was design ed to examine the effectiveness of intravenous lignocaine in patients with intractable painful diabetic neuropathy . RESEARCH DESIGN AND METHODS Fifteen patients with painful diabetic peripheral neuropathy , who had appeared to respond to previous lignocaine infusions , completed a double-blind , placebo-controlled crossover trial of two doses of intravenous lignocaine ( 5 and 7.5 mg/kg ) versus saline . Infusions were administered in r and om order over 4 h at four weekly intervals . The effect of treatment on pain perception was assessed using the McGill Pain Question naire ( MPQ ) , a daily pain diary , hours of sleep , fasting blood glucose , and use of other pain-relieving medication . RESULTS Both doses of lignocaine significantly ( P<.05 to P<.001 for the different measures ) reduced the severity of pain compared with placebo . This reduction was present at both 14 and 28 days after the infusion . The qualitative nature of the pain was also significantly ( P<.05 to P<.01 ) modified by lignocaine compared with placebo for up to 28 days . The preceding dose 4 weeks earlier significantly ( P<.01 and P<.001 ) affected the response to the next dose . There were no significant effects of treatment on the other measures of response . There were no significant side effects of the treatment . CONCLUSIONS This study shows that intravenous lignocaine ameliorates pain in some diabetic participants with intractable neuropathic pain who have failed to respond to or are intolerant of available conventional therapy Objective : To investigate the effects of IV lidocaine on spontaneous and evoked pain ( allodynia and hyperalgesia ) due to peripheral nerve injury ( postherpetic neuralgia or nerve trauma ) using quantitative sensory testing . Method : The authors r and omized 22 patients to receive lidocaine 5 mg/kg IV during 30 minutes or placebo in a double-blind crossover design and 16 patients subsequently received mexiletine on an open basis titrated from 400 to 1,000 mg per day ( mean 737 mg/day ) . Results : Lidocaine induced a significant decrease in ongoing pain for up to 6 hours with a peak effect 60 to 120 minutes postinjection . The drug also decreased mechanical dynamic allodynia and static ( punctate ) mechanical allodynia/hyperalgesia , but not thermal allodynia and hyperalgesia . The effects of lidocaine and mexiletine on spontaneous pain intensity were significantly higher in patients with concomitant mechanical allodynia in comparison with those without allodynia . Conclusions : These data indicate modality-specific antihyperalgesic effects of IV lidocaine in patients with peripheral nerve injury . Patients with mechanical allodynia may be good c and i date s for treatment with local anesthetic-like drugs and possibly with other sodium-channel blockers Basic research indicates that systemic local‐anaesthetic‐type drugs that block sodium channels are effective in pain due to nerve damage . These drugs were first used as analgesics in the 1950s and they are still commonly used to try to relieve neuropathic pain and incident pain caused by cancer . As they are potentially toxic , these drugs should not be used without proven effectiveness . For these reasons , a systematic review of r and omized controlled trials of systemically administered local‐anaesthetic‐type drugs in chronic pain was performed . Main outcomes were pain relief or pain intensity difference and adverse effects . Twenty‐one reports were found , and four publications were excluded . In the remaining 17 studies ( 450 patients ) , 10 used intravenous lignocaine , two used intranasal lignocaine , four used oral mexiletine and one used oral tocainide BACKGROUND AND OBJECTIVES Sciatica is a neuropathic pain syndrome caused by compression and /or inflammation of spinal nerve roots by herniated disc material , and its treatment is therefore usually aim ed at reducing compression and inflammation . Studies have shown that both systemic local anesthetics and N-methyl-D-aspartate ( NMDA ) receptor antagonists may produce analgesia in a variety of neuropathic pain syndromes . The present study evaluated the analgesic efficacy of i.v . infusions of the local anesthetic lidocaine , the NMDA receptor antagonist amantadine , and a placebo in sciatica . METHODS Thirty patients with sciatica , as confirmed by physical examination and imaging studies , were enrolled in a r and omized , double-blind , three-arm crossover trial . Infusions of amantadine ( 2.5 mg/kg ) , lidocaine ( 5 mg/kg ) , and a placebo were administered over a 2-hour period , 2 - 7 days apart from each other . Spontaneous pain ( visual analog scale ) and evoked pain ( straight leg raise ) were measured every 30 minutes for 3 hours . RESULTS Lidocaine reduced spontaneous pain as compared with amantadine and with the placebo for all measurements and at a significant level at the 30 ( P < .05 ) , 120 , and 180 ( P < .01 ) minute time points . Maximal pain reduction from the baseline was 62 + /- 7 % for lidocaine , 43 + /- 7 % for amantadine , and 47 + /- 7 % for the placebo . Straight leg raise test also significantly improved with lidocaine ( from 30 to 37 degrees ; P < .05 ) , as compared to amantadine ( 34 - 36 degrees ) and to the placebo ( 32 - 34 degrees ) . All three treatments were relatively well tolerated . CONCLUSIONS Intravenous lidocaine , rather than amantadine , reduces both spontaneous and evoked sciatic pain Objective To assess the efficacy of caudal epidural steroid or saline injection in chronic lumbar radiculopathy in the short ( 6 weeks ) , intermediate ( 12 weeks ) , and long term ( 52 weeks ) . Design Multicentre , blinded , r and omised controlled trial . Setting Outpatient multidisciplinary back clinics of five Norwegian hospitals . Participants Between October 2005 and February 2009 , 461 patients assessed for inclusion ( presenting with lumbar radiculopathy > 12 weeks ) . 328 patients excluded for cauda equina syndrome , severe paresis , severe pain , previous spinal injection or surgery , deformity , pregnancy , ongoing breast feeding , warfarin therapy , ongoing treatment with non-steroidal anti-inflammatory drugs , body mass index > 30 , poorly controlled psychiatric conditions with possible secondary gain , and severe comorbidity . Interventions Subcutaneous sham injections of 2 mL 0.9 % saline , caudal epidural injections of 30 mL 0.9 % saline , and caudal epidural injections of 40 mg triamcinolone acetonide in 29 mL 0.9 % saline . Participants received two injections with a two week interval . Main outcome measures Primary : Oswestry disability index scores . Secondary : European quality of life measure , visual analogue scale scores for low back pain and for leg pain . Results Power calculations required the inclusion of 41 patients per group . We did not allocate 17 of 133 eligible patients because their symptoms improved before r and omisation . All groups improved after the interventions , but we found no statistical or clinical differences between the groups over time . For the sham group ( n=40 ) , estimated change in the Oswestry disability index from the adjusted baseline value was −4.7 ( 95 % confidence intervals −0.6 to −8.8 ) at 6 weeks , −11.4 ( −6.3 to −14.5 ) at 12 weeks , and −14.3 ( −10.0 to −18.7 ) at 52 weeks . For the epidural saline intervention group ( n=39 ) compared with the sham group , differences in primary outcome were −0.5 ( −6.3 to 5.4 ) at 6 weeks , 1.4 ( −4.5 to 7.2 ) at 12 weeks , and −1.9 ( −8.0 to 4.3 ) at 52 weeks ; for the epidural steroid group ( n=37 ) , corresponding differences were −2.9 ( −8.7 to 3.0 ) , 4.0 ( −1.9 to 9.9 ) , and 1.9 ( −4.2 to 8.0 ) . Analysis adjusted for duration of leg pain , back pain , and sick leave did not change this trend . Conclusions Caudal epidural steroid or saline injections are not recommended for chronic lumbar radiculopathy . Trial registration Current Controlled Trials IS RCT N No 12574253 INTRODUCTION Low back pain and lumbar radicular pain are the leading causes of job loss worldwide . Therapeutic approaches to lumbar radicular pain , including sciatica and spinal canal stenosis , are diverse . Many clinicians use 80 mg long-acting glucocorticoids in epidural steroid injections ( ESI ) . The aim of this study is to compare the clinical response of 80 mg versus 40 mg methylprednisolone in ESI . METHODS 84 patients with newly exacerbated lumbar radicular pain were r and omly al located into two groups . 43 patients under went ESI with 80 mg Depo-Medrol and 41 age- and sex-matched cases received 40 mg Depo-Medrol as the comparison group . The pain in the second week , and every month thereafter was assessed using a visual analogue scale ( VAS ) . RESULTS Remarkable improvement in one month VAS occurred in 64 cases ( 75 percent ) from both groups . VAS values between 80 mg and 40 mg groups were comparable in the two-week ( p-value is 0.827 ) and three-month ( p-value is greater than 0.746 ) post-injection periods . Slightly better results were shown in patients in the 40 mg group after one month . CONCLUSION In the case of lumbar radicular pain , ESI with low dose ( 40 mg ) methylprednisolone is as effective as high dose ( 80 mg ) with comparable results and less adverse profile BACKGROUND Neuropathic pain commonly affects the back and legs and is associated with severe disability and psychological illness . It is unclear how patients with predominantly neuropathic pain due to failed back surgery syndrome ( FBSS ) compare with patients with other chronic pain conditions . AIMS To present data on characteristics associated with FBSS patients compared with those with complex regional pain syndrome , rheumatoid and osteoarthritis , and fibromyalgia . METHODS The PROCESS ( Prospect i ve R and omized Controlled Multicenter Trial of the Effectiveness of Spinal Cord Stimulation , IS RCT N 77527324 ) trial r and omized 100 patients to spinal cord stimulation ( n = 52 ) plus conventional medical management ( CMM ) or CMM alone ( n = 48 ) . Baseline patient parameters included age , sex , time since last surgery , employment status , pain location and severity ( visual analogue scale ) , health-related quality of life ( HRQoL ) , level of disability , medication , and nondrug therapies . Reference population data was drawn from the literature . RESULTS At baseline , patients in the PROCESS study had a similar age and gender profile compared with other conditions . PROCESS patients suffered from greater leg pain and had lower HRQoL. PROCESS patients treatment cost was higher and they commonly took opioids , while antidepressants and nonsteroidal anti-inflammatory drugs were more often used for other conditions . Prior to baseline , 87 % of patients had tried at least 4 different treatment modalities . CONCLUSIONS Patients suffering from chronic pain of neuropathic origin following FBSS often fail to obtain adequate relief with conventional therapies ( eg , medication , nondrug therapies ) and suffer greater pain and lower HRQoL compared with patients with other chronic pain conditions . Neuropathic FBSS patients may require alternative and possibly more ( cost- ) effective treatments , which should be considered earlier in their therapeutic management Background : Neuropathic pain is often severe and resistant to pharmacological treatment . The aims of the present study were to assess the analgesic effect of ketamine and lidocaine and to investigate if measurement of different variables of sensibility could be used to identify responders . We also wanted to study if treatment result ed in changes of sensibility BACKGROUND Postherpetic neuralgia is a complication of acute herpes zoster characterized by severe pain and paraesthesia in the skin area affected by the initial infection . There is evidence that the N-methyl-D-aspartate receptor is involved in the development of hypersensitivity states and it is known that magnesium blocks the N-methyl-D-aspartate receptor . METHOD A double-blind , placebo-controlled , cross-over study was conducted in which magnesium sulphate was administered as an i.v . infusion . Spontaneous pain was recorded and qualitative sensory testing with cotton wool was performed in seven patients with postherpetic neuralgia before and after the i.v . administration of either magnesium sulphate 30 mg kg(-1 ) or saline . RESULTS During the administration , pain scores were significantly lower for magnesium compared with placebo at 20 and 30 min ( P=0.016 ) but not at 10 min . I.V. magnesium sulphate was safe , well-tolerated and effective in patients with postherpetic neuralgia . CONCLUSION The present study supports the concept that the N-methyl-D-aspartate receptor is involved in the control of postherpetic neuralgia At the end of a long week in the office , you sink back into your chair , reflecting on some of the more memorable patients you cared for and counseled . Through gentle history taking , you discovered that urinary incontinence is the underlying cause of an elderly patient 's increasing social isolation . During a careful physical examination , you detected bruising on the torso of a woman with chronic headaches and began to explore the longst and ing abusive relationship between the woman and her alcoholic partner . You discontinued procainamide therapy in a 72-year-old man who had asymptomatic premature ventricular contractions after myocardial infa rct ion . To prevent bleeding from esophageal varices , you started -blocker therapy in a woman with long-st and ing cryptogenic cirrhosis and portal hypertension . In couples ' therapy , discussing the future quality of life of a middle-aged gay man with human immunodeficiency virus infection , you journeyed through emotionally intense dialogue about advance directives . You presented the risk factors for major and minor bleeding to a 39-year-old woman who was considering warfarin therapy because of recently diagnosed atrial fibrillation and valvular heart disease . You listened to , made diagnoses for , treated , advised , and comforted many patients . Yet there were some hiccoughs in your practice along the way . You stumbled while debating the pros and cons of breast cancer screening with a healthy 48-year-old woman who has been staying current with information on the Internet . You question ed the merits of a personalized walking program suggested to you by a motivated 66-year-old man with severe claudication . Explaining that you wanted to review the best current evidence on these issues , you resolved to address your uncertainties before these patients made their next office visits , in a week 's time . Sighing deeply , you acknowledge that you have little time to read . You subscribe to three journals , which you browse months after they arrive-either when your journal stack becomes precariously high or when your guilt is sufficiently motivational . You sometimes find the conclusions of individual articles conflicting or confusing . You know that some of the decisions and suggestions you made this week , specifically your decisions about stopping procainamide therapy and starting -blocker therapy and your advice about bleeding risks from anticoagulant therapy , were based on the best current research evidence [ 1 - 3 ] . On the other h and , your patients ' inquiries about breast cancer screening and exercise treatment for claudication highlight your need for a concise , current , rigorous synthesis of the best available evidence on each of these topics : in brief , a systematic review [ 4 , 5 ] . Incorporating Research Evidence into Clinical Decision Making The foregoing scenario is familiar to practitioners . In a typical week , we encounter patients with diverse problems ; exercise numerous clinical , interpersonal , and technical skills ; and make many decisions . The factors that affect these decisions and their outcomes are complex . For instance , each patient has unique sociodemographic characteristics , cultural circumstances , and personal preferences . Each physician has unique knowledge , experiences , and values . Moreover , practitioners and their patients make decisions within the context of a rapidly changing health care system that influences the availability , accessibility , and cost of diagnostic tests and therapies [ 6 ] . Timely , useful evidence from the biomedical literature should be an integral component of clinical decision making . If one treatment has been shown to be better than another , we need to know , so that we can recommend the treatment to the appropriate patients . The worldwide effort to develop new tests and treatments , and to determine their usefulness , has never been stronger , and our patients and their families expect us to be fonts of the knowledge that results from this effort [ 7 ] . Unfortunately , it is easy for current best research evidence to pass us by [ 8 ] . We may lack the time , motivation , and basic skills needed to find , critically appraise , and synthesize information , all of which we must do if we are to integrate the results of original studies into our practice . Fortunately , several potent methods are emerging that can greatly enhance our ability to interpret and apply research evidence ; foremost among them is the systematic review . This article begins a series in Annals that will examine systematic review s in detail and explore their many applications . Systematic review s represent the best chance that most practitioners will have to underst and and accurately apply the key signals arising from the robust and increasingly productive search for solutions to medical problems . A properly conducted systematic review faithfully summarizes the evidence from all relevant studies on the topic of interest , and it does so concisely and transparently . What Is a Systematic Review ? Systematic review s are scientific investigations in themselves , with pre-planned methods and an assembly of original studies as their subjects . They synthesize the results of multiple primary investigations by using strategies that limit bias and r and om error [ 9 , 10 ] . These strategies include a comprehensive search of all potentially relevant articles and the use of explicit , reproducible criteria in the selection of articles for review . Primary research design s and study characteristics are appraised , data are synthesized , and results are interpreted . When the results of primary studies are summarized but not statistically combined , the review may be called a qualitative systematic review . A quantitative systematic review , or meta- analysis , is a systematic review that uses statistical methods to combine the results of two or more studies . The term overview is sometimes used to denote a systematic review , whether quantitative or qualitative . Summaries of research that lack explicit descriptions of systematic methods are often called narrative review s. Review articles are one type of integrative publication ; practice guidelines , economic evaluations , and clinical decision analyses are others . These other types of integrative articles often incorporate the results of systematic review s. For example , practice guidelines are systematic ally developed statements intended to assist practitioners and patients with decisions about appropriate health care for specific clinical circumstances [ 11 ] . Evidence -based practice guidelines are based on systematic review s of the literature , appropriately adapted to local circumstances and values . Economic evaluations compare both the costs and the consequences of different courses of action ; the knowledge of consequences that are considered in these evaluations is often generated by systematic review s of primary studies . Decision analyses quantify both the likelihood and the valuation of the expected outcomes associated with competing alternatives . Differences between Systematic and Narrative Review s All review s , narrative and systematic alike , are retrospective , observational research studies and are therefore subject to systematic and r and om error . Accordingly , the quality of a review - and thus its worth-depends on the extent to which scientific review methods have been used to minimize error and bias . This is the key feature that distinguishes traditional narrative review s from systematic review s ( Table 1 ) . If a review is prepared according to the steps outlined in the right column of Table 1 , it is more likely to be systematic and to provide unbiased conclusions . If review methods approximate those found in the middle column of Table 1 , the article is more likely to be a narrative review , and the conclusions are less likely to be based on an unbiased summary of all relevant evidence . Table 1 . Differences between Narrative Review s and Systematic Review s Systematic review s are generated to answer specific , often narrow , clinical questions in depth . These questions can be formulated explicitly according to four variables : a specific population and setting ( such as elderly out patients ) , the condition of interest ( for example , hypertension ) , an exposure to a test or treatment ( such as pharmacologic management ) , and one or more specific outcomes ( such as cardiovascular and cerebrovascular events and mortality ) [ 12 ] . Thus , an example of a well-formulated , clinical ly relevant question is , Does pharmacologic treatment of hypertension in the elderly prevent strokes and myocardial infa rct ions or delay death ? If the question that is driving the review is not clear from the title , abstract , or introduction , or if no methods section is included , the paper is more likely to be a narrative review than a systematic review [ 13 ] . Most narrative review articles deal with a broad range of issues related to a given topic rather than addressing a particular issue in depth [ 9 ] . For example , a narrative review on diabetes ( such as that which might be found in a textbook chapter ) might include sections on the physiology and pathophysiology of carbohydrate , lipid , and protein metabolism ; the epidemiology of and prognosis associated with diabetes ; diagnostic and screening approaches ; and preventive , therapeutic , rehabilitative , and palliative interventions . Thus , narrative review s may be most useful for obtaining a broad perspective on a topic ; they are less often useful in furnishing quantitative answers to specific clinical questions . Narrative review s are appropriate for describing the history or development of a problem and its management . Narrative review s may better describe cutting-edge developments if research is scant or preliminary or if studies are very limited by flawed design or execution [ 13 ] . They may be particularly useful for discussing data in light of underlying theory and context . Narrative review s can draw analogies and can conceptually integrate two independent fields of research , such as Abstract Patients with neuropathic pain secondary to failed back surgery syndrome ( FBSS ) typically experience persistent pain , disability , and reduced quality of life . We hypothesised that spinal cord stimulation ( SCS ) is an effective therapy in addition to conventional medical management ( CMM ) in this patient population . We r and omised 100 FBSS patients with predominant leg pain of neuropathic radicular origin to receive spinal cord stimulation plus conventional medical management ( SCS group ) or conventional medical management alone ( CMM group ) for at least 6 months . The primary outcome was the proportion of patients achieving 50 % or more pain relief in the legs . Secondary outcomes were improvement in back and leg pain , health‐related quality of life , functional capacity , use of pain medication and non‐drug pain treatment , level of patient satisfaction , and incidence of complications and adverse effects . Crossover after the 6‐months visit was permitted , and all patients were followed up to 1 year . In the intention‐to‐treat analysis at 6 months , 24 SCS patients ( 48 % ) and 4 CMM patients ( 9 % ) ( p < 0.001 ) achieved the primary outcome . Compared with the CMM group , the SCS group experienced improved leg and back pain relief , quality of life , and functional capacity , as well as greater treatment satisfaction ( p ⩽ 0.05 for all comparisons ) . Between 6 and 12 months , 5 SCS patients crossed to CMM , and 32 CMM patients crossed to SCS . At 12 months , 27 SCS patients ( 32 % ) had experienced device‐related complications . In selected patients with FBSS , SCS provides better pain relief and improves health‐related quality of life and functional capacity compared with CMM alone OBJECT Chronic complex regional pain syndrome-Type I ( CRPS-I ) is a painful , disabling disorder for which no treatment with proven effect is available . In the present r and omized controlled trial , the authors assessed the effectiveness of spinal cord stimulation ( SCS ) in reducing pain due to CRPS-I at the 5-year follow-up . METHODS The authors performed a r and omized trial in a 2:1 ratio in which 36 patients with CRPS-I were allocated to receive SCS and physical therapy ( PT ) and 18 patients to receive PT alone . Twenty-four patients who received SCS+PT also underwent placement of a permanent spinal cord stimulator after successful test stimulation ; the remaining 12 patients did not receive a permanent stimulator . The authors assessed pain intensity , global perceived effect , treatment satisfaction , and health-related quality of life . Patients were examined before r and omization , before implantation , and every year until 5 years thereafter . Ten patients were excluded from the final analysis . RESULTS At 5 years posttreatment , SCS+PT produced results similar to those following PT for pain relief and all other measured variables . In a subgroup analysis , the results with regard to global perceived effect ( p=0.02 ) and pain relief ( p=0.06 ) in 20 patients with an implant exceeded those in 13 patients who received PT . CONCLUSIONS Despite the diminishing effectiveness of SCS over time , 95 % of patients with an implant would repeat the treatment for the same result INTRODUCTION : Lumbar epidural steroid injection can be accomplished by one of three methods : caudal ( C ) , interlaminar ( IL ) , or transforaminal ( TF ) . In this study we sought to determine the efficacy of these techniques for the management of radicular pain associated with lumbar disk herniations . METHODS : Ninety patients aged 18–60 years with L5-S1 disk herniations and radicular pain were r and omly assigned to one of these groups to have epidural steroid injection therapy every 2 wk for a maximum of three injections . Pain relief , disability , and activity levels were assessed . RESULTS : Pain relief was significantly more effective with TF injections . At 24 wk from the initiation of this study , pain relief was as follows : C : complete pain relief : 1/30 , partial pain relief : 16/30 , and no relief : 13/30 ; IL : complete pain relief : 3/30 , partial pain relief : 15/30 , and no relief : 12/30 ; and TF : complete pain relief : 9/30 , partial pain relief : 16/30 , and no relief : 5/30 . CONCLUSIONS : The TF route of epidural steroid placement is more effective than the C or IL routes . We attribute this observation to a higher incidence of steroid placement in the ventral epidural space when the TF method is used |
11,842 | 25,474,592 | CCT results in no significant difference in service use , social functioning or quality of life compared with st and ard voluntary care .
People receiving CCT were , however , less likely to be victims of violent or non-violent crime .
It is unclear whether this benefit is due to the intensity of treatment or its compulsory nature .
Short periods of conditional leave may be as effective ( or non-effective ) as formal compulsory treatment in the community . | BACKGROUND There is controversy as to whether compulsory community treatment ( CCT ) for people with severe mental illness ( SMI ) reduces health service use , or improves clinical outcome and social functioning .
OBJECTIVES To examine the effectiveness of CCT for people with SMI . | After nearly three decades of studies evaluating the legal practice of involuntary outpatient commitment , there is yet little consensus about its effectiveness and only limited implementation . Debate continues over how best to assist adults with serious mental illnesses who are unable or unwilling to participate in prescribed community treatment and as a result experience repeated involuntary hospitalizations or involvement with the criminal justice system . The authors comment on the Oxford Community Treatment Order Evaluation Trial ( OCTET ) , a recently conducted r and omized trial of outpatient commitment , and discuss the limitations of the study 's design for resolving the persistent question of whether compulsory treatment is more effective than purely voluntary treatment for this difficult-to-reach target population . The authors conclude that the search for a definitive and generalizable r and omized trial of outpatient commitment may be a quixotic quest ; the field should , rather , welcome the results of well-conducted , large-scale , quasi-experimental and naturalistic studies with rigorous multivariable statistical controls The use of coercion to assure that people with a mental illness receive treatment has been the focus one of the longest running controversies among mental health professionals . Until quite recently , however , this debate has been almost entirely based on abstract principles . Empirical research concerning coercion was quite limited . Recently , however , research in this field has blossomed . The development of a vali date d measure of perceived coercion has spawned a variety of new studies . A five-nation study in Sc and inavia has begun the difficult task of assessing the impact of different legal systems and systems of care on perceived coercion . Two new studies have used r and om assignment design s to study the impact of outpatient commitment . This article review s these and other studies and describes what they do , and do not , tell us about coercion in mental health treatment OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate Supervised community treatment to address ' revolving door ' care is part of the new Mental Health Act in Engl and and Wales . Two recent epidemiological studies in Australia ( n>118 000 ) , as well as a systematic review of all previous literature using appropriately matched or r and omised controls ( n=1108 ) , suggest that it is unlikely to help How does society protect some of its most vulnerable and disadvantaged patients while respecting individual autonomy ? This is the dilemma facing many Canadian jurisdictions as they consider the extension of compulsory treatment to community setting s. Canada is not unique but part of a trend to enforce outpatient treatment in many jurisdictions , including Australia , New Zeal and , the United States , and the European Union ( 1,2 ) . What is the basis for this enthusiasm ? Certainly , research published in this journal has endorsed the measure to varying degrees ( 3 ) , as does the position paper of the Canadian Psychiatric Association ( 4 ) . We wonder whether this confidence is misplaced , and we critically examine several troubling aspects of the literature on CTOs . Opinion Is Not Evidence One approach to the evaluation of CTOs has been to ask practising psychiatrists for their opinion on the utility of the orders ( 3 ) . These suggest general support for the measure . However , surveys of psychiatrists ' views on CTOs provide only Level 3 evidence , in contrast to the Level 1 evidence from appropriately conducted RCTs and the Level 2 evidence from well- design ed non- RCT studies , such as case-control studies or interrupted time series . Such surveys have little place in an era of evidence -based practice and , in the absence of other data , would not be accepted as a reason to introduce any other psychiatric intervention . No Controls , Little Evidence Early uncontrolled studies , largely from the United States , suggested that patients on CTOs had reduced rates of rehospitalization and shorter stays in hospital , associated with increased compliance . However , there were no significant differences between the 2 groups when control subjects not subject to a compulsory treatment order were included ( 5 - 7 ) . The weakness of uncontrolled design s is the difficulty in determining the reason for any change in outcome . Aside from the effect of the intervention , other possible explanations include regression to the mean , other treatment , life events , or changes in social circumstances . These often overestimate the effect of the intervention of interest . Controlled studies without r and omization also have shortcomings . There may always be another reason why patients were placed on treatment and the control subjects were not . They may be less insightful about their illness or more likely to have a history of aggressive behaviour . Only one matched control study controlled for forensic history ( 7 ) . What About RCTs ? RCTs address many of these problems but are very difficult to conduct where mental health legislation policy is implemented at a state , provincial , or national level . There have therefore only been 2 RCTs , and both were in the United States ( New York and North Carolina ) ( 8 - 11 ) . These trials have been the subject of much debate in terms of subjects , design , analysis , and generalizability . Selection and Follow-Up Bias : Were the Patients Typical ? Both RCTs excluded patients with a history of violence from r and omization . Although underst and able from an ethical and legal st and point , this limits their applicability because recent dangerousness , particularly violence against others , is often the reason for compulsory treatment in hospital or in the community . One study did include a nonr and omized violent subgroup in the analysis , but this negates the whole point of an RCT ( see below ) ( 9 - 11 ) . Selection bias was further compounded by high dropout rates . Of the 577 patients identified as eligible for participation in the New York and North Carolina studies , including the violent subgroup , only 292 ( 51 % ) were followed up 1 year later . Although the North Carolina study had a higher completion rate among r and omized patients than the New York study ( 82 % and 45 % , respectively ) , data were not available for all patients for all of the outcomes . The 1 -year follow-up is therefore of a highly selected and potentially unrepresentative population that was not dangerous and was sufficiently compliant to participate in baseline and follow-up assessment s. Aims and method Community treatment orders ( CTOs ) were introduced in Scotl and in 2005 , but are controversial owing to a lack of supportive r and omised evidence . The non-r and omised studies provide mixed results on their efficacy and utility . We aim ed to examine hospital bed day usage across Scotl and both before and after CTOs were initiated in a national cohort of patients , spanning 5 years . Results In total , 1558 individuals who were subject to a CTO between 2007 and 2012 , of whom 63 % were male , were included . After CTO initiation the number of hospital bed days fell , on average , from 66 to 39 per annum per patient . Those with a longer psychiatric history appeared to benefit more from a CTO , in terms of reduced time in hospital . Clinical implication s Our data offer cautious support for the use of CTOs in routine practice , in terms of reducing time spent in psychiatric hospital . This finding is balanced by the more rigorous r and omised studies which do not find any benefit to CTOs Background : Supervised Discharge Orders ( SDOs ) were introduced in 1995 , as an amendment to the Mental Health Act in Engl and and Wales . They require patients to abide by specific conditions on discharge from hospital , but can not enforce medication compliance . On introduction , SDOs were received with scepticism by the psychiatric profession . The purpose of this study was to describe the use of SDOs in Engl and and the characteristics of patients made subject to these orders , and to evaluate the effectiveness of the order in securing treatment compliance on discharge from hospital . Method : A survey was conducted of 170 mental health provider Trusts in Engl and . Interviews with senior managers in 12 Trusts and associated Local Authorities were subjected to qualitative analysis , and a cohort of patients subject to SDOs in 56 r and omly sample d Trusts was described . Results : SDOs were being used for 596 patients ( 1.2 per 100,000 total population ) at the survey date in 1999 , and use had been increasing steadily since its introduction . The order is not systematic ally considered for all potential cases . The majority of the 182 patients in the cohort had complied , if sometimes intermittently , with conditions of the order . Conclusions : For patients compliant with SDOs , the pressures necessary to treat effectively need not involve powers to enforce medication compliance This study examines self-reported coercion in subjects with severe mental illness who were r and omly assigned in an experimental study to continue under , or be released from , involuntary outpatient commitment ( OPC ) subsequent to hospital discharge . After review of bivariate relationships , multivariable analyses demonstrated significantly higher levels of reported coercion among subjects who experienced longer periods of OPC ; who were African American ; who were single and not cohabiting ; and who had ongoing substance abuse problems , poor insight into illness , and severe symptoms . Case managers ' verbal reminders to subjects about the consequences of nonadherence to treatment partially account for higher reports of coercion . Previous reports from this study have found that OPC , if sustained and combined with frequent outpatient mental health services , can improve some outcomes . The current analyses demonstrate that a consequence of OPC is increased perceptions of coercion in the treatment process , which is partially explained by the increased attention by case managers to noncompliance with treatment PURPOSE The study evaluated whether seclusion and coercive incidents would be reduced in extent and number if involuntary medication was the first choice of intervention . Patients admitted to an acute psychiatric ward were r and omly allocated to two groups . In Group 1 , involuntary medication was the intervention of first choice for dealing with agitation and risk of violence . In Group 2 , seclusion was the intervention of first choice . Patients ' characteristics between the groups were compared by Pearson χ(2 ) and two- sample t-tests ; the incidence rates and risk ratios ( RRs ) were calculated to examine differences in number and duration of coercive incidents . In Group 1 , the relative risk of being secluded was lower than in Group 2 , whereas the risk of receiving involuntary medication was higher . However , the mean duration of the seclusion incidents did not differ significantly between the two groups ; neither did the total number of coercive incidents . Although the use of involuntary medication could successfully replace and reduce the number of seclusions , alternative interventions are needed to reduce the overall number and duration of coercive incidents . A new policy for managing acute aggression - such as involuntary medication - can be implemented effectively only if certain conditions are met The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas OBJECTIVE The authors ' goal was to evaluate the effectiveness of outpatient commitment in reducing victimization among people with severe mental illness . METHOD One hundred eighty-four involuntarily hospitalized patients were r and omly assigned to be released ( N=99 ) or to continue under outpatient commitment ( N=85 ) after hospital discharge . An additional group of patients with a recent history of serious violent behavior ( N=39 ) was nonr and omly assigned to at least a brief period of outpatient commitment following hospital disharge . All three groups were followed for 1 year , and case management services plus additional outpatient treatment were provided to all subjects . Outcome data were based on interviews with the patients and informants as well as service records . RESULTS Subjects who were ordered to outpatient commitment were less likely to be criminally victimized than those who were released without outpatient commitment . Multivariate analysis indicated that each additional day of outpatient commitment reduced the risk of criminal victimization and that outpatient commitment had its effect through improved medication adherence , reduced substance use or abuse , and fewer violent incidents . CONCLUSIONS Protection from criminal victimization appears to be a positive , unintended consequence of outpatient commitment BACKGROUND Compulsory supervision outside hospital has been developed internationally for the treatment of mentally ill people following widespread deinstitutionalisation but its efficacy has not yet been proven . Community treatment orders ( CTOs ) for psychiatric patients became available in Engl and and Wales in 2008 . We tested whether CTOs reduce admissions compared with use of Section 17 leave when patients in both groups receive equivalent levels of clinical contact but different lengths of compulsory supervision . METHODS OCTET is a non-blinded , parallel-arm r and omised controlled trial . We postulated that patients with a diagnosis of psychosis discharged from hospital on CTOs would have a lower rate of readmission over 12 months than those discharged on the pre-existing Section 17 leave of absence . Eligible patients were those involuntarily admitted to hospital with a diagnosis of psychosis , aged 18 - 65 years , who were deemed suitable for supervised outpatient care by their clinicians . Consenting patients were r and omly assigned ( 1:1 ratio ) to be discharged from hospital either on CTO or Section 17 leave . R and omisation used r and om permuted blocks with lengths of two , four , and six , and stratified for sex , schizophrenic diagnosis , and duration of illness . Research assistants , treating clinicians , and patients were aware of assignment to r and omisation group . The primary outcome measure was whether or not the patient was admitted to hospital during the 12-month follow-up period , analysed with a log-binomial regression model adjusted for stratification factors . We did all analyses by intention to treat . This trial is registered , number IS RCT N73110773 . FINDINGS Of 442 patients assessed , 336 patients were r and omly assigned to be discharged from hospital either on CTO ( 167 patients ) or Section 17 leave ( 169 patients ) . One patient withdrew directly after r and omisation and two were ineligible , giving a total sample of 333 patients ( 166 in the CTO group and 167 in the Section 17 group ) . At 12 months , despite the fact that the length of initial compulsory outpatient treatment differed significantly between the two groups ( median 183 days CTO group vs 8 days Section 17 group , p<0·001 ) the number of patients readmitted did not differ between groups ( 59 [ 36 % ] of 166 patients in the CTO group vs 60 [ 36 % ] of 167 patients in the Section 17 group ; adjusted relative risk 1·0 [ 95 % CI 0·75 - 1·33 ] ) . INTERPRETATION In well coordinated mental health services the imposition of compulsory supervision does not reduce the rate of readmission of psychotic patients . We found no support in terms of any reduction in overall hospital admission to justify the significant curtailment of patients ' personal liberty . FUNDING National Institute of Health Research BACKGROUND The CRIMSON ( CRisis plan IMpact : Subjective and Objective coercion and eNgagement ) study is an individual level , r and omised controlled trial that compared the effectiveness of Joint Crisis Plans ( JCPs ) with treatment as usual for people with severe mental illness . The JCP is a negotiated statement by a patient of treatment preferences for any future psychiatric emergency , when he or she might be unable to express clear views . We assessed whether the additional use of JCPs improved patient outcomes compared with treatment as usual . METHODS Patients were eligible if they had at least one psychiatric admission in the previous 2 years and were on the Enhanced Care Programme Approach register . The study was done with 64 generic and specialist community mental health teams in four English mental health care provider organisations ( trusts ) . Hypotheses tested were that , compared with the control group , the intervention group would experience : fewer compulsory admissions ( primary outcome ) ; fewer psychiatric admissions ; shorter psychiatric stays ; lower perceived coercion ; improved therapeutic relationships ; and improved engagement . We stratified participants by centre . The research team but not participants nor clinical staff were masked to allocation . This study is registered with Clinical Trials.gov , number IS RCT N11501328 . FINDINGS 569 participants were r and omly assigned ( 285 to the intervention group and 284 to the control group ) . No significant treatment effect was seen for the primary outcome ( 56 [ 20 % ] sectioned in the control group and 49 [ 18 % ] in the JCP group ; odds ratio 0·90 [ 95 % CI 0·58 - 1·39 , p=0·63 ] ) or any secondary outcomes , with the exception of an improved secondary outcome of therapeutic relationships ( 17·3 [ 7·6 ] vs 16·0 [ 7·1 ] ; adjusted difference -1·28 [ 95 % CI -2·56 to -0·01 , p=0·049 ] ) . Qualitative data supported this finding . INTERPRETATION Our findings are inconsistent with two earlier JCP studies , and show that the JCP is not significantly more effective than treatment as usual . There is evidence to suggest the JCPs were not fully implemented in all study sites , and were combined with routine clinical review meetings which did not actively incorporate patients ' preferences . The study therefore raises important questions about implementing new interventions in routine clinical practice . FUNDING Medical Research Council UK and the National Institute for Health Research OBJECTIVE The goal of this study was to evaluate the effectiveness of involuntary outpatient commitment in reducing rehospitalizations among individuals with severe mental illnesses . METHOD Subjects who were hospitalized involuntarily were r and omly assigned to be released ( N = 135 ) or to continue under outpatient commitment ( N = 129 ) after hospital discharge and followed for 1 year . Each subject received case management services plus additional outpatient treatment . Outpatient treatment and hospital use data were collected . RESULTS In bivariate analyses , the control and outpatient commitment groups did not differ significantly in hospital outcomes . However , subjects who underwent sustained periods of outpatient commitment beyond that of the initial court order had approximately 57 % fewer readmissions and 20 fewer hospital days than control subjects . Sustained outpatient commitment was shown to be particularly effective for individuals with nonaffective psychotic disorders , reducing hospital readmissions approximately 72 % and requiring 28 fewer hospital days . In repeated measures multivariable analyses , the outpatient commitment group had significantly better hospital outcomes , even without considering the total length of court-ordered outpatient commitments . However , in subsequent repeated measures analyses examining the role of outpatient treatment among psychotically disordered individuals , it was also found that sustained outpatient commitment reduced hospital readmissions only when combined with a higher intensity of outpatient treatment . CONCLUSIONS Outpatient commitment can work to reduce hospital readmissions and total hospital days when court orders are sustained and combined with intensive treatment , particularly for individuals with psychotic disorders . This use of outpatient commitment is not a substitute for intensive treatment ; it requires a substantial commitment of treatment re sources to be effective Objective : The objective of this study was to investigate the readmission rate , and the level of patient disturbance and community care associated with readmission following Community Treatment Orders ( CTOs ) in New South Wales , Australia . Method : The readmission rates of all patients given CTOs within a 4-year period and a matched comparison group were investigated . The following factors were compared before , during and following a CTO : medication non-compliance , number of clinical services and duration of disturbed behaviour preceding hospitalisations . Results : Of 123 patients on CTOs ( mean length , 288 days ; SD , 210 days ) , 38 were readmitted during the CTO , the majority in the first 3 months and a further 21 patients were readmitted following termination of the CTO . Evidence of lower severity of illness in the comparison patients prevented meaningful evaluation of the readmission rates of the two groups . While on CTOs , patients receiving depot medications showed high compliance and a significantly reduced readmission rate compared with that of patients receiving oral medications . In the 2 months prior to hospitalisations during CTOs , compared with those before or after CTOs , patients received more frequent consultations and showed a shorter duration of medication non-compliance and disturbed behaviour . The level of services in the 3 months following discharge were comparable for patients on CTOs and the comparison group . Conclusions : CTOs may reduce rehospitalisations by use of depot medication . Earlier and possibly more frequent readmissions in the CTO group shortened the disturbance associated with illness recurrence . It would appear that to establish a control group with equivalent severity of disorder necessary to evaluate the impact of CTOs requires a r and om allocation design OBJECTIVE The types and amounts of crime experienced by persons with severe mental illness were examined to better underst and criminal victimization in this population . METHODS Subjects were 331 involuntarily admitted psychiatric in patients who were ordered by the court to outpatient commitment after discharge . Extensive interviews provided information on subjects ' experience with crime in the previous four months and their perceived vulnerability to victimization , as well as on their living conditions and substance use . Medical records provided clinical data . RESULTS The rate of nonviolent criminal victimization ( 22.4 percent ) was similar to that in the general population ( 21.1 percent ) . The rate of violent criminal victimization was two and a half times greater than in the general population --8.2 percent versus 3.1 percent . Being an urban resident , using alcohol or drugs , having a secondary diagnosis of a personality disorder , and experiencing transient living conditions before hospitalization were significantly associated with being the victim of a crime . In the multivariate analysis , substance use and transient living conditions were strong predictors of criminal victimization ; no demographic or clinical variable was a significant predictor . ( Given the relatively high crime rates , subjects ' perceived vulnerability to victimization was unexpectedly low ; only 16.3 percent expressed concerns about personal safety . Those with a higher level of education expressed greater feelings of vulnerability . CONCLUSIONS The study found a substantial rate of violent criminal victimization among persons with severe and persistent mental illness . Results suggest that substance use and homelessness make criminal victimization more likely Recent evidence suggests that involuntary outpatient commitment ( OPC ) , when appropriately applied , can improve adherence with psychiatric treatment , decrease hospital recidivism and arrests , and lower the risk of violent behavior in persons with severe mental illness . Presumably these are benefits that improve quality of life ( QOL ) ; however , insofar as OPC involves legal coercion , the undesirable aspects of OPC could also exert a negative effect on quality of life , thus off setting clinical benefits . Involuntarily hospitalized subjects , awaiting discharge under outpatient commitment , were r and omly assigned to be released or continue under outpatient commitment in the community after hospital discharge , and were followed for one year . Quality of life was measured at baseline and 12 months follow-up . Treatment characteristics and clinical outcomes were also measured . Subjects who underwent longer periods of outpatient commitment had significantly greater quality of life as measured at the end of the 1 year study . Multivariable analysis showed that the effect of OPC on QOL was mediated by greater treatment adherence and lower symptom scores . However , perceived coercion moderated the effect of OPC on QOL . Involuntary outpatient commitment , when sustained over time , indirectly exerts a positive effect on subjective quality of life for persons with SMI , at least in part by improving treatment adherence and lowering symptomatology Involuntary outpatient commitment ( OPC ) is a civil justice procedure intended to enhance compliance with community mental health treatment , to improve functioning , and to reduce recurrent dangerousness and hospital recidivism . The research literature on OPC indicates that it appears to improve outcomes in rates of rehospitalization and length of stay . However , all studies to date have serious method ological limitations because of selection bias ; lack of specification of target population s ; unclear operationalization of OPC ; unmeasured variability in type , frequency , and intensity of treatment ; as well as other confounding factors . To address limitations in these studies , the authors design ed a r and omized controlled trial ( RCT ) of OPC , combined with community-based case management , which is now under way in North Carolina . This article describes ethical dilemmas in design ing and implementing an RCT of a legally coercive intervention in community-based setting s. These ethical dilemmas challenge the experimental validity of an RCT but can be successfully addressed with , careful planning and negotiation OBJECTIVE The study evaluated the effectiveness of a three-year outpatient commitment pilot program established in 1994 at Bellevue Hospital in New York City . METHODS A total of 142 participants were r and omly assigned ; 78 received court-ordered treatment , which included enhanced services , and 64 received the enhanced-service package only . Between 57 and 68 percent of the subjects completed interviews at one , five , and 11 months after hospital discharge . Outcome measures included rehospitalization , arrest , quality of life , symptomatology , treatment noncompliance , and perceived level of coercion . RESULTS On all major outcome measures , no statistically significant differences were found between the two groups . No subject was arrested for a violent crime . Eighteen percent of the court-ordered group and 16 percent of the control group were arrested at least once . The percentage rehospitalized during follow-up was about the same for both groups-51 percent and 42 percent , respectively . The groups did not differ significantly in the total number of days hospitalized during the follow-up period . Participants ' perceptions of their quality of life and level of coercion were about the same . From the community service providers ' perspective , patients in the two groups were similarly adherent to their required treatments . CONCLUSIONS All results must be qualified by the fact that no pick-up order procedures for noncompliant subjects in the court-ordered group were implemented during the study , which compromised the differences between the conditions for the two groups , and that persons with a history of violence were excluded from the program This study examines potential improvement in treatment adherence during a study of involuntary outpatient commitment among individuals with severe mental illnesses . Involuntarily hospitalized subjects , awaiting discharge under outpatient commitment , were r and omly assigned to be released or continue under outpatient commitment after hospital discharge . A nonr and omized group with a recent history of serious violence was also studied under outpatient commitment . R and omized control and outpatient commitment groups did not differ significantly in group comparisons of treatment adherence . However , analyses of all subjects , including nonr and omized violent subjects , showed that those who underwent sustained periods of outpatient commitment ( 6 months or more ) were significantly more likely to remain adherent with medication and other treatment , compared with those who underwent only brief outpatient commitment or none . Administration of depot antipsychotics also significantly improved treatment adherence independently of the effect of sustained outpatient commitment . Sustained periods of outpatient commitment may significantly improve adherence with community-based mental health treatment for persons with severe mental illness and thus may help improve other clinical outcomes affected by adherence OBJECTIVE A r and omized controlled trial of outpatient commitment was conducted in North Carolina to provide empirical data on involuntary outpatient commitment and to evaluate its effectiveness in improving outcomes among persons with severe mental illnesses . METHODS A total of 331 involuntarily hospitalized patients awaiting discharge under outpatient commitment were r and omly assigned to be released or to undergo outpatient commitment . Each received case management services and outpatient treatment . Participants in both groups were monitored for one year . After the initial 90-day outpatient commitment order , a patient could receive a renewable 180-day extension . Patients in the control group were immune from outpatient commitment for one year . Information was obtained from self-reports and reports of several informants as well as from outpatient treatment , hospital , and arrest records . RESULTS In most bivariate analyses , outcomes for the outpatient commitment group and the control group did not differ significantly when the duration of outpatient commitment was not taken into account . However , patients who underwent sustained outpatient commitment and who received relatively intensive outpatient treatment had fewer hospital admissions and fewer days in the hospital , were more likely to adhere to community treatment , and were less likely to be violent or to be victimized . Extended outpatient commitment was also associated with fewer arrests of participants with a combined history of multiple rehospitalizations and previous arrests . The intervention was particularly effective among individuals with psychotic disorders . CONCLUSIONS Outpatient commitment can improve treatment outcomes when the court order is sustained and combined with relatively intensive community treatment . A court order alone can not substitute for effective treatment in improving outcomes BACKGROUND Violent behaviour among persons with severe mental illness ( SMI ) causes public concern and is associated with illness relapse , hospital recidivism and poor outcomes in community-based treatment . AIMS To test whether involuntary out-patient commitment ( OPC ) may help to reduce the incidence of violence among persons with SMI . METHOD One-year r and omised trial of the effectiveness of OPC in 262 subjects with psychotic or major mood disorders and a history of hospital recidivism . Involuntarily hospitalised subjects awaiting OPC were r and omly assigned to release or court-ordered treatment after discharge . Those with a recent history of serious assault remained under OPC until expiry of the court order ( up to 90 days ) ; then OPC orders were renewed at clinical /court discretion . Control subjects had no OPC . Four-monthly follow-up interviews with subject , case manager and collateral informant took place and service records were collected . RESULTS A significantly lower incidence of violent behaviour occurred in subjects with > or = 6 months ' OPC . Lowest risk of violence was associated with extended OPC combined with regular out-patient services , adherence to prescribed medications and no substance misuse . CONCLUSIONS OPC may significantly reduce risk of violent behaviour in persons with SMI , in part by improving adherence to medications while diminishing substance misuse BACKGROUND Community treatment orders ( CTOs ) have not been shown in r and omised trials to reduce readmission to hospital in patients with psychosis , but these trials have been short ( 11 - 12 months ) . We previously investigated the effect of CTOs on readmission rates over 12 months in a r and omised trial ( OCTET ) . Here , we present follow-up data for a cohort of individuals recruited to our original trial to examine the long-term effect of CTOs on readmissions and the risk of patients disengaging from mental health services temporarily or enduringly . METHODS For OCTET , an open-label , parallel , r and omised controlled trial , we recruited patients aged 18 - 65 years involuntarily admitted to mental health hospitals in 32 trusts in Engl and , with a diagnosis of psychosis and deemed suitable for CTOs by their clinicians . Between Nov 10 , 2008 , and Feb 22 , 2011 , we recruited and r and omly assigned 336 eligible patients ( 1:1 ) to be discharged on either a CTO ( n=167 ) or to voluntary status via Section 17 leave ( control group ; n=169 ) . For the analysis presented in this report , we assessed data at 36 months for 330 of these patients . We tested rates of readmission to hospital , time to first readmission , number of readmissions , and duration of readmission in patients assigned to CTO versus those assigned to control , and in all patients with CTO experience at any time in the 36 months versus those without . We also tested whether duration of CTO affected readmission outcomes in patients with CTO experience . We examined discontinuation ( ≥60 days between clinical contacts ) and disengagement from services ( no clinical contact for ≥90 days with no return to contact ) in the whole cohort . OCTET is registered with is rct n.com , number IS RCT N73110773 . FINDINGS We obtained data for 330 patients in the relevant period between Nov 10 , 2008 and Feb 22 , 2014 ( 36 months after the last patient was r and omly assigned to OCTET ) . We identified no difference between the r and omised groups in the numbers of patients readmitted ( 100 [ 61 % ] of 165 CTOs vs 113 [ 68 % ] of 165 controls ; relative risk 0·88 [ 95 % CI 0·75 - 1·03 ] ) , number of readmissions ( mean 2·4 readmissions [ SD 1·91 ] vs 2·2 [ 1·43 ] ; incident density ratio [ IDR ] 0·97 [ 95 % CI 0·76 - 1·24 ] ) , duration of readmissions ( median 117·5 days [ IQR 63 - 303 ] vs 139·5 days [ 63·0 - 309·5 ] ; IDR 0·84 [ 95 % CI 0·51 - 1·38 ] ) , or time to first readmission ( median 601·0 days [ 95 % CI 387·0 - 777·0 ] vs 420·0 days [ 352·0 - 548·0 ] ; hazard ratio [ HR ] 0·81 [ 95 % CI 0·62 - 1·06 ] ) . The CTO experience group had significantly more readmissions than the group without ( IDR 1·39 [ 95 % CI 1·07 - 1·79 ] ) and we noted no significant difference between groups in readmission rates , duration of readmission , or time to first readmission . We did not identify a linear relationship between readmission outcomes and duration of CTO . 19 ( 6 % ) patients disengaged from services ( 12 [ 7 % ] of 165 CTOs vs 7 [ 4 % ] of 165 controls ) . Longer duration of compulsion was associated with later disengagement ( HR 0·946 [ 95 % CI 0·90 - 0·99 , p=0·023 ) . 187 ( 57 % ) experienced no discontinuities , and we noted no significant difference between the CTO and control groups for time to disengagement or number of discontinuities . Levels of discontinuity were associated with compulsion ( IDR 0·973 [ 95 % CI 0·96 - 0·99 , p<0·0001 ] . We identified no effect of baseline characteristics on the associations between compulsion and disengagement . INTERPRETATION We identified no evidence that increased compulsion leads to improved readmission outcomes or to disengagement from services in patients with psychosis over 36 months . The level of persisting clinical follow-up was much higher than expected , irrespective of CTO status , and could partly account for the absence of CTO effect . The findings from our 36-month follow-up support our original findings that CTOs do not provide patient benefits , and the continued high level of their use should be review ed . FUNDING National Institute for Health Research BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials This study took preliminary steps to explore the relationship between involuntary outpatient commitment ( OPC ) and the risk of homelessness among individuals with severe mental disorders . Involuntarily hospitalized patients were r and omly assigned to be released or maintained under OPC following hospital discharge . Multivariate analyses demonstrated that involuntary OPC was associated with a significant decrease in the risk of homelessness during the first 4 months following hospital discharge for participants with severe functional impairment at baseline . OPC did not appear to affect risk of homelessness among participants with mild-to-moderate functional impairment . Co-occurring substance abuse , treatment nonadherence , and outpatient services intensity were found to be strongly associated with episodes of homelessness . This study suggests that involuntary OPC may provide a short-term reduction in the risk of homelessness among a subgroup of treatment-reluctant individuals with severe mental disorders combined with severe functional impairment Objective : This study examined the effectiveness of community treatment orders ( CTOs ) used in the treatment of patients with schizophrenia . The hypotheses were that CTOs enhance outcome for patients whose mental health would otherwise be compromised by poor adherence with treatment and that CTOs would enable this when either oral or depot antipsychotic medication was prescribed . Method : This was a naturalistic study using a retrospective mirror-image design . The sample consisted of patients with schizophrenia ( n = 94 ) who were treated on a CTO between November 1996 and October 1999 . Two subgroups were defined : patients treated with oral antipsychotic medication ( n = 31 ) , and patients treated with depot medication ( n = 63 ) . Data were gathered via file review using a question naire . Results : For the whole sample and both subgroups the findings included significant increased number of service contacts , decreased number of admissions and decreased length of inpatient stay . For the total sample numbers of crisis team referrals and other episodes of relapse were significantly decreased . For the subgroup on depot medication there was a non-significant trend towards fewer crisis team referrals and a significant decrease in other episodes of relapse . There were no significant differences for the oral subgroup in crisis team referrals or other episodes of relapse . Conclusions : This study provides further evidence that CTOs may be effective in improving the outcome for selected persons with schizophrenia and some evidence that they may enhance the outcome for selected patients with schizophrenia on oral antipsychotic medication Studies of involuntary outpatient commitment ( OPC ) among persons with severe mental illness have concluded that OPC is only effective in improving treatment outcomes when it is sustained for 6 months or longer and is combined with frequent outpatient services . This article explores factors that influence the delivery of outpatient services to subjects in a r and omized trial of OPC and finds 2 general patterns . Outpatient visits were more frequent among all subjects with apparent clinical need , regardless of study assignment , and among subjects whose OPC was sustained beyond an initial court order . These results suggest that , in practice , sustained OPC represents a consensual agreement between clinicians and the court to more intensively address the complex needs of persons with severe and persistent mental illness |
11,843 | 15,528,776 | Despite the heterogeneity in trial design , the results of this review suggest that nutritional supplements may improve the cognitive functioning of elderly persons and do no harm . | BACKGROUND The effectiveness of nutritional supplementation in improving cognitive functioning is evaluated in elderly people . | Based on research demonstrating associations between folate , B-12 and B-6 vitamins and cognition and mood , we investigated the effects of short-term supplementation in 211 healthy younger , middle-aged and older women who took either 750 microg of folate , 15 microg of vitamin B-12 , 75 mg of vitamin B-6 or a placebo daily for 35 d. In addition , we examined associations between dietary intake of these vitamins and cognition and mood . Usual dietary intake status was estimated using a retrospective , self-report , quantified food frequency question naire . Participants completed alternate forms of st and ardized tests of cognitive processing re sources , memory , executive function , verbal ability and self-report mood measures before and after supplementation . Supplementation had a significant positive effect on some measures of memory performance only , and no effect on mood . Dietary intake status was associated with speed of processing , recall and recognition and verbal ability BACKGROUND Frail elders are at risk of suboptimal micronutrient status , functional decline , and neurologic disorders . The influence of oral multimicronutrients in physiologic doses and of moderately intense physical exercise on homocysteine ( Hcy ) , methylmalonic acid ( MMA ) , and neurologic functioning have not yet been investigated . OBJECTIVE Our goal was to determine the effects of enriched foods and exercise on blood vitamins , Hcy , MMA , and neuropsychological functioning in the frail . DESIGN A 17-wk r and omized controlled intervention trial was used to study 1 ) enriched foods plus a social program , 2 ) regular foods plus exercise , 3 ) enriched foods plus exercise , and 4 ) regular foods plus a social program . Enriched foods contained multiple micronutrients ( 25 - 100 % of the Dutch recommended dietary allowances ) ; exercises focused on strength , coordination , flexibility , and endurance . Vitamin ( cobalamin , red blood cell folate , and pyridoxal 5'-phosphate ) , Hcy , and MMA concentrations were measured and 2 neuropsychological tests were conducted . RESULTS Vitamin concentrations were higher in the supplemented groups than in the unsupplemented groups ( P < 0.001 ; total n = 130 ) . Compared with baseline , cobalamin in the supplemented groups was increased by 22 % , plasma folate by 101 % , red blood cell folate by 87 % , and pyridoxal 5'-phosphate by 68 % . Concentrations in the unsupplemented groups changed by -2 % , -6 % , 1 % , and -13 % , respectively . Hcy decreased by 25 % and MMA by 30 % in the supplemented groups , compared with a small increase in Hcy ( 2 % ) and decrease in MMA ( 9 % ) in the unsupplemented groups . Exercise did not significantly affect vitamin , Hcy , or MMA concentrations . No significant effect of either intervention was observed on the neuropsychological tests . CONCLUSIONS The decrease in Hcy and MMA in frail elders confirms a sub clinical metabolic deficiency state . Enriched foods containing physiologic amounts of micronutrients have a beneficial effect on these metabolites . No effects of B vitamins on mental health were identified Paulinia cupana ( guarana ) is a Brazilian plant given great prestige in popular medicine , for example as being a potent stimulator of brain functions . The authors assessed the effects of the long-term administration of guarana on the cognition of normal , elderly volunteers . Forty-five volunteers were studied , with a r and om distribution in three experimental groups : placebo ( n = 15 ) , caffeine ( n = 15 ) , and guarana ( n = 15 ) , in a double-blind study . There were no significant cognitive alterations in these volunteers Objective : To determine the efficacy of acetyl-l-carnitine ( ALCAR ) on the rate of decline in early-onset AD patients . Methods : A 1-year , multicenter , double-blind , placebo-controlled , r and omized trial was conducted . Subjects were 45 to 65 years old , with a diagnosis of probable AD according to National Institute of Neurological Communicative Disorders – Alzheimer ’s Disease and Related Disorders Association criteria and had a Mini-Mental State Examination ( MMSE ) score between 12 and 26 . They were treated with ALCAR ( 1 g tid ) or placebo . Primary outcome measures were the Alzheimer ’s Disease Assessment Scale – Cognitive Component and the Clinical Dementia Rating Scale . Secondary measures included the ADAS Non-Cognitive Subscale , the MMSE , an Activities of Daily Living Scale ( ADL ) , and a Clinician-Based Impression of Change ( CIBIC ) . Results : Two-hundred twenty-nine patients were enrolled and r and omized to drug treatment , with 117 taking placebo and 112 taking ALCAR . There were no significant differences between the two groups at baseline . For the primary outcome measures , there were no significant differences between the treatment groups on the change from baseline to endpoint in the intent-to-treat analysis . In the completer sample only , there was less deterioration in the MMSE for the ALCAR-treated subjects . There was no difference in rate of decline on the CIBIC and the ADL scale . There were no significant differences in the incidence of adverse events by treatment arm . Conclusion : Overall , in a prospect ively performed study in young-onset AD patients , ALCAR failed to slow decline . Less decline was seen on the MMSE in the completer sample only , with the difference being mediated by reducing decline in attention . A combination of ALCAR and a cholinesterase inhibitor should be tested for additivity OBJECTIVES To assess the longitudinal effects of acety-L-carnitine ( ALC ) on patients diagnosed with Alzheimer 's disease . DESIGN Longitudinal , double-blind , parallel-group , placebo-controlled . SETTING Twenty-four outpatient sites across the United States . PARTICIPANTS A total of 334 subjects diagnosed with probable Alzheimer 's disease by NINCDS-ADRDA criteria . These data were originally reported by Thal and colleagues ( 1996 ) . MEASUREMENTS Cognitive subscale of the Alzheimer Disease Assessment Scale ( ADAS ) given every 3 months for 1 year . RESULTS The average rate of change was estimated using the trilinear approach , which allows for periods of both change and stability . Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS ( 0.68 points/month ) . However , a multiple regression analysis revealed a statistically significant Age x Drug interaction characterized by younger subjects benefiting more from ALC , significant , cutpoint for ALC benefit was 61 years of age . CONCLUSIONS ALC slows the progression of Alzheimer 's disease in younger subjects , and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials BACKGROUND There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer 's disease . METHODS We conducted a double-blind , placebo-controlled , r and omized , multicenter trial in patients with Alzheimer 's disease of moderate severity . A total of 341 patients received the selective monoamine oxidase inhibitor selegiline ( 10 mg a day ) , alpha-tocopherol ( vitamin E , 2000 IU a day ) , both selegiline and alpha-tocopherol , or placebo for two years . The primary outcome was the time to the occurrence of any of the following : death , institutionalization , loss of the ability to perform basic activities of daily living , or severe dementia ( defined as a Clinical Dementia Rating of 3 ) . RESULTS Despite r and om assignment , the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups , and this variable was highly predictive of the primary outcome ( P<0.001 ) . In the unadjusted analyses , there was no statistically significant difference in the outcomes among the four groups . In analyses that included the base-line score on the Mini-Mental State Examination as a covariate , there were significant delays in the time to the primary outcome for the patients treated with selegiline ( median time , 655 days ; P=0.012 ) , alpha-tocopherol ( 670 days , P=0.001 ) or combination therapy ( 585 days , P=0.049 ) , as compared with the placebo group ( 440 days ) . CONCLUSIONS In patients with moderately severe impairment from Alzheimer 's disease , treatment with selegiline or alpha-tocopherol slows the progression of disease A r and omized , double-blind , placebo-controlled , parallel-group clinical trial was carried out to compare 24-week periods of treatment with 1 g acetyl-l-carnitine twice daily and placebo in the treatment of patients with dementia of the Alzheimer type . A total of 36 patients entered the trial , of whom 20 patients ( 7 active , 13 placebo ) completed the full 24 weeks . Whilst several of the efficacy indices showed little change in either group during the trial , there was an apparent trend for more improvement in the acetyl-l-carnitine group in relation to the Names Learning Test and a computerized Digit Recall Test , both related to aspects of short-term memory . Similarly , there was a trend for reaction time in the computerized classification test to show less deterioration in the active treatment group . Changes within groups , and changes between groups , failed to reach statistical significance , at least partially because of the small number of patients available for analysis . Two indices of overall therapeutic benefit showed a trend for less deterioration in the active-treatment group than in the placebo group . Nausea and /or vomiting occurred in 5 patients in the acetyl-l-carnitine group . Laboratory tests revealed no signs of drug toxicity . The results suggest that acetyl-l-carnitine may have a beneficial effect on some clinical features of Alzheimer-type dementia , particularly those related to short-term memory 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 In two double-blind , placebo-controlled clinical studies of the nootropic compound acetyl-L-carnitine on the electroencephalogram ( EEG ) and impaired brain functions of elderly out patients with mild to moderate cognitive decline of the organic brain syndrome , statistically significant effects could be detected after eight weeks ( on the EEG ) , and after 12 weeks of treatment ( on the physician 's clinical global impression and the patient-rated level of activities of daily living ) . Side-effects of acetyl-L-carnitine were generally minor and overall rare . Longer treatment periods and further specifications with regard to the aetiopathology and degree of cognitive impairment are recommended for further clinical studies of this promising compound Acetyl levocarnitine hydrochloride has been reported to retard dementia in patients with Alzheimer 's disease . In a double-blind , parallel design , placebo-controlled pilot study of 30 mild to moderately demented patients with probable Alzheimer 's disease , tests of memory , attention , language , visuospatial , and constructional abilities were administered , and the level of acetyl levocarnitine was measured in the cerebrospinal fluid . Patients were then r and omly assigned to receive acetyl levocarnitine hydrochloride ( 2.5 g/d for 3 months followed by 3 g/d for 3 months ) or placebo . After 6 months , the acetyl levocarnitine group demonstrated significantly less deterioration in timed cancellation tasks and Digit Span ( forward ) and a trend toward less deterioration in a timed verbal fluency task . No differences were found in any other neuropsychological test results . A subgroup with the lowest baseline scores , receiving acetyl levocarnitine , had significantly less deterioration on the verbal memory test and a significant increase in cerebrospinal fluid acetyl levocarnitine levels compared with those receiving placebo . These results suggest that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer 's disease and stress the need for a larger study of this drug This study evaluates the effects of vitamin B-6 supplementation ( 20 mg pyridoxine HCL daily for 3 months ) on mood and performance in 38 self-supporting healthy men , aged between 70–79 years . Effects were compared with 38 controls who received placebo and were matched for age , plasma pyridoxal-5′-phosphate ( PLP ) concentration and intelligence score . Before and after drug intervention vitamin B-6 status was determined , and mood and performance were measured by means of a computerized testing system . In addition , the phasic pupil response was measured in order to assess mental effort . Positive effects of vitamin B-6 supplementation were only found with respect to memory , especially concerning long-term memory . In view of the finding that mental performance improvement and Δ PLP values were most strongly correlated within an intermediate range of Δ PLP , it is suggested that cognitive effects are primarily associated with a certain range of vitamin B-6 status increment . The general conclusion is that vitamin B-6 supplementation improves storage of information modestly but significantly A 1-year , double-blind , placebo-controlled , r and omized , parallel-group study compared the efficacy and safety of acetyl-L-carnitine hydrochloride ( ALCAR ) with placebo in patients with probable Alzheimer 's disease ( AD ) . Subjects with mild to moderate probable AD , aged 50 or older , were treated with 3 g/day of ALCAR or placebo ( 1 g tid ) for 12 months . Four hundred thirty-one patients entered the study , and 83 % completed 1 year of treatment . The Alzheimer 's Disease Assessment Scale cognitive component and the Clinical Dementia Rating Scale were the primary outcome measures .Overall , both ALCAR- and placebo-treated patients declined at the same rate on all primary and most secondary measures during the trial . In a sub analysis by age that compared early-onset patients ( aged 65 years or younger at study entry ) with late-onset patients ( older than 66 at study entry ) , we found a trend for early-onset patients on ALCAR to decline more slowly than early-onset AD patients on placebo on both primary endpoints . In addition , early-onset patients tended to decline more rapidly than older patients in the placebo groups . Conversely , late-onset AD patients on ALCAR tended to progress more rapidly than similarly treated early-onset patients . The drug was very well tolerated during the trial . The study suggests that a subgroup of AD patients aged 65 or younger may benefit from treatment with ALCAR whereas older individuals might do more poorly . However , these preliminary findings are based on post hoc analyses . A prospect i ve trial of ALCAR in younger patients is underway to test the hypothesis that young , rapidly progressing subjects will benefit from ALCAR treatment . NEUROLOGY 1996;47 : 705 - Because a previous short-term study demonstrated a statistically significant , but not clinical ly important , improvement in cognitive test scores during thiamine treatment in patients with dementia of the Alzheimer 's type , a 12-month , double-blind , parallel-group study was conducted to examine whether long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer 's type . Fifteen subjects were enrolled and 10 completed the 1-year study . Data are available for two additional subjects through the first 9 months of study . No significant differences were found between the placebo and thiamine groups at any point during the study . In both groups , overall means for the Mini-Mental State Examination , verbal learning , and naming scores decreased significantly over the 12-month study period . These results do not support the hypothesis that long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer 's type A double-blind cross-over study was carried out on the clinical effectiveness of acetyl-L-carnitine on 12 elderly subjects undergoing rehabilitation for acute cerebral circulatory insufficiency compared with a placebo . Significant differences between the drug and placebo were found in memory , number and word tests and in the responses to simple stimuli and the performance of the maze test . There were no side-effects to the drug OBJECTIVES To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia ( PA ) . DESIGN R and omized , double-blind , placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month . SETTING Two geriatric hospitals in the North Western Health Care Network , Melbourne , Australia . PARTICIPANTS Thirty-one in patients with serum vitamin B12 levels between 100 and 150 pmol/L , without PA , other malabsorption disorders , or progressive neurological or terminal illness . The mean age was 81.4 years . INTERVENTION After informed consent , a medical and drug history was taken and the Mini-Mental State Examination ( MMSE ) completed . A dietitian made assessment of oral cobalamin intake . Blood was taken for serum vitamin B12 , serum and red cell folate assay , full blood examination , fasting serum gastrin , parietal and intrinsic factor antibodies , fasting serum homocysteine , and creatinine . Patients were then r and omized to receive 10 microg oral cyanocobalamin , 50 microg oral cyanocobalamin , or placebo treatment for 1 month , after which the investigations and clinical examinations were repeated . MEASUREMENTS Percentage change in the level of vitamin B12 , homocysteine , folate , and red cell parameters and absolute changes in MMSE were calculated and compared between groups . The groups were compared on the number of responders who improved their level of B12 by 20 % . Chi-square calculations on changes in serum vitamin B12 concentration were also performed . RESULTS Mean serum vitamin B12 + /- st and ard deviation improved by 51.7 + /- 47.1 % in the 50-microg group , 40.2 + /- 34.4 % in the 10-microg group , and 11.7 + /- 24.5 % in the placebo group . The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group ( P=.044 ) . The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group ( P=.186 ) . Eight of 10 subjects in each treatment group were classified as responders , compared with two of 11 in the placebo group ( P=.004 ) . Homocysteine levels fell in patients receiving cyanocobalamin , but this fall failed to reach statistical significance . There were no significant changes in the other parameters measured . CONCLUSION Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12 . This result has implication s for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12 The aim of this study was to evaluate the efficacy and tolerability of L-acetylcarnitine therapy in the senile brain . The trial was conducted on a double-blind basis , with a total of 40 patients divided into two groups of 20 , treated for 40 days with L-acetylcarnitine and placebo , respectively -- the therapeutic regimen being two 500 mg tablets t.i.d . Mental parameters of the senile brain were assessed at 0 , 20 and 40 days of treatment , while basal and final values were recorded for a number of laboratory tests . Statistical analysis of results confirmed that short-term , intensive L-acetylcarnitine treatment can determine a significant improvement of the main mental parameters of the senile brain , without incidence of significant side effects Objective : To study the relationships between dietary macronutrient intakes and age-related changes in cognitive functions . Methods : We investigated these associations in the prevalence survey ( 1992 through 1993 ) of the Italian Longitudinal Study on Aging ( ILSA ) . The population -based sample of 5,632 subjects of the ILSA , age 65 to 84 years , was identified from the electoral rolls of eight Italian municipalities . In this study , st and ardized test batteries assessing global cognitive functions ( Mini-Mental State Examination [ MMSE ] ) , selective attention ( Digit Cancellation Test [ DCT ] ) , and episodic memory ( Babcock Story Recall Test ) , and a semi-quantitative food frequency question naire evaluating macronutrient energy intakes , were performed on 278 nondemented elderly subjects from the r and omized cohort of Casamassima , Bari ( n = 704 ) . Results : There was an inverse relationship between monounsaturated fatty acids ( MUFAs ) energy intake and cognitive decline ( MMSE < 24 ) . The effect of education on the odds of having a MMSE score < 24 decreased exponentially with the increase of MUFA intakes ( over 2,400 kJ ; odds ratio , 0.69 ) . Moreover , a significant inverse association was observed between MUFA intakes and DCT score ( odds ratio , 0.99 ) . No association was found between nutritional variables and episodic memory . Conclusions : In an elderly population of Southern Italy with a typical Mediterranean diet , high MUFA intakes appeared to be protective against age-related cognitive decline . Prospect i ve clinical trials are needed to evaluate the impact of specific dietary macronutrient intakes on the age-related changes of cognitive functions Thiamine is important not only in the metabolism of acetylcholine but also in its release from the presynaptic neuron . Pathologic , clinical , and biochemical data suggest that thiamine deficiency is detrimental to the cholinergic system and that thiamine-dependent enzymes may be altered in Alzheimer 's disease . Two previous studies reported contradictory results in patients with dementia of Alzheimer 's type treated with 3 g/day of thiamine . In the present study , we examined the effects of 3 to 8 g/day thiamine administered orally . Our results suggest that thiamine at these pharmacologic dosages may have a mild beneficial effect in dementia of Alzheimer 's type . The mechanism of the observed effect is unknown , but the findings warrant further investigation , not only for their therapeutic implication s but for their possible etiologic clues . In addition , the results suggest long-term carry-over effects that should be considered in the design of future studies In a double-blind , placebo-controlled , parallel-group , r and omized clinical trial , we studied the efficacy of long-term ( 1-year ) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer 's disease . We employed 14 outcome measures to assess functional and cognitive impairment . After 1 year , both the treated and placebo groups worsened , but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures , reaching statistical significance for the Blessed Dementia Scale , logical intelligence , ideomotor and buccofacial apraxia , and selective attention . Adjusting for initial scores with analysis of covariance , the treated group showed better scores on all outcome measures , reaching statistical significance for the Blessed Dementia Scale , logical intelligence , verbal critical abilities , long-term verbal memory , and selective attention . The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample . Reported adverse events were relatively mild , and there was no significant difference between the treated and placebo groups either in incidence or severity It has been hypothesized that acetyl-L-carnitine has a cholinomimetic action . It is for this reason that it has been used in the therapy of Alzheimer 's type senile dementia impairment . In the present controlled double-blind study the authors followed two r and omized homogeneous groups of both sexes of 30 patients each , aged over 65 years and suffering from mild mental impairment . One group of patients underwent therapy with acetyl-L-carnitine , 2 g/day for three months , while the other group was treated with a placebo . The statistical evaluation of the results was carried-out using non-parametric methods ( Friedman-Nemenyi two-way ANOVA ) . It was possible to affirm that the acetyl-L-carnitine treated patients showed statistically significant improvement in the behavioural scales , in the memory tests , in the attention barrage test and in the Verbal Fluency test . These satisfactory results confirm the therapeutic importance of acetyl-L-carnitine in the treatment of elderly patients with mental impairment , which could be related principally to acetylcholine defects 1 . A double-blind controlled crossover trial of 6 gm of inositol daily vs glucose for one month each was carried out in 11 Alzheimer patients . 2 . Overall CAMCOG scores showed a trend for greater improvement with inositol that was not significant . 3 . Language and orientation improved significantly more on inositol than on placebo . There were no serious side effects . 4 . Higher doses of inositol should be studied in Alzheimer 's Disease for longer periods The aim of this study was to assess the effect of vitamin and /or glucose energy supplementation in elderly medical patients on an intention-to-treat basis . One hundred and six elderly medical in- patients were entered into a double-bind placebo-controlled factorial trial of glucose energy and vitamin supplementation . Supplementation was given for 1 month . This trial was design ed to detect a > 2 kg increase in weight and > 3 g/l increase in serum albumin between active and placebo supplementation in 100 patients with 90 % power ( p < 0.05 ) . Other outcome measures included changes in Barthel activities of daily living , length of stay , and mental test score ( MTS ) . No interaction between vitamin and glucose supplementation was demonstrated . Active energy supplementation with glucose alone was associated with a + 0.6 kg change in weight and + 0.7 g/l change in albumin [ 95 % confidence interval ( CI ) -0.8 , + 2.0 and -1.3 , + 2.8 , respectively ] . The respective changes for active vitamin supplementation were -0.6 kg for weight and + 0.5 g/l for albumin ( 95 % CI -2.1 , + 0.8 and -1.5 , + 2.6 , respectively ) . There were no significant differences in mental test score , Barthel score , or length of stay between the two groups . Compliance with the glucose energy supplementation was poor with only one-third of patients consuming more than 50 % of the offered drink . We conclude that the giving of glucose alone and /or vitamin supplementation in elderly patient is of no benefit on an intention-to-treat basis OBJECTIVE To examine the effects of cobalamin repletion on cognition in elderly subjects with low serum cobalamin and evidence of cognitive dysfunction . DESIGN Time series data collected in an open trial of parenteral cobalamin therapy . SETTING S Outpatient geriatric assessment centers , inpatient geropsychiatry unit , and tertiary care university hospital . PARTICIPANTS Twenty-two subjects with low serum cobalamin ( less than 150 pmol/L ) and evidence of cognitive dysfunction were entered consecutively over an 8-month period of time . Eighteen subjects completed the study . INTERVENTIONS Subjects received 1000 micrograms of cyanocobalamin intramuscularly daily for 1 week , then weekly for 1 month , then monthly thereafter for a minimum of six months . OUTPATIENT MEASURE : The Mattis Dementia Rating Scale ( DRS ) was administered both before and at least 6 months after full cobalamin replacement therapy . The hypothesis that cognitive improvement was dependent on the duration of cognitive symptoms was formulated a posteriori . RESULTS After a minimum of 6 months of cobalamin therapy , 11 of 18 patients showed cognitive improvement . There was a striking correlation between duration of cognitive symptoms and response to therapy . Patients symptomatic for less than 12 months gained an average of twenty points on the DRS ( paired t test P = 0.0076 ) , whereas patients symptomatic greater than 12 months lost an average of three points ( paired t test P = .34 ) . Two patients symptomatic for only 3 months normalized their DRS scores , gaining 31 and 28 points , respectively . CONCLUSION There may be a time-limited window of opportunity for effective intervention in patients with cognitive dysfunction and low serum cobalamin |
11,844 | 22,076,477 | Most models yielded relatively poor discrimination in both internal and external validation .
This poor discriminatory accuracy of existing models might be because of a lack of knowledge about risk factors , heterogeneous subtypes of breast cancer , and different distributions of risk factors across population s. In addition the concordance statistic itself is insensitive to measure the improvement of discrimination . | The number of risk prediction models has been increasingly developed , for estimating about breast cancer in individual women .
However , those model performances are question able .
We therefore have conducted a study with the aim to systematic ally review previous risk prediction models .
The results from this review help to identify the most reliable model and indicate the strengths and weaknesses of each model for guiding future model development . | Introduction A number of breast cancer risk prediction models have been developed to provide insight into a woman 's individual breast cancer risk . Although circulating levels of estradiol in postmenopausal women predict subsequent breast cancer risk , whether the addition of estradiol levels adds significantly to a model 's predictive power has not previously been evaluated . Methods Using linear regression , the authors developed an imputed estradiol score using measured estradiol levels ( the outcome ) and both case status and risk factor data ( for example , body mass index ) from a nested case-control study conducted within a large prospect i ve cohort study and used multiple imputation methods to develop an overall risk model including both risk factor data from the main cohort and estradiol levels from the nested case-control study . Results The authors evaluated the addition of imputed estradiol level to the previously published Rosner and Colditz log-incidence model for breast cancer risk prediction within the larger Nurses ' Health Study cohort . The follow-up was from 1980 to 2000 ; during this time , 1,559 invasive estrogen receptor-positive breast cancer cases were confirmed . The addition of imputed estradiol levels significantly improved risk prediction ; the age-specific concordance statistic increased from 0.635 ± 0.007 to 0.645 ± 0.007 ( P < 0.001 ) after the addition of imputed estradiol . Conclusion Circulating estradiol levels in postmenopausal women appear to add to other lifestyle factors in predicting a woman 's individual risk of breast cancer Key Summary Points Risk prediction models are statistical models used to predict the probability of an outcome on the basis of the values of 1 or more risk factors ( markers ) . The accuracy of the model 's predictions is typically summarized with statistics that describe the model 's discrimination and calibration . Risk stratification tables are a more informative way to assess and compare the models . The tables illustrate the distribution of predictions across risk categories . That illustration allows users to assess 3 key measures of the models ' value for guiding medical decisions : the models ' calibration , ability to stratify people into clinical ly relevant risk categories , and accuracy at classifying patients into higher- and lower-risk categories . This information is contained in the margins of the risk stratification table rather than in its cells . The tables should only be used to compare risk prediction models when one of the models contains all of the markers that are contained in the other ( nested models ) ; they should not be used to compare models with different sets of markers ( nonnested models ) . The table predictions require corrections when casecontrol data are used . The recent epidemiologic and clinical literature is filled with studies evaluating statistical models that predict risk for disease or some other adverse event ( 15 ) . Because risk prediction models are intended to help patients and clinicians make decisions , evaluation of these models requires methods that differ from those used to assess models describing disease etiology . This is because the characteristics of the models are less important than their value for guiding decisions . Cook and colleagues ( 1 , 6 ) recently proposed a new approach to evaluate risk prediction models : a risk stratification table . This methodology appropriately focuses on the key purpose of a risk prediction model , which is to classify individuals into clinical ly relevant risk categories , and it has therefore been widely adopted in the literature ( 24 ) . We examine the risk stratification approach in detail in this article , identifying the relevant information that can be abstract ed from a risk stratification table and caution ing against misuses of the method that frequently occur in practice . We use a recently published study of a breast cancer risk prediction model by Tice and colleagues ( 2 ) to illustrate the concepts . Background A risk prediction marker is any measure that is used to predict a person 's risk for an event . It may be a quantitative measure , such as high-density lipoprotein cholesterol level , or a qualitative measure , such as family history of disease . Risk predictors are also risk factors , in the sense that they will necessarily be strongly associated with the risk for disease . But a large , significant association does not assure that the marker has value in predicting risk for many people . A risk prediction model is a statistical model that combines information from several markers . Common types include logistic regression models , Cox proportional hazard models , and classification trees . Each type of model produces a predicted risk for each person by using information in the model . Consider , for example , a model predicting breast cancer risk that includes age as the only predictor . The result ing risk prediction for a woman of a given age is simply the proportion of women her age who develop breast cancer . The woman 's predicted risk will change if more information is included in the model . For instance , if family history information is added , her predicted risk will be the proportion of women her age and with her family history who develop breast cancer . The purpose of a risk prediction model is to accurately stratify individuals into clinical ly relevant risk categories . This risk information can be used to guide clinical or policy decisions , for example , about preventive interventions for persons or disease screening for sub population s identified as high risk , or to select persons for inclusion in clinical trials . The value of a risk prediction model for guiding these kinds of decisions can be judged by the extent to which the risk calculated from the model reflects the fraction of persons in the population with actual events ( its calibration ) ; the proportions in which the population is stratified into clinical ly relevant risk categories ( its stratification capacity ) ; and the extent to which participants with events are assigned to high-risk categories and those without events are assigned to low-risk categories ( its classification accuracy ) . Risk prediction models are commonly evaluated by using the receiver-operating characteristic ( ROC ) curve ( 4 , 7 ) , which is a st and ard tool for evaluating the discriminatory accuracy of diagnostic or screening markers . This curve shows the true-positive rate plotted against the false-positive rate for rules that classify persons by using risk thresholds that vary over allpossible values . Receiver-operating characteristic curves are generally not helpful for evaluating risk prediction models because they do not provide information about the actual risks that the models predict or about the proportion of participants who have high or low risk values . Moreover , when comparing ROC curves for 2 risk prediction models , the models are aligned according to their false-positive rates ( that is , different risk thresholds are applied to the 2 models to achieve the same false-positive rate ) . This is clearly inappropriate . In addition , the area under the ROC curve or c-statistic , a commonly reported summary measure that can be interpreted as the probability that the predicted risk for a participant with an event is higher than that for a participant without an event , has little direct clinical relevance . Clinicians are never asked to compare risks for a pair of patients one who will eventually have the event and one who will not . Neither the ROC curve nor the c-statistic relates to the practical task of predicting risks for clinical decision making . Cook and colleagues ( 1 , 6 ) propose using risk stratification tables to evaluate the incremental value of a new marker , or the benefit of adding a new marker ( for example , C-reactive protein ) , to an established set of risk predictors ( for example , Framingham risk predictors , such as age , diabetes , cholesterol level , smoking , and low-density lipoprotein cholesterol levels ) . In these stratification tables , risks calculated from models with and without the new marker are cross-tabulated . This approach represents a substantial improvement over the use of ROC methodology because it displays the risks calculated by use of the model and the proportions of individuals in the population who are stratified into the risk groups . We will provide an example of this approach and show how information about model calibration , stratification capacity , and classification accuracy can be derived from a risk stratification table and used to assess the added value of a marker for clinical and health care policy decisions . Example Tice and colleagues ( 2 ) published a study that builds and evaluates a model for predicting breast cancer risk by using data from 1095484 women in a prospect i ve cohort and incidence data from the Surveillance , Epidemiology , and End Results data base . Age , race or ethnicity , family history , and history of breast biopsy were used to model risk with a Cox proportional hazard model . The study focused on the benefit of adding breast density information to the model . The hazard ratio for breast density in the multivariate model ( extremely dense vs. almost entirely fat ) was estimated as 4.2 for women younger than age 65 years and 2.2 for women age 65 years or older . This suggests that breast density is strongly associated with disease riskthat is , that breast cancer rates are higher among women with higher breast density . However , it does not describe the value of breast density for helping women make informed clinical decisions , which requires knowledge of the frequency distribution of breast density in the population . To evaluate the added value of breast density , Tice and colleagues defined 5-year breast cancer risk categories as low ( # # lt##1 % ) , low to intermediate ( 1 % to 1.66 % ) , intermediate to high ( 1.67 % to 2.5 % ) , and high ( # # gt##2.5 % ) . The 1.67 % cutoff for intermediate risk was presumably chosen on the basis of recommendations by the American Society of Clinical Oncology ( 8) and the Canadian Task Force on Preventive Health Care ( 9 ) to counsel women with 5-year risks greater than this threshold about considering tamoxifen for breast cancer prevention . Tice and colleagues used a risk stratification table ( Table 1 ) to compare risk prediction models with and without breast density . Table 1 . Five-Year Risks for Breast Cancer as Predicted by Models That Do and Do Not Include Breast Density Calibration Assessing model calibration is an important first step in evaluating any risk prediction model . Good calibration is essential ; it means that the model-predicted probability of an event for a person with specified predictor values is the same as or very close to the proportion of all persons in the population with those same predictor values who experience the event ( 10 ) . With many predictors , and especially with continuous predictors , we can not evaluate calibration at each possible predictor value because there are too few participants with exactly those values . Instead , the st and ard approach is to place persons within categories of predicted risk and to compare the category values with the observed event rates for participants in each category . The calibration of the risk prediction models for breast cancer can be assessed by comparing the proportions of events in the margins of Table 1 with the corresponding row and column labels . For the model without breast density , the proportions of observed events within each risk category are in the far-right Total column and they generally agree Objectives To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk , in whom specialist referral might be indicated . Design Prospect i ve multicentre cohort . Setting Five centres in Auckl and , New Zeal and ; Adelaide , Australia ; Manchester and London , United Kingdom ; and Cork , Republic of Irel and . Participants 3572 “ healthy ” nulliparous women with a singleton pregnancy from a large international study ; data on pregnancy outcome were available for 3529 ( 99 % ) . Main outcome measure Pre-eclampsia defined as ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg , or both , on at least two occasions four hours apart after 20 weeks ’ gestation but before the onset of labour , or postpartum , with either proteinuria or any multisystem complication . Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37 + 0 weeks ’ gestation . In the stepwise logistic regression the comparison group was women without pre-eclampsia . Results Of the 3529 women , 186 ( 5.3 % ) developed pre-eclampsia , including 47 ( 1.3 % ) with preterm pre-eclampsia . Clinical risk factors at 14 - 16 weeks ’ gestation were age , mean arterial blood pressure , body mass index ( BMI ) , family history of pre-eclampsia , family history of coronary heart disease , maternal birth weight , and vaginal bleeding for at least five days . Factors associated with reduced risk were a previous single miscarriage with the same partner , taking at least 12 months to conceive , high intake of fruit , cigarette smoking , and alcohol use in the first trimester . The area under the receiver operating characteristics curve ( AUC ) , under internal validation , was 0.71 . Addition of uterine artery Doppler indices did not improve performance ( internal validation AUC 0.71 ) . A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15 % or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors . Nine per cent of nulliparous women would be referred for a specialist opinion , of whom 21 % would develop pre-eclampsia . The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with st and ard care was 5.5 and 12.2 , respectively . Conclusions The ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other population s. If vali date d , it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added . Trial registration ACTRN12607000551493 The analytical effect of the number of events per variable ( EPV ) in a proportional hazards regression analysis was evaluated using Monte Carlo simulation techniques for data from a r and omized trial containing 673 patients and 252 deaths , in which seven predictor variables had an original significance level of p < 0.10 . The 252 deaths and 7 variables correspond to 36 events per variable analyzed in the full data set . Five hundred simulated analyses were conducted for these seven variables at EPVs of 2 , 5 , 10 , 15 , 20 , and 25 . For each simulation , a r and om exponential survival time was generated for each of the 673 patients , and the simulated results were compared with their original counterparts . As EPV decreased , the regression coefficients became more biased relative to the true value ; the 90 % confidence limits about the simulated values did not have a coverage of 90 % for the original value ; large sample properties did not hold for variance estimates from the proportional hazards model , and the Z statistics used to test the significance of the regression coefficients lost validity under the null hypothesis . Although a single boundary level for avoiding problems is not easy to choose , the value of EPV = 10 seems most prudent . Below this value for EPV , the results of proportional hazards regression analyses should be interpreted with caution because the statistical model may not be valid The Gail model is considered the best available means for estimating risk of breast cancer development , but it has not yet been applied systematic ally and vali date d in Turkish female population . This study was design ed to evaluate the performance of the Gail model for Turkish female population . Additionally duration of breastfeeding was examined as a possible risk factor . Our analysis included 650 patients with invasive breast carcinoma ( group 1 ) and 640 women with negative results who had undergone a screening mammography on visiting a mammary care unit ( group 2 ) . Two groups were compared with regard to individual risk factors included in the Gail model and also duration of breastfeeding . The Gail model was used to predict 5-year risk for each woman . Age and first live birth ≥30 years were associated with an increased relative risk for breast cancer development . Age at menarche , previous breast biopsy , atypical hyperplasia , and number of first degree relatives with breast cancer were found to be non-significant . The Gail model showed 13.3 % sensitivity and 92 % specificity in estimating the risk of breast cancer development in Turkish women . Positive predictive value was 63 % , negative predictive value was 51.9 % , and validity index was 53.1 % . Duration of breastfeeding was significantly longer in group 1 than 2 ( median 17 vs. 13 months ) . The proportion of parous women with no breastfed was higher in group 1 than 2 . The currently used Gail model does not seem to be an appropriate breast cancer risk assessment tool for Turkish female population BACKGROUND Evaluations of epidemiologic risk factors in relation to breast cancer classified jointly by estrogen receptor ( ER ) and progesterone receptor ( PR ) status have been inconsistent . To address this issue , we conducted a prospect i ve evaluation of risk factors for breast cancer classified according to receptor status . METHODS During 1 029 414 person-years of follow-up of 66 145 women participating in the Nurses ' Health Study from 1980 through 2000 , we identified 2096 incident cases of breast cancer for which information on ER/PR status was available : 1281 were ER+/PR+ , 318 were ER+/PR- , 80 were ER-/PR+ , and 417 were ER-/PR- . We fit a log-incidence model of breast cancer and used polychotomous logistic regression to compare coefficients for breast cancer risk factors in patients with different ER/PR status . To test for differences in risk factor odds ratios based on marginal ER/PR categories , we evaluated ER status controlling for PR status and vice versa . The predictive ability of our log-incidence model to discriminate between women who would develop ER+/PR+ breast cancer and those who would not ( and similarly for ER-/PR- breast cancer ) was evaluated by using receiver operator characteristic curve analysis . All statistical tests were two-sided . RESULTS We observed statistically significant heterogeneity among the four ER/PR categories for some risk factors ( age , menopausal status , body mass index [ BMI ] after menopause , the one-time adverse effect of first pregnancy , and past use of postmenopausal hormones ) but not for others ( benign breast disease , family history of breast cancer , alcohol use , and height ) . The one-time adverse association of first pregnancy with incidence was present for PR- but not for PR+ tumors after controlling for ER status ( P = .007 ) . However , the association of BMI after menopause with incidence was present for PR+ but not PR- tumors ( P = .005 ) . Statistically significant differences in the incidence of ER+ and ER- tumors were seen with age , both before and after menopause ( P = .003 ) , and with past use of postmenopausal hormones ( P = .01 ) . Area under the receiver operator characteristic curve , adjusted for age , was 0.64 ( 95 % confidence interval [ CI ] = 0.63 to 0.66 ) for ER+/PR+ tumors and 0.61 ( 95 % CI = 0.58 to 0.64 ) for ER-/PR- tumors . CONCLUSIONS Incidence rates and risk factors for breast cancer differ according to ER and PR status . Thus , to accurately estimate breast cancer risk , breast cancer cases should be divided according to the ER and PR status of the tumor Summary Background . Estimating an individual woman ’s absolute risk for breast cancer is essential for decision making about screening and preventive recommendations . Although the current st and ard , the Gail model , is well calibrated in population s , it performs poorly for individuals . Mammographic breast density ( BD ) may improve the predictive accuracy of the Gail model . Methods . Prospect i ve observational cohort of 81,777 women in the San Francisco Mammography Registry presenting for mammography during 1993 through 2002 who had no prior diagnosis of breast cancer . Breast density was rated by clinical radiologists using the Breast Imaging Reporting and Data System classification ( almost entirely fat ; scattered fibrogl and ular densities ; heterogeneously dense ; extremely dense ) . Breast cancer cases were identified through linkage to Northern California Surveillance Epidemiology End Results ( SEER ) program . We compared the predictive accuracy of models with Gail risk , breast density , and the combination . All models were adjusted for age and ethnicity . Results . During 5.1 years of follow-up , 955 women were diagnosed with invasive breast cancer . The Gail model had modest predictive accuracy ( concordance index ( c-index ) 0.67 ; 95 % CI 0.65–0.68 ) . Adding breast density to the model increased the predictive accuracy to 0.68 ( 95 % CI .66–.70 , p < 0.01 compared with the Gail model alone ) . The model containing only breast density adjusted for age and ethnicity had predictive accuracy equivalent to the Gail model ( c-index 0.67 , 95 % CI 0.65–0.68 ) . Conclusion . The addition of breast density measured by BI-RADS categories minimally improved the predictive accuracy of the Gail model . A model based on breast density alone adjusted for age and ethnicity was as accurate as the Gail model BACKGROUND Gail et al. developed a statistical model for estimating the risk of developing breast cancer in white women screened annually with mammography . This model is used for counseling and for admission to clinical trials . PURPOSE We evaluated the model prospect ively in a cohort of women with a family history of breast cancer . METHODS We followed women who participated in the American Cancer Society 1987 Texas Breast Screening Project . The model was evaluated by comparing the observed ( O ) and expected ( E ) numbers of breast cancers using composite background rates from both the Breast Cancer Detection and Demonstration Project and the Surveillance , Epidemiology , and End Results program of the National Cancer Institute . Data were partitioned by adherence to American Cancer Society screening guidelines . RESULTS The Gail et al. model predicted the risk well among women who adhered to the American Cancer Society guidelines ( O/E = 1.12 ; 95 % confidence interval = 0.75 - 1.61 ) but overpredicted risk for women who did not adhere to the guidelines . There was an indication that the model overpredicted risk for women younger than 60 years old and underpredicted risk in women aged 60 years and older . CONCLUSIONS Overall , the Gail et al. model accurately predicts risk in women with a family history of breast cancer and who adhere to American Cancer Society screening guidelines . Thus , the model should be used as it was intended , for women who receive annual mammograms BACKGROUND The Gail model 2 ( GM ) for predicting the absolute risk of invasive breast cancer has been used for counseling and to design intervention studies . Although the GM has been vali date d in US population s , its performance in other population s is unclear because of the wide variation in international breast cancer rates . METHODS We used data from a multicenter case-control study in Italy and from Italian cancer registries to develop a model ( IT-GM ) that uses the same risk factors as the GM . We evaluated the accuracy of the IT-GM and the GM using independent data from the Florence-European Prospect i ve Investigation Into Cancer and Nutrition ( EPIC ) cohort . To assess model calibration ( i.e. , how well the model predicts the observed numbers of events in subsets of the population ) , we compared the number of expected incident breast cancers ( E ) predicted by these models with the number of observed incident breast cancers ( O ) , and we computed the concordance statistic to measure discriminatory accuracy . RESULTS The overall E/O ratios were 0.96 ( 95 % confidence interval [ CI ] = 0.84 to 1.11 ) and 0.93 ( 95 % CI = 0.81 to 1.08 ) for the IT-GM and the GM , respectively . The IT-GM was somewhat better calibrated than GM in women younger than 50 years , but the GM was better calibrated when age at first live birth categories were considered ( e.g. , 20- to 24-year age-at-first-birth category E/O = 0.68 , 95 % CI = 0.53 to 0.94 for the IT-GM and E/O = 0.75 , 95 % CI = 0.58 to 1.03 for the GM ) . The concordance statistic was approximately 59 % for both models , with 95 % confidence intervals indicating that the models perform statistically significantly better than pure chance ( concordance statistic of 50 % ) . CONCLUSIONS There was no statistically significant evidence of miscalibration overall for either the IT-GM or the GM , and the models had equivalent discriminatory accuracy . The good performance of the IT-GM when applied on the independent data from the Florence-EPIC cohort indicates that GM can be improved for use in population s other than US population s. Our findings suggest that the Italian data may be useful for revising the GM to include additional risk factors for breast cancer BACKGROUND Risk prediction models for breast cancer can be improved by the addition of recently identified risk factors , including breast density and use of hormone therapy . We used prospect i ve risk information to predict a diagnosis of breast cancer in a cohort of 1 million women undergoing screening mammography . METHODS There were 2,392,998 eligible screening mammograms from women without previously diagnosed breast cancer who had had a prior mammogram in the preceding 5 years . Within 1 year of the screening mammogram , 11,638 women were diagnosed with breast cancer . Separate logistic regression risk models were constructed for premenopausal and postmenopausal examinations by use of a stringent ( P<.0001 ) criterion for the inclusion of risk factors . Risk models were constructed with 75 % of the data and vali date d with the remaining 25 % . Concordance of the predicted with the observed outcomes was assessed by a concordance ( c ) statistic after logistic regression model fit . All statistical tests were two-sided . RESULTS Statistically significant risk factors for breast cancer diagnosis among premenopausal women included age , breast density , family history of breast cancer , and a prior breast procedure . For postmenopausal women , the statistically significant factors included age , breast density , race , ethnicity , family history of breast cancer , a prior breast procedure , body mass index , natural menopause , hormone therapy , and a prior false-positive mammogram . The model may identify high-risk women better than the Gail model , although predictive accuracy was only moderate . The c statistics were 0.631 ( 95 % confidence interval [ CI ] = 0.618 to 0.644 ) for premenopausal women and 0.624 ( 95 % CI = 0.619 to 0.630 ) for postmenopausal women . CONCLUSION Breast density is a strong additional risk factor for breast cancer , although it is unknown whether reduction in breast density would reduce risk . Our risk model may be able to identify women at high risk for breast cancer for preventive interventions or more intensive surveillance Despite years of research and hundreds of reports on tumor markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons why multiple studies of the same marker lead to differing conclusions . A variety of method ological problems have been cited to explain these discrepancies . Unfortunately , many tumor marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results . The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute – European Organisation for Research and Treatment of Cancer ( NCI – EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omized trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines provide helpful suggestions on how to present data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply |
11,845 | 21,392,646 | These results are of considerable public health importance , because this dietary pattern can be easily adopted by all population groups and various cultures and cost-effectively serve for primary and secondary prevention of the MS and its individual components | OBJECTIVES The aim of this study was to meta-analyze epidemiological studies and clinical trials that have assessed the effect of a Mediterranean diet on metabolic syndrome ( MS ) as well as its components .
BACKGROUND The Mediterranean diet has long been associated with low cardiovascular disease risk in adult population . | 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 < 0.022 ) . HDL cholesterol increased ( 0.1 mmol/l + /- 0.02 ) only on the LCM ( p < 0.002 ) . The 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 Mediterranean-inspired diets have been shown to decrease cholesterol levels in patients with hypercholesterolaemia , who frequently exhibit endothelial dysfunction . The aims of the present study are to improve endothelial function by dietary intervention in healthy subjects with lipid levels representative of a Western population . Twenty-two healthy subjects ( mean total cholesterol , 5.6 mmol/l ) were given a Mediterranean-inspired diet rich in omega-3 fatty acids and sterol esters , but low in saturated fat , or an ordinary Swedish diet , for 4 weeks in a r and omized cross-over study . The composition of the diets were : in the Swedish diet , 2090 kcal ( where 1 kcal=4.184 kJ ; 48 % of energy from carbohydrate , 15 % from protein and 36 % from fat ) and 19 g of fibre ; in the Mediterranean-inspired diet , 1869 kcal ( 48 % of energy from carbohydrate , 16 % from protein , 34 % from fat ) and 40 g of fibre . After each dietary period , fasting blood lipids , insulin and glucose levels , as well as apo B ( apolipoprotein B ) and LDL ( low-density lipoprotein ) particle size , were analysed . Endothelial-dependent and -independent vasodilation was measured invasively by venous occlusion plethysmography , and arterial distensibility was assessed by echocardiography tracking . Fibrinolytic capacity across the forearm , as well as oxidative stress measured through urinary F(2)-isoprostane , were evaluated . Total , LDL- and apo B-cholesterol and triacylglycerol ( triglyceride ) concentrations were decreased by 17 % , 22 % , 16 % and 17 % respectively , after the Mediterranean-inspired diet compared with the Swedish diet ( P < 0.05 for all ) . However , no differences in plasma concentrations of insulin and glucose and LDL particle size , endothelial function , arterial distensibility , fibrinolytic capacity or oxidative stress were detected . Treatment for 4 weeks with a Mediterranean-inspired diet decreased blood lipids in healthy individuals with a low-risk profile for cardiovascular disease . This beneficial effect was not mirrored in vascular function or oxidative stress evaluation BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality BACKGROUND Diet has been reported to influence arterial blood pressure , and evidence indicates that the Mediterranean diet reduces cardiovascular mortality . OBJECTIVE The objective was to examine whether the Mediterranean diet , as an entity , and olive oil , in particular , reduce arterial blood pressure . DESIGN Arterial blood pressure and several sociodemographic , anthropometric , dietary , physical activity , and clinical variables were recorded at enrollment among participants in the Greek arm of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Of these participants , 20 343 had never received a diagnosis of hypertension and were included in an analysis in which systolic and diastolic blood pressure were regressed on the indicated possible predictors , including a 10-point score that reflects adherence to the Mediterranean diet and , alternatively , the score 's individual components and olive oil . RESULTS The Mediterranean diet score was significantly inversely associated with both systolic and diastolic blood pressure . Intakes of olive oil , vegetables , and fruit were significantly inversely associated with both systolic and diastolic blood pressure , whereas cereals , meat and meat products , and ethanol intake were positively associated with arterial blood pressure . Mutual adjustment between olive oil and vegetables , which are frequently consumed together , indicated that olive oil has the dominant beneficial effect on arterial blood pressure in this population . CONCLUSIONS Adherence to the Mediterranean diet is inversely associated with arterial blood pressure , even though a beneficial component of the Mediterranean diet score-cereal intake-is positively associated with arterial blood pressure . Olive oil intake , per se , is inversely associated with both systolic and diastolic blood pressure BACKGROUND Greater adherence to the Mediterranean diet has been associated with a lower incidence of cardiovascular disease and cancer . OBJECTIVE We studied the effect of the Mediterranean diet on total antioxidant capacity ( TAC ) in 3042 participants who had no clinical evidence of cardiovascular disease . DESIGN During 2001 - 2002 , a r and om sample of 1514 men and 1528 women aged 18 - 89 y from the Attica area of Greece was selected . TAC was measured with an immune-diagnostic assay . Food consumption was evaluated with a vali date d food-frequency question naire , and adherence to the Mediterranean diet was assessed on the basis of a diet score that incorporated the inherent characteristics of this diet . RESULTS TAC was positively correlated with diet score . The participants in the highest tertile of the diet score had , on average , 11 % higher TAC levels than did the participants in the lowest tertile , even after adjustment for relevant confounders ( P < 0.01 ) . On the other h and , the participants in the highest tertile of the diet score had , on average , 19 % lower oxidized LDL-cholesterol concentrations than did the participants in the lowest tertile ( P < 0.01 ) . An additional analysis showed that TAC was positively correlated with the consumption of olive oil ( rho = 0.54 , P = 0.002 ) and of fruit and vegetables ( rho = 0.34 and rho = 0.31 , respectively ; P < 0.001 for both ) , whereas it was inversely associated with the consumption of red meat ( rho = -0.35 , P = 0.02 ) . CONCLUSION Greater adherence to the Mediterranean diet is associated with elevated TAC levels and low oxidized LDL-cholesterol concentrations , which may explain the beneficial role of this diet on the cardiovascular system BACKGROUND Although the typical diet of the Mediterranean region has received much recognition over the past several years for its association with substantial health benefits , it remains unknown whether its favorable effects are mediated through changes in adiponectin concentrations . OBJECTIVE The objective was to determine whether adherence to a Mediterranean-type diet is associated with higher plasma adiponectin concentrations . DESIGN This study was a prospect i ve and cross-sectional evaluation of plasma adiponectin concentrations and dietary data from 987 diabetic women from the Nurses ' Health Study who had no history of cardiovascular disease at the time blood was drawn in 1990 . RESULTS Women who scored highest on a 9-point scale that measures adherence to a Mediterranean-type dietary pattern tended to be older , were less likely to be current smokers , had lower body mass indexes and waist circumferences , and had higher total energy intakes , physical activities , and plasma adiponectin concentrations than did women with the lowest scores . Median plasma adiponectin concentrations were 23 % higher in women who most closely followed a Mediterranean-type diet than in low adherers after adjustment for age and energy intake ( P < 0.01 ) . Body composition , lifestyle , and medical history explained some , but not all , of the observed association between diet and adiponectin concentrations because high adherers tended to have greater adiponectin concentrations than did moderate or low adherers , even after adjustment for these variables . CONCLUSIONS Our data suggest that , of the several components of the Mediterranean dietary pattern score , alcohol , nuts , and whole grains show the strongest association with adiponectin concentrations . Close adherence to a Mediterranean-type diet is associated with higher adiponectin concentrations BACKGROUND An important therapeutic goal for patients with type 2 diabetes is weight loss , which improves metabolic abnormalities . Ad libitum low-fat diets cause weight loss in nondiabetic population s. Compared with diets higher in monounsaturated fat , however , eucaloric low-fat diets may increase plasma triacylglycerol concentrations and worsen glycemic control in persons with type 2 diabetes . OBJECTIVE We investigated whether , in type 2 diabetes patients , an ad libitum low-fat diet would cause greater weight loss than would a high-monounsaturated fat diet and would do this without increasing plasma triacylglycerol concentrations or worsening glycemic control . DESIGN Eleven patients with type 2 diabetes were r and omly assigned to receive an ad libitum low-fat , high-carbohydrate diet or a high-monounsaturated fat diet , each for 6 wk . The diets offered contained 125 % of the estimated energy requirement to allow self- selection of food quantity . The response variables were body weight ; fasting plasma lipid , lipoprotein , glucose , glycated hemoglobin A(1c ) , and fructosamine concentrations ; insulin sensitivity ; and glucose disposal . RESULTS Body weight decreased significantly ( 1.53 kg ; P < 0.001 ) only with the low-fat diet . Plasma total , LDL- , and HDL-cholesterol concentrations tended to decrease during both diets . There were no interaction effects between diet and the lipid profile response over time . Plasma triacylglycerol concentrations , glycemic control , and insulin sensitivity did not differ significantly between the 2 diets . CONCLUSION Contrary to expectations , the ad libitum , low-fat , high-fiber diet promoted weight loss in patients with type 2 diabetes without causing unfavorable alterations in plasma lipids or glycemic control A r and omised crossover study of eight overweight or obese men ( aged 24 - 49 years , BMI 25.5 - 31.3 kg/m(2 ) ) , who followed two diets for 4 weeks each , was performed to determine whether substitution of saturated fat with monounsaturated fat affects body weight and composition . Subjects were provided with all food and beverages as modules ( selected ad libitum ) of constant macronutrient composition , but differing energy content . The % total energy from saturated fat , monounsaturated fat and polyunsaturated fat was 24 , 13 and 3 % respectively on the saturated fatty acid (SFA)-rich diet and 11 , 22 and 7 % respectively on the monounsaturated fatty acid (MUFA)-rich diet . MUFA accounted for about 80 % of the unsaturated fats consumed on both diets . Body composition , blood pressure , energy expenditure ( resting and postpr and ial metabolic rates , substrate oxidation rate , physical activity ) , serum lipids , the fatty acid profile of serum cholesteryl esters and plasma glucose and insulin concentrations were measured before and after each diet period . Significant ( P < or = 0.05 ) differences in total cholesterol and the fatty acid composition of serum cholesteryl esters provided evidence of dietary adherence . The men had a lower weight ( -2.1 ( SE 0.4 ) kg , P=0.0015 ) and fat mass ( -2.6 ( SE 0.6 ) kg , P=0.0034 ) at the end of the MUFA-rich diet as compared with values at the end of the SFA-rich diet . No significant differences were detected in energy or fat intake , energy expenditure , substrate oxidation rates or self-reported physical activity . Substituting dietary saturated with unsaturated fat , predominantly MUFA , can induce a small but significant loss of body weight and fat mass without a significant change in total energy or fat intake The Mediterranean diet is receiving increasing attention in cardiovascular epidemiology . The association of adherence to the Mediterranean diet with the incidence of hypertension was evaluated among 9,408 men and women enrolled in a dynamic Spanish prospect i ve cohort study during 1999 - 2005 . Dietary intake was assessed at baseline with a vali date d semiquantitative food frequency question naire , and a 9-point Mediterranean diet score was constructed . During a median follow-up period of 4.2 years ( range , 1.9 - 7.9 ) , 501 incident cases of hypertension were identified . After adjustment for major hypertension risk factors and nutritional covariates , adherence to the Mediterranean diet was not associated with hypertension ( the hazard ratio was 1.10 ( 95 % confidence interval ( CI ) : 0.81 , 1.41 ) for moderate adherence and 1.12 ( 95 % CI : 0.79 , 1.60 ) for high adherence ) . However , it was associated with reduced changes in mean levels of systolic blood pressure ( moderate adherence , -2.4 mm Hg ( 95 % CI : -4.0 , -0.8 ) ; high adherence , -3.1 mm Hg ( 95 % CI : -5.4 , -0.8 ) ) and diastolic blood pressure ( moderate adherence , -1.3 mm Hg ( 95 % CI : -2.5 , -0.1 ) ; high adherence , -1.9 mm Hg ( 95 % CI : -3.6 , -0.1 ) ) after 6 years of follow-up . These results suggest that adhering to a Mediterranean-type diet could contribute to the prevention of age-related changes in blood pressure OBJECTIVE We examined associations between two Mediterranean diet ( MD ) adherence indexes ( the MD index , MDI , and the MD score , MDS ) and several blood biomarkers of diet and disease . SUBJECTS We studied 328 individuals from Catalonia ( Northeastern Spain ) , ages 18 - 75 , who provided fasting blood sample s , a subset of the 2346 individuals as part of a larger representative and r and om sample from the 1992 - 1993 Catalan Nutritional Survey . DESIGN AND METHOD Diet was measured using 24-h recalls . Biomarkers studied were plasma levels of beta-carotene , alpha-tocopherol , retinol , vitamins B12 , C and folates as well as serum total cholesterol , HDL cholesterol , LDL cholesterol and triglycerides . Multivariate linear regression was used to analyse associations of the nutrient biomarkers with the dietary pattern indexes , adjusting for potential confounders . RESULTS AND CONCLUSIONS Subjects with higher MD adherence , as measured by the two dietary indexes , had significantly higher plasma concentrations of beta-carotene , folates , vitamin C , alpha-tocopherol and HDL cholesterol . The most highly significant relationship was that between folates and the adherence to the MD Pattern , as determined by both indexes . These research findings suggest the potential usefulness of biomarkers as complementary tools for assessing adherence to a dietary pattern . This type of data not only informs the development of robust dietary adherence indexes , but it also provides specific clues about the potential physiological mechanisms that explain the beneficial effects of the MD pattern on chronic disease risk BACKGROUND The " Mediterranean " diet and statin treatment have both independently been shown to improve survival and reduce the risk of cardiovascular events in patients with ischemic heart disease ( IHD ) , but no studies have evaluated the effect of this combination on endothelial function . We therefore sought to evaluate the effect of the combination dietary intervention and lipid-lowering treatment on brachial vasoreactivity . METHODS A total of 131 consecutive patients with documented IHD and a serum cholesterol level > or = 5 mmol/L ( 193 mg/dL ) were r and omized to receive Mediterranean dietary advice ( n = 68 ) or no specific dietary advice ( n = 63 ) . Endothelial function was assessed at baseline and after 12 months with noninvasive ultrasound scanning vessel-wall tracking of brachial artery flow-mediated vasodilatation ( FMD ) . All patients started statin treatment with Fluvastatin ( 40 mg once daily ) at baseline . RESULTS A total of 115 patients completed the study . At baseline , FMD was 4.30 % + /- 4.89 % in the control group versus 4.32 % + /- 6.15 % in the intervention group ( P = not significant ) . After 12 months of follow-up , FMD was significantly higher in the intervention group ( control group 5.72 % + /- 4.87 % vs intervention group 8.62 % + /- 6.60 % , P < .01 ) . This was accompanied by a larger intake of fatty fish and a significant decrease in triglyceride levels . In multivariate analysis , r and omization status was a significant predictor of FMD after adjustment for classic cardiovascular risk factors and vessel size ( P = .02 ; beta = -2.66 [ -4.91 ; -0.41 ] ) . CONCLUSION Dietary intervention with the Mediterranean diet and statin treatment improve FMD in the brachial artery in patients with IHD and hypercholesterolemia to a greater degree than statin treatment alone OBJECTIVE Nuclear transcription factor kappaB ( NF-kappaB ) plays a key role in the inflammatory response and can be modulate by dietary fat . We have examined the effect of three diets , with different fat composition , on the activation of NF-kappaB on peripheral blood mononuclear cells ( P BMC s ) . METHODS Sixteen healthy men followed three 4-week diets , in a r and omised crossover design : a Western diet , rich in saturated fat ( SFA ) [ 22 % SFA , 12 % monounsaturated fat ( MUFA ) and 0 , 4 alpha-linolenic acid ] ; a Mediterranean diet [ < 10 % SFA , 24 % MUFA and 0.4 % alpha-linolenic acid ] , and a low fat diet enriched in alpha-linolenic acid [ < 10 % SFA , 12 % MUFA and 2 % alpha-linolenic acid ] . NF-kappaB ( electrophoretic mobility shift assay ) in mononuclear cells and plasma concentrations ( ELISA ) of soluble vascular cellular adhesion molecule 1 ( VCAM-1 ) were examined after either diets . RESULTS Western diet increased 2.7-fold NF-kappaB compared with the Mediterranean diet ( p=0.038 ) and 1.79-fold with the alpha-linolenic acid diet ( p=0.07 ) . No differences were found between the last two . Furthermore , an increase on plasma VCAM-1 was observed with the Western diet ( p<0.05 ) . CONCLUSIONS The Mediterranean diet diminished NF-kappaB activation in mononuclear cells , compared with Western diet , supporting its cardioprotective properties . The effect of the n-3 enriched diet was intermediate BACKGROUND AND AIMS Diets high in monounsaturated fatty acids ( MUFA ) such as a Mediterranean diet may reduce the risk of cardiovascular diseases by improving insulin sensitivity and serum lipids . Besides being high in MUFA , a Mediterranean diet also contains abundant plant foods , moderate wine and low amounts of meat and dairy products , which may also play a role . We compared the effects of a high MUFA-diet with a diet high in saturated fatty acids ( SFA ) and the additional effect of a Mediterranean diet on insulin sensitivity and serum lipids . METHODS AND RESULTS A r and omized parallel controlled-feeding trial was performed , in 60 non-diabetics ( 40 - 65 y ) with mild abdominal obesity . After a two week run-in diet high in SFA ( 19 energy-% ) , subjects were allocated to a high MUFA-diet ( 20 energy-% ) , a Mediterranean diet ( MUFA 21 energy-% ) , or the high SFA-diet , for eight weeks . The high MUFA and the Mediterranean diet did not affect fasting insulin concentrations . The high MUFA-diet reduced total cholesterol ( -0.41 mmol/L , 95 % CI -0.74 , -0.09 ) and LDL-cholesterol ( -0.38 mmol/L , 95 % CI -0.65 , -0.11 ) compared with the high SFA-diet , but not triglyceride concentrations . The Mediterranean diet increased HDL-cholesterol concentrations ( + 0.09 mmol/L , 95 % CI 0.0 , 0.18 ) and reduced the ratio of total cholesterol/HDL-cholesterol ( -0.39 , 95 % CI -0.62 , -0.16 ) compared with the high MUFA-diet . CONCLUSION Replacing a high SFA-diet with a high MUFA or a Mediterranean diet did not affect insulin sensitivity , but improved serum lipids . The Mediterranean diet was most effective , it reduced total and LDL-cholesterol , and also increased HDL-cholesterol and reduced total cholesterol/HDL-cholesterol ratio Background We aim ed to investigate if overweight and obese adults " close " to Mediterranean diet present better insulin , lipids profile and better pressure levels , compared to individuals close to a more Westernized diet . Methods The ATTICA study is a population -based cohort that has r and omly enrolled 3042 adult men and women , stratified by age – gender , from the greater area of Athens , during 2001–2002 . Of them , in this work were have studied 1762 participants with excess body weight , meaning overweight ( BMI : 25–29.9 kg/m2 ) and obese ( BMI > 30 kg/m2 ) . 1064 were men and 698 women ( 20–89 years old ) . Adherence to Mediterranean diet was assessed through a diet-score that was based on a vali date d food-frequency question naire . Blood pressure was measured and also fasting glucose , insulin and blood lipids . Insulin sensitivity was also assessed by the homeostasis model assessment ( HOMA ) approach ( glucose × insulin/22.5 ) . Results Individuals with excess bodyweight in the highest tertile of diet score , were more insulin sensitive than those in the lowest tertile ( 11.4 % lower HOMA , p = 0.06 ) , had 13 % lower levels of total cholesterol ( p = 0.001 ) and 3 mmHg decrease of systolic blood pressure levels ( p < 0.001 ) , when adjusted for age , sex and BMI . Multivariate analysis after taking into account several confounders demonstrated that insulin sensitivity , total cholesterol and systolic blood pressure were independently but only modestly correlated with Mediterranean diet in people with excess bodyweight . Conclusion Adherence to Mediterranean diet is modeslty associated with a better insulin sensitivity , lower levels of total cholesterol and lower levels of systolic blood pressure in overweight and obese subjects . This may suggest that compared to general population , the beneficial effect of this diet in cardiovascular system of excess body weight people is limited OBJECTIVE Aging is associated with endothelial dysfunction . We studied the acute and longer-term effects of vitamin C compared to a ' Mediterranean-type ' diet on endothelial function in healthy older subjects . METHODS Bilateral venous occlusion plethysmography was used to measure forearm blood flow in subjects aged 57 - 80 years . Responses to cumulative intra-arterial doses of the endothelium-dependent dilator bradykinin ( BK ; n=56 ; 20 , 40 , 80 pmol/min ) and the nitric oxide donor glyceryl trinitrate ( GTN ; n=54 ; 4 , 8 , 16 nmol/min ) , were determined alone and in the presence of vitamin C ( 25 mg/min ) . We then r and omised 54 subjects to a ' healthy ' diet ( n=18 ) , vitamin C ( 1 g/day ; n=18 ) or placebo for 6 weeks and reassessed endothelial and smooth muscle function . RESULTS Acute intra-arterial vitamin C did not alter dilatation to BK or GTN . Similar increases in plasma vitamin C occurred on oral vitamin C ( 83+/-4 to 135+/-8 micromol/l ) and ' healthy ' diet ( 84+/-5 to 135+/-27 micromol/l ; P<0.01 for both ) , with no change seen on placebo . Treatment with a ' healthy ' diet but not oral vitamin C improved endothelium-dependent ( P=0.043 ) and endothelium-independent dilatation ( P=0.011 ) . CONCLUSIONS A ' Mediterranean-type ' diet rich in vitamin C improves vascular function . Neither acute intra-arterial nor sustained administration of oral vitamin C improves vascular function in healthy older subjects OBJECTIVE Few multiple lifestyle behavior change programs have been design ed to reduce the risk of coronary heart disease in postmenopausal women with type 2 diabetes . This study tested the effectiveness of the Mediterranean Lifestyle Program ( MLP ) , a comprehensive lifestyle self-management program ( Mediterranean low-saturated fat diet , stress management training , exercise , group support , and smoking cessation ) , in reducing cardiovascular risk factors in postmenopausal women with type 2 diabetes . RESEARCH DESIGN AND METHODS Postmenopausal women with type 2 diabetes ( n = 279 ) were r and omized to either usual care ( control ) or treatment ( MLP ) conditions . MLP participants took part in an initial 3-day retreat , followed by 6 months of weekly meetings , to learn and practice program components . Biological end points were changes in HbA(1c ) , lipid profiles , BMI , blood pressure , plasma fatty acids , and flexibility . Impact on quality of life was assessed . RESULTS Multivariate ANCOVAs revealed significantly greater improvements in the MLP condition compared with the usual care group on HbA(1c ) , BMI , plasma fatty acids , and quality of life at the 6-month follow-up . Patterns favoring intervention were seen in lipids , blood pressure , and flexibility but did not reach statistical significance . CONCLUSIONS These results demonstrate that postmenopausal women with type 2 diabetes can make comprehensive lifestyle changes that may lead to clinical ly significant improvements in glycemic control , some coronary heart disease risk factors , and quality of life OBJECTIVES We studied the effect of the Mediterranean diet on plasma levels of C-reactive protein ( CRP ) , white blood cell counts , interleukin (IL)-6 , tumor necrosis factor (TNF)-alpha , amyloid A , fibrinogen , and homocysteine . BACKGROUND To the best of our knowledge , the mechanism(s ) by which the Mediterranean diet reduces cardiovascular risk are not well understood . METHODS During the 2001 to 2002 period , we r and omly enrolled 1,514 men ( 18 to 87 years old ) and 1,528 women ( 18 to 89 years old ) from the Attica area of Greece ( of these , 5 % of men and 3 % of women were excluded because of a history of cardiovascular disease ) . Among several factors , adherence to the Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet . Higher values of the score meant closer adherence to the Mediterranean diet . RESULTS Participants who were in the highest tertile of the diet score had , on average , 20 % lower CRP levels ( p = 0.015 ) , 17 % lower IL-6 levels ( p = 0.025 ) , 15 % lower homocysteine levels ( p = 0.031 ) , 14 % lower white blood cell counts ( p = 0.001 ) , and 6 % lower fibrinogen levels ( p = 0.025 ) , as compared with those in the lowest tertile . The findings remained significant even after various adjustments were made . Borderline associations were found regarding TNF-alpha ( p = 0.076 ) , amyloid A levels ( p = 0.19 ) , and diet score . CONCLUSIONS Adherence to the traditional Mediterranean diet was associated with a reduction in the concentrations of inflammation and coagulation markers . This may partly explain the beneficial actions of this diet on the cardiovascular system BACKGROUND Mediterranean and high carbohydrate diets play a dominant role in the prevention of atherosclerosis as a result of their lipid lowering effect . However , diets can also have a protective effect in other ways , such as modulating tissue factor expression in circulating monocytes . METHODS AND RESULTS Forty-one subjects participated in this r and omised crossover study consisting of three dietary periods : a saturated fat enriched diet ( SFA ) , a low fat and high carbohydrate diet ( CHO ) , and a Mediterranean diet . Plasma levels of total cholesterol , triglycerides , low density lipoprotein ( LDL-C ) and high density lipoprotein ( HDL-C ) were determined at the end of each dietary period , as was the expression of tissue factor ( TF ) in circulating monocytes isolated from blood sample s. Total cholesterol , LDL-C , HDL-C and TF expression were lower after the Mediterranean and high carbohydrate diets than after the SFA diet , and there was a positive correlation between LDL-C levels and monocyte TF expression . CONCLUSIONS High carbohydrate and Mediterranean diets reduce the expression of TF in circulating monocytes BACKGROUND Abdominal obesity ( AO ) is associated with increased risk of cardiovascular disease and type 2 diabetes , whereas the Mediterranean diet exerts a cardioprotective effect . OBJECTIVE We examined whether a close adherence to a Mediterranean-style diet improves endothelial function in individuals with AO . DESIGN We recruited 90 subjects with AO without cardiovascular disease or type 2 diabetes . Participants were r and omly assigned to the intervention or control group . Both groups were instructed to follow a Mediterranean-style diet for 2 mo . Subjects in the intervention group additionally had to follow a specific relevant daily and weekly food plan with close supervision by a dietitian and provision of basic foods . Flow-mediated dilatation ( FMD ) , lipids , C-reactive protein ( CRP ) , and insulin resistance with the homeostasis model assessment ( HOMA-IR ) were measured . RESULTS After 2 mo , subjects in the intervention group increased their intake of total fat due to higher consumption of monounsaturated fatty acids as well as intakes of dietary fiber , vitamin C , and alcohol compared with the control group ( all P < 0.05 ) . The intervention group also increased FMD ( 2.05 % ; 95 % CI : 0.97 , 3.13 % ) , whereas no effect was found in the control group ( -0.32 % ; 95 % CI : -1.31 , 0.67 % ) . Changes in lipids and CRP concentrations did not differ between the 2 groups , whereas diastolic blood pressure decreased in the intervention group ( -6.44 mm Hg ; 95 % CI : -8.57 , -4.31 mm Hg ) compared with the control group ( -0.76 mm Hg ; 95 % CI : -2.83 , 1.31 mm Hg ) . Finally , there was a trend for a reduction in HOMA-IR in the intervention group compared with the control group ( P = 0.072 ) . CONCLUSION Close adherence to a Mediterranean-style diet achieved by close dietetic supervision improves endothelial function in subjects with AO BACKGROUND AND AIM The oxidative modifications of low-density lipoprotein ( LDL ) are crucial for the atherosclerosis process . The aim of this study was to determine if the minimally modified LDL , obtained after the ingestion of three different diets , produce differential effects on the vascular cell adhesion molecule-1 ( VCAM-1 ) and E-selectin expression in human umbilical endothelial cells ( HUVECs ) . METHODS AND RESULTS Twenty healthy young males were exposed to three dietary periods . Each period lasted four weeks . During the first period , all subjects consumed a saturated fat ( SFA ) enriched diet ( 38 % fat , 20 % SFA ) . The second and third dietary periods were administered following a r and omized crossover design : a low fat high carbohydrates diet ( CHO diet ) and a Mediterranean diet . LDL particles , isolated during each dietary period , were oxidized by exposure to UV light and incubated for 48 h with HUVEC . Thereafter , 100 U/mL of TNF-alpha was added and incubation continued for 6 h. Cellular ELISA determined adhesion molecules expression . Lag time , propagation rate and total amounts of formed conjugated dienes were calculated in LDL incubated with 10mumol/L Cu(2 + ) . When compared to the SFA diet , LDL isolated from the Mediterranean and CHO diets induced a lower expression of VCAM-1 and E-selectin in HUVECS ( P<0.007 ) . There were no differences between both lipid lowering diets . However , lag time of LDL from the Mediterranean diet was higher than with the CHO diet ( P<0.042 ) . This parameter was inversely correlated with E-selectin expression ( r=-0.497 ; P<0.04 ) . CONCLUSION Our results suggest that both the Mediterranean and CHO diets may decrease the pro-inflammatory environment induced by modified LDL in endothelial cells BACKGROUND AND AIM The effect of the quality of dietary fat on body composition is unknown . Our objective was to determine whether body composition is modified by the isocaloric substitution of a diet rich in saturated fat by a diet high in monounsaturated fat ( Mediterranean diet ) or a carbohydrate-rich diet in overweight subjects with hypercholesterolemia . METHODS AND RESULTS The study involved 34 hypercholesterolemic males aged 18 - 63 years with a body mass index ( BMI ) of 28.2 ( 2.6 ) , all of whom consumed a diet rich in saturated fat ( SAT ) for 28 days . They were then r and omly divided into two groups of 17 subjects and underwent two dietary periods of 28 days each in a crossover design : a Mediterranean diet high in monounsaturated fat ( MONO ) and a carbohydrate-rich diet ( CHO ) . The order of the diets was different for the two group . The CHO diet contained 57 % CHO and 28 % total fat ( < 10 % saturated fat , 12 % monounsaturated fat and 6 % polyunsaturated fat ) ; the Mediterranean diet contained 47 % CHO and 38 % fat ( < 10 % saturated fat , 22 % monounsaturated fat--75 % of which was provided by olive oil- and 6 % polyunsaturated fat ) . The variables measured at the end of each dietary intervention period were : 1 ) body composition by means of bioelectrical impedance ; 2 ) plasma lipoproteins using enzymatic techniques ; and 3 ) fatty acids in cholesterol esters by means of gas chromatography . BMI and the waist/hip ratio remained the same during the three dietary periods . A decrease in fat was observed when changing from a saturated fat diet ( 23.3 ( 6.3 ) kg ) to a Mediterranean diet ( 20.8 ( 7.2 ) kg ) ( p < 0.05 ) , or a carbohydrate-rich diet ( 20.6 ( 6.7 ) kg ) ( p < 0.05 ) . Lean mass increased when changing from a SAT diet ( 58.4 ( 7.0 ) kg ) to a CHO diet ( 60.2 ( 7.0 ) kg ) ( p < 0.05 ) . CONCLUSION The isocaloric substitution of a saturated fat-rich diet by a Mediterranean or carbohydrate-rich diet decreases total body fat in hypercholesterolemic males Objective : The objective of this trial was to compare the effect on the susceptibility of plasma Low Density Lipoprotein ( LDL ) to oxidative modifications of consumption of two oleic rich diets , prepared with two different plant oils , virgin olive oil (OL)1 and refined high monounsaturated fatty acids ( MUFA sunflower oil ( SU ) ) , with the susceptibility of plasma LDL to oxidation after an National Cholesterol Education Program step 1 ( NCEP-I ) phase diet . Design : A r and omized crossover design .Subjects and interventions : Twenty-two healthy normolipidemic young males consumed an NCEP-I diet for a 4-week period . Subjects were then assigned to two diets each of 4-weeks duration . Group one was placed on an olive oil enriched diet ( 40 % fat , 22 % MUFA ) followed by a 4-week period of a MUFA diet enriched in sunflower oil ( 40 % fat , 22 % MUFA ) . In group two , the order of the diets was reversed . Results : Both MUFA diets induced a decrease in saturated ( 14:0 , 16:0 , and 18:0 ) and an increase in monounsaturated and polyunsaturated n-6 ( 18:2 , 20:3 , and 20:5 ) plasma LDL-phospholipid fatty acids , compared to the NCEP-I diet ( P<0.01 ) . No significant differences in lag times were observed between the olive oil and the NCEP-I diet periods . However there was a greater inhibition time ( P<0.001 ) when subjects consumed the MUFA rich sunflower oil diet compared to the NCEP-I diet . These differences were probably related to the relative enrichment of plasma LDL particles in α-tocopherol due to the high vitamin E content of the MUFA-rich sunflower oil . Indeed , the α-tocopherol content was positively correlated with lag time ( r=0.338 ; P<0.008 ) . Conclusion : Our findings suggest that changes in plasma LDL α-tocopherol content with practical solid-food diets can decrease its susceptibility to oxidation . Sponsorship : This work has been supported by grants from the Investigaciones de la Seguridad Social ( FIS 92/0182 , to Francisco Pérez Jiménez ) ; and from Koype Co , And újar , Jaén , Spain . European Journal of Clinical Nutrition ( 2000 ) 54 , CONTEXT : Long-term success in weight loss with dietary treatment has been elusive . OBJECTIVE : To evaluate a diet moderate in fat based on the Mediterranean diet compared to a st and ard low-fat diet for weight loss when both were controlled for energy . DESIGN : A r and omized , prospect i ve 18 month trial in a free-living population . PATIENTS : A total of 101 overweight men and women ( 26.5–46 kg/m2).INTERVENTION : ( 1 ) Moderate-fat diet ( 35 % of energy ) ; ( 2 ) low-fat diet ( 20 % of energy).MAIN OUTCOME MEASUREMENTS : Change in body weight . RESULTS : After 18 months , 31/50 subjects in the moderate-fat group , and 30/51 in the low fat group were available for measurements . In the moderate-fat group , there were mean decreases in body weight of 4.1 kg , body mass index of 1.6 kg/m2 , and waist circumference of 6.9 cm , compared to increases in the low-fat group of 2.9 kg , 1.4 kg/m2 and 2.6 cm , respectively ; P≤0.001 between the groups . The difference in weight change between the groups was 7.0 kg . ( 95 % CI 5.3 , 8.7 ) . Only 20 % ( 10/51 ) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54 % ( 27/50 ) in the moderate-fat group , ( P<0.002 ) . The moderate-fat diet group was continued for an additional year . The mean weight loss after 30 months compared to baseline was 3.5 kg ( n=19 , P=0.03 ) . CONCLUSIONS : A moderate-fat , Mediterranean-style diet , controlled in energy , offers an alternative to a low-fat diet with superior long-term participation and adherence , with consequent improvements in weight loss Mediterranean diet is associated with lower incidence of coronary heart disease , and two r and omised trials indicated that it improves prognosis of coronary patients . These trials , however , relied on a total of 100 deaths and evaluated design er diets in the clinical context . We have evaluated the association of adherence to the modified Mediterranean diet , in which unsaturates were substituted for monounsaturates , with survival among elderly with previous myocardial infa rct ion within the European Prospect i ve Investigation into Cancer and nutrition ( EPIC ) study . As of December 2003 , after a median follow-up of 6.7 years , 2671 EPIC participants from nine countries were 60 years or older and had prevalent myocardial infa rct ion but no stroke or cancer at enrolment , complete information on dietary intakes and important covariates and known survival status . Adherence to the modified Mediterranean diet was assessed through a 10-unit-scale . Mortality ratio in relation to modified Mediterranean diet was estimated through Cox regression controlling for possible confounding . Increased adherence to modified Mediterranean diet by two units was associated with 18 % lower overall mortality rate ( 95 % confidence interval 7–27 % , fixed effects model ) . There was no significant heterogeneity by sex , age at enrolment , or country , although the association tended to be less evident among northern Europeans . Associations between food groups contributing to the modified Mediterranean diet and mortality were generally weak . A diet inspired by the Mediterranean pattern that can be easily adopted by Western population s is associated with substantial reduction of total mortality of coronary patients in the community Aims /hypothesisMost studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat , carbohydrate , fibre , fruits and vegetables . Instead , we aim ed to compare diets that were available during human evolution with more recently introduced ones . Methods Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were r and omised to receive ( 1 ) a Palaeolithic ( ‘ Old Stone Age ’ ) diet ( n = 14 ) , based on lean meat , fish , fruits , vegetables , root vegetables , eggs and nuts ; or ( 2 ) a Consensus ( Mediterranean-like ) diet ( n = 15 ) , based on whole grains , low-fat dairy products , vegetables , fruits , fish , oils and margarines . Primary outcome variables were changes in weight , waist circumference and plasma glucose AUC ( AUC Glucose0–120 ) and plasma insulin AUC ( AUC Insulin0–120 ) in OGTTs . Results Over 12 weeks , there was a 26 % decrease of AUC Glucose0–120 ( p = 0.0001 ) in the Palaeolithic group and a 7 % decrease ( p = 0.08 ) in the Consensus group . The larger ( p = 0.001 ) improvement in the Palaeolithic group was independent ( p = 0.0008 ) of change in waist circumference ( −5.6 cm in the Palaeolithic group , −2.9 cm in the Consensus group ; p = 0.03 ) . In the study population as a whole , there was no relationship between change in AUC Glucose0–120 and changes in weight ( r = −0.06 , p = 0.9 ) or waist circumference ( r = 0.01 , p = 1.0 ) . There was a tendency for a larger decrease of AUC Insulin0–120 in the Palaeolithic group , but because of the strong association between change in AUC Insulin0–120 and change in waist circumference ( r = 0.64 , p = 0.0003 ) , this did not remain after multivariate analysis . Conclusions /interpretationA Palaeolithic diet may improve glucose tolerance independently of decreased waist circumference CONTEXT Obesity is an independent risk factor for cardiovascular disease , which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue . OBJECTIVE To determine the effect of a program of changes in lifestyle design ed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance . DESIGN AND SETTING R and omized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy . PATIENTS One hundred twenty premenopausal obese women ( body mass index > or = 30 ) aged 20 to 46 years without diabetes , hypertension , or hyperlipidemia . INTERVENTIONS The 60 women r and omly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10 % or more through a low-energy Mediterranean-style diet and increased physical activity . The control group ( n = 60 ) was given general information about healthy food choices and exercise . MAIN OUTCOME MEASURES Lipid and glucose intake ; blood pressure ; homeostatic model assessment of insulin sensitivity ; and circulating levels of interleukin 6 ( IL-6 ) , interleukin 18 ( IL-18 ) , C-reactive protein ( CRP ) , and adiponectin . RESULTS After 2 years , women in the intervention group consumed more foods rich in complex carbohydrates ( 9 % corrected difference ; P<.001 ) , monounsaturated fat ( 2 % ; P = .009 ) , and fiber ( 7 g/d ; P<.001 ) ; had a lower ratio of omega-6 to omega-3 fatty acids ( -5 ; P<.001 ) ; and had lower energy ( -310 kcal/d ; P<.001 ) , saturated fat ( -3.5 % ; P = .007 ) , and cholesterol intake ( -92 mg/d ; P<.001 ) than controls . Body mass index decreased more in the intervention group than in controls ( -4.2 ; P<.001 ) , as did serum concentrations of IL-6 ( -1.1 pg/mL ; P = .009 ) , IL-18 ( -57 pg/mL ; P = .02 ) , and CRP ( -1.6 mg/L ; P = .008 ) , while adiponectin levels increased significantly ( 2.2 microg/mL ; P = .01 ) . In multivariate analyses , changes in free fatty acids ( P = .008 ) , IL-6 ( P = .02 ) , and adiponectin ( P = .007 ) levels were independently associated with changes in insulin sensitivity . CONCLUSION In this study , a multidisciplinary program aim ed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance AIMS To compare the effects of a high-carbohydrate ( CHO ) diet and a high-monounsaturated fatty acid ( MUFA ) diet on LDL oxidative resistance in free-living individuals with Type 2 diabetes mellitus . METHODS Twenty-two men and women out- patients with Type 2 diabetes , with mean age 61 years and in fair metabolic control ( HbA1c<8.0 % ) , were enrolled at a university hospital lipid clinic in a r and omized , crossover feeding trial comparing two isocaloric diets for 6 weeks each : CHO ( fat , 28 % energy ) and MUFA ( fat , 40 % energy ) based on virgin olive oil . Outcome measurements were changes in LDL susceptibility to oxidation , body weight , glycaemic control , and lipoprotein profiles . RESULTS Planned and observed diets were well matched . Participants preferred the MUFA diet over the CHO diet . The lag time of conjugated diene formation during Cu2 + -induced LDL oxidation was similar after the CHO and MUFA diets ( 36.4 + /- 12.2 min and 36.0 + /- 13.7 min , respectively ) . Body weight , glycaemic control , total triglycerides , and total , LDL- and HDL-cholesterol levels also were similar after the two diets . Compared with the CHO diet , the MUFA diet lowered VLDL-cholesterol by 35 % ( P=0.023 ) and VLDL triglyceride by 16 % ( P=0.016 ) . CONCLUSIONS Natural food-based high-CHO and high-MUFA diets have similar effects on LDL oxidative resistance and metabolic control in subjects with Type 2 diabetes . A MUFA diet is a good alternative to high-CHO diets for nutrition therapy of diabetes because it also has a beneficial effect on the lipid profile and superior patient acceptance The endothelium helps regulate vascular tone through the release of vasodilator and vasoconstrictor substances ( 1 ) , but this regulatory function is altered in hypercholesterolemia ( 2 ) . Endothelial dysfunction plays a central role in the development of atherosclerosis ( 3 ) . Diet is the cornerstone of hypercholesterolemia treatment . Studies in animals have shown that dietary therapies restore endothelium-dependent vasodilatation to normal ( 4 ) . However , the information available in humans is scarce and was obtained mainly in studies of diets rich in polyunsaturated n-3 fatty acids ( 5 ) . The U.S. National Cholesterol Education Program ( NCEP ) recommends a low-fat , lowsaturated fat diet for the primary prevention of atherosclerosis ( 6 ) ; this diet is referred to as the stage 1 diet ( NCEP-1 ) . In addition , a diet high in monounsaturated fat , which is a common diet in Mediterranean countries , has been related to decreased risk for coronary heart disease ( 7 ) , and the Lyon Diet Heart Study found that a Mediterranean diet rich in linolenic acid reduced cardiovascular events ( 8) . At present , the effect of these diets on endothelial function in humans is unknown . Our aim was to investigate endothelial function after substituting each of these potentially cardioprotective diets for a saturated fatenriched diet in hypercholesterolemic patients . Methods Patients Twenty-two white hypercholesterolemic men attending the Lipid Clinic at the Reina Sofia University Hospital in Crdoba , Spain , volunteered to participate in the study . All patients were 18 to 65 years of age ( mean [ SD ] , 40.5 14.7 years ) and had plasma cholesterol concentrations greater than 5.2 mmol/L ( 200 mg/dL ) . None had chronic illness , were extremely physically active , or had any known secondary cause of hypercholesterolemia . Patients were excluded if they had a family history of premature coronary heart disease or if they had taken vitamin supplements or medication known to affect plasma lipid levels in the 6 months before the study . Patients were encouraged to maintain their regular lifestyles and regular levels of physical activity . Intervention The study design included an initial 28-day period during which all patients consumed a diet high in saturated fat , with 15 % protein , 47 % carbohydrates , and 38 % fat ( 20 % saturated fat , 12 % monounsaturated fat , and 6 % polyunsaturated fat ) constituting energy intake . Following this period , two groups of 10 and 12 patients each were r and omly assigned in a crossover design to two diets for two 28-day periods : the NCEP-1 diet and a diet high in monounsaturated fat ( a typical Mediterranean diet enriched with olive oil ) . Group 1 was placed on the Mediterranean diet followed by the NCEP-1 diet , while the order of the diets for patients in group 2 was reversed . The NCEP-1 diet consisted of 57 % carbohydrates and 28 % fat ( < 10 % saturated fat , 12 % monounsaturated fat , and 6 % polyunsaturated fat ) . The Mediterranean diet consisted of 47 % carbohydrates and 38 % fat ( < 10 % saturated fat , 22 % monounsaturated fat , and 6 % polyunsaturated fat ) . Olive oil provided 75 % of the total monounsaturated fat consumed during the Mediterranean diet . Dietary cholesterol was maintained at a constant level ( 3 mmol/4800 kJ ) during the three periods . We did not include washout periods between the three stages of dietary intervention because washout is unnecessary when dietary intervention lasts longer than 3 weeks ( 9 ) . The Human Investigation Review Committee at Reina Sofa University Hospital approved the study , and informed consent was obtained from all patients . The experimental diets followed the U.S. Department of Agriculture food tables and Spanish food composition tables . Twenty menus were prepared with common food items and were rotated during the experimental period . Dietary adherence was determined by measuring fatty acid enrichment of low-density lipoprotein ( LDL ) cholesterol esters at the end of each diet , since changes in dietary fatty acids induce a parallel change in the composition of LDL cholesterol esters . Blood Sampling and Biochemical Determinations At the end of each diet , after a 12-hour overnight fast , venous blood sample s were collected in tubes containing EDTA ( 1 g/L ) . Cholesterol and triglycerides were assayed by using enzymatic procedures . High-density lipoprotein cholesterol level was measured after precipitation of apolipoprotein Bcontaining lipoproteins with phosphowolframic acid . Low-density lipoprotein cholesterol level was calculated by using the Friedewald formula . Apolipoprotein A-I and apolipoprotein B concentrations were determined by using turbidimetry . Plasma levels of cell adhesion molecules ( vascular cell adhesion molecule-1 [ VCAM-1 ] and intercellular cell adhesion molecule-1 [ ICAM-1 ] ) and P-selectin were determined by using enzyme-linked immunosorbent assay . Endothelial Function A noninvasive method described by Celermajer and colleagues ( 10 ) was used to evaluate endothelial function . This technique uses postischemic vasodilatation , causing enhanced flow in the proximal brachial artery and shear stressinduced vasodilatation considered endothelium dependent . The diameter of the right brachial artery was measured at the end of each dietary period by using two-dimensional ultrasonography images , with a 7-MHz linear array transducer and a st and ard 128XP/10 system ( Acuson Corp. , Mountain View , California ) . Scans were taken at rest , during reactive hyperemia ( endothelium-dependent vasodilatation ) , again at rest ( 10 minutes ) , and after 400 g of sublingual glyceryl trinitrate . Two independent observers who were unaware of clinical details and the stage of the experiment measured vessel diameter . The resistance index was also measured by each observer . Statistical Analysis The sample size calculations indicated that a minimum of 15 patients was required per group ( based on a minimal expected increase in the brachial artery diameter [ mean SD ] of 0.08 mm 0.05 mm , an value of 0.025 , a power of 0.90 , and a 10 % estimated loss to follow-up ) . For each diet , we used analysis of variance for repeated measures to test for dietary effects on plasma lipid levels and endothelial function . When significant effects were detected ( P<0.05 ) , the Bonferroni test was used for a post hoc comparison . For example , to determine whether consumption of the three diets modified levels of LDL cholesterol , we initially used the analysis of variance test , which indicated that the diets differ ( P<0.001 ) . Subsequently , we performed a post hoc test using the Hochberg modification of the Bonferroni procedure ( 11 ) to establish in which pair of diets differences were produced , taking into consideration that each independent variable had three possible paired comparisons . Triglyceride values were logarithmically transformed to achieve an approximately normal distribution , and statistical tests were performed on the transformed values . Role of the Funding Sources The funding sources had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the paper for publication . Results Adherence to the diets was excellent , as suggested by the absence of significant events recorded in the participants ' diaries and the composition of plasma cholesteryl esters found in LDL cholesterol . Compared with the NCEP-1 diet , palmitic acid increased significantly during the saturated fat diet ( P=0.01 ) and oleic acid levels increased significantly during the Mediterranean diet ( P=0.02 ) . At the end of each dietary period , measurement of endothelial function showed no significant differences in the basal diameters of the brachial artery ( Table 1 ) or in the glyceryl trinitrateinduced vasodilatation . Flow-associated vasodilatation of the brachial artery was significantly higher after the Mediterranean diet ( P = 0.027 ) than after the saturated fat diet ( 13.5 % vs. 9.9 % ) . However , we did not observe significant differences in flow-associated vasodilatation between the saturated fat diet and the NCEP-1 diet ( 9.9 % vs. 11.1 % ) . The resistance index was higher after flow-associated vasodilatation ( the endothelium-dependent value ) ( P = 0.003 ) and after glyceryl trinitrateinduced vasodilatation ( P=0.002 ) during the saturated fat diet than during the Mediterranean diet or the NCEP-1 diet ( P=0.008 ) . P-Selectin levels were lower during the Mediterranean diet and the NCEP-1 diet ( P = 0.003 and P = 0.068 , respectively ) than during the saturated fat diet . We did not find significant differences in plasma concentrations of VCAM-1 and ICAM-1 among the three diets . Table 1 . Flow-Associated Vasodilatation ( Endothelium-Dependent ) ; Glyceryl TrinitrateInduced Vasodilatation ( Endothelium-Independent ) ; and Plasma Levels of Soluble Intercellular Cell Adhesion Molecule-1 , Vascular Cell Adhesion Molecule-1 , and P-Selectin at the End of Each Dietary Period Compared with the saturated fat diet ( Table 2 ) , the NCEP-1 and Mediterranean diets were associated with a decrease in plasma cholesterol level ( P=0.001 ) , LDL cholesterol level ( P<0.001 ) , and apolipoprotein B level ( P=0.002 ) but did not significantly change high-density lipoprotein cholesterol , apolipoprotein A-I , or triglyceride levels . In addition , we found a negative correlation between LDL cholesterol levels and flow-associated vasodilatation ( r = 0.23 ; P=0.036 ) . Changes in LDL cholesterol levels were positively correlated with P-selectin levels ( r = 0.275 ; P=0.030 ) , while flow-associated vasodilatation was negatively correlated with P-selectin levels ( r = 0.372 ; P=0.018 ) . Table 2 . Plasma Lipid and Apolipoprotein Concentrations at the End of Each Dietary Period Discussion In our study , replacement of a saturated fatenriched diet by a monounsaturated fatenriched diet and an NCEP-1 diet increased endothelium-dependent vasodilatation . The increase in flow-associated vasodilatation observed with the consumption of a diet high in monounsaturated fat suggests that this diet improves endothelial function . Our patients had primary Objective : We investigated the association between adherence to Mediterranean diet and fasting indices of glucose homoeostasis , in a Greek adult population . Methods : During 2001–2002 we r and omly enrolled 1514 men and 1528 women ( 18–89 years old ) without history of CVD , from the Attica area . Diabetes mellitus ( type 2 ) and impaired fasting glucose ( IFG ) were defined according to the established ADA criteria . Insulin resistance was evaluated by HOMA-IR . Dietary habits were assessed through a vali date d food frequency question naire and a diet score ( range 0–55 ) was developed ( higher values means greater adherence to the Mediterranean diet ) . Results : The overall prevalence of diabetes type 2 was 7.9 % in men and 6.0 % in women ( P = 0.05 ) . Mean diet score was 26.3 ± 6.8 in normoglycemic , 25.7 ± 6.4 in IFG and 22.2 ± 5.8 in diabetic subjects ( p < 0.001 ) . In normoglycemic subjects who were in the upper tertile of the diet score we observed 7 % lower glucose ( p < 0.05 ) , 5 % lower insulin ( p < 0.05 ) and 15 % lower HOMA-IR ( p < 0.01 ) levels compared to subjects in the lower tertile of the diet score . Additionally , in diabetic/IFG participants who where in the upper tertile of the diet score we observed 15 % lower glucose ( p < 0.05 ) , 15 % lower insulin ( p < 0.05 ) and 27 % lower HOMA-IR ( p < 0.01 ) levels compared to those in the lower tertile . However , multiple regression analysis , adjusted for age , sex , BMI , waist-to-hip ratio , physical activity , smoking status , and presence of hypertension and hypercholesterolemia , confirmed the previous associations in normoglycemic , but not in diabetic/IFG people . Conclusion : An inverse association was observed between adherence to Mediterranean diet and indices of glucose homeostasis , only in normoglycemic people In a prospect i ve , r and omised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infa rct prudent diet . After a first myocardial infa rct ion , patients were r and omly assigned to the experimental ( n = 302 ) or control group ( n = 303 ) . Patients were seen again 8 weeks after r and omisation , and each year for 5 years . The experimental group consumed significantly less lipids , saturated fat , cholesterol , and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma . Serum lipids , blood pressure , and body mass index remained similar in the 2 groups . In the experimental group , plasma levels of albumin , vitamin E , and vitamin C were increased , and granulocyte count decreased . After a mean follow up of 27 months , there were 16 cardiac deaths in the control and 3 in the experimental group ; 17 non-fatal myocardial infa rct ion in the control and 5 in the experimental groups : a risk ratio for these two main endpoints combined of 0.27 ( 95 % CI 0.12 - 0.59 , p = 0.001 ) after adjustment for prognostic variables . Overall mortality was 20 in the control , 8 in the experimental group , an adjusted risk ratio of 0.30 ( 95 % CI 0.11 - 0.82 , p = 0.02 ) . An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death BACKGROUND AND AIMS Mediterranean diet is associated with a reduced risk for cardiovascular disease ( CVD ) . Use of plant stanols decreases low density lipoprotein cholesterol ( LDL-C ) concentrations . We compared the effects of the Mediterranean diet and plant stanol esters on vascular risk factors and estimated CVD ( eCVD ) risk . METHODS AND RESULTS In this prospect i ve , r and omized , placebo-controlled study , 150 mildly hypercholesterolaemic subjects were r and omized to Mediterranean diet , a spread containing plant stanol esters ( 2 g/day ) or a placebo spread . Vascular risk factors were assessed every month for 4 months and the eCVD risk was calculated using the PROspect ive- Cardiovascular-Munster ( PROCAM ) , Framingham , and Reynolds risk engines . Placebo had no significant effect on risk factors or eCVD risk . Mediterranean diet gradually induced a significant reduction in total cholesterol ( TC ) , LDL-C , triglycerides , high sensitivity C-reactive protein ( hsCRP ) , blood pressure and eCVD risk ( 24 - 32 % ) . The plant stanol ester spread reduced ( by 1 month ) TC ( -14 % ) , LDL-C ( -16 % ) , hsCRP ( -17 % ) , and estimated CVD risk ( 26 - 30 % ) . eCVD risk reduction was sustained at 4th months when the gradual Mediterranean diet eCVD risk reduction became comparable to that of the stanol group . CONCLUSIONS Plant stanol esters yielded an early , by 1st treatment month , reduction of eCVD risk that result ed from a TC , LDL-C , and hsCRP decrease . eCVD risk reduction on the Mediterranean diet result ed from a change in several CVD risk factors and equaled that of plant stanol at 4 months . The consumption of plant stanol esters by moderately hypercholesterolaemic patients may be a useful option to reduce CVD risk in those who do not adopt a Mediterranean diet CONTEXT Limited information exists on the interaction between diet and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) and the interaction 's effect on serum lipid and lipoprotein levels , insulin sensitivity , and circulating antioxidant vitamin and provitamin levels . OBJECTIVE To evaluate the separate and combined effects of diet and simvastatin therapy on serum levels of lipids , lipoproteins , antioxidants , and insulin . DESIGN , SETTING , AND PARTICIPANTS R and omized , controlled crossover trial conducted from August 1997 to June 1998 in 120 previously untreated hypercholesterolemic men aged 35 to 64 years who were recruited from the community in Turku , southwestern Finl and . INTERVENTIONS After a 4- to 6-week placebo run-in period , participants were r and omly allocated to a habitual diet ( n = 60 ) or dietary treatment group ( n = 60 ) , and each of these groups was further r and omized in a double-blind crossover fashion to receive simvastatin ( 20 mg/d ) or placebo , each for 12 weeks ( n = 30 in each group ) . The main goals of the dietary treatment were to reduce energy intake from saturated plus trans-unsaturated fats to no more than 10 % by replacing them partly with monounsaturated and polyunsaturated fats rich in omega-3 fatty acids and to increase intake of fruits , vegetables , and dietary fiber . MAIN OUTCOME MEASURES Changes in levels of total , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) cholesterol ; triglycerides ; apolipoprotein B ; insulin ; glucose ; and antioxidants at week 12 of each treatment period , compared among the 4 groups . RESULTS Dietary treatment decreased levels of total cholesterol by 7.6 % ( P<.001 ) , LDL cholesterol by 10.8 % ( P<.001 ) , HDL cholesterol by 4.9 % ( P = .01 ) , apolipoprotein B by 5.7 % ( P = .003 ) , serum insulin by 14.0 % ( P = .02 ) , and alpha-tocopherol by 3.5 % ( P = .04 ) . Simvastatin decreased levels of total cholesterol by 20.8 % , LDL cholesterol by 29.7 % , triglycerides by 13.6 % , apolipoprotein B by 22.4 % , alpha-tocopherol by 16.2 % , beta-carotene by 19.5 % , and ubiquinol-10 by 22.0 % ( P<.001 for all ) and increased levels of HDL cholesterol by 7.0 % ( P<.001 ) and serum insulin by 13.2 % ( P = .005 ) . Glucose levels remained unchanged in all groups . The effects of dietary treatment and simvastatin were independent and additive . CONCLUSIONS A modified Mediterranean-type diet rich in omega-3 fatty acids efficiently potentiated the cholesterol-lowering effect of simvastatin , counteracted the fasting insulin-elevating effect of simvastatin , and , unlike simvastatin , did not decrease serum levels of beta-carotene and ubiquinol-10 Objective : To ascertain whether simple dietary advice to increase the consumption of Mediterranean foods , given in a clinical setting , leads to reduced mortality after a myocardial infa rct ion . Design : Data were used from the GISSI-Prevenzione clinical trial , analysed as a cohort study with adjustment for treatment allocation . Setting : A total of 172 centres in Italy . Subjects : A total of 11 323 men and women with myocardial infa rct ion . All subjects received advice to increase their consumption of fish , fruit , raw and cooked vegetables and olive oil . Measurements : The intakes of the five foods were assessed at baseline , 6 , 18 and 42 months . Associations of food intakes , a combined dietary score , and the risk of death over 6.5 y were estimated adjusting for several non-dietary variables , using pooled logistic regression . Results : Subjects generally improved their diet according to the advice given . All foods were associated with a significant reduction in risk of death . Compared with people in the worst dietary score quarter , the odds ratio for those in the best score quarter was 0.51 ( 95 % CI 0.44–0.59 ) . A good diet had a protective effect in sub-groups defined by age , sex , smoking , r and omized treatment and concomitant drug therapy . Conclusions : Myocardial infa rct ion patients can respond positively to simple dietary advice , and this can be expected to lead to a substantial reduction in the risk of early death . Regardless of any drug treatment prescribed , clinicians should routinely advise patients with myocardial infa rct ion to increase their frequency of consumption of Mediterranean foods Obesity is a cardiovascular risk factor associated with endothelial dysfunction , but the effect of different weight loss strategies on endothelial function is not known . The effect of diet on endothelial function in two hypocaloric diets , a very-low-carbohydrate diet ( A ) and a Mediterranean diet ( M ) , was measured by brachial artery flow-mediated dilation ( FMD ) . Design Using a longitudinal , r and omized , open study design , subjects were engaged in a 2-month weight loss diet . FMD , inflammatory cytokines [ interleukin-6 ( IL-6 ) and tumour necrosis factor-alpha ] and a marker of oxidative stress [ 8-iso-prostagl and in F2alpha ( 8-iso-PGF2alpha ) ] were measured in subjects on three occasions : before initiating the diet ( T0 ) , after 5 - 7 days of dieting ( T5 ) and after 2 months of dieting ( T60 ) . The very short- and medium-term time points were established to discriminate respectively the effect of the diet itself ( T5 ) from that of weight loss ( T60 ) . Twenty overweight/obese but otherwise healthy women ( BMI : 27 - 34.9 kg m(-2 ) ; age 30 - 50 years ) completed the study . Results Group A lost more weight ( mean + /- SEM ; -7.6 + /- 0.8 kg ) than group M ( -4.9 + /- 0.6 kg , P = 0.014 ) at T60 . The FMD was not significantly different between the two groups at T0 ( group A : 12.2 + /- 2.9 % vs. group B : 10.3 + /- 2.3 % , P = ns ) . In group A , FMD was significantly reduced at T5 and returned to baseline at T60 ; in group M , FMD increased at T5 and returned to baseline at T60 ( P = 0.007 for diet x time interaction ) . Serum concentrations of IL-6 and 8-iso-PGF2alpha were not significantly different between the two groups at T0 and increased significantly at T5 only in group A ( P < 0.001 and P < 0.005 respectively ) . Conclusion As endothelial dysfunction is known to be associated with acute cardiovascular events , this study suggests that the cardiovascular risk might be increased in the first days of a very-low-carbohydrate diet |
11,846 | 32,190,340 | SGLT2is significantly improved HbA1c [ mean difference - 0.80 ( 95%CI - 0.96 to - 0.64)% , p < 0.00001 ] , TG [ mean difference - 16.42 ( 95%CI - 22.71 to - 10.12 ) mg/dL , p < 0.00001 ] , and HDL-C [ mean difference 3.36 ( 95%CI 2.73 to 3.98 ) mg/dL , p < 0.00001 ] , but significantly deteriorated LDL-C [ mean difference 3.00 ( 95%CI 1.18 to 4.82 ) mg/dL , p < 0.001 ] .
Conclusion The present results suggest that in Asian patients with type 2 diabetes mellitus , TG and HDL-C values were better , while LDL-C values were worse with SGLT2is than with a placebo .
However , the negative impact of SGLT2is on lipid profiles was modest .
The present results will be informative for SGLT2is users with concerns regarding the effects of SGLT2is on lipid profiles | Background Few systematic review s have examined the effects of sodium-glucose co-transporter 2 inhibitors ( SGLT2is ) on lipid profiles in Asian patients with type 2 diabetes mellitus .
We conducted a systematic review with a meta- analysis to summarize the available literature and confirm the effects of SGLT2is on lipid profiles in these patients . | PURPOSE To evaluate the influence of renal function on the efficacy and safety of the sodium glucose cotransporter 2 inhibitor luseogliflozin ( TS-071 ) in Japanese patients with type 2 diabetes mellitus ( T2DM ) . METHODS Study 1 was a 52-week , Phase III study to evaluate the efficacy and safety of 2.5 mg/d luseogliflozin ( or increased to 5 mg/d ) in patients with T2DM with moderate renal impairment . During the initial 24 weeks , efficacy and safety of luseogliflozin were compared with placebo . Study 2 was a pooled analysis of four 52-week , Phase III studies of luseogliflozin , including Study 1 , to evaluate the efficacy and safety of luseogliflozin in patients with various degrees of renal function . Patients were stratified into 3 groups by baseline estimated glomerular filtration rate ( eGFR ) : normal renal function ( ≥90 mL/min/1.73 m(2 ) ) , mild impairment ( ≥60 to < 90 mL/min/1.73 m(2 ) ) , and moderate impairment ( ≥30 to < 60 mL/min/1.73 m(2 ) ) . Patients with moderate impairment were further divided into those with mild-moderate ( ≥45 to < 60 mL/min/1.73 m(2 ) ) and moderate-severe ( ≥30 to < 45 mL/min/1.73 m(2 ) ) . In both studies , efficacy end points included changes in glycated hemoglobin ( HbA1c ) level , fasting plasma glucose ( FPG ) level , and body weight . The safety end points included adverse events ( AEs ) and laboratory parameters . FINDINGS In Study 1 , HbA1c , FPG , and body weight significantly decreased at Week 24 in patients treated with luseogliflozin compared with patients treated with placebo , with the decrease in these parameters also observed with luseogliflozin at Week 52 . The incidence of AEs was similar between groups . In Study 2 , 1030 patients were included ( normal , 275 ; mildly impaired , 598 ; and moderately impaired , 157 ) . At Week 52 , HbA1c , FPG , and body weight were significantly decreased from baseline in all groups . In between-group comparisons , the decreases in HbA1c and body weight were significantly smaller in patients with moderate impairment than in those with normal function ; however , the HbA1c-lowering efficacy was reduced by nearly half , whereas the efficacy of body weight lowering was not so much diminished in the moderate impairment group . Furthermore , a scatter plot showed that changes in HbA1c were more influenced by baseline HbA1c than by baseline eGFR . The incidence of AEs during 52 weeks was similar among all groups , with the majority being mild . IMPLICATION S Luseogliflozin improved glycemic control and reduced body weight in all eGFR groups , and its efficacy on HbA1c lowering was reduced in those with moderate renal impairment . Luseogliflozin was well tolerated and safe , with no significant safety issues identified , regardless of baseline eGFR . The study is registered with Clinical Trials Information/JapicCTI of the Japan Pharmaceutical Information Center , and the study registry identification numbers are JapicCTI-111507 , JapicCTI-111508 , JapicCTI-111509 , and JapicCTI-111543 Background Evidence concerning the importance of glucose lowering in the prevention of cardiovascular ( CV ) outcomes remains controversial . Given the multi-faceted pathogenesis of atherosclerosis in diabetes , it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone . The SGLT-2 inhibitor empagliflozin improves glucose control , body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes . The aim of the ongoing EMPA-REG OUTCOME ™ trial is to determine the long-term CV safety of empagliflozin , as well as investigating potential benefits on macro-/microvascular outcomes . Methods Patients who were drug-naïve ( HbA1c ≥7.0 % and ≤9.0 % ) , or on background glucose-lowering therapy ( HbA1c ≥7.0 % and ≤10.0 % ) , and were at high risk of CV events , were r and omized ( 1:1:1 ) and treated with empagliflozin 10 mg , empagliflozin 25 mg , or placebo ( double blind , double dummy ) superimposed upon the st and ard of care . The primary outcome is time to first occurrence of CV death , non-fatal myocardial infa rct ion , or non-fatal stroke . CV events will be prospect ively adjudicated by an independent Clinical Events Committee . The trial will continue until ≥691 confirmed primary outcome events have occurred , providing a power of 90 % to yield an upper limit of the adjusted 95 % CI for a hazard ratio of < 1.3 with a one-sided α of 0.025 , assuming equal risks between placebo and empagliflozin ( both doses pooled ) . Hierarchical testing for superiority will follow for the primary outcome and key secondary outcomes ( time to first occurrence of CV death , non-fatal myocardial infa rct ion , non-fatal stroke or hospitalization for unstable angina pectoris ) where non-inferiority is achieved . Results Between Sept 2010 and April 2013 , 592 clinical sites r and omized and treated 7034 patients ( 41 % from Europe , 20 % from North America , and 19 % from Asia ) . At baseline , the mean age was 63 ± 9 years , BMI 30.6 ± 5.3 kg/m2 , HbA1c 8.1 ± 0.8 % , and eGFR 74 ± 21 ml/min/1.73 m2 . The study is expected to report in 2015 . Discussion EMPA-REG OUTCOME ™ will determine the CV safety of empagliflozin in a cohort of patients with type 2 diabetes and high CV risk , with the potential to show cardioprotection . Trial registration Clinical trials.gov Aims We examined the efficacy , safety and tolerability of canagliflozin , a sodium glucose co-transporter 2 inhibitor , in Japanese patients with type 2 diabetes ( T2DM ) undergoing diet and exercise therapy . Methods Patients aged 20–80 years with T2DM diagnosed ≥3 months previously , and HbA1c of 6.9–9.9 % were r and omized to 50 , 100 , 200 or 300 mg canagliflozin or placebo once daily for 12 weeks . The primary and secondary endpoints were changes in HbA1c , fasting plasma glucose ( FPG ) , urinary glucose/creatinine and postpr and ial glycaemic parameters following a meal test . The safety assessment s included adverse events ( AEs ) and clinical laboratory tests . Results Overall , 383 patients were r and omized to receive either placebo ( n = 75 ) , or 50 mg ( n = 82 ) , 100 mg ( n = 74 ) , 200 mg ( n = 77 ) or 300 mg canagliflozin ( n = 75 ) . At week 12 , significant reductions in HbA1c were observed in all canagliflozin groups relative to placebo ( −0.61 , –0.80 , –0.79 and −0.88 % for 50 , 100 , 200 and 300 mg , respectively , versus + 0.11 % for placebo ; all , p < 0.01 ) . FPG and postpr and ial glycaemic parameters improved significantly in the canagliflozin groups . Body weight was significantly decreased by canagliflozin . No deaths or drug-related serious AEs were reported . There was no dose-dependent increase in the incidence of AEs in the canagliflozin groups . The incidence of hypoglycaemia was low ; episodes were not severe or dose dependent . Canagliflozin did not affect serum creatinine levels or the urinary albumin/creatinine ratio . Conclusions Treatment with canagliflozin for 12 weeks significantly improved glycaemic control and reduced body weight in Japanese patients with T2DM . Canagliflozin was well tolerated Background As a first-line diabetes drug that is widely prescribed around the world , metformin has been demonstrated to be effective in reducing microvascular risk , in addition to lowering glucose levels . Specifically , metformin use has been shown to be associated with improved lipid profiles , such as increased levels of high-density lipoprotein cholesterol ( HDL-C ) . However , no study has been performed to examine the differential response in HDL-C levels to metformin treatment by race/ethnicity . Methods Here , based on a re- analysis of the data from the Diabetes Prevention Program , which involved pre-diabetic participants receiving 850 mg of metformin twice daily , we compared the lipid profile changes following the metformin use . The participants were composed of 602 Whites , 221 African Americans ( AAs ) and 162 Hispanics . Results We found that the one-year metformin treatment result ed in a significant increase in HDL-C levels in Whites ( p = 0.002 ) and AAs ( p = 0.016 ) , but not in Hispanics . Consistently , both Whites ( p = 0.018 ) and AAs ( p = 0.020 ) had more pronounced changes in HDL-C levels than Hispanics following metformin treatment . Conclusion This result suggests a notion that Whites and AAs are more responsive than Hispanics to one-year metformin use in HDL-C level changes , and that racial and ethnic identity is a factor to consider when interpreting the effects of metformin treatment on lipid profiles Introduction This study was design ed to determine the efficacy and tolerability of empagliflozin monotherapy in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Methods Patients with glycosylated hemoglobin ( HbA1c ) ≥7.0–≤10 % were r and omized via an interactive web response system , and treated double-blind with empagliflozin 5 , 10 , 25 , 50 mg , or placebo once daily for 12 weeks . The primary endpoint was change from baseline in HbA1c at week 12 . Other endpoints included percentage of patients with HbA1c < 7.0 % and changes from baseline in fasting plasma glucose ( FPG ) , body weight , and systolic blood pressure ( SBP ) at week 12 . Results A total of 547 patients were r and omized and treated with empagliflozin 5 mg ( n = 110 ) , 10 mg ( n = 109 ) , 25 mg ( n = 109 ) , 50 mg ( n = 110 ) , or placebo ( n = 109 ) for 12 weeks . Adjusted mean [ 95 % confidence interval ( CI ) ] differences vs. placebo in changes from baseline in HbA1c were −0.72 % ( −0.87 , −0.57 ) with empagliflozin 5 mg , −0.70 % ( −0.85 , −0.55 ) with 10 mg , −0.95 % ( −1.10 , −0.80 ) with 25 mg , and −0.91 ( −1.06 , −0.76 ) with 50 mg ( all p < 0.001 ) . More patients with HbA1c ≥7.0 % at baseline reached HbA1c < 7.0 % with empagliflozin ( 19–33 % ) than placebo ( 3 % ) . Compared with placebo , empagliflozin reduced FPG , body weight ( p < 0.001 for all doses for both endpoints ) and SBP ( p = 0.001 , p = 0.014 and p = 0.003 for empagliflozin 10 , 25 , and 50 mg , respectively ) . Adverse events were reported by 42 % of patients receiving placebo and 33–38 % of patients receiving empagliflozin . There were few reports of confirmed hypoglycemic adverse events or events consistent with urinary tract infection or genital infection in any treatment group . Conclusions Empagliflozin monotherapy for 12 weeks in Japanese patients with T2DM reduced HbA1c , FPG , body weight and SBP , and was well tolerated SUMMARY Abstract Background Combination therapy with canagliflozin and insulin was investigated in a prescribed sub study of the canagliflozin Cardiovascular Assessment Study ( CANVAS ) ; however , it was not evaluated in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Since the usage profile of insulin therapy and pathologic features of Japanese patients differ from those of Caucasian patients , we determined the clinical benefit of such a combination therapy in Japanese patients . Methods Patients who had inadequate glycemic control despite insulin , diet and exercise therapies were r and omized into placebo ( n = 70 ) and canagliflozin 100 mg ( n = 76 ) groups that were administered once daily in addition to their prior insulin therapy in this double-blind , placebo-controlled study . The primary endpoint was the change in glycated hemoglobin ( HbA1c ) levels from the baseline to week 16 . Results There was a statistically significant decrease in HbA1c levels from the baseline in the canagliflozin group ( −0.97 ± 0.08 % ) compared with the placebo group ( 0.13 ± 0.08 % ) at week 16 [ last observation carried forward ( LOCF ) ] . The decrease in HbA1c levels in the canagliflozin group was independent of the insulin regimen ( premixed , long-acting and long-acting plus rapid- or short-acting ) . Compared with the placebo group , canagliflozin significantly decreased fasting plasma glucose levels ( −34.1 ± 4.8 vs −1.4 ± 5.0 mg/dL ) and body weights ( −2.13 ± 0.25 vs 0.24 ± 0.26 % ) , and significantly increased HDL cholesterol ( 3.3 ± 1.0 vs −0.5 ± 1.0 mg/dL ) and HOMA2- % B ( 10.15 ± 1.37 vs 0.88 ± 1.42 % ) . The overall incidence of adverse events was similar between the two groups . The incidence and incidence per subject-year exposure of hypoglycemia ( hypoglycemic symptoms and /or decreased blood glucose ) were slightly higher in the canagliflozin group ( 40.0 % and 7.97 ) than in the placebo group ( 29.6 % and 4.51 ) . However , hypoglycemic events in both groups were mild in severity and dose-reduction of insulin by < 10 % from the baseline following hypoglycemic events decreased the incidence per subject-year exposure in the canagliflozin group . The incidence of hypoglycemia between the groups did not differ according to the insulin regimen . Conclusion Canagliflozin in combination with insulin was effective in improving glycemic control and reducing body weight and well tolerated by Japanese patients with T2DM . Trial Registration Clinical Trials.gov identifier : Abstract Aims / Introduction To determine the efficacy and safety of ipragliflozin in combination with metformin in Asian patients with type 2 diabetes mellitus . Material s and Methods This phase 3 , multicenter , placebo‐controlled , double‐blind , parallel‐group study was carried out at 18 sites in Korea and 12 sites in Taiwan . After an 8‐week washout period for patients using drugs other than metformin and a 2‐week run‐in period , patients were r and omized to either 50 mg ipragliflozin or a placebo for 24 weeks while continuing metformin . Efficacy outcomes included the changes in hemoglobin A1c , fasting plasma glucose ( FPG ) and bodyweight from baseline to the end of treatment ( with last observation carried forward ) . Safety outcomes included treatment‐emergent adverse events . Results Between November 2011 and January 2013 , 171 patients were r and omized to and administered ipragliflozin ( n = 87 ) or a placebo ( n = 83 ) . The mean changes ( st and ard deviation ) in hemoglobin A1c were −0.94 % ( 0.75 % ) and −0.47 % ( 0.81 % ) in the ipragliflozin and placebo groups , respectively ( between‐group difference −0.46 % , P < 0.001 ) . The changes in fasting plasma glucose and bodyweight were also significantly greater in the ipragliflozin group , with between‐group differences of −14.1 mg/dL and −1.24 kg , respectively ( both P < 0.001 ) . The most common treatment‐emergent adverse events ( ipragliflozin vs placebo ) were upper respiratory tract infection ( 9.2 % vs 12.0 % ) and urinary tract infection ( 6.9 % vs 2.4 % ) . Conclusions These results show that ipragliflozin is effective and well tolerated when used in combination with metformin in Asian patients with type 2 diabetes mellitus Canagliflozin is a sodium glucose co‐transporter 2 inhibitor in development for treatment of type 2 diabetes mellitus ( T2DM ) . This study evaluated the efficacy and safety of canagliflozin in subjects with T2DM and stage 3 chronic kidney disease [ CKD ; estimated glomerular filtration rate ( eGFR ) ≥30 and < 50 ml/min/1.73 m2 ] Background In recent years , several oral antidiabetic drugs with new mechanisms of action have become available , exp and ing the number of treatment options . Sodium/glucose cotransporter-2 ( SGLT2 ) inhibitors are a new class of oral antidiabetic drugs with an insulin-independent mechanism promoting urinary glucose excretion . We report the results of a combined Phase 2 and 3 clinical study ( Japic CTI-101349 ) of the SGLT2 inhibitor tofogliflozin ( CSG452 , RG7201 ) in Japanese patients with type 2 diabetes mellitus . Methods The efficacy and safety of tofogliflozin were assessed in this multicenter , placebo-controlled , r and omized , double-blind parallel-group study involving 230 patients with type 2 diabetes mellitus with inadequate glycemic control on diet/exercise therapy . Between 30 October 2010 and 28 February 2012 , patients at 33 centers were r and omized to either placebo ( n = 56 ) or tofogliflozin ( 10 , 20 , or 40 mg ; n = 58 each ) orally , once daily for 24 weeks . The primary efficacy endpoint was the change from baseline in HbA1c at week 24 . Results Overall , 229 patients were included in the full analysis set ( placebo : n = 56 ; tofogliflozin 10 mg : n = 57 ; tofogliflozin 20 and 40 mg : n = 58 each ) . The least squares ( LS ) mean change ( 95 % confidence interval ) from baseline in HbA1c at week 24 was −0.028 % ( −0.192 to 0.137 ) in the placebo group , compared with −0.797 % ( −0.960 to −0.634 ) in the tofogliflozin 10 mg group , −1.017 % ( −1.178 to −0.856 ) in the tofogliflozin 20 mg group , and −0.870 % ( −1.031 to −0.709 ) in the tofogliflozin 40 mg group ( p < 0.0001 for the LS mean differences in all tofogliflozin groups vs placebo ) . There were also prominent decreases in fasting blood glucose , 2-h postpr and ial glucose , and body weight in all tofogliflozin groups compared with the placebo group . The main adverse events were hyperketonemia , ketonuria , and pollakiuria . The incidence of hypoglycemia was low . Furthermore , most adverse events were classified as mild or moderate in severity . Conclusions Tofogliflozin 10 , 20 , or 40 mg administered once daily as monotherapy significantly decreased HbA1c and body weight , and was generally well tolerated in Japanese patients with type 2 diabetes mellitus . Phase 3 studies were recently completed and support the findings of this combined Phase 2 and 3 study .Trial registration This study was registered in the JAPIC clinical trials registry ( ID : Japic%CTI-101349 ) OBJECTIVE Dapagliflozin is a highly selective , orally active inhibitor of renal sodium-glucose cotransporter 2 that reduces hyperglycemia by increasing urinary glucose excretion . The goal of this study was to evaluate dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes whose disease was inadequately controlled with diet and exercise . METHODS In this Phase III , multicenter , parallel-group , double-blind study , drug-naive patients with glycosylated hemoglobin ( HbA1c ) levels ≥7.0 % to ≤10.5 % ( ≥53-≤91 mmol/mol ) were r and omized ( by using an interactive voice response system ) to receive placebo ( n = 132 ) , dapagliflozin 5 mg ( n = 128 ) , or dapagliflozin 10 mg ( n = 133 ) . The primary end point was mean change from baseline in HbA1c level at week 24 ( last-observation-carried-forward ) . Secondary end points included changes in fasting plasma glucose , 2-hour postpr and ial glucose , body weight , and other glycemic parameters . RESULTS Baseline characteristics were balanced across groups . Most patients ( 89 % ) were Chinese , median disease duration was 0.2 year , and mean HbA1c level was 8.26 % . Most patients ( 87 % ) completed the study . At week 24 , mean reductions in HbA1c were -0.29 % for placebo versus -1.04 % and -1.11 % for dapagliflozin 5 and 10 mg , respectively ( P < 0.0001 for both doses ) . Changes in fasting plasma glucose were 2.5 , -25.1 , and -31.6 mg/dL ( 0.14 , -1.39 , and -1.75 mmol/L ) for placebo , dapagliflozin 5 mg , and dapagliflozin 10 mg . Changes in 2-hour postpr and ial glucose were 1.1 , -46.8 , and -54.9 mg/dL ( 0.06 , -2.60 , and -3.05 mmol/L ) . Reductions in body weight were -0.27 , -1.64 , and -2.25 kg . Proportions of patients achieving HbA1c levels < 7.0 % ( 53 mmol/mol ) were 21.3 % , 42.6 % , and 49.8 % . Adverse events ( AEs ) occurred in 63.6 % , 61.7 % , and 60.9 % of patients , and serious AEs occurred in 1.5 % , 3.9 % , and 3.0 % of patients . No deaths occurred . Hypoglycemia was uncommon ( 1.5 % , 0.8 % , and 0.8 % ) ; no hypoglycemic event led to discontinuation . Genital infections occurred in 0.8 % , 3.1 % , and 4.5 % of patients and urinary tract infections in 3.0 % , 3.9 % , and 5.3 % of patients . No AEs of renal infection or pyelonephritis were reported . No changes in renal function or AEs of renal failure occurred . CONCLUSIONS Compared with placebo , dapagliflozin 5 and 10 mg demonstrated clinical ly and statistically significant improvements in HbA1c levels after 24 weeks of treatment . Dose-dependent , statistically significant reductions in fasting plasma glucose , postpr and ial glucose , and weight were also observed for both doses compared with placebo . AEs and serious AEs were balanced across groups , with low rates of hypoglycemia and no increase in renal events . Genital infections and urinary tract infections were more common with dapagliflozin . Dapagliflozin as monotherapy in these drug-naive Asian patients was well tolerated , significantly improving glycemic control with the additional benefit of weight loss OBJECTIVE Only a small number of population -based cohort studies have directly compared the predictive value of low-density lipoprotein cholesterol ( LDL-C ) and non-high-density lipoprotein cholesterol ( non-HDLC ) for coronary artery disease in Asian population s , such as Japan . METHODS We performed an 11.9-year cohort study of 4694 men and women , aged 30 - 74 years , selected r and omly from an urban general population in Japan . Baseline LDL-C levels were estimated using the Friedewald formula . The predictive values of LDL-C and non-HDLC for myocardial infa rct ion ( MI ) and stroke were compared . RESULTS AND CONCLUSION During the follow-up period , there were 80 incident cases of MI and 139 of stoke , comprised of 23 intracerebral hemorrhages , 85 cerebral infa rct ions and 31 other types of stroke . The Hazard ratio ( HR ) for MI was highest in the top quintile of LDL-C ( HR : 3.03 , 95 % CI , 1.32 - 6.96 ) when male and female data were combined . The HR for MI was also highest in the top quintile of non-HDLC ( HR : 2.97 , 95 % CI , 1.26 - 6.97 ) . Analysis of trends showed a significant positive relationship between MI incidence and serum LDL-C and non-HDLC levels ( both P=0.02 ) . However , there was no relationship between the incidence of any subtype of stroke and either LDL-C or non-HDLC . The predictive value of LDL-C and non-HDLC for MI , assessed by calculating the differences in the -2 logarithm likelihood ( -2ln [ L ] ) and area under the curve ( AUC ) , were almost similar OBJECTIVE To determine the optimal diet for improving glucose and lipid profiles in obese patients with type 2 diabetes during moderate energy restriction . RESEARCH DESIGN AND METHODS A total of 35 free-living obese patients with type 2 diabetes were assigned to one of three 1,600 kcal/day diets for 12 weeks . The diets were high carbohydrate ( 10 % fat , 4 % saturated ) , high monounsaturated fat ( MUFA ) ( 32 % fat , 7 % saturated ) , or high saturated fat ( SFA ) ( 32 % fat , 17 % saturated ) . RESULTS Diet composition did not affect the magnitude of weight loss , with subjects losing an average of 6.6 + /- 0.9 kg . Energy restriction and weight loss result ed in reductions in fasting plasma glucose ( -14 % ) , insulin ( -27 % ) , GHb ( -14 % ) , and systolic ( -7 % ) and diastolic blood pressure ( -10 % ) levels and the glucose response area ( -17 % ) independent of diet composition . Diet composition did affect the lipoprotein profile . LDL was 10 % and 17 % lower with the high-carbohydrate and high-MUFA diets , respectively , whereas no change was observed with the high-SFA diet ( P < 0.001 for effect of diet ) . HDL was transiently reduced on the high-carbohydrate diet at weeks 1 , 4 , and 8 , whereas higher fat consumption maintained these levels . The total cholesterol : HDL ratio , although significantly reduced on the high-MUFA diet ( P < 0.01 ) , was not different from the other two diets after adjustment for baseline differences . CONCLUSIONS Energy restriction , independent of diet composition , improves glycemic control ; however , reducing SFA intake by replacing SFA with carbohydrate or MUFA reduces LDL maximally during weight loss and to a greater degree than has been shown in weight-stable studies AIMS The long-term efficacy and safety of canagliflozin , a sodium glucose co-transporter 2 inhibitor , was evaluated over 104 weeks in patients aged 55 - 80 years with type 2 diabetes mellitus ( T2DM ) inadequately controlled on a stable antihyperglycaemic agent regimen . METHODS In this r and omized , double-blind , phase III study , patients received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period ( N = 714 ) and a 78-week extension period ( n = 624 ) . Efficacy endpoints at week 104 included change from baseline in glycated haemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) and systolic blood pressure , and percent change from baseline in body weight and fasting plasma lipids . Safety was assessed by adverse event ( AE ) reports . RESULTS At week 104 , canagliflozin 100 and 300 mg were associated with reductions in HbA1c versus placebo ( -0.32 and -0.43 % vs 0.17 % , respectively ; overall mean baseline , 7.7 % ) and more patients achieved HbA1c < 7.0 % with canagliflozin 100 and 300 mg than with placebo ( 35.8 and 41.9 % vs 20.3 % , respectively ) . Reductions in FPG , body weight and systolic blood pressure , and increases in high-density lipoprotein cholesterol ( HDL-C ) and low-density lipoprotein cholesterol ( LDL-C ) were seen with canagliflozin compared with placebo . The overall incidence rates of AEs over 104 weeks were 88.0 , 89.8 and 86.1 % with canagliflozin 100 and 300 mg and placebo , respectively ; serious AE rates were low across treatment groups . The incidence rates of urinary tract infections , genital mycotic infections and osmotic diuresis- and volume depletion-related AEs were higher with canagliflozin than with placebo . CONCLUSION Canagliflozin improved glycaemic control , reduced body weight and systolic blood pressure , and was generally well tolerated in patients aged 55 - 80 years with T2DM over 104 weeks AIMS To evaluate the efficacy and safety of canagliflozin , a sodium glucose co-transporter 2 inhibitor , in Asian patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled by metformin or metformin in combination with sulphonylurea . METHODS In this 18-week , r and omized , double-blind , placebo-controlled phase III study , patients ( N = 676 ) received canagliflozin 100 or 300 mg or placebo once daily . The primary efficacy endpoint was change in glycated haemoglobin ( HbA1c ) level from baseline at week 18 . Additional endpoints included change in fasting plasma glucose ( FPG ) and percent change in body weight . Adverse events ( AEs ) were recorded throughout the study . Efficacy and safety were assessed in the overall population and in two strata based on background therapy . RESULTS At week 18 , canagliflozin 100 and 300 mg provided significant reductions from baseline in HbA1c compared with placebo ( -0.97 , -1.06 and -0.47 % , respectively ; p < 0.001 ) . Relative to placebo , canagliflozin 100 and 300 mg also significantly reduced FPG ( -1.0 and -1.4 mmol/l ) and body weight [ -2.2 % ( -1.5 kg ) and -2.3 % ( -1.6 kg ) ] . Both canagliflozin doses lowered systolic blood pressure ( BP ) compared with placebo . The overall incidence of AEs was 38.6 , 43.2 and 42.0 % with canagliflozin 100 and 300 mg and placebo , respectively . The incidence of genital mycotic infections and urinary tract infections was low and similar across groups . Efficacy and safety findings in the two strata were generally consistent with the overall population . CONCLUSIONS Canagliflozin provided glycaemic improvements and reductions in body weight and systolic BP , and was generally well tolerated in Asian patients with T2DM on metformin or metformin in combination with sulphonylurea Abstract Objective : Luseogliflozin – a novel , orally bioavailable , 1-thio-d-glucitol derivative and a selective sodium glucose cotransporter 2 inhibitor – has shown efficacy and tolerability in previous phase 2 studies . This phase 3 , r and omized , double-blind , placebo-controlled , comparative study aim ed to confirm the superiority of 24 week luseogliflozin 2.5 mg monotherapy over placebo in reducing hemoglobin A1c ( HbA1c ) levels in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Methods : Patients with HbA1c levels of 6.9%–10.5 % were r and omized to receive luseogliflozin 2.5 mg or placebo once daily for 24 weeks ( n = 79 in each group ) . The primary endpoint was change from baseline in HbA1c at end of treatment . Secondary endpoints included change from baseline in fasting plasma glucose ( FPG ) and postpr and ial plasma glucose ( PPG ) following a meal tolerance test , body weight , and abdominal circumference . Safety assessment s included adverse events ( AEs ) , clinical laboratory tests , and vital signs . Results : At the end of treatment , HbA1c was significantly decreased from baseline in the luseogliflozin 2.5 mg group ( −0.63 % ) versus the placebo group ( 0.13 % ) , with a between-group difference of −0.75 % ( p < 0.001 ) . Additionally , significant reductions in FPG , PPG , body weight , and abdominal circumference were noted with luseogliflozin compared with placebo ( all p < 0.05 ) . Luseogliflozin was well tolerated ; there was no significant difference between groups in the incidence of AEs ( luseogliflozin , 59.5 % ; placebo , 57.0 % ) . No AEs led to study drug discontinuation . Most AEs were mild in severity , with no severe AE reported . Limitations of this study include its short study duration and small sample size . Conclusion : Luseogliflozin monotherapy for 24 weeks was superior to placebo in reducing HbA1c levels . It also reduced FPG , PPG , body weight , and abdominal circumference and was well tolerated in Japanese patients with T2DM . Clinical trial registration : JapicCTI-111661 Objective : To examine the efficacy and safety of canagliflozin monotherapy , a sodium/glucose co-transporter 2 inhibitor , in Japanese type 2 diabetes patients . Methods : In this double-blind , multi-centre Phase III study , patients aged ≥ 20 years with hemoglobin A1c ( HbA1c ) 7.0 – 10.0 % on diet/exercise therapy alone received placebo or canagliflozin ( 100 or 200 mg ) once daily for 24 weeks . The main outcome measure was the change in HbA1c from baseline to Week 24 . Results : The changes in HbA1c ( −0.74 and −0.76 vs + 0.29 % ) , fasting plasma glucose ( 1 mg/dl = 0.0555 mmol/l ; −31.6 and −31.9 vs + 3.7 mg/dl ) , 2-h plasma glucose after 75-g glucose load ( −84.9 and −79.0 vs −0.5 mg/dl ) , body weight ( percent change : −3.76 and −4.02 vs −0.76 % ) and systolic blood pressure ( −7.88 and −6.24 vs −2.72 mmHg ) were significantly greater with 100 and 200 mg canagliflozin than with placebo ( all , p < 0.05 ) . Genital infections in females ( 6.5 , 6.3 and 0 % ) and asymptomatic hypoglycemia ( 4.4 , 5.6 and 2.2 % ) , but not symptomatic hypoglycemia ( 2.2 , 1.1 and 1.1 % ) , were more frequent in the 100- and 200-mg groups than in the placebo group . Conclusion : Canagliflozin significantly improved glycemic control and was well tolerated AIMS To evaluate the efficacy and safety of the selective sodium glucose co-transporter 2 inhibitor dapagliflozin in Japanese patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled by diet and exercise . METHODS Patients received placebo or dapagliflozin ( 5 or 10 mg ) once daily for 24 weeks . The primary outcome measure was change from baseline in glycated haemoglobin ( HbA1c ) . RESULTS Patients ( N = 261 ) had modestly elevated baseline HbA1c ( mean ≈ 7.5 % ) and most had mild or moderate renal impairment ( estimated glomerular filtration rate range 43 - 103 ml/min/1.73 m(2 ) ) . Greater reductions in mean HbA1c level were observed with dapagliflozin ( 5 mg , -0.41 % ; 10 mg , -0.45 % ) than with placebo ( -0.06 % ) at week 24 and these were greater in patients with higher baseline HbA1c levels . Fasting plasma glucose ( FPG ) was also significantly reduced with dapagliflozin ( 5 mg , -8.6 mg/dl ; 10 mg , -13.7 mg/dl ) compared with placebo ( + 5.8 mg/dl ) . Dapagliflozin significantly reduced body weight ( 5 mg , -2.13 kg ; 10 mg , -2.22 kg ) compared with placebo ( -0.84 kg ) . Overall , 47.7 and 64.8 % of patients with dapagliflozin 5 and 10 mg , respectively , and 51.7 % with placebo experienced ≥ 1 adverse event , mostly mild or moderate , and unrelated to study treatment . Two patients on dapagliflozin 10 mg reported hypoglycaemia . Four patients across all groups reported events suggestive of genital infection and four of urinary tract infection . No events of pyelonephritis were reported . CONCLUSION Dapagliflozin ( 5 and 10 mg ) was well tolerated and effective in reducing HbA1c , FPG and body weight over 24 weeks in Japanese patients with T2DM inadequately controlled by diet and exercise Abstract Objective : Luseogliflozin is a novel sodium glucose cotransporter 2 inhibitor for type 2 diabetes mellitus ( T2DM ) treatment . An exploratory Phase II study was conducted to assess the efficacy and safety of several doses of luseogliflozin in Japanese T2DM patients . Patients and methods : Japanese T2DM patients aged 20–74 years with hemoglobin A1c ( HbA1c ) of 6.9–10.5 % , fasting plasma glucose ( FPG ) ≥126 mg/dL and on diet therapy were r and omized in a double-blind manner to receive luseogliflozin ( 0.5 , 2.5 , or 5 mg ) or placebo once daily for 12 weeks ( n = 61 , 61 , 61 , and 56 , respectively ) . The primary endpoint was the change in HbA1c from baseline to end of treatment . Other endpoints included FPG , 2 h postpr and ial plasma glucose ( PPG ) in a meal tolerance test ( MTT ) , and body weight . Drug safety was also assessed . Trial registration : Japan Pharmaceutical Information Center ( identifier : JapicCTI-090908 ) . Results : Changes in HbA1c from baseline to end of treatment were −0.36 , −0.62 , and −0.75 % in the 0.5 , 2.5 , and 5 mg luseogliflozin groups , respectively , versus + 0.06 % in the placebo group ( all P < 0.001 ) . The reductions in FPG and 2 h-PPG in the MTT were also significantly greater in the luseogliflozin groups ( all P < 0.01 ) without increases in insulin levels from baseline . Luseogliflozin reduced body weight at all doses . There were no significant differences in the incidences of adverse events among groups . Most adverse events were mild in severity . There were no serious adverse events . Conclusions : Although this was a small-scale study with a short duration , all tested doses of luseogliflozin significantly improved glycemic control , reduced body weight , and were well tolerated in Japanese T2DM patients over the 12-week treatment period Abstract Objectives : Luseogliflozin is a selective sodium glucose cotransporter 2 inhibitor under development for the treatment of type 2 diabetes mellitus ( T2DM ) . This phase II study was conducted to confirm the efficacy and safety of luseogliflozin monotherapy at doses of up to 10 mg in Japanese patients with T2DM . Patients and methods : Patients with hemoglobin A1c ( HbA1c ) of 6.9–10.5 % on diet therapy were r and omized in a double-blind manner to treatment with 1 , 2.5 , 5 , or 10 mg luseogliflozin or placebo for 12 weeks ( n = 56 , 56 , 54 , 58 , and 58 , respectively ) . Trial registration : Japan Pharmaceutical Information Center ( identifier : Japic CTI-101191 ) . Main outcome measures : The primary endpoint was the change in HbA1c from baseline to the end of treatment . Other endpoints included fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) and body weight . Adverse events were recorded throughout the study . Results : HbA1c decreased significantly at the end of treatment in the 1 , 2.5 , 5 , and 10 mg luseogliflozin groups compared with placebo ( −0.29 , −0.39 , −0.46 , and −0.43 % , respectively , versus + 0.22 % ; all P < 0.001 ) , as did FPG and PPG ( all P < 0.001 ) . Body weight also decreased significantly in all luseogliflozin groups compared with placebo ( all P < 0.001 ) . The incidence rates of adverse events ( 40.0–50.0 % ) were not significantly different among the five groups . The overall incidence of hypoglycemia was low . Limitations of this study include the short study duration and the relatively small sample size . Conclusions : In Japanese patients with T2DM , luseogliflozin was well tolerated , improved glycemic control , and reduced body weight over 12 weeks of treatment at all tested doses . Doses of ≥2.5 mg achieved similar improvements in glycemic control |
11,847 | 23,315,046 | There is great inconsistency in reported characteristics of Hispanics in health research . | The size and diversity of the Hispanic population in the United States has dramatically increased , with vast implication s for health research . | OBJECTIVE To determine whether racial/ethnic differences in colon cancer screening are independent of socioeconomic and personal risk factors . DESIGN Baseline cross-section for a prospect i ve cohort . METHOD We recruited adults between 2000 and 2002 to undergo a question naire and venipuncture to study cancer risks . RESULTS Among 5595 adults over 50 years old , 40.3 % reported sigmoidoscopy or colonoscopy within the prior five years ; rates were 48.0 % for Whites , 32.8 % for Blacks , 27.9 % for Hispanics , 30.3 % for Asians , and 33.3 % for others . Adjusting for age , gender , access to care ( as income and insurance ) , and risk profile ( as cancer in family , smoking , and obesity ) , Blacks and Hispanics were less likely to have been screened than Whites . CONCLUSIONS Screening for colon cancer is low , especially among racial/ethnic minorities . Sociocultural factors merit closer attention CONTEXT A 1990 National Institutes of Health Consensus Conference recommended that patients with stage III colon cancer receive adjuvant chemotherapy because survival was improved in clinical trials in patients who received a 5-fluorouracil-based regimen . OBJECTIVE To determine whether adjuvant chemotherapy is used in the community as a st and ard of practice that improves outcome and whether it failed to benefit any specific sets of patients . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve data from 85 934 patients with stage III colon cancer from 560 hospital cancer registries were entered into the National Cancer Data Base between 1990 and 2002 and included st and ard clinical , pathological , and first course of treatment variables . MAIN OUTCOME MEASURES Prevalence of adjuvant chemotherapy usage and 5-year survival in patients treated in US hospitals . RESULTS Adjuvant chemotherapy use increased from 39 % in 1991 to 64 % in 2002 but was lower in black , female , and elderly patients . It improved 5-year survival from almost 8 % in 1991 to more than 16 % in 1997 compared with surgery alone . Adjuvant chemotherapy increases survival in elderly patients as much as it does in younger patients . However , the benefit of adjuvant chemotherapy in blacks and those with high- grade cancers is not as great . CONCLUSIONS Adjuvant chemotherapy use has increased from 1990 to 2002 for patients with stage III colon cancer with an associated increase in 5-year survival of 16 % . The benefit of adjuvant chemotherapy seems to be lower in black patients and high- grade cancers . Women have the same benefit but are less often treated . Elderly patients have the same benefit as younger patients but are less frequently treated . New options for adjuvant therapy in 2004 - 2005 may further improve the outcome of patients with stage III colon cancer Background : Evidence about the accuracy of self-reports of colorectal cancer ( CRC ) screening is lacking . We conducted a validation protocol in a r and omized trial to increase CRC screening among high-risk individuals . Methods : First-degree relatives ( n = 1,280 ) of CRC cases who were due for CRC screening were included in the parent trial . All subjects who completed the follow-up interview ( n = 948 ) were asked to participate in validation activities . Self-reports of receipt of CRC screening during the 12-month study period were verified via physicians . Results : Although 60 % ( n = 567 ) verbally agreed , only 171 subjects ( 18 % of original sample ) returned the signed validation form with the physician name and contact information and a medical information release statement . The signed forms were mailed to physicians with a $ 10 incentive and the request to list the date s of recent CRC screening tests . One hundred twenty-three physicians ( 72 % of physicians contacted , 13 % of original sample ) returned completed validation forms . Rates of agreement were low across all three screening types with physicians verifying self-reported screening for 29 % of fecal occult blood testing , 56 % of sigmoidoscopy , 55 % of colonoscopy , and 57 % of any screening test . Conclusion : Validation of self-report using the type of protocol we used for subjects receiving medical care in many community setting s may be unfeasible and cost inefficient . Given the overall low participation rate in validation activities and considerable challenges in collecting high quality data , conclusions about the accuracy of self-reported CRC screening are difficult to make based on the results of this study . ( Cancer Epidemiol Biomarkers Prev 2008;17(4):791–8 Colorectal cancer is the second leading cause of cancer death in the United States.1 Appropriate screening can reduce incidence of and mortality from colorectal cancer.2–5 The US Preventive Services Task Force recommends that all average-risk individuals aged 50 years and older receive colorectal cancer screening.6 The American Cancer Society recommends several acceptable approaches to screening , including an annual 3-card home fecal occult blood test.7 The Healthy People 2010 objective is to increase the proportion of people aged 50 and older who have received a fecal occult blood test within the preceding 2 years to at least 50%.8 Lack of knowledge , confidence , and skills ; negative attitudes toward the tests themselves ; fear of the consequences of screening ; and inadequate social support all have been suggested as possible barriers to colorectal cancer screening,9 whereas positive attitudes toward colorectal cancer screening and physician encouragement have been associated with receipt of a fecal occult blood test with a home stool kit.10 Despite these studies , gaps remain in what is known about barriers to successful interventions to increase colorectal cancer screening , particularly in minority population s.11,12 This study is based on the assumption that identification and definition of barriers to colorectal cancer screening in low-income , underserved minority population s can help guide the development of effective interventions Abstract The present study was design ed to assess ethnic disparities in CRC screening rates in a low-income population and to examine factors that could account for those differences . Participants were r and omly selected and asked to complete a question naire about CRC screening . After controlling for gender , age , education , income , health insurance , and family history of CRC , differences in screening rates as a function of ethnicity remained . Physicians ' recommendations and perceived efficacy of screening were also strong predictors of CRC screening . Psychological factors accounted in part for differences in screening rates between European Americans and Mexican Americans Colorectal carcinoma ranks as the second most common cancer and the second leading cause of cancer death in the United States . Hispanics are less likely than their non‐Hispanic white counterparts to have ever received a fecal occult blood test ( FOBT ) or sigmoidoscopy/colonoscopy . Little is known about the barriers to screening in the Hispanic population Background : Diabetics have been found to have a greater risk of colorectal cancer than non-diabetics . Methods : We examined whether this relationship differed by ethnic group , cancer site or tumour stage in a population -based prospect i ve cohort , including 3549 incident colorectal cancer cases identified over a 13-year period ( 1993–2006 ) among 199 143 European American , African American , Native Hawaiian , Japanese American and Latino men and women in the Multiethnic Cohort . Results : Diabetics overall had a significantly greater risk of colorectal cancer than did non-diabetics ( relative risk (RR)=1.19 , 95 % confidence interval (CI)=1.09–1.29 , P-value (P)<0.001 ) . Positive associations were observed for colon cancer , cancers of both the right and left colon , and cancers diagnosed at a localised and regional/distant stage . The association with colorectal cancer risk was significantly modified by smoking status ( PInteraction=0.0044 ) , with the RR being higher in never smokers ( RR=1.32 , 95 % CI=1.15–1.53 , P<0.001 ) than past ( RR=1.19 , 95 % CI=1.05–1.34 , P=0.007 ) and current smokers ( RR=0.90 , 95 % CI=0.70–1.15 , P=0.40 ) . Conclusion : These findings provide strong support for the hypothesis that diabetes is a risk factor for colorectal cancer Objective : There is evidence that non-English speakers in the United States receive lower quality health care and preventive services than English speakers . We tested the hypothesis that Spanish-speaking women would respond differently to an intervention to increase up-to- date status for cancer screening . Study Design and Setting : A multisite r and omized controlled trial showed that scripted telephone support , provided by a Prevention Care Manager ( PCM ) , increased up-to- date rates for breast , cervical , and colorectal cancer screening . This subgroup analysis investigated the relative efficacy of the PCM among women who chose to communicate with the PCM in Spanish versus English . Results : Of 1,346 women in this analysis , 63 % were Spanish speakers . Whereas the PCM intervention increased cancer screening rates generally , Spanish-speaking women seemed to benefit disproportionately more than English-speaking women for cervical cancer screening ( unadjusted odds ratio , 1.77 ; 95 % confidence interval , 1.03 - 3.05 ) . In addition , in this exploratory analysis , there was a trend toward Spanish-speaking women receiving more benefit than English-speaking women from the intervention in increased breast and colorectal cancer screening rates . Conclusion : Spanish-speaking women seemed to benefit more than did English-speaking women from a bilingual telephone support intervention aim ed at increasing cancer screening rates . ( Cancer Epidemiol Biomarkers Prev 2007;16(10):2058–64 Background This paper presents the study design , intervention components , and baseline data from Open Doors to Health , a study design ed to address social context ual factors in colorectal cancer ( CRC ) prevention for low-income , racial/ethnic minority population s. Methods A cluster r and omized design with 12 housing sites as the primary sampling units was used : 6 sites were assigned to a " Peer-led plus Screening Access " ( PL ) condition , and 6 were assigned to " Screening Access only " ( SCR ) condition . Study -related outcomes were CRC screening , physical activity ( measured as mean steps/day ) , and multivitamin use . Results At baseline ( unweighted sample size = 1554 ) , two-thirds self-reported that they were current with screening recommendations for CRC ( corrected for medical records validation , prevalence was 52 % ) , with half having received a colonoscopy ( 54 % ) ; 96 % had health insurance . Mean steps per day was 5648 ( se mean = 224 ) , and on average 28 % of the sample reported regular multivitamin use . Residents reported high levels of social support [ mean = 4.40 ( se = .03 ) ] and moderately extensive social networks [ mean = 2.66 ( se = .02 ) ] . Conclusion Few studies have conducted community-based studies in public housing communities ; these data suggest areas for improvement and future opportunities for intervention development and dissemination . Findings from the r and omized trial will determine the effectiveness of the intervention on our health-related outcomes as well as inform future avenues of research OBJECTIVE Health promotion efforts directed at Latinos may be more effective when culturally adapted methods are used . Our study was design ed to test a novel communication modality for promoting colorectal cancer ( CRC ) prevention and screening messages among Latinos . METHODS We compared a culturally aligned , brief storytelling educational intervention ( ST ) to a numeric risk tool intervention ( NR ) based on the Harvard Cancer Risk Index . Both interventions included risk factor information and recommendations for primary prevention and screening for CRC . Sixty-four Latinos ( mean age 46.8 , 86 % female ) were r and omized and completed pre- and post-tests . RESULTS Participants in ST indicated intent to add significantly more servings of vegetables ( p=.030 ) and more minutes of exercise ( p=.018 ) to daily routines than those in NR . Most respondents ( ST and NR ) reported intentions to recommend CRC screening to friends and relatives . CONCLUSIONS These data provide support for storytelling 's potential to promote health behavior change with cultural relevance for Latinos . PRACTICE IMPLICATION S Storytelling shows promise as an effective method for reaching one of the historically underserved ethnic groups with cancer prevention and screening information Background Minority racial/ethnic groups have low colorectal cancer ( CRC ) screening rates . Objective To evaluate a culturally tailored intervention to increase CRC screening , primarily using colonoscopy , among low income and non-English speaking patients . Design R and omized controlled trial conducted from January to October of 2007 . Setting Single , urban community health center serving a low-income , ethnically diverse population . Patients A total of 1,223 patients 52 - 79 years of age overdue for CRC screening , r and omized to intervention ( n = 409 ) vs. usual care control ( n = 814 ) groups . InterventionIntervention patients received an introductory letter with educational material followed by phone or in-person contact by a language -concordant “ navigator . ” Navigators ( n = 5 ) were community health workers trained to identify and address patient-reported barriers to CRC screening . Individually tailored interventions included patient education , procedure scheduling , translation and explanation of bowel preparation , and help with transportation and insurance coverage . Rates of colorectal cancer screening were assessed for intervention and usual care control patients . Results Over a 9-month period , intervention patients were more likely to undergo CRC screening than control patients ( 27 % vs. 12 % for any CRC screening , p < 0.001 ; 21 % vs. 10 % for colonoscopy completion , p < 0.001 ) . The higher screening rate result ed in the identification of 10.5 polyps per 100 patients in the intervention group vs. 6.8 in the control group ( p = 0.04 ) . Limitations Patients were from one health center . Some patients may have obtained CRC screening outside our system . Conclusions A culturally tailored , language -concordant navigator program design ed to identify and overcome barriers to colorectal cancer screening can significantly improve colonoscopy rates for low income , ethnically and linguistically diverse patients . Clinical Trials.gov registration number : OBJECTIVE To test a multimedia patient education program on colorectal cancer ( CRC ) screening that was design ed specifically for the Hispanic/Latino community , and developed with input from community members . METHODS A total of 270 Hispanic/Latino adults , age 50 - 80 years , participated in Spanish for all phases of this pretest-posttest design . Patients were r and omly assigned to a version of the multimedia program that opened with either a positive or negative introductory appeal . Structured interviews assessed screening relevant knowledge ( anatomy and key terms , screening options , and risk information ) , past screening behavior , willingness to consider screening options , intention to discuss CRC screening with the doctor , and reactions to the multimedia patient education program . RESULTS The multimedia program significantly increased knowledge of anatomy and key terms ( e.g. , polyp ) , primary screening options ( FOBT , flexible sigmoidoscopy , colonoscopy ) , and risk information as well as willingness to consider screening ( p<.001 for all ) . No significant differences emerged between positive and negative introductory appeals on these measures , intention to discuss CRC screening with their doctor , or rating the multimedia program . CONCLUSION Multimedia tools developed with community input that are design ed to present important health messages using graphics and audio can reach Hispanic/Latino adults across literacy levels and ethnic background s. Additional research is needed to determine effects on actual screening behavior . PRACTICE IMPLICATION S Despite promising results for engaging a difficult-to-reach audience , the multimedia program should not be considered a st and -alone intervention or a substitute for communication with physicians . Rather , it is a priming mechanism intended to prepare patients for productive discussion s of CRC screening PURPOSE The purpose of this analysis was to assess the impact of pretreatment factors on quality of life ( QOL ) in cancer patients . METHODS AND MATERIAL S Pretreatment QOL ( via Functional Assessment of Cancer Therapy [ FACT ] , version 2 ) was obtained in 1,428 patients in several prospect i ve Radiation Therapy Oncology Group ( RTOG ) trials including nonmetastatic head- and -neck ( n = 1139 ) , esophageal ( n = 174 ) , lung ( n = 51 ) , rectal ( n = 47 ) , and prostate ( n = 17 ) cancer patients . Clinical ly meaningful differences between groups were defined as a difference of 1 st and ard error of measurement ( SEM ) . RESULTS The mean FACT score for all patients was 86 ( 20.7 - 112 ) with SEM of 5.3 . Statistically significant differences in QOL were observed based on age , race , Karnofsky Performance Status , marital status , education level , income level , and employment status , but not by gender or primary site . Using the SEM , there were clinical ly meaningful differences between patients < /=50 years vs. > /=65 years . Hispanics had worse QOL than whites . FACT increased linearly with higher Karnofsky Performance Status and income levels . Married patients ( or live-in relationships ) had a better QOL than single , divorced , or widowed patients . College graduates had better QOL than those with less education . CONCLUSION Most pretreatment factors meaningfully influenced baseline QOL . The potentially devastating impact of a cancer diagnosis , particularly in young and minority patients , must be addressed BACKGROUND Latino immigrants face a higher burden of colorectal cancer ( CRC ) and screening rates are low . OBJECTIVE To assess the effectiveness of a multilevel intervention in increasing the rate of CRC screening among Latino immigrants . DESIGN A r and omized controlled trial , with r and omization at the physician level . PARTICIPANTS Pairs of 65 primary care physicians and 65 Latino immigrant patients participated , 31 in the intervention and 34 in the control group . INTERVENTIONCRC educational video in Spanish on a portable personal digital video display device accompanied by a brochure with key information for the patient , and a patient-delivered paper-based reminder for their physician . MEASUREMENTS Completed CRC screening , physician recommendation for CRC screening , and patient adherence to physician recommended CRC screening . RESULTS The overall rate of completed screening for CRC was 55 % for the intervention and 18 % for the control group ( p = 0.002 ) . Physicians recommended CRC screening for 61 % of patients in the intervention group versus 41 % in the control group ( p = 0.08 ) . Of those that received a recommendation , 90 % in the intervention group adhered to it versus 26 % in the control group ( p = 0.007 ) . CONCLUSIONS The intervention was successful in increasing rates of completed CRC screening primarily through increasing adherence after screening was recommended . Additional efforts should focus on developing new strategies to increase physician recommendation for CRC screening , while employing effective patient adherence interventions OBJECTIVES : Although the association between distal neoplasia on sigmoidoscopy and proximal colonic pathology on follow-up colonoscopy has been well-described , it is not known if these findings are consistent across ethnic groups . The aim of this study was to evaluate ethnic variations in the prevalence of proximal neoplasia on follow-up colonoscopy after a neoplastic lesion is found on sigmoidoscopy . METHODS : Consecutive asymptomatic patients at average-risk for colorectal cancer who were referred for screening flexible sigmoidoscopy were prospect ively enrolled . Colonoscopy was recommended for all patients with a polyp on flexible sigmoidoscopy , regardless of size . Advanced neoplasms were defined as adenomas ≥10 mm in diameter or any adenoma , regardless of size , with villous histology , high- grade dysplasia , or cancer . RESULTS : Among the 2,207 patients who had sigmoidoscopy , 970 were Caucasian , 765 were African American , 395 were Hispanic , and 77 were Asian . The prevalence of neoplasia in the distal colon was 12.6 % in Caucasians , 11.2 % in African Americans , 15.9 % in Hispanics , and 24.7 % in Asians ( p= 0.002 ) . Of the 290 patients with neoplastic lesions on sigmoidoscopy , follow-up colonoscopy identified neoplasms in the proximal colon in 63.9 % of Caucasians , 59.3 % of African Americans , 66.7 % of Hispanics , and 26.3 % of Asians ( p= 0.01 ) . Advanced neoplasms in the proximal colon were highest in African Americans ( 34.9 % ) and lowest in Asians ( 10.5 % ) . CONCLUSIONS : In our study population , Asians demonstrated a higher prevalence of distal colonic neoplasia and a lower prevalence of proximal colonic neoplasia compared to non-Asians . Future studies should explore ethnic variation in colonic neoplasia prevalence and location since ethnic variation could lead to tailored colorectal cancer screening strategies Background : Increasing colorectal cancer screening ( CRCS ) can have a substantial positive impact on morbidity and mortality . Objectives : The purpose of this report is to describe the development and feasibility testing of a computer-based , theory-guided educational program design ed to increase CRCS . Research Design : This mixed- methods study used focus groups and subsequent r and omized controlled trial design . Subjects : Participants ( N = 199 ) were r and omized to an intervention or control group ; 75 % were African American ; mean age was 57.36 ( SD = 6.8 ) ; 71 % were male . Measures : Previously vali date d measures on knowledge , beliefs , and screening test adherence were used to establish pre- and post-intervention perceptions . Feasibility was measured by response and completion rates , and participants ’ perceptions of the program . Results : Before feasibility testing , the program was presented to 2 focus groups . Changes were made to the program based on discussion , leading to a visually appealing , easy to underst and and navigate , self-paced program . In the RCT pilot test that followed , of the participants in the intervention group , 80 % said the education helped them decide to get CRCS ; 49 % agreed it helped them overcome barriers ; 91 % agreed it was useful , 68 % thought it raised new concerns about cancer , but only 30 % said it made them worry about CRC ; 95 % agreed their doctor 's office should continue giving such education , and 99 % said they would inform family about the program . Conclusions : The response rate of 83 % demonstrated feasibility of conducting colorectal cancer education in the primary care setting ; overall the program was well received ; participants averaged 23 minutes to complete it . Participants sought no help from attending data collectors and navigated the revised touch screen program with ease . Computer-based education is feasible in primary care clinics BACKGROUND Minority population s in the United States , especially blacks and Hispanics , are generally underrepresented among participants in clinical trials . Here , we report the experience of enrolling ethnic minorities in a large cancer screening trial . METHODS The Prostate , Colorectal , Lung and Ovarian ( PLCO ) Cancer Screening Trial is a multicenter r and omized trial design ed to evaluate the effectiveness of screening for the PLCO cancers . Subjects were recruited at 10 U.S. centers between 1993 and 2001 . One screening center had a major special recruitment effort for blacks and another center had a major special recruitment effort for Hispanics . RESULTS Among almost 155,000 subjects enrolled in PLCO , minority enrollment was as follows : black ( 5.0 % ) , Hispanic ( 1.8 % ) and Asian ( 3.6 % ) . This compares to an age-eligible population in the combined catchment areas of the PLCO centers that was 14.0 % black , 2.9 % Hispanic and 5.4 % Asian , and an age-eligible population across the U.S. that was 9.5 % black , 6.5 % Hispanic and 3.0 % Asian . About half ( 45 % ) of Hispanics were recruited at the center with the special Hispanic recruitment effort . Seventy percent of blacks were recruited at two centers ; the one with the major special recruitment effort and a center in Detroit whose catchment area was 20 % black among age-eligibles . Blacks , Hispanics and ( non-Hispanic ) whites were all more highly educated , less likely to currently smoke and more likely to get regular exercise than their counterparts in the general population . CONCLUSION Significant efforts were made to recruit racial/ ethnic minorities into PLCO , and these efforts result ed in enrollment levels that were comparable to those seen in many recent cancer screening or prevention trials . Blacks and Hispanics were nonetheless underrepresented in PLCO compared to their levels among age-eligibles in the overall U.S. population or in the aggregate PLCO catchment areas High circulating concentration of insulin-like growth factor-I ( IGF-I ) and low circulating concentration of IGF binding protein-3 ( IGFBP-3 ) have been associated with increased risk for breast , prostate , and colorectal cancers . Building on previous work in the Multiethnic Cohort ( MEC ) showing significant differences in IGF-I levels across racial/ethnic groups , we investigated which lifestyle and dietary factors are associated with levels of IGF-I and IGFBP-3 in a r and om sample of 1,000 MEC participants , which included Native Hawaiian , African American , Japanese , Latino , and White men and women . Crude analyses confirmed the existence of differences in protein levels with race/ethnicity , sex , age , and body size . Reproductive , physical activity , smoking , and diet variables had less consistent effects . In multivariate analyses , IGF-I levels were lower and IGFBP-3 were higher in females versus males . IGF-I and IGFBP-3 declined with increasing age in both genders . Women in the highest quartile of body mass index showed depressed IGF-I and IGFBP-3 levels ; in men , height was significantly positively associated with both proteins . In women , alcohol was directly associated with IGFBP-3 . Both proteins were lowest among female Latinos . IGF-I was highest among female African Americans . In men , IGFBP-3 was lowest among African Americans . Overall , although these factors were statistically significant determinants of IGF-related protein levels , they did not explain much of the variation in these levels . A positive correlation was found between IGF-I levels ( ng/mL ) and colon cancer incidence rates ( per 100,000 ) within the MEC by race/ethnicity for both sexes but not for either breast or prostate cancer Studies of migrants , along with geographic and temporal variations in incidence , indicate that colorectal cancer is especially sensitive to changes in environmental factors , including , most importantly , diet . The goal of this research was to examine the changes in dietary practice s that may be consistent with the changing incidence of colorectal cancer in the Los Angeles Mexican-American population . Cancer incidence and dietary intake data were available for over 35,000 Latinos of Mexican national origin currently participating in the prospect i ve Multiethnic Cohort Study , representing the largest sample of Mexican-origin Latinos of any such study in the United States . The data set is unique in that changes in cancer rates and in dietary behaviors across three generations could be examined . Most of the change in colorectal cancer rates occurred between the first and second generations , and , correspondingly , nearly all the dietary change also occurred between the first and second generations . Although some food traditions were retained by Mexican Americans , the dietary changes due to acculturation were significant and support an association between colorectal cancer risk and certain dietary components , notably , alcohol as a risk factor and nonstarch polysaccharides and vegetables as protective factors Methylenetetrahydrofolate reductase ( MTHFR ) is a key regulatory enzyme in the metabolism of folate , a nutrient that has been inversely related to colorectal cancer risk . The common C677 T variant in the MTHFR gene results in a reduced activity of this enzyme , thereby increasing the availability of folate for the production of thymidylate and purine for DNA synthesis and repair . We investigated the association of the 677TT genotype with colorectal cancer in a case-control study of 822 cases and 2,021 controls nested within the Multiethnic Cohort Study . The Multiethnic Cohort Study is a large prospect i ve study of men and women of Japanese , White , African American , Latino , and Native Hawaiian origin , residing in Hawaii and Los Angeles . After adjusting for covariates , we found an inverse association between colorectal cancer risk and the TT genotype , with odds ratios ( OR ; and 95 % confidence intervals ) for the CC , CT , and TT genotypes of 1.00 , 1.01 ( 0.84 - 1.21 ) , and 0.77 ( 0.58 - 1.03 ) , respectively . This association was similar in both sexes , stronger at high levels of folate intake , and limited to light and nondrinkers ( P for interaction with ethanol = 0.02 ) . An analysis by subsite ( rectum versus colon ) and stage ( regional/distant versus in situ/localized ) showed that the inverse association with the TT genotype was limited to colon tumors , especially those diagnosed at an advanced stage . The OR for the TT versus CC genotype for early- and late-stage colon cancer was 0.88 ( 0.58 - 1.33 ) and 0.52 ( 0.32 - 0.85 ) , respectively ( P for difference in OR = 0.04 ) . The frequency of the T allele was relatively low in African Americans ( 0.13 ) and Native Hawaiians ( 0.22 ) , consistent with their greater likelihood of presenting at a late stage when diagnosed with colorectal cancer . This study corroborates previous findings of an inverse association of the MTHFR 677TT genotype with colorectal cancer , especially at high levels of folate and low levels of ethanol intake . It also suggests that this effect may be specific to advanced colon cancer BACKGROUND Preferences toward endoscopists have been shown to be a barrier to colorectal cancer screening in certain patient population s. OBJECTIVE To evaluate sex and ethnicity preferences for endoscopists in a largely Hispanic population . METHODS This was a prospect i ve cross-sectional study . Patients were given an anonymous question naire in which information on demographics and sex/ethnic preferences for endoscopists was determined . Bivariate and multivariate models were used to assess factors that affected outcome variables . RESULTS A total of 438 patients were included ( 213 men , 225 women ; mean age 62 years ) . Predominant ethnicities were white ( 44 % ) and Hispanic ( 45 % ) . Twenty-six percent and 17 % of patients expressed sex and ethnicity preferences , respectively . Women ( 30.8 % ) , particularly Hispanic women ( 35 % ) , had a sex preference more often than men ( 20.4 % ; P < .05 ) . Hispanics had an ethnicity preference more often than white patients ( P < .01 ) . Lower education level , being a first-generation immigrant , family history of colorectal cancer , having a concurrent preference for obstetrician/gynecologist , and ethnicity preference for endoscopist were associated with the presence of a sex preference for the endoscopist ( P < .05 ) . Being a first-generation immigrant and having an ethnicity preference for a primary care provider or the sex of the endoscopist were significantly associated with a preference for the ethnicity of the endoscopist ( P < .05 ) . LIMITATIONS Results are based on self-report . Limited study factors were also assessed . CONCLUSIONS Among a predominant Hispanic population , sex and ethnicity preferences for endoscopists are often seen . They may coexist , increase the likelihood of the presence of one when the other is present , and likely influence compliance with colorectal cancer screening BACKGROUND Colorectal cancer ( CRC ) screening rates are increasing , but they are still low , particularly in ethnic minority groups . In many re source -poor setting s , fecal occult blood test ( FOBT ) is the main screening option . INTERVENTION Culturally tailored telephone counseling by community health advisors employed by a community-based organization , culturally tailored brochures , and customized FOBT kits . DESIGN RCT . Participants were r and omized to ( 1 ) basic intervention : culturally tailored brochure plus FOBT kit ( n=765 ) ; ( 2 ) enhanced intervention : brochure , FOBT plus telephone counseling ( n=768 ) ; or ( 3 ) usual care ( n=256 ) . SETTING / PARTICIPANTS Latino and Vietnamese primary care patients at a large public hospital . MAIN OUTCOME MEASURES Self-reported receipt of FOBT or any CRC screening at 1-year follow-up . RESULTS 1358 individuals ( 718 Latinos and 640 Vietnamese ) completed the follow-up survey . Self-reported FOBT screening rates increased by 7.8 % in the control group , by 15.1 % in the brochure group , and by 25.1 % in the brochure/telephone counseling group ( p<0.01 for differences between each intervention and usual care and for the difference between brochure/telephone counseling and brochure alone ) . For any CRC screening , rates increased by 4.1 % in the usual care group , by 11.9 % in the FOBT/brochure group , and by 21.4 % in the brochure/telephone counseling group ( p<0.01 for differences between each intervention and usual care and for the difference between the basic and the enhanced intervention ) . CONCLUSIONS An intervention that included culturally tailored brochures and tailored telephone counseling increased CRC screening in Latinos and the Vietnamese . Brochure and telephone counseling together had the greatest impact . Future research should address replication and dissemination of this model for Latinos and Vietnamese in other communities , and adaptation of the model for other groups |
11,848 | 26,894,274 | The most examined correlates were biological and demographic factors .
Age ( increasing ) was a correlate of children ’s motor competence .
Weight status ( healthy ) , sex ( male ) and socioeconomic background ( higher ) were consistent correlates for certain aspects of motor competence only .
Physical activity and sport participation constituted the majority of investigations in the behavioral attributes and skills category .
Whilst we found physical activity to be a positive correlate of skill composite and motor coordination , we also found indeterminate evidence for physical activity being a correlate of object control or locomotor skill competence .
Indeed our findings do suggest that evidence for some correlates differs according to how motor competence is operationalized | Background Gross motor competence confers health benefits , but levels in children and adolescents are low .
While interventions can improve gross motor competence , it remains unclear which correlates should be targeted to ensure interventions are most effective , and for whom targeted and tailored interventions should be developed .
Objective The aim of this systematic review was to identify the potential correlates of gross motor competence in typically developing children and adolescents ( aged 3–18 years ) using an ecological approach . | The objectives of this study were to examine the effects of diabetes during pregnancy on the long-term motor development of the offspring and to study possible correlations between glycemic control and motor development . We compared the motor development of 57 children , 5- to 12-years-of-age , born to 48 mothers with well-controlled diabetes , to the motor development of 57 control children matched by age , birth order , and parental socio-economic status . Children born to mothers with diabetes performed less well than controls in fine and gross motor functions on the Bruininks-Oseretsky Test of Motor Proficiency . A negative correlation existed between the test scores of the children whose mothers had diabetes and the severity of hyperglycemia as assessed by blood glycosylated hemoglobin levels and acetonuria . Motor ability of the children of mothers with diabetes had a high correlation with biological and environmental variables . These results suggest that diabetes during pregnancy may affect the developing brain , inducing long-term mild motor deficiency . The effects seem to result from the adverse effects of diabetic metabolic factors , and the effects correlate with the degree of diabetes control . The combination of metabolic functioning of women with diabetes and home environment may affect the motor development of their children PURPOSE The purpose of this study was to evaluate the Hunter Illawarra Kids Challenge Using Parent Support physical activity program in overweight children . METHODS A multisite r and omized controlled trial was conducted with three intervention arms : 1 ) child-centered physical activity skill development program ( Activity ) , 2 ) parent-centered dietary modification program ( DIET ) , or 3 ) both programs combined ( PA+DIET ) . Movement skill proficiency , perceived athletic competence , accelerometer-assessed physical activity , and parent-reported time spent in screen behaviors were assessed at baseline , 6 months , and 12 months in 165 prepubertal children aged 5.5 - 9 yr ( 59 % girls , 78 % obese ) . Differences in changes in outcomes between groups were assessed using linear mixed models . RESULTS Compared with the diet group , the activity group ( mean ( 95 % confidence interval ) : + 7.7 units ( 3.8 - 11.6 units ) ) and the activity + diet group ( + 6.7 units ( 2.9 - 10.5 units ) ) displayed 11%-13 % greater improvement in overall movement skill proficiency ( gross motor quotient ) at 6 months . Perceived athletic competence increased across groups at follow-up ( across groups : 6 months = + 0.21 units ( 0.11 - 0.31 units ) , 12 months = + 0.21 units ( 0.07 - 0.35 units ) ) . Groups did not differ statistically for change in physical activity outcomes . Total screen time ( min·wk(-1 ) ) decreased in all groups at 6 months ( across groups : -385.4 ( -501.0 to -269.8 ) ) and in the activity group ( -261.8 ( -470.5 to -53.1 ) ) and activity + diet group ( -340.5 ( -534.6 to -146.4 ) ) at 12 months . The diet group reported greater reductions in TV or DVD viewing time at 6 months compared with the activity group ( 248.6 ( 24.0 - 473.3 ) ) . CONCLUSIONS The activity and the activity + diet programs were efficacious in improving overweight children 's movement skill proficiency . All programs were efficacious in reducing time spent in screen behaviors . Other correlates may need to be targeted in addition to movement skills to increase physical activity among overweight children Differences in the age of attainment of motor skills between boys and girls have been established in previous studies . It has been noted that boys develop ball skills earlier than girls and that girls acquire manual dexterity before boys . The purpose of this study was to determine if the same differences could be identified in a group of typically developing seven and eight year old children using the Movement Assessment Battery for Children Test ( MABC Test ) . In this study , a physiotherapist administered the MABC Test to 103 r and omly selected children ( boys-60 , girls-43 ) . The MABC Test examines children 's motor skills in the areas of manual dexterity , ball skills and balance . Results were analyzed using analysis of variance ( ANOVA ) . The ANOVA results indicated significant differences between boys ' and girls ' ball skill scores and manual dexterity scores PURPOSE To test for relationships between objective ly measured habitual physical activity and fundamental movement skills in a relatively large and representative sample of preschool children . METHODS Physical activity was measured over 6 d using the Computer Science and Applications ( CSA ) accelerometer in 394 boys and girls ( mean age 4.2 , SD 0.5 yr ) . Children were scored on 15 fundamental movement skills , based on the Movement Assessment Battery , by a single observer . RESULTS Total physical activity ( r=0.10 , P<0.05 ) and percent time spent in moderate to vigorous physical activity ( MVPA ) ( r=0.18 , P<0.001 ) were significantly correlated with total movement skills score . Time spent in light-intensity physical activity was not significantly correlated with motor skills score ( r=0.02 , P>0.05 ) . CONCLUSIONS In this sample and setting , fundamental movement skills were significantly associated with habitual physical activity , but the association between the two variables was weak . The present study questions whether the widely assumed relationships between motor skills and habitual physical activity actually exist in young children AIM The objective of this study was to determine relationships between body composition and motor and physical competence of Grade 1 learners living in the North West Province of South Africa . METHODS Data were collected by means of a stratified r and om sampling procedure from 816 Grade 1 learners ( 419 boys , 397 girls ) with a mean age of 6.84 years ( + 0.39 SD ) , in the NW-CHILD- study . Height , weight , skinfolds ( subscapular , triceps , calf ) and waist circumference were measured . International cut-off values were used to classify the subjects in normal , overweight or obese categories . Motor and physical competence was measured by using the Bruiniks-Oseretsky Test of Motor Proficiency-2 SF and the Test of Gross Motor Development 2 . RESULTS One out of 10 learners were overweight or obese . Fine motor precision , balance , running speed and agility and strength correlated significantly with BMI with no clear relationships with object control skills and upper limb-coordination . CONCLUSION A clear relationship was found between body composition and most of the motor and physical fitness competencies of Grade 1 learners . Intervention strategies to improve the body composition of overweight children and accompanying motor proficiency back logs and physical fitness deficiencies are recommended PURPOSE Physical activity ( PA ) declines dramatically during adolescence , and activity levels are consistently lower among children living in low-income communities . Competency in a range of fundamental movement skills ( FMS ) may serve as a protective factor against the decline in PA typically observed during adolescence . The purpose of this study was to evaluate the effect of a 12-month multicomponent PA and FMS intervention on children attending primary schools in low-income communities . METHODS The Supporting Children 's Outcomes using Rewards , Exercise , and Skills intervention was evaluated using a cluster r and omized controlled trial . The sample included 25 classes from eight primary schools located in low-income communities . Participants were 460 children ( 54.1 % girls ) age 8.5 ± 0.6 yr . Primary outcomes were objective ly measured PA ( ActiGraph GT3X and GT3X+ accelerometers ) , FMS competency ( Test of Gross Motor Development 2 , six locomotor and six object control skills ) , and cardiorespiratory fitness ( 20-m multistage fitness test ) assessed at baseline , midprogram ( 6-months ) , and at posttest ( 12 months ) . Linear mixed models , adjusted for sex , age , body mass index z-score , socioeconomic status , ethnicity , and school class as a r and om factor , were used to assess the effect of the intervention . RESULTS At midprogram , there were no significant intervention effects for any of the outcomes . At posttest ( study 's primary time point ) , there were intervention effects for daily moderate-to-vigorous PA ( MVPA ) ( adjusted mean difference , 12.7 min·d of MVPA ; 95 % confidence interval ( CI ) , 5.0 - 20.5 ) , overall FMS competency ( 4.9 units ; 95 % CI , -0.04 to 9.8 ) , and cardiorespiratory fitness ( 5.4 laps ; 95 % CI , 2.3 - 8.6 ) . CONCLUSIONS A school-based multicomponent PA and FMS intervention maintained daily MVPA , improved overall FMS competency , and increased cardiorespiratory fitness among children attending primary schools in low-income communities |
11,849 | 22,915,173 | Overall , the articles pointed to a tendency of lower mean temperatures in groups with alternating therapy .
Few adverse effects were reported .
Although there was a tendency towards the reduction of mean temperatures with alternating antipyretics compared to the use of one antipyretic alone , there is not enough evidence to say that alternating antipyretic therapy is more effective than monotherapy | OBJECTIVE To summarize the existing evidence on the efficacy of therapy with alternating antipyretics compared to monotherapy in the management of fever in children . | OBJECTIVE To evaluate the efficacy of different antipyretic agents and their highest recommended doses for preventing febrile seizures . DESIGN R and omized , placebo-controlled , double-blind trial . SETTING Five hospitals , each working as the only pediatric hospital in its region . PARTICIPANTS A total of 231 children who experienced their first febrile seizure between January 1 , 1997 , and December 31 , 2003 . The children were observed for 2 years . INTERVENTIONS All febrile episodes during follow-up were treated first with either rectal diclofenac or placebo . After 8 hours , treatment was continued with oral ibuprofen , acetaminophen , or placebo . MAIN OUTCOME MEASURE Recurrence of febrile seizures . RESULTS The children experienced 851 febrile episodes , and 89 of these included a febrile seizure . Febrile seizure recurrences occurred in 54 of the 231 children ( 23.4 % ) . There were no significant differences between the groups in the main measure of effect , and the effect estimates were similar , as the rate was 23.4 % ( 46 of 197 ) in those receiving antipyretic agents and 23.5 % ( 8 of 34 ) in those receiving placebo ( difference , 0.2 ; 95 % confidence interval , -12.8 to 17.6 ; P = .99 ) . Fever was significantly higher during the episodes with seizure than in those without seizure ( 39.7 degrees C vs 38.9 degrees C ; difference , 0.7 degrees C ; 95 % confidence interval , -0.9 degrees C to -0.6 degrees C ; P < .001 ) , and this phenomenon was independent of the medication given . CONCLUSIONS Antipyretic agents are ineffective for the prevention of recurrences of febrile seizures and for the lowering of body temperature in patients with a febrile episode that leads to a recurrent febrile seizure A descriptive profile for antipyretic drug action has been documented for children . However , a linked pharmacokinetic – pharmacodynamic ( PK/PD ) model is central to the underst and ing of antipyretic drug action in febrile children . This was examined for previously reported data from 178 febrile children who received a single oral dose of acetaminophen ( APAP ) ( 12.5 mg/kg ) , ibuprofen ( IBU ) ( 5 or 10 mg/kg ) , or placebo . Rectal temperatures and plasma levels ( μg/ml ) of APAP and IBU were measured for up to 12 hr after drug administration . Nonlinear regression analyses were applied to these measurements and yielded simultaneous solutions of an integrated one-compartment PK , link , and SigmoidEmaxeffect model in 102/153 febrile children given APAP or IBU . The PK parameters ( tlag , ka , β , T1/2β , AUC0–∞,Vd/F , and Clp/F ) were not different than those reported previously , except the APAPkawas significantly lower . The link component yieldedkeos of 0.58±0.06 ( X±SE ) , 0.70±0.11 and 0.57 ± 0.11 hr-1for APAP , IBU05 , and IBU10 , respectively : the SigmoidEmaxcomponent yieldedEC50s ( μg/ml ) and sigmoidicity ( γ ) of 4.63±0.39 and 3.98±0.42 for APAP , 11.33±1.35 and 3.97±0.58 for IBU05 and 12.83±1.89 and 4.27±0.63 for IBU10 . On visual inspection of the efficacy – time profiles of the febrile children , a number of them had an apparent linear function ( slope ; Δ ° C/hr ) and /or a sinusoidal cyclic function “ confounding ” st and ard approaches to PD analysis . Thus , the temperature profiles of 91/102 children given APAP or IBU required the addition of a slope ( Δ ° C/hr ) and /or a sinusoidal cyclic function to the SigmoidEmaxcomponent to fit the data satisfactorily . All 22 children given a placebo also required a slope and /or a cyclic function in their PD model . The residual Δ ° Cs ( observed-predicted ) of the placebo group were not significantly different from 0 . Thus , no placebo antipyretic effect was observed . Dose dependency of IBUAUC0–∞was confirmed ; doubling the dose from 5 to 10 mg/kg increased theAUC0→∞by only 1.5-fold . The confounding effect of initial temperature ( Tempi ) on antipyretic efficacy in all treatment groups except placebo was also confirmed to expose nonlinear pharmacodynamics . A significant ( p=0.03 ) contribution ofTempi(but not age ) on the value of the slope function was found . There was no consistent effect of age orTempi , on the cyclic component of the integrated model of antipyresis . In addition , a multiple linear relationship of age and Tempiwas observed with a large number of the PK , link , and PD variables in those who received IBU . Dose , age , and Tempiinteracted with β in a significant multiple linear relationship withAUC0–∞. The effects of IBU dose , age , and Tempiare pervasive and cascade down the chain of events leading to the PD response . The etiology of pyresis may create the slope function , the magnitude of which may be partially due to the underlying disease . In some cases , the cyclic function may be explained by temperature regulation . Regardless of their cause , both confound analysis of drug action and make the simple , unmodified SigmoidEMaxeffect model less than satisfactory for interpretation of antipyretic drug effects . The influence of Tempion the magnitude of antipyretic drug response is also a finding with major impact on PD investigations of antipyretic medications . In children receiving IBU , dose and age are also confounders , in addition toTempi . A multiplicity of covariables must be taken into account when developing appropriate dosing regimens for these antipyretics in febrile children BACKGROUND Many pediatricians recommend , and many parents administer , alternating or combined doses of ibuprofen and acetaminophen for fever . Limited data support this practice with st and ard US doses . OBJECTIVE This study compared the antipyretic effect of 3 different treatment regimens in children , using either ibuprofen alone , ibuprofen combined with acetaminophen , or ibuprofen followed by acetaminophen over a single 6-hour observation period . METHODS Febrile episodes from children aged 6 to 84 months were r and omized into the 3 treatment groups : a single dose of ibuprofen at the beginning of the observation period ; a single dose of ibuprofen plus a single dose of acetaminophen at the beginning of the observation period ; or ibuprofen followed by acetaminophen 3 hours later . Ibuprofen was administered at 10 mg/kg ; acetaminophen at 15 mg/kg . Temperatures were measured hourly for 6 hours using a temporal artery thermometer . The primary outcome was temperature difference between treatment groups . Adverse-event data were not collected in this single treatment period study . RESULTS Sixty febrile episodes in 46 children were assessed . The mean ( SD ) age of the children was 3.4 ( 2.2 ) years , and 31 ( 51.7 % ) were girls . Differences among temperature curves were significant ( P < 0.001 ; the combined and alternating arms had significantly better antipyresis compared with the ibuprofen-alone group at hours 4 to 6 ( hour 4 , P < 0.005 ; hours 5 and 6 , P < 0.001 ) . All but one of the children in the combined and alternating groups were afebrile at hours 4 , 5 , and 6 . In contrast , for those receiving ibuprofen alone , 30 % , 40 % , and 50 % had temperatures > 38.0 ° C at hours 4 , 5 , and 6 , respectively ( hour 4 , P = 0.002 ; hours 5 and 6 , P < 0.001 ) . CONCLUSION During a single 6-hour observation period for these participating children , combined and alternating doses of ibuprofen and acetaminophen provided greater antipyresis than ibuprofen alone at 4 to 6 hours . Clinical Trials.gov identifier : NCT00267293 A comparison of different antipyretics in children with malaria showed a small effect of naproxen , but not of metamizol , on the reduction of fever peaks . Antipyretic treatment had no effect on fever clearance and therefore should be used cautiously in the treatment of malaria Purpose LATIN is a multinational case – control study design ed to identify risk factors for agranulocytosis and to estimate the incidence rate of the disease in some Latin American countries . Methods Each study site in Brazil , Argentina and Mexico conducted an active search of agranulocytosis patients in hematology clinics and looked for possible associations with drug use . Results The overall incidence rate was 0.38 cases per 1 million inhabitant – years . Agranulocytosis patients more often took medications already associated with agranulocytosis than controls ( p = 0.01 ) , mainly methimazole ( OR 44.2 , 95 % CI 6.8 to infinity ) . The population attributable risk percentage ( etiologic fraction ) was 56 % . The use of nutrient supplements was more frequent among patients than controls ( p = 0.03 ) . Conclusions Agranulocytosis seems to be very rare in Latin America . The lower than expected number of cases identified during the study period precluded estimation of the risk associated to individual drugs , with the exception of methimazol . However , this is the longest series of agranulocytosis cases ever gathered in Latin America , and information on drug exposures was collected prospect ively . The conclusion is that drug-induced agranulocytosis does not seem to be a major public health problem in the study regions OBJECTIVE To compare the antipyretic benefit of acetaminophen or ibuprofen monotherapy with an alternating regimen of both drugs in young children aged 6 to 36 months . DESIGN R and omized , double-blind , parallel-group trial . SETTING Three primary pediatric community ambulatory centers in central Israel . PARTICIPANTS A total of 464 children aged 6 to 36 months with fever . INTERVENTION Infants were assigned to receive either acetaminophen ( 12.5 mg/kg per dose every 6 hours ) ( n = 154 ) or ibuprofen ( 5 mg/kg per dose every 8 hours ) ( n = 155 ) or to receive alternating acetaminophen and ibuprofen ( every 4 hours ) ( n = 155 ) for 3 days after a loading dose . MAIN OUTCOME MEASURES Temperature , stress score , amount of antipyretic received , total days that the infant or caregiver was absent from day care or work , respectively , at the 3-day time point , recurrence of fever , and number of emergency department visits . RESULTS The group given the alternating regimen was characterized by a lower mean temperature , more rapid reduction of fever , receiving less antipyretic medication , less stress , and less absenteeism from day care as compared with the other groups ; all of the differences were statistically significant ( P < .001 ) . None of the regimens were associated with a significantly higher number of emergency department visits ( P = .65 ) or serious long-term complications ( P = .66 ) . The drug used for initial loading had no effect on outcome in any of the groups . CONCLUSIONS An alternating treatment regimen of acetaminophen ( 12.5 mg/kg per dose ) and ibuprofen ( 5 mg/kg per dose ) every 4 hours for 3 days , regardless of the initial loading medication , is more effective than monotherapy in lowering fever in infants and children The antipyretic effect of nimesulide has not been adequately compared with paracetamol and ibuprofenparacetamol combination in children . Hence , a r and omized , double blind , and parallel groups ’ design and multicenter study was conducted on children with respiratory tract infections . Eighty-nine patients with temperatures above 38.5 ° C were r and omly administered nimesulide ( 1.5 mgJkgJdose ) , paracetamol ( 10.0 mgJkgJdose ) , or ibuprofen- patients combination ( 10.0 mgJkgJdose ) , thrice daily for five days . The axillary temperature was recorded at the baseline and at different time intervals post administration of drugs . The hematological and biochemical investigations were performed at the basal level and at the end of the treatment period . The adverse drug reactions were monitored during the trial . All the drugs produced a significant fall in temperature as compared to their respective basal values ( p<0.001 ) . However , on looking at the change in temperatures at different time intervals from the respective basal levels , no significant difference was found among all the drugs . Surprisingly , nimesulide had a tendency to raise serum glutamate pyruvate transaminase and serum glutamate oxaloacetate transaminase levels as compared to its baseline values . There was no marked adverse effect of the drugs on other hematological and biochemical parameters investigated . No other serious adverse reaction occurred in the study . Ibuprofen-paracetamol combination , nimesulide , and paracetamol had almost similar antipyretic effects in children Abstract Objective : To compare the effectiveness and rate of temperature reduction of three antipyretic medications in febrile children . Design : A single-dose , r and omised , prospect i ve , modified double-blind , parallel clinical trial . Setting : The paediatric emergency department of a university hospital that has 13 000 annual visits . Study participants : 252 otherwise healthy children aged 6 months to 14 years with acute , intercurrent , febrile illness . Interventions : Enrolled children were assigned to receive a single dose of oral ibuprofen 10 mg/kg , oral nimesulide 2.5 mg/kg , or parenteral dipyrone 10 mg/kg . Main outcome measures and results : Axillary temperature was measured at the time of antipyretic administration and at 30 , 45 , 60 and 120 minutes thereafter . All three medications were effective in reducing the axillary temperature during the 2-hour testing period . The rates of axillary temperature change between the three medications were significantly different for the ibuprofen and dipyrone groups ( p = 0.023 ) . In addition , the axillary temperature in the dipyrone group was significantly lower than that in the ibuprofen group ( p = 0.036 ) at 120 minutes . There was no significant difference in antipyretic effect between the nimesulide group and the other two groups during the testing period . Within each group the difference between initial temperature and the temperature at the end of the testing period was statistically significant ( p = 0.036 ) for the dipyrone group only . Conclusions : All three antipyretic medications were effective in reducing the axillary temperature in febrile children . Although administration of intramuscular dipyrone seemed to be more effective than ibuprofen , this relationship was not significant when nimesulide was considered . In addition , in view of its known side effects and the problems associated with intramuscular administration in children , the preference for orally administered nimesulide or ibuprofen over dipyrone in the setting of the emergency department seems more logical provided that the child accepts oral therapy This study compared the antipyretic effectiveness of acetaminophen , ibuprofen , and dipyrone in young children with fever . The results were based on a modified double-blind , r and omized , multinational trial that evaluated 628 febrile children , aged 6 months to 6 year . All three drugs lowered temperature in the 555 patients completing the study . Temperature normalization rates in the ibuprofen and dipyrone groups ( 78 % and 82 % , respectively ) were significantly higher than the acetaminophen group ( 68 % , P=0.004 ) . After 4 to 6 hours , mean temperature in the dipyrone group was significantly lower than the other groups , demonstrating longer temperature normalization with dipyrone . All three drugs showed comparable tolerability profiles The pharmacokinetics of racemic ibuprofen and its stereoisomers have been described in adults , but little has been reported for children . The pharmacodynamics of acetaminophen and ibuprofen have not been well described in either adults or children . Children ( N = 39 ; age range , 11 months to 11½ years ) were r and omly selected to receive a single dose of either 6 mg/kg of liquid ibuprofen or 10 to 15 mg/kg of liquid acetaminophen ( mean ± dose given , 11.6 ± 0.7 ) . Pharmacokinetic and pharmacodynamic analyses were performed with temperature as the effect parameter and mean acetaminophen , total ibuprofen , and ibuprofen stereoisomer concentrations over time . Time of maximum serum concentrations for ibuprofen was 54.05 minutes versus 27.0 minutes for acetaminophen , time to maximum temperature decrease was 183 minutes for ibuprofen and 133 minutes for acetaminophen . Temperature reduction for the ibuprofen dose was significantly different than that of the acetaminophen dose at later time points ( 240 , 300 , 360 , 420 , and 480 minutes ) . Further pharmacokinetic‐pharmacodynamic studies with use of individual ibuprofen stereoisomers and other dosing regimens are indicated OBJECTIVE To determine the prevalence of self-medication in children and adolescents in the municipalities of Limeira and Piracicaba , state of São Paulo , and to correlate results with sociodemographic indicators and with the use of health care services ( public or private ) . METHODS Descriptive population -based study of a simple r and om sample from the two municipalities , comprised of 772 inhabitants from 85 urban census sectors selected through cluster sampling . INCLUSION CRITERIA age < or = 18 years ; interview with one parent/tutor ; consumption of at least one drug in the previous 15 days . Subjects were divided into two study groups according to their pattern of drug use : self-medication ( lay advice ) and medical prescription . Linear association tests , descriptive analysis of variables and multiple logistic regression tests were carried out to analyze data . RESULTS The prevalence of self-medication was 56.6 % . Mothers ( 51 % ) and drugstore employees ( 20.1 % ) were most frequently responsible for self-medication . The main groups of self-prescribed drugs were : analgesic/antipyretic and non-hormonal anti-inflammatory drugs ( 52.9 % ) ; drugs acting on the respiratory tract ( 15.4 % ) and gastrointestinal drugs ( 9.6 % ) ; and systemic antibiotics ( 8.6 % ) . The situation that most commonly motivated self-medication were respiratory diseases ( 17.2 % ) , fever ( 15 % ) , and headache ( 14 % ) . Subjects in the age group of 7 - 18 years ( odds ratio = 2.81 ) and public health care users ( odds ratio = 1.52 ) showed increased risk for self-medication . CONCLUSIONS The prevalence of self-medication in children and adolescents was high , which reinforces the need for public health interventions aim ing at preventing this practice Methods A prospect i ve , r and omized double-blind placebo control study comparing the efficacy of acetaminophen to acetaminophen alternated with ibuprofen in 38 healthy outpatient children 6 months to 6 years presenting to the outpatient clinic with fever > 38 ° C was conducted . Temperatures were recorded at 0 , 3 , 4 , 5 , and 6 hours . Side effect diaries and parental perception of efficacy were filled out hourly by parents . Results There were no significant differences in temperature between the 2 groups at times 0 , 3 , and 6 hours . The alternating group had significantly lower mean temperatures at both 4 hours ( 38.0 ° C vs 37.4 ° C ; P = .05 ) and 5 hours ( 37.1 ° C vs 37.9 ° C ; P = .0032 ) . Parents did not perceive any difference in fever control between the groups . Conclusions An alternating regimen of acetaminophen with ibuprofen significantly decreased fever at 4 and 5 hours compared with acetaminophen alone . However , parents did not perceive a difference in efficacy A r and omised open label study of the combined use of paracetamol and ibuprofen to rapidly reduce fever is reported . The advantage of using both medications is less than half a degree centi grade in the first hour , and insufficient to warrant routine use OBJECTIVES To establish the relative clinical effectiveness and cost-effectiveness of paracetamol plus ibuprofen compared with paracetamol and ibuprofen separately for time without fever , and the relief of fever-associated discomfort in young children who can be managed at home . DESIGN The trial design was a single-centre ( multisite ) , individually r and omised , blinded , three-arm trial comparing paracetamol and ibuprofen together with paracetamol or ibuprofen separately . SETTING There were three recruitment setting s , as follows : ' local ' where research nurses were recruited from NHS primary care sites ; ' remote ' where NHS sites notified the study of potentially eligible children ; and ' community ' where parents contacted the study in response to local media advertisements . PARTICIPANTS Children aged between 6 months and 6 years with fever > or = 37.8 degrees C and < or = 41 degrees C due to an illness that could be managed at home . INTERVENTIONS The intervention was the provision of , and advice to give , the medicines for up to 48 hours : paracetamol every 4 - 6 hours ( maximum of four doses in 24 hours ) and ibuprofen every 6 - 8 hours ( maximum of three doses in 24 hours ) . Every parent received two bottles , with at least one containing an active medicine . Parents , research nurses and investigators were blinded to treatment allocation by the use of identically matched placebo medicines . The dose of medicine was determined by the child 's weight : paracetamol 15 mg/kg and ibuprofen 10 mg/kg per dose . RESULTS For additional time without fever in the first 4 hours , use of both medicines was superior to use of paracetamol alone [ adjusted difference 55 minutes , 95 % confidence interval ( CI ) 33 to 77 minutes ; p < 0.001 ] and may have been as good as ibuprofen ( adjusted difference 16 minutes , 95 % CI -6 to 39 minutes ; p = 0.2 ) . Both medicines together cleared the fever 23 minutes ( 95 % CI 2 - 45 minutes ; p = 0.015 ) faster than paracetamol alone , but no faster than ibuprofen alone ( adjusted difference -3 minutes , 95 % CI 24 - 18 minutes ; p = 0.8 ) . For additional time without fever in the first 24 hours , both medicines were superior to paracetamol ( adjusted difference 4.4 hours , 95 % CI 2.4 - 6.3 hours ; p < 0.001 ) or ibuprofen ( adjusted difference 2.5 hours , 95 % CI 0.6 - 4.5 hours ; p = 0.008 ) alone . No reduction in discomfort or other fever-associated symptoms was found , although power was low for these outcomes . An exploratory analysis showed that children with higher discomfort levels had higher mean temperatures . No difference in adverse effects was observed between treatment groups . The recommended maximum number of doses of paracetamol and ibuprofen in 24 hours was exceeded in 8 % and 11 % of children respectively . Over the 5-day study period , paracetamol and ibuprofen together was the cheapest option for the NHS due to the lower use of health-care services:14 pounds [ st and ard deviation ( SD ) 23 pounds ] versus 20 pounds ( SD 38 pounds ) for paracetamol and 18 pounds ( SD 40 pounds ) for ibuprofen . Both medicines were also cheapest for parents because the lower use of health care services result ed in personal saving on travel costs and less time off work : 24 pounds ( SD 46 pounds ) versus 26 pounds ( SD 63 pounds ) for paracetamol and 30 pounds ( SD 91 pounds ) for ibuprofen . This more than compensated for the extra cost of medication . However , statistical evidence for these differences was weak due to lack of power . Overall , a quarter of children were ' back to normal ' by 48 hours and one-third by day 5 . Five ( 3 % ) children were admitted to hospital , two with pneumonia , two with bronchiolitis and one with a severe , but unidentified ' viral illness ' . CONCLUSIONS Young children who are unwell with fever should be treated with ibuprofen first , but the relative risks ( inadvertently exceeding the maximum recommended dose ) and benefits ( extra 2.5 hours without fever ) of using paracetamol plus ibuprofen over 24 hours should be considered . However , if two medicines are used , it is recommended that all dose times are carefully recorded to avoid accidentally exceeding the maximum recommended dose . Manufacturers should consider supplying blank charts for this purpose . Use of both medicines should not be discouraged on the basis of cost to either parents or the NHS . Parents and clinicians should be aware that fever is a relatively short-lived symptom , but may have more serious prognostic implication s than the other common symptom presentations of childhood |
11,850 | 10,864,543 | There is some limited evidence that routine treatment of children in areas where helminths are common has effects on weight gain , but this is not consistent between trials .
There is insufficient evidence as to whether this intervention improves cognitive performance | OBJECTIVE To summarise the effects of anthelmintic drug treatment on growth and cognitive performance in children . | The prevalence rate of ascariasis in primary school children in northern Jakarta , Indonesia varies from 60 % to 90 % . An association between helminthic infection and educational achievement has long been recognized . This study was carried out in the northern part of Jakarta among primary school children 6 - 8 years of age . Treatment of ascariasis and health education were used as the interventions . Before the interventions , basic data on socioeconomic status , epidemiology , infection with Ascaris lumbricoides , nutritional status , and cognitive function were collected . After the interventions , only data on infection with A. lumbricoides , nutritional status , and cognitive function were collected . The children were divided into five groups . Group I was given an anthelminthic ( mebendazole ) , group II was provided with health education , group III was given an antihelminthic and provided with health education , group IV was given a placebo ( controls ) , and group V consisted of egg-negative children , who also served as controls . Data from 336 students were analyzed by analysis of covariance . Parasitologic examinations showed a mean prevalence rate of 58.4 % for A. lumbricoides infection in the pre-intervention children and a mean prevalence rate of 40.6 % in the post-intervention children . Concerning nutritional status , approximately 80 % of the children showed good scores in the pre- and post-treatment data , and only a small percentage ( 0.9 - 16.2 % ) showed mild or moderate malnutrition . No significant difference was found between the pre- and post-treatment nutritional status . The results of the cognitive test showed that the group treated with mebendazole showed significant improvement in the Colored Progressive Matrices and Coding test . Children also showed an improvement in their learning ability , concentration , and eye-h and coordination after five months of receiving this intervention We studied growth in infected children given one dose ( 600 mg ) or two doses of albendazole per school year . Children were examined and allocated at r and om within sex by descending hookworm egg count to one of three groups : placebo ( n = 93 ) , one dose ( 1x , n = 96 ) or two doses ( 2x , n = 95 ) . Each child was treated and then re-examined and treated 3.6 and 8.2 mo later ( Exams 2 and 3 ) . The 1x and 2x groups gained significantly more by Exam 3 than the placebo group in weight ( 1.1 and 0.9 kg more , respectively ) , percent weight-for-age ( 3.3 and 2.7 percentage points more ) , percent weight-for-height ( 3.1 and 2.9 percentage points more ) , percent arm circumference-for-age ( 2.3 and 2.0 percentage points more ) and triceps and subscapular skinfolds but did not differ significantly from each other . The placebo group showed significant decreases between exams ( P < 0.0002 ) in percent weight-for-age and percent arm circumference-for-age and no change in percent weight-for-height , whereas the 1x and 2x groups exhibited significant increases ( P < 0.005 ) . At Exam 3 , arithmetic mean egg reduction rates for the 1x and 2x groups were 84 and 95 % for hookworm , 42 and 32 % for Trichuris and 55 and 87 % for Ascaris , respectively . We conclude that one or two doses of albendazole per year result ed in similar growth improvements , despite reinfection , in school-age children in an area where these helminths and poor growth are prevalent We studied physical fitness with the Harvard Step Test , growth , and appetite in primary school boys infected with hookworm ( 96 % baseline prevalence ) , Trichuris trichiura ( 98 % prevalence ) and Ascaris lumbricoides ( 41 % prevalence ) who received a single 600-mg dose of albendazole or an identical placebo . Boys were examined , allocated at r and om within pairs by descending hookworm egg count to placebo ( n = 26 ) or albendazole ( n = 27 ) groups , treated , and re-examined 4 mo later . Four months after treatment , the albendazole group showed highly significant improvements in fitness score , resting heart rate , and heart rates at 1 , 2 , 3 and 4 min after the Harvard Step Test , whereas the placebo group had not changed significantly . The albendazole group also exhibited significantly more rapid growth judged by weight gain ( 1.0 kg greater than the placebo group , P < 0.0002 ) , height increment ( 0.6 cm more , P < 0.003 ) , arm circumference ( 0.3 cm more , P < 0.0002 ) , and triceps and subscapular skinfolds ( 1.0 mm more , P < 0.0002 ) , and showed improved appetite with objective and subjective measures . We conclude that single-dose treatment with albendazole can allow improved physical fitness , growth , and appetite in school-age children in areas where these helminths and poor growth are highly prevalent A r and omized controlled trial was conducted in eastern Zaire to assess the effects of high dose vitamin A supplementation and regular deparasitation on the growth of 358 moderately malnourished preschool children , discharged from the hospital . The treatment groups received either vitamin A ( 60 mg of oily solution of retinyl palmitate , 30 mg if aged < 12 mo ) every 6 mo or mebendazole ( 500 mg ) every 3 mo ; the control group received no supplementation . Anthropometric data were gathered at baseline and after 6 and 12 mo of follow-up . Serum retinol concentrations were measured at baseline and after 3 mo . The three groups did not differ in sociodemographic indicators , age and sex composition , nutritional status and serum retinol concentrations at baseline . In children who were vitamin A deficient at baseline , adjusted mean weight and mid-upper arm circumference ( MUAC ) increments were higher in the vitamin A-supplemented group than in the control group [ annual increment in weight and MUAC in vitamin A vs. control group : 2.088 vs. 1.179 kg ( P = 0.029 ) and 2.24 vs. 0.95 cm ( P = 0.012 ) , respectively ] , whereas growth increment did not differ between the dewormed group and the control group . In children who were not vitamin A deficient at baseline , growth increment did not differ between the vitamin A-supplemented and control groups , whereas weight gain was lower in the dewormed group than in the control group . Vitamin A-supplemented boys gained more weight and height than control boys , whereas vitamin A-supplemented girls gained less height than control girls . Dewormed boys and girls gained less weight than control boys and girls . Programs to improve vitamin A status by high dose vitamin A supplementation may improve growth of preschool children who are vitamin A deficient , whereas deworming does not We evaluated the effects of the Zanzibar school-based deworming program on the iron status of primary school children . Parasitologic and nutritional assessment s were carried out at baseline , 6 mo , and 12 mo in 4 nonprogram schools ( n = 1002 ) , 4 schools in which students received twice-yearly deworming ( n = 952 ) , and 4 schools in which students received thrice-yearly deworming ( n = 970 ) with 500 mg generic mebendazole . Schools were r and omly selected for evaluation and allocated to program groups . Relative to no treatment , thrice-yearly deworming caused significant decreases in protoporphyrin concentrations and both deworming regimens caused marginally significant increases in serum ferritin concentrations . The average annual changes in protoporphyrin concentrations were -5.9 and -23.5 micromol/mol heme in the control and thrice-yearly deworming groups , respectively ( P < 0.001 ) . The average changes in ferritin concentration were 2.8 and 4.5 microg/L , respectively ( P = 0.07 ) . Deworming had no effect on annual hemoglobin change or prevalence of anemia . However , the relative risk of severe anemia ( hemoglobin < 70 g/L ) was 0.77 ( 95 % confidence limits : 0.39 , 1.51 ) in the twice-yearly deworming group and 0.45 ( 0.19 , 1.08 ) in the thrice-yearly deworming group . The effects on prevalence of high protoporphyrin values and incidence of moderate-to-severe anemia ( hemoglobin < 90 g/L ) were significantly greater in children with > 2000 hookworm eggs/g feces at baseline . We estimate that this deworming program prevented 1260 cases of moderate-to-severe anemia and 276 cases of severe anemia in a population of 30,000 schoolchildren in 1 y. Where hookworm is heavily endemic , deworming programs can improve iron status and prevent moderate and severe anemia , but deworming may be needed at least twice yearly One-hundred eighty-five Bangladeshi children age 1 1/2 to 8 yr with no Ascaris lumbricoides infection or with light , moderate , or heavy infection were r and omly assigned to treatment of placebo groups , with treatment given in a double-blind fashion . The groups were comparable for nutritional and socioeconomic parameters . Treatment consisted of a single dose of piperazine citrate administered twice within a 2-wk period . The cure rates for the low , moderate , and heavy A. lumbricoides infected subgroups were 53 , 31 , and 36 % , respectively . With more severe infections , worm eradication was more difficult and the rate of reinfection after treatment was more rapid . The rate of reinfection was significantly different for the low A. lumbricoides infected treatment and placebo subgroups for 5 months after treatment , for the moderate treatment and placebo subgroups for 3 months after treatment , and for the heavy A. lumbricoides infected treatment and placebo subgroups there was a difference , although not significant , for 1 month after treatment . Anthropometric measurements were obtained for a period of 11 months . Analysis of covariance revealed no significant difference for change of weight , change of height , weight-for age , weight-for-height , height-for-age , triceps skinfold , midarm circumference , and the abdominal girth to chest circumference ratio between the treatment and placebo groups after drug administration . The results of this study do not support single dose worm therapy as a means to enhance growth Growth , activity , appetite and intestinal helminth infections were compared for 55 Kenyan primary school children with hookworm ( 93 % prevalence ) , T. trichiura ( 84 % prevalence ) and A. lumbricoides ( 29 % prevalence ) before and 9 wk after treatment with three 400-mg doses of albendazole ( Zentel ) or placebo . Fecal sample s were examined for helminth eggs using a modified Kato technique . Activity was measured during free-play with motion recorders on the dominant thigh . Children rated their appetites on a 5-point scale . After baseline measurements , children were r and omly allocated to the albendazole-treated ( n = 28 ) and placebo ( n = 27 ) groups , treated , and re-examined 9 wk later . At follow-up , egg counts were significantly lower than at baseline in the albendazole-treated group ( P < or = 0.002 ) , and gains in activity , reported appetite and most indices of growth were significantly greater for the albendazole-treated group than for the placebo group . We conclude that treatment of undernourished school children for intestinal helminth infections with albendazole may improve growth and appetite and increase spontaneous physical activity One hundred fifty-nine children aged 24 to 61 months with 60 % ascariasis prevalence and 21.5 % giardiasis prevalence in rural Guatemala were studied prospect ively for 1 yr . They were divided into four groups comparable for age , sex , socioeconomic status , and past growth experience as judged by slopes of height and weight on age . Each group was r and omly assigned to the following 2-monthly treatment regimens : group I , placebo , group II , piperazine , group III , metronidazole ; group IV , piperazine and metronidazole . Height and weight were measured every 3 months and stools were examined for parasites every 4 months . Piperazine administration decreased the prevalence of ascariasis to 33.8 % at the end of the study but growth remained unaltered . Metronidazole administration decreased the prevalence of giardiasis to 2.5 % at the end of the study and was accompanied by increased growth as judged by delta weight , delta % weight for age , slope of weight on age , delta height , delta % height for age and slope of height on age . It is suggested that failure of antiascaris treatment to enhance growth in this study may be because of 1 ) absence of severe malnutrition in the subjects , 2 ) adequacy of dietary protein , 3 ) possible low worm load , and 4 ) failure to eradicate ascariasis . The findings suggest that giardiasis is associated with reduced growth in preschool children The effects of treating Trichuris trichiura infections were investigated in 407 Jamaican children age 6 to 12 y. The children were r and omly assigned to receive treatment ( albendazole ) or a placebo . The outcome variables included growth , tests of reading , spelling and arithmetic , and school attendance . After 6 mo of treatment , there was no significant main effect on any of the outcomes . However , there were significant treatment-by-infection intensity interactions with spelling ( P < 0.05 ) and body mass index ( P < 0.01 ) , and a significant treatment-by-stunting interaction with school attendance ( P < 0.01 ) . In spelling , the children with heavy infections showed improvements with treatment that approached significance ( P = 0.06 ) , whereas those with lower intensities did not . However , the children with lower infection intensities had increased body mass index with treatment ( P = 0.02 ) , although there was no difference in children with heavy infections . In school attendance , the stunted children improved with treatment ( P < 0.04 ) , whereas there was no difference in the nonstunted children . These findings suggest that in the sample of Jamaican children examined , the treatment of T. trichiura was more likely to benefit school performance in children of poor nutritional status and those with heavy infections , and to improve weight gain in children with lighter infection intensities A double-blind placebo trial was conducted to determine the effect of moderate to high loads of Trichuris trichiura ( whipworm ) infection on the cognitive functions of 159 school children ( age 9 - 12 years ) in Jamaica . Infected children were r and omly assigned to Treatment or Placebo groups . A third group of r and omly selected uninfected children were assigned to a Control for comparative purpose s. The improvement in cognitive function was evaluated using a stepwise multiple linear regression , design ed to control for any confounding variables . The expulsion of worms led to a significant improvement in tests of auditory short-term memory ( P less than 0.02 ; P less than 0.01 ) , and a highly significant improvement in the scanning and retrieval of long-term memory ( P less than 0.001 ) . After 9 weeks , treated children were no longer significantly different from an uninfected Control group in these three tests of cognitive function . The removal of T. trichiura was more important than Ascaris lumbricoides in determining this improvement . The results suggest that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy Tested 47 first-year primary school children at a mission school in rural Zaire for cognitive ability with the Kaufman Assessment Battery for Children ( K-ABC ) adopted to the language of Kituba . Within a day of this test , each child was evaluated for blood hemoglobin ( Hgb ) level and the presence of intestinal parasites . Half of the children received an iron supplement ( 20 mg Fe ) for 30 days and those children positive for the intestinal parasites of ankylostome or ascaris were r and omly selected to receive either a vermifuge treatment or placebo . All of the children were again evaluated medically and cognitively 4 weeks after the initiation of treatment . Using discriminant analysis , performance on the Mental Processing Composite of the K-ABC 1 month after treatment in combination with increases in blood Hgb result ed in the successful classification of 74 % in terms whether a child had received both iron supplement and vermifuge treatment ( p = .007 ) . With respect to our home evaluation for each child , factors related to the nutritional and economic well-being of the home environment proved a reliable marker for Simultaneous Processing ability . However , the present findings also suggest that over the short-term , changes in blood Hgb that accompany both vermifuge and iron supplement treatment together can improve certain aspects of cognitive ability , perhaps by means of heightened attentional capacity This r and omized , placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths ( albendazole ) and lymphatic filariasis ( ivermectin ) . Children were infected with Ascaris ( 29.2 % ) , Trichuris ( 42.2 % ) , and hookworm ( 6.9 % ) , with 54.7 % of children having one or more of these parasites . Wuchereria bancrofti microfilaria were found in 13.3 % of the children . Children were r and omly assigned to treatment with placebo , albendazole , ivermectin , or combined therapy . Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone . Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone . Only combination therapy result ed in significantly greater gains in height ( hookworm-infected children ) or weight ( Trichuris-infected children ) compared with the placebo group . Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and result ed in nutritional benefits not found with either drug alone This study examined the relationship between intestinal helminthiases and growth in urban slum schoolchildren . Children ( n = 330 ) who received single doses of either pyrantel , albendazole , or placebo at baseline and again at 6 months were followed and examined fully at 0 , 3 , 6 , and 12 months for helminth infections and anthropometry . Results of treatments indicated that all groups reduced their prevalence and intensity toward the period of the study . Reductions in intensity of both infections in the treatment groups were observed large in 3 and 12 months , whereas at 6 months reached mostly the initial level of infection . There was no significant difference in growth changes between the dewormed ( once and twice ) and the placebo groups . However , after controlling for some potential confounding factors , there was a significant relationship between reduction of A. lumbricoides infection and height gain at 3 and 12 months ( both P < 0.05 ) . In addition , there was a significant association between reduction in T. trichiura infection and increased midarm circumference at 3 and 12 months ( P < 0.002 and P < 0.08 , respectively ) . We conclude that treatment of helminth infections in school-age children may improve growth in areas where malnutrition and helminth infections are prevalent The impact of albendazole ( 400 mg ) and praziquantel ( 40 mg/kg body weight ) treatment of schoolchildren was compared with placebo according to the presence of anaemia ( haemoglobin concentration < 11 . 0 g/dl ) and heavy ( > 5000 epg ) or light ( < 5000 epg ) hookworm egg load . The study was conducted in rural Tanga . Medication was administered in September 1994 and children were followed-up in January 1995 . Overall , anthelminthic treatment reduced the fall in haemoglobin concentration compared with that observed in the placebo group ( - 0.11 g/dl vs. - 0.35 g/dl ; P = 0.02 ) . Anthelminthic treatment was of greatest benefit to the 9 % of children with both anaemia and heavy hookworm egg load ( + 0.67 g/dl vs. - 0.67 g/dl ) and was also of significant benefit to the 38 % of children with anaemia and light hookworm egg load ( + 0.07 g/dl vs. - 0.21 g/dl ) . It was of no significant benefit to children who were not anaemic . This study suggests that single-dose anthelminthic treatment distributed in schools in this area achieves haematological benefits in nearly half of children infected with S. haematobium and geohelminths ( 37 % of total population ) BACKGROUND We aim ed to find out whether symptomless infection with Trichuris trichiura is associated with impairment of growth and to assess the effect of a multiple-doses regimen of anthelmintic drugs on the growth of children . METHODS In a community based trial , 622 Mexican children were r and omly allocated one of three treatment regimens : 3 days of albendazole 400 mg daily ( high efficacy ) ; one dose of albendazole 400 mg ( moderate efficacy ) ; one dose of pyrantel ( pyrantel embonate ) 11 mg/kg ( low efficacy ) . Growth was monitored for 12 months . Analyses were by intention to treat . FINDINGS 113 ( 18 % ) children were lost to follow-up--34 from the pyrantel group , 45 from the albendazole 400 mg group , and 34 from the albendazole 1200 mg group . Among the 127 children with heavy pretreatment infections , albendazole 1200 mg was better than pyrantel in terms of an increase in arm circumference ( mean 0.26 cm , p=0.044 ) . Among the 381 children with low pretreatment levels of infection , changes in weight ( mean difference between groups -0.33 kg , p=0.036 ) , arm circumference ( -0.18 cm , p=0.0095 ) , and thickness of triceps skinfold ( -0.41 mm , p=0.0031 ) were less in children on albendazole 1200 mg than in those on pyrantel . INTERPRETATION Symptomless trichuriasis impairs growth and albendazole or pyrantel may affect growth , independently of a therapeutic action on parasites . Possible toxic effects of high-dose albendazole require further investigation Stool specimens from a sample of schoolchildren at six schools in Kweneng District were examined for hookworm infection , using the brine flotation method . Necator americanus was the only hookworm identified . The western part of the District forms part of the Kalahari Desert , and in four villages here 90 % , 88 % , 88 % and 86 % of the children were infected . In two villages in the eastern non-desert part , only 13 % and 9 % were infected . Most infections were light . There was no significant correlation between severity of infection and anaemia . In one school ( 228 pupils ; 86 % infected with hookworm ) , half the children were treated with tetrachloroethylene ( 0.1 ml/kg , maximum 5 ml ) and the other half with placebo . Two weeks after treatment the prevalence of infection were 28 % and 75 % respectively ( p less than 0.001 ) , and five months after treatment 51 % and 69 % ( p less than 0.05 ) . Measured over the five-month period there were no significant changes in haemoglobin and nutritional status ( weight/height ) . Based on the results of the survey , a hookworm mass treatment programme was not recommended The study examines the effect of moderate to high worm burdens of Trichuris trichiura infection on the cognitive functions of 159 school children ( age 9–12 years ) in Jamaica , using a double-blind placebo-controlled protocol . Results were evaluated by using a forward-stepwise multiple linear regression . Removal of worms led to a significant improvement in tests of auditory short-term memory ( p < 0.017 ; p < 0.013 ) , and scanning and retrieval of long-term memory ( p < 0.001 ) . Nine weeks after treatment , there were no longer significant differences between the treated children and an uninfected Control group in these three tests of cognitive function . It is concluded that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy A 2-year investigation , consisting of a controlled , non-blind , 3-monthly chemotherapeutic intervention trial , based on transmission dynamics of Ascaris lumbricoides infection , was undertaken to prove or refute the role of A. lumbricoides as a contributor to childhood malnutrition . The study involved 1206 children aged 2 - 12 years in 21 villages in Myanmar [ Burma ] starting in August 1984 . The intervention and non-intervention villages were comparable regarding almost all the important baseline variables , including prevalences of Ascaris infection ( 80.8 vs 83.0 % ) and of malnutrition of grade 2 and above for height-for-age ( 58.4 vs 55.8 % ) and for weight-for-age ( 48.2 vs 47.8 % ) . The intensity of Ascaris infection was related to the degree of malnutrition . A significant increment of height gain was found , starting after the 6th month , and of weight gain after the 24th month , of the study among the treated 2 - 10 years old children when compared with the non-treated ones . By the end of 24 months , the height and weight gains per child were 0.65 cm and 0.93 kg respectively . Lesser increments in height-for-age and weight-for-age were also observed after successive treatments among the treated children with initially higher mean worm burdens . The findings are discussed in the context of causal relationship between ascariasis and malnutrition in children The effects of mild to moderate infections of Trichuris trichiura on cognitive functions were investigated in Jamaican children aged 7 to 10 years . In all , 189 infected children and 100 uninfected classmates were studied . The infected children were r and omly assigned to receive treatment ( albendazole ) or a placebo . All children were given cognitive tests on enrolment and 14 weeks later . These included verbal fluency ( generation of ideas ) , digit span ( working memory ) , number choice ( speed of processing of visual stimuli ) , visual search ( sustained attention ) and a French Vocabulary test ( paired-associate learning ) . At baseline , the infected children had lower scores than the uninfected ones in fluency ( P = 0.01 ) , search ( P = 0.02 ) and French ( P = 0.01 ) . Treatment effects were examined among infected children and there was no significant treatment effect for any of the tests . However , there was a significant treatment by weight-for-age interaction in fluency ( P < 0.05 ) . The children with low weight-for-age ( Z-score < -1 ) improved with treatment while there was no improvement with treatment among the other children . We concluded that treatment of children with mild to moderate T. trichiura infections using albendazole produces little benefit in cognition if they are adequately nourished ; however , undernourished children are more likely to benefit OBJECTIVE To determine whether successful deworming for 6 months in children with high levels of Ascaris improves physical growth . SUBJECTS Two hundred twenty-eight children ( mean age , 9.7 years ) in a highl and Indian town in Guatemala . DESIGN Children were r and omly assigned to receive albendazole or placebo at baseline and 12 weeks . Children and field workers were both blind to the group assignment . OUTCOME MEASURES Children 's heights , weights , and mid-upper-arm circumferences were measured at baseline and 12 and 24 weeks . Fecal egg counts were taken at 0 , 2 , 12 , 14 , and 24 weeks to estimate the helminth burden ( eggs per gram of feces [ epg ] ) . RESULTS Baseline helminth prevalences were Ascaris , 91 % , and Trichuris , 82 % . Ascaris intensities were high : half of the children had moderate burdens ( 10 000 to 50 000 epg ) , and 25 % had heavy burdens ( > 50 000 epg ) . Trichuris burdens were light ( 72 % < 1000 epg ) . The albendazole and placebo groups did not differ at baseline in epg , age , anthropometry , or socioeconomic status . The two rounds of treatment successfully reduced the Ascaris burdens but had less effect on Trichuris . At 6 months the treatment group showed a small gain in weight ( 0.18 kg ) compared with the placebo group but no improvement in height or mid-upper-arm circumference . CONCLUSIONS The successful removal of ascaris in a population of school-aged children with relatively high loads may have modest effects on weight gain . Ascaris is one of the most common infections in school-aged children , but its effect on the host may be less than that of other helminths We studied physical fitness with the Harvard step test ( HST ) , in primary schoolboys infected with hookworm ( 91 % baseline prevalence ) , Trichuris trichiura ( 94 % ) and Ascaris lumbricoides ( 39 - 40 % ) who received a single 400 mg dose of albendazole or an identical placebo . Boys were examined , allocated at r and om to placebo or albendazole groups , treated , and re-examined 7 weeks later . The 2 groups did not differ significantly before treatment in age , anthropometry , haemoglobin levels , prevalence or intensity of the 3 helminth infections , or in initial HST fitness scores and heart rates . Seven weeks after treatment , the albendazole group ( n = 18 ) exhibited significant improvements in fitness scores and heart rates at 1 , 2 , 3 , and 4 min after the HST while in the placebo group ( n = 15 ) these quantities had not changed significantly . After treatment , the albendazole group had significant decreases in the logarithmic egg counts for hookworm ( 80 % reduction in arithmetic means ) and A. lumbricoides ( 100 % reduction ) ; T. trichiura egg counts did not change significantly . The placebo group showed a borderline increase in the logarithms of hookworm egg counts and no significant change in T. trichiura and A. lumbricoides egg counts . Multiple regression analysis showed that the significant linear predictors of increase in HST score after treatment were decrease in resting heart rate after treatment , and decreases in hookworm egg counts and logarithms of A. lumbricoides egg counts after treatment . We conclude that single dose treatment with albendazole , despite continual exposure to reinfection , can allow improved physical fitness in schoolboys in areas where soil-transmitted helminths and protein-energy malnutrition are highly prevalent An 18-month study was conducted from February 1989 to August 1990 to examine the effect of regular deworming on child growth and nutritional status . A sample of 1402 children , from 2 to 6 years old , were divided into a treatment group and a control group . The 688 children in the treatment group received a 500 mg single dose of mebendazole , while the 714 children in the control group were given a placebo . Height , weight and mid-upper arm circumference ( MUAC ) were measured on monthly household visits . Growth was measured in terms of the change in height-for-age , weight-for-age , weight-for-height and MUAC over 18 months . The initial prevalence of infection was estimated from a r and om sample of 96 children ( 49 treated , 47 control ) . The initial overall prevalence of Ascaris lumbricoides , Trichuris trichiura and hookworm was 71 , 44 and 10 % respectively . The final prevalence of infection , estimated from a r and om sample of 265 children , was A. lumbricoides 6 % , T. trichiura 6 % and hookworm 2 % in the mebendazole group compared with 64 , 18 and 19 % respectively in the placebo group . Despite the successful treatment of helminths , there was no significant improvement in the growth of treated children compared with their untreated counterparts in terms of the change in z-scores of height-for-age , weight-for-age , weight-for-height and MUAC . The factors which may have contributed to this outcome are discussed Appetite and growth were studied in primary schoolboys ( 6 - 10 years ) infected with Ascaris lumbricoides ( 86 % ) and Trichuris trichiura ( 100 % ) who received a single dose of pyrantel pamoate ( which has little or no effect on Trichuris trichiura ) or a placebo . Boys were examined , allocated at r and om by descending Ascaris egg count to pyrantel ( PR , n = 36 ) or placebo ( PL , n = 36 ) groups , treated , and re-examined 3 and 7 weeks later . The 2 groups did not differ significantly before treatment in helminth infections , appetite , or growth . Three and 7 weeks after treatment , the PR group exhibited significantly greater increases than did the PL group in weight ( 0.2 kg and 0.4 kg more , respectively ) and percentage weight-for-age ( 0.6 % and 1.7 % points more , respectively ) . Appetite increased significantly in the PR group at 3 and 7 weeks ( P < 0.0005 and P < 0.01 , respectively ) but not in the PL group . The prevalence and intensity of A. lumbricoides infection were greatly reduced in the PR group at 3 and 7 weeks ( both P < 0.0001 ) but not in the PL group . We conclude that treatment with pyrantel pamoate may improve appetite and growth in school children in areas where A. lumbricoides infections and poor growth are highly prevalent Intestinal helminths are among the most common infections in school-age children . Of 246 children , aged 7 - 12 years , attending school in rural Guatemala , 91 % carried Ascaris lumbricoides and 82 % carried Trichuris trichiura . These children were r and omly assigned to receive either albendazole or placebo at 0 and 12 weeks in a ' double-blind ' study of the effects of deworming on indicators of school performance . Albendazole successfully rid the children of Ascaris but it was less effective against Trichuris . The children 's performance in tests of reading and vocabulary were measured at 0 and 24 weeks , the Peabody picture vocabulary test was given at 24 weeks , and attendance was measured throughout the school year . Comparison of the treated and placebo groups showed no positive effect of deworming . The treated children were largely free of Ascaris for at least 6 months , but during that period we could not detect any improvement in reading , vocabulary , or attendance . The effects of being Trichuris-free were not examined because of the limited effectiveness of albendazole against this worm at the dosage used To access the effectiveness of the treatment of soil-transmitted helminthiasis ( STH ) on the growth of primary school children , 353 children were block stratified to receive either mebendazole plus pyrantel oxantel pamoate every three months or a placebo . The children were followed for two years with 89 % completing the trial . Follow-up stools indicated that the treatment was efficacious for ascariasis and trichuriasis . There was virtually no hookworm infection . The children were malnourished as measured by the number below -2 SD of height and weight st and ards . There was no difference in height or weight between the treatment and control groups by sex initially or at the end of two years of follow-up . The treatment of Ascaris and Trichuris had no effect on growth parameters . The effect of STH on growth may be mediated through hookworm infections We studied the growth of primary schoolchildren with hookworm ( 87 % ) , T. trichiura ( 97 % ) , and A. lumbricoides ( 49 % ) who received a single 400 mg dose of albendazole or an identical placebo . Children were allocated at r and om to placebo ( PL , n = 72 ) or albendazole ( A , n = 78 ) groups , treated , and re-examined 6 months later . The A group gained significantly more than the PL group in weight ( 1.3 kg ) , percent weight for age ( 4.5 % age points ) , percent height for age ( 0.5 % age points ) , percent weight for height ( 4.3 % age points ) , percent arm circumference ( 2.9 % age points ) , and in triceps and subscapular skinfold thicknesses ( 1.2 mm ) . The PL group showed significant decreases between exams in percent weight for age , percent height for age , percent weight for height , percent arm circumference for age , and skinfold thicknesses for age . The A group had highly significant increases ( P less than 0.0002 ) in all of these parameters except height for age . From Exam 1 to 2 , the A group exhibited decreases ( P less than 0.0002 ) in geometric means eggs per gram of feces ( epg ) : for hookworm , means = 1,183 epg at Exam 1 vs. 136 epg at Exam 2 ( 67 % egg reduction ) ; for T. trichiura , means = 2,857 epg at Exam 1 vs. 1,061 epg at Exam 2 ( 28 % egg reduction ) ; and for A. lumbricoides , means = 86 epg at Exam 1 vs. 2 epg at Exam 2 ( 91 % egg reduction ) . The PL group had a borderline increase in geometric means hookworm egg count , no significant change in T. trichiura egg count , and a small but significant decrease in A. lumbricoides egg count . Decreases in intensities of all infections were significant predictors of growth improvement . Hookworm egg count entered the equations for all 6 measurements , and A. lumbricoides and T. trichiura entered 4/6 equations . Single dose treatment with albendazole , despite continual exposure to infection , can permit improved growth rates in areas where intestinal helminths and protein-energy malnutrition are highly prevalent Three hundred forty-one Tanzanian preschool children were r and omly assigned to levamisole or placebo treatment given at three-month intervals . Weights and heights were measured at the tri-monthly treatment visits for a period of one year . Among the 273 children who were seen and weighed at the one-year follow-up visit , the rate of weight gain was 8 per cent greater for those receiving levamisole than for placebo-treated controls ( p = .06 ) . In 78 children known to be infected with Ascaris at baseline , the rate of weight gain was 21 per cent greater in children treated with levamisole than in those receiving placebo ( p = .03 ) . The rate of height gain was no different for treatment and placebo groups Trichuris trichiura is extremely prevalent worldwide and there is concern that this geohelminth may affect the cognitive function of children in developing countries . A r and om-controlled , double-blind , treatment trial was conducted in Jamaican children with light to moderate infections . This was part of a research programme involving several studies in Jamaica . Ninety-seven subjects , each with a minimum of 1200 T. trichiura eggs/g faeces , were r and omly assigned to placebo ( N = 48 ) or treatment ( N = 49 ) groups . Each pair of infected children was matched with an uninfected classmate ( N = 48 ) . All children were given seven cognitive function tests : French-learning ; digit spans ( forwards and backwards ) , Corsi block span ; fluency ; picture search ; and silly sentences . Albendazole was given to the treatment group and the other groups received a placebo . Three months later , these treatments were repeated , and the cognitive function battery was given again . On pre-test , the infected groups performed significantly poorer only in the silly-sentence test ( analysis of variance F-value = 8.17 ; two degrees of freedom ; P < 0.001 ) . There was no significant improvement with treatment in any of the tests . Taking into account these findings and those of the other Jamaican studies , it is therefore probable that light to moderate Trichuris infections have little effect on cognitive functioning in school children who have adequate nutritional status |
11,851 | 26,114,883 | These results suggest that expression of PD-L1 is associated with worse survival in solid tumors .
However , the correlations between PD-L1 and prognosis are variant among different tumor types . | BACKGROUND Numerous agents targeting PD-L1/PD-1 check-point are in clinical development .
However , the correlation between PD-L1 expression and prognosis of solid tumor is still in controversial .
Here , we elicit a systematic review and meta- analysis to investigate the potential value of PD-L1 in the prognostic prediction in human solid tumors . | BACKGROUND Blockade of programmed death 1 ( PD-1 ) , an inhibitory receptor expressed by T cells , can overcome immune resistance . We assessed the antitumor activity and safety of BMS-936558 , an antibody that specifically blocks PD-1 . METHODS We enrolled patients with advanced melanoma , non-small-cell lung cancer , castration-resistant prostate cancer , or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks . Response was assessed after each 8-week treatment cycle . Patients received up to 12 cycles until disease progression or a complete response occurred . RESULTS A total of 296 patients received treatment through February 24 , 2012 . Grade 3 or 4 drug-related adverse events occurred in 14 % of patients ; there were three deaths from pulmonary toxicity . No maximum tolerated dose was defined . Adverse events consistent with immune-related causes were observed . Among 236 patients in whom response could be evaluated , objective responses ( complete or partial responses ) were observed in those with non-small-cell lung cancer , melanoma , or renal-cell cancer . Cumulative response rates ( all doses ) were 18 % among patients with non-small-cell lung cancer ( 14 of 76 patients ) , 28 % among patients with melanoma ( 26 of 94 patients ) , and 27 % among patients with renal-cell cancer ( 9 of 33 patients ) . Responses were durable ; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up . To assess the role of intratumoral PD-1 lig and ( PD-L1 ) expression in the modulation of the PD-1-PD-L1 pathway , immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients . Of 17 patients with PD-L1-negative tumors , none had an objective response ; 9 of 25 patients ( 36 % ) with PD-L1-positive tumors had an objective response ( P=0.006 ) . CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer , melanoma , or renal-cell cancer ; the adverse-event profile does not appear to preclude its use . Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00730639 . ) Therapies that target the programmed death-1 ( PD-1 ) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types . One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 lig and ( PD-L1 ) and its ligation to PD-1 on antigen-specific CD8 + T cells ( termed adaptive immune resistance ) . Here we show that pre-existing CD8 + T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy . We analysed sample s from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy ( pembrolizumab ) using quantitative immunohistochemistry , quantitative multiplex immunofluorescence , and next-generation sequencing for T-cell antigen receptors ( TCRs ) . In serially sample d tumours , patients responding to treatment showed proliferation of intratumoral CD8 + T cells that directly correlated with radiographic reduction in tumour size . Pre-treatment sample s obtained from responding patients showed higher numbers of CD8- , PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours , with close proximity between PD-1 and PD-L1 , and a more clonal TCR repertoire . Using multivariate analysis , we established a predictive model based on CD8 expression at the invasive margin and vali date d the model in an independent cohort of 15 patients . Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8 + T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance The development of human cancer is a multistep process characterized by the accumulation of genetic and epigenetic alterations that drive or reflect tumour progression . These changes distinguish cancer cells from their normal counterparts , allowing tumours to be recognized as foreign by the immune system . However , tumours are rarely rejected spontaneously , reflecting their ability to maintain an immunosuppressive microenvironment . Programmed death-lig and 1 ( PD-L1 ; also called B7-H1 or CD274 ) , which is expressed on many cancer and immune cells , plays an important part in blocking the ‘ cancer immunity cycle ’ by binding programmed death-1 ( PD-1 ) and B7.1 ( CD80 ) , both of which are negative regulators of T-lymphocyte activation . Binding of PD-L1 to its receptors suppresses T-cell migration , proliferation and secretion of cytotoxic mediators , and restricts tumour cell killing . The PD-L1–PD-1 axis protects the host from overactive T-effector cells not only in cancer but also during microbial infections . Blocking PD-L1 should therefore enhance anticancer immunity , but little is known about predictive factors of efficacy . This study was design ed to evaluate the safety , activity and biomarkers of PD-L1 inhibition using the engineered humanized antibody MPDL3280A . Here we show that across multiple cancer types , responses ( as evaluated by Response Evaluation Criteria in Solid Tumours , version 1.1 ) were observed in patients with tumours expressing high levels of PD-L1 , especially when PD-L1 was expressed by tumour-infiltrating immune cells . Furthermore , responses were associated with T-helper type 1 ( TH1 ) gene expression , CTLA4 expression and the absence of fractalkine ( CX3CL1 ) in baseline tumour specimens . Together , these data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1 , and is re-invigorated on antibody treatment Purpose : The aberrant expression of programmed cell death 1 lig and s 1 and 2 ( PD-Ls ) on tumor cells dampens antitumor immunity , result ing in tumor immune evasion . In this study , we investigated the expression of PD-Ls in human hepatocellular carcinoma ( HCC ) to define their prognostic significance after curative surgery . Experimental Design : Immunohistochemistry was used to investigate PD-Ls expression as well as granzyme B+ cytotoxic and FoxP3 + regulatory T cell infiltration on tissue microarrays containing 240 r and omly selected HCC patients who underwent surgery . The results were further verified in an independent cohort of 125 HCC patients . PD-Ls expression on HCC cell lines was detected by Western blot assay . Results : Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression . Although patients with higher expression of PD-L2 also had a poorer survival , the difference in recurrence was not statistically significant . Multivariate analysis identified tumor expression of PD-L1 as an independent predictor for postoperative recurrence . No correlation was found between PD-Ls expression and granzyme B+ lymphocyte infiltration , whereas a significant positive correlation was detected between PD-Ls expression and FoxP3 + lymphocyte infiltration . In addition , tumor-infiltrating cytotoxic and regulatory T cells were also independent prognosticators for both survival and recurrence . The prognostic value of PD-L1 expression was vali date d in the independent data set . Conclusion : Our data suggest for the first time that PD-L1 status may be a new predictor of recurrence for HCC patients and provide the rationale for developing a novel therapy of targeting the PD-L1/PD-1 pathway against this fatal malignancy BACKGROUND Programmed death 1 ( PD-1 ) protein , a T-cell coinhibitory receptor , and one of its lig and s , PD-L1 , play a pivotal role in the ability of tumor cells to evade the host 's immune system . Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in pre clinical models . METHODS In this multicenter phase 1 trial , we administered intravenous anti-PD-L1 antibody ( at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight ) to patients with selected advanced cancers . Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression . RESULTS As of February 24 , 2012 , a total of 207 patients --75 with non-small-cell lung cancer , 55 with melanoma , 18 with colorectal cancer , 17 with renal-cell cancer , 17 with ovarian cancer , 14 with pancreatic cancer , 7 with gastric cancer , and 4 with breast cancer -- had received anti-PD-L1 antibody . The median duration of therapy was 12 weeks ( range , 2 to 111 ) . Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9 % of patients . Among patients with a response that could be evaluated , an objective response ( a complete or partial response ) was observed in 9 of 52 patients with melanoma , 2 of 17 with renal-cell cancer , 5 of 49 with non-small-cell lung cancer , and 1 of 17 with ovarian cancer . Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up . CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression ( objective response rate of 6 to 17 % ) and prolonged stabilization of disease ( rates of 12 to 41 % at 24 weeks ) in patients with advanced cancers , including non-small-cell lung cancer , melanoma , and renal-cell cancer . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00729664 . ) |
11,852 | 18,454,878 | The primary outcome measure was significant improvement on the key depression measure .
Results Components which were found to significantly predict improvement were the revision of professional roles , the provision of a case manager who provided direct feedback and delivered a psychological therapy , and an intervention that incorporated patient preferences into care .
Nurse , psychologist and psychiatrist delivered care were effective , but pharmacist delivery was not .
Training directed to general practitioners was significantly less successful than interventions that did not have training as the most important intervention .
Community interventions were effective .
Conclusion Case management is important in the provision of care in general practice .
Certain community models of care ( education programs ) have potential while others are not successful in their current form ( pharmacist monitoring ) | Background There is still debate as to which features , types or components of primary care interventions are associated with improved depression outcomes .
Previous review s have focused on components of collaborative care models in general practice setting s. This paper aims to determine the effective components of depression care in primary care through a systematic examination of both general practice and community based intervention trials . | The long-term effectiveness of a structured health education program ( HEP ) for spouses and frail older adults was evaluated in a staff model health maintenance organization ( HMO ) . HEP is a multicomponent group program that includes emotion-focused and problem-focused coping strategies , education , and support . For caregivers , HEP was more effective than usual care ( UC ) in reducing depression , increasing knowledge of community services and how to access them , and changing caregivers ' feelings of competence and the way they respond to the caregiving situation . For care recipients , HEP was more effective than UC in preventing increases in somatic symptoms and symptoms of anxiety/insomnia . ( ( c ) 2004 APA , all rights reserved Abstract Objective To evaluate the efficacy of two internet interventions for community-dwelling individuals with symptoms of depression — a psychoeducation website offering information about depression and an interactive website offering cognitive behaviour therapy . Design R and omised controlled trial . Setting Internet users in the community , in Canberra , Australia . Participants 525 individuals with increased depressive symptoms recruited by survey and r and omly allocated to a website offering information about depression ( n = 166 ) or a cognitive behaviour therapy website ( n = 182 ) , or a control intervention using an attention placebo ( n = 178 ) . Main outcome measures Change in depression , dysfunctional thoughts ; knowledge of medical , psychological , and lifestyle treatments ; and knowledge of cognitive behaviour therapy . Results Intention to treat analyses indicated that information about depression and interventions that used cognitive behaviour therapy and were delivered via the internet were more effective than a credible control intervention in reducing symptoms of depression in a community sample . For the intervention that delivered cognitive behaviour therapy the reduction in score on the depression scale of the Center for Epidemiologic Studies was 3.2 ( 95 % confidence interval 0.9 to 5.4 ) . For the “ depression literacy ” site ( BluePages ) , the reduction was 3.0 ( 95 % confidence interval 0.6 to 5.2 ) . Cognitive behaviour therapy ( MoodGYM ) reduced dysfunctional thinking and increased knowledge of cognitive behaviour therapy . Depression literacy ( BluePages ) significantly improved participants ' underst and ing of effective evidence based treatments for depression ( P < 0.05 ) . Conclusions Both cognitive behaviour therapy and psychoeducation delivered via the internet are effective in reducing symptoms of depression Abstract Objectives : To determine the acceptability of two psychological interventions for depressed adults in the community and their effect on caseness , symptoms , and subjective function . Design : A pragmatic multicentre r and omised controlled trial , stratified by centre . Setting : Nine urban and rural communities in Finl and , Republic of Irel and , Norway , Spain , and the United Kingdom . Participants : 452 participants aged 18 to 65 , identified through a community survey with depressive or adjustment disorders according to the international classification of diseases , 10th revision or Diagnostic and Statistical Manual of Mental Disorders , fourth edition . Interventions : Six individual sessions of problem solving treatment ( n=128 ) , eight group sessions of the course on prevention of depression ( n=108 ) , and controls ( n=189 ) . Main outcome measures : Completion rates for each intervention , diagnosis of depression , and depressive symptoms and subjective function . Results : 63 % of participants assigned to problem solving and 44 % assigned to prevention of depression completed their intervention . The proportion of problem solving participants depressed at six months was 17 % less than that for controls , giving a number needed to treat of 6 ; the mean difference in Beck depression inventory score was −2.63 ( 95 % confidence interval −4.95 to −0.32 ) , and there were significant improvements in SF-36 scores . For depression prevention , the difference in proportions of depressed participants was 14 % ( number needed to treat of 7 ) ; the mean difference in Beck depression inventory score was −1.50 ( −4.16 to 1.17 ) , and there were significant improvements in SF-36 scores . Such differences were not observed at 12 months . Neither specific diagnosis nor treatment with antidepressants affected outcome . Conclusions : When offered to adults with depressive disorders in the community , problem solving treatment was more acceptable than the course on prevention of depression . Both interventions reduced caseness and improved subjective function Background .Depression is common in primary care , but rates of adequate care are low . Little is known about the role of patient treatment preferences in encouraging entry into care . Objectives .To examine whether a primary care based depression quality improvement ( QI ) intervention design ed to accommo date patient and provider treatment choice increases the likelihood that patients enter depression treatment and receive preferred treatment . Methods .In 46 primary care clinics , patients with current depressive symptoms and either lifetime or current depressive disorder were identified through screening . Treatment preferences , patient characteristics , and use of depression treatments were assessed at baseline and 6 months by patient self-report . Matched clinics were r and omized to usual care ( UC ) or 1 of 2 QI interventions . Data were analyzed using logistic regression models . Results .For patients not in care at baseline , the QI interventions increased rates of entry into depression treatment compared with usual care ( adjusted percentage : 50.0 % ± 5.3 and 33.0 % ± 4.9 for interventions vs. 15.9 % ± 3.6 for usual care ; F = 12.973 , P < 0.0001 ) . Patients in intervention clinics were more likely to get treatments they preferred compared with those in usual care ( adjusted percentage : 54.2 % ± 3.3 and 50.7 % ± 3.1 for interventions vs. 40.5 % ± 3.1 for usual care ; F = 6.034 , P < 0.003 ) ; however , in all clinics less than half of patients preferring counseling reported receiving it . Conclusions .QI interventions that support patient choice can improve the likelihood of patients receiving preferred treatments . Patient treatment preference appears to be related to likelihood of entering depression treatment , and patients preferring counseling may require additional interventions to enhance entry into treatment BACKGROUND Many people who are depressed do not receive any professional help and their beliefs about the helpfulness of treatment do not always correspond with those of health professionals . To facilitate choices about treatment , the present study examined the effects of providing depressed people in the community with evidence on whether various treatment options work . METHOD A r and omized controlled trial was carried out with 1094 persons selected at r and om from the community who screened positive for depressive symptoms and agreed to participate . Participants were mailed either an evidence -based consumer guide to treatments for depression or , as a control , a general brochure on depression . Outcomes were the rated usefulness of the information provided , changes in attitudes to depression treatments , actions taken to reduce depression , and changes in depressive symptoms , anxiety symptoms and disability . RESULTS Participants rated the evidence -based consumer guide as more useful than the control brochure . Attitudes to some treatments changed . Improvements in symptoms and disability did not differ significantly between interventions . CONCLUSION Providing people who are depressed with evidence on which treatments work produces some changes in attitudes and behaviour . However , this intervention may need to be enhanced if it is to produce symptom change The aim of this controlled study was to evaluate a 1-year learner-centred educational project in end-of-life care for home care staff in a rural district of Sweden . Another rural district in the same region served as a control area . A 20-item question naire measuring attitudes towards end-of-life care was design ed , and the Hospital Anxiety and Depression ( HAD ) scale was used to measure mental well being . Increased agreement to 18 of 20 attitude statements was seen in the education group , while 2 of 20 items showed a decreased agreement in the control group . Test retest reliability of the 20-item question naire was good ( r = 0.92 ) . The total HAD score decreased from 8.3 pretest to 5.3 post-test in the education group ( 95 % CI=2.1– 3.7 ; P<0.001 ) , and was 6.8 for both years in the control group . Our study shows that a comprehensive educational programme not only improved attitudes towards end-of-life care , but also the mental well being of the home care staff |
11,853 | 26,414,020 | For instance , intensive lowering of blood pressure has reduced major cardiovascular events by 11 % ( 6 ) . | Type 1 diabetes mellitus ( T1DM ) , one of the most common chronic diseases in childhood and adolescence , is increasing in prevalence in the United States ( 1 ) .
The l and mark DCCT ( Diabetes Control and Complications Trial ) and its related longitudinal study ( EDIC [ Epidemiology of Diabetes Interventions and Complications ] ) found that intensive glycemic control prevents development and progression of micro- and macrovascular complications ( 2 , 3 ) and death ( 4 ) .
Because knowledge acquisition alone is insufficient for behavioral changes ( 13 , 14 ) , the focus for DSME has shifted from traditional didactic approaches to more patient-centered methods that incorporate interaction , problem-solving , and other behavioral approaches and techniques ( 11 , 1517 ) .
Moreover , programs need to be tailored to the needs of the target population , such as developmental milestones in children or unique personal challenges during adolescence or adulthood ( 18 ) .
Few systematic review s on education and training in T1DM have been conducted over the past decade ( 1921 ) .
Anticipating high diversity in program content and delivery mechanisms , our evaluation also explores effect modification by program factors . | AIMS To evaluate the effectiveness of a family-centred group education programme , in adolescents with Type 1 diabetes . METHODS Three hundred and five adolescents with Type 1 diabetes ; age 13.1 ± 1.9 years , diabetes duration 5.6 ± 3.3 years , BMI 20.9 ± 3.7 kg/m(2 ) , HbA(1c ) 78 ± 6 mmol/mol ( 9.3 ± 1.9 % ) were r and omly allocated to the Families and Adolescents Communication and Teamwork Study ( FACTS ) diabetes education programme ; ( six 90-min monthly sessions attended by parents and adolescents incorporating skills training and family teamwork ) or conventional clinical care . Primary outcome was HbA(1c ) at 18 months ( 12 months post-intervention ) . Secondary outcomes were HbA(1c ) at 9 months , psychosocial outcomes , adolescent quality of life , well-being , family responsibility and insulin dose adjustment behaviours at 12 months ( 6 months post-intervention ) and episodes of severe hypoglycaemia and diabetic ketoacidois during the 12 months post-intervention . All analyses are intention to treat . RESULTS Session attendance was poor with 48/158 families ( 30.4 % ) not attending any sessions and only 75/158 ( 47.5 % ) families attending ≥ 4 group education sessions . All biomedical and psychosocial outcomes were comparable between groups . At 18 months there was no significant difference in HbA(1c ) in either group and no between-group differences over time : intervention group 75 mmol/mol ( 9.0 % ) to 78 mmol/mol ( 9.3 % ) , control group 77 mmol/mol ( 9.2 % ) to 80 mmol/mol ( 9.5 % ) . Adolescents perceived no changes in parental input at 12 months . CONCLUSION Poor attendance of group education sessions delivered in routine clinics was a major challenge . More personalized educational approaches may be required to support and motivate families who are struggling to integrate the dem and s of intensive insulin regimens into their daily lives 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 < 0.001 ) . 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 Evaluated the effects of stress management training ( SMT ) for adolescents with diabetes in a 9-month controlled treatment- outcome study . Nine patients were r and omly assigned to a stress management group while another 10 patients served as controls and received st and ard outpatient treatment . The treatment program consisted of 10 sessions over 3 months , 3 additional sessions over 3 months , and a 3-month follow-up without treatment . Diabetes-specific stress decreased significantly for patients in the SMT group over the course of the intervention and follow-up . However , metabolic control , regimen adherence , coping styles , and self-efficacy about diabetes were unchanged . These findings suggest a SMT program for adolescents with diabetes may be helpful in reducing diabetes-specific stress , but additional procedures are necessary to improve adherence , coping styles , and metabolic control OBJECTIVE The objective of this study was to compare the relative effectiveness of two modes of delivering Behavioral Family Systems Therapy for Diabetes ( BFST-D ) to improve adherence and glycemic control among adolescents with type 1 diabetes with suboptimal glycemic control ( HbA1c ≥9.0 % [ ≥74.9 mmol/mol ] ) : face to face in clinic ( Clinic ) and Internet videoconferencing ( Skype ) conditions . RESEARCH DESIGN AND METHODS Adolescents aged 12 to 18 years and at least one adult caregiver were r and omized to receive BFST-D via the Clinic or Skype condition . Participants completed up to 10 therapy sessions within a 12-week period . Changes in youth- and parent-reported adherence and glycemic control were compared before and after the intervention and at follow-up assessment . RESULTS Using an intent-to-treat analytic approach , no significant between-group differences were identified between the before , after , and follow-up assessment s. Groups were collapsed to examine the overall effects of BFST-D on adherence and glycemic control . Results identified that statistically significant improvements in adherence and glycemic control occurred from before to after the intervention ; improvements were maintained at 3-month follow-up . CONCLUSIONS Delivery of BFST-D via Internet-based videoconferencing is viable for addressing nonadherence and suboptimal glycemic control in adolescents with type 1 diabetes , potentially reducing important barriers to care for youth and families OBJECTIVE : To test the effect on diabetes management outcomes of a low-intensity , clinic-integrated behavioral intervention for families of youth with type 1 diabetes . METHODS : Families ( n = 390 ) obtaining care for type 1 diabetes participated in a 2-year r and omized clinical trial of a clinic-integrated behavioral intervention design ed to improve family diabetes management practice s. Measurement of hemoglobin A1c , the primary outcome , was obtained at each clinic visit and analyzed central ly . Blood glucose meter data were downloaded at each visit . Adherence was assessed by using a semistructured interview at baseline , mid- study , and follow-up . Analyses included 2- sample t tests at predefined time intervals and mixed-effect linear-quadratic models to assess for difference in change in outcomes across the study duration . RESULTS : A significant overall intervention effect on change in glycemic control from baseline was observed at the 24-month interval ( P = .03 ) . The mixed-effect model showed a significant intervention by age interaction ( P < .001 ) . Among participants aged 12 to 14 , a significant effect on glycemic control was observed ( P = .009 for change from baseline to 24-month interval ; P = .035 for mixed-effect model across study duration ) , but there was no effect among those aged 9 to 11 . There was no intervention effect on child or parent report of adherence ; however , associations of change in adherence with change in glycemic control were weak . CONCLUSIONS : This clinic-integrated behavioral intervention was effective in preventing the deterioration in glycemic control evident during adolescence , offering a potential model for integrating medical and behavioral sciences in clinical care Background Few interventions have effectively improved health outcomes among youth with diabetes in chronic poor metabolic control . Purpose This study aims to determine whether multisystemic therapy ( MST ) , an intensive , home-based , tailored family treatment , was superior to weekly telephone support for improving regimen adherence and metabolic control among adolescents with chronic poor metabolic control . Methods A r and omized controlled trial was conducted with 146 adolescents with types 1 or 2 diabetes . Data were collected at baseline , 7 months ( treatment termination ) , and 12 months ( 6 months follow-up ) . Results Adolescents receiving MST had significantly improved metabolic control at 7 ( 1.01 % decrease ) and 12 months ( 0.74 % decrease ) compared to adolescents in telephone support . Parents of adolescents receiving MST reported significant improvements in adolescent adherence . However , adolescent-reported adherence was unchanged . Conclusions MST improved health outcomes among adolescents with chronic poor metabolic control when compared to telephone support . Home-based approaches may provide a viable means to improve access to behavioral interventions for such youth The purpose of this pilot study was to test the hypothesis that adolescents with type 1 diabetes can learn to become better problem solvers in diabetes self-care and thereby improve their metabolic control . METHODS Fifty-three adolescents aged 13 to 17 with type 1 diabetes were r and omly assigned to either a 6-week problem-solving diabetes education program or to a control group ( usual care ) . Al C levels were obtained as well as assessment s of problem solving , frequency of behavior , level of responsibility , and 24-hour behavior recall at baseline and 6 months . RESULTS The experimental group participants showed significantly improved problem-solving test scores and Al C values from baseline to 6 months , changes not evident in the control group . At 6 months , the experimental group participants were doing blood glucose testing more often than those in the control group . However , there was no significant difference in problem-solving test scores or Al C values . CONCLUSIONS This 6-week intervention for adolescents with diabetes result ed in better problem-solving skills , more frequent blood glucose testing , and improved Al C values . The results suggest that a diabetes problem-solving program for adolescents can be effective in improving metabolic control OBJECTIVE To examine the impact of a Cognitive Behavior Therapy (CBT)-based intervention on HbA(1c ) , self-care behaviors and psychosocial factors among poorly controlled adult type 1 diabetes patients . METHODS Ninety-four type 1 diabetes patients were r and omly assigned to either an intervention group or a control group . The intervention was based on CBT and was mainly delivered in group format , but individual sessions were also included . All subjects were provided with a continuous glucose monitoring system ( CGMS ) during two 3-day periods . HbA(1c ) , self-care behaviors and psychosocial factors were measured up to 48 weeks . RESULTS Significant differences were observed with respect to HbA(1c ) ( P<0.05 ) , well-being ( P<0.05 ) , diabetes-related distress ( P<0.01 ) , frequency of blood glucose testing ( P<0.05 ) , avoidance of hypoglycemia ( P<0.01 ) , perceived stress ( P<0.05 ) , anxiety ( P<0.05 ) and depression ( P<0.05 ) , all of which showed greater improvement in the intervention group compared with the control group . A significant difference ( P<0.05 ) was registered with respect to non-severe hypoglycemia , which yielded a higher score in the intervention group . CONCLUSION This CBT-based intervention appears to be a promising approach to diabetes self-management . PRACTICE IMPLICATION S Diabetes care may benefit from applying tools commonly used in CBT . For further scientific evaluation in clinical practice , there is a need for specially educated diabetes care teams , trained in the current approach , as well as cooperation between diabetes care teams and psychologists trained in CBT The feasibility of a family-based clinic-integrated behavioral intervention to improve family management of type 1 diabetes was evaluated . In each of four clinical sites , 30 - 32 families ( a total of 122 ) were r and omized to intervention or usual care comparison groups . The WE*CAN intervention , based on family problem-solving methods , was delivered during three routine clinic visits by trained ' Health Advisors ' . Of eligible families across the four sites , 83 % agreed to participate , of whom 96 % completed the baseline , mid-term , and postintervention assessment s. Families participated in an average of 2.85 intervention sessions over an 8-month period . The intervention was integrated into the clinic setting without impairing clinic flow and was implemented with fidelity and consistency across sites by trained non-professionals . The findings provide evidence of the feasibility of conducting a multisite trial to evaluate the effects of a clinic-integrated problem-solving intervention to improve family management . Many lessons were learned that provide guidance for recruitment , measurement , and intervention for the larger clinical trial OBJECTIVE Youth with type 1 diabetes frequently do not achieve glycemic targets . We aim ed to improve glycemic control with a Care Ambassador ( CA ) and family-focused psychoeducational intervention . RESEARCH DESIGN AND METHODS In a 2-yr , r and omized , clinical trial , we compared three groups : ( i ) st and ard care , ( ii ) monthly outreach by a CA , and ( iii ) monthly outreach by a CA plus a quarterly clinic-based psychoeducational intervention . The psychoeducational intervention provided realistic expectations and problem-solving strategies related to family diabetes management . Data on diabetes management and A1c were collected , and participants completed surveys assessing parental involvement in management , diabetes-specific family conflict , and youth quality of life ( QOL ) . The primary outcome was A1c at 2 yr ; secondary outcomes included maintaining parent involvement and avoiding deterioration in glycemic control . RESULTS We studied 153 youth ( 56 % female , median age 12.9 yr ) with type 1 diabetes ( mean A1c 8.4 ± 1.4 % ) . There were no differences in A1c across treatment groups . Among youth with suboptimal baseline A1c ≥ 8 % , more youth in the psychoeducation group maintained or improved their A1c and maintained or increased parent involvement than youth in the other two groups combined ( 77 vs. 52 % , p = 0.03 ; 36 vs. 11 % , p = 0.01 , respectively ) without negative impact on youth QOL or increased diabetes-specific family conflict . CONCLUSIONS No differences in A1c were detected among the three groups at 2 yr . The psychoeducational intervention was effective in maintaining or improving A1c and parent involvement in youth with suboptimal baseline glycemic control The aim of this study was to assess the feasibility and efficacy of an Interactive Educational and Support Group programme ( IESG ) for patients with type 1 diabetes . A sample of 96 type 1 diabetic out patients was studied measuring the effects of participation in IEGS on metabolic control and diabetes-related quality of life ( QoL ) . Those refusing to participate ( n=48 ) and a sample of 37 patients who were not invited to IESG ( control ) where studied for comparison . After one year , participants showed a significant ( p<0.05 ) improvement of HbA1c from 7.7±1.6 to 7.2±1.5 % , whereas no variation of HbA1c was observed in non- participants and controls . No significant variation of QoL was observed in any of the three groups . At two-years follow-up , HbA1c of the patients attending IESG was not significantly different from that at one-year follow-up , and it was significantly lower than that observed at enrolment . QoL showed a significant improvement at 2 years with respect to baseline and oneyear follow-up . In conclusion , this programme appears to be effective in the improvement of medium term metabolic control and Objective : To investigate the impact of intensive lifestyle education on dietary practice s , exercise and metabolic measurements in people with insulin-dependent diabetes mellitus ( IDDM ) . Design : Sixty-one volunteer subjects with IDDM were r and omised to intensive ( Group 1 ) or st and ard ( Group 2 ) education programmes for six months . During a second six month period of observation Group 1 subjects received routine surveillance for their condition and those in Group 2 were given intensive advice ( phase 2 ) . Current insulin regimens were modified to optimise glycaemic control before the start of the intervention phase . Nutrient intakes , weight , blood pressure , glycated haemoglobin ( HbA ) , plasma lipids , lipoproteins and maximal oxygen consumption ( VO max ) were measured at the time of recruitment and at three monthly intervals during the trial and phase 2 . Setting : Department of Human Nutrition at the University of Otago . Results : Glycated haemoglobin decreased significantly in both groups between recruitment and r and omisation , the improvement being sustained during the six months of the r and omised trial and for group 1 during the six months of post trial observation . A further decrease was seen in Group 2 during the second six month period when they were given intensive advice . Comparable changes were seen with total and low density lipoprotein ( LDL ) cholesterol in Group 1 during the trial , but significant decreases were only seen in Group 2 in association with intensive intervention ( phase 2 ) . These changes occurred in parallel with increases in intakes of carbohydrate and monounsaturated fatty acids , a reduction in intakes of total and saturated fat , and an improvement in maximum oxygen consumption . Conclusions : A lifestyle programme for people with IDDM results in modest changes in diet and exercise habits sufficient to improve measures of glycaemic control and lipoprotein mediated risk of coronary heart disease independent of changes in insulin regime . More innovative approaches to achieve lifestyle changes are required to meet current recommendations which in turn are likely to produce even greater beneficial changes than those observed here . Sponsorship : This study was supported by the Eli Lilly Research Grant ( Eli Lilly and Company ( New Zeal and ) Ltd ) , The Deans Research Grant ( Otago Medical School , New Zeal and ) and The New Zeal and Dietetic Association ( Abbott Award ) OBJECTIVE To evaluate the efficacy of two office-based treatments design ed to prevent deterioration in glycemic control in young adolescents with type 1 diabetes in a r and omized clinical trial . An individualized , more intensive family teamwork Coping skills program was compared with a diabetes Education treatment . RESEARCH DESIGN AND METHODS A baseline assessment was followed by four brief treatment sessions and immediate posttesting over the course of 1.5 years . Families of 226 early adolescents ( ages 11–14 ) were r and omized to receive either individualized coping skills education or diabetes education as adjunctive treatment to quarterly medical appointments . Continued follow-up occurred at 3.5-month intervals for a long-term follow-up of up to 3 years . A post hoc Usual Care group facilitated comparisons of glycemic control . RESULTS Growth curve analysis showed that both treatment groups successfully prevented deterioration in adolescent disease care and simultaneously improved adolescent and parent quality of life that included indicators of more effective communication and reduced adherence barriers — without a concomitant increase in diabetes-related or general family conflict . However , contrary to expectation , the Education group was more efficacious than the Coping group in improvement of disease adherence and glycemic control over a 3-year follow-up . CONCLUSIONS Low-intensity office-based quarterly treatment can maintain or improve disease care adherence in early adolescence when provided to adolescent/parent dyads . Better outcomes are achieved when treatment goals and techniques match the needs of the targeted population OBJECTIVE — Studies showing that family communication and conflict resolution are critical to effective management of type 1 diabetes in adolescents have stimulated interest in evaluating psychological treatments targeting these processes . Previous trials have shown that Behavioral Family Systems Therapy ( BFST ) improved parent-adolescent relationships but not treatment adherence or glycemic control . This study evaluates a revised intervention , BFST for Diabetes ( BFST-D ) , modified to achieve greater impact on diabetes-related family conflict , treatment adherence , and metabolic control . RESEARCH DESIGN AND METHODS —A sample of 104 families of adolescents with inadequate control of type 1 diabetes was r and omized to either remain in st and ard care ( SC ) or to augmentation of that regimen by 12 sessions of either a multifamily educational support ( ES ) group or 12 sessions of BFST-D over 6 months . Pertinent measures were collected at baseline and at follow-up evaluations at 6 , 12 , and 18 months . RESULTS —BFST-D was significantly superior to both SC and ES in effects on A1C , while effects on treatment adherence and family conflict were equivocal . Improvement in A1C appeared to be mediated by improvement in treatment adherence . A significantly higher percentage of BFST-D youth achieved moderate or greater improvement ( > 0.5 SD ) in treatment adherence compared with the SC group at each follow-up and the ES group at 6 and 18 months . Change in treatment adherence correlated significantly with change in A1C at each follow-up . CONCLUSIONS —These results support the efficacy of BFST-D in improving A1C , but further research is needed to identify the mechanisms of this effect and to achieve cost-effective dissemination of the intervention OBJECTIVE —To assess the social-cognitive , behavioral , and physiological outcomes of a self-management intervention for youth with type 1 diabetes . RESEARCH DESIGN AND METHODS —A total of 81 youth with type 1 diabetes aged 11–16 years were r and omized to usual care versus a “ diabetes personal trainer ” intervention , consisting of six self-monitoring , goal - setting , and problem-solving sessions with trained nonprofessionals . Assessment s were completed at baseline and multiple follow-up intervals . A1C data were obtained from medical records . ANCOVA adjusting for age and baseline values were conducted for each outcome . RESULTS —At both short-term and 1-year follow-up , there was a trend for an overall intervention effect on A1C ( short-term F = 3.71 , P = 0.06 ; 1-year F = 3.79 , P = 0.06 ) and a significant intervention-by-age interaction , indicating a great effect among older than younger youth ( short-term F = 4.78 , P = 0.03 ; 1-year F = 4.53 , P = 0.04 ) . Subgroup analyses demonstrated no treatment group difference among younger youth but a significant difference among the older youth . No treatment group differences in parent or youth report of adherence were observed . CONCLUSIONS —The diabetes personal trainer intervention demonstrated significant effects in A1C among middle adolescents Background Providing care for adolescents with type 1 diabetes is complex , dem and ing , and often unsuccessful . Guided self-determination ( GSD ) is a life skills approach that has been proven effective in caring for adults with type 1 diabetes . To improve care , GSD was revised for adolescents , their parents , and interdisciplinary healthcare providers ( HCP ) to create GSD-Youth ( GSD-Y ) . We evaluated the impact of GSD-Y after it was integrated into pediatric outpatient visits versus treatment-as-usual , focusing on glycemic control and the development of life skills in adolescents with type 1 diabetes . Methods Seventy-one adolescents ( mean age : 15 years , mean duration of diabetes : 5.7 years , mean HbA1c : 77 mmol/mol ( 9.1 % ) , upon entering the study ) from two pediatric departments were r and omized into a GSD-Y group ( n = 37 , GSD-Y was provided during individual outpatient sessions ) versus a treatment-as-usual group ( n = 34 ) . The primary outcome was the HbA1c measurement . The secondary outcomes were life skills development ( assessed by self-reported psychometric scales ) , self-monitored blood glucose levels , and hypo- and hyperglycemic episodes . The analysis followed an intention-to-treat basis . Results Fifty-seven adolescents ( 80 % ) completed the trial , and 53 ( 75 % ) completed a six-month post-treatment follow-up . No significant effect of GSD-Y on the HbA1c could be detected in a mixed-model analysis after adjusting for the baseline HbA1c levels and the identity of the HCP ( P = 0.85 ) . GSD-Y significantly reduced the amotivation for diabetes self-management after adjusting for the baseline value ( P = 0.001 ) . Compared with the control group , the trial completion was prolonged in the GSD-Y group ( P < 0.001 ) , requiring more visits ( P = 0.05 ) with a higher rate of non-attendance ( P = 0.01 ) . GSD-Y parents participated in fewer of the adolescents ’ visits ( P = 0.05 ) compared with control parents . Conclusions Compared with treatment-as-usual , GSD-Y did not improve HbA1c levels , but it did decrease adolescents ’ amotivation for diabetes self-management . Trial registration http://www.controlled-trials.com/is rct n/ search .html?srch=54243636%26sort=3%26dir = desc%26max=10%26Su bmi t = SU BMI T , registered on 10 January 2010 . Life skills for adolescents with type 1 diabetes and their parents Background Diets of children with type 1 diabetes are low in fruits , vegetables , and whole grains , and high in foods of minimal nutritional value , increasing risk for future adverse health outcomes . This 18-month r and omized clinical trial tested the effect of a family-based behavioral intervention integrating motivational interviewing , active learning , and applied problem-solving on the primary outcomes of dietary intake and glycemic control among youth with type 1 diabetes . Methods A parallel-group study with equal r and omization was conducted at an outpatient , free-st and ing , multidisciplinary tertiary diabetes center in the United States . Eligible youth were those age 8–16 years with type 1 diabetes diagnosis ≥1 year and hemoglobin A1c ( HbA1c ) ≥6.5 % and ≤10.0 % . Participants were 136 parent-youth dyads ( treatment n = 66 , control n = 70 ) . The intervention consisted of 9 in-clinic sessions delivered to the child and parent ; control condition comprised equivalent assessment s and number of contacts without dietary advice . Dietary intake was assessed using 3-day diet records at 6 time points across the 18-month study . Dietary outcomes included the Healthy Eating Index-2005 ( HEI2005 ; index measuring conformance to the 2005 United States Dietary Guidelines for Americans ) and Whole Plant Food Density ( WPFD ; number of cup or ounce equivalents per 1000 kcal of whole grains , whole fruit , vegetables , legumes , nuts , and seeds consumed ) . HbA1c was obtained every 3 months . Overall comparison of outcome variables between intervention and usual care groups was conducted using permutation tests . Results There was a positive intervention effect across the study duration for HEI2005 ( p = .015 ) and WPFD ( p = .004 ) . At 18 months , HEI2005 was 7.2 greater ( mean ± SE 64.6 ± 2.0 versus 57.4 ± 1.6 ) , and WPFD was 0.5 greater ( 2.2 ± 0.1 versus 1.7 ± 0.1 ) in the intervention group versus control . There was no difference between groups in HbA1c across the study duration . Conclusions This behavioral nutrition intervention improved dietary quality among youth with type 1 diabetes , but did not impact glycemic control . Findings indicate the potential utility of incorporating such strategies into clinical care , and suggest that improvement in diet quality can be achieved in families living with this burdensome disease . Trial registration Clinical trials.gov registration number : OBJECTIVE To describe a 2-year follow-up of A1C outcomes of a self-regulation intervention for youth with type 1 diabetes . RESEARCH DESIGN AND METHODS A total of 81 youths with type 1 diabetes ages 11–16 years were r and omized to usual care versus a diabetes personal trainer intervention consisting of six self-monitoring , goal - setting , and problem-solving sessions with trained nonprofessionals . A1C data were obtained from medical records 2 years postintervention , and ANCOVA adjusting for age and baseline A1C was conducted . RESULTS An overall intervention effect on A1C ( 8.93 % control vs. 8.43 % intervention ; F = 8.24 , P = 0.05 ) and a significant intervention-by-age interaction ( F = 9.88 ; P = 0.002 ) were observed , indicating a greater effect among older than younger youths . Subgroup analyses demonstrated no treatment group differences among pre-/early adolescents but a significant difference in A1C among middle adolescents ( 9.61 % control vs. 8.46 % intervention ; F = 7.20 , P = 0.011 ) . CONCLUSIONS Findings indicate maintenance of intervention effects on A1C observed at 1-year follow-up Objectives In a r and omized controlled trial , adults with Type 1 diabetes and suboptimal glycemic control who received motivational enhancement therapy ( MET ) plus cognitive behavioral therapy ( CBT ) had a greater reduction in their 12-month hemoglobin A1c ( HbA1c ) than those who received usual care ( UC ) . We tested whether improvements in glycemic control persisted up to 4 years after r and omization . Methods In the original trial , participants were r and omized to UC ( n = 121 ) , 4 sessions of MET ( n = 117 ) , or 4 sessions of MET plus 8 sessions of CBT ( n = 106 ) . Of the 344 patients who participated in the original trial , 260 ( 75.6 % ) consented to take part in this posttrial study . A linear mixed model was fitted to available measurements to assess whether intervention effects on HbA1c at 12 months were sustained at 2 , 3 , and 4 years . Results Estimated mean HbA1c level was lower for participants in the two intervention arms when compared with UC at 2 , 3 , and 4 years , but none of the differences were statistically significant . At 4 years , estimated mean HbA1c level for MET plus CBT was 0.28 % ( 95 % confidence interval = −0.22 % to 0.77 % ) lower than that for UC , and estimated mean HbA1c level for MET was 0.17 % ( 95 % confidence interval = −0.33 % to 0.66 % ) lower than that for UC . Conclusions There was no evidence of benefit for patients r and omized to MET plus CBT at 2 , 3 , or 4 years . Larger studies are needed to estimate long-term treatment effects with greater precision . Current models of psychological treatments in diabetes may need to be intensified or include maintenance sessions to maintain improvements in glycemic control . Abbreviations RCT = r and omized controlled trial ; MET = motivational enhancement therapy ; CBT = cognitive behavioral therapy ; UC = usual AIMS The Families , Adolescents and Children 's Teamwork Study ( FACTS ) is a family-centred structured education programme for children and adolescents with Type 1 diabetes . It aims to integrate group-based diabetes education into routine care , enhance parental responsibility for self management and improve glycaemic control . METHODS A r and omized wait-list control group study allocated participants to either the immediate ( four educational sessions during year 1 ) or delayed intervention ( four educational sessions during year 2 ) . In both groups , glycated haemoglobin ( HbA1c ) was measured 3-monthly and participants completed the Paediatric Quality of Life Inventory ( PedsQL ) , Problem Areas in Diabetes Scale ( PAID ) and Diabetes Family Responsibility Question naire ( DFRQ ) before and after the intervention . RESULTS Intention-to-treat analysis showed no significant difference in HbA1c or parental responsibility between participants r and omized to the immediate or delayed programme . However , during 12 months ' follow-up , families who attended > or = 2 sessions reported increased parental involvement ( P = 0.01 ) , and in children/adolescents who attended > or = 2 sessions HbA1c fell by 0.29 % compared with an increase of 0.11 % in non-attenders ( P = 0.04 ) . CONCLUSION This family-centred education programme has been integrated into paediatric diabetes care with potential benefits on parental involvement and glycaemic control , but further study is warranted before routine application into clinical care Background : Poor management of type 1 diabetes mellitus ( T1DM ) may result in serious medical complications . Psychological intervention may improve adherence to medical regimens ; however , access to trained professionals is limited , particularly in rural communities . Telehealth interventions may address this by allowing families to access services at home ; however , little is known about the efficacy of such services . Method : This study presents results from a pilot trial of a r and omized waitlist controlled trial of Telehealth Behavioral Therapy ( TBT ) for youths with T1DM . Primary outcome measures were adherence to the diabetes regimen , glycemic control , and level of family discord . Thirty-two youths ( 23 female ) with T1DM ( aged 9 to 17 years ) and one parent or caregiver participated . Telehealth Behavioral Therapy sessions were conducted thrice weekly for 12 weeks by phone and lasted an average of 15 min each . Results : Results indicated that youths in treatment decreased their hemoglobin A1c by 0.74 compared to 0.09 in the waitlist , though this was not statistically significant . Youths in treatment reported increased unsupportive and decreased caring parental behaviors . Conclusion : Telehealth Behavioral Therapy improves access to knowledgeable providers and results in a clinical ly significant improvement in glycemic control . Despite some youths experiencing an increase in unsupportive parental behaviors , TBT is a promising method of service delivery that warrants further investigation BACKGROUND Type 1 diabetes ( T1D ) in children and young people is increasing worldwide with a particular increase in children under the age of 5 years . Fewer than one in six children and young people achieve glycosylated fraction of haemoglobin ( HbA1c ) values in the range identified as providing best future outcomes . There is an urgent need for clinic-based pragmatic , feasible and effective interventions that improve both glycaemic control and quality of life ( QoL ) . The intervention offers both structured education , to ensure young people know what they need to know , and a delivery model design ed to motivate self-management . OBJECTIVE To assess the feasibility of providing a clinic-based structured educational group programme incorporating psychological approaches to improve long-term glycaemic control , QoL and psychosocial functioning in a diverse range of young people . DESIGN The study was a pragmatic , cluster r and omised control trial with integral process and economic evaluation . SETTING Twenty-eight paediatric diabetes services across London , south-east Engl and and the Midl and s. R AND OMISATION Minimised by clinic size , age ( paediatric or adolescent ) and specialisation ( district general hospital clinic or teaching hospital/tertiary clinic ) . ALLOCATION Half of the sites were r and omised to the intervention arm and half to the control arm . Allocation was concealed until after clinics had consented and the first participant was recruited . Where possible , families were blind to allocation until recruitment finished . PARTICIPANTS Forty-three health-care practitioners ( 14 teams ) were trained in the intervention . The study recruited 362 children aged 8 - 16 years , diagnosed with T1D for > 12 months , with a mean 12-month HbA1c level of ≥ 8.5 % . INTERVENTION Two 1-day workshops taught intervention delivery . A detailed manual and re sources were provided . The intervention consists of four group education sessions led by a paediatric diabetes specialist nurse with another team member . OUTCOMES The primary outcome was glycaemic control , assessed at the individual level using venous HbA1c values , measured at baseline , 12 and 24 months . Secondary outcomes were directly and indirectly related to diabetes management , including hypoglycaemic episodes , hospital admissions , diabetes regimen , knowledge , skills and responsibility for diabetes management , intervention compliance , clinic utilisation , emotional and behavioural adjustment , and general and diabetes-specific QoL. PROCESS EVALUATION Question naires , semistructured interviews , informal discussion following observation sessions , fieldwork notes and case note review were used to collect qualitative and quantitative data from key stakeholder groups at specific time points in the trial . STATISTICAL ANALYSES Primary and secondary analyses were intention-to-treat comparisons of outcomes at 12 and 24 months , using analysis of covariance with a r and om effect for clinic . Prespecified subgroup analyses based on age , gender , initial HbA1c value and socioeconomic status were estimated from models that included an interaction term . The economic analysis compared long-term costs and predicted quality -adjusted life-years ( QALYs ) . RESULTS The intervention did not improve HbA1c at 12 months [ intervention effect 0.11 ; 95 % confidence interval ( CI ) -0.28 to 0.50 ; p = 0.584 ] or 24 months ( intervention effect 0.03 ; 95 % CI -0.36 to 0.41 ; p = 0.891 ) . A total of 298/362 patients ( 82.3 % ) provided blood sample s at 12-month follow-up , and 284/362 ( 78.5 % ) provided blood sample s at 24-month follow-up . Follow-up question naires were completed by 307 patients ( 85.3 % ) at 12 months and by 295 patients ( 81.5 % ) at 24 months . Intervention group parents at 12 months ( 95 % CI 0.74 ; 0.03 to 1.52 ) and young people at 24 months ( 0.85 ; 95 % CI 0.03 to 1.61 ) had higher scores on the diabetes family responsibility question naire . Young people reported reduced happiness with body weight at 12 months ( -0.56 ; 95 % CI -1.03 to -0.06 ) . Only 68 % of groups were run . Of the 180 families recruited , 96 ( 53 % ) attended at least one module . Reasons for low uptake included difficulties organising groups , and work and school commitments . Young people with higher HbA1c levels were less likely to attend . Parents and young people who attended groups described improved family relationships , improved knowledge and underst and ing , greater confidence and increased motivation to manage diabetes . Twenty-four months after the intervention , nearly half of the young people reported that the groups had made them want to try harder and that they had carried on trying . A high- quality , complex , pragmatic trial of structured education can be delivered alongside st and ard care in NHS diabetes clinics . Health-care providers benefited from behaviour change skill training and can deliver pragmatic aspects of a National Institute for Health and Care Excellence (NICE)-compliant structured education programme after relatively brief training . The process evaluation provides insight into aspects of the model , and highlights strengths and aspects that may have contributed to the failure to influence primary and secondary outcomes . Current NHS practice dominates CASCADE ( Child and Adolescent Structured Competencies Approach to Diabetes Education ) in that it achieves the same number of QALYs at a lower cost . The mean cost of providing the intervention was £ 5098 per site or £ 683 per child . Members of paediatric diabetes services trained to deliver the CASCADE structured education package using behaviour change techniques did not improve glycaemic control in patients compared with control subjects 1 and 2 years after the intervention . The training workshops for practitioners were well evaluated ; however , more intensive training was needed . The intervention cost £ 683 per patient but was not cost-effective because it did not improve metabolic control . CONCLUSIONS A high- quality , complex , pragmatic trial of structured education can be successfully conducted alongside st and ard care in NHS diabetes clinics . Pragmatic components of a NICE-compliant structured education programme can be successfully delivered following a relatively brief 2-day training while paediatric health-care professionals benefit from training in behaviour change skills . The study provides invaluable information on barriers and opportunities regarding future , similar interventions . A low dropout rate and good attendance for the subgroup that attended the intervention suggests there might be improved uptake if offered to young people with lower HbA1c . Testing whether this approach can be more successful with a robust ongoing supervisory element should be a target of further research . TRIAL REGISTRATION Current Controlled Trials IS RCT N52537669 . 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. 20 . See the NIHR Journals Library website for further project information OBJECTIVE To determine whether a 6-month home-based intervention program in adolescents with poorly controlled diabetes improves metabolic control and whether benefits are maintained after the intervention . RESEARCH DESIGN AND METHODS Adolescents with a mean HbA1c of > 9.0 % over the preceding 12 months received either routine care in a diabetes clinic and an ambulatory intervention for 6 months ( n = 37 ) or routine care only ( n = 32 ) . A diabetes educator provided monthly home visits and weekly phone contact to educate and support the adolescents in setting goals for insulin adjustment , blood glucose monitoring , and target blood glucose range . There was no systematic change in the frequency of insulin injections . After the intervention , there was a 12-month follow-up when the intervention and control groups both received only routine care . Outcome measures were HbA1c and Diabetes Knowledge Assessment ( DKN ) . RESULTS During the intervention , mean HbA1c fell ( baseline : 11.1 + /- 1.3 % , 6 months : 9.7 + /- 1.6 % ; P = 0.0001 ) and mean knowledge scores increased ( P = 0.0001 ) in the intervention group but not in control subjects . However , this improvement in HbA1c and increase in knowledge was not maintained in the intervention group at 12- and 18-month follow-up assessment s. Parents ' knowledge scores also improved significantly from baseline levels in the intervention group at 6 and 12 months ( P = 0.001 , P = 0.005 , respectively ) . CONCLUSIONS An ambulatory program improves metabolic control and knowledge in adolescents with poorly controlled type 1 diabetes ; however , it is effective only while the intervention is maintained OBJECTIVE To report 1-year results of newly developed method , guided self-determination ( GSD ) , applied in group training ( GSD-GT ) for Type 1 diabetes patients with persistent poor glycaemic control . METHODS GSD was design ed on the basis of qualitative research to help patients develop life skills with diabetes using worksheets filled in at home and coached by nurses in mutual reflection . We r and omized 18 - 49-year-old adults at a Danish university hospital to either 16 h GSD-GT in 2001 or to similar training 1 year later . INCLUSION CRITERIA mean A1C > or = 8.0 % for at least 2 years , disease onset < or = 40 years and insulin treatment from onset . RESULTS Thirty GSD-GT patients and 20 controls completed the study . GSD-GT patients did better than control patients in terms of ( a ) increased autonomy support perceived from health professionals ( p<0.01 ) ; ( b ) higher frequency of self-monitored blood glucoses ( p<0.001 ) ; ( c ) increased perceived competence in managing diabetes ( p<0.01 ) ; ( d ) fewer diabetes-related problems ( p<0.05 ) ; and ( e ) improved glycaemic control ( p<0.01 ) . CONCLUSION GSD was effective in improving life skills with diabetes , including A1C , over a period of 1 year . PRACTICE IMPLICATION S GSD is a worthy c and i date for further research . We consider it adjustable to people with type 2 diabetes and other chronic conditions OBJECTIVE To evaluate an ambulatory , family-focused intervention aim ed at optimizing STUDY DESIGN Study design We r and omly assigned 105 children and adolescents , 8 to 17 years of age , with T1DM for < or = 6 years , to a family-focused teamwork ( TW ) intervention or to st and ard multidisciplinary diabetes care ( SC ) . Patients in both study groups were seen at 3- to 4-month intervals and were followed prospect ively for 1 year . Measures of family involvement in diabetes tasks , DFC , and quality of life were performed at baseline and after 1 year . Hemoglobin A1c was measured at each visit . RESULTS Patients ( n = 100 ) completed follow-up , ( 50 in TW and 50 in SC ) . At entry , A1c was 8.4 % + /- 1.3 % in TW and 8.3 % + /- 1.0 % in SC . After 1 year , A1c was 8.2 % + /- 1.1 % in TW compared with 8.7 % + /- 1.5 % in SC ( P < .05 ) . Both groups had similar frequencies of blood glucose monitoring ( BGM ) and insulin dosing . Families exposed to the TW intervention maintained or increased family involvement significantly more than families exposed to SC ( P = .05 ) . In multivariate analysis , the TW intervention and the daily frequency of BGM significantly predicted A1c ( R ( 2 ) = 0.17 , P = .05 ) . Despite increased family involvement , the TW group reported no increase in DFC or decrease in quality of life . CONCLUSIONS The ambulatory TW intervention prevented the expected deterioration in glycemic control seen with SC in youths with T1DM of < or = 6 years ' duration . Successful family involvement may assist in the preservation of health and the prevention of long-term diabetes complications for youth with diabetes OBJECTIVE To design and evaluate an office-based intervention aim ed at maintaining parent-adolescent teamwork in diabetes management tasks without increasing diabetes-related family conflict . RESEARCH DESIGN AND METHODS There were 85 patients ( aged 10 - 15 years , mean 12.6 years ) with type 1 diabetes ( mean duration 5.5 years ; mean HbA1c 8.5 % ) who were r and omly assigned to one of three study groups -- teamwork , attention control , and st and ard care-- and followed for 24 months . At each visit , parent involvement in insulin administration and blood glucose monitoring was assessed . The teamwork and attention control interventions were integrated into routine ambulatory visits over the first 12 months ( four medical visits ) . Measures of diabetes-related family conflict were collected at baseline and after 12 months . All patients were followed for an additional 12 months with respect to glycemic control . RESULTS In the teamwork group , there was no major deterioration ( 0 % ) in parent involvement in insulin administration , in contrast to 16 % major deterioration in the combined comparison ( attention control and st and ard care ) group ( P < 0.03 ) . Similarly , no teamwork families showed major deterioration in parent involvement with blood glucose monitoring versus 11 % in the comparison group ( P < 0.07 ) . On both the Diabetes Family Conflict Scale and the Diabetes Family Behavior Checklist , teamwork families reported significantly less conflict at 12 months . An analysis of HbA1c over the 12- to 24-month follow-up period indicated that more adolescents in the teamwork group ( 68 % ) than in the comparison group ( 47 % ) improved their HbA1c ( P < 0.07 ) . CONCLUSIONS The data demonstrate that parent involvement in diabetes management tasks can be strengthened through a low-intensity intervention integrated into routine follow-up diabetes care . Moreover , despite increased engagement between teen and parent centered around diabetes tasks , the teamwork families showed decreased diabetes-related family conflict . Within the context of a broader cultural recognition of the protective function of parent involvement in the lives of adolescents , the findings of this study reinforce the potential value of a parent-adolescent partnership in managing chronic disease This study evaluated the effectiveness of a family-based , multidisciplinary , behavior-modification program ( SHAPEDOWN ) adapted for obese adolescents with insulin-dependent diabetes mellitus ( IDDM ) , a unique and understudied population . Eleven test subjects participated in the SHAPEDOWN program , and 9 comparison subjects received st and ard nutrition care for subjects with IDDM . Mean age of the experimental and control subjects was 13.9 and 15.2 years , respectively , and the two groups were 121 % and 126 % overweight , respectively . The program comprised 14 weekly sessions in which subject and parents participated in separate groups taught by a dietitian , a psychologist , and a child health associate . Data were collected at baseline , at 3 months , and at 15 months . Compared with st and ard treatment , the intervention significantly increased body image . Self-esteem improved clinical ly in four subjects in the experimental group but in only one subject in the st and ard treatment group . Change in percent overweight at 15 months was -3 % for the experimental group and + 0.9 % for the st and ard treatment group ; however , the difference was not statistically significant . This mean loss in percent overweight of subjects is comparable with that reported in a nondiabetic group in which age and percent overweight were similar . The change in percent overweight from baseline to 15 months in the two groups combined shows a positive correlation with triceps skinfold thickness and a negative correlation with obesity-related behavior . Changes in glycated hemoglobin were not significantly different . We conclude that this program proved effective in improving body image and self-esteem in obese adolescents with IDDM . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To determine whether multisystemic therapy ( MST ) , an intensive , home-based psychotherapy , could decrease rates of hospital utilization and related costs of care among adolescents with poorly controlled type diabetes . METHODS Thirty-one adolescents were r and omly assigned to receive either MST or st and ard care . MST lasted approximately 6 months , and all participants were followed for 9 months . Rates of inpatient admissions and emergency room ( ER ) visits were calculated for a 9-month pre study period and during the 9 months of study participation . The relationship between changes in inpatient admissions and changes in metabolic control was also investigated . RESULTS Intervention participants had a decreasing number of inpatient admissions from the baseline period to the end of the study , whereas the number of inpatient admissions increased for controls . Use of the emergency room did not differ . Related medical charges and direct care costs were significantly lower for adolescents receiving MST . Correlational analyses conducted with a subset of participants indicated that decreases in inpatient admissions were associated with improved metabolic control for MST but not control participants . CONCLUSIONS Findings suggest that MST has the potential to decrease inpatient admissions among adolescents with poorly controlled type 1 diabetes The primary purpose of the present study was to determine whether multisystemic therapy ( MST ) , an intensive , home-based psychotherapy , improved regimen adherence , metabolic control , and rates of hospitalization for diabetic ketoacidosis ( DKA ) among adolescents with chronically poorly controlled Type 1 diabetes 6 months after the completion of treatment . A r and omized controlled trial was conducted with 127 adolescents and their families . Mean participant age was 13.2 years . Sixty-three percent of participants were African American , and 51 % were female . Data were collected at baseline , treatment termination , and 6-month follow-up . Changes in glycated hemoglobin ( HbA1c ) , frequency of blood glucose testing ( BGT ) , and rate of DKA admissions were assessed . In intent-to-treat analyses , a main effect of MST on DKA admissions was found at both treatment termination and follow-up . Improvements in BGT were moderated by family composition ; only 2-parent MST families maintained improvements at follow-up . Improvements in HbA1c for the MST group at treatment termination were lost at follow-up . Results show that intensive , home-based psychotherapy created stable reductions in serious lapses in adherence , as indexed by episodes of DKA , among youth with poorly controlled diabetes OBJECTIVES To determine whether ( i ) motivational enhancement therapy ( MET ) + cognitive behaviour therapy ( CBT ) compared with usual care , ( ii ) MET compared with usual care , ( iii ) or MET + CBT compared with MET was more effective in improving glycaemic control when delivered by general nurses with additional training in these techniques . DESIGN A three-arm parallel r and omised controlled trial as the gold st and ard design to test the effectiveness of psychological treatments . SETTING The recruiting centres were diabetes clinics in seven acute trusts in south-east London and Greater Manchester . PARTICIPANTS Adults ( 18 - 65 years ) with a confirmed diagnosis of type 1 diabetes for a minimum duration of 2 years and a current glycated ( or glycosylated ) haemoglobin ( HbA1c ) value between 8.2 % and 15.0 % . INTERVENTIONS The control arm consisted of usual diabetes care which varied between the hospitals , but constituted at least three monthly appointments to diabetes clinic . The two treatments arms consisted of usual care with MET and usual care with MET + CBT . MAIN OUTCOME MEASURES The primary outcome was HbA1c at 12 months from r and omisation . Secondary outcome measures were 1-year costs measured by the Client Service Receipt Inventory at baseline , 6 months and 12 months ; quality of life-years [ quality -adjusted life-years ( QALYs ) ] measured by the SF-36 ( Short Form-36 Health Survey Question naire ) and EQ-5D ( European Quality of Life-5 Dimensions ) at baseline and 12 months . RESULTS One thous and six hundred and fifty-nine people with type 1 diabetes were screened and 344 were r and omised to MET + CBT ( n = 106 ) , MET ( n = 117 ) and to usual care ( n = 121 ) . The 12-month follow-up rate for HbA1c was 88 % ( n = 305 ) . The adjusted mean 12-month HbA1c was 0.45 % lower in those treated with MET + CBT [ 95 % confidence interval ( CI ) 0.16 % to 0.79 % , p = 0.008 ] than for usual care ; 0.16 % lower in those treated with MET ( 95 % CI 0.20 % to 0.51 % , p = 0.38 ) than for usual care ; and 0.30 % lower with MET + CBT than with MET ( 95 % CI -0.07 % to 0.66 % , p = 0.11 ) . The higher the HbA1c , and the younger the participant at baseline , the greater was the reduction in HbA1c . The interventions had no effect on secondary outcomes such as depression and quality of life . The economic evaluation was inconclusive . Both interventions were associated with increased health care costs than for usual care alone . There was no significant difference in social costs . Cost effectiveness ratios , up to one year , varied considerably according to whether QALY estimates were based on EQ-5D or SF-36 and whether imputed or complete data were used in the analyses . CONCLUSIONS A combination of MET and CBT may be useful for patients with persistent sub-optimal diabetic control . MET alone appears less effective than usual care . Economic evaluation was inconclusive . TRIAL REGISTRATION Current Controlled Trials IS RCT N77044517 IMPORTANCE Whether mortality in type 1 diabetes mellitus is affected following intensive glycemic therapy has not been established . OBJECTIVE To determine whether mortality differed between the original intensive and conventional treatment groups in the long-term follow-up of the Diabetes Control and Complications Trial ( DCCT ) cohort . DESIGN , SETTING , AND PARTICIPANTS After the DCCT ( 1983 - 1993 ) ended , participants were followed up in a multisite ( 27 US and Canadian academic clinical centers ) observational study ( Epidemiology of Diabetes Control and Complications [ EDIC ] ) until December 31 , 2012 . Participants were 1441 healthy volunteers with diabetes mellitus who , at baseline , were 13 to 39 years of age with 1 to 15 years of diabetes duration and no or early microvascular complications , and without hypertension , preexisting cardiovascular disease , or other potentially life-threatening disease . INTERVENTIONS AND EXPOSURES During the clinical trial , participants were r and omly assigned to receive intensive therapy ( n = 711 ) aim ed at achieving glycemia as close to the nondiabetic range as safely possible , or conventional therapy ( n = 730 ) with the goal of avoiding symptomatic hypoglycemia and hyperglycemia . At the end of the DCCT , after a mean of 6.5 years , intensive therapy was taught and recommended to all participants and diabetes care was returned to personal physicians . MAIN OUTCOMES AND MEASURES Total and cause-specific mortality was assessed through annual contact with family and friends and through records over 27 years ' mean follow-up . RESULTS Vital status was ascertained for 1429 ( 99.2 % ) participants . There were 107 deaths , 64 in the conventional and 43 in the intensive group . The absolute risk difference was -109 per 100,000 patient-years ( 95 % CI , -218 to -1 ) , with lower all-cause mortality risk in the intensive therapy group ( hazard ratio [ HR ] = 0.67 [ 95 % CI , 0.46 - 0.99 ] ; P = .045 ) . Primary causes of death were cardiovascular disease ( 24 deaths ; 22.4 % ) , cancer ( 21 deaths ; 19.6 % ) , acute diabetes complications ( 19 deaths ; 17.8 % ) , and accidents or suicide ( 18 deaths ; 16.8 % ) . Higher levels of glycated hemoglobin ( HbA1c ) were associated with all-cause mortality ( HR = 1.56 [ 95 % CI , 1.35 - 1.81 per 10 % relative increase in HbA1c ] ; P < .001 ) , as well as the development of albuminuria ( HR = 2.20 [ 95 % CI , 1.46 - 3.31 ] ; P < .001 ) . CONCLUSIONS AND RELEVANCE After a mean of 27 years ' follow-up of patients with type 1 diabetes , 6.5 years of initial intensive diabetes therapy was associated with a modestly lower all-cause mortality rate when compared with conventional therapy . TRIAL REGISTRATION clinical trials.gov Identifiers : NCT00360815 and NCT00360893 AIM To describe experience from a behavioural medicine intervention among poorly controlled adult type 1 diabetes patients , in terms of feasibility , predictors and associations of improved glycaemic control . METHODS Data were collected on 94 poorly controlled adult type 1 diabetes patients who were r and omised to a study evaluating the effects of a behavioural medicine intervention . Statistics covered descriptive and comparison analysis . Backward stepwise regression models were used for predictive and agreement analyses involving socio-demographic and medical factors , as well as measures of diabetes self-efficacy ( DES ) , diabetes locus of control ( DLOC ) , self-care activities ( SDSCA ) , diabetes-related distress ( Swe-PAID-20 ) , fear of hypoglycaemia ( HFS ) , well-being ( WBQ ) , depression ( HAD ) and perceived stress ( PSS ) . RESULTS The participation rate in the study was 41 % and attrition was 24 % . Of those patients actually participating in the behavioural medicine intervention , 13 % withdrew . From the regression models no predictors or associations of improvement in HbA(1c ) were found . CONCLUSIONS The programme proved to be feasible in terms of design and methods . However , no clear pattern was found regarding predictors or associations of improved metabolic control as the response to the intervention . Further research in this area is called for Context Psychological issues can interfere with behavior modification that is necessary to manage type 1 diabetes , so psychological therapy might improve diabetes control . Contribution This r and omized , controlled trial compared motivational enhancement therapy with and without cognitive behavior therapy with usual care in 344 adults with type 1 diabetes ( average baseline hemoglobin A1c level , 9.4 % ) . Patients who received motivational enhancement therapy plus cognitive behavior therapy had a greater decrease in hemoglobin A1c over 12 months than patients who received usual care ( difference between groups , 0.46 % ) . No other improvements were observed . Implication Motivational enhancement therapy plus cognitive behavior therapy led to only small improvements in diabetes control , despite a total of 16 therapy sessions prescribed over 6 months . The Editors Suboptimal glycemic control in type 1 diabetes is common , despite the effectiveness of intensive insulin therapies , continuous subcutaneous insulin infusion pumps , and structured education programs ( 13 ) . Depression , anxiety , and disordered eating patterns are common in persons with diabetes and are associated with suboptimal glycemic control , complications , and death ( 412 ) . Diabetes-related anxieties related to hypoglycemia , complications , self-injections , and glucose self-testing are also well recognized ( 13 , 14 ) . The effectiveness of psychological treatments in improving glycemic control in adults with type 1 diabetes has not been established ( 15 ) . One reason may be that previous trials have not specifically targeted the broad range of diabetes-related problems ( 15 ) . Evidence in substance misuse setting s suggests that adding cognitive behavior therapy to motivational enhancement therapy may increase efficacy ( 16 ) . Motivational enhancement therapy is a brief ( usually 1 to 4 sessions ) counseling method for enhancing motivation to change problematic health behaviors by exploring and resolving the ambivalence about change ( 17 ) . Motivational enhancement therapy is effective in improving alcohol misuse and smoking , and preliminary evidence suggests that it may be effective in diabetes ( 18 , 19 ) . Cognitive behavior therapy is a longer therapy ( usually a minimum of 6 to 12 sessions ) that aims to enable the patient to identify , challenge , and substitute unhelpful cognitions and behaviors with more constructive ones ( 20 , 21 ) . In diabetes , several trials have predominantly used behavioral techniques ( 2225 ) and , more recently , cognitive techniques ( 2628 ) , but this novel method of integrating motivational enhancement therapy and cognitive behavior therapy has yet to be tested in diabetes setting s. One question we examined when we design ed the trial was whether diabetes nurses could be trained to deliver psychological treatments , because such a model of intervention could be used more widely than one that relied on psychologists . We added cognitive behavior therapy to motivational enhancement therapy as 1 of the interventions , rather than cognitive behavior therapy alone , because we aim ed to reach a group of patients who had persistent problems with diabetes control and were more likely to be ambivalent about change . Our objective of this r and omized , controlled trial ( RCT ) was to determine whether motivational enhancement therapy plus cognitive behavior therapy was more effective than usual care in improving glycemic control in adults with type 1 diabetes and persistent , suboptimal glycemic control and whether motivational enhancement therapy alone was more effective than usual care in improving glycemic control . The secondary objective was to assess whether either psychological intervention was more effective than usual care in improving depressive symptoms , fear of hypoglycemia , diabetes self-care behaviors , body mass index , and diabetes quality of life . Methods Design We followed the CONSORT ( Consoli date d St and ards of Reporting Trials ) guidelines ( 29 ) . The Clinical Trials Unit , Institute of Psychiatry , King 's College London , London , United Kingdom , sponsored the trial . The South West Multi-Centre Research Ethics Committee and the ethics committees of all participating hospitals approved the trial . A trial steering committee and data monitoring and ethics committee oversaw the conduct of the study . All participants provided signed informed consent . Setting Five hospitals in southeast London ( King 's College Hospital , Guy 's and St Thomas ' Hospitals , Lewisham Hospital , and Mayday University Hospital ) , and 3 hospitals in Greater Manchester ( Manchester Royal Infirmary , North Manchester General , and Stockport General Hospital/Stepping Hill Hospitals ) , United Kingdom , served as the recruiting centers . Participants Local clinicians screened their hospital data bases or lists to identify patients with type 1 diabetes . Adults ( age 18 to 65 years ) with type 1 diabetes for at least 2 years who had persistent , suboptimal glycemic control were c and i date s for inclusion into the study . Type 1 diabetes was defined as onset at age younger than 35 years and onset of insulin therapy within 6 months of diagnosis or ketones in the urine . Persistent , suboptimal glycemic control was defined as having at least 2 records of hemoglobin A1c levels between 8.2 % and 15 % : one measurement in the past 12 months and the second being the current ( in other words , at recruitment ) hemoglobin A1c level . We excluded participants if they did not speak English , were pregnant , had a short-term or serious medical illness defined by the treating physician , had advanced diabetes complications ( registered blind , serum creatinine levels # # gt##300 mol/L [ # # gt##3.39 mg/dL ] ) , had known hemaglobinopathy , had psychotic disorders , had alcohol dependence , were in psychotherapy , or had been in a structured diabetes education program less than 3 months previously . We did not exclude persons with major depression unless they were receiving antidepressant therapy initiated less than 2 months prior . Before patients were r and omly assigned , they had at least 1 session of nurse-delivered diabetes education and received a fact sheet containing the minimum accepted level of diabetes knowledge ( 30 ) . The hemoglobin A1c level was measured by ion-exchange , high-pressure liquid chromatography by using analyzers at each participating clinic : Menarini HA-8140 , HA-8121 , or HA-8160 ( Menarini Diagnostics , Florence , Italy ) ; Tosoh 2.2 Plus ( Tosoh Medics , Foster City , California ) ; or Variant II HPLC System ( Bio-Rad Laboratories , Hercules , California ) , by using methods aligned with the Diabetes Control and Complications Trial ( 1 , 31 ) . Baseline Measures We collected data on the following baseline characteristics : sociodemographic factors ( age , sex , employment status , educational level , ethnicity , marital status ) ; lifestyle factors ( current smoking status and units of alcohol intake per week ) ; physical health ( hemoglobin A1c level ) ; resting blood pressure ( mm Hg ) , body mass index ( kg/m2 ) ; total r and om cholesterol level ( moL/L [ mg/dL ] ) ; duration of diabetes ( years ) ; presence of diabetes complications ( early morning albumincreatinine ratio level ) ; peripheral neuropathy ( screened using the 10-g monofilament ) ; retinopathy status coded as none or any ( treated , nonsight-threatening , and sight-threatening ) from retinal color photographs or fundoscopy assessment s ; and depressive symptoms assessed on the well-vali date d and reliable self-reported Patient Health Question naire-9 ( score range , 0 to 27 ; scores 10 represent major depressive disorder ) ( 32 ) . We measured diabetes-related cognitions and behaviors on the revised Hypoglycaemia Fear Survey ( 33 , 34 ) , which consists of 10 behavior items ( score range , 0 to 40 ) and 13 worry items ( score range , 0 to 52 ) self-rated on 5-point Likert scales . The revised Summary of Diabetes Self-Care Activities asks how many days in the last 7 days the participant engaged in diet , exercise , and blood sugar testing ( score range , 0 to 7 days ) ( 35 ) . Higher scores denote a greater tendency to maintain high blood glucose levels and fear of hypoglycemia , respectively . Quality of life was measured by satisfaction and impact subscales of the Diabetes Quality of Life scale ( score range per subscale , 1 to 5 ) ( 36 ) . R and omization We prepared a computer-generated r and omization list , stratified by hospital site , which used blocks of r and om sizes ( 3 , 6 , 9 , and 12 ) in advance . The data base manager of the Clinical Trials Unit , who was independent of the study , held the list electronically in a password-protected data base . Allocation could only be revealed to the recruiting research er , who then assigned each participant after obtaining consent . We collected all baseline measures before r and omization . The laboratory technicians , who were blinded to the allocation throughout the study and the self-reported psychological measures , assessed hemoglobin A1c levels , which was the main outcome . The research ers , study participants , and nurse therapists were not blinded to allocation after r and omization because of the nature of delivering psychological treatments . Interventions Usual Care All 3 groups continued to receive usual diabetes care . The participating hospitals agreed to a protocol of minimum st and ards of diabetes care for persons with suboptimal glycemic control on the basis of national guidelines aim ing toward hemoglobin A1c levels of 7 % or less with no problematic hypoglycemia ( 30 ) . The frequency of clinic attendance was expected to vary depending on patient and clinic factors , but all patients were offered a minimum of 2 to 4 clinic appointments per year . At the time of the study , 2 hospital centers offered basalbolus intensive insulin therapy in combination with structured education programs and continuous , subcutaneous insulin infusion pumps ( King 's College Hospital and Guy 's and St Thomas ' Hospitals ) ( 3 ) . Treatment protocol s did not substantially change during the study . Usual Care with Motivational Enhancement Therapy We developed a OBJECTIVE In a r and omized , multi-centre trial , the efficacy of a self-management-oriented education programme ( PRIMAS ) for people with type 1 diabetes was compared with an established education programme as control group ( CG ) . Primary outcome was the effect on glycaemic control in a 6-month follow-up . Secondary outcomes were the impact on emotional aspects , self-management related aspects and hypoglycaemia problems . METHODS The study was conducted in an outpatient setting . 160 participants were r and omized . Baseline characteristics in PRIMAS and CG were similar ( age 45.1±13.5 vs. 45.9±13.1 years , p=.716 ; diabetes duration 18.8±12.3 vs. 19.8±13.4 years , p=.615 ; BMI 26.5±4.6 vs. 27.5±5.0kg/m(2 ) , p=.236 ; HbA1c 8.3±1.1 vs. 8.1±1.0 % , p=.236 ) . RESULTS At follow-up there was a significant 0.4 percentage points greater reduction of HbA1c in PRIMAS compared to CG ( Δ -0.4±1.0 % vs. Δ 0.0±0.6 % ; p=.012 ) . Also , diabetes-related distress ( Δ -0.3±0.7 vs. -0.1±0.4 , p=.032 ) and dissatisfaction with diabetes treatment ( Δ -3.3±6.9 vs. -1.9±5.6 , p=.024 ) decreased more in PRIMAS . Diabetes empowerment ( Δ 2.6±5.9 vs. 0.8±5.1 , p=.037 ) and diabetes self-efficacy ( Δ 1.4±3.6 vs. 0.2±4.0 , p=.013 ) increased in PRIMAS . Incidence of severe hypoglycemia , hypoglycemia awareness , diabetes knowledge , and self-care behaviour improved in both groups with no significant differences between groups . CONCLUSION PRIMAS is more effective in lowering HbA1c than a previously established education programmes and also showed superiority in reducing diabetes-related distress and increasing diabetes empowerment , diabetes self-efficacy and satisfaction with insulin therapy The purpose of this pilot study was to test the hypothesis that children can learn to become more independent in their own diabetes self management without compromising their metabolic control . Twenty four children ( ages 8 to 12 years ) with insulin- dependent diabetes mellitus ( IDDM ) were matched by age and race , then r and omly assigned either to a 6-week , self management education program ( experimental ) or to receive usual care ( control ) . A question naire was administered to the parents to determine the frequency with which 35 diabetes management behaviors were performed and the degree to which children assumed responsibility for these behaviors . Glycohemoglobin levels were monitored at baseline and at posttreatment , 12 weeks after baseline . At the posttreatment , children in the experimental group were found to be assuming significantly more responsibility for their diabetes self-care than were children in the control group . No decrease in the frequency with which self-care behaviors were performed was observed , and metabolic control was maintained . The results suggest that a diabetes self-management education program for children ages 8 to 12 years can be effective in facilitating children becoming more responsible for their own diabetes management AIM To determine the potential effect sizes for the Flexible Lifestyle for Youth ( FL3X ) behavioural intervention to improve glycaemic control ( HbA(1c ) ) and quality of life for at-risk adolescents with Type 1 diabetes . METHODS Participants [ n = 61 ; age 12 - 16 years , HbA(1c ) 64 - 119 mmol/mol ( 8 - 13 % ) ] were r and omized to FL3X ( minimum three sessions ) or usual care . Effect sizes ( Cohen 's d ) , comparing the mean difference between the groups , were calculated . RESULTS Study retention ( 95 % ) , attendance at intervention sessions ( 87 % attended all three sessions ) and acceptability were high ( 100 % of the adolescents and 91 % of parents would recommend the programme to others ) . Overall , 41 % of participants in the intervention group and 24 % of participants in the control group were ' responders ' [ HbA(1c ) decreased by > 6 mmol/mol ( 0.5 % ) ; d = 0.37 ] . HbA(1c ) levels decreased ( d = -0.18 ) , diabetes-specific quality of life increased ( d = 0.29 ) , but generic quality of life decreased ( d = -0.23 ) in the intervention compared with the control group . CONCLUSIONS The FL3X programme merits further study for improving HbA(1c ) and diabetes-specific quality of life in adolescents with Type 1 diabetes . ( Clinical trials registry no. : NCT01286350 ) We evaluated a cognitive behaviour therapy – based programme to improve glycaemic control and psychosocial wellbeing in adolescents with type 1 diabetes . A total of 147 adolescents aged 13–16 years were r and omized to the intervention ( n = 73 ) or st and ard care ( n = 74 ) . The primary outcome was glycaemic control at 3 and 12 months post r and omization , and secondary measures were stress , self-efficacy and quality of life . Mixed-effects regression models were used to assess differences in means between groups at each time point . There was little evidence of differences in glycaemic control between groups . However , psychosocial wellbeing improved in the intervention group compared to the control group . Recommendations for future programmes are discussed . The trial is registered with the Australian New Zeal and Clinical Trials Registry ( ACTRN12608000368336 ) AIMS We piloted a motivational and solution-focused therapy group intervention to improve glycaemic control in young people 11 - 17 years with poorly controlled Type 1 diabetes ( mean annual HbA1c > 8.5 % ) . METHODS Seventy-seven subjects agreed to be assessed for a pilot non-r and omized controlled trial . Subjects completed psychological question naires and were given feedback design ed to encourage entry into the intervention . Twenty-one young people opted to enter the intervention groups ( cases ) . Two intervention groups consisting of five to six subjects were conducted in each age b and 10 - 13 years and 14 - 17 years . Twenty of those who did not opt to join the groups were r and omly selected to act as controls . Cases and controls were well matched for age , HbA1c , duration of diabetes and socio-economic status . RESULTS The intervention produced a significant improvement of 1.5 % in HbA1c in cases ( P<0.05 ) at 4 - 6 months post intervention compared with no change in controls . This improvement was partly maintained at 7 - 12 months post intervention . CONCLUSIONS These pilot data suggest that a motivational/solution-focused group intervention is promising in improving HbA1c in adolescents and should be investigated further in a r and omized controlled trial BACKGROUND Although maintaining nearly normal glycemia delays onset and slows progression of diabetes complications , many patients with diabetes and their physicians struggle to achieve glycemic targets . The best methods to support patients as they follow diabetes prescriptions and recommendations are unclear . METHODS To test the efficacy of a behavioral diabetes intervention in improving glycemia in long- duration , poorly controlled diabetes , we r and omized 222 adults with diabetes ( 49 % type 1 ) ( mean [ SD ] age , 53 [ 12 ] years ; mean [ SD ] disease duration 18 [ 12 ] years ; mean [ SD ] hemoglobin A(1c ) [ HbA(1c ) ] concentration , 9.0 % [ 1.1 % ] ) to attend ( 1 ) a 5-session manual-based , educator-led structured group intervention with cognitive behavioral strategies ( structured behavioral arm ) ; ( 2 ) an educator-led attention control group education program ( group attention control ) ; or ( 3 ) unlimited individual nurse and dietitian education sessions for 6 months ( individual control ) . Outcomes were baseline and 3- , 6- , and 12-month postintervention HbA(1c ) levels ( primary ) and frequency of diabetes self-care , 3-day pedometer readings , 24-hour diet recalls , average number of glucose checks , physical fitness , depression , coping style , self-efficacy , and quality of life ( secondary ) . RESULTS Linear mixed modeling found that all groups showed improved HbA(1c ) levels ( P < .001 ) . However , the structured behavioral arm showed greater improvements than the group and individual control arms ( 3-month HbA(1c ) concentration changes : -0.8 % vs -0.4 % and -0.4 % , respectively ( P = .04 for group × time interaction ) . Furthermore , participants with type 2 disease showed greater improvement than those with type 1 ( P = .04 for type of diabetes × time interaction ) . Quality of life , glucose monitoring , and frequency of diabetes self-care did not differ by intervention over time . CONCLUSIONS A structured , cognitive behavioral program is more effective than 2 control interventions in improving glycemia in adults with long- duration diabetes . Educators can successfully use modified psychological and behavioral strategies . TRIAL REGISTRATION clinical trials.gov Identifier : NCT000142922 |
11,854 | 31,585,960 | This study constitutes a detailed mapping and assessment of the prognostic models for outcome prediction in COPD patients . | OBJECTIVE To map and assess prognostic models for outcome prediction in patients with chronic obstructive pulmonary disease ( COPD ) . | Background Limited information is available about predictors of short-term outcomes in patients with exacerbation of chronic obstructive pulmonary disease ( e COPD ) attending an emergency department ( ED ) . Such information could help stratify these patients and guide medical decision-making . The aim of this study was to develop a clinical prediction rule for short-term mortality during hospital admission or within a week after the index ED visit . Methods This was a prospect i ve cohort study of patients with e COPD attending the EDs of 16 participating hospitals . Recruitment started in June 2008 and ended in September 2010 . Information on possible predictor variables was recorded during the time the patient was evaluated in the ED , at the time a decision was made to admit the patient to the hospital or discharge home , and during follow-up . Main short-term outcomes were death during hospital admission or within 1 week of discharge to home from the ED , as well as at death within 1 month of the index ED visit . Multivariate logistic regression models were developed in a derivation sample and vali date d in a validation sample . The score was compared with other published prediction rules for patients with stable COPD . Results In total , 2,487 patients were included in the study . Predictors of death during hospital admission , or within 1 week of discharge to home from the ED were patient age , baseline dyspnea , previous need for long-term home oxygen therapy or non-invasive mechanical ventilation , altered mental status , and use of inspiratory accessory muscles or paradoxical breathing upon ED arrival ( area under the curve ( AUC ) = 0.85 ) . Addition of arterial blood gas parameters ( oxygen and carbon dioxide partial pressures ( PO2 and PCO2 ) ) and pH ) did not improve the model . The same variables were predictors of death at 1 month ( AUC = 0.85 ) . Compared with other commonly used tools for predicting the severity of COPD in stable patients , our rule was significantly better . Conclusions Five clinical predictors easily available in the ED , and also in the primary care setting , can be used to create a simple and easily obtained score that allows clinicians to stratify patients with e COPD upon ED arrival and guide the medical decision-making process BACKGROUND AND OBJECTIVE Hospitalization for exacerbation of COPD is associated with a high risk of mortality . A risk-prediction model using information easily obtained on admission could help to identify high-risk individuals . The CURB65 score was developed to predict mortality risk in community acquired pneumonia . A retrospective study found that this score was also associated with mortality in COPD exacerbations . We conducted a prospect i ve study to assess the utility of the CURB65 score in acute COPD exacerbations . METHODS Consecutive patients with physician diagnosed COPD exacerbations admitted to a public hospital during a 1-year period were studied prospect ively . The CURB65 scores were calculated from information obtained at initial hospital presentation . CURB65 = one point each for Confusion , Urea > 7 mmol/L , Respiratory rate ≥ 30/min , low Blood pressure , age ≥ 65 years . RESULTS 30-day mortality data were available for 249 of 252 patients . CURB65 scores on admission significantly predicted risk of death during the hospital admission and at 30 days . The 30-day mortality by score groups were : low risk ( scores 0 - 1 ) 2.0 % ( 2/98 ) , moderate risk ( score 2 ) 6.7 % ( 6/90 ) and high risk ( scores 3 - 5 ) 21.3 % ( 13/61 ) . CURB65 scores were not predictive of 1-year mortality . CONCLUSIONS A simple 6-point score based on confusion , blood urea , respiratory rate , blood pressure and age can be used to stratify patients with COPD exacerbation into different management groups . The CURB65 score was as effective in predicting early mortality in our cohort of acute COPD exacerbations as it was in previous cohorts with community acquired pneumonia . Our findings suggest that CURB65 scores can help clinicians to assess patients with exacerbation of COPD The aim of the present prospect i ve multicentric study was to develop a simple rule for the prediction of poor outcome in patients presenting to emergency departments with initially non-life threatening-chronic obstructive pulmonary disease ( COPD ) exacerbations in a real-life setting . All patients with an acute exacerbation of COPD visiting the emergency departments of 103 hospitals during a 3-month period were included , except those who immediately required intensive care unit admission and /or ventilatory support . The data collected included patient characteristics , in-hospital outcomes ( mortality and length of stay ) and mode of discharge ( unsupported or need for post-hospital assistance ) . The in-hospital mortality rate was 7.4 % ( 59 out of 794 ) . Independent prognostic factors were age , number of clinical signs of severity ( among cyanosis , impaired neurological status , lower limb oedema , asterixis and use of accessory inspiratory or expiratory muscles ) and dyspnoea grade in the stable state . The need for post-hospital support was also predicted by female sex . In order to construct and vali date a prediction score for mortality based on these items , patients were r and omly allocated to a derivation and a validation cohort . The prediction score showed good discrimination , with a c-statistic of 0.79 in the derivation cohort and 0.83 in the validation cohort . Thus simple purely clinical factors can reliably predict the risk of death and requirement for post-hospital support in an initially non-life threatening-acute exacerbation of chronic obstructive pulmonary disease . Their use needs to be prospect ively vali date SETTING Reported predictors of the adverse evolution of patients with chronic obstructive pulmonary disease exacerbations ( e COPD ) are various and inconsistent in the bibliography . OBJECTIVE To develop clinical prediction rules for short-term outcomes in e COPD patients attending an emergency department ( ED ) . DESIGN Prospect i ve cohort study of patients with an e COPD . Short-term outcomes were admission to an intensive care unit ( ICU ) , admission to an intermediate respiratory care unit ( IRCU ) and death in these groups . Multivariate logistic regression models were developed for each of the outcomes . RESULTS Predictors of ICU or IRCU admission were use of long-term home oxygen therapy ( LT-HOT ) or non-invasive mechanical ventilation ( NIMV ) , elevated PCO2 and decreased pH upon ED arrival ( area under the curve [ AUC ] 0.87 in the derivation sample ; 0.89 in the validation sample ) . Among those admitted to an ICU or IRCU , predictors of death were increased age , use at home of LT-HOT or NIMV , use of inspiratory accessory muscles upon ED arrival and altered Glasgow Coma Scale ( < 15 points ) ( AUC 0.78 ) . CONCLUSIONS Three clinical predictors available in the ED can be used to create a simple score to predict the need for intensive treatment among e COPD patients . Such a score can be a tool for clinical practice Background The use of a severity score to help orientation decisions could improve the efficiency of care for acute exacerbations of COPD ( AE COPD ) . We previously developed a score ( ‘ 2008 score ’ , based on age , dyspnea grade at steady state and number of clinical signs of severity ) predicting in-hospital mortality in patients with AE COPD visiting emergency departments ( EDs ) . External validity of this score remained to be assessed . Objectives To test the predictive properties of the ‘ 2008 score ’ in a population of patients hospitalized in medical respiratory wards for AE COPD , and determine whether a new score specifically derived from this population would differ from the previous score in terms of components or predictive performance . Methods Data from a cohort study in 1824 patients hospitalized in a medical ward for an AE COPD were analyzed . Patients were categorized using the 2008 score and its predictive characteristics for in-hospital mortality rates were assessed . A new score was developed using multivariate logistic regression modeling in a r and omly selected derivation population sample followed by testing in the remaining population ( validation sample ) . Robustness of results was assessed by case-by-case validation . Results The 2008 score was characterized by a c-statistic at 0.77 , a sensitivity of 69 % and a specificity of 76 % for prediction of in-hospital mortality . The new score comprised the same variables plus major cardiac comorbidities and was characterized by a c-statistic of 0.78 , a sensitivity of 77 % and specificity of 66 % . Conclusions A score using simple clinical variables has robust properties for predicting the risk of in-hospital death in patients hospitalized for AE COPD . Adding cardiac comorbidities to the original score increased its sensitivity while decreasing its specificity Background In patients with acute hypercapnic respiratory failure ( AHRF ) during exacerbations of COPD , mortality can be high despite noninvasive ventilation ( NIV ) . For some , AHRF is terminal and NIV is inappropriate . However there is no definitive method of identifying patients who are unlikely to survive . The aim of this study was to identify factors associated with inpatient mortality from AHRF with respiratory acidosis due to COPD . Methods COPD patients presenting with AHRF and who were treated with NIV were studied prospect ively . The forced expiratory volume in 1 second ( FEV1 ) , World Health Organization performance status ( WHO-PS ) , clinical observations , a composite physiological score ( Early Warning Score ) , routine hematology and biochemistry , and arterial blood gases prior to commencing NIV , were recorded . Results In total , 65 patients were included for study , 29 males and 36 females , with a mean age of 71 ± 10.5 years . Inpatient mortality in the group was 33.8 % . Mortality at 30 days and 12 months after admission were 38.5 % and 58.5 % , respectively . On univariate analysis , the variables associated with inpatient death were : WHO-PS ≥ 3 , long-term oxygen therapy , anemia , diastolic blood pressure < 70 mmHg , Early Warning Score ≥ 3 , severe acidosis ( pH < 7.20 ) , and serum albumin < 35 g/L. On multivariate analysis , only anemia and WHO-PS ≥ 3 were significant . The presence of both predicted 68 % of inpatient deaths , with a specificity of 98 % . Conclusion WHO-PS ≥ 3 and anemia are prognostic factors in AHRF with respiratory acidosis due to COPD . A combination of the two provides a simple method of identifying patients unlikely to benefit from NIV The aim of this study was to develop and vali date a new method : a classification and regression tree ( CART ) based on easily accessible measures to predict mortality in patients with stable chronic obstructive pulmonary disease ( COPD ) . This was a prospect i ve study of two independent prospect i ve cohorts : a derivation cohort with 611 recruited patients and a validation cohort with 348 patients , all followed for 5 yrs . CART analysis was used to predict 5-yr mortality risk using the following covariates from the derivation cohort : age , % predicted forced expiratory volume in 1 s ( FEV1 ) , dyspnoea , physical activity , general health and number of hospital admissions for COPD exacerbations in the previous 2 yrs . Age ( ≥75 or < 75 yrs ) provided the first branch of the COPD -CART . The highest mortality risk ( 0.74 ) was seen in patients > 75 yrs of age with higher levels of dyspnoea and FEV1 < 50 % pred . Patients with the lowest risk of 5-yr mortality ( 0.04 ) were < 55 yrs of age with FEV1 > 35 % pred and one or no recent hospitalisations for COPD exacerbations . A simple decision tree that uses variables commonly gathered by physicians can provide a quick assessment of the severity of the disease , as measured by the risk of 5-yr mortality BACKGROUND Mortality rate , the possible factors affecting mortality and intubation in patients with acute exacerbation of chronic obstructive pulmonary diseases ( COPD ) and hypercapnic respiratory failure ( RF ) are yet unclear . OBJECTIVE To identify the possible factors affecting mortality and intubation in COPD patients . DESIGN A prospect i ve study using data obtained over the first 24h of respiratory intensive care unit ( RICU ) admission . Consecutive admissions of 656 patients were monitored and 151 of them who had acute exacerbation of COPD and hypercapnic RF were enrolled . SETTING University hospital , Department of Chest Diseases , RICU . RESULTS Mean age was 65.1 years . The mean APACHE II score was 23.7 . Eighty-seven patients ( 57.6 % ) received mechanical ventilation ( MV ) via an endotracheal tube for more than 24 h. Twenty-two patients received non-invasive ventilation ( NIV ) . Fifty patients died ( 33.1 % ) in hospital during the study period . The mortality rate was 52.9 % in patients in need of MV . In the multivariate analysis , the need for intubation , inadequate metabolic compensation for respiratory acidosis , and low ( = bad ) Glasgow Coma Score ( GCS ) were determined as independent factors associated with mortality . The low GCS ( OR : 0.61 ; CI : 0.48 - 0.78 ) and high APACHE II score ( OR : 1.24 ; CI : 1.11 - 1.38 ) were determined as factors associated with intubation . CONCLUSION The most important predictors related to hospital mortality were the need for invasive ventilation and complications to MV . Adequate metabolic compensation for respiratory acidosis at admittance is associated with better survival . A high APACHE II score and loss of consciousness ( low GCS ) were independent predictors of a need to intubate patients Background Forced expiratory volume in one second ( FEV1 ) is used to diagnose and establish a prognosis in chronic obstructive pulmonary disease ( COPD ) . Using multi-dimensional scores improves this predictive capacity . Two instruments , the BODE-index ( Body mass index , Obstruction , Dyspnea , Exercise capacity ) and the HADO-score ( Health , Activity , Dyspnea , Obstruction ) , were compared in the prediction of mortality among COPD patients . Methods This is a prospect i ve longitudinal study . During one year ( 2003 to 2004 ) , 543 consecutively COPD patients were recruited in five outpatient clinics and followed for three years . The endpoints were all-causes and respiratory mortality . Results In the multivariate analysis of patients with FEV1 < 50 % , no significant differences were observed in all-cause or respiratory mortality across HADO categories , while significant differences were observed between patients with a lower BODE ( less severe disease ) and those with a higher BODE ( greater severity ) . Among patients with FEV1 ≥ 50 % , statistically significant differences were observed across HADO categories for all-cause and respiratory mortality , while differences were observed across BODE categories only in all-cause mortality . Conclusions HADO-score and BODE-index were good predictors of all-cause and respiratory mortality in the entire cohort . In patients with severe COPD ( FEV1 < 50 % ) the BODE index was a better predictor of mortality whereas in patients with mild or moderate COPD ( FEV1 ≥ 50 % ) , the HADO-score was as good a predictor of respiratory mortality as the BODE-index . These differences suggest that the HADO-score and BODE-index could be used for different patient population s and at different healthcare levels , but can be used complementarily Background : The assessment of the severity of chronic obstructive pulmonary disease ( COPD ) should involve a multidimensional approach that is now clearly shown to be better than using spirometric impairment alone . The aim of this study is to vali date and compare novel tools without an exercise test and to extend prognostic value to patients with less severe impairment of Forced expiratory volume 1 s. Methods : A prospect i ve , observational , primary care cohort study identified 458 eligible patients recruited from the primary care clinics in the northeast of Engl and in 1999–2002 . A new prognostic indicator - body mass index , airflow obstruction and dyspnea ( BOD ) together with the conventional prognostic indices age , dyspnea and airflow obstruction ( ADO ) , global initiative for chronic obstructive lung disease ( GOLD ) and new GOLD matrix were studied . We also sought to improve prognostication of BOD by adding age ( A ) and smoking history as pack years ( S ) to vali date BODS ( BOD with smoking history ) and BODAS ( BOD with smoking history and age ) as prognostic tools and the predictive power of each was analyzed . Results : The survival of the 458 patients was assessed after a median of 10 years when the mortality was found to be 33.6 % . The novel indices BOD , BODS , and BODAS were significantly predictive for all-cause mortality in our cohort . Furthermore with ROC analysis the C statistics for BOD , BODS , and BODAS were 0.62 , 0.66 , and 0.72 , respectively ( P < 0.001 for each ) , whereas ADO and GOLD stages had a C statistic of 0.70 ( P < 0.001 ) and 0.56 ( P < 0.02 ) , respectively . GOLD Matrix was not significant in this cohort . Conclusion : BOD , BODS , and BODAS scores are vali date d predictors of all-cause mortality in a primary care cohort with COPD BACKGROUND The concept of clinical control in COPD has been developed to help in treatment decisions , but it requires validation in prospect i ve studies . METHOD This international , multicenter , prospect i ve study aim ed to vali date the concept of control in COPD [ control = stability ( no exacerbations or impairment in CAT scores ) + low impact ( low level of symptoms ) ] . Data from the screening visit was used to : investigate the level of control , compare characteristics of patients according to the control status , and perform a sensitivity analysis of the levels of control using either clinical criteria or question naires ( COPD Assessment Test -CAT- or Clinical COPD Question naire -CCQ- ) . RESULTS A total of 314 patients were analysed , mean age was 68.5 years and mean FEV1 was 52.6 % of predicted . According to the prespecified criteria 21 % of patients were classified as controlled , all of them with mild/moderate COPD ( Body mass index , Obstruction , Dyspnea and Exacerbations , -BODEx-index < 5 ) . A high level of dyspnea , a high CAT score or an exacerbation in the previous 3 months were found , using univariate analysis , to be the main reasons for patients not being classified as controlled . Multivariate analysis showed that female sex , chronic bronchitis and having exacerbations in the previous year were associated with uncontrolled COPD . Changing the severity cut off of BODEx from 5 to 3 did not change significantly the percentage of patients fulfilling the criteria of control . CONCLUSIONS The proposed criteria of control were only fulfilled by 21 % of patients . The suggested cut offs and their predictive value for poor outcomes need to be refined in prospect i ve studies Purpose Acute COPD exacerbations account for much of the rising disability and costs associated with COPD , but data on predictive risk factors are limited . The goal of the current study was to develop a robust , clinical ly based model to predict frequent exacerbation risk . Patients and methods Patients identified from the Optimum Patient Care Research Data base ( OPCRD ) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio < 0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before ( predictor year ) and year after ( outcome year ) study index date . The data set contained potential risk factors including demographic , clinical , and comorbid variables . Following univariable analysis , predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression . Sensitivity analyses were conducted for sub population s of patients without any asthma diagnosis ever and those with question naire data on symptoms and smoking pack-years . The full predictive model was vali date d against 1 year of prospect i ve OPCRD data . Results The full data set contained 16,565 patients ( 53 % male , median age 70 years ) , including 9,393 patients without any recorded asthma and 3,713 patients with question naire data . The full model retained eleven variables that significantly predicted two or more exacerbations , of which the number of exacerbations in the preceding year had the strongest association ; others included height , age , forced expiratory volume in 1 second , and several comorbid conditions . Significant predictors not previously identified included eosinophilia and COPD Assessment Test score . The predictive ability of the full model ( C statistic 0.751 ) changed little when applied to the validation data set ( n=2,713 ; C statistic 0.735 ) . Results of the sensitivity analyses supported the main findings . Conclusion Patients at risk of exacerbation can be identified from routinely available , computerized primary care data . Further study is needed to vali date the model in other patient population Background Prediction of future exacerbations of chronic obstructive pulmonary disease ( COPD ) is a major concern for long-term management of this disease . Aim To determine which of three multidimensional assessment systems ( the body mass index , obstruction , dyspnea , and exercise capacity [ BODE ] index ; dyspnea , obstruction , smoking , exacerbations [ DOSE ] index ; or age , dyspnea , obstruction [ ADO ] index ) is superior for predicting exacerbations . Methods This was a 2-year prospect i ve cohort study of COPD patients . Pulmonary function tests , the 6-minute walk distance ( 6MWD ) , Modified Medical Respiratory Council ( MMRC ) dyspnea scores , chest computed-tomography measurements , and body composition were analyzed , and predictions of exacerbation by the three assessment systems were compared . Results Among 183 patients who completed the study , the mean annual exacerbation rate was 0.57 events per patient year , which correlated significantly with lower predicted forced expiratory volume in 1 second ( FEV1 ) ( P < 0.001 ) , lower transfer coefficient of the lung for carbon monoxide ( % DLco/VA ) ( P = 0.021 ) , lesser 6MWD ( P = 0.016 ) , higher MMRC dyspnea score ( P = 0.001 ) , higher DOSE index ( P < 0.001 ) , higher BODE index ( P = 0.001 ) , higher ADO index ( P = 0.001 ) , and greater extent of emphysema ( P = 0.002 ) . For prediction of exacerbation , the areas under the curves were larger for the DOSE index than for the BODE and ADO indices ( P < 0.001 ) . Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation . Conclusion In this study , the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices Background : It is crucial to identify risk factors for poor evolution of patients admitted to hospital with chronic obstructive pulmonary disease ( COPD ) in order to provide adequate intensive therapy and closer follow-up . Objectives : To identify predictors of adverse outcomes in patients hospitalised for exacerbation of COPD . Methods : A prospect i ve , observational study was conducted in patients admitted for exacerbation of COPD . Demographic and clinical parameters were evaluated , including different multidimensional prognostic scores . Adverse outcomes included the following : death during hospitalisation or 1-month follow-up , intensive care unit admission , invasive or non-invasive mechanical ventilation , prolonged hospitalisation ( > 11 days ) and COPD -related emergency visit or readmission within 1 month after discharge . Univariate and multivariate analysis were performed . Results : Of 155 patients included , an adverse outcome occurred in 69 ( 45 % ) . Patients with an adverse outcome had lower forced expiratory volume in 1 s ( p = 0.004 ) and more frequent exacerbations ( p = 0.011 ) , more frequently used oxygen at home ( p = 0.042 ) and presented with lower pH ( p < 0.001 ) , lower ratio of arterial oxygen pressure to the fraction of inspired oxygen ( p = 0.006 ) , higher arterial carbon dioxide pressure ( p < 0.001 ) and a worse score on several prognostic indices at admission . Independent predictors of adverse outcome were exacerbation of COPD in the previous year [ odds ratio 3.9 , 95 % confidence interval ( CI ) 1.6–9.9 ; p = 0.004 ] , hypercapnia ( odds ratio 9.4 , 95 % CI 3.7–23.6 ; p < 0.001 ) and hypoxaemia ( odds ratio 4.3 , 95 % CI 1.5–12.6 ; p = 0.008 ) . In the presence of all three characteristics , the probability of an adverse outcome was 95 % , while hypercapnia was the strongest prognostic factor with a risk of 54 % . Conclusions : Patients with previous exacerbation of COPD , hypercapnia and hypoxaemia had the highest risk of an unfavourable evolution . The calculation of prognostic indices did not provide additional discriminative power Chronic obstructive pulmonary disease ( COPD ) has a rising global incidence and acute exacerbation of COPD ( AE COPD ) carries a high health-care economic burden . Classification and regression tree ( CART ) analysis is able to create decision trees to classify risk groups . We analysed routinely collected laboratory data to identify prognostic factors for inpatient mortality with AE COPD from our large district hospital . Data from 5,985 patients with 9,915 admissions for AE COPD over a 7-year period were examined . R and omly allocated training ( n = 4,986 ) or validation ( n = 4,929 ) data sets were developed and CART analysis was used to model the risk of all-cause death during admission . Inpatient mortality was 15.5 % , mean age was 71.5 ( ±11.5 ) years , 56.2 % were male , and mean length of stay was 9.2 ( ±12.2 ) days . Of 29 variables used , CART analysis identified three ( serum albumin , urea , and arterial pCO2 ) to predict in-hospital mortality in five risk groups , with mortality ranging from 3.0 to 23.4 % . C statistic indices were 0.734 and 0.701 on the training and validation sets , respectively , indicating good model performance . The highest-risk group ( 23.4 % mortality ) had serum urea > 7.35 mmol/l , arterial pCO2 > 6.45 kPa , and normal serum albumin ( > 36.5 g/l ) . It is possible to develop clinical ly useful risk prediction models for mortality using laboratory data from the first 24 h of admission in AE COPD Introduction Chronic Obstructive Pulmonary Disease ( COPD ) is characterized by high morbidity and mortality . Lung computed tomography parameters , individually or as part of a composite index , may provide more prognostic information than pulmonary function tests alone . Aim To investigate the prognostic value of emphysema score and pulmonary artery measurements compared with lung function parameters in COPD and construct a prognostic index using a contingent staging approach . Material - Methods Predictors of mortality were assessed in COPD out patients whose lung computed tomography , spirometry , lung volumes and gas transfer data were collected prospect ively in a clinical data base . Univariate and multivariate Cox proportional hazard analysis models with bootstrap techniques were used . Results 169 patients were included ( 59.8 % male , 61.1 years old ; Forced Expiratory Volume in 1 second % predicted : 40.5±19.2 ) . 20.1 % died ; mean survival was 115.4 months . Age ( HR = 1.098 , 95 % Cl = 1.04–1.252 ) and emphysema score ( HR = 1.034 , 95 % CI = 1.007–1.07 ) were the only independent predictors of mortality . Pulmonary artery dimensions were not associated with survival . An emphysema score of 55 % was chosen as the optimal threshold and 30 % and 65 % as suboptimals . Where emphysema score was between 30 % and 65 % ( intermediate risk ) the optimal lung volume threshold , a functional residual capacity of 210 % predicted , was applied . This contingent staging approach separated patients with an intermediate risk based on emphysema score alone into high risk ( Functional Residual Capacity ≥210 % predicted ) or low risk ( Functional Residual Capacity < 210 % predicted ) . This approach was more discriminatory for survival ( HR = 3.123 ; 95 % CI = 1.094–10.412 ) than either individual component alone . Conclusion Although to an extent limited by the small sample size , this preliminary study indicates that the composite Emphysema score-Functional Residual Capacity index might provide a better separation of high and low risk patients with COPD , than other individual predictors alone BACKGROUND AND OBJECTIVE Chronic obstructive pulmonary disease ( COPD ) is a pulmonary disease with systemic involvement . Several multidimensional indices have been developed to predict long-term outcomes . However , these indices have not been compared and vali date d in Taiwanese patients with COPD . METHODS A prospect i ve , observational , hospital-based study was design ed , and a total of 621 patients were recruited from May 2006 to December 2011 . Patients followed at least 1 year were enrolled and 594 patients eligible for inclusion . Three prognostic indices -- the ADO ( age , dyspnoea and airflow obstruction ) , BODEx ( body mass index , airflow obstruction , dyspnoea and exacerbations ) , and CPI ( the COPD Prognostic Index)--were vali date d and the predictive power of each was analysed . RESULTS The median follow-up of the 594 patients was 33 months ( range 1 - 72 months ) , and the mortality rate was 19.2 % ( 114 deaths ) . All indices were significantly predictive for all-cause mortality in our validation cohort . Furthermore , the C statistics of the three indices , indicating their predictive accuracy , were all > 0.7 ( area under the curve of the CPI 0.718 , P < 0.001 , ADO 0.702 , P < 0.001 , BODEx 0.702 , P < 0.001 ) . CONCLUSIONS ADO , BODEx and CPI scores are useful predictors of all-cause mortality with significantly discriminative properties in Taiwanese patients with COPD Ninety six middle aged male patients with chronic bronchitis with relatively well preserved ventilatory function who were resident in Queensl and , New South Wales , or Victoria took part in a prospect i ve study to determine the relationship of various factors to the rate of decline of the FEV1 . Thirty of the subjects withdrew , leaving 66 to be followed for four to six years . The mean rate of decline of the FEV1 was 58.6 ( SD 51.4 ) ml/year . The subjects ' ventilatory responses to bronchodilator and to methacholine ( measures of bronchial lability ) were significantly related to each other and to sputum eosinophilia . With a linear model for the data on 57 patients who had methacholine and skin tests the rate of decline of the FEV1 was found , after adjustment had been made for other variables , to be significantly related to State of residence , current smoking , response to bronchodilator , age , and occupational exposure to dust . Response to bronchodilator was interchangeable with response to methacholine . With the five variables in the model none of the following factors was related to the rate of decline of the FEV1:FEV1 on entry , FEV1 % predicted normal , FEV1/VC% , skin test reaction , occupation on entry , history of sinusitis and rhinitis , and height . When data from all 66 subjects were introduced into the model , in addition to the five significant individual variables ( FEV1/VC% X response to bronchodilator ) was significantly related to the rate of decline of the FEV1 . Of these prognostic indices , response to bronchodilator was independent of the initial FEV1 , FEV/VC% , and FEV1 % predicted . The difference between States , which was not explained by differences due to sampling or withdrawal of subjects , was due to a low rate of decline in Queensl and Background Chronic obstructive pulmonary disease ( COPD ) is associated with increased mortality and poor health-related quality of life ( HRQoL ) compared with the general population . The objective of this study was to identify clinical characteristics which predict mortality and very poor HRQoL among the COPD population and to develop a Bayesian prediction model . Methods The data consisted of 738 patients with COPD who had visited the Pulmonary Clinic of the Helsinki and Turku University Hospitals during 1995–2006 . The data set contained 49 potential predictor variables and two outcome variables : survival ( dead/alive ) and HRQoL measured with a 15D instrument ( very poor HRQoL < 0.70 vs. typical HRQoL ≥ 0.70).In the first phase of model validation we r and omly divided the material into a training set ( n = 538 ) , and a test set ( n = 200 ) . This procedure was repeated ten times in r and om fashion to obtain independently created training sets and corresponding test sets . Modeling was performed by using the training set , and each model was tested by using the corresponding test set , repeated in each training set . In the second phase the final model was created by using the total material and eighteen most predictive variables . The performance of six logistic regressions approaches were shown for comparison purpose s. Results In the final model , the following variables were associated with mortality or very poor HRQoL : age at onset , cerebrovascular disease , diabetes , alcohol abuse , cancer , psychiatric disease , body mass index , Forced Expiratory Volume ( FEV1 ) % of predicted , atrial fibrillation , and prolonged QT time in ECG . The prediction accuracy of the model was 77 % , sensitivity 0.30 , specificity 0.95 , positive predictive value 0.68 , negative predictive value 0.78 , and area under the ROC curve 0.69 . While the sensitivity of the model reminded limited , good specificity , moderate accuracy , comparable or better performance in classification and better performance in variable selection and data usage in comparison to the logistic regression approaches , and positive and negative predictive values indicate that the model has potential in predicting mortality and very poor HRQoL in COPD patients . Conclusion We developed a Bayesian prediction model which is potentially useful in predicting mortality and very poor HRQoL in patients with COPD OBJECTIVE To identify risk factors for late recovery and failure after ambulatory treatment of exacerbations of chronic bronchitis ( CB ) and chronic obstructive pulmonary disease ( COPD ) . METHODS Observational , non-r and omised study of risk factors carried out in 2001 and 2002 in Primary Care practice s. Patients aged 40 or older diagnosed with an exacerbation of CB or COPD of probable bacterial etiology were included in the study and followed up for 10 days . Patients were treated with amoxicillin plus clavulanic acid ( co-amoxiclav ) 500 - 125 mg tds for 10 days , clarithromycin 500 mg bd for 10 days or moxifloxacin 400 mg od for 5 days . RESULTS Two hundred and fifty-two general practitioners participated , registering 1147 valid patients . The rate of failure at day 10 was 15.1 % without significant differences among the antibiotic treatments . Median time to recovery was 5 days . Factors significantly associated with late recovery ( > 5 days ) on multivariate analysis were : use of long-term oxygen ( OR=1.96 ; 95%CI=1.35 - 2.85 ) ; use of short-acting beta-2 agonists ( OR=1.51 ; 1.17 - 1.92 ) . The use of moxifloxacin had a " protective " effect against late recovery compared to co-amoxiclav ( OR=0.34 ; 0.26 - 0.45 ) and clarithromycin ( OR=0.41 ; 0.31 - 2.85 ) . Factors associated with therapeutic failure were : previous hospitalisation ( OR=1.61 ; 1.08 - 2.42 ) ; and 2 or more exacerbations the previous year ( OR=1.51 ; 1.04 - 2.17 ) ; criteria of CB had a protective effect against failure ( OR=0.53 ; 0.35 - 0.79 ) . CONCLUSIONS There are readily identifiable risk factors for ambulatory treatment failure of exacerbations of CB and COPD . In addition , long-term oxygen therapy and short-acting beta-2 agonists are associated with late recovery , and the use of moxifloxacin compared with co-amoxiclav and clarithromycin is associated with faster recovery of symptoms Frequent COPD exacerbations have a large impact on morbidity , mortality and health-care expenditures . By 2020 , the World Health Organization expects COPD and COPD exacerbations to be the third leading cause of death world-wide . Furthermore , In 2005 it was estimated that COPD exacerbations cost the U.S. health-care system 38 billion dollars . Studies attempting to determine factors related to COPD readmissions are still very limited . Moreover , few have used a organized machine-learning , sensitivity analysis approach , such as a R and om Forest ( RF ) statistical model , to analyze this problem . This study utilized the RF machine learning algorithm to determine factors that predict risk for multiple COPD exacerbations in a single year . This was a retrospective study with a data set of 106 patients . These patients were divided r and omly into training ( 80 % ) and validating ( 20 % ) data -sets , 100 times , using approximately sixty variables intially , which in prior studies had been found to be associated with patient readmission for COPD exacerbation . In an interactive manner , an RF model was created using the training set and vali date d on the testing data set . Mean area-under-curve ( AUC ) statistics , sensitivity , specificity , and negative/positive predictive values ( NPV , PPV ) were calculated for the 100 runs . The following variables were found to be important predictors of patients having at least two COPD exacerbations within one year : employment , body mass index , number of previous surgeries , administration of azithromycin/ceftriaxone/moxifloxacin , and admission albumin level . The mean AUC was 0.72 , sensitivity of 0.75 , specificity of 0.56 , PPV of 0.7 and NPV of 0.63 . Histograms were used to confirm consistent accuracy The RF design has consistently demonstrated encouraging results . We expect to vali date our results on new patient groups and improve accuracy by increasing our training data set . We hope that identifying patients at risk for frequent readmissions will improve patient outcome and save valuable hospital re sources Background : To assist physicians with difficult decisions about hospital admission for patients with acute exacerbation of chronic obstructive pulmonary disease ( COPD ) presenting in the emergency department , we sought to identify clinical characteristics associated with serious adverse events . Methods : We conducted this prospect i ve cohort study in 6 large Canadian academic emergency departments . Patients were assessed for st and ardized clinical variables and then followed for serious adverse events , defined as death , intubation , admission to a monitored unit or new visit to the emergency department requiring admission . Results : We enrolled 945 patients , of whom 354 ( 37.5 % ) were admitted to hospital . Of 74 ( 7.8 % ) patients with a subsequent serious adverse event , 36 ( 49 % ) had not been admitted after the initial emergency visit . Multivariable modelling identified 5 variables that were independently associated with adverse events : prior intubation , initial heart rate ≥ 110/minute , being too ill to do a walk test , hemoglobin < 100 g/L and urea ≥ 12 mmol/L. A preliminary risk scale incorporating these and 5 other clinical variables produced risk categories ranging from 2.2 % for a score of 0 to 91.4 % for a score of 10 . Using a risk score of 2 or higher as a threshold for admission would capture all patients with a predicted risk of adverse events of 7.2 % or higher , while only slightly increasing admission rates , from 37.5 % to 43.2 % . Interpretation : In Canada , many patients with COPD suffer a serious adverse event or death after being discharged home from the emergency department . We identified high-risk characteristics and developed a preliminary risk scale that , once vali date d , could be used to stratify the likelihood of poor outcomes and to enable rational and safe admission decisions Purpose Forecasting hospitalization in patients with COPD has gained significant interest in the field of COPD care . There is a need to find simple tools that can help clinicians to stratify the risk of hospitalization in these patients at the time of care . The perception of quality of life has been reported to be independently associated with hospitalizations , but question naires are impractical for daily clinical use . Individual questions from valid question naires can have robust predictive abilities , as has been suggested in previous reports , as a way to use patient-reported outcomes to forecast important events like hospitalizations in COPD . Our primary aim was to assess the predictive value of individual questions from the Chronic Respiratory Question naire Self- Assessment Survey ( CRQ-SAS ) on the risk of hospitalization and to develop a clinical ly relevant and simple algorithm that clinicians can use in routine practice to identify patients with an increased risk of hospitalization . Patients and methods A total of 493 patients with COPD prospect ively recruited from an outpatient pulmonary clinic completed the CRQ-SAS , demographic information , pulmonary function testing , and clinical outcomes . The cohort had a mean age of 70 years , was 54 % male , with forced expiratory volume in 1 second percentage predicted 42.8±16.7 , and modified Medical Research Council dyspnea scale score of 2±1.13 . Results Our analysis vali date d the original CRQ-SAS domains . Importantly , recursive partitioning analysis identified three CRQ-SAS items regarding fear or panic of breathlessness , dyspnea with basic activities of daily living , and depressive symptoms that were highly predictive of hospitalization . We propose a robust ( area under the curve = 0.70 ) but short and easy algorithm for daily clinical care to forecast hospitalizations in patients with COPD . Conclusion We identified three themes – fear of breathlessness , dyspnea with basic activities of daily living , and depressive symptoms – as important patient-reported outcomes to predict hospitalizations , and propose a short and easy algorithm to forecast hospitalizations in patients with COPD Background Various studies have tried to delimit the predictors of hospital length of stay ( LOS ) for patients with exacerbated chronic obstructive pulmonary disease ( e COPD ) , but have been disadvantaged by certain limiting factors . Objective Our goal was to prospect ively identify predictors of LOS in these patients and to vali date our results . Design This was a prospect i ve cohort study . Participants Subjects were patients with e COPD who visited 16 hospital emergency departments ( EDs ) and who were admitted to the hospital . Main Measures Data were recorded on possible predictor variables at the ED visit , on admission and 24 hours later , during hospitalization , and on discharge . LOS and prolonged LOS ( ≥ 9 days , considering the 75th percentile of LOS in our sample ) were the outcomes of interest . Multivariate multilevel linear and logistic regression models were employed . Results A total of 1,453 patients were equally divided between derivation and validation sample s. The hospital variable was the best predictor of LOS . Multivariate predictors of LOS , as log-transformed variables , were the hospital , baseline dyspnea and physical activity levels and fatigue at 24 hours , intensive care or intensive respiratory care unit admission , the need for antibiotics , and complications during hospitalization . Predictors of prolonged LOS were also the hospital , baseline dyspnea and fatigue at 24 hours , ICU or IRCU admission , and complications during hospitalization ( AUC : 0.77 ) . Models were vali date d in the validation sample ( AUC : 0.75 ) . Conclusions We identified a number of modifiable factors , including baseline dyspnea , physical activity level , and hospital variability , that influenced the LOS of patients with e COPD who were admitted to the hospital Background : Limited information is available regarding the factors related to short-term hospital admission following an exacerbation of chronic obstructive pulmonary disease ( e COPD ) . Objectives : The aim of this study was to identify variables related to short-term admission in patients with an e COPD . Methods : This was a prospect i ve cohort study of patients with an e COPD who attended an emergency department ( ED ) at 1 of 16 hospitals . Information on possible predictor variables was recorded during the ED stay , 24 h after admission to the hospital or after ED discharge home , and at hospital discharge or 1 week later if discharged home from the ED . An admission after an e COPD within 2 months was the outcome of interest . Multivariate models were employed for patients admitted to the hospital or discharged home from the ED . Results : For patients discharged home from the ED , e COPD -related hospital admissions in the previous year [ odds ratio ( OR ) 1.98 and 2.33 ] , pCO2 at ED admission ( ORs 2.02 and 2.90 ) , the number of ED visits within 1 week of the index ED visit ( OR 5.14 ) and dyspnea level 1 week after the index ED visit ( ORs 2.66 and 1.40 ) were predictors of short-term admission [ area under the curve ( AUC ) 0.82 ] . For patients admitted to the hospital during the index ED visit , baseline FEV1 % ( ORs 1.32 and 1.88 ) , e COPD -related hospital admissions in the previous year ( ORs 1.28 and 2.51 ) , severe baseline dyspnea ( OR 2.57 ) and dyspnea level 1 week after the index ED visit ( ORs 2.15 and 1.74 ) were predictors of short-term readmission ( AUC 0.73 ) . Conclusions : Just a few easily recorded parameters may allow clinicians to identify patients at a higher risk of short-term readmission and establish preventive strategies Background : Readmission after hospital discharge is common in patients with acute exacerbations ( AE ) of chronic obstructive pulmonary disease ( COPD ) . Although frailty predicts hospital readmission in patients with chronic nonpulmonary diseases , no multidimensional frailty measures have been vali date d to stratify the risk for patients with COPD . Aim : The aim of this study was to explore multidimensional frailty as a potential risk factor for readmission due to a new exacerbation episode during the 90 days after hospitalization for AE- COPD and to test whether frailty could improve the identification of patients at high risk of readmission . We hypothesized that patients with moderate-to-severe frailty would be at greater risk for readmission within that period of follow up . A secondary aim was to test whether frailty could improve the accuracy with which to discriminate patients with a high risk of readmission . Our investigation was part of a wider study protocol with additional aims on the same study population . Methods : Frailty , demographics , and disease-related factors were measured prospect ively in 102 patients during hospitalization for AE- COPD . Some of the baseline data reported were collected as part of a previously study . Readmission data were obtained on the basis of the discharge summary from patients ’ electronic files by a research er blinded to the measurements made in the previous hospitalization . The association between frailty and readmission was assessed using bivariate analyses and multivariate logistic regression models . Whether frailty better identifies patients at high risk for readmission was evaluated by area under the receiver operator curve ( AUC ) . Results : Severely frail patients were much more likely to be readmitted than nonfrail patients ( 45 % versus 18 % ) . After adjusting for age and relevant disease-related factors in a final multivariate model , severe frailty remained an independent risk factor for 90-day readmission ( odds ratio = 5.19 ; 95 % confidence interval : 1.26–21.50 ) . Age , number of hospitalizations for exacerbations in the previous year and length of stay were also significant in this model . Additionally , frailty improved the predictive accuracy of readmission by improving the AUC . Conclusions : Multidimensional frailty predicts the risk of early hospital readmission in patients hospitalized for AE- COPD . Frailty improved the accuracy of discriminating patients at high risk for readmission . Identifying patients with frailty for targeted interventions may reduce early readmission rates RATIONALE Accurate prediction of mortality helps select patients for interventions aim ed at improving outcome . OBJECTIVES Because chronic obstructive pulmonary disease is characterized by low- grade systemic inflammation , we hypothesized that addition of inflammatory biomarkers to established predictive factors will improve accuracy . METHODS A total of 1,843 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study were followed for 3 years . Kaplan-Meier curves , log-rank analysis , and Cox proportional hazards analyses determined the predictive value for mortality of clinical variables , while C statistics assessed the added discriminative power offered by addition of biomarkers . MEASUREMENTS AND MAIN RESULTS At recruitment we measured anthropometrics , spirometry , 6-minute walk distance , dyspnea , BODE index , history of hospitalization , comorbidities , and computed tomography scan emphysema . White blood cell and neutrophil counts , serum or plasma levels of fibrinogen , chemokine lig and 18 , surfactant protein D , C-reactive protein , Clara cell secretory protein-16 , IL-6 and -8 , and tumor necrosis factor-α were determined at recruitment and subsequent visits . A total of 168 of the 1,843 patients ( 9.1 % ) died . Nonsurvivors were older and had more severe airflow limitation , increased dyspnea , higher BODE score , more emphysema , and higher rates of comorbidities and history of hospitalizations . The best predictive model for mortality using clinical variables included age , BODE , and hospitalization history ( C statistic of 0.686 ; P < 0.001 ) . One single biomarker ( IL-6 ) significantly improved the C statistic to 0.708 , but this was further improved to 0.726 ( P = 0.003 ) by the addition of all biomarkers . CONCLUSIONS The addition of a panel of selected biomarkers improves the ability of established clinical variables to predict mortality in chronic obstructive pulmonary disease . Clinical trial registered with www . clinical trials.gov ( NCT00292552 ) OBJECTIVE The aim of our study was to investigate the mortality predictive factors after a severe exacerbations of COPD admitted to a Spanish respiratory intermediate care unit ( IRCU ) . PATIENTS AND METHODS Prospect i ve observational 2 years study , where we included all episodes of acute exacerbations of COPD with hypercapnic respiratory failure admitted in an IRCU . We analyzed different sociodemographic , functional and clinical variables including physical activity . RESULTS We collected data from 102 consecutive episodes admitted to IRCU ( 90.1 % men ) . Mean age was 69.4±10.6 . The mean APACHE II was 19.6±5.0 and 9.5 % presented a failure of other non respiratory organ . Non invasive ventilation was applied in 75.3 % of the episodes and this treatment failed in 11.6 % of them . The duration of stay in the IRCU was 3.5±2.1 days and 8.0±5.3 days in the hospital . The hospital mortality rate was 6.9 % , and another 12.7 % after 90 days of discharged . In order to predict hospital mortality , multivariant statistics identified a model with AUC of 0.867 , based in 3 variables : the number of previous year admission for COPD exacerbation ( p=0,048 ) , the respiratory rate after 2 hours of treatment in the IRCU ( p=0.0484 ) and the severity of the disease established with ADO score ( p=0.0241 ) . CONCLUSIONS The number of previous year admission for COPD exacerbation , the severity of the disease established with ADO score , the respiratory rate after 2 hours of treatment , allow us to identify what patients with a COPD exacerbation admitted in a IRCU can die during this episode A survey-based COPD severity scoring algorithm could prove useful for targeted disease management and risk-adjustment . For this purpose , we sought to prospect ively vali date a COPD severity score that had previously been cross-sectionally vali date d. Using a population -based sample of 267 adults with self-reported physician-diagnosed COPD , we examined the extent to which this COPD severity score predicts future respiratory hospitalizations , emergency department ( ED ) visits , and outpatient visits . Structured telephone interviews , conducted at baseline and on an annual basis in two subsequent years , determined COPD severity scores and health-care utilization . A basic predictive model for respiratory-specific health-care utilization was developed using sociodemographics , tobacco history , and medical comorbidity data in multivariate logistic regression analysis . The added predictive value of the COPD severity score over and above this basic model was then evaluated by testing the change in model concordance indices . Our analysis demonstrated that the COPD severity score did , in fact , increase the concordance-index of models predicting future respiratory hospitalizations ( increase from 80 % to 87 % ; P = 0.03 ) , ED visits ( 64 % to 82 % , P = 0.003 ) , and outpatient visits ( 59 % to 77 % , P < 0.0001 ) . In a separate analysis , both a greater baseline severity score and worsening of the severity score over time were prospect ively associated with each outcome studied ( P < 0.05 for each ) . In conclusion , the COPD severity score adds predictive value in estimating future respiratory-specific health-care utilization and is longitudinally responsive to evolving changes in COPD status over time . This severity score may be used to adjust for disease severity or to identify high-risk population This study reports the costs associated with rehabilitation among participants in the National Emphysema Treatment Trial ( NETT ) , and evaluates factors associated with adherence to rehabilitation . Pulmonary rehabilitation is recommended for moderate-to-severe COPD and required by the Centers for Medicare and Medicaid Services ( CMS ) prior to lung volume reduction surgery ( LVRS ) . Between January 1998 and July 2002 , 1,218 subjects with emphysema and severe airflow limitation ( FEV1 ≤ 45 % predicted ) were r and omized . Primary outcome measures were design ated as mortality and maximal exercise capacity 2 years after r and omization . Pre-r and omization , estimated mean total cost per patient of rehabilitation was $ 2,218 ( SD $ 314 ; 2006 dollars ) for the medical group and $ 2,187 ( SD $ 304 ) for the surgical group . Post-r and omization , mean cost per patient in the medical and surgical groups was $ 766 and $ 962 respectively . Among patients who attended ≥ 1 post-r and omization rehabilitation session , LVRS patients , patients with an FEV1 ≥ 20 % predicted , and higher education were significantly more likely to complete rehabilitation . Patients with depressive and anxiety symptoms , and those who live > 36 miles compared to < 6 miles away were less likely to be adherent . Patients who underwent LVRS completed more exercise sessions than those in the medical group and were more likely to be adherent with post-r and omization rehabilitation . A better underst and ing of patient factors such as socioeconomic status , depression , anxiety and transportation issues may improve adherence to pulmonary rehabilitation Rationale : Hyperglycaemia predicts a poor outcome in Intensive Care Unit ( ICU ) patients . Whether this is true for respiratory failure necessitating non-invasive ventilation ( NIV ) is not known . Objectives : To determine whether hyperglycaemia within 24 h of admission independently predicts outcome of NIV during acute decompensated ventilatory failure complicating chronic obstructive pulmonary disease ( COPD ) exacerbations . Methods : Patients with COPD presenting with acute hypercapnic respiratory failure at University Hospital Aintree between June 2006 and September 2007 and receiving NIV within 24 h of admission were studied prospect ively . R and om blood glucose levels were measured before NIV administration . Results : 88 patients ( mean baseline pH 7.25 , PaCO2 10.20 kPa , and PaO2 8.19 kPa ) met the inclusion criteria , with NIV normalising arterial pH off therapy in 79 ( 90 % ) . After multivariate logistic regression , the following predicted outcome : baseline respiratory rate ( OR 0.91 ; 95 % CI 0.84 to 0.99 ) , r and om glucose ⩾7 mmol/l ( OR 0.07 ; 95 % CI 0.007 to 0.63 ) and admission APACHE II ( Acute Physiology and Chronic Health Evaluation II ) score ( OR 0.75 ; 95 % CI 0.62 to 0.90 ) . The combination of baseline respiratory rate ( RR ) < 30 breaths/min and r and om glucose < 7 mmol/l increased prediction of NIV success to 97 % , whilst use of all three factors was 100 % predictive . Conclusions : In acute decompensated ventilatory failure complicating COPD , hyperglycaemia upon presentation was associated with a poor outcome . Baseline RR and hyperglycaemia are as good at predicting clinical outcomes as the APACHE II score . Combining these variables increases predictive accuracy , providing a simple method of early risk stratification Background Acute exacerbations represent a significant burden for patients with moderate-to-severe chronic obstructive pulmonary disease . Each exacerbation episode is frequently associated with a lengthy recovery and impaired quality of life . Prognostic factors for out patients that may predict poor outcome after treatment with antibiotics recommended in the guidelines , are not fully understood . We aim ed to identify pretherapy factors predictive of clinical failure in elderly ( ≥60 years old ) out patients with acute Anthonisen type 1 exacerbations . Trial registration NCT00656747 . Methods Based on the moxifloxacin in AE COPD s ( acute exacerbations of chronic obstructive pulmonary disease ) trial ( MAESTRAL ) data base , this study evaluated pretherapy demographic , clinical , sputum bacteriological factors using multivariate logistic regression analysis , with internal validation by bootstrap replicates , to investigate their possible association with clinical failure at end of therapy ( EOT ) and 8 weeks posttherapy . Results The analyses found that the independent factors predicting clinical failure at EOT were more frequent exacerbations , increased respiratory rate and lower body temperature at exacerbation , treatment with long-acting anticholinergic drugs , and in vitro bacterial resistance to study drug . The independent factors predicting poor outcome at 8 weeks posttherapy included wheezing at preexacerbation , mild or moderate ( vs extreme ) sleep disturbances , lower body temperature at exacerbation , forced expiratory volume in 1 second < 30 % , lower body mass index , concomitant systemic corticosteroids for the current exacerbation , maintenance long-acting β2-agonist and long-acting anticholinergic treatments , and positive sputum culture at EOT . Conclusion Several bacteriological , historical , treatment-related factors were identified as predictors of early ( EOT ) and later ( 8 weeks posttherapy ) clinical failure in this older outpatient population with moderate-to-severe chronic obstructive pulmonary disease . These patients should be closely monitored and sputum cultures considered before and after treatment INTRODUCTION Since exacerbations of chronic obstructive pulmonary disease ( COPD ) cause both a great impact on the progression of the disease and generate high health expenditures , there is a need to develop tools to evaluate their prognosis . METHOD Multicenter , observational , prospect i ve study that evaluated the prognostic utility of the COPD Assessment Test ( CAT ) in severe exacerbations of COPD . Anthropometric and clinical variables were analyzed : smoking , history of exacerbations during the previous year , drug treatment , degree of baseline dyspnea , comorbidities ; laboratory variables at admission ( complete blood count , arterial blood gas and biochemistry ) and CAT scores in the first 24 h of admission , on the third day , at discharge and at 3 months . RESULTS We evaluated 106 patients ( 91 males ) with a mean age of 71.1 ( SD 9.8 years ) , mean FEV1 45.2 % ( 14.7 % ) and average CAT score at admission of 24.7 points ( 7.1 ) . At three months after discharge , treatment failure was observed in 39 ( 36.8 % ) patients : 14 ( 13.2 % ) presented an exacerbation without the need for hospital admission , 22 were readmitted ( 20.8 % ) and 3 ( 2.8 % ) died during follow-up . The three factors associated with increased risk of failure were a reduction less than 4 units in the CAT at discharge compared to admission , lower hemoglobin levels and treatment with domiciliary oxygen . CONCLUSIONS A change of ≤4 points in the CAT score at discharge compared to that obtained at admission due to a severe exacerbation of COPD , helps to predict therapeutic failure such as a new exacerbation , readmission or death in the subsequent three months Background Creating an easy-to-use instrument to identify predictors of short-term ( 30/60-day ) mortality after an exacerbation of chronic obstructive pulmonary disease ( e COPD ) could help clinicians choose specific measures of medical care to decrease mortality in these patients . The objective of this study was to develop and vali date a classification and regression tree ( CART ) to predict short term mortality among patients evaluated in an emergency department ( ED ) for an e COPD . Methods We conducted a prospect i ve cohort study including participants from 16 hospitals in Spain . COPD patients with an exacerbation attending the emergency department ( ED ) of any of the hospitals between June 2008 and September 2010 were recruited . Patients were r and omly divided into derivation ( 50 % ) and validation sample s ( 50 % ) . A CART based on a recursive partitioning algorithm was created in the derivation sample and applied to the validation sample . Results Two thous and four hundred eighty-seven patients , 1252 patients in the derivation sample and 1235 in the validation sample , were enrolled in the study . Based on the results of the univariate analysis , five variables ( baseline dyspnea , cardiac disease , the presence of paradoxical breathing or use of accessory inspiratory muscles , age , and Glasgow Coma Scale score ) were used to build the CART . Mortality rates 30 days after discharge ranged from 0 % to 55 % in the five CART classes . The lowest mortality rate was for the branch composed of low baseline dyspnea and lack of cardiac disease . The highest mortality rate was in the branch with the highest baseline dyspnea level , use of accessory inspiratory muscles or paradoxical breathing upon ED arrival , and Glasgow score < 15 . The area under the receiver-operating curve ( AUC ) in the derivation sample was 0.835 ( 95 % CI : 0.783 , 0.888 ) and 0.794 ( 95 % CI : 0.723 , 0.865 ) in the validation sample . CART was improved to predict 60-days mortality risk by adding the Charlson Comorbidity Index , reaching an AUC in the derivation sample of 0.817 ( 95 % CI : 0.776 , 0.859 ) and 0.770 ( 95 % CI : 0.716 , 0.823 ) in the validation sample . Conclusions We identified several easy-to-determine variables that allow clinicians to classify e COPD patients by short term mortality risk , which can provide useful information for establishing appropriate clinical care . Trial registration NCT02434536 BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is usually assessed using FEV(1 ) to establish the diagnosis and the severity of the disease . However , COPD is now considered a systemic disease . AIM To evaluate the utility of the Health-Activity-Dyspnoea-Obstruction ( HADO ) score for classifying the severity of COPD and predicting outcomes . DESIGN Prospect i ve longitudinal clinical study . METHODS We studied 611 consecutive patients with stable COPD in five out-patient clinics of a teaching hospital . We measured dyspnoea degree , pulmonary function ( by spirometry ) , self-reported level of daily physical activity and overall health condition . Outcome measures included health-related quality of life ( HRQoL ) parameters ( as measured by the generic SF-36 Health Survey and by two specific question naires , the St George Respiratory Question naire and the Chronic Respiratory Question naire ) and mortality at 3 years follow-up . RESULTS Based on the HADO score , COPD was classified as mild in 26.7 % of patients , moderate in 53.3 % , and severe in 20 % . There were statistically significant correlations between these three levels of severity and HRQoL parameters and vital status . After adjustment for relevant covariates , the HADO score reliably predicted survival and vital status . DISCUSSION The HADO score can be easily obtained in an out-patient clinic , and distinguishes groups of COPD patients by their disease severity . The HADO score is better than FEV(1 % ) alone for predicting mortality at 3 years BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is characterized by an incompletely reversible limitation in airflow . A physiological variable -- the forced expiratory volume in one second (FEV1)--is often used to grade the severity of COPD . However , patients with COPD have systemic manifestations that are not reflected by the FEV1 . We hypothesized that a multidimensional grading system that assessed the respiratory and systemic expressions of COPD would better categorize and predict outcome in these patients . METHODS We first evaluated 207 patients and found that four factors predicted the risk of death in this cohort : the body-mass index ( B ) , the degree of airflow obstruction ( O ) and dyspnea ( D ) , and exercise capacity ( E ) , measured by the six-minute-walk test . We used these variables to construct the BODE index , a multidimensional 10-point scale in which higher scores indicate a higher risk of death . We then prospect ively vali date d the index in a cohort of 625 patients , with death from any cause and from respiratory causes as the outcome variables . RESULTS There were 25 deaths among the first 207 patients and 162 deaths ( 26 percent ) in the validation cohort . Sixty-one percent of the deaths in the validation cohort were due to respiratory insufficiency , 14 percent to myocardial infa rct ion , 12 percent to lung cancer , and 13 percent to other causes . Patients with higher BODE scores were at higher risk for death ; the hazard ratio for death from any cause per one-point increase in the BODE score was 1.34 ( 95 percent confidence interval , 1.26 to 1.42 ; P<0.001 ) , and the hazard ratio for death from respiratory causes was 1.62 ( 95 percent confidence interval , 1.48 to 1.77 ; P<0.001 ) . The C statistic for the ability of the BODE index to predict the risk of death was larger than that for the FEV1 ( 0.74 vs. 0.65 ) . CONCLUSIONS The BODE index , a simple multidimensional grading system , is better than the FEV1 at predicting the risk of death from any cause and from respiratory causes among patients with COPD INTRODUCTION Decisions about the intensity of treatment for patients with acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) are influenced by predictions about survival and quality of life . Evidence suggests that these predictions are poorly calibrated and tend to be pessimistic . AIM The aim of this study was to develop an outcome prediction model for COPD patients to support treatment decisions . METHODS A prospect i ve multi-centre cohort study in Intensive Care Units ( ICU ) and Respiratory High Dependency Units ( RHDU ) in the UK recruited patients aged 45 years and older admitted with an exacerbation of obstructive lung disease . Data were collected on patients ' characteristics prior to ICU admission , and on their survival and quality of life after 180 days . An outcome prediction model was developed using multivariate logistic regression and bootstrapping . RESULTS Ninety-two ICUs ( 53 % of those in the UK ) and three RHDUs took part . A total of 832 patients were recruited . Cumulative 180-day mortality was 37.9 % . Using data available at the time of admission to the units , a prognostic model was developed which had an estimated area under the receiver operating characteristic curve ( ' c ' ) of 74.7 % after bootstrapping that was more discriminating than the clinicians ( P = 0.033 ) and was well calibrated . DISCUSSION This study has produced an outcome prediction model with slightly better discrimination and much better calibration than the participating clinicians . It has the potential to support risk adjustment and clinical decision making about admission to intensive care The clinical significance of high heart rate in chronic obstructive pulmonary disease ( COPD ) is unexplored . We investigated the association between resting heart rate , pulmonary function , and prognosis in subjects with COPD . 16 696 subjects aged ≥40 years from the Copenhagen City Heart Study , a prospect i ve study of the general population , were followed for 35.3 years , 10 986 deaths occurred . Analyses were performed using time-dependent Cox-models and net reclassification index ( NRI ) . Resting heart rate increased with severity of COPD ( p<0.001 ) . Resting heart rate was associated with both cardiovascular and all-cause mortality across all stages of COPD ( p<0.001 ) . Within each stage of COPD , resting heart rate improved prediction of median life expectancy ; the difference between < 65 bpm and > 85 bpm was 5.5 years without COPD , 9.8 years in mild ( Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) stage I ) , 6.7 years in moderate ( GOLD stage II ) and 5.9 years in severe/very severe COPD ( GOLD stage III/IV ) , ( p<0.001 ) . Resting heart rate significantly improved risk prediction when added to GOLD stage ( categorical NRI 4.9 % , p = 0.01 ; category less NRI 23.0 % , p<0.0001 ) or forced expiratory volume in 1 s % predicted ( categorical NRI 7.8 % , p = 0.002 ; category less NRI 24.1 % , p<0.0001 ) . Resting heart rate increases with severity of COPD . Resting heart rate is a readily available clinical variable that improves risk prediction in patients with COPD above and beyond that of pulmonary function alone . Resting heart rate may be a potential target for intervention in COPD OBJECTIVE To analyze prospect ively the factors related to the success of noninvasive ventilation ( NIV ) in the treatment of acute exacerbations of chronic airflow limitation ( CAFL ) and to generate a multiple regression model in order to detect which patients can be successfully treated by this method . SETTING A respiratory medicine ward of a referral hospital . METHODS AND PRINCIPAL RESULTS Initially , we examined 44 episodes of acute respiratory failure in 36 patients with CAFL in whom mechanical ventilation was advisable . In 34 of 44 episodes ( 77 % ) , NIV was used successfully . Patients in whom NIV succeeded had a lower FEV(1 ) prior to admission , a higher level of consciousness ( LC ) , and significant improvements in PaCO(2 ) , pH , and LC after 1 h of NIV . A logistic regression model consisting of baseline FEV(1 ) and PaCO(2 ) values , initial PaCO(2 ) , pH , and LC values on admission , and PaCO(2 ) values after 1 h of NIV allowed us to correctly classify > 95 % of the 44 episodes in which the outcome was successful . In the second part of the study , we prospect ively vali date d the equation in another 15 consecutive CAFL patients with acute hypercapnic respiratory failure . NIV successfully treated 12 patients ( 80 % ) , and the model correctly classified 14 patients ( 93 % ) . CONCLUSION Good LC at the beginning of NIV and improvements in pH , PaCO(2 ) , and LC values after 1 h of NIV are associated with successful responses to NIV in COPD patients with acute hypercapnic respiratory failure . Our vali date d multiple regression model confirms that these variables predict the result of NIV in acute hypercapnic failure in CAFL patients Background How well the 2011 Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) classification prognosticates for Asian patients with COPD is unknown . Objective The authors aim ed to study the predictive utility of the GOLD 2011 classification for exacerbations and mortality as compared with other multidimensional tools in an Asian population . Methods In all , 1,110 COPD patients were prospect ively followed between March 2008 and March 2013 . They were classified using the 2011 and 2007 GOLD guidelines , modified Medical Research Council score , St. George ’s Respiratory Question naire ( SGRQ ) , and Body mass index , Obstruction , Dyspnea ( BOD ) index . Outcome measures were exacerbations and mortality . Multivariable survival analyses and receiver operating characteristic ( ROC ) curves were used to assess the different classification systems . Results Time-to-event analyses demonstrated earlier exacerbations in 2011 ’s GOLD D when compared with GOLD A ( hazard ratio [ HR ] 0.54 , 95 % confidence interval [ CI ] : 0.31–0.95 , P=0.032 ) and GOLD B ( HR 0.62 , 95 % CI : 0.45–0.85 , P=0.003 ) and higher mortality when compared with GOLD A ( HR 0.37 , 95 % CI : 0.16–0.88 , P=0.025 ) and GOLD B ( HR 0.46 , 95 % CI : 0.31–0.70 , P<0.001 ) . The areas under the ROC curve for GOLD 2011 , GOLD 2007 , modified Medical Research Council , St. George ’s Respiratory Question naire , and BOD index were 0.62 , 0.59 , 0.61 , 0.60 , and 0.61 , respectively , for the prediction of exacerbations and 0.71 , 0.70 , 0.71 , 0.71 , and 0.72 , respectively , for the prediction of mortality ( ROC comparator , P>0.05 ) . Conclusion The 2011 GOLD classification predicts exacerbations and mortality moderately well in Asian COPD patients . Its prognostic utility is similar to that of other multidimensional systems Introduction Chronic obstructive pulmonary disease ( COPD ) exacerbations have a negative impact on the quality of life of patients and the evolution of the disease . We have investigated the prognostic value of several health-related quality of life question naires to predict the appearance of a composite event ( new ambulatory or emergency exacerbation , hospitalization , or death ) over a 1-year follow-up . Methods This was a multicenter , prospect i ve , observational study . Patients completed four question naires after recovering from an exacerbation ( COPD Assessment Test [ CAT ] , a Clinical COPD Question naire [ CCQ ] , COPD Severity Score [ COPD SS ] , and Airways Question naire [ AQ20 ] ) . Patients were followed-up until the appearance of the composite event or for 1 year , whichever came first . Results A total of 497 patients were included in the study . The majority of them were men ( 89.7 % ) , with a mean age of 68.7 ( SD 9.2 ) years , and a forced expiratory volume in 1 second of 47.1 % ( SD 17.5 % ) . A total of 303 ( 61 % ) patients experienced a composite event . Patients with an event had worse mean scores of all question naires at baseline compared to patients without event : CAT=12.5 vs 11.3 ( P=0.028 ) ; CCQ=2.2 vs 1.9 ( P=0.013 ) ; COPD SS=12.3 vs 10.9 ( P=0.001 ) ; AQ20=8.3 vs 7.5 ( P=0.048 ) . In the multivariate analysis , only previous history of exacerbations and CAT score ≥13.5 were significant risk factors for the composite event . A CAT score ≥13.5 increased the predictive value of previous exacerbations with an area under the receiver operating characteristic curve of 0.864 ( 95 % CI : 0.829–0.899 ; P=0.001 ) . Conclusion The predictive value of previous exacerbations significantly increased only in one of the four trialled question naires , namely in the CAT question naire . However , previous history of exacerbations was the strongest predictor of the composite event We evaluated comorbidity , hospitalization , and mortality in chronic obstructive pulmonary disease ( COPD ) , with special attention to risk factors for frequent hospitalizations ( more than three during the follow-up period ) , and prognostic factors for death . Two hundred eighty-eight consecutive COPD patients admitted to respiratory medicine wards in four hospitals for acute exacerbation were enrolled from 1999 to 2000 in a prospect i ve longitudinal study , and followed up until December 2007 . The Charlson index without age was used to quantify comorbidity . Clinical and biochemical parameters and pulmonary function data were evaluated as potential predictive factors of mortality and hospitalization . FEV1 , RV , PaO2 , and PaCO2 were used to develop an index of respiratory functional impairment ( REFI index ) . Hypertension was the most common comorbidity ( 64.2 % ) , followed by chronic renal failure ( 26.3 % ) , diabetes mellitus ( 25.3 % ) , and cardiac diseases ( 22.1 % ) . Main causes of hospitalization were exacerbation of COPD ( 41.2 % ) and cardiovascular disease ( 34.4 % ) . Most of the 56 deaths ( 19.4 % ) were due to cardiovascular disease ( 67.8 % ) . Mortality risk depended on age , current smoking , FEV1 , PaO2 , the REFI index , the presence of cor pulmonale , ischemic heart disease , and lung cancer . Number and length of hospital admissions depended on the degree of dyspnea and REFI index . The correct management of respiratory disease and the implementation of aggressive strategies to prevent or treat comorbidities are necessary for better care of COPD patients In order to describe the outcomes of patients hospitalized with an acute exacerbation of severe chronic obstructive pulmonary disease ( COPD ) and determine the relationship between patient characteristics and length of survival , we studied a prospect i ve cohort of 1,016 adult patients from five hospitals who were admitted with an exacerbation of COPD and a PaCO2 of 50 mm Hg or more . Patient characteristics and acute physiology were determined . Outcomes were evaluated over a 6 mo period . Although only 11 % of the patients died during the index hospital stay , the 60-d , 180-d , 1-yr , and 2-yr mortality was high ( 20 % , 33 % , 43 % , and 49 % , respectively ) . The median cost of the index hospital stay was $ 7,100 ( $ 4,100 to $ 16,000 ; interquartile range ) . The median length of the index hospital stay was 9 d ( 5 to 15 d ) . After discharge , 446 patients were readmitted 754 times in the next 6 mo . At 6 mo , only 26 % of the cohort were both alive and able to report a good , very good , or excellent quality of life . Survival time was independently related to severity of illness , body mass index ( BMI ) , age , prior functional status , PaO2/FI(O2 ) , congestive heart failure , serum albumin , and the presence of cor pulmonale . Patients and caregivers should be aware of the likelihood of poor outcomes following hospitalization for exacerbation of COPD associated with hypercarbia BACKGROUND a multidimensional approach-the BODE index-has been proposed for prognostic purpose s in chronic obstructive pulmonary disease ( COPD ) and theoretically seems to be well suited for elderly people , but there is a lack of data in this population , especially with respect to long-term survival . The objective of this study is to evaluate whether the BODE index can predict both long ( 5 years ) and very-long ( 10 and 15 years)-term mortality in an unselected population of elderly people with COPD better than a set of variables commonly taken into account in a geriatric multidimensional assessment ( MDA ) . METHODS : this was a multicentre , prospect i ve , population study . We used data from the SaRA study , which included 563 elderly people with COPD whose vital status was ascertained for up to 15 years after enrolment . The discriminative capacity of the BODE index in predicting mortality was derived from Cox proportional hazard models including the components of the BODE index and compared with that of an alternative model based on MDA variables : age , gender , physical disability , cognitive function and mood status . RESULTS : at 5 years , the HRs for mortality were 1.04 ( 95 % CI : 0.60 - 1.79 ) , 1.88 ( 1.10 - 3.22 ) and 3.55 ( 2.15 - 5.86 ) for quartiles 2 - 4 , respectively , compared with quartile 1 of the BODE index . The corresponding figures for 10-year mortality were 1.50 ( 1.01 - 2.24 ) , 2.11 ( 1.39 - 3.20 ) and 3.903 ( 2.62 - 5.82 ) , and for 15-year mortality were 1.68 ( 1.19 - 2.36 ) , 2.08 ( 1.44 - 3.01 ) and 3.78 ( 2.64 - 5.41 ) . Similar results were obtained using variables included in the usual MDA . CONCLUSIONS : Both the ' classic ' MDA and the BODE index are comparably associated with mortality , even at very long term , in elderly people with COPD STUDY OBJECTIVES Condition-specific measures of quality of life ( QOL ) for patients with COPD have been demonstrated to be highly reliable and valid , but they have not conclusively been shown to predict hospitalization or death . OBJECTIVE We sought to determine whether a brief , self-administered , COPD -specific QOL measure , the Seattle Obstructive Lung Disease Question naire ( SOLDQ ) , could accurately predict hospitalizations and death . DESIGN Prospect i ve cohort study . SETTING Patients enrolled in the primary care clinics at seven Department of Veterans Affairs ( VA ) medical centers participating in the Ambulatory Care Quality Improvement Project . PATIENTS Of 24,458 patients who completed a health inventory , 5,503 reported having chronic lung disease . The 3,282 patients who completed the baseline SOLDQ were followed for 12 months . MEASUREMENTS Hospitalization and all-cause mortality during the 1-year follow-up period . RESULTS During the follow-up period , 601 patients ( 18.3 % ) were hospitalized , 141 ( 4.3 % ) for COPD exacerbations , and 167 patients ( 5.1 % ) died . After adjusting for age , VA hospital site , distance to the VA hospital , employment status , and smoking status , the relative risk of any hospitalization among patients with scores on the emotional , physical , and coping skills scales of the SOLDQ that were in the lowest quartile , when compared to the highest quartile , were 2.0 ( 95 % confidence interval [ CI ] , 1.5 to 2.6 ) , 2.5 ( 95 % CI , 1.9 to 3.4 ) , and 1.9 ( 95 % CI , 1.5 to 2.5 ) , respectively . When hospitalizations were restricted to those specifically for COPD , the odds ratio ( OR ) for the lowest quartile of physical function was 6.0 ( 95 % CI , 3.1 to 11.5 ) . Similarly , patients in the lowest quartile of physical function also had an increased risk of death ( OR , 6.8 ; 95 % CI , 3.3 to 13.8 ) . When adjusted for comorbidity ( OR , 0.8 ; 95 % CI , 0.5 to 1.2 ) , long-term steroid use ( OR , 2.8 ; 95 % CI , 1.6 to 4.9 ) , and prior hospitalization for COPD ( OR , 4.5 ; 95 % CI , 2.2 to 9.2 ) , patients having baseline SOLDQ physical function scores in the lowest quartile had an odds of hospitalization for COPD that was fivefold higher than patients with scores in the highest quartile ( OR , 5.0 ; 95 % CI , 2.6 to 9.7 ) . CONCLUSIONS Lower QOL is a powerful predictor of hospitalization and all-cause mortality . Brief , self-administered instruments such as the SOLDQ may provide an opportunity to identify patients who could benefit from preventive interventions INTRODUCTION acute exacerbation of COPD ( AE COPD ) is a major cause of hospital admission , and predicts subsequent medium-term mortality . We aim ed to examine mortality predictors in patients discharged from hospital after AE COPD . METHODS we obtained baseline demographic and clinical data from 100 patients ( mean age (range)=73 ( 60 - 98 ) years ; 48 males ) admitted with AE COPD . All completed the following vali date d question naires : a quality of life question naire ( Breathing Problems Question naire ; BPQ ) ; a screening question naire for depression ( Brief Assessment Schedule Depression Cards ; BASDEC ) ; a disability question naire ( Manchester Respiratory Activities of Daily Living question naire ; MRADL ) . Following discharge all were prospect ively followed and survival/mortality at 12 months confirmed from hospital notes and by contacting general practitioners . RESULTS the prevalence of depression at recruitment was 56 % . One-year mortality in the whole group was 36 % . Odds ratios ( 95 % confidence intervals ) for mortality predictors ( univariate logistic regression analysis ) were : use of long-term oxygen therapy=2.72 ( 1.06 - 6.97 ) ; subsequent readmission=2.57 ( 1.08 - 6.12 ) ; MRADL score=0.87 ( 0.80 - 0.94 ) ( disability predicting death ) ; BASDEC score=1.13 ( 1.02 - 1.26 ) ( depression predicting death ) ; BPQ score=1.08 ( 1.04 - 1.12 ) ( low quality of life predicting death ) ; length of original hospital stay=1.03 ( 1.00 - 1.07 ) . On multivariate logistic regression analysis the only mortality predictor was BPQ with an odds ratio ( 95 % confidence limits ) of 1.13 ( 1.04 - 1.22 ) . In terms of mortality prediction for individuals , a threshold MRADL score of < 12 gave a sensitivity of 86 % , specificity of 55 % , positive predictive value of 88 % and negative predictive value of 52 % , with similar predictive values using BPQ as an independent variable . CONCLUSIONS 1-year mortality after AE COPD admission is high . The presence of depressive illness ( which is extremely common ) , and levels of both disability and impairment of quality of life are univariate predictors of 1-year mortality in this patient group . This model may be useful in predicting prognosis for individuals and thus in guiding treatment decisions BACKGROUND AND OBJECTIVE CRP is elevated in patients with acute exacerbations of COPD ( AE COPD ) , but there is little information on whether this biomarker can help to identify adverse short-term clinical outcomes . METHODS A 6-month prospect i ve study of all patients with AE COPD requiring hospital admission . Clinical , laboratory ( including plasma CRP levels at admission ) and functional data were recorded . The outcome variable ( the adverse outcome ) consisted of : ( i ) death in hospital or within 15 days of discharge , ( ii ) transfer to the intensive care unit , or ( iii ) development of acute heart failure during hospitalization . RESULTS Data from 147 patients with a total of 160 admissions were recorded . During follow up , 38 ( 23.7 % ) adverse outcomes were observed , including 13 ( 8.8 % ) and 8 ( 5.4 % ) patients who died during hospitalization or within 15 days of discharge , respectively . CRP at a level of 50 mg/L was related to an adverse outcome ( OR 4.9 , 95 % CI : 1.92 - 12.6 , P < 0.01 ) , although by itself it was neither sensitive nor specific ( area under the receiver operating characteristic curve ( AUC ) 0.69 , 95 % CI : 0.60 - 0.77 ) . However , a risk score derived from the combination of CRP with other variables , such as ' current smoker ' , ' at least two comorbidities ' and ' confusion , ' at admission showed good predictive ability to identify an adverse outcome ( AUC of 0.80 , 95 % CI : 0.72 - 0.88 ) . CONCLUSIONS Plasma CRP in combination with other variables obtained at admission may assist identification of high-risk patients with AE COPD BACKGROUND AND OBJECTIVE COPD is a complex condition with a heavy burden of disease . Many multidimensional tools have been studied for their prognostic utility but none has been universally adopted as each has its own limitations . We hypothesize that a multidimensional tool examining four domains , health-related quality of life , disease severity , systemic effects of disease and patient factors , would better categorize and prognosticate these patients . METHODS We first evaluated 300 patients and found four factors that predicted mortality : BMI , airflow obstruction , St George 's Respiratory Question naire and age ( BOSA ) . A 10-point index ( BOSA index ) was constructed and prospect ively vali date d in a cohort of 772 patients with all-cause mortality as the primary outcome . Patients were categorized into their respective BOSA quartile group based on their BOSA score . Multivariate survival analyses and receiver operator characteristic ( ROC ) curves were used to assess the BOSA index . RESULTS Patients in BOSA Group 4 were at higher risk of death compared with their counterparts in Group 1 ( hazard ratio ( HR ) : 0.29 , 95 % CI : 0.16 - 0.51 , P < 0.001 ) and Group 2 ( HR : 0.53 , 95 % CI : 0.34 - 0.82 , P = 0.005 ) . Race and gender did not affect mortality . The area under the ROC curve for BOSA index was 0.690 ± 0.025 while that for Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) 2011 was 0.641 ± 0.025 ( P = 0.17 ) . CONCLUSION The BOSA index predicts mortality well and it has at least similar prognostic utility as GOLD 2011 in Asian patients . The BOSA index is a simple tool that does not require complex equipment or testing . It has the potential to be used widely ABSTRACT Mortality is one of the most important outcomes in patients with chronic obstructive pulmonary disease ( COPD ) . Different predictors have been associated with mortality , including the patient 's level of physical activity ( PA ) . The objective of this work was to establish the relationship between changes in PA during a moderate-to-severe COPD exacerbation ( e COPD ) and 1-year mortality after the index event . This was a prospect i ve observational cohort study with recruitment of 2,484 patients with an e COPD attending the emergency department ( ED ) of 16 participating hospitals . Variables recorded included clinical and sociodemographic data from medical records , dyspnea , health-related quality of life , and PA before the index e COPD and 2 months after the hospital or ED discharge , as reported by the patient . In the multivariate analysis worsening changes in PA from baseline to 2 months after the ED index visit [ odds ratio ( ORs ) from 2.78 to 6.31 ] was related to 1-year mortality , using the age-adjusted Charlson comorbidity index ( OR : 1.22 ) , and previous use of long-term domiciliary oxygen therapy or non-invasive mechanical ventilation at home ( OR : 1.68 ) . The same variables were also predictive in the validation sample . Areas under the receiver operating characteristic curve in the derivation and validation sample were 0.79 and 0.78 , respectively . In conclusion , PA is the strongest predictor of dying in the following year , i.e. , those with worsened PA from baseline to 2 months after an e COPD or with very low PA levels have a higher risk BACKGROUND Exacerbations are a frequent cause of morbidity and mortality in COPD . It is crucial to identify risk factors for failure after treatment of exacerbations of COPD . This study evaluates the COPD severity score ( COPD SS ) as a predictor of clinical failure , together with other severity , activity and quality of life measurements , in patients with exacerbated COPD . METHOD Multicenter , prospect i ve , observational study in ambulatory patients with exacerbation of COPD . The patients completed the COPD SS , the London Chest Activities of Daily Living ( LCADL ) and the EuroQol 5D ( EQ-5D ) . A follow-up visit was scheduled one month after presentation with the exacerbation to assess the clinical evolution . RESULTS A total of 346 patients were included ( mean age 68.5 years ( SD=9.5 years and 90.7 % male ) and mean FEV(1)(% predicted ) 46.9 % ( SD=17 ) ) . After one month , 28.2 % of episodes were classified as failures , with half of them requiring hospital admission . Patients who failed were more frequently active smokers , with more severe dyspnoea at presentation and worse lung function . They had significantly worse scores of COPD SS , LCADL , EQ-5D index and EQ-5D visual analogue score ( VAS ) and shorter mean time walking per day . ROC analysis of relationship between COPD SS and failure gave AUC 0.72 , which improved only to 0.77 when the other significant variables in univariate analysis were considered . CONCLUSIONS Clinical failure after ambulatory treatment of exacerbation of COPD is frequent . Usual markers of severity ( impaired lung function , active smoking and severe dyspnoea ) are associated with failure ; however , a short severity question naire ( COPD SS ) provides better predictive value than the usual variables Background : The severity of chronic obstructive pulmonary disease ( COPD ) should not be based on the level of airflow limitation alone . A multicomponent index such as the DOSE index ( dyspnoea score ( D ) , level of airflow obstruction ( O ) , current smoking status ( S ) , and exacerbations ( E ) ) has the potential to predict important future outcomes in patients with COPD more effectively than the forced expiratory volume in one second . Health status deterioration should be prevented in COPD patients . Aims : To investigate whether the DOSE index can predict which patients are at risk of a clinical ly relevant change in health status . Methods : A prospect i ve cohort study was performed using data from primary and secondary care . The DOSE score was determined at baseline and the 2-year change in the Clinical COPD Question naire ( CCQ ) score was calculated . Linear regression analysis was performed for the effect of a high DOSE score ( ≥4 ) on the change in CCQ score . Results : The study population consisted of 209 patients ( 112 patients from primary care ) . Overall , a high DOSE score was a significant predictor of a change in CCQ score after 2 years ( 0.41 , 95 % CI 0.13 to 0.70 ) , particularly in primary care patients . Conclusions : A DOSE score of ≥4 has the ability to identify COPD patients with a greater risk of future worsening in health status BACKGROUND : Several cross‐sectional and short‐term studies suggest that patient‐reported outcomes ( PROs ) may be useful to help predict COPD exacerbations , but evidence from long‐term prospect i ve cohort studies is lacking . Our aim was to assess if PROs add to the prediction of exacerbations . METHODS : Four hundred eight primary care patients with COPD participated in the multicenter prospect i ve International Collaborative Effort on Chronic Obstructive Lung Disease : Exacerbation Risk Index Cohorts ( ICE COLD ERIC ) study . PROs included the Chronic Respiratory Disease Question naire , the Hospital Anxiety and Depression Scale , the Feeling Thermometer , and the LASA Physical Activity Question naire ( LAPAQ ) . Exacerbations during 4½ years were adjudicated by experts . We used negative binomial regression to assess the association between PROs and exacerbations while considering age , sex , airflow obstruction , previous exacerbations , and smoking status . We then assessed if adding PROs improved the predictive properties of widely used indices . RESULTS : Lower levels of dyspnea , fatigue , and anxiety and higher levels of physical activity were associated with a lower risk of exacerbations ( adjusted incidence rate ratio [ IRR ] , 0.90 ; 95 % CI , 0.84–0.97 ; P = .01 ; IRR , 0.93 ; 95 % CI , 0.86–1.00 ; P = .04 ; IRR , 1.03 ; 95 % CI , 1.00–1.06 ; P = .03 ; IRR , 0.93 ; 95 % CI , 0.87–0.99 ; P = .04 , respectively ) . The best prediction was when LAPAQ was added to the BMI , airflow obstruction , dyspnea , and previous exacerbations ( BODEx ) index ( area under the curve & Dgr;+0.02 , from 0.72–0.74 ) . However , this increase was not clinical ly relevant ( net reclassification improvement , 0.03 ; 95 % CI , −0.03 to 0.08 ) . CONCLUSIONS : Some domains of PROs are independently associated with exacerbations but do not lead to clearly improved prediction when added to established indices to predict exacerbations . There is still much room for improvement in the prediction of exacerbations . TRIAL REGISTRY : Clinical Trials.gov ; No. : NCT00706602 BACKGROUND Accurate prediction for prognosis is important for hospitalized patients with chronic obstructive pulmonary disease ( COPD ) requiring invasive mechanic ventilation ( IMV ) and for their family members to make end-of-life decisions . The response to therapy in such a patient population has rarely been investigated . The aim of the study was to evaluate the risk factors in these patients and investigate their response to IMV and the relationship between their responses and prognosis . METHODS A cohort of 138 patients with COPD requiring IMV > or= 12 hours for acute respiratory failure of diverse etiological factors during a 4-year period were retrospectively studied using prospect ively gathered data . All variables potentially related to hospital mortality were evaluated by univariate and multiple stepwise logistic regression analysis . RESULTS The mean age of all patients investigated was ( 65.7 + /- 11.6 ) years and the hospital mortality was 39.9 % ( 31.1 % with COPD exacerbation ) . Correction of acidosis ( pH > or= 7.30 ) was seen in 58 patients ( 69.9 % ) in survivors but only 12 patients ( 21.8 % ) in nonsurvivors ( P < 0.05 ) after ventilation . Using multivariate logistic analysis , the variables independently associated with hospital mortality were a higher acute physiology score before intubation , lower pH value measured 24 hours after the onset of ventilation and development of multiorgan dysfunction syndrome ( MODS ) . CONCLUSIONS In COPD patients requiring IMV , the postintubation pH value can not only reflect patients ' response to treatment , but also serve as an independent determinant of hospital mortality apart from other risk factors such as a higher preintubation APACHE II score and development of MODS . A close correlation between the response to IMV and prognosis was proved in these patients Aims To quantify the ability of N-terminal pro-brain natriuretic peptide ( NT pro-BNP ) to predict mortality and hospitalization in patients with chronic obstructive airways disease ( COPD ) . Methods Prospect i ve single-centre observational study of 140 consecutive patients aged at least 18 years with COPD between 27 March 2004 and 28 February 2008 ( median follow-up 3.9 years ) . Results Sixty-five ( 46 % ) men , 26 ( 19 % ) O2 therapy , 115 ( 82 % ) smokers , 38 ( 27 % ) patients receiving diuretics , 15 ( 11 % ) left-ventricular ejection fraction less than 45 % . Median [ interquartile range ( IQR ) ] NT pro-BNP concentration 16.2 ( 25.4 ) pmol/l . NT pro-BNP was higher in those with a dilated left atrium ( P < 0.001 ) , aortic stenosis ( P = 0.02 ) , left-ventricular systolic dysfunction ( P = 0.027 ) , right ventricular impairment ( P = 0.011 ) , atrial fibrillation ( P < 0.001 ) , patients receiving diuretics ( P = 0.010 ) and angiotensin-converting enzyme ( ACE ) inhibitors ( P = 0.006 ) . One-year mortality and hospitalization rates were 2.9 and 25.4 % . The median ( IQR ) time to hospitalization and length of first hospital stay : 383.5 ( 605 ) and 4.0 ( 7.0 ) days . NT pro-BNP was an excellent discriminator of right-ventricular impairment ( C statistic = 0.90 ) and predicted survival ( highest quartile versus lowest quartile relative risk = 3.02 , P = 0.001 ) , but not hospital admission . After adjustment this association was not significant . Conclusion NT pro-BNP predicts survival , but not hospital admission in patients with COPD . The ability of NT pro-BNP to independently predict death or hospitalization is superseded by the presence of a dilated left atrium , aortic stenosis and left-ventricular systolic dysfunction BACKGROUND The outcome after hospitalization for an exacerbation of chronic obstructive pulmonary disease ( COPD ) is unfavorable and uncertainty exists about factors predicting short and long-term prognosis . OBJECTIVE To identify clinical predictors of length of hospital stay ( LOS ) and three-year mortality after COPD exacerbations requiring hospitalization . DESIGN Retrospective analysis of prospect ively collected data . PARTICIPANTS AND METHODS All consecutive patients hospitalized with COPD exacerbation were enrolled . Disease severity was estimated by FEV1 , body mass index ( BMI ) , Medical Research Council ( MRC ) chronic dyspnoea scale , previous hospitalizations , need for long-term oxygen treatment ( LTOT ) , arterial oxygen and carbon dioxide partial pressures ( PaO2 and PaCO2 ) , pH and respiratory rate . Outcome was assessed by LOS and three-year mortality . MAIN RESULTS Out of 81 patients enrolled , three-year mortality data were available for 61 . LOS was related to BMI , MRC scale and respiratory rate . Three-year mortality was related to FEV1 , BMI , MRC scale , LTOT , and PaCO2 . Multiple logistic regression analysis demonstrated that MRC scale was the only independent determinant of LOS , [ p = 0.001 , odds ratio ( OR ) 7.67 ( 95 % CI 2.50–23.41 ) ] , whereas MRC scale and BMI predicted three-year mortality , [ p = 0.001 , OR 8.28 ( 95 % CI 2.25–30.47 ) and p = 0.006 , OR 6.91 ( 95 % CI 1.74–27.48 ) , respectively ] . Cox regression analysis demonstrated identical results . Using receiver-operator-optimized thresholds for these variables ( MRC > 2 and BMI < 25 kg/m2 ) , we propose a prediction model that accurately determines three-year mortality risk . CONCLUSIONS In this study , MRC scale and BMI predicted outcome after COPD hospitalization . Pending further validation , this predictive model may contribute to identify patients with poor outcome even when spirometric data are unavailable BACKGROUND Healthcare utilization , especially length of hospital stay and ICU admission , for acute exacerbation of chronic obstructive pulmonary disease ( AE COPD ) determine overall outcomes in terms of morbidity , mortality and cost burden . Predicting prolonged hospital stay ( PHS ) and prolonged intensive care ( PIC ) for AE COPD is useful for rational allocation of re sources in healthcare centres . AIM To characterize the pattern of healthcare utilization by COPD patients hospitalized for acute exacerbation , and to identify clinical and laboratory predictors of ' prolonged hospital stay ' ( PHS ) and ' prolonged intensive care'(PIC ) . MATERIAL S AND METHODS This study attempted through retrospective data analysis , to identify risk factors and evolve prediction models for increased healthcare utilization namely PHS and PIC for AE COPD . The data were extracted from 255 eligible admissions for AE COPD by 166 patients from Aug 2012 to July 2013 . Logistic regression analysis was used for identifying predictors and models were tested with area under receiver operating characteristic curve . RESULTS Independent predictors of prolonged hospital stay ( ≥ 6 days ) were chronic respiratory failure at baseline , low saturation at admission , high HbA1c level and positive isolates in sputum culture . Independent predictors of prolonged intensive care ( for ≥ 48 hours ) were past history of pulmonary tuberculosis , chronic respiratory failure at baseline , low saturation at admission , high leukocyte count and positive culture isolates in sputum . Prediction models evolved from variables available at admission showed AUC 0.805 ( 95 % CI 0.729 - 0.881 ) and 0.825 ( 95 % CI 0.75 - 0.90 ) for PHS and ICU admissions respectively . CONCLUSION Our prediction models derived from simple and easily available variables show good discriminative properties in predicting PHS and PIC for AE COPD . When prospect ively vali date d , these models are useful for rational allocation of services especially in re source limited setting Introduction : Acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) being common and often fatal , prognostic tools in AE COPD are lacking . Material s and Methods : A prospect i ve , observational study was carried out in fifty patients of AE COPD admitted in A and E department . Dyspnea , Eosinopenia , Consolidation , Acidemia and atrial Fibrillation ( DECAF ) score and elevated blood urea nitrogen , altered mental status , pulse > 109 , age > 65 ( BAP-65 ) score were calculated . Dyspnea was scored using extended Medical Research Council Dyspnoea score . Data were collected and analyzed using SPSS 17.0 software . Results : Forty-one patients were discharged and 9 ( 18 % ) died during treatment . Patients who were discharged and patients who died during hospital stay were compared . There was no significant difference in terms of sociodemographic variables , presence of comorbidities , and other markers of disease severity . A significant difference was found in blood counts , blood urea , serum creatinine , acidotic respiratory failure , and atrial fibrillation . A higher value of DECAF score and BAP-65 score was found more commonly in patients who died . Sensitivity for prediction of mortality for DECAF score and BAP-65 score was 100 % and specificity was 34.1 % and 63.4 % , respectively . Sensitivity for prediction of need for invasive ventilation for DECAF score and BAP-65 score was 80 % and 100 % , respectively , and specificity was 80 % and 60 % , respectively . Conclusion : Both DECAF and BAP-65 scores were found to be good predictors of mortality and need for ventilation in this pilot study OBJECTIVES To determine the effect of age , severity of lung disease , severity and frequency of exacerbation , steroid use , choice of an antibiotic , and the presence of comorbidity on the outcome of treatment for an acute exacerbation of COPD . DESIGN A retrospective chart analysis over 24 months . SETTING A university Veterans Affairs medical center . PATIENTS Out patients with COPD who were treated with an antibiotic over a period of 24 months for an acute exacerbation of COPD . METHODS Severity of an acute exacerbation of COPD was defined using the criteria of Anthonisen et al : increased dyspnea , increased sputum volume , and increased sputum purulence . Severity of lung disease was stratified based on FEV(1 ) percent predicted using American Thoracic Society guidelines ( stage I , FEV(1 ) > or = 50 % ; stage II , FEV(1 ) 35 to 49 % ; stage III , FEV(1 ) < 35 % ) . Treatment outcome was judged successful when the patient had no return visit in 4 weeks for a respiratory problem . Failure was defined as a return visit for persistent respiratory symptoms that required a change of an antibiotic in < 4 weeks . RESULTS One-hundred seven patients with COPD ( mean age + /- SD , 66.9 + /- 9.5 years ) experienced 232 exacerbations over 24 months . First-line antibiotics ( trimethoprim-sulfamethoxazole , ampicillin/amoxicillin , and erythromycin ) were used to treat 78 % of all exacerbations . Treatment failure was noted in 12.1 % of first exacerbations and 14 . 7 % of all exacerbations , with more than half the failures requiring hospitalization . Host factors that were independently associated with treatment failure included the following : FEV(1 ) < 35 % ( 46.4 % vs 22.4 % ; p = 0.047 ) , use of home oxygen ( 60.7 % vs 15.6 % ; p < 0 . 0001 ) , frequency of exacerbation ( 3.8 + /- 2.0 vs 1.6 + /- 0.91 ; p < 0 . 001 ) , history of previous pneumonia ( 64.3 % vs 35.1 p < 0.007 ) , history of sinusitis ( 28.6 % vs 8.8 % ; p < 0.009 ) and use of maintenance steroids ( 32.1 % vs 15.2 % p = 0.052 ) . Using stepwise logistic regression analysis to identify the top independent variables , the use of home oxygen ( p = 0.0002 ) and frequency of exacerbation ( p < 0.0001 ) correctly classified failures in 83.3 % of the patients . Surprisingly , age , the choice of an antibiotic , and the presence of any one or more comorbidity did not affect the treatment outcome . CONCLUSION The results of our study suggest that patient host factors and not antibiotic choice may determine treatment outcome . Prospect i ve studies in appropriately stratified patients are needed to vali date these findings RATIONALE The rate of annual change in FEV1 is highly variable among patients with chronic obstructive pulmonary disease ( COPD ) . Reliable blood biomarkers are needed to predict prognosis . OBJECTIVES To explore plasma biomarkers associated with an annual change in FEV1 in patients with COPD . METHODS Plasma sample s of 261 subjects , all Japanese , with COPD from the 5-year Hokkaido COPD cohort study were analyzed as a hypothesis-generating cohort , and the results were vali date d using data of 226 subjects with and 268 subjects without airflow limitation , mainly white , from the 4-year COPD Quantification by Computed Tomography , Biomarkers , and Quality of Life ( CBQ ) study conducted in Denmark . The plasma sample s were measured using Human CardiovascularMAP ( Myriad RBM , Austin , TX ) , which could analyze 50 biomarkers potentially linked with inflammatory , metabolic , and tissue remodeling pathways , and single ELISAs were used to confirm the results . MEASUREMENTS AND MAIN RESULTS Higher plasma adiponectin levels and a lower leptin/adiponectin ratio at enrollment were significantly associated with an annual decline in FEV1 even after controlling for age , sex , height , and body mass index in the Hokkaido COPD cohort study ( P = 0.003 , P = 0.004 , respectively ) . A lower plasma leptin/adiponectin ratio was also significantly associated with an annual decline in FEV1 in subjects with airflow limitation in the CBQ study ( P = 0.014 ) , the patients of which had largely different clinical characteristics compared with the Hokkaido COPD cohort study . There were no significant associations between lung function decline and adipokine levels in subjects without airflow limitation . CONCLUSIONS A lower leptin/adiponectin ratio was associated with lung function decline in patients with COPD in two independent Japanese and Western cohort studies of population s of different ethnicity . Measure of systemic adipokines may provide utility in predicting patients with COPD at higher risk of lung function decline This study aim ed to identify the risk factors for relapse after ambulatory treatment of acute exacerbations of chronic bronchitis ( AECB ) that can easily be used in a primary care setting . Data were prospect ively collected on 2,414 ambulatory patients with AECB from 268 general practice s located throughout Spain . A multivariate model to identify risk factors independently associated with failures was developed and vali date d from the information recorded at the inclusion visit and at 30-days follow-up visit . A total of 507 patients relapsed ( 21 % ) ; of these , 84 required admission ( 16.5 % ) . The multivariate model for prediction of the risk of relapse included 2,414 cases : 1,689 for the developmental sample and 725 in the validation sample . The model obtained contained three readily-obtainable variables : ischaemic heart disease ( odds ratio (OR)=1.63 ; 95 % confidence interval (CI)=1.07 - 2.47 ) , degree of dyspnoea ( OR = 1.31 ; 1.14 - 1.50 ) and number of visits to the general practitioner the previous year ( OR = 1.07 ; 1.04 - 1.10 ) . The model calibrated well in developmental and validation sample s ( goodness-of-fit tests : p = 0.295 and p = 0.637 , respectively ) . Severity of the exacerbation was not associated with increased risk of relapse in either univariate or multivariate analysis . The present results suggest that baseline characteristics of the patients such as degree of dyspnoea , coexisting ischaemic heart disease and number of previous visits to the general practitioner for respiratory problems are strongly associated with increased risk of relapse after ambulatory treatment of acute exacerbations of chronic bronchitis . In contrast , exacerbation severity was not associated with clinical failure . Guidelines for management of acute exacerbations of chronic bronchitis should consider such risk factors and advocate intensive broad spectrum treatment and closer follow-up of patients exhibiting them OBJECTIVES Prognostic challenges hinder the identification of patients with advanced chronic obstructive pulmonary disease ( COPD ) for timely palliative interventions . We postulate that a two-minute derivative ( two-minute walking distance [ 2MWD ] ) of a st and ard six-minute walk test ( 6MWT ) can identify frail subjects with poorer survival for early palliative intervention . The primary outcome of interest is mortality at 18 months . Secondary objectives include evaluation of the relationship between the 2MWD and ability to self-care , dyspnea-related disabilities , nutrition , forced expiratory volume in first second ( FEV1 ) , quality of life ( QoL ) , and comorbidity burden . DESIGN AND SETTING One hundred twenty-four subjects with stage 3 and 4 COPD were recruited and followed up . Ability to self-care , dyspnea-related disabilities , airflow limitation , nutrition , and QoL were measured by using modified Barthel index ( MBI ) , Modified Medical Research Council ( MMRC ) dyspnea scale , FEV1 ( % predicted ) , BODE [ BMI ( B ) , FEV1(O ) , MMRC(D ) , 6MWT(E ) ] index , up date d ADO [ Age(A ) , MMRC(D ) , FEV1(O ) ] index , Subjective Global Assessment ( SGA ) , and St. George 's Respiratory Question naire ( SGRQ ) , respectively . Survival data were prospect ively collected and analyzed . RESULTS The 2MWD correlates highly with BODE and predicts up date d ADO independent of age , co-morbidities , long-term oxygen therapy ( LTOT ) , body mass index , and FEV1 . Log-rank test performed with Kaplan-Meier plots demonstrates that 2MWD ≤80 m significantly predicts survival time ( p < 0.05 ) . Cox proportional hazard regression shows a 3.6-time greater probability of 18-month mortality ( hazard ratio [ HR ] 3.57 ; 95 % confidence interval [ CI ] 1.26 - 10.13 ; p < 0.05 ) . In addition , 2MWD strongly predicted MBI and MMRC , independent of age , co-morbidities , LTOT , body mass index , and FEV1 . Subjects with 2MWD ≤80 m have a poorer ability to self-care ( median MBI 90 vs. 100 ) , lower FEV1 ( 32.9 % ± 9.8 % vs. 38.1 % ± 9.4 % ) , poorer QoL ( mean SGRQ 46.6 ± 16.2 vs. 36.6 ± 13.3 ) , and greater dyspnea-related disability ( mean MMRC 1.7 ± 0.7 vs. 0.9 ± 0.6 ) , and they are more malnourished ( 40.4 % vs. 9.7 % ; RR 1.51 ) ( all p < 0.001 ) . CONCLUSION 2MWD ≤80 m identifies subjects with higher mortality , greater functional dependence , poorer in nutrition , greater dyspnea , and lower QoL. Incorporation of 2MWD into composite prognostic indices can enhance predictive accuracy and identify patients requiring early proactive palliative interventions BACKGROUND Identification of persons with chronic obstructive pulmonary disease ( COPD ) at risk for acute exacerbations ( AEs ) targets them for close monitoring . OBJECTIVES We examined the ability of a novel index combining physical activity and systemic inflammation to identify persons at risk for AEs . METHODS In an observational cohort study of 167 persons with COPD , we assessed daily step count , a direct measure of physical activity , with the StepWatch Activity Monitor and measured plasma C-reactive protein ( CRP ) and IL-6 levels . AEs and COPD -related hospitalizations were assessed prospect ively over a median of 16 months . Predictors of AEs and COPD -related hospitalizations were assessed using negative binomial models . MEASUREMENTS AND MAIN RESULTS Median daily step count was 5,203 steps ( interquartile range , 3,627 - 7,024 ) . Subjects with daily step count ≤ 5,203 and CRP > 3 mg/l had an increased rate of AEs ( rate ratio [ RR ] , 2.06 ; 95 % confidence interval [ CI ] , 1.30 - 3.27 ) and COPD -related hospitalizations ( RR , 3.51 ; 95 % CI , 1.73 - 7.11 ) compared with subjects with daily step count > 5,203 and CRP ≤ 3 mg/l , adjusting for FEV1 % predicted and prednisone use for AE in the previous year . Similarly , subjects with daily step count ≤ 5,203 and IL-6 > 2 pg/ml had an increased rate of AEs ( RR , 2.04 ; 95 % CI , 1.14 - 3.63 ) and COPD -related hospitalizations ( RR , 4.27 ; 95 % CI , 1.56 - 11.7 ) compared with subjects with daily step count > 5,203 and IL-6 ≤ 2 pg/ml . CONCLUSIONS An index combining daily step count and systemic inflammation can predict AEs and COPD -related hospitalizations . A validation study in a separate cohort is needed to confirm the utility of the proposed index as a clinical tool to risk stratify persons with COPD The morbidity and mortality due to asthma and chronic bronchitis are still rising in several countries . The aim of this study was to investigate whether early detection of patients with fast progressive asthma or chronic bronchitis in general practice was possible from a cross-sectional assessment of symptoms , smoking behaviour , quality of life , physical signs of the chest , allergy , and lung function . Data of 162 patients who had participated in a long-term r and omized controlled intervention study in general practice were analysed . Fifty-six out of the 162 patients showed fast progressive disease ( FPD , a rapid annual decline in FEV1 in combination with a high exacerbation rate ) . Measurements at the start of the study were used in a logistic regression analysis in order to detect the patients at risk ( with FPD ) . A lower maximal expiratory flow at 50 % of expired volume ( MEF50 ) was related to an increased risk of FPD in both asthma and chronic bronchitis ( relative risks of 16.8 and 8.0 respectively , p less than 0.05 ) . Most lung function indices , but also quality of life and pack years , were significant predictors of FPD in chronic bronchitis ( p less than 0.05 ) . However , it was not possible to detect FPD reliably with these predictors separately or even with the combination of several relevant clinical variables ; 18 % of the patients with chronic bronchitis and 22 % of the patients with asthma were still misclassified . It was concluded from this study that more than one measurement over time ( monitoring ) is necessary to detect the patients at risk . Monitoring should include assessment s of objective ventilatory function indices ( PEFR , FEV1 or MEF50 ) OBJECTIVE To assess the relationship of personality and clinical characteristics with survival in patients with advanced chronic obstructive pulmonary disease ( COPD ) . DESIGN Prospect i ve double-blind study . SETTING Outpatient clinic of a teaching Veterans Affairs Hospital in central New York . PATIENT PARTICIPATION : Sixteen male patients ( mean age , 62.2 + /- 2.5 years ) with severe COPD INTERVENTIONS : Patients were administered Minnesota Multiphasic Personality Inventory ( MMPI ) test ; their clinical features were recorded from hospital records at the time of admission into the study . All were followed up for 4 years after the initial assessment or until their death . MEASUREMENTS AND MAIN RESULTS The nine survivors and seven nonsurvivors were similar in age , pulmonary function test ( PFT ) results , oxygenation , number of medications , or concomitant illnesses . However , the nonsurvivors had higher MMPI and clinical illness scores compared with the survivors ( p < 0.01 and < 0.05 , respectively ) . CONCLUSIONS The 4-year mortality in male veterans with severe COPD is influenced by overall psychological distress and difficulty in coping with their disease , which seem to be important prognostic indicators irrespective of PFT results or oxygenation Objective : Abnormal airway colonization in patients with chronic obstructive pulmonary disease ( COPD ) needing invasive mechanical ventilation ( IMV ) is considered a first step in the acquisition of nosocomial pneumonia . Noninvasive ventilation ( NIV ) could potentially avoid this , but airway colonization has not been studied in patients who undergo NIV . We hypothesized that patients undergoing NIV would have lower rates of colonization than patients undergoing IMV . The aim of the study was to assess the microbial airway colonization in patients with exacerbated COPD needing NIV and IMV . Design : A 2-yr prospect i ve cohort study . Setting : Respiratory intensive and intermediate care unit . Patients : Eighty-six patients with exacerbated COPD undergoing NIV on admission ( 64 successes and 22 failures , according to subsequent intubation ) , and 51 patients undergoing IMV on admission . Interventions : Quantitative culture specimens of sputum or tracheal aspirate were collected on admission and at follow-up ( day 3 ) during NIV or IMV , respectively . Clinical assessment , including severity scores , and arterial blood gas measurements were also determined . Measurements and Main Results : Compared with the NIV-success group , colonization by potentially pathogenic microorganisms was greater in the NIV-failure group on admission ( 13 [ 59 % ] vs. 14 [ 22 % ] ; p < .001 ) and at follow-up while patients still underwent NIV ( 14 [ 93 % ] vs. 7 [ 14 % ] ; p < .001 ) , and it was even higher than during IMV at follow-up ( 20 [ 50 % ] ; p = .027 ) . Colonization by nonfermenting Gram-negative bacilli , mainly Pseudomonas aeruginosa , was significantly associated with NIV failure on admission ( OR , 5.6 ; p = .016 ) and at follow-up ( OR , 23.5 ; p < .001 ) . Moreover , colonization by these microorganisms at follow-up ( OR , 8.8 ; p = .008 ) and inadequate antimicrobial treatment ( OR 11.3 ; p = .001 ) were associated with increased hospital mortality . Conclusions : Airway colonization by nonfermenting Gram-negative bacilli is strongly associated with NIV failure . Because it occurs before intubation , this would be a marker rather than just a consequence of NIV failure necessitating intubation . The efficacy of decreasing airway colonization in preventing NIV failure needs to be assessed Background Hospitalization for a severe exacerbation of COPD ( e COPD ) is an important event in the natural history of COPD . Identifying factors related to mortality 1 year after hospitalization could help determine interventions to reduce mortality . Methods In a prospect i ve , observational , multicentre study , we evaluated data from two cohorts : the Spanish audit of hospital COPD exacerbation care ( our derivation sample ) and the Spanish cohort of the European audit of COPD exacerbation care ( our validation sample ) . The endpoint was all-cause mortality . Mortality was determined by local research managers of the participating hospitals and matched the official national index records in Spain . Results In the multivariate analysis , factors independently related to an increase in mortality were older age , cardio-cerebro-vascular and /or dementia comorbidities , PaCO2 > 55 mmHg measured at emergency department arrival , hospitalizations for COPD exacerbations in the previous year , and hospital characteristics . The area under the receiver-operating curve for this model was 0.75 in the derivation cohort and 0.76 in the validation cohort . Conclusion One-year mortality following the index hospitalization for an exacerbation of COPD was related to clinical characteristics of the patient and of the index event , previous events of similar severity , and characteristics of the hospital where the patient was treated Objective To describe prognostic factors , clinical course , and hospital outcome of patients with chronic obstructive pulmonary disease admitted to an intensive care unit for acute respiratory failure . Design Analysis of prospect ively collected data . Setting A multidisciplinary intensive care unit of an inner-city university hospital . Patients Patients with chronic obstructive pulmonary disease admitted to an intensive care unit for acute respiratory failure from August 1995 through July 1998 . Measurements and Main Results Data were obtained concerning demographics , arterial blood gas , Acute Physiology and Chronic Health Evaluation ( APACHE ) II score , sepsis , mechanical ventilation , organ failure , complications , and hospital mortality rate . Fifty-nine percent of patients were male , 63 % white , and 36 % African-American ; the mean age was 63.1 ± 8.9 yrs . Noninvasive mechanical ventilation was tried in 40 % of patients and was successful in 54 % of them . Invasive mechanical ventilation was required in 61 % of the 250 admissions . Sepsis developed in 31 % of patients , nonpulmonary organ failure in 20 % , pneumothorax in 3 % , and acute respiratory distress syndrome in 2 % . Multiple organ failure developed in 31 % of patients with sepsis compared with 3 % without sepsis ( p < .0001 ) . Predicted and observed hospital mortality rates were 30 % and 15 % , respectively . Differences in age and arterial carbon dioxide and oxygen tensions between survivors and nonsurvivors were not significant . Arterial pH was lower in nonsurvivors than in survivors ( 7.21 vs. 7.25 , p = .0408 ) . The APACHE II-predicted mortality rate ( p = .0001 ; odds ratio , 1.046 ; 95 % confidence interval , 1.022–1.070 ) and number of organ failures ( p < .0001 ; odds ratio , 5.524 ; 95 % confidence interval , 3.041–10.031 ) were independent predictors of hospital outcome ; invasive mechanical ventilation was not an independent predictor . Conclusions Physiologic abnormalities at admission to an intensive care unit and development of nonrespiratory organ failure are important predictors of hospital outcome for critically ill patients with chronic obstructive pulmonary disease who have acute respiratory failure . Improved outcome would require prevention and appropriate treatment of sepsis and multiple organ failure Abstract Long-term outcome prediction in COPD is challenging . We conducted a prospect i ve 5–7-year follow-up study in patients with COPD to determine the association of exacerbation type , discharge levels of inflammatory biomarkers including procalctionin ( PCT ) , C-reactive protein ( CRP ) , white blood cell count ( WBC ) and plasma proadrenomedullin ( ProADM ) , alone or combined with demographic/ clinical characteristics , with long-term all-cause mortality in the COPD setting . The analyzed cohort comprised 469 patients with index hospitalization for pneumonic ( n = 252 ) or non-pneumonic ( n = 217 ) COPD exacerbation . Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/ primary care physicians . We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve ( AUC ) . After a median [ 25th–75th percentile ] 6.1 [ 5.6–6.5 ] years , mortality was 55 % ( 95%CI 50%–59 % ) . Discharge ProADM concentration was strongly associated with 5–7-year non-survival : adjusted hazard ratio (HR)/10-fold increase ( 95%CI ) 10.4 ( 6.2–17.7 ) . Weaker associations were found for PCT and no significant associations were found for CRP or WBC . Combining ProADM with demographic/ clinical variables including age , smoking status , BMI , New York Heart Association dyspnea class , exacerbation type , and comorbidities significantly improved long-term predictive accuracy over that of the demographic/ clinical model alone : AUC ( 95%CI ) 0.745 ( 0.701–0.789 ) versus 0.727 ( 0.681–0.772 ) , p = .043 . In patients hospitalized for COPD exacerbation , discharge ProADM levels appeared to accurately predict 5–7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/ clinical mortality risk assessment RATIONALE Patients with chronic obstructive pulmonary disease ( COPD ) are afflicted by comorbidities . Few studies have prospect ively evaluated COPD comorbidities and mortality risk . OBJECTIVES To prospect ively evaluate COPD comorbidities and mortality risk . METHODS We followed 1,664 patients with COPD in five centers for a median of 51 months . Systematic ally , 79 comorbidities were recorded . We calculated mortality risk using Cox proportional hazard , and developed a graphic representation of the prevalence and strength of association to mortality in the form of a " comorbidome " . A COPD comorbidity index ( COPD specific comorbidity test [ COTE ] ) was constructed based on the comorbidities that increase mortality risk using a multivariate analysis . We tested the COTE index as predictor of mortality and explored whether the COTE index added predictive information when used with the vali date d BODE index . MEASUREMENTS AND MAIN RESULTS Fifteen of 79 comorbidities differed in prevalence between survivors and nonsurvivors . Of those , 12 predicted mortality and were integrated into the COTE index . Increases in the COTE index were associated with an increased risk of death from COPD -related ( hazard ratio [ HR ] , 1.13 ; 95 % confidence interval , 1.08 - 1.18 ; P < 0.001 ) and non- COPD -related causes ( HR , 1.18 ; 95 % confidence interval , 1.15 - 1.21 ; P < 0.001 ) . Further , increases in the BODE and COTE were independently associated with increased risk of death . A COTE score of greater than or equal to 4 points increased by 2.2-fold the risk of death ( HR , 2.26 - 2.68 ; P < 0.001 ) in all BODE quartile . CONCLUSIONS Comorbidities are frequent in COPD and 12 of them negatively influence survival . A simple disease-specific comorbidities index ( COTE ) helps assess mortality risk in patients with COPD ABSTRACT The aim of this study was to identify a multivariate model to predict poor outcomes after admission for exacerbation of chronic obstructive pulmonary disease ( COPD ) . We performed a multicenter , observational , prospect i ve study . Patients admitted to hospital for COPD were followed up for 3 months . Relevant clinical variables at admission were selected . For each variable , the best cut-offs for the risk of poor outcome were identified using receiver operating characteristic ( ROC ) curves . Finally , a stepwise logistic regression model was performed . A total of 106 patients with a mean age of 71.1 ( 9.8 ) years were included . The mean maximum expiratory volume in the first second (FEV1)(% ) was 45.2 % , and the mean COPD assessment test ( CAT ) score at admission was 24.8 ( 7.1 ) . At 3 months , 39 ( 36.8 % ) patients demonstrated poor outcomes : death ( 2.8 % ) , readmission ( 20.8 % ) or new exacerbation ( 13.2 % ) . Variables included in the logistic model were : previous hospital admission , FEV1 < 45 % , Charlson ≥ 3 , hemoglobin (Hb)<13 g/L , PCO2 ≥ 46 mmHg , fibrinogen ≥ 554 g/L , C-reactive protein (CRP)≥45 mg/L , leukocyte count < 9810 × 109/L , purulent sputum , long-term oxygen therapy ( LTOT ) and CAT ≥ 31 at admission . The final model showed that Hb < 13 g/L ( OR = 2.46 , 95%CI 1.09–6.36 ) , CRP ≥ 45 mg/L ( OR = 2.91 , 95%CI : 1.11–7.49 ) and LTOT ( 3.07 , 95%CI : 1.07–8.82 ) increased the probability of poor outcome up to 82.4 % . Adding a CAT ≥ 31 at admission increased the probability to 91.6 % ( AUC = 0.75 ; p = 0.001 ) . Up to 36.8 % of COPD patients had a poor outcome within 3 months after hospital discharge , with low hemoglobin and high CRP levels being the risk factors for poor outcome . A high CAT at admission increased the predictive value of the model Purpose There is currently no measure to predict a treatability of long-acting β-2 agonist ( LABA ) or long-acting muscarinic antagonist ( LAMA ) in patients with chronic obstructive pulmonary disease ( COPD ) . We aim ed to build prediction models for the treatment response to these bronchodilators , in order to determine the most responsive medication for patients with COPD . Methods We performed a prospect i ve open-label crossover study , in which each long-acting bronchodilator was given in a r and om order to 65 patients with stable COPD for 4 weeks , with a 4-week washout period in between . We analyzed 14 baseline clinical traits , expression profiles of 31,426 gene transcripts , and damaged-gene scores of 6,464 genes acquired from leukocytes . The gene expression profiles were measured by RNA microarray and the damaged-gene scores were obtained after DNA exome sequencing . Linear regression analyses were performed to build prediction models after using factor and correlation analyses . Results Using a prediction model for a LABA , traits found associated with the treatment response were post-bronchodilator forced expiratory volume in 1 second , bronchodilator reversibility ( BDR ) to salbutamol , expression of three genes ( CLN8 , PCSK5 , and SKP2 ) , and damage scores of four genes ( EPG5 , FNBP4 , SCN10A , and SPTBN5 ) ( R2=0.512 , p<0.001 ) . Traits associated with the treatment response to a LAMA were COPD assessment test score , BDR , expression of four genes ( C1orf115 , KIAA1618 , PRKX , and RHOQ ) and damage scores of three genes ( FBN3 , FDFT1 , and ZBED6 ) ( R2=0.575 , p<0.001 ) . The prediction models consisting only of clinical traits appeared too weak to predict the treatment response , with R2=0.231 for the LABA model and R2=0.121 for the LAMA model . Conclusion Adding the expressions of genes and damaged-gene scores to the clinical traits may improve the predictability of treatment response to long-acting bronchodilators BACKGROUND Weak cough may result in the failure of noninvasive positive pressure ventilation ( NPPV ) in patients with AE COPD . However , no detailed descriptions have yet been published for the measurement of cough strength and associated outcomes in AE COPD patients . METHODS This study prospect ively enrolled 261 AE COPD patients who received NPPV . Semiquantitative cough strength score ( SCSS , ranging from 0 = weak to 5 = strong ) was recorded before NPPV . Patients who required intubation were defined as NPPV failures . RESULTS NPPV failed in 55 patients ( 21.1 % ) . Weak cough ( SCSS ≤3 , OR = 8.1 ) , high disease severity ( APACHE II score > 19 , OR = 3.8 ) , and malnutrition ( total proteins ≤58 g/L , OR = 2.8 ) were independent risk factors for NPPV failure . Patients with 1 , 2 , and 3 risk factors were 4.7 , 13.6 , and 21.6 times more likely , respectively , to experience NPPV failure compared with patients with no risk factors . The NPPV failure rates were 80 % , 40 % , and 10.2 % in patients with SCSS of 0–1 , 2–3 , and 4–5 , respectively ( p < 0.001 ) . Compared with NPPV success patients , NPPV failure patients stayed longer in ICU ( 10.1 ± 7.9 days vs. 6.5 ± 4.6 days , p < 0.001 ) , and they had higher ICU costs ( € 2986 ± 1906 vs. € 5680 ± 3,604 , p < 0.001 ) , higher hospital costs ( € 6714 ± 7025 vs. € 10,399 ± 9,509 , p = 0.009 ) , and higher hospital mortality ( 72.7 % vs. 4.4 % , p < 0.001 ) . Moderate accuracy to distinguish NPPV failure by APACHE II score , SCSS , and total proteins was evidence d by ROC curves , with areas under the curve of 0.71 , 0.78 , and 0.67 , respectively . A combination of all three factors reached good accuracy , with an area under the curve of 0.86 . CONCLUSION AE COPD patients with weak cough had a high risk of NPPV failure . SCSS , APACHE II scores , and total proteins were predictors of NPPV failure . Combined , these factors increased the power to predict NPPV failure Using clinical and cl aims records from the National Emphysema Treatment Trial , we sought to identify factors that accurately predicted COPD exacerbations . This prospect i ve cohort study consisted of subjects with severe emphysema r and omized to medical therapy . Exacerbations were defined as a hospitalization or emergency department visit for COPD . Patient characteristics obtained before r and omization were entered as independent variables in multivariable logistic regression models to estimate the risk of exacerbation . Discrimination was determined using the area under the receiver operator characteristic curve ( AUC ) . Baseline measures included demographics , body mass index , pulmonary function , arterial blood gases , radiology studies , dyspnea ( Shortness of Breath Question naire — SOBQ ) , health-related quality of life ( St. George 's Respiratory Question naire — SGRQ ) , 6-minute walk , exercise capacity , medication use , prior exacerbations and co-morbidity . In 610 participants , 26.6 % had a COPD exacerbation over 1-year follow-up . In a model incorporating spirometry , PaO2 , dyspnea , prior exacerbations and co-morbidity , a 5-point decrement in percent predicted FEV1 ( OR 1.16 , 95 % CI 1.00–1.34 ) and a 5-point worsening in SOBQ ( OR 1.08 , 1.02–1.14 ) independently predicted exacerbations ( AUC for full model 0.68 ) . Combining physiologic variables , dyspnea , prior exacerbations and co-morbidity may be useful in identifying patients at high risk for COPD exacerbations Background : Hospital readmissions for acute exacerbation of chronic obstructive pulmonary disease ( COPD ) are one of the leading causes of healthcare expenditures worldwide . Objectives : To identify risk factors for hospital readmission in COPD patients . Methods : We prospect ively evaluated 129 consecutive patients hospitalized for acute exacerbation of COPD . Clinical , spirometric and arterial blood gas variables were measured during hospitalization . Socioeconomic characteristics , comorbidity , dyspnea , functional dependence , depression , social support and quality of life were also analyzed . Readmission was defined as one or more hospitalizations in the following year . Results : During the follow-up period , 75 ( 58.5 % ) patients were readmitted . In bivariate analysis , readmission was associated with previous hospitalization for COPD in the past year , dyspnea scale , PaCO2 at discharge , depression , cor pulmonale , chronic domiciliary oxygen and quality of life measured by the St. George ’s Respiratory Question naire . In multivariate analysis , the best predictor of readmission was the combination of hospitalization for COPD in the previous year ( odds ratio , OR : 4.27 ; 95 % confidence interval , CI : 1.5–12 ) , the total score of the St. George ’s Respiratory Question naire ≧50 points ( OR : 2.36 ; 95 % CI : 1.03–5.04 ) and PaCO2 at discharge ≧45 mm Hg ( OR : 2.18 ; 95 % CI : 0.84–5.06 ) . With this model , the probability of readmission for patients without any of these variables was 7 % , while it was 70 % for the patients with all three variables present . Conclusion : The combination of quality of life , hospitalization for COPD in the previous year and hypercapnia at discharge are useful predictors of readmission at 1 year BACKGROUND The peripheral blood eosinophil count might help identify those patients with chronic obstructive pulmonary disease ( COPD ) who will experience fewer exacerbations when taking inhaled corticosteroids ( ICS ) . Previous post-hoc analyses have proposed eosinophil cutoffs that are both arbitrary and limited in evaluating complex interactions of treatment response . We modelled eosinophil count as a continuous variable to determine the characteristics that determine both exacerbation risk and clinical response to ICS in patients with COPD . METHODS We analysed data from three AstraZeneca r and omised controlled trials of budesonide-formoterol in patients with COPD with a history of exacerbations and available blood eosinophil counts . Patients with any history of asthma were excluded . Negative binomial regression analysis was done using splines for modelling of continuous variables to study the primary outcome of annual exacerbation rate adjusted for exposure time and study design . The trials are registered with Clinical Trials.gov , NCT00206167 , NCT00206154 , and NCT00419744 . FINDINGS 4528 patients were studied . A non-linear increase in exacerbations occurred with increasing eosinophil count in patients who received formoterol alone . At eosinophil counts of 0·10 × 109 cells per L or more , a significant treatment effect was recorded for exacerbation reduction with budesonide-formoterol compared with formoterol alone ( rate ratio 0·75 , 95 % CI 0·57 - 0·99 ; pinteraction=0·015 ) . Interactions were observed between eosinophil count and the treatment effects of budesonide-formoterol over formoterol on St George 's Respiratory Question naire ( pinteraction=0·0043 ) and pre-bronchodilator FEV1 ( linear effect p<0·0001 , pinteraction=0·067 ) . Only eosinophil count and smoking history were independent predictors of response to budesonide-formoterol in reducing exacerbations ( eosinophil count , pinteraction=0·013 ; smoking history , pinteraction=0·015 ) . INTERPRETATION In patients with COPD treated with formoterol , blood eosinophil count predicts exacerbation risk and the clinical response to ICS . FUNDING AstraZeneca BACKGROUND Reducing the probability of future exacerbations is one of the main goals of pulmonary rehabilitation ( PR ) in COPD . Recent studies identified predictors of future exacerbations . However , PR might alter both predictors and number of exacerbations . OBJECTIVES This secondary analysis examined which predictors assessed at both the beginning and the end of PR predict the risk of moderate ( i.e. use of cortisone and /or antibiotics ) and severe ( hospitalization ) exacerbations in the year after PR . METHODS A total of n = 383 COPD patients ( 34.7 % female , mean age = 57.8 years ( SD = 7.1 ) , mean FEV1%pred = 51.0 ( SD = 14.9 ) ) who attended a 3-week inpatient PR were included . Number of moderate and severe exacerbations were assessed one year after PR ( T2 ) via question naires . Potential predictors were assessed at the beginning ( T0 ) and the end ( T1 ) of PR . Negative binomial regression models were used . RESULTS The mean numbers of severe (Ms)/moderate ( Mm ) exacerbations in the year after PR ( Ms , t2 = 0.19 ; Mm , t2 = 1.07 ) was reduced compared to the numbers of exacerbations in the year before PR ( Ms , t1 = 0.50 , p < 0.001 ; Mm , t1 = 1.21 , p = 0.051 ) . Previous exacerbations , retirement , change in dyspnea ( for severe exacerbations ) and dyspnea at T1 ( for moderate exacerbations ) were identified as significant predictors . CONCLUSIONS PR might alter associations between predictors and future exacerbations . Dyspnea at the end of PR or change in dyspnea are better predictors than dyspnea at the beginning of PR BACKGROUND Chronic obstructive pulmonary disease ( COPD ) exacerbation increases mortality and re sources used associated with hospitalization . We studied whether early home monitoring reduces the rate of readmission and if there are any predictor variables . PATIENTS AND METHODS We performed a prospect i ve , controlled , parallel-group study in patients who were hospitalized for COPD . Patients whose residence was within less than 15 km from the hospital were assigned to an interventional group ( home visits by nurses about 48 - 72hours after discharge ) , the remainder were assigned to a conventional care group . The rate of rehospitalization within the first month was compared between the two groups , as well as those variables that showed a predictive capability . RESULTS Seventy one patients were included : 35 in the conventional care group and 36 in the interventional group . In the latter , the treatment was modified in 13 patients ( 36 % ) . The hospital readmission rate was 17 % , which was similar in both groups ( P=.50 ) . For every 5-year increase in age , the risk for readmission was 2.54 ( 95%CI , 1.06 - 5.07 ) and for each increase of 10mmHg in PaCO(2 ) , the risk of readmission was 8.34 ( 95%CI , 2.43 - 18.55 ) . CONCLUSIONS Early home monitoring did not decrease the readmission rate during the first month . Older age and high PaCO(2 ) are factors that identify the group with a high risk for rehospitalization IMPORTANCE Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease ( COPD ) have profound and long-lasting adverse effects on patients . OBJECTIVE To test the hypothesis that elevated levels of inflammatory biomarkers in individuals with stable COPD are associated with an increased risk of having exacerbations . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study examining 61,650 participants with spirometry measurements from the Copenhagen City Heart Study ( 2001 - 2003 ) and the Copenhagen General Population Study ( 2003 - 2008 ) . Of these , 6574 had COPD , defined as a ratio between forced expiratory volume in 1 second ( FEV1 ) and forced vital capacity below 0.7 . MAIN OUTCOMES AND MEASURES Baseline levels of C-reactive protein ( CRP ) and fibrinogen and leukocyte count were measured in participants at a time when they were not experiencing symptoms of exacerbations . Exacerbations were recorded and defined as short-course treatment with oral corticosteroids alone or in combination with an antibiotic or as a hospital admission due to COPD . Levels of CRP and fibrinogen and leukocyte count were defined as high or low according to cut points of 3 mg/L , 14 μmol/L , and 9 ×10(9)/L , respectively . RESULTS During follow-up , 3083 exacerbations were recorded ( mean , 0.5/participant ) . In the first year of follow-up , multivariable-adjusted odds ratios for having frequent exacerbations were 1.2 ( 95 % CI , 0.7 - 2.2 ; 17 events/1000 person-years ) for individuals with 1 high biomarker , 1.7 ( 95 % CI , 0.9 - 3.2 ; 32 events/1000 person-years ) for individuals with 2 high biomarkers , and 3.7 ( 95 % CI , 1.9 - 7.4 ; 81 events/1000 person-years ) for individuals with 3 high biomarkers compared with individuals who had no elevated biomarkers ( 9 events/1000 person-years ; trend : P = 2 × 10(-5 ) ) . Corresponding hazard ratios using maximum follow-up time were 1.4 ( 95 % CI , 1.1 - 1.8 ) , 1.6 ( 95 % CI , 1.3 - 2.2 ) , and 2.5 ( 95 % CI , 1.8 - 3.4 ) , respectively ( trend : P = 1 × 10(-8 ) ) . The addition of inflammatory biomarkers to a basic model including age , sex , FEV1 percent predicted , smoking , use of any inhaled medication , body mass index , history of previous exacerbations , and time since most recent prior exacerbation improved the C statistics from 0.71 to 0.73 ( comparison : P = 9 × 10(-5 ) ) . Relative risks were consistent in those with milder COPD , in those with no history of frequent exacerbations , and in the 2 studies separately . The highest 5-year absolute risks of having frequent exacerbations in those with 3 high biomarkers ( vs no high biomarkers ) were 62 % ( vs 24 % ) for those with Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) grade s C-D ( n = 558 ) , 98 % ( vs 64 % ) in those with a history of frequent exacerbations ( n = 127 ) , and 52 % ( vs 15 % ) for those with GOLD grade s 3 - 4 ( n = 465 ) . CONCLUSIONS AND RELEVANCE Simultaneously elevated levels of CRP and fibrinogen and leukocyte count in individuals with COPD were associated with increased risk of having exacerbations , even in those with milder COPD and in those without previous exacerbations . Further investigation is needed to determine the clinical value of these biomarkers for risk stratification BACKGROUND Despite its large clinical and economic significance , measuring and improving the outcomes of patients hospitalized for chronic obstructive pulmonary disease ( COPD ) is only beginning to emerge as a national priority for policy makers and payers . OBJECTIVE To facilitate the public reporting of hospital outcomes , we developed a risk-st and ardized measure of hospital 30-day mortality for patients admitted with exacerbation of COPD . DESIGN Hierarchical logistic regression model . SETTING / PATIENTS Medicare Part A and Part B cl aims in a r and om sample of half of all admissions for patients admitted to acute care hospitals in 2008 ( development cohort ) and remaining 2008 admissions ( validation cohort ) . We also assessed model performance and predictive ability in 2007 and 2009 data . MEASUREMENTS Hospital risk-st and ardized 30-day mortality rates . RESULTS The model development sample consisted of 150,035 admissions at 4537 nonfederal acute care US hospitals , with a mean unadjusted hospital 30-day mortality rate of 8.6 % . The mean risk-st and ardized mortality rate was 8.6 % and ranged from 5.9 % to 13.5 % . The development and validation models had good discrimination ( areas under the receiver operating characteristic curve 0.72 and 0.72 , respectively ) and predictive ability ( predicted mortality at the 1st and 10th deciles 1.5 % , 23.7 % , and 1.6 % , 23.8 % , respectively ) and showed no evidence of over-fitting . CONCLUSIONS A 30-day mortality model based on administrative cl aims had similar discrimination to other public reporting models and can be used to compare risk-adjusted outcomes for patients with exacerbations of COPD and to track changes in outcomes over time . The high mortality and variation in rates across institutions suggest opportunities to improve quality of care Background Hospitalisation for acute exacerbations of COPD is associated with high risk of readmission . However , no tool has been vali date d to stratify patients at discharge for risk of readmission . Aim To evaluate the ability of the 4 m gait speed ( 4MGS ) , a surrogate marker of frailty , to predict risk of future readmission in hospitalised patients with an acute exacerbation of COPD ( AE COPD ) . Methods 213 patients hospitalised with an AE COPD were recruited prospect ively . 4MGS was measured on day of discharge . Logistic regression models were used to assess the association between 4MGS and readmission at 90 days after discharge . Results Baseline characteristics of the cohort : 52 % men ; mean age 72 years ; median FEV1 35%predicted . Mean ( SD ) 4MGS at hospital discharge was 0.61 ( 0.26 ) ms−1 . Significant increased rates of all-cause readmission at 90 days were seen across quartiles of decreasing 4MGS ( Q4 fastest : 11.5 % ; Q3 : 20.4 % ; Q2 : 30.2 % ; Q1 slowest : 48.2 % ; ptrend<0.001 ) . Compared with Q4 , those in the slowest 4MGS quartile had unadjusted ORs ( 95 % CIs ) for 90-day readmission of 7.12 ( 2.61 to 19.44 ) for the whole cohort and 11.56 ( 3.08 to 43.35 ) in those aged 65 or over . A multivariate model incorporating 4MGS , Charlson Index , hospital admission in past year , FEV1%predicted and number of exacerbations in past year in those aged 65 or over predicted 90-day readmission with a C-statistic of 0.86 . Conclusions The 4MGS , a surrogate marker of physical frailty , independently predicts the risk of readmission in older patients hospitalised for acute exacerbation of COPD . Trial registration number NCT01507415 Abstract Although pharmacological treatment of COPD exacerbation ( COPD E ) includes antibiotics and systemic steroids , a proportion of patients show worsening of symptoms during hospitalization that characterize treatment failure . The aim of our study was to determine in-hospital predictors of treatment failure ( ≤ 7 days ) . Prospect i ve data on 110 hospitalized COPD E patients , all treated with antibiotics and systemic steroids , were collected ; on the seventh day of hospitalization , patients were divided into treatment failure ( n = 16 ) or success ( n = 94 ) . Measures of inflammatory serum biomarkers were recorded at admission and at day 3 ; data on clinical , laboratory , microbiological , and severity , as well data on mortality and readmission , were also recorded . Patients with treatment failure had a worse lung function , with higher serum levels of C-reactive protein ( CRP ) , procalcitonin ( PCT ) , tumour necrosis factor-alpha ( TNF-α ) , interleukin ( IL ) 8 , and IL-10 at admission , and CRP and IL-8 at day 3 . Longer length of hospital stay and duration of antibiotic therapy , higher total doses of steroids and prevalence of deaths and readmitted were found in the treatment failure group . In the multivariate analysis , + 1 mg/dL of CRP at admission ( OR , 1.07 ; 95 % CI , 1.01 to 1.13 ) and use of penicillins or cephalosporins ( OR , 5.63 ; 95 % CI , 1.26 to 25.07 ) were independent variables increasing risk of treatment failure , whereas cough at admission ( OR , 0.20 ; 95 % CI , 0.05 to 0.75 ) reduces risk of failure . In hospitalized COPD E patients CRP at admission and use of specific class of antibiotics predict in-hospital treatment failure , while presence of cough has a protective role |
11,855 | 19,548,964 | RESULTS Lower pCO(2 ) levels in PD subjects are a consistent finding during the baseline/resting condition , the challenge , and recovery phases .
Tidal volume and minute volume are increased in PD subjects relative to controls during the baseline/resting condition .
However , the most robust finding is a higher than normal respiratory variability , which appears to be a promising factor for the identification of respiratory etiopathological pathways in PD .
Respiratory variability might be a c and i date for a biological marker of PD : an abnormal breathing pattern as found in panic disorder ( PD ) patients compared with controls might indicate instability of the respiratory homeostasis | OBJECTIVE To provide a systematic review of studies investigating respiration in PD and comments on relative inconsistencies . | Previous studies have shown unequivocally a lack of pituitary-adrenocortical stress hormone activation during lactate-induced panic attacks despite considerable psychopathological alterations , signs of arousal and several vegetative symptoms regularly occurring during stressful conditions . To study the possible inhibitory action of atrial natriuretic hormone ( ANH ) on adrenocorticotrophic hormone ( ACTH ) and cortisol release in humans , 10 patients with panic disorder ( DSM-III-R ) received sodium lactate and placebo ( 0.9 % saline ) infusions and ten healthy comparison subjects additionally received a 2.5 % saline infusion and the response of ANH , vasopressin , ACTH , cortisol , and several biochemical and physiological cardiovascular parameters were measured . In comparison to placebo , lactate infusion led to enhanced ANH levels in both non-panicking comparison subjects and panickers . Importantly , panickers showed significantly lower baseline levels of ANH than comparison subjects followed by a faster release . No significant concomitant changes in vasopressin , ACTH , and cortisol were observed . During lactate infusion , heart rate was accelerated considerably in the two groups ; in contrast , the reduction of pCO2 indicated an enhanced ventilation only in panickers . The pattern of ANH release can not be attributed simply to either the volume load administered , the cardiac activation or an osmotic effect since neither 0.9 nor 2.5 % saline result ed in comparable effects . Additional central nervous mechanisms must be considered for the increased ANH concentrations in lactate-induced panic attacks . We propose that the release of ANH is an intrinsic mechanism contributing to the apparent unresponsiveness of the pituitary-adrenocortical system in lactate-induced panic attacks . In addition , we surmise that ANH may also play a role in the yet unknown mechanisms for termination of panic attacks , e.g. either by inhibitory actions on the locus coeruleus or by bronchiorelaxation and consecutive decatastrophization Experiments design ed to establish the effects of video games on breathing patterns have led to contradictory results . Several authors reported that video games tended to increase breathing frequency ( i.e. to reduce breath duration ) , whereas others reported the opposite . We postulated that video games contain different psychophysiological components which may have opposite effects on breathing pattern . On the one h and , arousal and emotion may tend to stimulate breathing . On the other , focusing attention on the game may prompt subject to inhibit any movement -- including breathing -- which might be a potential nuisance variable . The aim of this study was to assess the specific effects of the attentional load in an experimental environment characterized by its low emotional impact . We measured breathing variables , cardiac frequency and cortisol levels in 10 healthy children ( mean age = 9.2 + /- 1.5 years ) who were familiar with the environment , the experimenter and the video game . Breath duration rose significantly , from 2.56 to 3.16 s , as a function of game difficulty . Cortisol levels , heart rate and the thoracic contribution to breathing displayed no significant changes . Taken together , these data suggest that focusing attention on the game tended to inhibit breathing and that previous contradictory reports in this respect were due to the confounding effects of emotion BACKGROUND Dysregulated respiratory control may play a role in the pathophysiology of panic disorder . This could be due to abnormalities in brain stem respiratory nuclei or to dysregulation at higher brain levels . Results from previous studies using the doxapram model of panic have yielded an unclear picture . A brief cognitive manipulation reduced doxapram-induced hyperventilation in patients , suggesting that higher level inputs can substantially alter their respiratory patterns . However , respiratory abnormalities persisted , including a striking irregularity in breathing patterns . METHODS To directly study respiratory irregularity , breath-by-breath records of tidal volume ( V(t ) ) and frequency ( f ) from previously studied subjects were obtained . Irregularity was quantified using von Neumann 's statistic and calculation of " sigh " frequency in 16 patients and 16 matched control subjects . Half of each group received a st and ard introduction to the study and half received a cognitive intervention design ed to reduce anxiety/distress responses to the doxapram injection . RESULTS Patients had significantly greater V(t ) irregularity relative to control subjects . Neither the cognitive intervention nor doxapram-induced hyperventilation produced significant changes in V(t ) irregularity . The V(t ) irregularity was attributable to a sighing pattern of breathing that was characteristic of panic patients but not control subjects . Patients also had somewhat elevated f irregularity relative to control subjects . CONCLUSIONS The irregular breathing patterns in panic patients appear to be intrinsic and stable , uninfluenced by induced hyperventilation or cognitive manipulation . Further study of V(t ) irregularity and sighs are warranted in efforts to localize dysregulated neural circuits in panic to brain stem or midbrain levels RATIONALE Psychologic factors are increasingly recognized to influence the onset and course of asthma . Previous cross-sectional community-based studies have provided evidence for a relatively specific association between asthma and panic . OBJECTIVES To examine concurrent and longitudinal associations between asthma and panic in young adults . MEASUREMENTS AND MAIN RESULTS Prospect i ve community-based cohort study of young adults ( n = 591 ) followed between ages 19 and 40 . Information was derived from six subsequent semistructured diagnostic interviews conducted by professionals . Cross-sectionally ( over the whole study period ) , asthma was more strongly associated with panic disorder ( odds ratio [ OR ] = 4.0 ; 95 % confidence interval [ CI ] , 1.7 , 9.3 ) than with any panic , which included panic disorder and panic attacks ( OR = 2.1 ; 95 % CI , 1.1 , 4.5 ) . Longitudinally , after adjusting for potentially confounding variables , active asthma predicted subsequent panic disorder ( OR = 4.5 ; 95 % CI , 1.1 , 20.1 ) , and the presence of panic disorder predicted subsequent asthma activity ( OR = 6.3 ; 95 % CI , 2.8 , 14.0 ) . Asthma predicted any panic ( OR = 2.7 ; 95 % CI , 1.1 , 7.1 ) , whereas any panic did not predict subsequent asthma activity . Associations were stronger in smokers than in nonsmokers , and stronger in women than in men . Smoking , early-childhood anxiety , and a family history of allergy were important confounders of the asthma-panic association . CONCLUSIONS This is the first long-term follow-up study on asthma and panic . It showed dose-response-type relationships between panic and asthma , and bidirectional longitudinal associations between the two conditions . It provided evidence for familial factors and smoking as possible shared etiologic explanations Progesterone administration increase VE in man , but its effects on ventilatory response to hypercapnia and hypoxia have not been well documented . Accordingly , VE , HVR , and HCVR were measured during placebo and MPA administration in 11 normal men . The effect of MPA ( 20 mg orally q 8 hr for 32 hr ) on T degrees , metabolic rate ( VO2 and VCO2 ) was also determined . With MPA , T degrees , rose 0.4 degrees C + /- 0.0008 ( S.E.M. ) p less than 0.0001 ) , VE increased 0.46 + /- 0.16 L/min ( p less than 0.01 ) , and VO2 and VCO2 did not change significantly . HCVR ( measured under hyperoxic conditions during rebreathing ) increased significantly ( P less than 0.01 ) from 2.9 + /- 0.33 L/min/mm Hg ( placebo ) to 4.0 + /- 0.29 ( MPA ) . HVR was measured as the shape parameter A , so that when A increased , HVR was augmented . During MPA , HVR increased from A = 132 + /- 19.1 to 179 + /- 20.5 ( P less than 0.02 ) . We conclude that 60 mg of MPA daily in normal men increases VE and chemosensitivity as measured by the ventilatory response to hypercapnia and hypoxia The goals of this study were to a ) confirm prior evidence that the respiratory stimulant doxapram induces panic attacks and produces excessive hyperventilation in patients with panic disorder and b ) explore the impact of cognitive mediators on symptom and respiratory responses . Method : Thirty-two subjects ( 16 patients and 16 controls ) received doxapram ( 0.5 mg/kg ) and placebo infusions while symptom , respiratory , and heart rate responses were monitored . Subjects were r and omly assigned to receive either a st and ard introduction or a cognitive intervention design ed to reduce the panic responses of panic patients to laboratory challenges . Results : Doxapram was a potent and specific panicogenic agent , inducing panic in 75 % of patients and 12.5 % of controls . Compared with controls , patients also showed a greater decrease in end tidal carbon dioxide ( CO2 ) and greater increases in minute ventilation , respiratory frequency , and heart rate . The cognitive intervention substantially attenuated the excessive hyperventilatory response of patients but did not fully normalize their breathing patterns . Tidal volume was the only respiratory measure not significantly altered by the cognitive intervention . Conclusions : In patients with panic disorder , doxagram ( 0.5 mg/kg ) triggers panic attacks about as potently as 7 % CO2 and more potently than 5 % CO2 or lactate . Psychological factors can modulate the appearance of ventilatory abnormalities in panic patients , but persistent respiratory disturbances were still seen . Psychological factors and respiratory physiology both appear to be important phenomena in laboratory panic OBJECTIVE The authors assessed the substance and diagnostic specificity of carbon-dioxide-induced panic since , in addition to the specific biochemical effects of inhaled carbon dioxide ( CO2 ) , simple physiologic distress is also frequently implicated as a panicogenic factor during respiratory challenge studies with CO2 in patients with anxiety disorders . METHOD Eighteen patients with panic disorder , 20 with social phobia , and 23 psychiatrically normal subjects inhaled a mixture of 35 % CO2 and 65 % O2 for 30 seconds through a face mask . They also breathed for 30 seconds through a valve reducing the diameter of the airway . A double-blind , counterbalanced , r and omized design was used . RESULTS In spite of important similarities between the two interventions , including the induction of equal amounts of subjective respiratory distress , carbon dioxide inhalation was significantly more potent than increased airway resistance in provoking panic in the anxiety disorder patients . The patients with panic disorder were significantly more sensitive to CO2 than were the patients with social phobia or the normal subjects . CONCLUSIONS Carbon dioxide inhalation appears to have a specific panicogenic effect in panic patients that goes beyond simple breathlessness BACKGROUND Disordered breathing among patients with panic disorder , including hyperventilation during attacks and increased anxiogenic response to carbon dioxide ( CO2 ) inhalation , is well established . We wished to assess whether there is a change in the physiological response to CO2 after patients have undergone antipanic therapy with either tricyclic antidepressants or cognitive behavioral therapy ( CBT ) . METHODS Twenty-nine patients with panic disorder underwent baseline CO2 sensitivity testing using the traditional Read rebreathing method and then received either antidepressant treatment ( n = 21 ) or CBT ( n = 8) . After completing treatment , CO2 testing was repeated . A comparison sample of 14 normal volunteers also had two CO2 sensitivity tests , separated by an average of 21.6 ( SD = 8.8 ) weeks . RESULTS Using a liberal st and ard , in which all CO2 sensitivity tests whose correlations between minute ventilation and end-tidal CO2 were at least .75 were used , patients , but not controls , demonstrated a significant reduction in CO2 sensitivity between the first and second test . Using a more conservative .90 correlation st and ard reduced the sample size available and result ed in trend reduction in patients but no significant change in controls . There was a suggestion that the change was most pronounced in treatment responders , although the number of patient nonresponders is extremely small in this sample . CONCLUSIONS These data indicate that treatment reduces CO2 sensitivity in patients with panic disorder . We speculate that manipulation of the serotonergic and noradrenergic neurotransmission systems , both known to play a role in the control of respiration , may have a specific effect in reducing respiratory hyperactivity in panic disorder Panic disorder ( PD ) and asthma share many common characteristics and have been found in epidemiological studies to be significantly comorbid . To investigate possible reasons for this overlapping , the authors evaluated 51 patients with asthma , assessing the prevalence of PD and sporadic panic attacks , the temporal relationship between these two disorders , and the familial risk for PD in the families of asthmatics . The results showed significantly higher prevalences of PD , sporadic panic attacks , and social phobia in asthmatics than those reported for the general population . In 9 ( 90 % ) of the asthmatics with PD , asthma appeared first . Finally , the morbidity risk for PD in families of asthmatics with PD ( 13.5 % ) was significantly higher than in families of asthmatics without evidence of panic ( 2 % ) . Our results suggest that the high prevalence of PD in asthmatics might be related to a facilitating effect of asthma on the development of PD in subjects with familial predisposition to PD In the present study we investigated the effect of mental stress on respiration using unpleasant sounds . To compare the center output of each stimuli , subjects took part in one session divided into two phases : a mental stress test and a physical loading test . The purpose of this study was not only to investigate ventilatory response in emotions caused by mental stress and physical load , but also to determine the relationship between respiratory pattern and personality . Ten normal subjects were measured for VE ( minute ventilation ) , VT ( tidal volume ) , RR ( respiratory rate ) , Vo2 ( O2 consumption ) , Vco2 ( CO2 production ) and FETco2 ( end-tidal CO2 concentration ) on a breath-by-breath basis ; the subjects were given Spielberger 's State Trait Anxiety Inventory ( STAI ) before beginning this experiment . Unpleasant emotions caused by mental stress altered the breathing pattern . VE increase was achieved by the combination of VT and RR disregarding the subjects ' personality . However , subjects with high anxiety RR increased more than VT result ing in a positive correlation between the trait anxiety score and RR . We found that a dominant RR increase was observed not only in the mental stress test but also in the physical loading test . In the physical load , there was a positive correlation between the state anxiety score and RR . These results indicate that respiratory patterns are related to personality anxiety . These findings may provide important evidence relating respiratory function to psychological aspects The Hyperventilation Provocation Test ( HVPT ) has become a routine procedure in the diagnosis of hyperventilation syndrome ( HVS ) . During an HVPT the patient voluntarily overbreathes for several minutes to produce hypocapnia . The test is considered positive if the induced symptoms are recognized by the patient as similar to those experienced in daily life . The present study tests the assumption that hypocapnia is the primary trigger for symptoms during an HVPT . In a r and omized double-blind crossover design . 115 patients suspected of HVS and 40 healthy controls performed an HVPT and a placebo test ( PT , isocapnic overbreathing ) . The HVPT induced more symptoms than the PT , especially more neuromuscular symptoms , cerebral symptoms , paresthesias , and temperature sensations . However , the absolute difference between the number of symptoms induced by the HVPT and PT was small . In patients , the PT induced 66 % of symptoms induced by the HVPT . In the control group this percentage was 60 % . The low specificity of the HVPT implies that symptom recognition during the HVPT is invalid as a diagnostic criterion for HVS Cholecystokinin-tetrapeptide ( CCK-4 ) and placebo were injected to 11 panic disorder patients . CCK-4 induced a panic attack identical to spontaneous panic attacks in all patients ; placebo did not induce any attacks . The role of CCK-4 in anxiety disorders is discussed During Phase II of the Cross-National Panic Study , descriptions of the patient 's last severe panic attack were collected for 1168 patients . Statistical analysis indicated that patients could be divided into two groups , characterised by the presence or absence of prominent respiratory symptoms . The two groups did not differ on demographic variables or coexisting diagnoses , but they did differ on psychopathology on entry to the study and treatment outcome . The group with prominent respiratory symptoms suffered more spontaneous panic attacks and responded to imipramine , whereas the group without prominent respiratory symptoms suffered more situational panic attacks and responded more to alprazolam . It is important to distinguish spontaneous and situational panic attacks , to aid choice of treatment Disordered breathing may play an important role in the pathophysiology of panic disorder . Several studies have now indicated that panic disorder patients have greater respiratory variability than normal controls . In this study , we examine baseline respiratory measures in four diagnostic groups to determine whether greater respiratory variability is specific to panic disorder and whether effective anti-panic treatment alters respiratory variability . Patients with panic disorder , major depression , or premenstrual dysphoric disorder , and normal control subjects underwent two respiratory exposures ( 5 % and 7 % CO(2 ) inhalation ) , while in a canopy system . Panic disorder patients returned after 12 weeks of either anti-panic medication or cognitive behavioral therapy , and were retested . Normal control subjects were also retested after a period of 12 weeks . Panic disorder patients had significantly greater respiratory variability at baseline than normal control subjects and patients with major depression . The premenstrual dysphoric patients also had greater variability than the normal control group . Panic disorder patients who panicked to 7 % CO(2 ) inhalation had significantly greater baseline variability than panic disorder patients who did not panic . Anti-panic treatment did not significantly alter baseline respiratory variability . Our data suggest that increased respiratory variability may be an important trait feature for some panic disorder patients and may make them more vulnerable to CO(2)-induced panic BACKGROUND Hyperventilation syndrome ( HVS ) describes a set of somatic and psychological symptoms thought to result from episodic or chronic hyperventilation . Recognition of symptoms during the hyperventilation provocation test ( HVPT ) is the most widely used criterion for diagnosis of HVS . We have investigated the validity of the HVPT and of the concept of HVS . METHODS In a r and omised , double-blind , crossover design , the ability of 115 patients with suspected HVS to recognise symptoms during the HVPT was compared with the ability to recognise symptoms during a placebo test ( isocapnic overbreathing , with carbon dioxide levels maintained by manual titration ) . 30 patients who had positive results on the HVPT underwent ambulatory transcutaneous monitoring of pCO2 to ascertain whether they hyperventilated during spontaneous symptom attacks . FINDINGS Of the 115 patients who underwent the HVPT and the placebo test , 85 ( 74 % ) reported symptom recognition during the HVPT ( positive diagnosis HVS ) . Of that subset , 56 were also positive on the placebo test ( false-positive ) , and 29 were negative on the placebo test ( true-positive ) . False-positive and true-positive patients did not differ in symptom profile or in physiological variables . During ambulatory monitoring ( 15 true-positive , 15 false-positive ) 22 attacks were registered . Transcutaneous end-tidal , pCO2 decreased during only seven . The decreases were slight and apparently followed the onset of the attack , which suggests that hyperventilation is a consequence rather than a cause of the attack . There were no apparent differences between false-positive and true-positive patients . INTERPRETATION The HVPT is invalid as a diagnostic test for HVS . Hyperventilation seems a negligible factor in the experience of spontaneous symptoms . The term HVS should be avoided |
11,856 | 25,108,741 | The use of the EC can reduce the number of cigarettes smoked and withdrawal symptoms , but the AEs reported are mainly related to a short period of use . | BACKGROUND To investigate the efficacy and the adverse effects ( AEs ) of the electronic cigarette , we performed a systematic review of published studies . | Background Cigarette smoking is a tough addiction to break . Therefore , improved approaches to smoking cessation are necessary . The electronic-cigarette ( e-Cigarette ) , a battery-powered electronic nicotine delivery device ( ENDD ) resembling a cigarette , may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption . Efficacy and safety of these devices in long-term smoking cessation and /or smoking reduction studies have never been investigated . Methods In this prospect i ve proof-of-concept study we monitored possible modifications in smoking habits of 40 regular smokers ( unwilling to quit ) experimenting the ' Categoria ' e-Cigarette with a focus on smoking reduction and smoking abstinence . Study participants were invited to attend a total of five study visits : at baseline , week-4 , week-8 , week-12 and week-24 . Product use , number of cigarettes smoked , and exhaled carbon monoxide ( eCO ) levels were measured at each visit . Smoking reduction and abstinence rates were calculated . Adverse events and product preferences were also review ed . Results Sustained 50 % reduction in the number of cig/day at week-24 was shown in 13/40(32.5 % ) participants ; their median of 25 cigs/day decreasing to 6 cigs/day ( p < 0.001 ) . Sustained 80 % reduction was shown in 5/40(12.5 % ) participants ; their median of 30 cigs/day decreasing to 3 cigs/day ( p = 0.043 ) . Sustained smoking abstinence at week-24 was observed in 9/40(22.5 % ) participants , with 6/9 still using the e-Cigarette by the end of the study . Combined sustained 50 % reduction and smoking abstinence was shown in 22/40 ( 55 % ) participants , with an overall 88 % fall in cigs/day . Mouth ( 20.6 % ) and throat ( 32.4 % ) irritation , and dry cough ( 32.4 % ) were common , but diminished substantially by week-24 . Overall , 2 to 3 cartridges/day were used throughout the study . Participants ' perception and acceptance of the product was good . Conclusion The use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit ( http:// Clinical Trials.gov number NCT01195597 ) Background While electronic cigarettes are forbidden in several countries , their sales are exploding in many others . Although e-cigarettes have been proposed as long-term substitutes for traditional smoking or as a tool for smoking cessation , very scarce data are available on their efficacy and safety . We describe the protocol of a 5-year multicentric prospect i ve study aim ed to evaluate short- and long-term adherence to e-cigarette smoking and the efficacy of e-cigarettes in reducing and /or quitting traditional cigarette smoking . The study will also compare the health effects of electronic vs traditional vs mixed cigarette smoking . Methods / design From June to December 2013 , we will enroll adult smokers of : ( EC ) e-cigarettes ( self-reported inhaling ≥ 50 puffs per week since ≥ 6 months ) ; ( TC ) traditional cigarettes ( ≥ 1 per day since ≥ 6 m ) ; ( Mixed ) both electronic and traditional cigarettes ( ≥1 per day since ≥ 6 m ) . Eligible subjects will be requested participation through newspaper advertisements and direct contact at the shops . Each subject will have to compile a structured question naire at enrolment and after 6 , 12 , 24 , 36 and 60 months . The level of carbon monoxide in expired after breath will be evaluated in all subjects declaring no traditional cigarette smoking in any follow-up phase , using portable carbon monoxide analyzers . The primary outcomes are traditional smoking cessation rates and number of smoked cigarettes . Secondary outcomes include adherence to e-cigarettes , self-reported adverse events , quality of life , and time to hospital admission for one among cardiovascular diseases , chronic obstructive pulmonary diseases , cancer of the lung , esophagus , larynx , oral cavity , bladder , pancreas , kidney , stomach , cervix , and myeloid leukemia . Admissions will be checked using official discharge data of the Abruzzo Region . A minimum of 500 subjects in each group will be enrolled , for a total of 1500 participants . Cox proportional hazards analysis will be used to calculate adjusted relative hazards of smoking cessation by each variable . Discussion Data on long-term efficacy and safety of e-cigarettes will be of utmost importance to form the basis for guidelines and regulatory decisions on e-cigarettes . Trial registration The protocol has been registered ( NCT01785537 ) and approved by the Ethics Committee of the University of Chieti ( Record n. 6 ; 25 - 03 - 2013 ) Background Electronic cigarettes ( e-cigarettes ) are becoming increasingly popular with smokers worldwide . Users report buying them to help quit smoking , to reduce cigarette consumption , to relieve tobacco withdrawal symptoms , and to continue having a ‘ smoking ’ experience , but with reduced health risks . Research on e-cigarettes is urgently needed in order to ensure that the decisions of regulators , healthcare providers and consumers are based on science . Methods ECLAT is a prospect i ve 12-month r and omized , controlled trial that evaluates smoking reduction/abstinence in 300 smokers not intending to quit experimenting two different nicotine strengths of a popular e-cigarette model ( ‘ Categoria ’ ; Arbi Group Srl , Italy ) compared to its non-nicotine choice . GroupA ( n = 100 ) received 7.2 mg nicotine cartridges for 12 weeks ; GroupB ( n = 100 ) , a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges ; GroupC ( n = 100 ) received no-nicotine cartridges for 12 weeks . The study consisted of nine visits during which cig/day use and exhaled carbon monoxide ( eCO ) levels were measured . Smoking reduction and abstinence rates were calculated . Adverse events and product preferences were also review ed . Results Declines in cig/day use and eCO levels were observed at each study visits in all three study groups ( p<0.001 vs baseline ) , with no consistent differences among study groups . Smoking reduction was documented in 22.3 % and 10.3 % at week-12 and week-52 respectively . Complete abstinence from tobacco smoking was documented in 10.7 % and 8.7 % at week-12 and week-52 respectively . A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study . Participants ’ perception and acceptance of the product under investigation was satisfactory . Conclusion In smokers not intending to quit , the use of e-cigarettes , with or without nicotine , decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects . Trial Registration Clinical Trials.gov NCT01164072 Electronic cigarettes ( e-cigarettes ) are battery operated devices that deliver nicotine via inhaled vapour . Few studies have evaluated acute effects on craving and mood , and none have explored effects on cognition . This study aim ed to explore the effects of the White Super e-cigarette on desire to smoke , nicotine withdrawal symptoms , attention and working memory . Eighty-six smokers were r and omly allocated to either : 18 mg nicotine e-cigarette ( nicotine ) , 0 mg e-cigarette ( placebo ) , or just hold the e-cigarette ( just hold ) conditions . Participants rated their desire to smoke and withdrawal symptoms at baseline ( T1 ) , and five ( T2 ) and twenty ( T3 ) minutes after using the e-cigarette ad libitum for 5 min . A subset of participants completed the Letter Cancellation and Brown-Peterson Working Memory Tasks . After 20 min , compared with the just hold group , desire to smoke and some aspects of nicotine withdrawal were significantly reduced in the nicotine and placebo group ; the nicotine e-cigarette was superior to placebo in males but not in females . The nicotine e-cigarette also improved working memory performance compared with placebo at the longer interference intervals . There was no effect of nicotine on Letter Cancellation performance . To conclude , the White Super e-cigarette alleviated desire to smoke and withdrawal symptoms 20 min after use although the nicotine content was more important for males . This study also demonstrated for the first time that the nicotine e-cigarette can enhance working memory performance . Further evaluation of the cognitive effects of the e-cigarette and its efficacy as a cessation tool is merited Background : Cigarette smoking is a tough addiction to break . This dependence is the most common dual diagnosis for individuals with schizophrenia . Currently three effective drugs are approved for smoking cessation : nicotine replacement therapy ( NRT ) , varenicline and bupropion . However , some serious side effects of varenicline have been reported , including depression , suicidal thoughts , and suicide . The use of bupropion also has side effects . It should not be used by people who have epilepsy or any condition that lowers the seizure threshold , nor by people who take a specific class of drugs called monoamine oxidase inhibitors . Hence , there are pharmacodynamic reason to believe they could precipitate or exacerbate psychosis . For its capacity to deliver nicotine and provide a coping mechanism for conditioned smoking cues by replacing some of the rituals associated with smoking gestures , electronic-cigarettes may reduce nicotine withdrawal symptoms without serious side effects . Our recent work with ECs in healthy smokers not intending to quit consistently show surprisingly high success rates . We hypothesised that these positive findings could be replicated in difficult patients with schizophrenia This tool may help smokers with schizophrenia remain abstinent during their quitting attempts or to reduce cigarette consumption . Efficacy and safety of these devices in long-term smoking cessation and /or smoking reduction studies have never been investigated for this special population . Methods : In this study we monitored possible modifications in smoking habits of 14 smokers ( not intending to quit ) with schizophrenia experimenting with the “ Categoria ” e-Cigarette with a focus on smoking reduction and smoking abstinence . Study participants were invited to attend six study visits : at baseline , week-4 , week-8 , week-12 week-24 and week 52 . Product use , number of cigarettes smoked , carbon monoxide in exhaled breath ( eCO ) and positive and negative symptoms of schizophrenia levels were measured at each visit . Smoking reduction and abstinence rates were calculated . Adverse events were also review ed . Results : Sustained 50 % reduction in the number of cig/day at week-52 was shown in 7/14 ( 50 % ) participants ; their median of 30 cig/day decreasing significantly to 15 cig/day ( p = 0.018 ) . Sustained smoking abstinence at week-52 was observed in 2/14 ( 14.3 % ) participants . Combined sustained 50 % reduction and smoking abstinence was shown in 9/14 ( 64.3 % ) participants . Nausea was observed in 2/14 ( 14.4 % ) of participants , throat irritation in 2/14 ( 14.4 % ) of participants , headache in 2/14 ( 14.4 % ) of participants , and dry cough in 4/14 ( 28.6 % ) of participants . However , these adverse events diminished substantially by week-24 . Overall , one to two cartridges/day were used throughout the study . Positive and negative symptoms of schizophrenia are not increased after smoking reduction/cessation in patients using e-cigarettes . Conclusions : We have shown for the first time that the use of e-cigarette substantially decreased cigarette consumption without causing significant side effects in chronic schizophrenic patients who smoke not intending to quit . This was achieved without negative impacts on the symptoms of schizophrenia as assessed by SAPS and SANS symptoms scales AIMS To provide an initial abuse liability assessment of an electronic cigarette ( EC ) in current tobacco cigarette smokers . DESIGN The first of four within-subject sessions was an EC sampling session that involved six , 10-puff bouts ( 30 seconds inter-puff interval ) , each bout separated by 30 minutes . In the remaining three sessions participants made choices between 10 EC puffs and varying amounts of money , 10 EC puffs and a varying number of own br and cigarette ( OB ) puffs , or 10 OB puffs and varying amounts of money using the multiple-choice procedure ( MCP ) . The MCP was completed six times at 30-minute intervals , and one choice was reinforced r and omly at each trial . SETTING Clinical laboratory . PARTICIPANTS Twenty current tobacco cigarette smokers . MEASUREMENTS Sampling session outcome measures included plasma nicotine , cardiovascular response and subjective effects . Choice session outcome was the cross-over value on the MCP . FINDINGS EC use result ed in significant nicotine delivery , tobacco abstinence symptom suppression and increased product acceptability ratings . On the MCP , participants chose to receive 10 EC puffs over an average of $ 1.06 or three OB puffs and chose 10 OB puffs over an average of $ 1.50 ( P < 0.003 ) . CONCLUSIONS Electronic cigarettes can deliver clinical ly significant amounts of nicotine and reduce cigarette abstinence symptoms and appear to have lower potential for abuse relative to traditional tobacco cigarettes , at least under certain laboratory conditions Objectives To measure the short-term effects of an electronic nicotine delivery device ( “ e cigarette ” , ENDD ) on desire to smoke , withdrawal symptoms , acceptability , pharmacokinetic properties and adverse effects . Design Single blind r and omised repeated measures cross-over trial of the Ruyan V8 ENDD . Setting University research centre in Auckl and , New Zeal and . Participants 40 adult dependent smokers of 10 or more cigarettes per day . Interventions Participants were r and omised to use ENDDs containing 16 mg nicotine or 0 mg capsules , Nicorette nicotine inhalator or their usual cigarette on each of four study days 3 days apart , with overnight smoking abstinence before use of each product . Main outcome measures The primary outcome was change in desire to smoke , measured as “ area under the curve ” on an 11-point visual analogue scale before and at intervals over 1 h of use . Secondary outcomes included withdrawal symptoms , acceptability and adverse events . In nine participants , serum nicotine levels were also measured . Results Over 60 min , participants using 16 mg ENDD recorded 0.82 units less desire to smoke than the placebo ENDD ( p=0.006 ) . No difference in desire to smoke was found between 16 mg ENDD and inhalator . ENDDs were more pleasant to use than inhalator ( p=0.016 ) and produced less irritation of mouth and throat ( p<0.001 ) . On average , the ENDD increased serum nicotine to a peak of 1.3 mg/ml in 19.6 min , the inhalator to 2.1 ng/ml in 32 min and cigarettes to 13.4 ng/ml in 14.3 min . Conclusions The 16 mg Ruyan V8 ENDD alleviated desire to smoke after overnight abstinence , was well tolerated and had a pharmacokinetic profile more like the Nicorette inhalator than a tobacco cigarette . Evaluation of the ENDD for longer-term safety , potential for long-term use and efficacy as a cessation aid is needed . Trial registration No.12607000587404 , Australia and New Zeal and Clinical Trials INTRODUCTION Electronic cigarettes ( ECs ) are marketed as nicotine delivery devices . Two studies with EC-naïve participants suggest that ECs deliver little or no nicotine . In those studies , st and ard-sized ECs were used , though experienced EC users often use larger devices that house higher voltage and /or longer lasting batteries . Whether user experience and device characteristics influence EC nicotine delivery is uncertain . The purpose of the present study was to examine the effects of ECs in experienced users who were using their preferred devices . METHODS Eight EC users ( 3 women ) who had been using ECs for at least 3 months , completed one 5-hr session using devices they provided and the flavor/strength nicotine cartridges they selected . Sessions consisted of 4 phases : baseline , 10 puffs ( 30-s interpuff interval ) from the device , 1-hr ad lib puffing period , and a 2-hr rest period ( no puffing ) . Outcome measures in each phase included plasma nicotine concentration , heart rate , and subjective ratings of nicotine/product effects and abstinence symptoms . RESULTS Relative to baseline , plasma nicotine and heart rate increased significantly within 5 min of the first puff and remained elevated throughout the ad lib puffing period . Increases in ratings of direct effects of nicotine and product were observed as well as decreases in abstinence symptoms . CONCLUSIONS User experience and /or device characteristics likely influence EC nicotine delivery and other effects . Systematic manipulation of these and other variables could eluci date conditions that produce intended effects |
11,857 | 25,188,312 | Adjusting for the effect of NRTI backbone , treatment with DTG result ed in significantly higher odds of virologic suppression ( HIV RNA<50 copies/mL ) and increase in CD4 + cells/µL versus ATV/r , DRV/r , EFV , LPV/r , and RPV .
Dolutegravir had better or equivalent changes in total cholesterol , LDL , triglycerides , and lower odds of adverse events and discontinuation due to adverse events compared to all treatments .
Conclusion Three clinical trials of DTG have demonstrated comparable or superior efficacy and safety to DRV , RAL , and EFV in HIV-1–infected treatment-naive patients .
This network meta- analysis suggests DTG is also favorable or comparable to other commonly used third agents ( ATV/r , LPV/r , RPV , and EVG/c ) | Background A network meta- analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head r and omized controlled trials .
We estimated the relative efficacy and safety of dolutegravir ( DTG ) versus third agents currently recommended by guidelines , including ritonavir-boosted atazanavir ( ATV/r ) , ritonavir-boosted darunavir ( DRV/r ) , efavirenz ( EFV ) , cobicistat-boosted elvitegravir ( EVG/c ) , ritonavir-boosted lopinavir ( LPV/r ) , raltegravir ( RAL ) , and rilpivirine ( RPV ) , in treatment-naive HIV-1–infected patients . | BACKGROUND We report data from NEWART , a r and omised phase 4 clinical trial comparing virologic efficacy and safety of nevirapine ( NVP ) vs. ritonavir-boosted atazanavir ( ATV/r ) on a background of tenofovir/emtricitabine ( TDF/FTC ) in HIV-1-infected treatment-naïve patients . This study enrolled patients according to CD4-based initiation criteria for NVP ( < 250 cells/mm(3 ) for women and < 400 cells/mm(3 ) for men ) , to reduce the likelihood of symptomatic hepatic events . NEWART was design ed to support and confirm results from ARTEN , an international trial with similar design and study endpoints . METHODS A total of 152 patients were r and omised 1 : 1 to open-label NVP 200 mg twice daily or ATV/r ( 300/100 mg ) once daily , plus once daily TDF/FTC ( 300/200 mg ) . All participants met CD4(+ ) guidelines at entry . The primary endpoint for non-inferiority was virologic response prior to and at week 48 ( confirmed HIV plasma viral load < 50 copies/ml , without rebound or change in ARVs ) . Safety data , including plasma lipids , were recorded throughout the study . RESULTS The primary endpoint was achieved in 46/75 ( 61.3 % ) and 50/77 ( 64.9 % ) of patients taking NVP and ATV/r , respectively . Frequency of adverse events ( AEs ) was similar between arms , with 88.0 % of NVP-treated patients and 94.8 % of ATV/r-treated patients experiencing at least one AE . Nine patients ( 12 % ) in each arm experienced an AE that led to discontinuation . At week 48 , a significantly greater increase was seen in mean plasma HDL cholesterol ( HDL-C ) in the NVP arm ( 9.6 mg/dl ) vs. the ATV/r arm ( 3.5 mg/dl ) ; p = 0.016 . Also , total cholesterol (TC):HDL-C ratio on-treatment was -0.38 and -0.02 for the NVP and ATV/r arms , respectively ( p = 0.038 ) . CONCLUSIONS Efficacy results were consistent with the ARTEN study demonstrating that NVP was non-inferior to ATV/r when taken in combination with TDF/FTC . Rates of AEs were similar between the two arms , whereas HDL-C increased and TC : HDL-C decreased significantly more in patients taking NVP than ATV/r Introduction : Direct comparison of the efficacy and safety of different agents is needed to guide selection of optimal treatment regimens for therapy-naive HIV-1-infected patients . Methods : Gemini was a 48-week , multicenter , open-label , noninferiority trial in treatment-naive HIV-1-infected adults r and omized to either saquinavir/ritonavir ( SQV/r ) 1000 mg/100 mg twice a day or lopinavir/ritonavir ( LPV/r ) 400 mg/100 mg twice a day , each with emtricitabine/tenofovir 200 mg/300 mg every day . Results : A similar proportion of participants in the SQV/r ( n = 167 ) and LPV/r ( n = 170 ) arms had HIV-1 RNA levels < 50 copies per milliliter at week 48 : 64.7 % vs 63.5 % and estimated difference in proportion for noninferiority : 1.14 % , 96 % confidence interval : −9.6 to11.9 ( P < 0.012 ) , confirming that SQV/r was noninferior to LPV/r treatment . There were no significant differences in week 48 CD4 counts between arms . The rate and severity of adverse events were similar in both groups . There were no significant differences in the median change from baseline between arms in plasma lipids except for triglyceride levels , which were significantly higher in the LPV/r at week 48 . Conclusions : In treatment-naive , HIV-1-infected patients , SQV/r treatment was noninferior in virologic suppression at 48 weeks to LPV/r treatment and offered a better triglyceride profile In a r and omized control trial , Shahin Lockman and colleagues compare nevirapine-based therapy with lopinavir/ritonavir-based therapy for HIV-infected women without previous exposure to antiretroviral treatment Thomas Campbell and colleagues report findings of a r and omized trial conducted in multiple countries regarding the efficacy of antiretroviral regimens with simplified dosing OBJECTIVE To compare the efficacy and safety of fixed-dose abacavir/lamivudine ( ABC/3TC ) and tenofovir/emtricitabine ( TDF/FTC ) with ritonavir-boosted atazanavir ( ATV/r ) in treatment-naïve Japanese patients with HIV-1 infection . METHODS A 96-week multicenter , r and omized , open-label , parallel group pilot study was conducted . The endpoints were times to virologic failure , safety event and regimen modification . RESULTS 109 patients were enrolled and r and omly allocated ( 54 patients received ABC/3TC and 55 patients received TDF/FTC ) . All r and omized subjects were analyzed . The time to virologic failure was not significantly different between the two arms by 96 weeks ( HR , 2.09 ; 95 % CI , 0.72 - 6.13 ; p=0.178 ) . Both regimens showed favorable viral efficacy , as in the intention-to-treat population , 72.2 % ( ABC/3TC ) and 78.2 % ( TDF/FTC ) of the patients had an HIV-1 viral load < 50 copies/mL at 96 weeks . The time to the first grade 3 or 4 adverse event and the time to the first regimen modification were not significantly different between the two arms ( adverse event : HR 0.66 ; 95 % CI , 0.25 - 1.75 , p=0.407 ) ( regimen modification : HR 1.03 ; 95 % CI , 0.33 - 3.19 , p=0.964 ) . Both regimens were also well-tolerated , as only 11.1 % ( ABC/3TC ) and 10.9 % ( TDF/FTC ) of the patients discontinued the allocated regimen by 96 weeks . Clinical ly suspected abacavir-associated hypersensitivity reactions occurred in only one ( 1.9 % ) patient in the ABC/3TC arm . CONCLUSION Although insufficiently powered to show non-inferiority of viral efficacy of ABC/3TC relative to TDF/FTC , this pilot trial suggested that ABC/3TC with ATV/r is a safe and efficacious initial regimen for HLA-B*5701-negative patients , such as the Japanese population BACKGROUND Efavirenz with tenofovir-disoproxil-fumarate and emtricitabine is a preferred antiretroviral regimen for treatment-naive patients infected with HIV-1 . Rilpivirine , a new non-nucleoside reverse transcriptase inhibitor , has shown similar antiviral efficacy to efavirenz in a phase 2b trial with two nucleoside/nucleotide reverse transcriptase inhibitors . We aim ed to assess the efficacy , safety , and tolerability of rilpivirine versus efavirenz , each combined with tenofovir-disoproxil-fumarate and emtricitabine . METHODS We did a phase 3 , r and omised , double-blind , double-dummy , active-controlled trial , in patients infected with HIV-1 who were treatment-naive . The patients were aged 18 years or older with a plasma viral load at screening of 5000 copies per mL or greater , and viral sensitivity to all study drugs . Our trial was done at 112 sites across 21 countries . Patients were r and omly assigned by a computer-generated interactive web response system to receive either once-daily 25 mg rilpivirine or once-daily 600 mg efavirenz , each with tenofovir-disoproxil-fumarate and emtricitabine . Our primary objective was to show non-inferiority ( 12 % margin ) of rilpivirine to efavirenz in terms of the percentage of patients with confirmed response ( viral load < 50 copies per mL intention-to-treat time-to-loss-of-virological-response [ ITT-TLOVR ] algorithm ) at week 48 . Our primary analysis was by intention-to-treat . We also used logistic regression to adjust for baseline viral load . This trial is registered with Clinical Trials.gov , number NCT00540449 . FINDINGS 346 patients were r and omly assigned to receive rilpivirine and 344 to receive efavirenz and received at least one dose of study drug , with 287 ( 83 % ) and 285 ( 83 % ) in the respective groups having a confirmed response at week 48 . The point estimate from a logistic regression model for the percentage difference in response was -0.4 ( 95 % CI -5.9 to 5.2 ) , confirming non-inferiority with a 12 % margin ( primary endpoint ) . The incidence of virological failures was 13 % ( rilpivirine ) versus 6 % ( efavirenz ; 11%vs 4 % by ITT-TLOVR ) . Grade 2 - 4 adverse events ( 55 [ 16 % ] on rilpivirine vs 108 [ 31 % ] on efavirenz , p<0.0001 ) , discontinuations due to adverse events ( eight [ 2 % ] on rilpivirine vs 27 [ 8 % ] on efavirenz ) , rash , dizziness , and abnormal dreams or nightmares were more common with efavirenz . Increases in plasma lipids were significantly lower with rilpivirine . INTERPRETATION Rilpivirine showed non-inferior efficacy compared with efavirenz , with a higher virological-failure rate , but a more favourable safety and tolerability profile . FUNDING Tibotec BACKGROUND The aim of this study was to investigate the effect on fasting lipid parameters of switching to tenofovir disoproxil fumarate ( TDF ) plus emtricitabine ( FTC ) from abacavir ( ABC ) plus lamivudine ( 3TC ; both fixed-dose combinations ) , while maintaining ritonavir-boosted lopinavir ( LPV/r ) . METHODS This was an open-label r and omized two-arm 12-week controlled study in virologically suppressed HIV-infected patients with elevated cholesterol ( ≥5.2 mmol/l ) . Patients stable on ABC/3TC plus LPV/r either continued treatment or switched to TDF/FTC plus LPV/r for 12 weeks . St and ard efficacy and safety end points ( including fasting lipids ) were assessed . RESULTS In total , 85 subjects were treated ( n=42 ABC/FTC and n=43 TDF/3TC ) . A statistically significant decrease in total cholesterol was observed in the TDF/FTC group : from median ( IQR ) 6.22 mmol/l ( 5.91 - 6.77 ) at baseline to 5.75 mmol/l ( 5.04 - 6.18 ) at week 12 ( median [ IQR ] change from baseline -0.73 mmol/l [ -1.20- -0.18 ] ; P<0.001 ) . No notable change was observed for the ABC/3TC group . The difference between groups at week 12 was -0.82 mmol/l ( P<0.001 ) . For TDF/FTC ( but not for ABC/3TC ) , statistically significant reductions ( P<0.05 ) from baseline were observed in total , low-density lipoprotein , high-density lipoprotein (HDL)- and non-HDL cholesterol ( at weeks 4 and 12 ) . Statistically significant decreases were observed in median estimated creatinine clearance ( Cockcroft-Gault ) from baseline to week 12 for patients who switched to TDF/FTC ( -5.47 ml/min ) versus the ABC/3TC group ( -2.15 ml/min ; P=0.016 between groups ) . Virological suppression was maintained in both groups . No new safety issues were identified . CONCLUSIONS Switching to TDF/FTC from ABC/3TC was associated with rapid improvements in fasting lipid parameters and continued virological control in patients receiving LPV/r as the third component of antiretroviral therapy . The effect of these changes on clinical end points remains unclear and would need to be evaluated in a longer-term study Context Once-daily HIV treatment regimens are being used in clinical practice with the objective of improving patient acceptance and adherence . Objective To evaluate the efficacy and safety of saquinavir-soft-gelatin capsule (SGC)/ritonavir combination ( 1600 mg/100 mg ) vs efavirenz ( 600 mg ) both once daily and combined with 2 nucleoside analogs twice daily . Setting Twenty-six centers in the United States , Canada , and Puerto Rico . Patients A total of 171 antiretroviral naive HIV-infected individuals were enrolled in a 48-week , phase 3 , open-label , r and omized study .Main Outcome MeasureProportion of patients with HIV-RNA levels < 50 copies/mL. The pharmacokinetic profile of saquinavir-SGC was analyzed in a subset of r and omly selected patients . Results In the primary intent-to-treat population at week 48 , 51 % ( 38/75 ) and 71 % ( 55/77 ) of patients in the saquinavir-SGC/ritonavir and efavirenz groups , respectively , achieved HIV-RNA suppression < 50 copies/mL ( P = .5392 , 95 % 1-sided confidence interval [ CI ] = -33.5 % ) . In the on-treatment ( OT ) population , 73 % ( 38/52 ) and 93 % ( 54/58 ) of patients in the saquinavir-SGC/ritonavir and efavirenz groups , respectively , had effective viral suppression < 50 copies/mL ( P = .5015 , 95 % 1-sided CI = -33.4 % ) . Mean CD4 + cell counts increased by 239 and 204 cells/microliters ( mcL ) , in the saquinavir-SGC/ritonavir and efavirenz groups , respectively , in the OT analysis ( P = .058 ) . Both regimens were reasonably well tolerated , although more gastrointestinal adverse events were reported with saquinavir-SGC/ritonavir . Pharmacokinetic profiles in 6 patients showed an observed median Cmin at 24 hours of 429 ng/mL ( range , 68 - 1750 ng/mL ) . Conclusion Once-daily efavirenz was statistically superior to once-daily saquinavir-SGC/ritonavir . Gastrointestinal adverse effects were commonly associated with treatment failure in the saquinavir-SGC/ritonavir arm of the study 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 To study and compare the pattern of lipid profile changes in Thai HIV and tuberculosis ( TB ) co-infected patients after receiving two non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral therapy ( ART ) . MATERIAL AND METHOD From an open label , r and omized , comparative trial comparing treatment outcome between HIV and TB co-infected patients receiving nevirapine ( NVP ) or efavirenz ( EFV ) combined with stavudine and lamivudine , patient 's body mass index ( BMI ) , CD4 cell count , plasma HIV-1 RNA , fasting blood glucose , plasma total cholesterol ( TC ) , low density lipoprotein cholesterol ( LDL-C ) , high density lipoprotein cholesterol ( HDL-C ) , and triglyceride ( TG ) were collected at baseline , 24 , and 48 weeks of ART . RESULTS Of the 121 patients included in the present study , mean ( SD ) age was 36.9 ( 8.4 ) years and 66 % were male . After 48 weeks of ART the median ( IQR ) percentage of TC , LDL-C , HDL-C and TG values were 21.1 % ( 5.4 - 40.7 ) , 23.5 % ( -0.8 - 49.8 ) , 22.7 % ( 0 - 50 ) and -1.0 % ( -34.6 - 32.2 ) respectively . The median ( IQR ) percentage change of the HDL-C value was significantly higher in NVP-based than EFV-based ART ( 31.9 [ 9.6 - 50.0 ] vs. 12.2 [ -8.8 - 51.2 ] ; p = 0.03 ) . The proportions of patients with high TC ( 21.5 % ) and high LDL-C ( 29.2 % ) increased and low HDL-C ( 11.6 % ) decreased significantly at 48 weeks of ART compared to baseline ( all , p < 0.01 ) . The proportions of patients with high TC , high TG and low HDL-C were significantly higher in the EFV group than in the NVP group ( p = 0.03 for high TC , p = .01 for high TG and p < 0.01 for low HDL-C ) . CONCLUSION NNRTI-based ART is associated with increases of TC , LDL-C and HDL-C values in Thai HIV and TB co-infected patients . More favorable lipid profile is observed in NVP-based than EFV-based ART OBJECTIVES The efficacy and hepatic safety of the non-nucleoside reverse transcriptase inhibitors rilpivirine ( TMC278 ) and efavirenz were compared in treatment-naive , HIV-infected adults with concurrent hepatitis B virus ( HBV ) and /or hepatitis C virus ( HCV ) infection in the pooled week 48 analysis of the Phase III , double-blind , r and omized ECHO ( NCT00540449 ) and THRIVE ( NCT00543725 ) trials . METHODS Patients received 25 mg of rilpivirine once daily or 600 mg of efavirenz once daily , plus two nucleoside/nucleotide reverse transcriptase inhibitors . At screening , patients had alanine aminotransferase/aspartate aminotransferase levels ≤5 × the upper limit of normal . HBV and HCV status was determined at baseline by HBV surface antigen , HCV antibody and HCV RNA testing . RESULTS HBV/HCV coinfection status was known for 670 patients in the rilpivirine group and 665 in the efavirenz group . At baseline , 49 rilpivirine and 63 efavirenz patients [ 112/1335 ( 8.4 % ) ] were coinfected with either HBV [ 55/1357 ( 4.1 % ) ] or HCV [ 57/1333 ( 4.3 % ) ] . The safety analysis included all available data , including beyond week 48 . Eight patients seroconverted during the study ( rilpivirine : five ; efavirenz : three ) . A higher proportion of patients achieved viral load < 50 copies/mL ( intent to treat , time to loss of virological response ) in the subgroup without HBV/HCV coinfection ( rilpivirine : 85.0 % ; efavirenz : 82.6 % ) than in the coinfected subgroup ( rilpivirine : 73.5 % ; efavirenz : 79.4 % ) ( rilpivirine , P = 0.04 and efavirenz , P = 0.49 , Fisher 's exact test ) . The incidence of hepatic adverse events ( AEs ) was low in both groups in the overall population ( rilpivirine : 5.5 % versus efavirenz : 6.6 % ) and was higher in HBV/HCV-coinfected patients than in those not coinfected ( 26.7 % versus 4.1 % , respectively ) . CONCLUSIONS Hepatic AEs were more common and response rates lower in HBV/HCV-coinfected patients treated with rilpivirine or efavirenz than in those who were not coinfected Background Once-daily ( QD ) ritonavir 100 mg-boosted fosamprenavir 1400 mg ( FPV/r100 ) or atazanavir 300 mg ( ATV/r100 ) , plus tenofovir/emtricitabine ( TDF/FTC ) 300 mg/200 mg , have not been compared as initial antiretroviral treatment . To address this data gap , we conducted an open-label , multicenter 48-week study ( ALERT ) in 106 antiretroviral-naïve , HIV-infected patients ( median HIV-1 RNA 4.9 log10 copies/mL ; CD4 + count 191 cells/mm3 ) r and omly assigned to the FPV/r100 or ATV/r100 regimens . Results At baseline , the FPV/r100 or ATV/r100 arms were well-matched for HIV-1 RNA ( median , 4.9 log10 copies/mL [ both ] ) , CD4 + count ( mean , 176 vs 205 cells/mm3 ) . At week 48 , intent-to-treat : missing/discontinuation = failure analysis showed similar responses to FPV/r100 and ATV/r100 ( HIV-1 RNA < 50 copies/mL : 75 % ( 40/53 ) vs 83 % ( 44/53 ) , p = 0.34 [ Cochran-Mantel-Haenszel test ] ) ; mean CD4 + count change-from-baseline : + 170 vs + 183 cells/mm3 , p = 0.398 [ Wilcoxon rank sum test ] ) . Fasting total/LDL/HDL-cholesterol changes-from-baseline were also similar , although week 48 median fasting triglycerides were higher with FPV/r100 ( 150 vs 131 mg/dL ) . FPV/r100-treated patients experienced fewer treatment-related grade 2–4 adverse events ( 15 % vs 57 % ) , with differences driven by ATV-related hyperbilirubinemia . Three patients discontinued TDF/FTC because their GFR decreased to < 50 mL/min . Conclusion The all-QD regimens of FPV/r100 and ATV/r100 , plus TDF/FTC , provided similar virologic , CD4 + response , and fasting total/LDL/HDL-cholesterol changes through 48 weeks . Fewer FPV/r100-treated patients experienced treatment-related grade 2–4 adverse events Objective : To compare the efficacy of efavirenz ( EFV ) vs lopinavir/ritonavir ( LPV/r ) in combination with azidothymidine/lamivudine in antiretroviral therapy naive , HIV+ individuals presenting for care with CD4 + counts < 200/mm3 . Methods : Prospect i ve , r and omized , open label , multicenter trial in Mexico . HIV-infected subjects with CD4 < 200/mm3 were r and omized to receive open label EFV or LPV/r plus azidothymidine/lamivudine ( fixed-dose combination ) for 48 weeks . R and omization was stratified by baseline CD4 + cell count ( ≤100 or > 100/mm3 ) . The primary endpoint was the percentage of patients with plasma HIV-1 RNA < 50 copies/mL at 48 weeks by intention-to-treat analysis . Results : A total of 189 patients ( 85 % men ) were r and omized to receive EFV ( 95 ) or LPV/r ( 94 ) . Median baseline CD4 + were 64 and 52/mm3 , respectively ( P = not significant ) . At week 48 , by intention-to-treat analysis , 70 % of EFV and 53 % of LPV/r patients achieved HIV-1 RNA < 50 copies/mL [ estimated difference 17 % ( 95 % confidence interval 3.5 to 31 ) , P = 0.013 ] . The proportion with HIV-1 RNA < 400 copies/mL was 73 % with EFV and 65 % with LPV/r ( P = 0.25 ) . Virologic failure occurred in 7 patients on EFV and 17 on LPV/r . Mean CD4 + count increases ( cells/mm3 ) were 234 for EFV and 239 for LPV/r . Mean change in total cholesterol and triglyceride levels were 50 and 48 mg/dL in EFV and 63 and 116 mg/dL in LPV/r ( P = 0.24 and P < 0.01 ) . Conclusions : In these very advanced HIV-infected ARV-naive subjects , EFV-based highly active antiretroviral therapy had superior virologic efficacy than LPV/r-based highly active antiretroviral therapy , with a more favorable lipid profile BACKGROUND Treatment initiation at the time of primary human immunodeficiency virus ( HIV ) type 1 ( HIV-1 ) infection has become less frequent in recent years . METHODS In the French prospect i ve PRIMO Cohort , in which patients are enrolled at the time of primary HIV-1 infection , 30 % of the 552 patients recruited during 1996 - 2004 did not start receiving antiretroviral treatment during the first 3 months after diagnosis . We analyzed the patients ' clinical and immunological outcomes and examined potential predictors of disease progression . Progression was defined as the occurrence of an acquired immunodeficiency syndrome (AIDS)-related clinical event or a CD4 cell count < 350 cells/mm3 . RESULTS Fifty-six ( 34 % ) of the untreated patients experienced immunological progression during a median duration of follow-up of 24 months , and 1 of these patients had an AIDS-related event . The estimated risks of progression were 25 % , 34 % , and 42 % at 1 , 2 , and 3 years after enrollment , respectively . Compared with patients who did not have progression , those with progression had significantly lower CD4 cell counts at diagnosis ( 455 vs. 738 cells/mm3 ) , higher plasma HIV RNA levels ( 4.9 vs. 4.5 log10 copies/mL ) , and higher HIV DNA levels ( 3.3 vs. 3.0 log(10 ) copies/10(6 ) peripheral blood mononuclear cells [ P BMC s ] ) . All 3 parameters were significantly associated with progression in univariate analysis . In multivariate analysis , only the CD4 cell count and HIV DNA level were independently predictive of disease progression ( relative hazard for CD4 cell count , 1.84 per decrease of 100 cells/mm3 ; relative hazard for HIV DNA level , 2.73 per increase of 1 log(10 ) copies/10(6 ) P BMC s ) . CONCLUSIONS Both a low initial CD4 cell count and a high HIV DNA level are predictive of rapid progression of untreated primary HIV-1 infection . Affected patients may therefore benefit from close clinical and laboratory monitoring and /or early administration of treatment Background : Atazanavir , an azapeptide protease inhibitor ( PI ) , has pharmacokinetics that allow once-daily dosing , and it is not associated with significant PI-associated dyslipidemia . Methods : A r and omized , double-blind , double-dummy , active-controlled , 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily . The 810 treatment-naive patients were stratified by HIV RNA level . The primary efficacy end point was the proportion of treated patients with HIV RNA levels < 400 copies/mL through week 48 . Results : At week 48 , HIV RNA levels were < 400 copies/mL in 70 % of patients receiving atazanavir and 64 % of patients receiving efavirenz ( intent-to-treat , difference ; 95 % confidence interval : 5.2 % ; −1.2 % , 11.7 % ) . Median CD4 + cell counts increased at comparable magnitudes and rates in the 2 treatment arms ( mean change at week 48 : 176 cells/mm3 with atazanavir , 160 cells/mm3 with efavirenz ) . Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol , fasting low-density lipoprotein cholesterol , or fasting triglycerides over 48 weeks of therapy . Atazanavir-linked bilirubin elevations infrequently result ed in treatment discontinuation ( < 1 % ) . Atazanavir treatment did not increase fasting glucose or insulin levels . Conclusions : For initial HIV treatment , a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine OBJECTIVE To assess whether differences in safety profiles between nevirapine ( NVP ) and efavirenz ( EFV ) , as observed in the 2NN study , translated into differences in ' health related quality of life ' ( HRQoL ) . DESIGN A sub- study of the 2NN study , with antiretroviral-naive patients r and omly allocated to NVP ( once or twice daily ) , EFV or NVP+EFV , in addition to stavudine and lamivudine . METHODS Comparing differences in changes of HRQoL over 48 weeks as measured with the Medical Outcomes Study HIV Health Survey ( MOS-HIV ) question naire , using analysis of variance . RESULTS The 2NN study enrolled 1216 patients . No vali date d question naires were available for 244 patients , and 55 patients had no HRQoL data at all , leaving 917 patients eligible for this sub- study . A total of 471 ( 51 % ) had HRQoL measurements both at baseline and week 48 . The majority ( 69 % ) of patients without HRQoL measurements did , however , complete the study . The change in the physical health score ( PHS ) was 3.9 for NVP , 3.4 for EFV and 2.4 for NVP+EFV ( P=0.712 ) . For the mental health score ( MHS ) these values were 6.1 , 7.0 and 3.9 , respectively ( P=0.098 ) . A baseline plasma HIV-1 RNA concentration ( pVL ) > or = 100,000 copies/ml and a decline in pVL ( per log10 ) were independently associated with an increase of PHS . An increase of MHS was only associated with pVL decline . Patients experiencing an adverse event during follow-up had a comparable change in PHS but a significantly smaller change in MHS , compared with those without an adverse event . CONCLUSIONS First-line ART containing NVP and /or EFV leads to an improvement in HRQoL. The gain in HRQoL was similar for NVP and EFV , but slightly lower for the combination of these drugs Background : National initiatives offering non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy ( cART ) have exp and ed in sub-Saharan Africa . The Tshepo study is the first clinical trial evaluating the long-term efficacy and tolerability of efavirenz versus nevirapine-based cART among adults in Botswana . Methods : A 3-year r and omized study ( n = 650 ) using a 3 × 2 × 2 factorial design comparing efficacy and tolerability among : ( i ) zidovudine/lamivudine versus zidovudine/didanosine versus stavudine/lamivudine ; ( ii ) efavirenz versus nevirapine ; and ( iii ) community-based supervision versus st and ard adherence strategies . This paper focuses on comparison ( ii ) . Results : There was no significant difference by assigned NNRTI in time to virological failure with resistance ( log-rank P = 0.14 ) , nevirapine versus efavirenz [ risk ratio ( RR ) 1.54 , 95 % CI 0.86–2.70 ] . Rates of virological failure with resistance were 9.6 % nevirapine-treated ( 95 % CI 6.8–13.5 ) versus 6.6 % efavirenz-treated ( 95 % CI 4.2–10.0 ) at 3 years . Women receiving nevirapine-based cART trended towards higher virological failure rates when compared with efavirenz-treated women , Holm-corrected ( log-rank P = 0.072 ) , nevirapine versus efavirenz ( RR 2.22 , 95 % CI 0.94–5.00 ) . A total of 139 patients had 176 treatment-modifying toxicities , with a shorter time to event in nevirapine-treated versus efavirenz-treated patients ( RR 1.85 , 1.20–2.86 ; log-rank P = 0.0002 ) . Conclusion : Tshepo-treated patients had excellent overall immunological and virological outcomes , and no significant differences were observed by r and omized NNRTI comparison . Nevirapine-treated women trended towards higher virological failure with resistance compared with efavirenz-treated women . Nevirapine-treated adults had higher treatment modifying toxicity rates when compared with those receiving efavirenz . Nevirapine-based cART can continue to be offered to women in sub-Saharan Africa if patient education concerning toxicity is emphasized , routine safety monitoring chemistries are performed and the potential risk of efavirenz-related teratogenicity is considered BACKGROUND In countries with a high incidence of HIV and tuberculosis co-infection , nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs . We aim ed to compare efficacy and safety of a nevirapine-based antiretroviral therapy ( started at full dose ) with an efavirenz-based regimen in co-infected patients . METHODS We did a multicentre , open-label , r and omised , non-inferiority trial at three health centres in Maputo , Mozambique . We enrolled adults ( ≥18 years ) with tuberculosis and previously untreated HIV infection ( CD4 cell counts < 250 cells per μL ) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal . 4 - 6 weeks after the start of tuberculosis treatment , we r and omly allocated patients ( 1:1 ) with central r and omisation , block sizes of two to six , and stratified by site and CD4 cell count to nevirapine ( 200 mg twice daily ) or efavirenz ( 600 mg once daily ) , plus lamivudine and stavudine . The primary endpoint was virological suppression at 48 weeks ( HIV-1 RNA < 50 copies per mL ) in all patients who received at least one dose of study drug ( intention-to-treat population ) ; death and loss to follow-up were recorded as treatment failure . The non-inferiority margin for the difference of efficacy was 10 % . We assessed efficacy in intention-to-treat and per- protocol population s and safety in all patients who received study drug . This study is registered with Clinical Trials.gov , number NCT00495326 . FINDINGS Between October , 2007 , and March , 2010 , we enrolled 285 patients into each group . 242 ( 85 % ) patients in the nevirapine group and 233 ( 82 % ) patients in the efavirenz group completed follow-up . In the intention-to-treat population , 184 patients ( 64·6 % , 95 % CI 58·7 - 70·1 ) allocated nevirapine achieved virological suppression at week 48 , as did 199 patients ( 69·8 % , 64·1 - 75·1 ) allocated efavirenz ( one-sided 95 % CI of the difference of efficacy 11·7 % ) . In the per- protocol population , 170 ( 70·0 % , 63·8 - 75·7 ) of 243 patients allocated nevirapine achieved virological suppression at week 48 , as did 194 ( 78·9 % , 73·2 - 83·8 ) of 246 patients allocated efavirenz ( one-sided 95 % CI 15·4 % ) . The median CD4 cell count at r and omisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine . 20 patients allocated nevirapine ( 7 % ) had grade 3 - 4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz ( 6 % ) . Three patients had severe rash after receipt of nevirapine ( 1 % ) but no patients did after receipt of efavirenz . 18 patients in the nevirapine group died , as did 17 patients in the efavirenz group . INTERPRETATION Although non-inferiority of the nevirapine-regimen was not shown , nevirapine at full dose could be a safe , acceptable alternative for patients unable to tolerate efavirenz . FUNDING French Research Agency for HIV/AIDS and hepatitis ( ANRS ) Improved therapeutic strategies , including the introduction of protease inhibitors , have led to a striking decrease in HIV-related morbidity and mortality ( 1 , 2 ) . It is widely believed that adherence to an antiretroviral regimen is central to the likelihood that a patient will derive sustained benefit from therapy ( 3 , 4 ) . Conventional wisdom holds that two groups of patients are currently experiencing clinical and virologic failure . The first group consists of patients who have received multiple different antiretroviral drugs over a prolonged period of time and who may be infected predominantly with HIV strains that are resistant to multiple drugs . The second group comprises patients who adhere poorly to their antiretroviral regimen . The two groups are not mutually exclusive : Patients with suboptimal adherence may be more likely to have antiretroviral drugresistant HIV infection . The potential public health importance of adherence to therapy in prevention of transmission of drug-resistant virus has also been emphasized ( 5 ) . Patients with suboptimal adherence to antiretroviral therapy and poor adherence to use of safer-sex practice s , such as use of condoms , may infect others with their own antiretroviral drugresistant virus . Anecdotal experience suggests that physicians may be unwilling to prescribe combination antiretroviral therapy to patients whom they perceive to be at high risk for poor adherence ( 6 ) . Given the critical importance of adherence to therapy to patient outcome , secondary prevention of HIV infection , and willingness of providers to prescribe therapy , we prospect ively investigated the association between protease inhibitor adherence and patient outcome , factors related to adherence , and the accuracy of physicians ' prediction of patient adherence . We used a microelectronic monitoring system to assess adherence to antiretroviral therapy . Methods Study Sample The study was conducted at the HIV clinics of the Veterans Affairs Medical Center , Pittsburgh , Pennsylvania , and University of Nebraska Medical Center , Omaha , Nebraska . The HIV physicians at these clinics were primary care providers for the study patients . Each site also had a dedicated HIV nurse coordinator . From August 1997 to March 1999 , we enrolled consecutive patients with HIV infection who were already receiving a protease inhibitor ( experienced patients ) or who were to begin taking a protease inhibitor ( naive patients ) . Exclusion criteria were inability to give informed written consent ; expectation of continued use of a medication organizer to include protease inhibitors ; and residence in a nursing home , jail , or hospice , where medications were dispensed at least daily . Collection of Baseline Data At baseline , a study investigator used medical chart review to complete a 52-item question naire for each patient . The question naire covered demographic information ( age , sex , ethnicity , risk factors for HIV infection , educational and employment status , income ) , medical history ( years known to be HIV infected ; opportunistic infections ; history of schizophrenia , depression , or bipolar affective disorder ) , and medication use ( name , dose , and frequency of all antiretroviral agents , other antimicrobials , and other prescription therapies ) . The enrolling physician assessed use of illegal drugs and nonprescription therapies ( including herbal or alternative therapies ) by interview . Alcohol abuse was assessed by using the CAGE question naire ( cutting down , annoyance with criticism , guilty feelings , and use of eye-opener drinks ) ( 7 ) . Information about use of adherence aids ( such as personal reminders by significant others or timers , alarms , or other devices ) was specifically sought . The investigator asked study patients if they felt that their current symptoms were attributable to HIV infection , the antiretroviral medications , or both . In addition , patients were asked whether they agreed with such health beliefs as Do you think your antiretroviral therapy will make you live longer ? At baseline , each patient completed the Beck Depression Inventory and the General Health Question naire ( 8 , 9 ) , well-vali date d measures of psychiatric morbidity that have been widely used in patients with HIV infection ( 9 - 11 ) . Patients completed the inventories as a written task without the assistance of a physician or clinic nurse . At baseline , we used the following question to elicit a prediction of adherence to protease inhibitor therapy from the patient 's primary HIV physician and clinic nurse : Do you think that the patient is compliant with antiretroviral therapy , that is , taking greater than 80 % of the prescribed doses of antiretroviral medications ? This prediction was made after collection of the baseline information but before actual measurement of adherence using the microelectronic monitoring system had begun . Collection of Follow-up Data Every 3 months for the duration of the study , the study participants were asked whether any of the following had changed since their previous visit : employment , use of alcohol or illegal drugs , residence , attribution of symptoms to the antiretroviral therapy or HIV infection , and changes in medications . Patients completed a new Beck Depression Inventory and General Health Question naire . The primary HIV physician determined whether the patient had developed an opportunistic infection in the past 3 months . Laboratory Testing At baseline and every 3 months for the duration of the study , HIV RNA levels were measured by using the Roche Amplicor System ( Roche Diagnostics , Nutley , New Jersey ) and CD4 lymphocyte sub population assays were performed . Assessment of Adherence Adherence was measured by using the Medication Events Monitoring System ( MEMS ) ( Aprex , Union City , California ) . The MEMS TrackCap system consists of st and ard medication bottles that have a pressure-activated microprocessor in the cap ( 12 ) . The microprocessor records each opening and lists the date , time , and duration of opening . The information on medication dosing is retrieved by scanning the cap over a purpose -built communicator module . The information is then stored in a data base provided by Aprex . Although the MEMS TrackCap system can not prove consumption of the drug by the patient , prolonged deception by patients has been shown to be unlikely ( 13 ) . Patients were provided with a MEMS TrackCap bottle for each prescribed protease inhibitor ( including refrigerated ritonavir capsules ) . Use of the MEMS TrackCaps system was not possible for patients who were prescribed ritonavir from August 1998 onward because ritonavir capsules were no longer available . The patients could use their regular medication organizer for all other medications . The caps were scanned each time the patient presented to the HIV clinic . Patients were specifically instructed not to take extra doses out at any time ( for example , not to take out an extra dose in the morning for consumption at lunchtime ) . Patients were offered small pill bottles that could be easily carried in a coat pocket . Adherence rates were defined as the number of doses recorded by the MEMS TrackCap divided by the total number of doses prescribed during the monitoring period . To evaluate the effect of dosing frequency on adherence , dosing interval errors were defined as medication doses taken at a time other than that prescribed ( that is,<9 hours or>15 hours after the previous dose of a medication prescribed every 12 hours or<5 hours or>11 hours after the previous dose of a medication prescribed every 8 hours ) ( 12 ) . Definitions of Virologic and Clinical Outcomes Virologic failure was defined as an HIV RNA level greater than 400 copies/mL at the last study visit . Changes in CD4 lymphocyte counts were calculated as the difference between the count at the baseline visit and the count at the final study visit . Opportunistic infections were defined according to Centers for Disease Control and Prevention criteria ( 14 ) . Hospitalization for all causes was recorded as the number of nights spent in any acute-care hospital ; nursing homes and drug or alcohol rehabilitation facilities were excluded . Mortality was defined as all-cause mortality at any time during the study period . Statistical Analysis All data was entered into a computerized data base , PROPHET Statistics Version 6.0 ( AB Tech Corp. , Charlottesville , Virginia ) . The chi-square or Fisher test was used to compare categorical variables . Continuous variables were examined by using the t-test or the MannWhitney test . Baseline and follow-up values were compared by using the paired t-test or the Wilcoxon signed-rank test . To examine the relation between two continuous measures , a best-fit line was obtained . The slope of this line was then tested against the null hypothesis of a slope of zero . The Pearson correlation coefficient was also calculated . Cox proportional-hazards regression was used to evaluate the relation between adherence and time to virologic failure . In the Cox model , predictor variables found to be significant ( P<0.1 ) in univariate analysis were added to the model . Logistic regression models were used to assess the effects of multiple variables on adherence . Factors were entered into the regression model if they were found by univariate analysis to be significantly associated ( P<0.1 ) . To analyze time to return of detectable HIV RNA for patients with an undetectable viral load at baseline , KaplanMeier survival curves were computed for less than 95 % adherence and 95 % or greater adherence and were compared by using the MantelCox test . The McNemar test was used to compare the predictions of the clinical nurses and physicians . Ethical Considerations The study was approved by the institutional review boards of the two study centers . Patients were fully informed that their adherence to protease inhibitor therapy was being measured by using the MEMS TrackCap system . Results Patient Characteristics Of 99 patients enrolled in the study , 6 withdrew before follow-up data were collected ( BACKGROUND The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors ( NRTIs ) is recommended for initial therapy for patients with human immunodeficiency virus type 1 ( HIV-1 ) infection , but which of the two regimens has greater efficacy is not known . The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs . METHODS In an open-label study , we compared three regimens for initial therapy : efavirenz plus two NRTIs ( efavirenz group ) , lopinavir-ritonavir plus two NRTIs ( lopinavir-ritonavir group ) , and lopinavir-ritonavir plus efavirenz ( NRTI-sparing group ) . We r and omly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups . RESULTS At a median follow-up of 112 weeks , the time to virologic failure was longer in the efavirenz group than in the lopinavir-ritonavir group ( P=0.006 ) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups . At week 96 , the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89 % in the efavirenz group , 77 % in the lopinavir-ritonavir group , and 83 % in the NRTI-sparing group ( P=0.003 for the comparison between the efavirenz group and the lopinavir-ritonavir group ) . The groups did not differ significantly in the time to discontinuation because of toxic effects . At virologic failure , antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups . CONCLUSIONS Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group . The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance . ( Clinical Trials.gov number , NCT00050895 [ Clinical Trials.gov ] . ) BACKGROUND Coinfection with human immunodeficiency virus type 1 ( HIV-1 ) increases the risk of hepatitis B virus (HBV)-associated progressive liver disease . Lamivudine has potent activity against both HIV-1 and HBV ; however , lamivudine-resistance mutations in HBV frequently develop . METHODS Sub studies of the safety and efficacy of tenofovir disoproxil fumarate ( tenofovir DF ) for patients coinfected with HIV and HBV were undertaken within 2 phase 3 r and omized controlled trials involving antiretroviral therapy-experienced ( study 907 ) and -naive ( study 903 ) HIV-infected population s. Inclusion criteria were detection of hepatitis B surface antigen , an HBV DNA level > 106 copies/mL at baseline , and HBV DNA specimens available at week 24 ( study 907 ) and week 48 ( study 903 ) . RESULTS In study 907 , the mean decrease in HBV DNA was 4.9 log(10 ) , after 24 weeks , for 10 patients r and omized to receive tenofovir DF , compared with a mean increase of 1.2 log(10 ) for 2 patients r and omized to receive placebo ( P=.041 ) . The mean decrease in HBV DNA during tenofovir DF treatment was similar for patients with wild-type ( 5.3 log(10 ) ) and lamivudine-resistant ( 4.6 log(10 ) ) HBV strains . In study 903 , the mean decrease in HBV DNA was 3.0 log(10 ) , after 48 weeks , for 6 patients r and omized to receive lamivudine , compared with 4.7 log(10 ) for 5 patients r and omized to receive lamivudine and tenofovir DF ( P=.055 ) . Four patients developed tyrosine-methionine-aspartate-aspartate mutations , all in the lamivudine-only treatment arm . CONCLUSION Tenofovir DF has potent anti-HBV efficacy in antiretroviral therapy-experienced and -naive individuals coinfected with HIV and HBV Objective : HIV-1 RNA levels in peripheral blood are strongly associated with progression to AIDS , CD4 + T-cell decline , or death . Their predictive value is reportedly independent of the predictive value of CD4 + T-cell counts . Because the interrelations between these parameters of HIV-1 infection are poorly understood , we studied the kinetics and predictive value of serum HIV-1 RNA levels , CD4 + T-cell counts , and T-cell function . Design and methods : HIV RNA levels , CD4 + T-cell counts , and T-cell function were measured from seroconversion to AIDS in 123 homosexual men who seroconverted during a prospect i ve study and were followed over 10 years . Results : Two patterns of median HIV-1 RNA levels were found during infection : a steady-state and a ‘ U-shaped ’ curve . Steady-state high RNA levels were related to rapid disease progression . For the U-shaped curve , there were groups with high and low RNA levels related to disease progression . At 1 year after seroconversion , RNA level was the only marker that was strongly predictive . Furthermore , decreasing RNA levels in the first year following seroconversion were related to better prognosis than stable low levels . Low CD4 + T-cell count and T-cell function became predictive of progression to AIDS at 2 and 5 years after seroconversion , respectively . Conclusions : With ongoing infection , the predictive value of low CD4 + T-cell count and T-cell function increases , whereas the predictive value of high HIV-1 RNA level decreases . These findings reflect the observation that infection with HIV progressively leads towards immune deficiency , which in later stages is most predictive of disease progression CONTEXT Three-drug antiretroviral regimens are st and ard of care for initial treatment of human immunodeficiency virus 1 ( HIV-1 ) infection , but a 4-drug regimen could improve antiretroviral activity and be more effective than a 3-drug regimen . OBJECTIVE To compare the safety/efficacy of 3-drug vs 4-drug regimens for initial treatment of HIV-1 infection . DESIGN The AIDS Clinical Trials Group ( ACTG ) A5095 study , a r and omized , double-blind , placebo-controlled study with enrollment and follow-up conducted from March 22 , 2001 , to March 1 , 2005 , and enrolling treatment-naive , HIV-1-infected patients with HIV-1 RNA levels of 400 copies/mL or greater from US clinical trials units of the ACTG . INTERVENTIONS Zidovudine/lamivudine plus efavirenz ( 3-drug regimen ) vs zidovudine/lamivudine/abacavir plus efavirenz ( 4-drug regimen ) . MAIN OUTCOME MEASURES Time to virologic failure ( defined as time to first of 2 successive HIV-1 RNA levels > or = 200 copies/mL at or after week 16 ) , CD4 cell count changes , and grade 3 or 4 adverse events . HIV-1 RNA data were intent-to-treat , regardless of treatment changes . RESULTS Seven hundred sixty-five patients with a baseline mean HIV-1 RNA level of 4.86 log10 ( 72,444 ) copies/mL and CD4 cell count of 240 cells/mm3 were r and omized . After a median 3-year follow-up , 99 ( 26 % ) of 382 and 94 ( 25 % ) of 383 patients receiving the 3-drug and 4-drug regimens , respectively , reached protocol -defined virologic failure ; time to virologic failure was not significantly different ( hazard ratio , 0.95 ; 97.5 % confidence interval , 0.69 - 1.33 ; P = .73 ) . In planned subgroup analyses , increased risk for virologic failure was seen in non-Hispanic black patients ( adjusted hazard ratio , 1.66 ; 95 % confidence interval , 1.18 - 2.34 ; P = .003 ) . At 3 years , the HIV-1 RNA level was less than 200 copies/mL in 152 ( 90 % ) of 169 and 143 ( 92 % ) of 156 patients receiving the 3-drug and 4-drug regimens , respectively ( P = .59 ) , and less than 50 copies/mL in 144 ( 85 % ) of 169 and 137 ( 88 % ) of 156 patients ( P = .39 ) . CD4 cell count increases and grade 3 or 4 adverse events were not significantly different . CONCLUSIONS In treatment-naive patients , there were no significant differences between the 3-drug and 4-drug antiretroviral regimens ; overall , at least approximately 80 % of patients had HIV-1 RNA levels less than 50 copies/mL through 3 years . These results support current guidelines recommending 2 nucleosides plus efavirenz for initial treatment of HIV-1 infection ; adding abacavir as a fourth drug provided no additional benefit . CLINICAL TRIALS REGISTRATION clinical trials.gov Identifier : NCT00013520 Abstract Objectives : Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor ( NNRTI ) rilpivirine ( RPV ) was compared to efavirenz ( EFV ) in subset of 1,096 subjects who received emtricitabine/tenofovir disoproxil fumarate ( FTC/TDF ) in pooled data from 2 phase 3 studies . Methods : ECHO and THRIVE are double-blind , double-dummy , r and omized , active-controlled , non-inferiority phase 3 studies of RPV versus EFV plus 2 NRTIs in antiretroviral-naïve adult subjects . The primary and secondary endpoints were the proportion of subjects with HIV-1 RNA < 50 copies/mL using an intent-to-treat , time to loss of virologic response ( ITT-TLOVR ) analysis at weeks 48 and 96 , respectively . Safety , tolerability , immunologic response , adherence level , and other measures were also evaluated . Results : At week 48 , noninferior efficacy of RPV+FTC/TDF over EFV+FTC/TDF was established , and at week 96 RPV+FTC/TDF remained noninferior ( 77 % overall response rate in both groups ) . Through week 96 , rates of virologic failure were higher in the RPV+FTC/TDF group , with low and similar rates of virologic failure and resistance mutations occurring during the second year of follow-up . Treatment with RPV+FTC/TDF was associated with a lower rate of discontinuation due to adverse events and grade 2–4 adverse events including dizziness , abnormal dreams/nightmares , rash , and lipid abnormalities . Conclusions : The pooled ECHO and THRIVE studies demonstrated noninferiority of RPV+FTC/TDF in achieving virologic response with safety and tolerability advantages over EFV+FTC/TDF through 96 weeks . Higher rates of virologic failure in the RPV+FTC/TDF group were balanced with higher rates of discontinuations due to adverse events in the EFV+FTC/TDF group Background : The present primary analysis of AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects ( ARTEMIS ) compares the efficacy and safety of once-daily darunavir/ritonavir ( DRV/r ) with that of lopinavir/ritonavir ( LPV/r ) in treatment-naive patients . Methods : Patients with HIV-1 RNA at least 5000 copies/ml were stratified by HIV-1 RNA and CD4 cell count in a phase III , open-label trial , and r and omized to receive DRV/r 800/100 mg qd or LPV/r 800/200 mg total daily dose ( bid or qd ) plus fixed-dose tenofovir and emtricitabine for 192 weeks . The primary objective was to demonstrate non-inferiority of DRV/r as compared with LPV/r in HIV-1 RNA less than 50 copies/ml per- protocol time-to-loss of virologic response at 48 weeks . Results : Six hundred and eighty-nine patients were r and omized and treated ; mean baseline HIV-1 RNA : 4.85 log10 copies/ml and median CD4 count : 225 cells/μl . At 48 weeks , 84 % of DRV/r and 78 % of LPV/r patients achieved HIV-1 RNA less than 50 copies/ml ( estimated difference = 5.6 [ 95 % confidence interval −0.1–11]% ) , demonstrating non-inferiority of DRV/r as compared with LPV/r ( P < 0.001 ; per- protocol time-to-loss of virologic response ) . Patients with HIV-1 RNA at least 100 000 copies/ml had a significantly higher response rate with DRV/r ( 79 % ) versus LPV/r ( 67 % ; P < 0.05 ) . Median CD4 cell count increases ( non-completer = failure ; cells/μl ) were 137 for DRV/r and 141 for LPV/r . DRV/r had a lower incidence of possibly treatment-related grade 2–4 gastrointestinal-related adverse events ( 7 versus 14 % ) and treatment-related moderate-to-severe diarrhea ( 4 versus 10 % ) than LPV/r . Adverse events leading to discontinuation were DRV/r : 3 % and LPV/r : 7 % . Conclusion : DRV/r 800/100 mg qd was non-inferior to LPV/r 800/200 mg at 48 weeks , with a more favorable safety profile . Significantly higher response rates were observed with DRV/r in patients with HIV-1 RNA at least 100 000 copies/ml . DRV/r 800/100 mg offers a new effective and well tolerated once-daily , first-line treatment option for treatment-naive patients Background : Atazanavir ( ATV ) , the first once-daily protease inhibitor approved for the treatment of HIV-1 infection , is recommended for use in antiretroviral ( ARV ) treatment-naive and -experienced patients . Study AI424 - 089 was a prospect i ve , r and omized , open-label , 96-week study comparing 2 ATV-based treatment regimens in ARV-naive HIV-infected patients . Methods : Adults with HIV RNA levels ≥2000 copies/mL were r and omized ( 1:1 ) to once-daily ATV at a dose of 300 mg with ritonavir at a dose of 100 mg ( ATV300/RTV ) or ATV at a dose of 400 mg ( ATV400 ) ; both regimens included lamivudine and an investigational extended-release formulation of stavudine . The primary endpoint for this noninferiority study was the proportion of patients ( response rate ) with an HIV RNA load < 400 copies/mL at week 48 . Results : Response rates at week 48 were 86 % and 85 % on the ATV300/RTV and ATV400 regimens , respectively ( difference estimate [ 95 % confidence interval ] = 1.5 [ −8.2 to 11.1 ] ) . There were 3 and 10 patients with virologic failure in the ATV300/RTV and ATV400 groups , respectively . One patient ( ATV400 ) developed phenotypic resistance to ATV associated with an I50L substitution . Adverse event-related discontinuations were 8 % among ATV300/RTV-treated patients and < 1 % among ATV400-treated patients . Plasma lipid elevations were low with both regimens . Both regimens were well tolerated . Conclusions : These findings demonstrate the safety and efficacy of the ATV300/RTV regimen and confirm the safety and efficacy of ATV400 in an ARV-naive patient population BACKGROUND Atazanavir/ritonavir is as effective as lopinavir/ritonavir , with a more favourable lipid profile and less gastrointestinal toxicity , in treatment-experienced HIV-1-infected patients . We compared these two combinations directly in treatment-naive patients . METHODS In this open-label , international non-inferiority study , 883 antiretroviral-naive , HIV-1-infected patients were r and omly assigned to receive atazanavir/ritonavir 300/100 mg once daily ( n=440 ) or lopinavir/ritonavir 400/100 mg twice daily ( n=443 ) , in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily . R and omisation was done with a computer-generated central ised r and omisation schedule and was stratified by baseline levels of HIV RNA ( viral load ) and geographic region . The primary endpoint was the proportion of patients with viral load less than 50 copies per mL at week 48 . The main efficacy analysis was done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00272779 . FINDINGS At week 48 , 343 ( 78 % ) of 440 patients receiving atazanavir/ritonavir and 338 ( 76 % ) of 443 patients receiving lopinavir/ritonavir had achieved a viral load of less than 50 copies per mL ( difference 1.7 % , 95 % CI -3.8 to 7.1 ) . Mean increases from baseline in CD4 cell count were similar ( 203 cells per muL in the atazanavir/ritonavir group vs 219 cells per muL in the lopinavir/ritonavir group ) . 25 ( 6 % ) patients in the atazanavir/ritonavir group and 26 ( 6 % ) in the lopinavir/ritonavir group were virological failures by week 48 . Only two patients , both in the atazanavir/ritonavir group , had non-polymorphic protease inhibitor resistance mutations emerge on treatment , which conferred phenotypic resistance to atazanavir in one patient . Serious adverse events were noted in 51 ( 12 % ) of 441 patients in the atazanavir/ritonavir group and in 42 ( 10 % ) of 437 patients in the lopinavir/ritonavir group . Fewer patients in the atazanavir/ritonavir group than in the lopinavir/ritonavir group experienced grade 2 - 4 treatment-related diarrhoea ( 10 [ 2 % ] vs 50 [ 11 % ] ) and nausea ( 17 [ 4 % ] vs 33 [ 8 % ] ) . Grade 2 - 4 jaundice was seen in 16 ( 4 % ) of 441 patients in the atazanavir/ritonavir group versus none of 437 patients in the lopinavir/ritonavir group ; grade 3 - 4 increases in total bilirubin were seen in 146 ( 34 % ) of 435 patients on atazanavir/ritonavir and in one ( < 1 % ) of 431 patients on lopinavir/ritonavir . INTERPRETATION In treatment-naive patients , atazanavir/ritonavir once-daily demonstrated similar antiviral efficacy to lopinavir/ritonavir twice-daily , with less gastrointestinal toxicity but with a higher rate of hyperbilirubinaemia In a prospect i ve , open-label , 104-week study , patients who were infected with human immunodeficiency virus type 1 ( virus load , < 50 copies/mL ) and who were receiving protease inhibitor-based therapy were r and omly assigned to continue treatment with a protease inhibitor or to replace it with abacavir or efavirenz . Treatment failure , defined as virological failure ( virus load , > 500 copies/microL ) or any clinical or biochemical adverse event with a grade of > or=3 ( on the basis of the World Health Organization [ WHO ] or American Heart Association [ AHA ] scales ) , was the primary outcome measurement . Failure rates were more frequent in the group treated with protease inhibitors ( P<.01 ) , and there were no significant differences in the rate of treatment failure between the group treated with efavirenz and the group treated with abacavir . Tolerability was better in the groups treated with abacavir or with efavirenz versus those treated with protease inhibitors . Fewer patients who received efavirenz experienced viral rebound . Among all groups , the mean increase in the CD4 cell count was 131 cells/microL ( P<.001 ) , with no significant difference between groups . This switching strategy maintains optimal levels of virological suppression and may improve lipid profiles in most patients A r and omized , double-blind , double-dummy controlled , multicenter trial was conducted that involved 554 antiretroviral-naive human immunodeficiency virus-infected adults ( plasma HIV type 1 [ HIV-1 ] RNA level , > or=400 copies/mL ; CD4(+ ) cell count , > 100 cells/mm(3 ) ) and compared a 300-mg once-daily ( q.d . ) regimen of lamivudine ( 3TC ) versus a 150-mg twice-daily ( b.i.d . ) regimen of 3TC , combined with zidovudine ( 300 mg b.i.d . ) and efavirenz ( 600 mg q.d . ) , during a 48-week period . Treatments were considered equivalent if the 95 % confidence interval ( CI ) for the difference in proportions of patients achieving an HIV-1 RNA level of < 400 copies/mL was within the bound of -12 % to 12 % . At week 48 of the study , an intent-to-treat analysis in which patients with missing data were considered to have experienced treatment failure showed that the 3TC q.d . and 3TC b.i.d . regimens were equivalent ( HIV-1 RNA level < 400 copies/mL , 178 [ 64 % ] of 278 vs. 174 [ 63 % ] of 276 ; treatment difference , 1 % [ 95 % CI , -7.1 % to 8.9 % ] ; HIV-1 RNA level < 50 copies/mL , 165 [ 59 % ] of 278 vs. 168 [ 61 % ] of 276 ; treatment difference , 1.7 % [ 95 % CI , -9.7 % to 6.6 % ] ) . Median increase above baseline in CD4(+ ) cell count was similar ( q.d . group , + 144 cells/mm(3 ) ; b.i.d . group , + 146 cells/mm(3 ) ) , and the incidences of adverse events , disease progression , and HIV-associated conditions were comparable BACKGROUND Zidovudine , lamivudine , and efavirenz comprise a highly effective and well-tolerated triple regimen for antiretroviral-naive patients . Evaluating other unique nucleoside reverse-transcriptase inhibitor ( NRTI ) combinations for long-term viral suppression is desirable . METHODS This multicenter , r and omized , double-blind noninferiority clinical trial compared the efficacy and safety of abacavir with that of zidovudine plus lamivudine and efavirenz in 649 antiretroviral-naive HIV-infected patients . The primary objective was a comparison of proportions of patients achieving plasma HIV-1 RNA levels < or=50 copies/mL through week 48 of the study . RESULTS At study week 48 , 70 % of patients in the abacavir group , compared with 69 % in the zidovudine group , maintained confirmed plasma HIV-1 RNA levels of < or=50 copies/mL ( in the intent-to-treat exposed population ) . Virologic failure was infrequent ( 6 % in the abacavir group and 4 % in the zidovudine group ) . There was a significant CD4(+ ) cell response ( 209 cells/mm(3 ) in the abacavir group and 155 cells/mm(3 ) in the zidovudine group ) . Safety profiles were as expected . CONCLUSION Abacavir provided an effective and durable antiretroviral response that was noninferior to zidovudine , when combined with lamivudine and efavirenz BACKGROUND Durable suppression of replication of the human immunodeficiency virus ( HIV ) depends on the use of potent , well-tolerated antiretroviral regimens to which patients can easily adhere . METHODS We conducted an open-label , noninferiority study involving 517 patients with HIV infection who had not previously received antiretroviral therapy and who were r and omly assigned to receive either a regimen of tenofovir disoproxil fumarate ( DF ) , emtricitabine , and efavirenz once daily ( tenofovir-emtricitabine group ) or a regimen of fixed-dose zidovudine and lamivudine twice daily plus efavirenz once daily ( zidovudine-lamivudine group ) . The primary end point was the proportion of patients without baseline resistance to efavirenz in whom the HIV RNA level was less than 400 copies per milliliter at week 48 of the study . RESULTS Through week 48 , significantly more patients in the tenofovir-emtricitabine group reached and maintained the primary end point of less than 400 copies of HIV RNA per milliliter than did those in the zidovudine-lamivudine group ( 84 percent vs. 73 percent , respectively ; 95 percent confidence interval for the difference , 4 to 19 percent ; P=0.002 ) . This difference excludes the inferiority of the tenofovir DF , emtricitabine , and efavirenz regimen , indicating a significantly greater response with this regimen . Significant differences were also seen in the proportion of patients with HIV RNA levels of less than 50 copies per milliliter ( 80 percent in the tenofovir-emtricitabine group vs. 70 percent in the zidovudine-lamivudine group ; 95 percent confidence interval for the difference , 2 to 17 percent ; P=0.02 ) and in increases in CD4 cell counts ( 190 vs. 158 cells per cubic millimeter , respectively ; 95 percent confidence interval for the difference , 9 to 55 ; P=0.002 ) . More patients in the zidovudine-lamivudine group than in the tenofovir-emtricitabine group had adverse events result ing in discontinuation of the study drugs ( 9 percent vs. 4 percent , respectively ; P=0.02 ) . In none of the patients did the K65R mutation develop . CONCLUSIONS Through week 48 , the combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efavirenz and proved superior in terms of virologic suppression , CD4 response , and adverse events result ing in discontinuation of the study drugs . ( Clinical Trials.gov number , NCT00112047 . BACKGROUND The integrase inhibitor elvitegravir ( EVG ) has been co-formulated with the CYP3A4 inhibitor cobicistat ( COBI ) , emtricitabine ( FTC ) , and tenofovir disoproxil fumarate ( TDF ) in a single tablet given once daily . We compared the efficacy and safety of EVG/COBI/FTC/TDF with st and ard of care-co-formulated efavirenz (EFV)/FTC/TDF-as initial treatment for HIV infection . METHODS In this phase 3 trial , treatment-naive patients from outpatient clinics in North America were r and omly assigned by computer-generated allocation sequence with a block size of four in a 1:1 ratio to receive EVG/COBI/FTC/TDF or EFV/FTC/TDF , once daily , plus matching placebo . Patients and study staff involved in giving study treatment , assessing outcomes , and collecting and analysing data were masked to treatment allocation . Eligibility criteria included screening HIV RNA concentration of 5000 copies per mL or more , and susceptibility to efavirenz , emtricitabine , and tenofovir . The primary endpoint was HIV RNA concentration of fewer than 50 copies per mL at week 48 . The study is registered with Clinical Trials.gov , number NCT01095796 . FINDINGS 700 patients were r and omly assigned and treated ( 348 with EVG/COBI/FTC/TDF , 352 with EFV/FTC/TDF ) . EVG/COBI/FTC/TDF was non-inferior to EFV/FTC/TDF ; 305/348 ( 87·6 % ) versus 296/352 ( 84·1 % ) of patients had HIV RNA concentrations of fewer than 50 copies per mL at week 48 ( difference 3·6 % , 95 % CI -1·6 % to 8·8 % ) . Proportions of patients discontinuing drugs for adverse events did not differ substantially ( 13/348 in the EVG/COBI/FTC/TDF group vs 18/352 in the EFV/FTC/TDF group ) . Nausea was more common with EVG/COBI/FTC/TDF than with EFV/FTC/TDF ( 72/348 vs 48/352 ) and dizziness ( 23/348 vs 86/352 ) , abnormal dreams ( 53/348 vs 95/352 ) , insomnia ( 30/348 vs 49/352 ) , and rash ( 22/348 vs 43/352 ) were less common . Serum creatinine concentration increased more by week 48 in the EVG/COBI/FTC/TDF group than in the EFV/FTC/TDF group ( median 13 μmol/L , IQR 5 to 20 vs 1 μmol/L , -6 to 8 ; p<0·001 ) . INTERPRETATION If regulatory approval is given , EVG/COBI/FTC/TDF would be the only single-tablet , once-daily , integrase-inhibitor-based regimen for initial treatment of HIV infection . FUNDING Gilead Sciences BACKGROUND Antiretroviral therapy is complicated by drug interactions and contraindications . Novel regimens are needed . METHODS This open label study r and omly assigned treatment-naive , human immunodeficiency virus (HIV)-infected subjects to receive tenofovir-emtricitabine with efavirenz ( Arm I ) , with ritonavir-boosted atazanavir ( Arm II ) , or with zidovudine/abacavir ( Arm III ) . Pair-wise comparisons of differences in time-weighted mean change from baseline plasma HIV-RNA to week 48 formed the primary analysis . Treatment arms were noninferior if the upper limit of the 95 % confidence interval ( CI ) was < 0.5 log(10 ) copies/mL. Secondary objectives included virologic , immunologic and safety end points . RESULTS The intention-to-treat population comprised 322 patients ( Arm I , n = 114 ; Arm II , n = 105 ; and Arm III , n = 103 ) . Noninferiority for the primary end point was established . Analysis for superiority showed that Arm III was significantly less potent than Arm I ( -0.20 log(10 ) copies/mL ; 95 % CI , -0.39 to -0.01 log(10 ) copies/mL ; P = .038 ) . The proportions of patients on each of Arm I ( 95 % ) and Arm II ( 96 % ) with < 200 copies/mL were not different ( P = .75 ) , but the percentage of patients in Arm III with < 200 copies/mL ( 82 % ) was significantly lower ( P = .005 ) . CD4 + cell counts did not differ . Serious adverse events were more frequent in Arm III ( n = 30 ) than in Arm I or Arm II ( n = 15 for each ; P = .062 ) . CONCLUSIONS A novel quadruple nucleo(t)side combination demonstrated significantly less suppression of HIV replication , compared with the suppression demonstrated by st and ard antiretroviral therapy regimens , although it did meet the predetermined formal definition of noninferiority . Secondary analyses indicated statistically inferior virologic and safety performance . Efavirenz and ritonavir-boosted atazanavir arms were equivalent in viral suppression and safety BACKGROUND Antiretroviral therapy has greatly reduced HIV mortality and morbidity . However , the best sequence of regimens and implication s of initial regimen for long-term therapeutic success are not well defined . METHODS In INITIO , a large international r and omised trial , we compared antiretroviral therapy with two nucleoside analogue reverse transcriptase inhibitors ( didanosine+stavudine ) plus either a non-nucleoside reverse transcriptase inhibitor ( efavirenz , EFV ) or a protease inhibitor ( nelfinavir , NFV ) , or both ( EFV/NFV ) , in patients with HIV-1 infection who had not previously received antiretroviral drugs . Primary outcomes were proportion with undetectable HIV RNA in plasma , and change in CD4 count from baseline at 3 years . Analyses were by intention-to-treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N44582462 . FINDINGS We followed up 911 participants ( 297 EFV , 311 NFV , 303 EFV/NFV ) . At 3 years , the proportion with HIV RNA less than 50 copies per mL was highest in the EFV group ( 188 [ 74 % ] EFV , 162 [ 62 % ] NFV , 155 [ 62 % ] EFV/NFV ; p=0.004 ) . Mean ( 95 % CI ) increases in CD4 count were 316x10(6 ) cells per L ( 288 - 343 ) for EFV , 289x10(6 ) cells per L ( 262 - 316 ) for NFV , and 274x10(6 ) cells per L ( 231 - 291 ) for EFV/NFV ( p=0.1 ) . Fewer participants in the EFV group than in the other groups stopped adequate antiretroviral therapy for more than 30 days ( p=0.005 ) . Participants in the EFV/NFV group had shorter time to stopping the initial regimen ( p<0.0001 ) and to a treatment modifying adverse event ( p=0.04 ) than those in the other groups . INTERPRETATION Starting antiretroviral therapy with a three-drug/two-class regimen including efavirenz was better than starting with regimens including nelfinavir or efavirenz plus nelfinavir in terms of virological suppression and durability of the initial regimen . The shorter time on adequate antiretroviral therapy or to a treatment-modifying adverse event might explain the absence of additional benefit for the four-drug regimen BACKGROUND Dolutegravir ( S/GSK1349572 ) , a once-daily , unboosted integrase inhibitor , was recently approved in the United States for the treatment of human immunodeficiency virus type 1 ( HIV-1 ) infection in combination with other antiretroviral agents . Dolutegravir , in combination with abacavir-lamivudine , may provide a simplified regimen . METHODS We conducted a r and omized , double-blind , phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more . Participants were r and omly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily ( DTG-ABC-3TC group ) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily ( EFV-TDF-FTC group ) . The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48 . Secondary end points included the time to viral suppression , the change from baseline in CD4 + T-cell count , safety , and viral resistance . RESULTS A total of 833 participants received at least one dose of study drug . At week 48 , the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group ( 88 % vs. 81 % , P=0.003 ) , thus meeting the criterion for superiority . The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group ( 28 vs. 84 days , P<0.001 ) , as well as greater increases in CD4 + T-cell count ( 267 vs. 208 per cubic millimeter , P<0.001 ) . The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group ( 2 % vs. 10 % ) ; rash and neuropsychiatric events ( including abnormal dreams , anxiety , dizziness , and somnolence ) were significantly more common in the EFV-TDF-FTC group , whereas insomnia was reported more frequently in the DTG-ABC-3TC group . No participants in the DTG-ABC-3TC group had detectable antiviral resistance ; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group . CONCLUSIONS Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz-tenofovir DF-emtricitabine . ( Funded by ViiV Healthcare ; SINGLE Clinical Trials.gov number , NCT01263015 . ) Objective : Present 96-week data from ongoing ARTEMIS ( AntiRetroviral Therapy with TMC114 ExaMined In Naive Subjects ) trial . Methods : R and omized , open-label , phase III trial of antiretroviral-naive patients with HIV-1 RNA at least 5000 copies/ml ( stratified by HIV-1 RNA and CD4 cell count ) receiving darunavir/ritonavir ( DRV/r ) 800/100 mg once daily or lopinavir/ritonavir ( LPV/r ) 800/200 mg total daily dose ( twice daily or once daily ) and fixed-dose tenofovir/emtricitabine . Primary outcome measure was noninferiority of DRV/r vs. LPV/r in virologic response ( < 50 copies/ml , time-to-loss of virologic response ) at 96 weeks ( secondary outcome : superiority ) . Results : Six hundred eighty-nine patients were enrolled . At week 96 , significantly more DRV/r ( 79 % ) than LPV/r patients ( 71 % ) had viral load less than 50 copies/ml , confirming statistical noninferiority ( estimated difference : 8.4 % ; 95 % confidence interval 1.9–14.8 ; P < 0.001 ; per- protocol ) and superiority ( P = 0.012 ; intent-to-treat ) in virologic response . Median CD4 cell count increases from baseline were 171 and 188 cells/μl for DRV/r and LPV/r , respectively ( P = 0.57 ; noncompleter = failure ) . Overall , 4 % of DRV/r patients and 9 % of LPV/r patients discontinued treatment due to adverse events . Lower rates of grade 2–4 treatment-related diarrhea were seen with DRV/r ( 4 % ) vs. LPV/r ( 11 % ; P < 0.001 ) , whereas grade 2–4 treatment-related rash occurred infrequently in both arms ( 3 vs. 1 % , respectively ; P = 0.273 ) . DRV/r patients had smaller median increases in triglycerides ( 0.1 and 0.6 mmol/l , respectively , P < 0.0001 ) and total cholesterol ( 0.6 and 0.9 mmol/l , respectively ; P < 0.0001 ) than LPV/r patients ; levels remained below National Cholesterol Education Program cut-offs for DRV/r . Conclusion : At week 96 , once-daily DRV/r was both statistically noninferior and superior in virologic response to LPV/r , with a more favorable gastrointestinal and lipid profile , confirming DRV/r as an effective , well tolerated , and durable option for antiretroviral-naive patients BACKGROUND Dolutegravir has been shown to be non-inferior to an integrase inhibitor and superior to a non-nucleoside reverse transcriptase inhibitor ( NNRTI ) . In FLAMINGO , we compared dolutegravir with darunavir plus ritonavir in individuals naive for antiretroviral therapy . METHODS In this multicentre , open-label , phase 3b , non-inferiority study , HIV-1-infected antiretroviral therapy-naive adults with HIV-1 RNA concentration of 1000 copies per mL or more and no resistance at screening were r and omly assigned ( 1:1 ) to receive either dolutegravir 50 mg once daily or darunavir 800 mg plus ritonavir 100 mg once daily , with investigator-selected tenofovir-emtricitabine or abacavir-lamivudine . R and omisation was stratified by screening HIV-1 RNA ( ≤100,000 or > 100,000 copies per mL ) and nucleoside reverse transcriptase inhibitor ( NRTI ) selection . The primary endpoint was the proportion of patients with HIV-1 RNA concentration lower than 50 copies per mL ( Food and Drug Administration [ FDA ] snapshot algorithm ) at week 48 with a 12 % non-inferiority margin . This trial is registered with Clinical Trials.gov , NCT01449929 . FINDINGS Recruitment began on Oct 31 , 2011 , and was completed on May 24 , 2012 , in 64 research centres in nine countries worldwide . Of 595 patients screened , 484 patients were included in the analysis ( 242 in each group ) . At week 48 , 217 ( 90 % ) patients receiving dolutegravir and 200 ( 83 % ) patients receiving darunavir plus ritonavir had HIV-1 RNA of less than 50 copies per mL ( adjusted difference 7·1 % , 95 % CI 0·9 - 13·2 ) , non-inferiority and on pre-specified secondary analysis dolutegravir was superior ( p=0·025 ) . Confirmed virological failure occurred in two ( < 1 % ) patients in each group ; we recorded no treatment-emergent resistance in either group . Discontinuation due to adverse events or stopping criteria was less frequent for dolutegravir ( four [ 2 % ] patients ) than for darunavir plus ritonavir ( ten [ 4 % ] patients ) and contributed to the difference in response rates . The most commonly reported ( ≥10 % ) adverse events were diarrhoea ( dolutegravir 41 [ 17 % ] patients vs darunavir plus ritonavir 70 [ 29 % ] patients ) , nausea ( 39 [ 16 % ] vs 43 [ 18 % ] ) , and headache ( 37 [ 15 % ] vs 24 [ 10 % ] ) . Patients receiving dolutegravir had significantly fewer low-density lipoprotein values of grade 2 or higher ( 11 [ 2 % ] vs 36 [ 7 % ] ; p=0·0001 ) . INTERPRETATION Once-daily dolutegravir was superior to once-daily darunavir plus ritonavir . Once-daily dolutegravir in combination with fixed-dose NRTIs represents an effective new treatment option for HIV-1-infected , treatment-naive patients . FUNDING ViiV Healthcare and Shionogi & CONTEXT Tenofovir disoproxil fumarate ( DF ) is a once-daily nucleotide analogue reverse transcriptase inhibitor . OBJECTIVE To evaluate the efficacy and safety of tenofovir DF compared with stavudine in antiretroviral-naive patients . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , r and omized , double-blind study conducted at 81 centers in the United States , South America , and Europe from June 9 , 2000 , to January 30 , 2004 . A total of 753 patients infected with HIV who were antiretroviral naive were screened and 602 patients entered the study . INTERVENTION Patients were r and omized to receive either tenofovir DF ( n = 299 ) or stavudine ( n = 303 ) , with placebo , in combination with lamivudine and efavirenz . MAIN OUTCOME MEASURE Proportion of patients with HIV RNA levels of less than 400 copies/mL at week 48 . RESULTS In the primary intent-to-treat analysis in which patients with missing data or who added or switched antiretroviral medications before week 48 were considered as failures , the proportion of patients with HIV RNA of less than 400 copies/mL at week 48 was 239 ( 80 % ) of 299 in patients receiving tenofovir DF and 253 ( 84 % ) of 301 in patients receiving stavudine ( 95 % confidence interval , -10.4 % to 1.5 % ) , exceeding the predefined -10 % limit for equivalence . However , equivalence was demonstrated in the secondary analyses ( HIV RNA < 50 copies/mL ) at week 48 and through 144 weeks . Virologic failure was associated most frequently with efavirenz and lamivudine resistance . Through 144 weeks , the K65R mutation emerged in 8 and 2 patients in the tenofovir DF and stavudine groups , respectively ( P = .06 ) . A more favorable mean change from baseline in fasting lipid profile was noted in the tenofovir DF group at week 144 : for triglyceride levels ( + 1 mg/dL for tenofovir DF [ n = 170 ] vs + 134 mg/dL for stavudine [ n = 162 ] , P<.001 ) , total cholesterol ( + 30 mg/dL [ n = 170 ] vs + 58 mg/dL [ n = 162 ] , P<.001 ) , direct low-density lipoprotein cholesterol ( + 14 mg/dL [ n = 169 ] vs + 26 mg/dL [ n = 161 ] , P<.001 ) , and high-density lipoprotein cholesterol ( + 9 mg/dL [ n = 168 ] vs + 6 mg/dL [ n = 154 ] , P = .003 ) . Investigator-reported lipodystrophy was less common in the tenofovir DF group compared with the stavudine group ( 9 [ 3 % ] of 299 vs 58 [ 19 % ] of 301 , P<.001 ) . The number of bone fractures and the renal safety profile were similar between the 2 groups . CONCLUSIONS Through 144 weeks , the combination of tenofovir DF , lamivudine , and efavirenz was highly effective and comparable with stavudine , lamivudine , and efavirenz in antiretroviral-naive patients . However , tenofovir DF appeared to be associated with better lipid profiles and less lipodystrophy BACKGROUND To our knowledge , to date , no prospect i ve , r and omized , clinical trial has compared st and ard doses of efavirenz- and nevirapine-based antiretroviral therapy among patients with concurrent human immunodeficiency virus type 1 ( HIV-1 ) infection and tuberculosis ( TB ) who are receiving rifampicin . METHODS Rifampicin recipients with concurrent HIV-1 infection and TB were r and omized to receive antiretroviral therapy that included either efavirenz ( 600 mg per day ) or nevirapine ( 400 mg per day ) . Efavirenz and nevirapine concentrations at 12 h after dosing ( C12 ) were monitored at weeks 6 and 12 . CD4 + cell counts and HIV-1 RNA levels were assessed every 12 weeks . RESULTS One hundred forty-two patients were r and omized into 2 groups equally . The mean body weight of patients was 53 kg , the mean CD4 + cell count was 65 cells/mm3 , and the median HIV-1 RNA level was 5.8 log10 copies/mL. At weeks 6 and 12 , the mean C12 of efavirenz ( + /- st and ard deviation ) were 4.27+/-4.49 and 3.54+/-3.78 mg/L , respectively , and those for nevirapine were 5.59+/-3.48 and 5.6+/-2.65 mg/L , respectively . Interpatient variability in the efavirenz group was 2.3-fold greater than that in the nevirapine group ( coefficient of variation , 107 % vs. 47 % ) . At week 12 , 3.1 % of patients in the efavirenz group and 21.3 % in the nevirapine group had C12 values that were less than the recommended minimum concentrations ( odds ratio , 8.396 ; 95 % confidence interval , 1.808 - 38.993 ; P= .002 ) . Intention-to-treat analysis revealed that 73.2 % and 71.8 % of patients in the efavirenz and nevirapine groups , respectively , achieved HIV-1 RNA levels < 50 copies/mL at week 48 , with respective mean CD4 + cell counts of 274 and 252 cells/mm3 ( P > .05 ) . Multivariate analysis revealed that patients with low C12 values and those with a body weight < 55 kg were 3.6 and 2.4 times more likely , respectively , to develop all-cause treatment failure ( P < .05 ) . CONCLUSIONS Antiretroviral therapy regimens containing efavirenz ( 600 mg per day ) were less compromised by concomitant use of rifampicin than were those that contained nevirapine ( 400 mg per day ) in patients with concurrent HIV-1 infection and TB . Low drug exposure and low body weight are important predictive factors for treatment failure BACKGROUND Use of raltegravir with optimum background therapy is effective and well tolerated in treatment-experienced patients with multidrug-resistant HIV-1 infection . We compared the safety and efficacy of raltegravir with efavirenz as part of combination antiretroviral therapy for treatment-naive patients . METHODS Patients from 67 study centres on five continents were enrolled between Sept 14 , 2006 , and June 5 , 2008 . Eligible patients were infected with HIV-1 , had viral RNA ( vRNA ) concentration of more than 5000 copies per mL , and no baseline resistance to efavirenz , tenofovir , or emtricitabine . Patients were r and omly allocated by interactive voice response system in a 1:1 ratio ( double-blind ) to receive 400 mg oral raltegravir twice daily or 600 mg oral efavirenz once daily , in combination with tenofovir and emtricitabine . The primary efficacy endpoint was achievement of a vRNA concentration of less than 50 copies per mL at week 48 . The primary analysis was per protocol . The margin of non-inferiority was 12 % . This study is registered with Clinical Trials.gov , number NCT00369941 . FINDINGS 566 patients were enrolled and r and omly allocated to treatment , of whom 281 received raltegravir , 282 received efavirenz , and three were never treated . At baseline , 297 ( 53 % ) patients had more than 100 000 vRNA copies per mL and 267 ( 47 % ) had CD4 counts of 200 cells per microL or less . The main analysis ( with non-completion counted as failure ) showed that 86.1 % ( n=241 patients ) of the raltegravir group and 81.9 % ( n=230 ) of the efavirenz group achieved the primary endpoint ( difference 4.2 % , 95 % CI -1.9 to 10.3 ) . The time to achieve such viral suppression was shorter for patients on raltegravir than on efavirenz ( log-rank test p<0.0001 ) . Significantly fewer drug-related clinical adverse events occurred in patients on raltegravir ( n=124 [ 44.1 % ] ) than those on efavirenz ( n=217 [ 77.0 % ] ; difference -32.8 % , 95 % CI -40.2 to -25.0 , p<0.0001 ) . Serious drug-related clinical adverse events occurred in less than 2 % of patients in each drug group . INTERPRETATION Raltegravir-based combination treatment had rapid and potent antiretroviral activity , which was non-inferior to that of efavirenz at week 48 . Raltegravir is a well tolerated alternative to efavirenz as part of a combination regimen against HIV-1 in treatment-naive patients . FUNDING Merck BACKGROUND The non-nucleoside reverse transcriptase inhibitor ( NNRTI ) , rilpivirine ( TMC278 ; Tibotec Pharmaceuticals , County Cork , Irel and ) , had equivalent sustained efficacy to efavirenz in a phase 2b trial in treatment-naive patients infected with HIV-1 , but fewer adverse events . We aim ed to assess non-inferiority of rilpivirine to efavirenz in a phase 3 trial with common background nucleoside or nucleotide reverse transcriptase inhibitors ( N[t]RTIs ) . METHODS We undertook a 96-week , phase 3 , r and omised , double-blind , double-dummy , non-inferiority trial in 98 hospitals or medical centres in 21 countries . We enrolled adults ( ≥18 years ) not previously given antiretroviral therapy and with a screening plasma viral load of 5000 copies per mL or more and viral sensitivity to background N(t)RTIs . We r and omly allocated patients ( 1:1 ) using a computer-generated interactive web-response system to receive oral rilpivirine 25 mg once daily or efavirenz 600 mg once daily ; all patients received an investigator-selected regimen of background N(t)RTIs ( tenofovir-disoproxil-fumarate plus emtricitabine , zidovudine plus lamivudine , or abacavir plus lamivudine ) . The primary outcome was non-inferiority ( 12 % margin on logistic regression analysis ) at 48 weeks in terms of confirmed response ( viral load < 50 copies per mL , defined by the intent-to-treat time to loss of virologic response [ TLOVR ] algorithm ) in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT00543725 . FINDINGS From May 22 , 2008 , we screened 947 patients and enrolled 340 to each group . 86 % of patients ( 291 of 340 ) who received at least one dose of rilpivirine responded , compared with 82 % of patients ( 276 of 338 ) who received at least one dose of efavirenz ( difference 3.5 % [ 95 % CI -1.7 to 8.8 ] ; p(non-inferiority)<0.0001 ) . Increases in CD4 cell counts were much the same between groups . 7 % of patients ( 24 of 340 ) receiving rilpivirine had a virological failure compared with 5 % of patients ( 18 of 338 ) receiving efavirenz . 4 % of patients ( 15 ) in the rilpivirine group and 7 % ( 25 ) in the efavirenz group discontinued treatment due to adverse events . Grade 2 - 4 treatment-related adverse events were less common with rilpivirine ( 16 % [ 54 patients ] ) than they were with efavirenz ( 31 % [ 104 ] ; p<0.0001 ) , as were rash and dizziness ( p<0.0001 for both ) and increases in lipid levels were significantly lower with rilpivirine than they were with efavirenz ( p<0.0001 ) . INTERPRETATION Despite a slightly increased incidence of virological failures , a favourable safety profile and non-inferior efficacy compared with efavirenz means that rilpivirine could be a new treatment option for treatment-naive patients infected with HIV-1 . FUNDING Tibotec BACKGROUND Selection of first-line antiretroviral therapy requires consideration of efficacy as well as effects on lipids given the increased concern about cardiovascular risk in HIV-1 patients . METHODS ARTEN is a r and omized , open-label , non-inferiority trial that compares nevirapine ( NVP ) 200 mg twice daily or 400 mg once daily to atazanavir/ritonavir ( ATZ/r ) 300 mg/100 mg once daily , each combined with fixed-dose tenofovir disoproxil fumarate ( TDF ) 300 mg/emtricitabine ( FTC ) 200 mg once daily , in antiretroviral-naive HIV-1 patients with CD4(+ ) T-cell counts < 400 ( men ) and < 250 cells/mm(3 ) ( women ) . The primary end point was plasma HIV RNA<50 copies/ml at two consecutive visits prior to week 48 . RESULTS A total of 569 patients were r and omized and treated . Overall , 66.8 % of NVP and 65.3 % of ATZ/r patients achieved the primary end point ( difference 1.9 % , 95 % CI -5.9 - 9.8 % ) . Similar rates of serious adverse events were observed ( 9.6 % on NVP versus 8.8 % on ATZ/r ) , although discontinuations due to adverse events were more frequent with NVP than ATZ/r ( 13.6 % versus 3.6 % , respectively ) . None of the 28 patients virologically failing ATZ/r selected resistance mutations , while they were selected in 29/44 patients virologically failing NVP . NVP induced a significantly greater increase in high-density lipoprotein cholesterol ( HDL-c ) and apolipoprotein A1 from baseline than ATZ/r , whereas triglycerides increased significantly more with ATZ/r than NVP . Mean change from baseline in TC : HDL-c ratio was -0.24 for NVP and 0.13 for ATZ/r ( P=0.0001 ) . CONCLUSIONS NVP demonstrated at week 48 non-inferior antiviral efficacy compared with ATZ/r when given along with TDF/FTC , despite more drug-related discontinuations with NVP than ATZ/r . NVP was associated with a lower atherogenic lipid profile than ATZ/r although resistance mutations were more frequently selected with NVP than ATZ/r Background : Abacavir/lamivudine and tenofovir/emtricitabine fixed-dose combinations are commonly used first-line antiretroviral therapies , yet few studies have comprehensively compared their safety profiles . Methods : Forty-eight-week data are presented from this multicenter , r and omized , open-label study comparing the safety profiles of abacavir/lamivudine and tenofovir/emtricitabine , both administered with efavirenz , in HLA-B*5701-negative HIV-1-infected adults . Results : Three hundred eighty-five subjects were enrolled in the study . The overall rate of withdrawal was high ( 28 % ) . Changes in estimated glomerular filtration rate from baseline were similar between arms [ difference 0.953 mL·min−1·1.73 m−2 ( 95 % confidence interval : −1.445 to 3.351 ) , P = 0.435 ] . Urinary excretion of retinol-binding protein and β-2 microglobulin increased significantly more in the tenofovir/emtricitabine arm ( + 50 % ; + 24 % ) compared with the abacavir/lamivudine arm ( no change ; −47 % ) ( P < 0.0001 ) . A lower proportion achieved viral load < 50 copies per milliliter in the abacavir/lamivudine arm ( 114 of 192 , 59 % ) compared with the tenofovir/emtricitabine arm ( 137 of 193 , 71 % ) [ difference 11.6 % ( 95 % confidence interval : 2.2 to 21.1 ) ] . The overall virological failure rate was low . The adverse event rate was similar between arms ( except drug hypersensitivity , reported more in the abacavir/lamivudine arm ) . Conclusions : The study showed no difference in estimated glomerular filtration rate between the arms , however , increases in markers of tubular dysfunction were observed in the tenofovir/emtricitabine arm , the long-term consequence of which is unclear . A significant difference in efficacy favoring tenofovir/emtricitabine was observed BACKGROUND Lopinavir-ritonavir is a preferred protease inhibitor co-formulation for initial HIV-1 treatment . Fosamprenavir-ritonavir has shown similar efficacy and safety to lopinavir-ritonavir when each is combined with two nucleoside reverse transcriptase inhibitors . We compared the two treatments directly in antiretroviral-naive patients . METHODS This open-label , non-inferiority study included 878 antiretroviral-naive , HIV-1-infected patients r and omised to receive either fosamprenavir-ritonavir 700 mg/100 mg twice daily or lopinavir-ritonavir 400 mg/100 mg twice daily , each with the co-formulation of abacavir-lamivudine 600 mg/300 mg once daily . Primary endpoints were proportion of patients achieving HIV-1 RNA less than 400 copies per mL at week 48 and treatment discontinuations because of an adverse event . The intent-to-treat analysis included all patients exposed to at least one dose of r and omised study medication . This study is registered with Clinical Trials.gov , number NCT00085943 . FINDINGS At week 48 , non-inferiority of fosamprenavir-ritonavir to lopinavir-ritonavir ( 95 % CI around the treatment difference -4.84 to 7.05 ) was shown , with 315 of 434 ( 73 % ) patients in the fosamprenavir-ritonavir group and 317 of 444 ( 71 % ) in the lopinavir-ritonavir group achieving HIV-1 RNA less than 400 copies per mL. Treatment discontinuations due to an adverse event were few and occurred with similar frequency in the two treatment groups ( fosamprenavir-ritonavir 53 , 12 % ; lopinavir-ritonavir 43 , 10 % ) . Diarrhoea , nausea , and abacavir hypersensitivity were the most frequent drug-related grade 2 - 4 adverse events . Treatment-emergent drug resistance was rare ; no patient had virus that developed reduced susceptibility to fosamprenavir-ritonavir or lopinavir-ritonavir . INTERPRETATION Fosamprenavir-ritonavir twice daily in treatment-naive patients provides similar antiviral efficacy , safety , tolerability , and emergence of resistance as lopinavir-ritonavir , each in combination with abacavir-lamivudine Objectives : To compare efficacy , resistance development , and safety between rilpivirine and efavirenz in treatment-naive , HIV-1-infected adults with baseline viral load 100 000 copies/ml or less in the pooled 48-week data set of the ECHO ( Efficacy Comparison in treatment-naive HIV-infected subjects Of TMC278 and EFV ) and THRIVE ( TMC278 against HIV , in a once-daily RegImen Vs . Efavirenz ) trials . Design : Phase III , double-blind , double-dummy , r and omized trials . Methods : Patients received rilpivirine 25 mg once daily ( q.d . ) or efavirenz 600 mg q.d . with two nucleoside/tide reverse transcriptase inhibitors [ N(t)RTIs ] . This analysis considers the sub population of 368 rilpivirine and 330 efavirenz patients with baseline viral load 100 000 copies/ml or less . Results : Significantly higher 48-week response rates ( viral load < 50 copies/ml , intent-to-treat-time-to-loss-of-virological response ) were observed with rilpivirine vs. efavirenz [ 90 vs. 84 % , respectively ; difference 6.6 % ( 95 % confidence interval 1.6–11.5 % ) ] . The proportion of patients experiencing virological failure ( VFres ) was 5 % in each treatment group . A comparable proportion of VFres patients in each group developed nonnucleoside reverse transcriptase inhibitor resistance-associated mutations ( RAMs ) [ rilpivirine : 6/16 ( 38 % ) vs. efavirenz : 5/12 ( 42 % ) ] . A numerically higher proportion of rilpivirine VFres patients developed N(t)RTI RAMs [ 7/16 ( 44 % ) ] vs. efavirenz [ 2/12 ( 17 % ) ] ; P = 0.2232 . A significantly lower incidence for rilpivirine vs. efavirenz was observed for the following events : treatment-related grade 2–4 overall adverse events ( 17 vs. 30 % ; P < 0.0001 ) , rash ( any type ; 2 vs. 12 % ; P < 0.0001 ) , and neurological adverse events ( 19 vs. 40 % ; P < 0.0001 ) , including dizziness ( 10 vs. 29 % ; P < 0.0001 ) . There was no significant difference between groups in the total cholesterol/high-density lipoprotein cholesterol ratio . Conclusion : In treatment-naive patients with baseline viral load 100 000 copies/ml or less , rilpivirine along with two N(t)RTIs achieved a high response , with a comparable frequency of VFres and more favorable tolerability than efavirenz BACKGROUND Dolutegravir ( S/GSK1349572 ) is a once-daily HIV integrase inhibitor with potent antiviral activity and a favourable safety profile . We compared dolutegravir with HIV integrase inhibitor raltegravir , as initial treatment for adults with HIV-1 . METHODS SPRING-2 is a 96 week , phase 3 , r and omised , double-blind , active-controlled , non-inferiority study that began on Oct 19 , 2010 , at 100 sites in Canada , USA , Australia , and Europe . Treatment-naive adults ( aged ≥ 18 years ) with HIV-1 infection and HIV-1 RNA concentrations of 1000 copies per mL or greater were r and omly assigned ( 1:1 ) via a computer-generated r and omisation sequence to receive either dolutegravir ( 50 mg once daily ) or raltegravir ( 400 mg twice daily ) . Study drugs were given with coformulated tenofovir/emtricitabine or abacavir/lamivudine . R and omisation was stratified by screening HIV-1 RNA ( ≤ 100,000 copies per mL or > 100,000 copies per mL ) and nucleoside reverse transcriptase inhibitor backbone . Investigators were not masked to HIV-1 RNA results before r and omisation . The primary endpoint was the proportion of participants with HIV-1 RNA less than 50 copies per mL at 48 weeks , with a 10 % non-inferiority margin . Main secondary endpoints were changes from baseline in CD4 cell counts , incidence and severity of adverse events , changes in laboratory parameters , and genotypic or phenotypic evidence of resistance . Our primary analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01227824 . FINDINGS 411 patients were r and omly allocated to receive dolutegravir and 411 to receive raltegravir and received at least one dose of study drug . At 48 weeks , 361 ( 88 % ) patients in the dolutegravir group achieved an HIV-1 RNA value of less than 50 copies per mL compared with 351 ( 85 % ) in the raltegravir group ( adjusted difference 2·5 % ; 95 % CI -2·2 to 7·1 ) . Adverse events were similar between treatment groups . The most common events were nausea ( 59 [ 14 % ] patients in the dolutegravir group vs 53 [ 13 % ] in the raltegravir group ) , headache ( 51 [ 12 % ] vs 48 [ 12 % ] ) , nasopharyngitis ( 46 [ 11 % ] vs 48 [ 12 % ] ) , and diarrhoea ( 47 [ 11 % ] in each group ) . Few patients had drug-related serious adverse events ( three [ < 1 % ] vs five [ 1 % ] ) , and few had adverse events leading to discontinuation ( ten [ 2 % ] vs seven [ 2 % ] in each group ) . CD4 cell counts increased from baseline to week 48 in both treatment groups by a median of 230 cells per μL. Rates of grade d laboratory toxic effects were similar . We noted no evidence of treatment-emergent resistance in patients with virological failure on dolutegravir , whereas of the patients with virologic failure who received raltegravir , one ( 6 % ) had integrase treatment-emergent resistance and four ( 21 % ) had nucleoside reverse transcriptase inhibitors treatment-emergent resistance . INTERPRETATION The non-inferior efficacy and similar safety profile of dolutegravir compared with raltegravir means that if approved , combination treatment with once-daily dolutegravir and fixed-dose nucleoside reverse transcriptase inhibitors would be an effective new option for treatment of HIV-1 in treatment-naive patients . FUNDING ViiV Healthcare We prospect ively studied long-term antiretroviral adherence patterns and their impact on biologic outcomes for human immunodeficiency virus (HIV)-infected participants in 2 r and omized , multicenter clinical trials . For the period from baseline to month 12 of the study , participants who reported adherence levels of 100 % , 80%-99 % , and 0%-79 % had plasma HIV RNA levels that decreased by 2.77 , 2.33 , and 0.67 log(10 ) copies/mL , respectively ( P<.001 ) , whereas their CD4 counts increased by 179 , 159 , and 53 cells/mm(3 ) , respectively ( P<.001 ) . Adherence predicted nondetectable HIV RNA levels ( < 50 copies/mL ) at 12 months of follow-up ( P<.001 ) . The HIV RNA level was nondetectable in 72 % of participants who reported 100 % adherence at all 4 follow-up visits , compared with 66 % , 41 % , 35 % , and 13 % of participants who reported 100 % adherence at 3 , 2 , 1 , or 0 follow-up visits , respectively ( P<.001 ) . Nonwhite race was associated with poorer adherence ( P<.001 ) , and older age was associated with better adherence ( P<.001 ) Objective : To compare alternative class-sparing antiretroviral regimens in treatment-naive subjects . Design : Open-label , multicenter , r and omized trial of up to 3 consecutive treatment regimens over 96 weeks . Methods : Two hundred ninety-one subjects received abacavir ( ABC ) and lamivudine and efavirenz ( nonnucleoside reverse transcriptase inhibitors [ NNRTIs ] ) , ritonavir-boosted amprenavir ( protease inhibitor [ PI ] ) , or stavudine ( nucleoside reverse transcriptase inhibitor [ NRTI ] ) by r and om assignment . The primary end points were the percentages of subjects with plasma HIV-1 RNA levels < 400 copies/mL and time to treatment failure over 96 weeks . Results : Ninety percent of subjects completed 96 weeks of follow-up , and 79 % remained on study treatment . At week 96 , there were no differences between arms in the percentages of subjects with plasma HIV-1 RNA levels < 400 and < 50 copies/mL , mean changes in plasma HIV-1 RNA levels , time to treatment failure , time to first or second virologic failure , or CD4 + cell counts . The NNRTI arm had a greater percentages of subjects with RNA levels ≤50 copies/mL at weeks 24 and 48 and a greater overall duration of plasma HIV-1 RNA levels < 400 copies/mL. Three subjects in the NNRTI arm had treatment failure on their first regimen and switched therapy compared with 16 in the NRTI arm and 13 in the PI arm . Twenty-one subjects had hypersensitivity reactions attributed to ABC ( 7.3 % ) . Fewer drugs were used by subjects in the NNRTI arm , and fewer subjects in the NNRTI arm used 3 drug classes . Conclusions : All treatment regimens demonstrated excellent 96-week results . Secondary analyses favored the NNRTI regimen over the PI and NRTI regimens BACKGROUND Although efavirenz and lopinavir/ritonavir(r ) are both recommended antiretroviral agents in antiretroviral-naïve HIV-infected patients , there are few r and omized comparisons of their efficacy and tolerability . METHODS A multicenter and r and omized study was performed including 126 antiretroviral-naïve patients , r and omly assigned to efavirenz+Kivexa ( n=63 ) or lopinavir/r+Kivexa ( n=63 ) . Efficacy endpoints were the percentage of patients with HIV-RNA < or = 50 copies/mL at week 48 and CD4 recovery . Safety was assessed by comparing toxicity and discontinuations . Statistical analyses were performed on an intention-to-treat ( ITT ) basis ( Missing = Failure ) . RESULTS At week 48 , 56.7 % of patients in the efavirenz and 63.2 % in the lopinavir/r groups showed HIV-1 RNA < 50 copies/mL ( P=0.770 ) ( intention-to-treat analysis ; Missing = Failure ) . Only 1 ( 1.53 % ) patient from each group experienced virological failure . CD4 values increased in both groups ( 298 cells in the efavirenz group , P=0.001 ; 249 cells in the lopinavir/r group , P=0.002 ; P=0.126 between groups ) . HDL-cholesterol only increased in the efavirenz group ( from 39+/-12 mg/dL to 49+/-11 ; P=0.001 ) . Discontinuations were more frequent in the lopinavir/r group ( 36.5 % versus 28.5 % ; P=0.193 ) , but more patients with efavirenz interrupted due to toxicity ( 11.1 % versus 6.3 % ) ; most of them were attributed to hypersensitivity reaction . CONCLUSIONS Similar virological efficacy was observed for efavirenz and lopinavir/r , when administered with Kivexa in antiretroviral-naïve patients , while immunological improvement was slightly superior for efavirenz . The higher rate of discontinuation due to toxicity in the efavirenz group was related to a higher incidence of hypersensitivity reaction . Nowadays , the use of the new formulation of lopinavir/r and the HLA-B*5701 genotype test before starting abacavir should improve the safety profiles of these regimens Background : Abacavir sulfate/lamivudine ( ABC/3TC ) and tenofovir DF/emtricitabine ( TDF/FTC ) are widely used nucleoside reverse transcriptase inhibitors for initial HIV-1 treatment . This is the first completed , r and omized clinical trial to directly compare the efficacy , safety , and tolerability of these agents , each in combination with lopinavir/ritonavir in antiretroviral-naive patients . Methods : Six hundred and eighty-eight antiretroviral-naive , HIV-1-infected patients were r and omized in this double-blind , placebo-matched , multicenter , noninferiority study to receive a once-daily regimen of either ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg , both with lopinavir/ritonavir 800 mg/200 mg . Primary endpoints were the proportion of patients with HIV-1 RNA below 50 copies/ml at week 48 ( missing = failure , switch included analysis ) and the proportion of patients experiencing adverse events over 96 weeks . Results : At week 48 , 68 % in the ABC/3TC group vs. 67 % in the TDF/FTC group achieved an HIV-1 RNA below 50 copies/ml ( intent-to-treat exposed missing = failure , 95 % confidence interval on the difference −6.63 to 7.40 , P = 0.913 ) , demonstrating the noninferiority of ABC/3TC to TDF/FTC at week 48 . Noninferiority of the two regimens was sustained at week 96 ( 60 % vs. 58 % , respectively , 95 % confidence interval −5.41 to 9.32 , P = 0.603 ) . In addition , efficacy of both regimens was similar in patients with baseline HIV-1 RNA ≥ 100 000 copies/ml or CD4 + cell counts below 50 cells/μl . Median CD4 + recovery ( ABC/3TC vs. TDF/FTC , cells/μl ) was + 250 vs. + 247 by week 96 . Premature study discontinuation due to adverse events occurred in 6 % of patients in both groups . Protocol -defined virologic failure occurred in 14 % of patients in both groups . Conclusion : Both ABC/3TC and TDF/FTC provided comparable antiviral efficacy , safety , and tolerability when each was combined with lopinavir/ritonavir in treatment-naive patients BACKGROUND The combination of didanosine , lamivudine , and efavirenz ( ddI/3TC/EFV ) for the initial treatment of human immunodeficiency virus type 1 ( HIV-1 ) infection has been insufficiently analyzed in clinical trials . METHODS We conducted an open-label , r and omized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine-zidovudine tablet and EFV ( COM/EFV ) , both administered with food to improve tolerability and convenience . Patients were stratified by HIV-1 RNA level of < 5.0 log(10 ) or > or = 5.0 log(10 ) copies/mL. The primary end point was the percentage of patients with an HIV-1 RNA level of < 50 copies/mL at week 48 , determined by intention-to-treat analysis . RESULTS Three hundred sixty-nine patients were r and omized : 186 for ddI/3TC/EFV treatment and 183 for COM/EFV treatment . Both groups were well matched in terms of baseline characteristics ; 19.3 % of patients received a Centers for Disease Control and Prevention assessment of clinical category C , median HIV RNA level was 5.0 log(10 ) copies/mL , and median CD4(+ ) cell count was 208 cells/microL. At week 48 , by intention-to-treat analysis , 70 % of patients in the ddI/3TC/EFV group and 63 % of patients in the COM/EFV group had an HIV-1 RNA level of < 50 copies/mL ( treatment difference , 7.1 % ; 95 % confidence interval , -2.39 % to 16.59 % ) . Fourteen patients ( 8 % ) in the ddI/3TC/EFV arm ( not the COM/EFV arm ) and 26 patients ( 14 % ) in the COM/EFV arm ( not the ddI/3TC/EFV arm ) [ corrected ] discontinued the study medication because of adverse events ( P = .046 ) . One patient ( 1 % ) in the ddI/3TC/EFV arm and 11 patients ( 6 % ) in the COM/EFV arm discontinued medication because of hematological toxicity ( P = .003 ) . CONCLUSIONS At week 48 , ddI/3TC/EFV administered once per day with food did not have results inferior to those of COM/EFV treatment . A statistically significantly higher proportion of patients in the COM/EFV arm than in the ddI/3TC/EFV arm discontinued therapy because of adverse events , mainly because of hematological toxicity . CLINICAL TRIALS REGISTRATION NCT00256828 Background : STARTMRK , a phase III noninferiority trial of raltegravir-based versus efavirenz-based therapy in treatment-naive patients , remained blinded until its conclusion at 5 years . We now report the final study results . Methods : Previously untreated patients without baseline resistance to efavirenz , tenofovir , or emtricitabine were eligible for a r and omized study of tenofovir/emtricitabine plus either raltegravir or efavirenz . Yearly analyses were planned , with primary and secondary end points stipulated at weeks 48 and 96 , respectively . The primary efficacy outcome was the percentage of patients with viral RNA ( vRNA ) levels < 50 copies per milliliter counting noncompleters as failures ( NC = F ) . Changes from baseline CD4 count were computed using an observed-failure approach to missing data . No formal hypotheses were formulated for testing at week 240 . Results : Overall , 71 of 281 raltegravir recipients ( 25 % ) and 98 of 282 efavirenz recipients ( 35 % ) discontinued the study ; discontinuations due to adverse events occurred in 14 ( 5 % ) and 28 ( 10 % ) patients in the respective groups . In the primary NC = F efficacy analysis at week 240 , 198 of 279 ( 71.0 % ) raltegravir recipients and 171 of 279 ( 61.3 % ) efavirenz recipients had vRNA levels < 50 copies per milliliter , yielding a treatment difference { [ INCREMENT ] [ 95 % confidence interval ( CI ) ] = 9.5 ( 1.7 to 17.3)}. Generally comparable between-treatment differences were seen in both the protocol -stipulated sensitivity analyses and the prespecified subgroup analyses . The mean ( 95 % CI ) increments in baseline CD4 counts at week 240 were 374 and 312 cells per cubic millimeter in the raltegravir and efavirenz groups , respectively [ [ INCREMENT ] ( 95 % CI ) = 62 ( 22 to 102 ) ] . Overall , significantly fewer raltegravir than efavirenz recipients experienced neuropsychiatric side effects ( 39.1 % vs 64.2 % , P < 0.001 ) or drug-related clinical adverse events ( 52.0 % vs 80.1 % , P < 0.001 ) . Conclusions : In this exploratory analysis of combination therapy with tenofovir/emtricitabine in treatment-naive patients at week 240 , vRNA suppression rates and increases in baseline CD4 counts were significantly higher in raltegravir than efavirenz recipients . Over the entire study , fewer patients experienced neuropsychiatric and drug-related adverse events in the raltegravir group than in the efavirenz group . Based on better virologic and immunologic outcomes after 240 weeks , raltegravir/tenofovir/emtricitabine seemed to have superior efficacy compared with efavirenz/tenofovir/emtricitabine Abstract Background : The objective of this study was to compare the efficacy of ritonavir boosted atazanavir versus ritonavir boosted lopinavir or efavirenz , all in combination with 2 nucleoside analogue reverse transcriptase inhibitors ( NRTIs ) , over 144 weeks in antiretroviral-naïve HIV-1-infected individuals . Methods : A prospect i ve open-label r and omized controlled trial was conducted at 29 sites in Sweden and Norway between April 2004 and December 2009 . Patients were r and omized to receive either efavirenz 600 mg once daily ( EFV ) , or atazanavir 300 mg and ritonavir 100 mg once daily ( AZV/r ) , or lopinavir 400 mg and ritonavir 100 mg twice daily ( LPV/r ) . The primary endpoints were the proportion of patients with HIV-1 RNA < 50 copies/ml at 48 and 144 weeks . Results : Of 245 patients enrolled , 243 were r and omized and 239 received the allocated intervention : 77 EFV , 81 AZV/r , and 81 LPV/r . Median ( interquartile range ) CD4 cell counts at baseline were 150 ( 80–200 ) , 170 ( 80–220 ) , and 150 ( 90–216 ) per microlitre , respectively . At week 48 the proportion ( 95 % confidence interval ( CI ) ) of patients achieving HIV-1 RNA < 50 copies/ml was 86 (78–94)% in the EFV arm , 78 (69–87)% in the AZV/r arm and , 69 (59–78)% in the LPV/r arm in the intention-to-treat analysis . There was a significant difference between the EFV and LPV/r arm ( p = 0.014 ) . At week 144 , the proportion ( 95 % CI ) of patients achieving HIV-1 RNA < 50 copies/ml was 61 (50–72)% , 58 (47–69)% , 51 (41–63)% , respectively ( p = 0.8 ) . Patients with CD4 cell counts of ≤ 200/μl or HIV-1 RNA > 100,000 copies/ml at baseline had similar response rates in all arms . Conclusion : EFV was superior to LPV/r at week 48 , but there were no significant differences between the 3 arms in the long-term ( 144 weeks ) follow-up |
11,858 | 25,580,635 | Whereas no difference was found in clinical periodontal parameters , significant differences in inflammatory or metabolic parameters were found between overweight/obese and normal-weight patients , but existing evidence is weak | AIM The objective of this study was to investigate whether the response to periodontal treatment differs among obese , overweight or normal-weight patients . | BACKGROUND Evidence suggests an association between periodontal disease and coronary heart disease ( CHD ) . C-reactive protein ( CRP ) , fibrinogen , and white blood cell ( WBC ) counts are markers of inflammation , and their systemic levels have been associated with CHD risk . This pilot study investigated the effect of non-surgical periodontal therapy on systemic levels of CRP , fibrinogen , and WBC counts in subjects with CHD or no CHD ( NCHD ) . METHODS Twenty-seven angiographically defined patients with CHD and 18 subjects with NCHD aged > or=40 years were recruited for the study . Periodontal disease was measured through the clinical parameters bleeding on probing ( BOP ) and probing depth ( PD ) . All subjects received non-surgical periodontal therapy that included oral hygiene instructions and subgingival scaling and root planing . Systemic levels of inflammatory markers ( CRP , fibrinogen , and WBC counts ) were measured prior to and 1 month after periodontal therapy . RESULTS Seventeen subjects with CHD and 11 subjects with NCHD completed the study . Subjects with CHD or NCHD experienced significant reductions in BOP ( 59 % and 34 % , respectively ; P < 0.05 ) and PD ( 41 % and 35 % , respectively ; P < 0.05 ) , with non-significant intergroup differences ( P > 0.05 ) . In all subjects , CRP , fibrinogen , and WBC counts were reduced significantly ( 21 % to 40 % ) after periodontal therapy ( P < 0.05 ) . CONCLUSIONS Periodontal treatment result ed in significant decreases in BOP and PD and lowered serum inflammatory markers in patients with CHD or NCHD . This may result in a decreased risk for CHD in the treated patients . These findings will allow pursuit of a large-scale r and omized intervention trial in this population BACKGROUND Chronic infections , such as periodontitis , are associated with increased risk of systemic diseases driven by a persistent low- grade systemic inflammation and metabolic changes . Severity of periodontitis has also been associated with increased systolic blood pressure ( BP ) . However , the issue remains poorly investigated . We aim ed to estimate the effect of periodontal therapy on traditional and novel cardiovascular risk factors in systemically healthy individuals who have periodontitis . METHODS We enrolled 40 otherwise healthy patients with severe chronic generalized periodontitis in a 6-month pilot intervention trial . Individuals were r and omized either to a st and ard course of periodontal therapy ( subgingival scaling and root planing ) or an intensive one ( including the adjunctive use of a locally delivered antimicrobial , IPT ) . RESULTS Compared to control , IPT produced significant reductions in a cluster of inflammatory markers at 1 ( P = .0406 ) and 2 ( P = .0060 ) months together with an improvement in lipid markers at 2 ( P = .0320 ) and 6 ( P = .0432 ) months after therapy . Intensive periodontal therapy produced greater reductions in IL-6 at 1 ( 0.4 + /- 0.2 ng/L difference , 95 % CI 0.03 - 0.9 , P = .0284 ) and 2 months ( 0.3 + /- 0.2 ng/L difference , 95 % CI 0.1 - 0.8 , P = .0284 ) , together with decreases in C-reactive protein ( 0.4 + /- 0.2 mg/L difference , 95 % CI 0.01 - 0.8 , P = .0438 ) and total cholesterol ( 0.3 + /- 0.1 mmol/L difference , 95 % CI 0.04 - 0.6 , P = .0254 ) . Moreover , a 7 + /- 3-mm Hg decrease in systolic BP was observed at 2 months in the IPT group ( 95 % CI 1 - 12 , P = .0211 ) , and this difference was greater in current smokers ( 14 + /- 5 mm Hg 95 % CI 3 - 25 , P = 0.0124 ) . Intensive periodontal therapy subjects exhibited a 1.53 % + /- 1.20 % ( 95 % CI 1.05 - 2.24 , P = .0290 ) and 2.00 % + /- 1.42 % ( 95 % CI 0.98 - 4.09 , P = .0568 ) decreases in cardiovascular risk scores ( Framingham ) at 2 and 6 months , respectively , when compared to those in the st and ard group . CONCLUSIONS Our findings suggest that intensive periodontal treatment reduces systemic inflammatory markers and systolic BP , and improves lipid profiles with subsequent changes in cardiovascular risk when compared to st and ard therapy BACKGROUND Systemic inflammation may impair vascular function , and epidemiologic data suggest a possible link between periodontitis and cardiovascular disease . METHODS We r and omly assigned 120 patients with severe periodontitis to community-based periodontal care ( 59 patients ) or intensive periodontal treatment ( 61 ) . Endothelial function , as assessed by measurement of the diameter of the brachial artery during flow ( flow-mediated dilatation ) , and inflammatory biomarkers and markers of coagulation and endothelial activation were evaluated before treatment and 1 , 7 , 30 , 60 , and 180 days after treatment . RESULTS Twenty-four hours after treatment , flow-mediated dilatation was significantly lower in the intensive-treatment group than in the control-treatment group ( absolute difference , 1.4 % ; 95 % confidence interval [ CI ] , 0.5 to 2.3 ; P=0.002 ) , and levels of C-reactive protein , interleukin-6 , and the endothelial-activation markers soluble E-selectin and von Willebr and factor were significantly higher ( P<0.05 for all comparisons ) . However , flow-mediated dilatation was greater and the plasma levels of soluble E-selectin were lower in the intensive-treatment group than in the control-treatment group 60 days after therapy ( absolute difference in flow-mediated dilatation , 0.9 % ; 95 % CI , 0.1 to 1.7 ; P=0.02 ) and 180 days after therapy ( difference , 2.0 % ; 95 % CI , 1.2 to 2.8 ; P<0.001 ) . The degree of improvement was associated with improvement in measures of periodontal disease ( r=0.29 by Spearman rank correlation , P=0.003 ) . There were no serious adverse effects in either of the two groups , and no cardiovascular events occurred . CONCLUSIONS Intensive periodontal treatment result ed in acute , short-term systemic inflammation and endothelial dysfunction . However , 6 months after therapy , the benefits in oral health were associated with improvement in endothelial function OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND Studies investigating effects of periodontal treatment ( PT ) on markers of inflammation in healthy subjects show conflicting results . Few studies have investigated the effects of PT among subjects with coronary heart disease ( CHD ) risk factors . AIM To report the results of a pilot prospect i ve study on the effects of periodontal treatment on markers of inflammation among subjects with CHD risk factors . MATERIAL AND METHODS Seventy three patients aged 53+/-6 years ( 25 % males ) with chronic periodontitis , dyslipidemia and other CHD risk factors were subjected to PT consisting on root planning and oral metronidazol and amoxicillin for 7 days . Periodontal clinical parameters , serum C-reactive protein ( CRP ) , fibrinogen levels and erythrocyte sedimentation rate ( ESR ) were assessed before and at 6 weeks after PT . Polymorphisms at the ILlA-889 and IL1B+3954 genes were also genotyped . RESULTS After the treatment period , CRP levels significantly increased from 3.6+/-3.7 mg/ L to 5.4+/-5.7 mg/L ( p = 0.001 ) . No significant changes were observed in fibrinogen levels and ESR . Higher post-treatment CRP levels were significantly associated with the composite polymorphic genotype at the ILlA-889 and IL1B+3954 genes ( p = 0.0001 ) , and extensive periodontitis ( p = 0.005 ) . Moderate alcohol consumption appeared as a protective factor for CRP elevation ( p = 0.029 ) . CONCLUSIONS The increase of the CRP levels after PT in patients with CVD risk factors appeared associated with IL-1 gene polymorphisms and extensive periodontitis Most studies linking obesity and periodontal disease have been cross-sectional in design . We examined whether gains in body weight , waist circumference , and arm fat area are associated with periodontitis progression in 893 non-diabetic men followed for up to four decades in the prospect i ve VA Dental Longitudinal Study . Probing pocket depth ( PPD ) was measured by calibrated examiners . Repeated- measures generalized linear models estimated the mean cumulative numbers of teeth with PPD events ( PPD > 3 mm ) at each dental examination and the slopes associated with increasing numbers of affected teeth over time . Means were adjusted for baseline PPD , education , and cigarette pack-years , and time-dependent values of age , mean plaque score , cigarette packs/day , brushing , and flossing . Men who were overweight at baseline and gained weight most rapidly ( > 0.19 kg/yr or ~15 lb during follow-up ) had significantly more PPD events than men in the lowest tertile of weight gain ( ≤ -0.05 kg/yr ) . Overweight men whose waist circumference increased > 0.14–0.39 or > 0.39 cm/yr experienced more PPD events than men in the lowest tertile ( ≤ 0.14 cm/yr ) . Increase in arm fat area was associated with disease progression in normal-weight men . These results suggest that tracking adiposity changes with easily obtained anthropometric measures may help predict risk of periodontitis progression BACKGROUND We investigated the effect of oral alendronate ( ALN ) treatment on radiological and clinical measurements of periodontal disease in postmenopausal women without hormone replacement therapy . METHODS We evaluated the effect of 6 months of ALN treatment in 40 postmenopausal women , 55 to 65 years old with established periodontal disease , in a controlled , double-masked , prospect i ve study . Volunteers were paired by age and r and omized to receive ALN ( 10 mg/day ) or placebo for the study period . Periodontal mechanical treatment was carried out in both groups . At baseline and after treatment , clinical evaluation , hormone blood levels , distance from the crestal alveolar bone ( CAB ) to the cemento-enamel junction ( CEJ ) , calcaneus bone mineral density ( BMD ) , hormone levels , serum N-telopeptide ( NTx ) , and bone-specific alkaline phosphatase ( BSAP ) were assessed . RESULTS Periodontal disease conditions improved in both groups , but greater improvement in probing depth ( -0.8 + /- 0.3 mm versus -0.4 + /- 0.4 mm , P = 0.02 ) and gingival bleeding ( -0.3 % + /- 0.13 % versus -0.2 % + /- 0.06 % , P = 0.006 ) was found in the ALN treated group . Calcaneus BMD increased in the ALN treated group ( 68 + /- 47 mm3 versus -26 + /- 81 mm3 , P = 0.0006 ) . CAB-CEJ distance diminished in the ALN group ( -0.4 + /- 0.40 mm versus 0.60 + /- 0.53 mm , P = 0.00008 ) . Marginal reduction in both NTx and BSAP levels was found in the ALN group ( -9.4 + /- 6.6 nmol versus -4.3 + /- 4.7 nmol bone collagen equivalents , P = 0.08 , and -7.7 + /- 8.4 versus -1.5 + /- 5.0 U/l , P = 0.1 , respectively ) . Hormone levels were unchanged after treatment . Similar improvement of calcaneus BMD and CAB-CEJ distance with ALN treatment was found in obese and non-obese women . CONCLUSION ALN treatment improved periodontal disease and bone turnover in postmenopausal women AIM the purpose of the present study was to assess the effect of non-surgical periodontal therapy on glycaemic control of type 2 diabetes patients with moderate-to-severe periodontitis . MATERIAL S AND METHODS this was a r and omized , controlled clinical trial of patients with type 2 diabetes . A total of 60 patients with moderate-to-severe periodontal disease were assigned to either a periodontal treatment arm , consisting of scaling and root planing ( intervention group [ IG ] ) , or a delayed treatment arm that received periodontal care after 6 months ( control group [ CG ] ) . Periodontal parameters and glycosylated haemoglobin ( A1C ) were evaluated at 1 , 3 and 6 months . RESULTS all periodontal parameters improved significantly in the IG . A1C levels decreased statistically significantly more in the IG versus the CG ( 0.72%versus 0.13 % ; p<0.01 ) independently of other confounders . CONCLUSIONS this study provides evidence that periodontal treatment contributes to improved glycaemic control in type 2 diabetes mellitus patients . Larger controlled trials are needed to confirm if this finding is generalizable to other population s of patients with type 2 diabetes Severe periodontitis has been associated with increased systemic inflammation . In a three-arm preliminary r and omized trial , we investigated the impact of st and ard ( SPT ) and intensive periodontal therapy ( IPT ) on serum inflammatory markers and cholesterol levels . Medical and periodontal parameters , C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , total cholesterol , and LDL cholesterol were evaluated in 65 systemically healthy subjects suffering from severe generalized periodontitis . Two months after treatment , both SPT and IPT result ed in significant reductions in serum CRP compared with the untreated control ( 0.5 ± 0.2 mg/L for SPT , P = 0.030 and 0.8 ± 0.2 mg/L for IPT , P = 0.001 ) . Similar results were observed for IL-6 . Changes in inflammation were independent of age , gender , body mass index , and ethnicity , but a significant interaction between cigarette smoking and treatment regimen was found . The IPT group also showed a decrease in total and LDL cholesterol after 2 months . Analysis of these data indicates that periodontitis causes moderate systemic inflammation in systemically healthy subjects OBJECTIVES Chronic inflammation of periodontitis aggravates glycemic control in type 2 diabetic patients through aggravation of insulin resistance . Increased or decreased release of various inflammatory mediators , such as high sensitivity C-reactive protein ( hs-CRP ) , tumor necrosis factor (TNF)-α , interleukin (IL)-6 and adipokines , such as adiponectin , leptin , and resistin , are presumed to be responsible for developing and progressing insulin resistance . The purpose of this study was to examine the effects of periodontal treatment on glycemic control , serum inflammatory mediators and adipokines in type 2 diabetes patients with periodontitis . METHODS Twenty-one type 2 diabetic patients with periodontitis received periodontal treatment with topical antibiotics ( intervention group ) and 8 patients did not receive periodontal treatment ( control group ) . Periodontal examination , including probing pocket depth ( PPD ) and bleeding on probing ( BOP ) , and blood sampling were performed at baseline , 2 and 6 months after periodontal treatments . Glycated hemoglobin ( HbA1c ) , hs-CRP , TNF-α , IL-6 , adiponectin , leptin , and resistin were analyzed . RESULTS In the intervention group , improvements of PPD and BOP , decrease in HbA1c and elevation of serum adiponectin were observed , while in the control group , all parameters were not changed . Generalized linear model revealed that changes of serum adiponectin and TNF-α and change of BOP correlated significantly with the reduction of HbA1c at 6 months after periodontal treatments . CONCLUSION The results demonstrated that periodontal treatment improves periodontal status and glycemic control with elevation of serum adiponectin in type 2 diabetic patients . The results suggest that HbA1c is reduced by amelioration of insulin resistance due to elevated serum adiponectin after periodontal treatments Severe periodontitis is associated with elevated inflammatory markers in otherwise healthy population s. However , the nature of this association has not been determined . Our aim was to assess whether the degree of response to periodontal therapy was associated with changes in serological markers of systemic inflammation . Ninety-four systemically healthy subjects with severe generalized periodontitis participated in a prospect i ve six-month blind intervention trial . Periodontal parameters and inflammatory markers [ C-reactive Protein ( CRP ) and Interleukin-6 ( IL-6 ) ] were evaluated prior to and 2 and 6 mos after delivery of st and ard non-surgical periodontal therapy . Six months after treatment , significant reductions in serum IL-6 ( p < 0.001 , median decrease 0.2 ng/L , 95 % CI 0.1–0.4 ng/L ) and CRP ( p < 0.0001 , median decrease 0.5 mg/L , 95 % CI 0.4–0.7 ) were observed . Decreases in inflammatory markers were significant in subjects with above average clinical response to periodontal therapy after correction for possible confounders . Periodontitis may add to the systemic inflammatory burden of affected individuals OBJECTIVE To investigate the effect of conventional periodontal therapy on serum C-reactive protein ( CRP ) level and periodontal status in obese and normal-weight chronic periodontitis patients . METHODS This is a controlled clinical trial conducted at the King Abdulaziz University Faculty of Dentistry , Jeddah , Kingdom of Saudi Arabia between December 2009 and March 2011 . A total of 40 women affected with moderate to severe chronic periodontitis were selected ( 20 obese [ test group ] and 20 normal-weight [ control ] ) . Smokers , pregnant women , and subjects with any systemic disease were excluded . Serum CRP level and periodontal parameters , including clinical attachment level , probing depth , bleeding on probing and plaque scores were assessed at baseline , and 2 months after non-surgical periodontal treatment . RESULTS Periodontal therapy was effective in reducing gingival inflammation , as well as serum CRP level in the total sample and within each group . The pre-treatment mean level of serum CRP was 0.78 ( + /-0.51 ) and post- treatment was 0.55 ( + /-0.41 ) mg/l in the total sample ( p=0.001 ) . A tendency was observed toward a better systemic response to treatment in normal-weight compared to obese women , however , it was not statistically significant ( the mean changes in CRP levels after therapy were 0.28 [ + /-0.43 ] and 0.19 [ + /-0.32 ] mg/l ) . CONCLUSION Periodontal treatment is effective in reducing systemic inflammation as measured by serum CRP level , and obesity does not have a major negative impact on response to periodontal therapy OBJECTIVE The aim of this study was to find out if periodontal therapy has any effect on glycemic control of type 1 diabetes mellitus ( DM ) . SUBJECTS AND METHODS The periodontal health status of 65 type 1 diabetic subjects was assessed at the baseline and 8 weeks after completion of periodontal therapy . Glycemic control was assessed on both visits by measuring the percentage of glycosylated haemoglobin ( GHbA1c ) . The change in HbA1c ( DeltaHbA1c ) was assessed by using both a positive or negative change > or=0.5 % and any change in HbA1c . RESULTS The mean HbA1c level ( + /-SD ) of the whole study group was 8.6 % ( + /-1.5 ) at the baseline and 8.5 % ( + /-1.5 ) after treatment . Glycemic control improved during the study period in 23 subjects ( 35 % ) and worsened in 18 subjects ( 28 % ) . Approximately 78 % of the bleeding sites and 87 % of the sites with probing depth > or=4 mm presented healing . DeltaHbA1c associated significantly with baseline HbA1c but not with baseline periodontal health status or periodontal healing . CONCLUSION Regardless of a significant resolution of periodontal infection , a great majority of the subjects did not present any improvement in their glycemic control |
11,859 | 27,624,381 | Regarding drug classes , antipsychotics were most frequently used , followed by attention-deficit/hyperactivity disorder ( ADHD ) medication and antidepressants .
Both older age and psychiatric comorbidity were associated with higher prevalences of psychopharmacotherapy and psychotropic polypharmacy .
There were no time trends in psychopharmacotherapy prevalence observable .
Despite a lack of pharmacological treatment options for ASD core symptoms , the prevalence of psychopharmacotherapy and polypharmacy in ASD patients is considerable , which is probably due to the treatment of non-core ASD symptoms and psychiatric comorbidities . | OBJECTIVE The objective of this review was to examine prevalence and patterns of psychopharmacotherapy in individuals with autism spectrum disorder ( ASD ) . | OBJECTIVE The purpose of this study was to estimate the prevalence and time trends in prescriptions of methylpheni date , dexamphetamine , and atomoxetine in children and adolescents , within three diagnostic groups : 1 ) autism spectrum disorder ( ASD ) , 2 ) attention-deficit/hyperactivity disorder ( ADHD ) , and 3 ) other psychiatric disorders . METHODS Data from six different national registers were used and merged to identify a cohort of all children and adolescents born in Denmark between 1990 and 2001 ( n=852,711 ) . Sociodemographic covariates on cohort members and their parents and lifetime prescriptions of methylpheni date , dexamphetamine , and atomoxetine were extracted from the registers . Prescriptions were also stratified by duration ( < 6 months . vs.≥ 6 months ) . RESULTS Sixteen percent of 9698 children and adolescents with ASD ( n=1577 ) , 61 % of 11,553 children and adolescents with ADHD ( n=7021 ) and 3 % of 48,468 children and adolescents with other psychiatric disorders ( n=1537 ) were treated with one or more ADHD medications . There was a significant increase in prescription rates of these medications for all three groups . From 2003 to 2010 , youth 6 - 13 years of age with ASD , ADHD , and other psychiatric disorders had 4.7-fold ( 4.4 - 4.9 ) , 6.3-fold ( 6.0 - 6.4 ) , and 5.5-fold ( 5.0 - 5.9 ) increases , respectively , in prescription rates of ADHD medications . CONCLUSION This is the largest study to date assessing stimulant treatment in children and adolescents with ASD , and is the first prospect i ve study quantifying the change over time in the prevalence of treatment with ADHD medications in a population -based national cohort of children and adolescents with ASD . The prevalence of stimulant treatment in youth with ASD of 16 % is consistent with earlier studies . The past decade has witnessed a clear and progressive increase in the prescription rates of medications typically used to treat ADHD in children and adolescents in Denmark . This increase is not limited to only those with ADHD , but includes others with neuropsychiatric disorders , including ASD . The risks and benefits of this practice await further study OBJECTIVE . The objective of this study was to provide national estimates of psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders and to examine child and health system characteristics associated with psychotropic medication use . METHODS . This cross-sectional study used Medicaid cl aims for calendar year 2001 from all 50 states and Washington , DC , to examine 60641 children with an autism spectrum disorder diagnosis . Logistic regression with r and om effects was used to examine the child , county , and state factors associated with psychotropic medication use . RESULTS . Of the sample , 56 % used at least 1 psychotropic medication , 20 % of whom were prescribed ≥3 medications concurrently . Use was common even in children aged 0 to 2 years ( 18 % ) and 3 to 5 years ( 32 % ) . Neuroleptic drugs were the most common psychotropic class ( 31 % ) , followed by antidepressants ( 25 % ) and stimulants ( 22 % ) . In adjusted analyses , male , older , and white children ; those who were in foster care or in the Medicaid disability category ; those who received additional psychiatric diagnoses ; and those who used more autism spectrum disorder services were more likely to have used psychotropic drugs . Children who had a diagnosis of autistic disorder or who lived in counties with a lower percentage of white residents or greater urban density were less likely to use such medications . CONCLUSIONS . Psychotropic medication use is common among even very young children with autism spectrum disorders . Factors unrelated to clinical presentation seem highly associated with prescribing practice s. Given the limited evidence base , there is an urgent need to assess the risks , benefits , and costs of medication use and underst and the local and national policies that affect medication use This study examined change prospect ively in autism symptoms and maladaptive behaviors during a 4.5 year period in 241 adolescents and adults with an autism spectrum disorder who were 10–52 years old ( mean = 22.0 ) when the study began . Although many individuals ’ symptoms remained stable , a greater proportion of the sample experienced declines than increases in their level of autism symptoms and maladaptive behaviors , and there were significant improvements in mean levels of symptoms . Individuals with mental retardation had more autism symptoms and maladaptive behaviors than those without mental retardation , and they improved less over time . Compared to adolescents , older sample members ( 31 and older ) had fewer maladaptive behaviors and experienced more improvement in these behaviors over time OBJECTIVE . Data on the current costs of medical services for children with autism spectrum disorders are lacking . Our purpose for this study was to compare health care utilization and costs of children with and without autism spectrum disorders in the same health plan . PATIENTS AND METHODS . Participants included all 2- to 18-year-old children with autism spectrum disorders ( n = 3053 ) and a r and om sample of children without autism spectrum disorders ( n = 30529 ) who were continuously enrolled in the Kaiser Permanente Medical Care Program in northern California between July 1 , 2003 , and June 30 , 2004 . Data on health care utilization and costs were derived from health plan administrative data bases . MAIN OUTCOME MEASURES . Outcome measures included mean annual utilization and costs of health services per child . RESULTS . Children with autism spectrum disorders had a higher annual mean number of total clinic ( 5.6 vs 2.8 ) , pediatric ( 2.3 vs 1.6 ) , and psychiatric ( 2.2 vs 0.3 ) outpatient visits . A higher percentage of children with autism spectrum disorders experienced inpatient ( 3 % vs 1 % ) and outpatient ( 5 % vs 2 % ) hospitalizations . Children with autism spectrum disorders were nearly 9 times more likely to use psychotherapeutic medications and twice as likely to use gastrointestinal agents than children without autism spectrum disorders . Mean annual member costs for hospitalizations ( $ 550 vs $ 208 ) , clinic visits ( $ 1373 vs $ 540 ) , and prescription medications ( $ 724 vs $ 96 ) were more than double for children with autism spectrum disorders compared with children without autism spectrum disorders . The mean annual age- and gender-adjusted total cost per member was more than threefold higher for children with autism spectrum disorders ( $ 2757 vs $ 892 ) . Among the subgroup of children with other psychiatric conditions , total mean annual costs were 45 % higher for children with autism spectrum disorders compared with children without autism spectrum disorders ; excess costs were largely explained by the increased use of psychotherapeutic medications . CONCLUSIONS . The utilization and costs of health care are substantially higher for children with autism spectrum disorders compared with children without autism spectrum disorders . Research is needed to evaluate the impact of improvements in the management of children with autism spectrum disorders on health care utilization and costs Introduction : Antipsychotic polypharmacy ( APP ) , the concomitant use of ≥ 2 antipsychotics , is common in clinical practice . Prior review s have focused on the efficacy of APP , but no systematic review exists regarding the safety and tolerability of this practice . Areas covered : A systematic review of adverse effects associated with APP was conducted to prepare this review ; case series with ≥ 2 patients , chart review s , naturalistic , data base , cohort and r and omized studies that reported on the association between APP in general or specific APP combinations and global or specific adverse effect were included . Method ological limitations of available studies are discussed and recommendations for clinicians and future research are provided . Expert opinion : Across mostly small and uncontrolled studies , APP has been associated with increased global side effect burden , rates of Parkinsonian side effects , anticholinergic use , hyperprolactinemia , sexual dysfunction , hypersalivation , sedation/somnolence , cognitive impairment and diabetes . Effects on akathisia and mortality were inconclusive . Although some combinations , particularly aripiprazole augmentation of an agent with greater side effect burden , may reduce weight gain , dyslipidemia , hyperprolactinemia and sexual dysfunction , APP should remain a last-resort treatment option after monotherapy , switching and non-antipsychotic combinations have failed . More data are needed to further inform the individualized risk – benefit evaluation of APP |
11,860 | 28,449,385 | Linkage was often low after routine referral but higher if additional interventions were used to facilitate it . | BACKGROUND Home-based HIV counselling and testing ( HBHCT ) has the potential to increase HIV testing uptake in sub-Saharan Africa ( SSA ) , but data on linkage to HIV care after HBHCT are scarce .
We conducted a systematic review of linkage to care after HBHCT in SSA . | Introduction There is growing evidence concerning the acceptability and feasibility of home-based HIV testing . However , less is known about the cost-effectiveness of the approach yet it is a critical component to guide decisions about scaling up access to HIV testing . This study examined the cost-effectiveness of a home-based HIV testing intervention in rural South Africa . Methods Two alternatives : clinic and home-based HIV counselling and testing were compared . Costs were analysed from a provider ’s perspective for the period of January to December 2010 . The outcome , HIV counselling and testing ( HCT ) uptake was obtained from the Good Start home-based HIV counselling and testing ( HBHCT ) cluster r and omised control trial undertaken in KwaZulu-Natal province . Cost-effectiveness was estimated for a target population of 22,099 versus 23,864 people for intervention and control communities respectively . Average costs were calculated as the cost per client tested , while cost-effectiveness was calculated as the cost per additional client tested through HBHCT . Results Based on effectiveness of 37 % in the intervention ( HBHCT ) arm compared to 16 % in control arm , home based testing costs US$ 29 compared to US$ 38 per person for clinic HCT . The incremental cost effectiveness per client tested using HBHCT was $ 19 . Conclusions HBHCT was less costly and more effective . Home-based HCT could present a cost-effective alternative for rural ‘ hard to reach ’ population s depending on affordability by the health system , and should be considered as part of community outreach programs Introduction Linkage from HIV testing and counselling ( HTC ) to initiation of antiretroviral therapy ( ART ) is suboptimal in many national programmes in sub-Saharan Africa , leading to delayed initiation of ART and increased risk of death . Reasons for failure of linkage are poorly understood . Methods Semi-structured qualitative interviews were undertaken with health providers and HIV-positive primary care patients as part of a prospect i ve cohort study at primary health centres in Blantyre , Malawi . Patients successful and unsuccessful in linking to ART were included . Results Progression through the HIV care pathway was strongly influenced by socio-cultural norms , particularly around the perceived need to regain respect lost during a period of visibly declining health . Capacity to call upon the support of networks of families , friends and employers was a key determinant of successful progression . Over-busy clinics , non-functioning laboratories and unsuitable tools used for ART eligibility assessment ( WHO clinical staging system and central ized CD4 count measurement ) were important health systems determinants of drop-out . Conclusions Key interventions that could rapidly improve linkage include guarantee of same-day , same-clinic ART eligibility assessment s ; utilization of the support offered by peer-groups and community health workers ; and integration of HTC and ART programmes Background Antiretroviral therapy ( ART ) has been scaled-up rapidly in Africa . Programme reports typically focus on loss to follow-up and mortality among patients receiving ART . However , little is known about linkage and retention in care of individuals prior to starting ART . Methodology Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital . HIV testing registers , CD4 count results provided by the National Health Laboratory System and ART registers were linked . A r and om sample ( n = 885 ) was drawn from adults testing HIV positive through antenatal care , sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009 . All adults ( n = 103 ) testing HIV positive through TB services during the same time period were also included in the study . Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis . Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis . Findings Only 62.6 % of individuals attended for a CD4 count measurement within 6 months of testing HIV positive . Individuals testing through sexually transmitted infection services had the best ( 84.1 % ) and individuals testing on their own initiative ( 53.5 % ) the worst linkage to HIV care . One third of individuals with timely CD4 counts were eligible for ART and 66.7 % of those were successfully linked to ART care . Linkage to ART care was highest among antenatal care clients . Among individuals not yet eligible for ART only 46.3 % had a repeat CD4 count . Linkage to HIV care improved in patients tested in more recent calendar period . Conclusion Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity . More efforts are needed to link VCT scale-up to subsequent care Background The 2015 WHO recommendation of antiretroviral therapy ( ART ) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population . We investigated this approach in a cluster-r and omised trial in a high HIV prevalence setting in rural KwaZulu-Natal . We present findings from the first phase of the trial and report on uptake of home-based HIV testing , linkage to care , uptake of ART , and community attitudes about ART . Methods and Findings Between 9 March 2012 and 22 May 2014 , five clusters in the intervention arm ( immediate ART offered to all HIV-positive adults ) and five clusters in the control arm ( ART offered according to national guidelines , i.e. , CD4 count ≤ 350 cells/μl ) contributed to the first phase of the trial . Households were visited every 6 mo . Following informed consent and administration of a study question naire , each resident adult ( ≥16 y ) was asked for a finger-prick blood sample , which was used to estimate HIV prevalence , and offered a rapid HIV test using a serial HIV testing algorithm . All HIV-positive adults were referred to the trial clinic in their cluster . Those not linked to care 3 mo after identification were contacted by a linkage-to-care team . Study procedures were not blinded . In all , 12,894 adults were registered as eligible for participation ( 5,790 in intervention arm ; 7,104 in control arm ) , of whom 9,927 ( 77.0 % ) were contacted at least once during household visits . HIV status was ever ascertained for a total of 8,233/9,927 ( 82.9 % ) , including 2,569 ascertained as HIV-positive ( 942 tested HIV-positive and 1,627 reported a known HIV-positive status ) . Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial , 559 ( 47.5 % ) visited their cluster trial clinic within 6 mo . In the intervention arm , 89 % ( 194/218 ) initiated ART within 3 mo of their first clinic visit . In the control arm , 42.3 % ( 83/196 ) had a CD4 count ≤ 350 cells/μl at first visit , of whom 92.8 % initiated ART within 3 mo . Regarding attitudes about ART , 93 % ( 8,802/9,460 ) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive . Estimated baseline HIV prevalence was 30.5 % ( 2,028/6,656 ) ( 95 % CI 25.0 % , 37.0 % ) . HIV prevalence , uptake of home-based HIV testing , linkage to care within 6 mo , and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/μl did not differ significantly between the intervention and control clusters . Selection bias related to noncontact could not be entirely excluded . Conclusions Home-based HIV testing was well received in this rural population , although men were less easily contactable at home ; immediate ART was acceptable , with good viral suppression and retention . However , only about half of HIV-positive people accessed care within 6 mo of being identified , with nearly two-thirds accessing care by 12 mo . The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population . Trial registration Clinical Trials.gov Introduction We aim ed to quantify and identify associated factors of linkage to HIV care following home-based HIV counselling and testing ( HBHCT ) in the ongoing ANRS 12249 treatment-as-prevention ( TasP ) cluster-r and omized trial in rural KwaZulu-Natal , South Africa . Methods Individuals ≥16 years were offered HBHCT ; those who were identified HIV positive were referred to cluster-based TasP clinics and offered antiretroviral treatment ( ART ) immediately ( five clusters ) or according to national guidelines ( five clusters ) . HIV care was also available in the local Department of Health ( DoH ) clinics . Linkage to HIV care was defined as TasP or DoH clinic attendance within three months of referral among adults not in HIV care at referral . Associated factors were identified using multivariable logistic regression adjusted for trial arm . Results Overall , 1323 HIV-positive adults ( 72.9 % women ) not in HIV care at referral were included , of whom 36.9 % ( n=488 ) linked to care <3 months of referral ( similar by sex ) . In adjusted analyses ( n=1222 ) , individuals who had never been in HIV care before referral were significantly less likely to link to care than those who had previously been in care ( <33 % vs. > 42 % , p<0.001 ) . Linkage to care was lower in students ( adjusted odds-ratio [aOR]=0.47 ; 95 % confidence interval [ CI ] 0.24–0.92 ) than in employed adults , in adults who completed secondary school ( aOR=0.68 ; CI 0.49–0.96 ) or at least some secondary school ( aOR=0.59 ; CI 0.41–0.84 ) versus ≤ primary school , in those who lived at 1 to 2 km ( aOR=0.58 ; CI 0.44–0.78 ) or 2–5 km from the nearest TasP clinic ( aOR=0.57 ; CI 0.41–0.77 ) versus < 1 km , and in those who were referred to clinic after ≥2 contacts ( aOR=0.75 ; CI 0.58–0.97 ) versus those referred at the first contact . Linkage to care was higher in adults who reported knowing an HIV-positive family member ( aOR=1.45 ; CI 1.12–1.86 ) versus not , and in those who said that they would take ART as soon as possible if they were diagnosed HIV positive ( aOR=2.16 ; CI 1.13–4.10 ) versus not . Conclusions Fewer than 40 % of HIV-positive adults not in care at referral were linked to HIV care within three months of HBHCT in the TasP trial . Achieving universal test and treat coverage will require innovative interventions to support linkage to HIV care Background In high HIV prevalence setting s , offering HIV testing may be a reasonable part of contact tracing of index tuberculosis ( TB ) patients . We evaluated the uptake of HIV counselling and testing ( HCT ) among household contacts of index TB patients and the proportion of newly diagnosed HIV-infected persons linked into care as part of a household TB contact tracing study . Methods We recruited index TB patients at public health clinics in two South African provinces to obtain consent for household contact tracing . During scheduled household visits we offered TB symptom screening to all household members and HCT to individuals ≥14years of age . Factors associated with HCT uptake were investigated using a r and om effects logistic regression model . Results & Discussion Out of 1,887 listed household members ≥14 years old , 984 ( 52 % ) were available during a household visit and offered HCT of which 108 ( 11 % ) self-reported being HIV infected and did not undergo HCT . Of the remaining 876 , a total of 304 agreed to HCT ( 35 % ) ; 26 ( 8.6 % ) were newly diagnosed as HIV positive . In multivariable analysis , factors associated with uptake of HCT were prior testing ( odds ratio 1.6 ; 95 % confidence interval [ CI ] : 1.1–2.3 ) and another member in the household testing ( odds ratio 2.4 ; 95 % CI : 1.7–3.4 ) . Within 3 months of testing HIV-positive , 35 % reported initiating HIV care . Conclusion HCT as a component of household TB contact tracing reached individuals without prior HIV testing , however uptake of HIV testing was poor . Strategies to improve HIV testing in household contacts should be evaluated OBJECTIVE Antiretroviral therapy ( ART ) significantly decreases HIV-associated morbidity , mortality , and HIV transmission through HIV viral load suppression . In high HIV prevalence setting s , outreach strategies are needed to find asymptomatic HIV positive persons , link them to HIV care and ART , and achieve viral suppression . METHODS We conducted a prospect i ve intervention study in two rural communities in KwaZulu-Natal , South Africa , and Mbabara district , Ug and a. The intervention included home HIV testing and counseling ( HTC ) , point-of-care CD4 count testing for HIV positive persons , referral to care , and one month then quarterly lay counselor follow-up visits . The outcomes at 12 months were linkage to care , and ART initiation and viral suppression among HIV positive persons eligible for ART ( CD4≤350 cells/μL ) . FINDINGS 3,393 adults were tested for HIV ( 96 % coverage ) , of whom 635 ( 19 % ) were HIV positive . At baseline , 36 % of HIV positive persons were newly identified ( 64 % were previously known to be HIV positive ) and 40 % were taking ART . By month 12 , 619 ( 97 % ) of HIV positive persons visited an HIV clinic , and of 123 ART eligible participants , 94 ( 76 % ) initiated ART by 12 months . Of the 77 participants on ART by month 9 , 59 ( 77 % ) achieved viral suppression by month 12 . Among all HIV positive persons , the proportion with viral suppression ( < 1,000 copies/mL ) increased from 50 % to 65 % ( p=<0.001 ) at 12 months . INTERPRETATION Community-based HTC in rural South Africa and Ug and a achieved high testing coverage and linkage to care . Among those eligible for ART , a high proportion initiated ART and achieved viral suppression , indicating high adherence . Implementation of this HTC approach by existing community health workers in Africa should be evaluated to determine effectiveness and costs BACKGROUND For adults with human immunodeficiency virus ( HIV ) infection who have CD4 + T-cell counts that are greater than 200 and less than 350 per cubic millimeter and who live in areas with limited re sources , the optimal time to initiate antiretroviral therapy remains uncertain . METHODS We conducted a r and omized , open-label trial of early initiation of antiretroviral therapy , as compared with the st and ard timing for initiation of therapy , among HIV-infected adults in Haiti who had a confirmed CD4 + T-cell count that was greater than 200 and less than 350 per cubic millimeter at baseline and no history of an acquired immunodeficiency syndrome ( AIDS ) illness . The primary study end point was survival . The early-treatment group began taking zidovudine , lamivudine , and efavirenz therapy within 2 weeks after enrollment . The st and ard-treatment group started the same regimen of antiretroviral therapy when their CD4 + T-cell count fell to 200 per cubic millimeter or less or when clinical AIDS developed . Participants in both groups underwent monthly follow-up assessment s and received isoniazid and trimethoprim-sulfamethoxazole prophylaxis with nutritional support . RESULTS Between 2005 and 2008 , a total of 816 participants --408 per group -- were enrolled and were followed for a median of 21 months . The CD4 + T-cell count at enrollment was approximately 280 per cubic millimeter in both groups . There were 23 deaths in the st and ard-treatment group , as compared with 6 in the early-treatment group ( hazard ratio with st and ard treatment , 4.0 ; 95 % confidence interval [ CI ] , 1.6 to 9.8 ; P=0.001 ) . There were 36 incident cases of tuberculosis in the st and ard-treatment group , as compared with 18 in the early-treatment group ( hazard ratio , 2.0 ; 95 % CI , 1.2 to 3.6 ; P=0.01 ) . CONCLUSIONS Early initiation of antiretroviral therapy decreased the rates of death and incident tuberculosis . Access to antiretroviral therapy should be exp and ed to include all HIV-infected adults who have CD4 + T-cell counts of less than 350 per cubic millimeter , including those who live in areas with limited re sources . ( Clinical Trials.gov number , NCT00120510 . Home-based voluntary HIV counselling and testing ( HB-VCT ) has been reported to have a high uptake , but it has not been rigorously evaluated . We design ed a model for HB-VCT appropriate for wider scale-up , and investigated the acceptance of home-based counselling and testing , equity in uptake and negative life events with a cluster-r and omized trial . Thirty six rural clusters in southern Zambia were pair-matched based on baseline data and r and omly assigned to the intervention or the control arm . Both arms had access to st and ard HIV testing services . Adults in the intervention clusters were offered HB-VCT by local lay counsellors . Effects were first analysed among those participating in the baseline and post-intervention surveys and then as intention-to-treat analysis . The study was registered with www.controlled-trials.com , number IS RCT N53353725 . A total of 836 and 858 adults were assigned to the intervention and control clusters , respectively . In the intervention arm , counselling was accepted by 85 % and 66 % were tested ( n = 686 ) . Among counselled respondents who were cohabiting with the partner , 62 % were counselled together with the partner . At follow-up eight months later , the proportion of adults reporting to have been tested the year prior to follow-up was 82 % in the intervention arm and 52 % in the control arm ( Relative Risk ( RR ) 1.6 , 95 % CI 1.4 - 1.8 ) , whereas the RR was 1.7 ( 1.4 - 2.0 ) according to the intention-to-treat analysis . At baseline the likelihood of being tested was higher for women vs. men and for more educated people . At follow-up these differences were found only in the control communities . Measured negative life events following HIV testing were similar in both groups . In conclusion , this HB-VCT model was found to be feasible , with a very high acceptance and to have important equity effects . The high couple counselling acceptance suggests that the home-based approach has a particularly high HIV prevention potential Objective To assess the effect of home based HIV counselling and testing on the prevalence of HIV testing and reported behavioural changes in a rural subdistrict of South Africa . Design Cluster r and omised controlled trial . Setting 16 communities ( clusters ) in uMzimkhulu subdistrict , KwaZulu-Natal province , South Africa . Participants 4154 people aged 14 years or more who participated in a community survey . Intervention Lay counsellors conducted door to door outreach and offered home based HIV counselling and testing to all consenting adults and adolescents aged 14 - 17 years with guardian consent . Control clusters received st and ard care , which consisted of HIV counselling and testing services at local clinics . Main outcome measures Primary outcome measure was prevalence of testing for HIV . Other outcomes were HIV awareness , stigma , sexual behaviour , vulnerability to violence , and access to care . Results Overall , 69 % of participants in the home based HIV counselling and testing arm versus 47 % in the control arm were tested for HIV during the study period ( prevalence ratio 1.54 , 95 % confidence interval 1.32 to 1.81 ) . More couples in the intervention arm had counselling and testing together than in the control arm ( 2.24 , 1.49 to 3.03 ) . The intervention had broader effects beyond HIV testing , with a 55 % reduction in multiple partners ( 0.45 , 0.33 to 0.62 ) and a stronger effect among those who had an HIV test ( 0.37 , 0.24 to 0.58 ) and a 45 % reduction in casual sexual partners ( 0.55 , 0.42 to 0.73 ) . Conclusions Home based HIV counselling and testing increased the prevalence of HIV testing in a rural setting with high levels of stigma . Benefits also included higher uptake of couple counselling and testing and reduced sexual risk behaviour . Trial registration Current Controlled Trials IS RCT N31271935 BACKGROUND Male circumcision decreases HIV acquisition by 60 % , and antiretroviral therapy ( ART ) almost eliminates HIV transmission from HIV-positive people who are virally suppressed ; however , coverage of these interventions has lagged behind targets . We aim ed to assess whether community-based HIV testing with counsellor support and point-of-care CD4 cell count testing would increase uptake of ART and male circumcision . METHODS We did this multisite , open-label , r and omised controlled trial in six research -naive communities in rural South Africa and Ug and a. Eligible HIV-positive participants ( aged ≥16 years ) were r and omly assigned ( 1:1:1 ) in a factorial design to receive lay counsellor clinic linkage facilitation , lay counsellor follow-up home visits , or st and ard-of-care clinic referral , and then ( 1:1 ) either point-of-care CD4 cell count testing or referral for CD4 testing . HIV-negative uncircumcised men ( aged 16 - 49 years ) who could receive secure mobile phone text messages were r and omly assigned ( 1:1:1 ) to receive text message reminders , lay counsellor visits , or st and ard clinic referral . The study biostatistician generated the r and omisation schedule via a computer-generated r and om number program with varying block sizes ( multiples of six or three ) stratified by country . Primary outcomes for HIV-positive people were obtaining a CD4 cell count , linkage to an HIV clinic , ART initiation , and viral suppression at 9 months , and for HIV-negative uncircumcised men were visiting a circumcision facility and uptake of male circumcision at 3 months . We assessed social harms as a safety outcome throughout the study . We did the primary analyses by intention to treat . This trial is registered with Clinical Trials.gov , number NCT02038582 . FINDINGS Between June 6 , 2013 , and March 11 , 2015 , 15 332 participants were tested . 2339 ( 15 % ) participants tested HIV positive , of whom 1325 ( 57 % ) were r and omly assigned to receive lay counsellor clinic linkage facilitation ( n=437 ) , lay counsellor follow-up home visits ( n=449 ) , or st and ard clinic referral ( n=439 ) , and then point-of-care CD4 cell testing ( n=206 , n=220 , and n=213 , respectively ) or referral for CD4 testing ( n=231 , n=229 , and n=226 , respectively ) . 12 993 ( 85 % ) participants tested HIV negative , of whom 750 ( 6 % ) uncircumcised men were r and omly assigned to receive clinic referral ( n=230 ) , text message reminders ( n=288 ) , or lay counsellor follow-up visits ( n=232 ) . 1218 ( 93 % ) of 1303 HIV-positive participants were linked to care , but only 488 ( 37 % ) participants initiated ART . Overall , 635 ( 50 % ) of 1272 HIV-positive individuals achieved viral suppression at 9 months : 219 ( 52 % ) of 419 participants in the clinic facilitation group , 202 ( 47 % ) of 431 participants in the lay counsellor follow-up group , and 214 ( 51 % ) of 422 participants in the clinic referral group , with no significant differences between groups ( p=0·668 for clinic facilitation and p=0·273 for lay counsellor follow-up vs clinic referral ) . 523 ( 72 % ) of 734 HIV-negative men visited a circumcision facility , with no difference between groups . 62 ( 28 % ) of 224 men were circumcised in the male circumcision clinic referral group compared with 137 ( 48 % ) of 284 men in the text message reminder group ( relative risk 1·72 , 95 % CI 1·36 - 2·17 ; p<0·0001 ) and 106 ( 47 % ) of 226 men in the lay counsellor follow-up group ( 1·67 , 1·29 - 2·14 ; p=0·0001 ) . No cases of study -related social harm were reported , including probing about partnership separation , unintended disclosure , gender-based violence , and stigma . INTERPRETATION All the community-based strategies achieved high rates of linkage of HIV-positive people to HIV clinics , roughly a third of whom initiated ART , and of those more than 80 % were virally suppressed at 9 months . Uptake of male circumcision was almost two-times higher in men who received text message reminders or lay counsellor visits than in those who received st and ard-of-care clinic referral . Clinic barriers to ART initiation should be addressed in future strategies to increase the proportion of HIV-positive people accessing treatment and achieving viral suppression . FUNDING National Institute of Allergy and Infectious Diseases , National Institutes of Health |
11,861 | 28,012,361 | Although some studies demonstrated effective learning outcomes result ing from near-peer teaching , others were inconclusive .
The studies review ed focused on cognitive and psychomotor abilities of learners . | BACKGROUND Near Peer teaching ( NPT ) is reported as an effective pedagogical approach to student learning and performance .
Studies in medicine , nursing and health sciences have relied mainly on self-reports to describe its benefits , focusing on psychomotor and cognitive aspects of learning .
Despite increasing research reports on peer teaching internationally , little is known about the various domains of learning used in assessment of performance and objective learning outcomes of NPT .
OBJECTIVE To determine the domains of learning and assessment outcomes used in NPT in undergraduate health professional education . | PURPOSE : To see whether fourth-year medical students can teach the physical examination to first-year students as effectively as can faculty preceptors . METHOD : Ninety-three first-year students study ing the physical examination were r and omly assigned to one of ten fourth-year student preceptors or one of 15 faculty preceptors . Test results and course evaluations were compared by type of preceptor . Fourth-year student preceptors were surveyed regarding their experience . RESULTS : The mean test scores did not differ between the first-year students with fourth-year student preceptors and those with faculty preceptors . The first-year students rated the fourth-year student preceptors higher than they did the faculty preceptors . The fourth-year students rated their experience favorably . CONCLUSION : A select group of fourth-year medical students provides a successful alternative to faculty in the teaching of the physical examination to first-year students Aim : The aim of this study is to compare student teachers and clinical associate professors regarding the quality of procedural skills teaching in terms of participants ’ technical skills , knowledge and satisfaction with the teaching . Methods : This is an experimental , r and omized , controlled study comparing the teaching of student teachers and associate professors regarding participants ’ learning outcome and satisfaction with the teaching . Two skills are chosen for the experiment , IV-access and bladder catheterization . Learning outcome is assessed by a pre- and post testing of the participants ’ knowledge and skills . Participants evaluate satisfaction with teaching on nine statements immediately after the teaching . Results : In total 59 first year medical students are included as participants in the experiment . The students taught by student teachers perform just as well as the students taught by associate professors and in one skill – catheterization – they perform even better , mean post- minus pre-test scores 65.5 ( SD 12.9 ) vs. 35.0 ( SD 23.3 ) , One-way ANOVA , p < 0.0001 , effect size 1.62 . Student teachers receive significantly more positive evaluations than associate professors on several statements . Conclusion : Trained student teachers can be as good as associate professors in teaching clinical skills Peer tutoring is a potentially valuable re source in higher education . There are few published accounts of the impact of peer tutoring in medical education . College-wide experience of peer tutoring together with difficulties recruiting medical teachers for a communication programme led to the development of a peer-tutoring project . This paper reports the impact on first-year medical students of peer tutoring in patient-centred interviewing . After attending a preparatory workshop , third-year medical students co-facilitated their first-year colleagues in a session : Interviewing a Simulated Patient . First-year students completed written evaluations immediately after the session and two months later r and omly selected students were assessed in patient-centred interviews . The impact of the peer-tutoring experience was evaluated by comparing these outcomes for students in groups co-facilitated by peer tutors with those who worked in groups facilitated by medical teachers . The eight learning objectives were completely met by more than 56 % of students . However , there were statistically significant differences for four objectives with more students in groups facilitated by medical teachers completely meeting these objectives . Although the seven educational techniques used in the session were rated favourably by all students , two were rated as more effective in achieving the learning objectives by students in groups facilitated by medical teachers . Free-text comments revealed no differences between groups . Two months after the session , there were no differences between students in terms of interviewing skills as rated by trained observers and simulated patients , whilst simulated patients were more satisfied with interviews from students facilitated by peer tutors ( p < 0.02 ) . Peer tutors can support the acquisition of basic patient-centred interviewing skills in first-year medical students when contributing to one session of a structured programme . First-year students were receptive and willing to learn from their senior colleagues Abstract . Limited access to expert tutors is a problem that can be addressed by using tutors from different stages of medical or non-medical ( under- , post- ) graduate education . To address whether such differences in qualification affect the results of process evaluation by participants or their learning outcome ( exam results ) , we analysed the data of a 4-year prospect i ve study performed with 787 3rd-year medical students ( 111 groups of 5–10 participants ) taking an obligatory problem-based learning (PbL)-course of basic pharmacology . We compared peer tutors ( undergraduate medical students , ≥4th year ) , non-expert ( junior ) staff tutors ( physicians , pharmacists , veterinarians , biologists , or chemists during postgraduate education ) , and expert ( senior ) staff tutors ( completed postgraduate education ) . Evaluation scores related to PbL gave the highest values for senior staff-led groups . The tutor 's performance score of peer-led groups did not differ from those of staff-led groups , but the score obtained from groups tutored by junior staff was lower than that obtained with senior staff tutors . Students ' weekly preparation time tended to be lower in peer-led groups , while learning time spent specifically on exam preparation seemed to be increased compared to PbL-groups of staff tutors . As a putative confounding variable , tutors ' experience in coaching PbL-groups was also investigated . Groups led by experienced tutors , defined as tutors with at least one term of previous PbL tutoring , were found to have significantly higher evaluation scores . Interestingly , neither tutors ' subject-matter expertise ( peer students , junior staff , or senior staff ) nor their teaching- method expertise showed any influence on PbL-groups ' mean test scores in a written exam . This indicates that the effect of tutor expertise on the learning process is not associated with a difference in learning outcome when just factual knowledge is assessed by traditional methods OBJECTIVES Bedside sonography is a growing field of medicine , but there is little evidence about how to teach it to medical students . A peer-mentoring system may help pre clinical medical students learn bedside sonography . METHODS In 2008 and 2009 , participating first-year medical students completed an image recognition test at 0 , 2 , and 4 months and were r and omized to an early or a late intervention group . In h and s-on sessions , senior medical students taught the early intervention group how to perform a Trinity hypotensive ultrasound protocol between months 0 and 2 and then taught the late intervention group the Trinity protocol between months 2 and 4 . Participants completed a practical examination at month 4 . We measured the improvement in knowledge after the intervention and retention of knowledge and skills in the early intervention group at month 4 . First-year medical students completed precourse and postcourse surveys about comfort and skills with sonography . RESULTS Eighty-six first-year medical students enrolled ; 79 completed the precourse survey ; 54 completed all knowledge tests ; 52 completed the practical examination ; and 49 completed the postcourse survey . Of the 125 non participants , 109 completed the precourse survey , and 25 completed the postcourse survey . Participants ' knowledge scores increased by 30 % after the intervention . The early intervention group retained 92 % of the knowledge gained . Thirty-six percent of participants were able to complete the Trinity protocol in 15 minutes during the practical examination , with no significant difference between the early and late intervention groups . Participants responded positively about the experience and indicated that h and s-on sessions were helpful . CONCLUSIONS Peer mentoring is a useful method for teaching sonography to pre clinical medical students |
11,862 | 24,660,192 | Although no statistical difference was found between cement- and screw-retained reconstructions for survival or failure rates , screw-retained reconstructions exhibited fewer technical and biologic complications overall .
There were no statistically significant differences between the failure rates of the different reconstruction types ( I-SCs , I-FDPs , full-arch I-FDPs ) or abutment material s ( titanium , gold , ceramic ) .
The failure rate of cemented reconstructions was not influenced by the choice of a specific cement , though cement type did influence loss of retention | PURPOSE To assess the survival outcomes and reported complications of screw- and cement-retained fixed reconstructions supported on dental implants . | PURPOSE To compare the efficacy of immediate functionally loaded implants placed with a flapless procedure ( test group ) versus implants placed after flap elevation and conventional load-free healing ( control group ) in partially edentulous patients . MATERIAL S AND METHODS Forty patients were r and omized : 20 to the flapless immediately loaded group and 20 to the conventional group . To be immediately loaded , implants had to be inserted with a minimum torque > 45 Ncm . Implants in the immediately loaded group were provided with full acrylic resin temporary restorations the same day . Implants in the conventional group were submerged ( anterior region ) or left unsubmerged ( posterior region ) and were left load-free for 3 months ( m and ibles ) or 4 months ( maxillae ) . Provisional restorations were replaced with definitive single metal-ceramic crowns 1 month postloading . Outcome measures were prosthesis and implant failures , biological and prosthetic complications , postoperative edema , pain , and use of analgesics . Independent sample chi2 tests , Mann-Whitney tests , t tests , and paired t tests were used with a significance level of .05 . RESULTS Fifty-two implants were placed in the flapless group and 56 in the conventionally loaded group . In the flapless group , 1 flap had to be raised to control the direction of the bur and 1 implant did not reach the planned primary stability and was treated as belonging to the conventional group . After 3 years no dropouts or failures occurred . There was no statistically significant difference for complications ; however , patients in the conventional group had significantly more postoperative edema and pain and consumed more analgesics than those in the flapless group . Osstell values were significantly higher at baseline in the flapless group ( P = .033 ) . When comparing baseline data with years 1 , 2 , and 3 within each group , mean Osstell values of the flapless group did not increase , whereas there were statistically significant increases in the Periotest values . CONCLUSIONS Implants can be successfully placed flapless and loaded immediately without compromising success rates ; the procedure decreases treatment time and patient discomfort OBJECTIVE The purpose of this prospect i ve clinical study was to evaluate peri-implant soft-tissue conditions and esthetic fulfillment during a 3-year follow-up period following prosthetic rehabilitation . MATERIAL AND METHODS As part of a prospect i ve multi-center study , 152 ITI dental implants were placed in 80 patients in the maxillary anterior region . Fifty-nine crowns ( 38.82 % ) were cement retained , while 93 ( 61.18 % ) crowns were screw retained . At loading and 3 , 6 , 12 and 36 months post-loading , modified plaque index ( MPI ) , sulcus bleeding index ( SBI ) , keratinized mucosa ( KM ) , gingival level ( GL ) , and esthetic fulfillment were recorded . RESULTS All patients completed the study and no complications were reported . While statistically not significant at all time points , cement-retained crowns seemed to present a worsening trend in MPI and SBI scores . Interestingly , screw-retained crowns seemed to present an opposite picture , their MPI and SBI scores improved over time . While plaque accumulation , prophylaxis and depth of crown margin significantly affected levels of sulcus bleeding , prophylaxis alone played a key role in reducing plaque accumulation . No soft tissue recession was observed in either cement- or screw-retained crowns up to 3 years post-loading . Esthetic fulfillment survey revealed that patients did not have a preference for crown types ; however , dentists favored cement-retained over screw-retained crowns . CONCLUSIONS Peri-implant soft tissues responded more favorably to screw-retained crowns when compared with cement-retained crowns . However , no soft-tissue recession was observed in either type of crowns . Cement-retained crowns were preferred by dentists , while patients were equally satisfied with either type of crowns they received The aim of this study was to evaluate the survival and success rates of immediately restored implants with s and blasted , large-grit , acid-etched ( SLA ) surfaces over a period of 5 years . Twenty patients ( mean age , 47.3 years ) received a total of 21 SLA wide-neck implants in healed m and ibular first molar sites after initial periodontal treatment . To be included in the study , the implants had to demonstrate primary stability with an insertion torque value of 35 Ncm . A provisional restoration was fabricated chairside and placed on the day of surgery . Definitive cemented restorations were inserted 8 weeks after surgery . Community Periodontal Index of Treatment Needs ( CPITN ) indices and the radiographic distance between the implant shoulder and the first visible bone-implant contact ( DIB ) were measured and compared over the study period . The initial mean CPITN was 3.24 , and decreased over the study period to 1.43 . At the postoperative radiographic examination , the mean DIB was 1.41 mm for the 21 implants , indicating that part of the machined neck of the implants was placed slightly below the osseous crest . The mean DIB value increased to 1.99 mm at the 5-year examination . This increase proved to be statistically significant ( P < .0001 ) . Between the baseline and 5-year examinations , the mean bone crest level loss was 0.58 mm . Success and survival rates of the 21 implants after 5 years of function were 100 % . This 5-year study confirms that immediate restoration of m and ibular molar wide-neck implants with good primary stability , as noted by insertion torque values of at least 35 Ncm , is a safe and predictable procedure BACKGROUND Long-term follow-up studies ( i.e. , over 5 years ) , focusing on prosthetic outcomes and maintenance of implant-supported reconstructions in the edentulous maxilla , are scarce in the literature . PURPOSE The purpose of this study was to evaluate and report 10-year data on outcomes and maintenance of screw-retained implant-supported full-arch casted titanium-resin prostheses in the edentulous maxilla . MATERIAL S AND METHODS In the r and omized control trial cohort of 24 patients , the outcome and maintenance of 23 bridges were registered . RESULTS One patient dropped out of the study prior to the 10-year control . Of the 23 remaining patients , 21 still had their original frameworks ; one framework fractured after 8 years and one was remade after 7 years to create better support for the acrylic . The remaining 23 prostheses showed criteria of success , survival , and failure in 9 , 82 , and 9 % , respectively . Tightening of two assembly screws was necessary in one patient . No detrimental effects were seen because of long cantilever extensions or opposing dentition . A total of 4.7 resin-related complications per prosthesis were observed ; tooth fracture was the most common prosthetic complication . There was an indication of greater prevention in the number of resin-related complications with the use of lingual gold onlay compared with a resilient mouth guard , 0.71 and 1.67 , respectively per bridge . The bridges were removed and reinserted 0.83 times per patient . No abutment or abutment screw fractures were registered . CONCLUSION Fracture or wear of the reconstruction material s were considered predictable risks when using resin-based suprastructure material s. Status of opposing dentition and length of cantilevers did not confer additional risk . The use of a lingual gold onlay indicated prevention of resin-related complications . Future research should focus on the suprastructure material s to predict better overall treatment results of implant-supported full-arch bridges in the edentulous maxilla PURPOSE The possibility of expediting dental implant therapy by early or immediate loading protocol s requires long-term clinical investigation . The aim of this prospect i ve cohort trial was to determine the 3-year implant success rate and prosthesis complications associated with functional loading 3 weeks after 1-stage placement of Astra Tech single-tooth implants replacing maxillary anterior teeth . A secondary objective was to determine peri-implant tissue responses at these implants . MATERIAL S AND METHODS The peri-implant bone and mucosal conditions of 43 implants in 39 subjects were radiographically and clinical ly measured 3 years after implant placement . RESULTS Of the 48 patients originally treated , 39 patients and 43 implants were examined at the 3-year time point . Three of 54 implants failed within the first year . No additional failures were recorded since the 12-month reporting period . Peri-implant bone levels were stable for the 3-year period following implant placement . The change in marginal bone levels after 3 years was 0.42 + /- 0.59 mm . Papilla growth was measured at 1 and 3 years ( 0.61 + /- 0.95 mm and 0.74 + /- 0.79 mm , respectively ) . The buccal peri-implant tissue dimensions at the gingival zenith also increased at 1 and 3 years ( 0.34 + /- 0.94 mm and 0.51 + /- 1.42 mm , respectively ) . No abutment screw loosening or fracture occurred . DISCUSSION AND CONCLUSIONS Early loading of endosseous dental implants placed in healed ridges offers select benefits to clinicians and their patients PURPOSE To present long-term clinical and radiographic data on single-implant treatment in the anterior maxilla and to compare these results with comparable data of central implants supporting fixed prostheses in the edentulous maxilla . MATERIAL S AND METHODS A total of 38 patients consecutively restored with 47 single-implant crowns in the anterior maxilla were included in the single-implant ( study ) group . The implants in the edentulous group ( control ) were included by r and omly selecting one of the central implants ( closest to midline ) from 76 consecutively treated edentulous patients . Mean age was 25.4 years ( SD : 10.0 ) and 60.1 years ( SD : 11.6 ) at inclusion ( P < .001 ) for the study and control groups , respectively . Clinical and radiographic data were retrospectively retrieved from files holding up to 15 years of function in both groups . RESULTS No implants in the study group were lost ( cumulative success rate : 100 % ) , while 3 implants in the control group were lost ( cumulative success rate : 95.4 % ) . Ten single crowns were replaced ( 15-year cumulative survival rate : 77.0 % ) , and the study group showed more mucosal problems and fistulas compared to the implants in the control group ( P < .05 ) . Loose screws were a common problem in the single-implant group during the first 5 years of function , but bone loss did not differ significantly between patients with stable and loose screws/fistulas ( P > .05 ) or between study and control implants after 15 years ( P > .05 ) . CONCLUSIONS There is an obvious difference between the survival of the implants ( 100 % ) and original implant crowns ( 77 % ) in the study group . The present early single-implant restorations showed significantly more mechanical/fistula problems compared to central implants in the edentulous maxilla ( P < .05 ) , but bone response was similar for both groups during 15 years of follow-up . Bone loss was not affected by the level of the implant head in relation to the cementoenamel junction of adjacent teeth , nor was it affected by mechanical or mucosal problems or persistent fistulas of the single implants during the entire follow-up period Screw loosening is considered to be a common problem with both screw - retained and cemented implant restorations . A wider abutment platform , as well as using a torque driver to tighten specifically design ed screws may help prevent this loosening . However , there has been no clinical study evaluating either of these . To longitudinally compare the frequency of screw loosening in st and ard diameter , ( 3.75 and 4.0 mm ) implant supported prostheses to that of wide diameter , ( 5.0 and 6.0 mm ) implant supported prostheses that were h and tightened , and to evaluate whether using a torque driver would minimize or prevent this problem , if screw loosening occurred . A total of 213 dental implants in 106 patients were included in this prospect i ve longitudinal study . Of the implants 68 were wide diameter and 145 were st and ard diameter implants . Wide diameter implants showed 5.8 % screw loosening , while st and ard diameter implants showed 14.5 % screw loosening after insertion with only h and torquing . When these loose screws were tightened with a torque driver , there was no more loosening of screws . Within the limitations of this study , the wide diameter implants tested showed less screw loosening than the st and ard diameter implants when h and torqued . Additionally , within the scope of our study , using a torque driver to tighten the screws with the recommended force prevented this loosening from reoccurring in all cases The purpose of this study was to evaluate the survival and success of screw- versus cement-retained implant crowns over a 5-year period . This was a multi-center prospect i ve cohort study , consisting of patients who had ≥1 dental implant placed and restored in the anterior maxilla over a 5-year period . The primary predictor variable was the type of restoration ( screw- versus cement-retained ) . The outcome variables were clinician- or patient-reported measures related to soft tissue and restoration quality . Descriptive and bivariate statistics were computed to compare the screw- versus cement-retained groups . Kaplan – Meier statistics were computed for implant survival . Information was collected for 102 patients who had 214 implants placed during the study period . Complete data , amenable to analysis , were available for 99 ( 97.1 % ) patients and 193 ( 90.2 % ) implants . The restorations were approximately evenly divided between screw- ( 53.4 % ) and cement-retained ( 46.6 % ) . Approximately 49 % of patients in the sample were female ; the sample 's mean age was 47.3 ± 13.9 years ; each patient had an average of 2.0 ± 1.0 implants placed and restored . The mean time from prosthesis placement ( definitive ) to study endpoint was 61.9 ± 10.6 months . The overall implant survival rate was 96.4 % , with no statistically significant difference in survival between the screw- and cement-retained groups ( p = 0.45 ) . The majority of clinician- and patient-assessed outcomes were similar . The results of this study indicate that for the majority of clinician- and patient-assessed success parameters screw- and cement-retained restorations are equivalent in the anterior maxilla OBJECTIVE To evaluate the use of a single Astra Tech implant to support a two-unit cantilever fixed dental prosthesis . MATERIAL S AND METHOD Twenty-nine subjects with an edentulous space ( at least equivalent to two bicuspid units ) in the premolar/molar segments of the maxilla or m and ible with opposing natural teeth or a fixed/removable prosthesis were treated . They were provided with either a 4 or 5.0 mm diameter fixture MT OsseoSpeed . Prostheses were constructed using a cast-to abutment as a one-piece unit with porcelain fused to precious metal to allow direct screw retention . RESULTS Subjects expressed a high satisfaction with treatment , including appearance and function . The most important complication was abutment screw loosening . It occurred as a single episode in four subjects and in another six subjects the loosening was recurrent . Bone levels were stable and there were no significant differences in radiographic bone height between cantilever and non-cantilever sides of the implant at any time point . CONCLUSION Single implants can be successfully used to support two-unit cantilever FDPs in the premolar region . A common factor could not be identified in relation to abutment screw loosening In this multicenter prospect i ve study , the results achieved with the use of Brånemark implants for single tooth replacement were evaluated . The overall cumulative success rate was 95.9 % for implants and 91.1 % for crowns . Two of the 99 implants placed had to be removed before the prosthodontic stage of treatment ; thus , 97 were restored with CeraOne crowns . Seventy-seven implants were evaluated radiographically at the 1-year follow-up , 57 at 3 years , and 47 at 5 years . Mean marginal bone resorption was well within the limits set by Albrektsson et al in 1986 . The status of the soft tissue around crowns and adjacent teeth remained stable over the evaluation period . The gold abutment screw in the CeraOne system seems to have eliminated the problem of loosening abutment screws in single tooth replacements . The results suggest that the Brånemark system can be safely used for tissue-integrated replacement of single teeth AIM The purpose of this study was to evaluate the survival and success of early-loaded implants placed in the intraforaminal area of the edentulous m and ible , and the survival of the implant-supported fixed dental prostheses ( FDP ) . MATERIAL AND METHODS Thirty-seven patients ( 18.9 % male , mean age 64.5 years ) with edentulous lower jaws were treated with implant-supported FDPs in the m and ible . One hundred and eighty-five screw-type implants were placed in the intraforaminal area of the symphysis ( five implants per patient ) . Immediately after implant placement , a framework was fabricated and the FDP was manufactured on the framework . Within 2 weeks , the implants were rigidly connected and loaded with the implant-retained FDP . RESULTS During the 1 - 8-year observation period ( mean 4.5 years ) , a total of 32 implant-retained complications occurred . Nineteen implants were lost in 10 patients , result ing in a cumulative survival of 89.7 % . Nine implants in five patients did not osseointegrate . Although these implants were not removed , because stability within the connective tissue was acceptable and inflammation was absent , they were recorded as unsuccessful . Consequently , the cumulative success declined to 84.9 % . Four implants in three patients had clinical signs of periimplantitis ( 2.2 % of all implants ) . Denture-related complications included one complete failure , when one FDP had to be removed after the last of five implants had been replaced . Furthermore , 10 fractures of the framework occurred in six patients , three FDPs had to be adapted or modified , and the facing of the FDP had to be repaired 16 times in 11 patients . CONCLUSION Although one-stage early-loaded implants functioned well for most patients with edentulous m and ibles , immediate loading is associated with a larger number of implant-related complications than in other studies investigating delayed loading . Because of the substantial prosthetic complications and aftercare , this procedure can not be generally recommended PURPOSE The purpose of this prospect i ve clinical study was to compare titanium and gold-alloy abutments when used with cemented , implant-supported single-tooth crowns . For 4 years following prosthodontic rehabilitation , these abutments were evaluated with respect to peri-implant marginal bone levels and peri-implant soft tissue parameters . MATERIAL S AND METHODS During the years 1998 to 2000 , 20 patients were selected from a patient population receiving treatment in the Implantology Department at the University of Padova , Italy . They all presented with single-tooth bilateral edentulous sites in the premolar/molar region with adequate bone width , similar bone height on each side , and an occlusal scheme that allowed for the establishment of identical occlusal cusp/fossa contacts on each side . Each subject received two identical implants ( one in each edentulous site ) . One was r and omly selected to be restored with a titanium abutment and a cemented implant-supported single-tooth crown , and the other was restored with a gold-alloy abutment and a cemented implant-supported single tooth crown . Data on peri-implant marginal bone levels and soft tissue parameters were collected for 4 years after abutment and crown insertion placement and analyzed to determine whether there was a significant ( p < .001 ) difference with respect to the type of abutments ( titanium vs. gold alloy ) used . RESULTS All subjects completed the study . All 40 implants survived , result ing in a cumulative implant success rate of 100 % . Statistical analysis revealed no significant differences between the two groups with respect to peri-implant marginal bone levels and soft tissue parameters . CONCLUSIONS Within the limitations of this study , the results indicate that there was no evidence of different response with the peri-implant marginal bone and soft tissue when titanium or gold-alloy abutments were used in conjunction with the cemented , single-tooth implant restorations provided for this limited patient population . There was no evidence of different behavior of peri-implant marginal bone and of peri-implant soft tissue when titanium abutments or gold-alloy abutments were used for cemented single-tooth implant restorations in this limited patient population OBJECTIVES This prospect i ve multicentre study provides clinical experience up to 3 years to support a simplified treatment for m and ibular edentulism within 1 week by using one-stage implant surgery and a screw-retained full-arch bridge . METHODS Two hundred and fifty ITI Monotype ® implants were installed in 62 patients out of 66 patients ; 60 patients got four implants each and two got five implants . After 1 week , a final bridge was in function . Radiographs were taken as baseline for vertical bone loss up to 3 years post-loading for the whole cluster and specific effects of gender , centre , age , bone class , implant length over time were compiled . Clinical ( mPI , SBI ) and subjective parameters such as general oral hygiene and patient satisfaction were recorded and repeated at specified intervals up to 3 years . RESULTS Four patients were excluded at surgery and are not involved in the follow-ups . At 1 year , 61 patients ( 244 implants ) were evaluable and all bridges were in function . After 3 years , 49 patients ( 194 implants ) came to control . Eight patients died during the follow-up period . Three patients lost one implant each . The cumulative implant survival rate was 98.55 % and the success rate for the prosthesis was 100 % . As calculated from measurable radiographs , the mean bone level at baseline was 1.63±0.78 and at 1 and 3 years 2.50±0.60 and 2.56±0.74 , respectively . Using the mixed model analysis and Friedman test , the time in situ , centre and bone class had significant effect on the bone resorption and to some small extent even , the implant length . Gender and age were unaffected . Oral hygiene and patient satisfaction of the treatment were improved . CONCLUSIONS The results indicate that one-part self-tapping s and blasted , large-grit , acid-etched ( SLA ) implants are suitable for loading within 1 week . In the whole period , the mean bone crestal resorption was < 1 mm , which is in agreement with other similar studies PURPOSE The aim of this 5-year prospect i ve study was to compare the results of single-tooth implant treatments planned and performed at four general practitioners ' offices with the results from a specialist clinic . MATERIAL S AND METHODS The group comprised 38 patients . Nineteen patients , with 19 implants/crowns , were planned and treated by four general practitioners , and the outcome was compared to a matched group of patients from a specialist clinic . RESULTS Three patients did not complete the study . None of the implants failed ; one crown failed . This was a very positive result , as the single failure , a crown at the specialist clinic , was caused by an extraordinary trauma and was not related to a common cause such as bite forces or fatigue . No significant differences were observed between the groups when the radiographic findings were compared . Some minor differences , for bleeding and the position of the mucosal level around implants and adjacent teeth , were observed between the two groups . CONCLUSION The small discrepancies that were observed between treatment performed by the four general practitioners at their own offices and treatment performed at the specialist clinic were not regarded to be of any clinical importance . This indicates that complete single-tooth implant treatment may be performed for many patients by general practitioners who have received adequate training , allowing the possibility of referring complicated treatments to specialists and other treatments to general practitioners The use of dental implants is an established procedure for the treatment of partially edentulous patients . However , there is only little knowledge about the prosthetic outcome of implant-supported restorations . The purpose of this prospect i ve long-term study was to evaluate success rates of implant-supported restorations in partially edentulous patients three years after loading . The study group consisted of 76 patients ( 47 females , 29 males ) with 214 3i-implants ( machined surface ) . 64 implants were used to support single crowns , 81 implants for 81 splinted crowns ( 36 units ) , 17 implants for seven bridges and 61 implants for 23 cantilevered bridges . For prosthesis construction , UCLA-Abutments were used . Screw connection was achieved by gold-alloy-coated square head screws and titanium hexagon head screws . Clinical follow-up visits were performed at the time of prosthesis insertion , three months , six months , one year , two years and three years after insertion of the prosthesis . The evaluation of the superstructures was performed according to the success criteria defined by Walton ( 1998 ) . The success rate for the prosthetic reconstructions was estimated at 84.9 % 36 months after loading . The success rate was 88.6 % for fixed partial dentures , 86.4 % for single crowns and 76 % for cantilevered bridges . Technical problems included screw loosening , screw fractures , framework fractures , veneering material failures and failures because of implant loss and following remake or modification of the superstructures . Since mainly technical complications such as screw loosening and screw fractures were causing problems , the connection between implant and superstructure should be improved OBJECTIVES The purpose of this prospect i ve long-term study was to evaluate the incidence of the most common technical problems , namely screw loosening , screw fracture , fracturing of veneering porcelain and framework fracture in implant-supported fixed partial dentures ( FPDs ) , and assess the survival and success rate ( event-free survival ) after 5 years of function . MATERIAL S AND METHODS In 76 partially edentulous patients , a total of 205 3i-implants ( machined surface ) were placed and restored with 112 implant-supported FPDs ( 46 single crowns , 81 splinted crowns , seven FPD bridges and 23 FPDs with cantilevers ) . The survival rate of FPDs supported by implants was 94.5 % ( CI-95 : 90.1 - 98.8 ) after an average observation period of 5 years . The success rate ( event-free survival ) of the FPDs was 80 % ( CI-95 : 87.3 - 72.7 ) . After an observation period of 5 years the cumulative incidence of screw loosening was 6.7 % ( CI-95 : 1.8 - 11.5 ) , the cumulative incidence for screw fracture was 3.9 % ( CI-95 : 0.1 - 7.7 ) . Fracture of the veneering porcelain occurred in 5.7 % ( CI-95 : 1.2 - 10.2 ) of all FPDs . Fracturing of the suprastructure framework was rare ( 1 % ; CI-95 : 0 - 2.9 ) . The overall complication incidence after 5 years was highest in the group of FPDs with cantilever , which showed the lowest success rate 68.6 % ( CI-95 : 50 - 87.3 ) , followed by single crowns ( 77.6 % ; CI-95 : 53.3 - 100 ) and splinted crowns ( 86.1 % ; CI-95 : 59.5 - 100 ) . No complication occurred in FPD bridges . CONCLUSION Fixed partial dentures supported by 3i-implants showed low technical complications rates , the most common being loosening of the abutment screw . Managing these complications can cause extra amount of chair-side time and patient dissatisfaction BACKGROUND The CrescoTi Precision ( CTiP ) method ( CrescoTi Systems , Lausanne , Switzerl and ) has been introduced as an alternative method for the fabrication of precisely fitting titanium frameworks . The method is supposed to be used with all major implant systems , without the need for abutments . PURPOSE The objectives of this clinical and radiographic retrospective follow-up study were to report the clinical performances of " CTiP-fabricated " frameworks that are screw retained directly to Brånemark implants as opposed to Brånemark implant/abutment assemblies ( Nobel Biocare AB , Gothenburg , Sweden ) and to compare the clinical outcomes of these two modalities . MATERIAL S AND METHODS Thirty-six patients were provided with 46 fixed prostheses supported by 207 Brånemark regular-platform implants . Twenty-seven prostheses were placed on implant/abutment assemblies , and 19 were placed directly at " implant level . " The prostheses had been in function for 5 to 8 years at the time of the final examinations . RESULTS Three patients did not attend the final examination . All 43 prostheses in the 33 examined patients were still in function . No major mechanical framework complications were observed during the observation period . One implant was lost after loading . There was no difference in bone loss around the abutment-free implants when compared with the implants provided with abutments . CONCLUSIONS This long-term clinical test demonstrated that the CTiP technology constitutes a reliable prosthetic treatment concept in combination with Brånemark implants . The results also revealed that the frameworks could be connected directly to the implants without any negative consequences BACKGROUND Many longitudinal studies of different implant systems have been published but few controlled r and omized investigations have been reported . A 1-year report of a comparative study of ITI Dental Implant System implants ( Straumann AG , Waldenburg , Switzerl and ) and Brånemark System implants ( Nobel Biocare AB , Gothenburg , Sweden ) has been published by the present authors . This paper is a 3-year follow-up of that r and omized study . PURPOSE The aim of the study was to compare the outcome of fixed partial prostheses supported by ITI or Brånemark implants . The outcome was evaluated primarily in terms of survival rates and changes in marginal bone level . MATERIAL AND METHODS The study group comprised 28 patients with anterior residual dentition in the maxilla . The patients were provided with two to four implants on each side of the dentition and were r and omly allocated to Brånemark implants or ITI implants ; 77 ITI implants and 73 Brånemark implants were inserted . After 6 months abutment connections were made to both ITI and Brånemark implants . All patients were provided with fixed partial prostheses of gold-ceramic . The patients were followed up annually with clinical and radiographic examinations for 3 years RESULTS Two Brånemark implants and two ITI implants were lost . The Brånemark implants were lost before loading whereas the ITI implants were lost because of periimplantitis . The survival rate for both groups was 97.3 % . The mean marginal bone level of the Brånemark implants was situated 1.8 mm from the reference point at both the baseline and the 3-year examinations . The corresponding values for the ITI implants were 1.4 mm at baseline and 1.3 mm after 3 years . There was no significant difference between the implant systems with regard to bone level or bone level change . A steady state of the marginal bone level was calculated to have been reached after 3 years for 95.5 % of the Brånemark implants and 87.1 % of the ITI implants . Periimplantitis ( infection including pus and bone loss ) was observed with seven ITI implants but with none of the Brånemark implants . This difference was statistically significant . CONCLUSIONS No statistically significant differences were found between the implants studied , except for the frequency of periimplantitis , which was higher for the ITI implants . The survival rates were high , and the marginal bone loss was small for both systems A total of 114 ITI solid-screw implants was consecutively placed in 55 partially edentulous patients and restored with 68 fixed prostheses . The patients were followed for at least 5 years in a prospect i ve study that focused on implant success and longitudinal reactions of the peri-implant hard and soft tissues . During the study period , 5 implants failed and 15 implants were lost to follow-up , result ing in a cumulative survival rate of 95.3 % after 5 years of loading . The success analysis included additional strictly defined events ( " first occurrence of marginal bone loss > or = 4 mm , " " first occurrence of pocket depth > or = 4 mm , " and " first occurrence of crevicular fluid volume > or = 2.5 mm " ) and result ed in a cumulative 5-year success rate of 89.0 % . Median loss of marginal bone , as observed on radiographs , was 0.7 mm between implant placement and prosthetic treatment and 0.5 mm between prosthesis placement and the 5-year evaluation . Compared to the previous year 's value , the annual increase in marginal bone loss did not reach a level of statistical significance between 1 and 5 years of function , so that a steady state prevailed . The incidence of lingual-palatal surfaces affected with remarkable plaque deposits increased from 13 % after prosthesis placement to 23 % after 5 years . Sulcus Bleeding index , probing depth , attachment level , and crevicular fluid volume were used to describe the health of the peri-implant soft tissues . The research parameters remained almost unchanged and indicated a soft tissue response within physiologic levels . Most mechanical complications were experienced during the first year of loading and were related to loosening of occlusal screws , which occurred in 8 ( 12 % ) of 68 restorations PURPOSE The purpose of this prospect i ve multicenter study was to evaluate and compare the clinical performance of laser-welded titanium fixed partial implant-supported prostheses with conventional cast frameworks . MATERIAL S AND METHODS Forty-two partially edentulous patients were provided with Brånemark system implants and arranged into 2 groups . Group A was provided with a conventional cast framework with porcelain veneers in one side of the jaw and a laser-welded titanium framework with low-fusing porcelain on the other side . The patients in group B had an old implant prosthesis replaced by a titanium framework prosthesis . The patients were followed for 3 years after prosthesis placement . Clinical and radiographic data were collected and analyzed . RESULTS Only one implant was lost , and all prostheses were still in function after 3 years . The 2 framework design s showed similar clinical performance with few clinical complications . Only one abutment screw ( 1 % ) and 9 porcelain tooth units ( 5 % ) fractured . Four prostheses experienced loose gold screws ( 6 % ) . In group A , marginal bone loss was similar for both design s of prostheses , with a mean of 1.0 mm and 0.3 mm in the maxilla and m and ible , respectively . No bone loss was observed on average in group B. No significant relationship ( P > 0.05 ) was observed between marginal bone loss and placement of prosthesis margin or prosthesis design . CONCLUSION The use of laser-welded titanium frameworks seems to present similar clinical performance to conventional cast frameworks in partial implant situations after 3 years PURPOSE This study evaluated the 5-year clinical and radiographic performance of fixed implant-supported maxillary prostheses with either welded titanium or conventional cast-gold alloy frameworks . MATERIAL S AND METHODS Fifty-eight consecutive patients were provided with 349 osseointegrated Brånemark system implants in the edentulous maxilla at six different implant centers . Twenty-eight of the patients received , at r and om , prostheses with laser-welded titanium frameworks , and the remaining 30 patients had prostheses with conventional cast-gold alloy frameworks . Clinical and radiographic data were collected for 5 years after prosthesis placement . RESULTS The titanium and cast-gold framework groups exhibited similar cumulative survival and success rates ( CSR ) . The 5-year implant CSR from time of placement was 91.4 % and 94.0 % , respectively , and from prosthesis delivery the rate was 94.9 % and 95.6 % , respectively . The corresponding 5-year prosthesis CSRs were 96.4 % and 93.3 % . One patient from each group lost all the implants and turned to complete dentures within the first year of function . Another patient with a cast-gold framework had the prosthesis replaced after 4 years , basically because of problems with the veneering material . No fractures of implant components were observed during the follow-up period . Bone loss was on average 0.59 mm ( SD 0.97 mm ) during 5 years , with no statistical difference between the two groups . CONCLUSION Welded titanium frameworks presented a similar favorable clinical performance as conventional cast-gold alloy frameworks in fixed implant-supported prostheses in the edentulous maxilla after 5 years in function . Implant failures were concentrated in only a few patients in each study group To avoid the necessity of a removable provisional prosthesis , and therefore preserve the patient 's functional outcome , esthetics , and quality of life , a clinical protocol was developed to approach periodontally compromised patients presenting a full-arch irreversibly lost dentition : full-arch extraction and immediate replacement with a provisional acrylic resin implant-supported fixed partial denture ( FPD ) . A total of 23 periodontally compromised patients ( 11 women , 12 men ; 4 smokers , 4 controlled diabetics ) were included in this study . Pretreatment casts were taken and vertical dimension of occlusion was determined . In most patients , 6 Straumann implants were distributed along the arch according to the surgical guide or bone availability , with the most distal ones in the maxilla slightly tilted so they could emerge more distally . A total of 168 implants ( 146 Straumann , 10 Nobel Biocare , 8 Biomet 3i , and 4 Lifecore ) were placed ( 83 in the maxilla , 85 in the m and ible ) . Of those in the maxilla , 74 were loaded immediately ( implant stability quotient mentor [ ISQm ] > 70 ) and 9 placed with delayed loading ( ISQm =/ < 70 ) . Of the 85 implants placed in the m and ible , all were loaded immediately ( ISQm > 70 ) . If an FPD had not been fabricated already , impressions were taken during surgery to do so . The prosthesis was then adapted ( cemented or screwed ) to the 6 implants within the first 48 hours postsurgery . After 2 months , definitive impressions were taken , and a definitive porcelain-fused-to-metal implant-supported 12-element FPD was fabricated and cemented or screwed to all 6 implants . Of the 168 implants , 108 were immediate implants and 159 immediately loaded . Only 2 implants ( 1 in the m and ible , 1 in the maxilla ) did not osseointegrate . This yields a 3-year cumulative survival rate of 98.74 % ( 98.65 % in the maxilla , 98.82 % in the m and ible ) . From a total of 26 immediately loaded prostheses ( 12 in the maxilla , 14 in the m and ible ) , 6 were cemented and 20 screw-retained . The 3-year cumulative survival rate was 100 % . Immediate loading in m and ibular and maxillary periodontally compromised patients presents itself as a predictable technique with a 100 % cumulative survival rate for provisional and definitive prosthetic rehabilitations BACKGROUND Comparative long-term knowledge of different framework material s in the partially edentulous implant patient is not available . PURPOSE To report and compare 10-year data on free-st and ing implant-supported partial prostheses with laser-welded titanium ( test ) and conventional gold alloy ( control ) frameworks . MATERIAL S AND METHODS Altogether , 52 partially edentulous patients were consecutively provided with laser-welded prostheses ( n = 60 ) in the partially edentulous lower jaw ( test group ) . A control group of 52 r and omly selected patients with gold alloy castings ( n = 60 ) was used for comparison . Clinical and radiographic 10-year data were retrospectively collected and evaluated for both groups . RESULTS The overall 10-year implant cumulative survival rate ( CSR ) was 93.0 % ( loaded implants , 96.4 % ) , with a 10-year implant CSR of 91.5 and 94.7 % for test and control implants , respectively ( p > .05 ) . Out of a total of 22 lost implants , 17 implants ( 77.3 % ) were shorter than 10 mm . The overall 10-year prosthesis CSR was 93.7 % , with a corresponding 10-year CSR of 88.4 and 100 % for test and control groups , respectively ( p < .05 ) . Average 10-year bone loss was 0.46 mm ( SD 0.47 ) and 0.69 mm ( SD 0.53 ) for the test and control groups ( p < .001 ) , respectively . Only 1 % of the implants had > 3 mm accumulated bone loss after 10 years . Altogether , 10 of the prostheses in both groups had implant component mechanical problems ( 8.3 % ) . None of the frameworks or implants fractured , but more fractures of porcelain veneers were observed in the test group ( p < .05 ) . CONCLUSION The protocol of implant treatment in the partially edentulous jaw functioned well during 10 years , although prosthodontic maintenance was required . However , laser-welded titanium frameworks presented more problems as compared with gold alloy frameworks . More loaded implants were lost ( p < .05 ) , and higher incidence of porcelain chipping was noted in the test group ( p < .05 ) . However , bone loss was on an average lower for the test group during the 10 years of follow-up ( p < .001 ) PURPOSE A single-blind r and omized controlled split-mouth trial was performed to compare the 36-month outcomes of machined and titanium oxide-anodized ( ADZ ) dental implant surfaces immediately loaded with fixed partial dentures in the posterior m and ible . MATERIAL S AND METHODS Ten patients with bilateral partial edentulism in the posterior m and ible received 42 implants ; 20 were placed on the test side ( ADZ ) and 22 were placed on the control ( machined ) side . The implants were loaded within 24 hours after placement . Changes in the radiographic bone level ( RBL ) were measured on st and ardized periapical films at baseline , 12 months , and 36 months . The mean changes in RBL were compared using a paired t test , and the mean changes in RBL with regard to implant position and implant surface type were compared via two-way analysis of variance . RESULTS After 36 months of functional loading , the overall cumulative success rate for all implants was 95 % . The mean change in RBL at 36 months was 0.35 mm and 0.32 mm for ADZ and machined implants , respectively ( not statistically significantly different between groups ; P = .88 ) . A reduction in RBL was observed for both machined and ADZ implants between 12 and 36 months , but only the machined implants demonstrated a statistically significant decrease in RBL during the observation period . CONCLUSIONS No statistically significant differences in RBL change were found between machined and ADZ implant surfaces after 36 months in function , and both surfaces demonstrated minimal marginal bone remodeling . As such , immediate loading of ADZ and machined dental implants supporting fixed partial dentures may be a suitable long-term treatment option in the posterior m and ible Since single-tooth implant restorations were introduced 12 years ago ( Jemt 1986 ) , there has been continuous development both in the technical design and the aesthetic outcome of the treatment . In order to ensure high quality in single-tooth implant treatments a clinical follow-up study was carried out on patients treated with modifications to the original regimen . In this study 69 consecutive patients were provided with 80 single-tooth implant restorations . The patients were followed for 3 years . There was continuous development of the prosthetic design during the time of the study , allowing us to analyse possible prognostic differences for the different prosthetic treatments . This study confirms earlier reports which describe the single-tooth implant treatment as a safe method with few surgical complications and minimal marginal bone loss . Only 1 implant was lost during the follow-up period and the average marginal bone loss was 0.48 mm over the 3-year follow-up period . Crowns veneered with acrylic and with gold casted directly to the abutments , screwed onto the implants , led to recurring prosthetic complications and gave an appearance of rapid ageing . The first generation of crowns made following the Cera-One design , sometimes produced a gap between the crown and the abutment associated with significant marginal bone loss during the first year . Few surgical or prosthetic complications were noted with cemented all-ceramic constructions , although the number of these crowns in this study was limited OBJECTIVE Multiple experimental and animal studies have shown that topographic , mechanical and chemical properties of implant surfaces lead to in vivo responses such as increased bone formation , increased bone anchorage and reduced healing time . A fluoride modification of the titanium implant surface also seems to positively influence bone anchorage as compared with unmodified titanium implants . Using implant survival and marginal bone loss as primary outcome parameters , the purpose of the present prospect i ve study was to investigate whether a fluoride modification of the titanium implant surface has positive clinical effects . MATERIAL S AND METHODS The 17 patients included in this study received 49 Astra Tech OsseoSpeed implants for various indications in the maxilla and m and ible . Implants were either loaded immediately or after a mean healing period of 9.56 weeks . Fifteen patients were followed up clinical ly including radiographic examination for 5 years . Forty-two implants were assessed for implant survival , marginal bone loss , surgical and /or prosthetic complications , presence or absence of plaque , signs of inflammation and size of the papilla . RESULTS Of the original 17 patients , 15 patients were available for the full 60-month follow-up . One early implant failure occurred , leading to an implant survival rate of 97 % . Radiographic analyses demonstrated stable bone conditions with a mean marginal bone loss of 0.1 mm ( SD 0.4 mm , min -0.7 mm , max 1.7 mm ) after 5 years of function . Immediately loaded implants did not show a different mean marginal bone loss as compared with implants that were not loaded immediately . Repeated soft-tissue examinations revealed healthy conditions in terms of 6.1 % plaque and 4.2 % of the implants with signs of inflammation at the 5-year control . DISCUSSION Implants used in this study had high survival and success rates after 5 years . Marginal bone was well maintained , irrespective of the loading regime PURPOSE This prospect i ve clinical study evaluated an experimental implant abutment made of densely sintered zirconia with respect to peri-implant hard and soft tissue reaction as well as fracture resistance over time . MATERIAL S AND METHODS Twenty-seven consecutively treated patients with 54 single-tooth implants were included . Zirconia abutment ingots were individually shaped and set on the implants with gold screws . All-ceramic ( Empress I ) crowns were cemented using a composite cement . At the 1- and 4-year examinations , reconstructions were evaluated for technical problems ( fracture of abutment or crown , loosening of abutment screw ) . Modified Plaque and simplified Gingival Indices were recorded at implants and neighboring teeth , and peri-implant bone levels were radiographically determined . RESULTS All but 1 of the 27 patients with 53 restorations could be evaluated at 1 year , and 36 restorations in 18 patients were evaluated 4 years after abutment and crown insertion . The median observation period for the reconstructions was 49.2 months . No abutment fractures occurred . Abutment screw loosening was reported for 2 restorations at 8 months and 27 months , respectively . Mean Plaque Index was 0.4 ( SD 0.6 ) at abutments and 0.5 ( SD 0.6 ) at teeth ; mean Gingival Index was 0.7 ( SD 0.5 ) at abutments and 0.9 ( SD 0.5 ) at teeth . Mean marginal bone loss measured 1.2 mm ( SD 0.5 ) after 4 years of functional loading . CONCLUSION Zirconia abutments offered sufficient stability to support implant-supported single-tooth reconstructions in anterior and premolar regions . The soft and hard tissue reaction toward zirconia was favorable BACKGROUND Implant-supported single-tooth replacements are an increasingly used method to replace teeth , especially in young patients . Therefore , long-term validation of different treatment modalities with different implant systems is of great importance . PURPOSE The aim of the present study was to make a biologic , technical , and aesthetic evaluation of single-tooth replacement supported by the Astra Tech implant ( Astra Tech AB , Mölndal , Sweden ) during a 5-year period . MATERIAL S AND METHODS Twenty patients were divided into two consecutively treated groups . In group A the implants were placed " early " in the extraction sockets , and st and ard single-tooth abutments were used . In group B the implants were placed " delayed , " and preparable abutments were used . Clinical examinations including registration of plaque , bleeding , crown lengths , soft tissue marginal level , papilla height , complications , and radiography were performed yearly . At the 3-year control examination the patient and a dentist evaluated aesthetic appearance with a visual analog scale . RESULTS An implant survival rate of 100 % and a crown survival rate of 95 % over a period of 5 years were found . The mean loss of marginal bone adjacent to implants and neighboring teeth was less than 0.5 mm during the 5-year period , and there was no significant difference after crown placement between the treatment modality for group A and that for B. There were fewer clinical complications and repairs in group B than in group A. Soft tissue dimensions were more natural around implant crowns in group B as compared to group A , but this was not reflected in the patients ' satisfaction with aesthetic appearance . On the other h and the dentist judged the restorations in group B higher concerning aesthetics than in group A. CONCLUSION Implant-supported single-tooth replacement with the Astra Tech system is a reliable treatment result ing in a good 5-year prognosis and only few complications PURPOSE This study evaluated the clinical performance of cemented customized zirconia abutments . Additionally , the marginal fit between the selected implant components was measured and the clinical gingival response was monitored . MATERIAL S AND METHODS Twenty-five patients were consecutively selected for a prospect i ve study of 30 implant-supported single-tooth restorations . Customized titanium post and zirconia abutment complexes were prepared , and scanning electron microscopy ( SEM ) analysis was used to study bicomponent marginal gaps . The abutments were screwed onto the implants and restored with all-ceramic crowns . Plaque and gingival indices were recorded at 6 monthly intervals over a 36- to 44-month period . RESULTS SEM analysis showed mean marginal gaps of 10.161 microm ( SD : 0.7 ) horizontally and 4.783 microm ( SD : 0.67 ) vertically . Abutment fractures and screw loosening were neither reported nor observed throughout the clinical observation period . Mean Plaque Index scores were 0.57 ( SD : 0.32 ) on abutments and 0.74 ( SD : 0.34 ) on teeth , while mean Gingival Index scores were 0.54 ( SD : 0.2 ) on abutments and 0.72 ( SD : 0.3 ) on teeth . CONCLUSIONS These preliminary results suggest that metallic-zirconia abutments may be comparable to currently available esthetic implant abutments PURPOSE Long-term comparisons of frameworks at the implant or abutment level are not available , and knowledge of the clinical function of cobalt-chromium ( Co-Cr ) alloy frameworks is limited . Primarily , the aim of this study was to compare the 5-year clinical performance of frameworks with or without abutment connections to implants . Secondly , the outcomes of prostheses made from Co-Cr alloy with porcelain veneers to those made of commercially pure titanium ( CP Ti ) with acrylic veneers were compared . MATERIAL S AND METHODS The test groups comprised patients treated with screw-retained fixed prostheses made at the implant level according to the Cresco method in either dental porcelain-veneered Co-Cr alloy ( n = 15 ) or acrylic-veneered CP Ti ( n = 25 ) . A control group of 40 r and omly selected patients were provided with prostheses made at the st and ard abutment level in CP Ti with acrylic veneers . For all patients , clinical and radiologic 5-year data were retrospectively collected and evaluated . RESULTS Five-year implant cumulative survival rates ( CSRs ) were 98.6 % and 97.6 % for test and control groups , respectively ( P > .05 ) . No major differences in bone level were demonstrated between the groups after 5 years ( P > .05 ) . Significantly more complications occurred in the test groups compared to the control group ( P < .01 ) , with the most common complications being mucositis and fracture of veneers . CONCLUSIONS After 5 years , the clinical outcomes of implant-level prostheses made of porcelain-veneered Co-Cr or acrylic-veneered CP Ti seem comparable to acrylic-veneered titanium prostheses made at the st and ard abutment level regarding implant CSR and bone levels . However , more complications were registered in implant-level prostheses compared to the st and ard abutment-level prostheses PURPOSE The aim of this study was to compare definitive acrylic resin prostheses with or without a cast metal framework that were immediately loaded and supported by axial and tilted implants in completely edentulous patients after 3 years of function . MATERIAL S AND METHODS Patients who were completely or partially edentulous in one or both arches with severe atrophy of the posterior regions were selected for this study . All patients immediately received prosthetic rehabilitations , each supported by four implants ( two axial and two tilted ) . The patients were r and omized to receive a definitive prosthesis with a cast metal framework or one made of acrylic resin only . Follow-up visits were performed up to 36 months after implant insertion and included radiographic assessment s of bone levels around the implants . RESULTS Thirty-six patients participated , and 44 complete-arch immediately loaded prostheses ( 24 maxillary and 20 m and ibular ) , each supported by four implants ( in total 176 implants ) , were placed . In all , 21 screw-retained full-arch acrylic resin prostheses and 23 cast-metal-framework prostheses were delivered to the patients . The 3-year overall implant survival rate was 100 % for axially positioned implants and 96.59 % for tilted implants . Implant survival rates were 98.96 % in the maxilla and 97.5 % in the m and ible . None of the 44 fixed prostheses were lost during the observation period , representing a prosthetic survival rate of 100 % . No statistically significant differences were seen in crestal bone loss between tilted and axial implants at 12 , 24 , and 36 months in either arch . CONCLUSIONS The same clinical outcome was seen for patients treated with the so-called All on Four protocol , regardless of whether the acrylic resin restorations were reinforced with metal BACKGROUND No long-term clinical studies covering more than 5 years are available on Computer Numeric Controlled ( CNC ) milled titanium frameworks . AIM To evaluate and compare the clinical and radiographic performance of implant-supported prostheses provided with CNC titanium frameworks in the edentulous jaw with prostheses with cast gold-alloy frameworks during the first 10 years of function . MATERIAL AND METHODS Altogether , 126 edentulous patients were by r and om provided with 67 prostheses with titanium frameworks ( test ) in 23 maxillas and 44 m and ibles , and with 62 prostheses with gold-alloy castings ( control ) in 31 maxillas and 31 m and ibles . Clinical and radiographic 10-year data were collected for the groups and statistically compared on patient level . RESULTS The 10-year prosthesis and implant cumulative survival rate was 95.6 % compared with 98.3 % , and 95.0 % compared with 97.9 % for test and control groups , respectively ( p > .05 ) . No implants were lost after 5 years of follow-up . Smokers lost more implants than nonsmokers after 5 years of follow-up ( p < .01 ) . Mean marginal bone loss in the test group was 0.7 mm ( SD 0.61 ) and 0.7 mm ( SD 0.85 ) in the maxilla and m and ible , with similar pattern in the control group ( p > .05 ) , respectively . One prosthesis was lost in each group due to loss of implants , and one prosthesis failed due to framework fracture in the test group . Two metal fractures were registered in each group . More appointments of maintenance were needed for the prostheses in the maxilla compared with those in the m and ible ( p < .001 ) . CONCLUSION The frequency of complications was low with similar clinical and radiological performance for both groups during 10 years . CNC-milled titanium frameworks are a viable alternative to gold-alloy castings for restoring patients with implant-supported prostheses in the edentulous jaw BACKGROUND Long-term data comparing cemented and noncemented single-implant restorations has not been reported . AIM To compare clinical and radiographic performance of single-implant crown restorations made by either directly baked porcelain to custom-made TiAdapt titanium abutments ( Nobel Biocare AB , Göteborg , Sweden ) ( test ) or cement crowns onto CeraOne ( Nobel Biocare AB ) abutments ( control ) after 10 years in function . MATERIAL S AND METHODS Altogether , 35 consecutive patients were provided with 41 turned single Brånemark System implants ( Nobel Biocare AB ) in the partially edentulous upper jaw . By r and om , 15 and 20 patients were provided with 18 test and 23 control implant crowns , respectively . Thereafter , clinical and radiographic data were collected and compared between the two groups . RESULTS None of the implants were found loose during the follow-up period ( 100 % ) . Few clinical problems were observed , and the overall average marginal bone loss was 0.26 mm ( SD 0.64 ) during 10 years in function . After the final tightening of the crowns , no significant differences were observed between the test and control groups ( p > .05 ) . The head of the implants was placed on an average 6.3 mm ( SD 2.24 ) below the cement/enamel junction of the adjacent teeth ( range 2.5 - 10.0 mm ) . Implants with reported mechanical and /or mucosal problems or placed more apically in relation to the adjacent teeth did not present more bone loss as compared with implants with no problems or placed more coronally , respectively ( p > .05 ) . CONCLUSIONS There seems to be no obvious clinical or radiographic differences between the test and control single-implant restorations during 10 years of follow-up . Occasionally , some restorations presented loose abutment screws and /or fistulas during follow-up . This implies a certain need for maintenance where a one-piece single-implant protocol ( test ) allows both for a simple clinical procedure at placement without cementation problems , as well as for an easy and simple maintenance of installed single implant crowns in long-term function OBJECTIVES The purpose of this study was to evaluate the survival rate , success rate and primary complications associated with m and ibular fixed implant-supported rehabilitations with distal cantilevers over 5 years of function . MATERIAL AND METHODS In this prospect i ve multi-center trial , 45 fully edentulous patients were treated with implant-supported m and ibular hybrid prostheses with distal extension cantilevers . Data were collected at numerous time points , including but not limited to : implant placement , abutment placement , final prosthesis delivery , 3 months and 5 years post-loading . Biological , implant and prosthetic parameters defining survival and success were evaluated for each implant including : sulcus bleeding ndex ( SBI ) at four sites per implant , width of facial and lingual keratinized gingiva ( mm ) , peri-implant mucosal level ( mid-facial from the top of the implant collar , measured in mm ) , modified plaque index ( MPI ) at four sites per implant , mobility and peri-implant radiolucency . Survival was defined as implants or prostheses that did not need to be replaced . Success rate was defined as meeting well-established criteria that were chosen to indicate healthy peri-implant mucosa osseointegration , prostheses success and complications . RESULTS A total of 237 implants in 45 completely edentulous patients were included in the study . In each patient , four to six implants were placed to support hybrid prostheses with distal cantilevers . Cantilevers ranged in length from 6 to 21 mm , with an average length of 15.6 mm . The ages of the patients ranged from 34 to 78 with a mean age of 59.5 years . The survival rate of implants was 100 % ( 237/237 ) and for prostheses 95.5 % ( 43/45 ) . The overall treatment success rate was calculated as 86.7 % ( 39/45 ) . Of the six patients that have not met the criteria for success , two patients required replacement of the entire prosthesis and four patients presented > four complications events . CONCLUSION Fixed implant-supported rehabilitation with distal cantilever result ed in a reliable treatment modality over the 5-year observation period . Although biological parameters of MPI , SBI , keratinized tissue and peri-implant mucosal levels showed statistically significant differences over time , the mean values for each patient remained within the normal limits of oral health . Complications were categorized as biological or technical . The majority of complications were technical complications ( 54/79 ) and of these most involved fracture of the acrylic teeth and base ( 20/54 ) . While the survival rate was 100 % for implants and 95.5 % for prostheses , the application of strict criteria for treatment success result ed in an overall treatment success rate of 86.7 % PURPOSE The purpose of this controlled prospect i ve clinical study was to compare cemented and screw-retained implant-supported single-tooth crowns followed for 4 years following prosthetic rehabilitation with respect to peri-implant marginal bone levels , peri-implant soft tissue parameters , and prosthetic complications . MATERIAL S AND METHODS Twelve consecutive patients were selected from a patient population attending the Implantology Department at the University of Padova . They all presented with single-tooth bilateral edentulous sites in the canine/premolar/molar region with adequate bone width , similar bone height at the implant sites , and an occlusal scheme that allowed for the establishment of identical occlusal cusp/fossa contacts . Each patient received 2 identical implants ( 1 in each edentulous site ) . One was r and omly selected to be restored with a cemented implant-supported single-tooth crown , and the other was restored with a screw-retained implant-supported single-tooth crown . Data on peri-implant marginal bone levels and on soft tissue parameters were collected 4 years after implant placement and analyzed to determine whether there was a significant difference with respect to the method of retention ( cemented versus screw-retained ) . RESULTS All patients completed the study . All 24 implants survived , result ing in a cumulative implant success rate of 100 % . Statistical analysis revealed no significant differences between the 2 groups with respect to peri-implant marginal bone levels and soft tissue parameters . DISCUSSION The data obtained with this study suggested that the choice of cementation versus screw retention for single-tooth implant restorations is likely not based on clinical results but seems to be based primarily on the clinician 's preference . CONCLUSIONS Within the limitations of this study , the results indicate that there was no evidence of different behavior of the peri-implant marginal bone and of the peri-implant soft tissue when cemented or screw-retained single-tooth implant restorations were provided for this patient population The aim of the present study of single-tooth implants was to compare the success rate and marginal bone resorption of a narrow-diameter self-tapping implant placed in less available bone volume with the st and ard-diameter self-tapping implant placed in a well-dimensioned alveolar process . A new abutment technique and a different permanent abutment design were also evaluated . Fifty-five patients were included in the study ; 27 patients received 28 st and ard-diameter ( 3.75-mm ) implants , and 28 patients received 32 narrow-diameter ( 3.25-mm ) implants replacing either a central or a lateral incisor in the maxilla . In an attempt to create an ideal emergence profile and to regenerate papillae , individual acrylic resin tooth-shaped temporary abutments were fabricated , based on impressions made immediately following implant placement , and connected to the implant after 6 months . A minimum of 2 months were then allowed before definitive restorative procedures were performed . Impressions were always made at the implant level . Follow-up examinations were performed at 6 months after loading and 1 , 2 , and 3 years after loading . Two narrow-diameter implants were lost after 6 months , but no other failures were subsequently observed in any of the groups after that . In both groups , marginal bone loss followed the same pattern and was recorded radiographically to be a mean of 0.4 mm from the first to the last examination PURPOSE The present material reports on prosthodontic complications in a trial of 51 patients with prostheses supported by single-stage implants over a period of 36 months . MATERIAL S AND METHODS One hundred eighty-six single-stage implants were placed in 51 patients over a 3-year period in 2 carefully controlled prospect i ve clinical trials . Nineteen of the patients ( 103 implants ) were completely edentulous and restored with a maxillary complete denture and a m and ibular fixed-detachable complete prosthesis . Single metal-ceramic crowns or fixed partial dentures were fabricated for the remaining 32 patients ( 83 implants ) . The fixed restorations were either screw-retained or cemented . RESULTS All patients /implants were followed for a minimum of 3 years . Complications in the edentulous patients included fracture of denture teeth , fracture of the maxillary denture , and occlusal screw loosening . Occlusal screw loosening and loss of the resin composite access plug were the only complications observed in the patients treated with screw-retained restorations . No complications were found in the patients restored with cemented restorations on solid abutments . DISCUSSION Problems with prostheses were very common in the completely edentulous patients ( 13 of 19 patients encountered complications ) , possibly a result of increased bite force or inadequate laboratory technique . Tooth fractures were seen more frequently in men than in women . Complications occurred in only 5 of the 32 partially edentulous patients . CONCLUSION Complications were associated with laboratory-related procedures rather than the implant system itself PURPOSE The aim of this prospect i ve study was to present the results after 5 years of loading of 65 CeraOne ( Nobel Biocare ) crowns . MATERIAL S AND METHODS Sixty-two implants in the maxilla and 3 implants in the m and ible were placed in 57 patients . Sixty-two all-ceramic and three metal-ceramic crowns were cemented . The group comprised the first patients treated with the CeraOne prosthodontic concept . RESULTS Eight patients did not complete the study . Only one implant failed , giving a cumulative success rate for implants of 98.5 % . The failed implant was replaced : a crown was cemented and then followed for 5 years without any complications . Four crowns were recorded as failures , giving a cumulative success rate for crowns of 93.7 % . It should be observed that this result was very positive , as all crown failures were related to extraordinary causes and not one was a result of common bite forces or fatigue . The initial bone loss was in accordance with other studies on Brånemark implants , and a stable situation was recorded after 2 years for the supporting bone around implants and adjacent teeth when the conical implants were excluded . Soft tissues around implants and adjacent teeth appeared healthy , and the cementation and the placement of the abutment shoulder in the peri-implant sulcus did not cause any recession of the peri-implant mucosa . CONCLUSION CeraOne experienced virtually no complications and proved to be a highly predictable and safe prosthodontic concept . CeraOne also eliminated problems with abutment screw loosening and created a platform for good esthetic results and satisfied patients BACKGROUND Comparatively few studies with at least 5 years of follow-up are available that describe the use of implants in prosthetic rehabilitation of partially edentulous patients . R and omized , controlled clinical studies that evaluated the effect of different surface design s of screw-shaped implants on the outcome of treatment are also sparse . OBJECTIVE To determine , in a prospect i ve r and omized , controlled clinical trial , the outcome of restorative therapy in periodontitis-susceptible patients who , following basic periodontal therapy , had been restored with implants with either a machined- or a rough-surface topography . MATERIAL AND METHODS Fifty-one subjects ( mean age , 59.5 years ) , 20 males and 31 females who , following treatment of moderate-to-advanced chronic periodontitis , required implant therapy for prosthetic rehabilitation were recruited . Seventeen of the patients were current smokers . Following the active treatment , all subjects were included in an individually design ed maintenance program . A total of 56 fixed partial dentures ( FPDs ) and a total of 149 screw-shaped , and self-tapping implants ( Astra Tech implants ) -- 83 in the maxilla and 66 in the m and ible -- were installed in a two-stage procedure . Each patient received a minimum of two implants and by r and omization every second implant that was installed had been design ed with a machined surface and the remaining with a roughened Tioblast surface . Abutment connection was performed 3 - 6 months after implant installation . Clinical and radiographical examinations were performed following FPD connection and once a year during a 5-year follow-up period . The analysis of peri-implant bone-level alterations was performed on subject , FPD and implant levels . RESULTS Four patients and four FPDs were lost to the 5 years of monitoring . One implant ( machined surface ) did not properly integrate ( early failure ) , and was removed at the time of abutment connection . Three implants were lost during function and a further eight implants could not be accounted for at the 5-year follow-up examination . The overall failure rate at 5 years was 5.9 % ( subject level ) , 5.3 % ( FPD level ) and 2.7 % ( implant level ) . Radiographic signs of loss of osseointegration were not found at any of the implants during the 5-year observation period . During the first year in function there was on average 0.33 ( SD , 0.61 ) mm loss of peri-implant marginal bone on the subject and FPD levels and 0.31 ( 0.81 ) mm on the implant level . During the subsequent 4 years , the peri-implant bone-level alterations were small . The calculated annual change in peri-implant bone level was -0.02 ( 0.15 ) on subject and FPD levels and -0.03 ( 0.20 ) on the implant level . Thus , the mean total bone-level change over the 5-year interval amounted to 0.41 mm on all three levels of analysis . In the interval between baseline and 5 years , the machined and the Tioblast implants lost on average 0.33 and 0.48 mm , respectively ( p>0.05 ) . CONCLUSION The present r and omized , controlled clinical trial that included partially edentulous periodontitis-susceptible subjects demonstrated that bone loss ( i ) during the first year of function as well as annually thereafter was small and ( ii ) did not vary between implants with machined- or rough-surface design In a r and omized prospect i ve study , two implant systems were compared in forty consecutive patients treated for m and ibular edentulism . The patients were r and omly allotted for treatment by the Brånemark two-stage ( submerged ) system ( BRS ) , or the ITI(R ) one-stage ( non-submerged ) system . In all , 102 Brånemark selftapping implants and 106 ITI hollow screw implants were installed and all patients were treated with full bridges . Biological and prosthodontic parameters , complications , success rates , clinical efficacy , patient satisfaction and re source requirements were evaluated . No differences were found in plaque accumulation , bleeding or complications during the follow-up period . The BRS group showed deeper periimplant sulcus , less attached mucosa , larger bridge-mucosa distance and higher Periotest values . Prosthetic complications were not related to the configuration of the implant systems . After 3 years , the cumulative success rates were 97.9 % and 96.8 % for the Brånemark and ITI systems , respectively ( difference not statistically significant ) . One implant in the BRS group had failed to osseointegrate at the time of abutment connection , and another was lost after 2 years due to progressive breakdown of bone . In the ITI group , three implants showed progressive bone loss after 1 - 3 years associated with periimplant infection . All 40 bridges were intact and remained stable throughout the study . There was general patient satisfaction , but about half the Brånemark patients reported difficulty in coping with the surgical procedures . Treatment time was similar for the two systems . It is concluded that both systems meet the current requirements for dental implant systems in the treatment of m and ibular edentulism |
11,863 | 28,693,541 | Discussion Sex differences in HPA axis reactivity appear to be present in childhood , although evidence is not unequivocal . | Background In adults , hypothalamus – pituitary – adrenal ( HPA ) axis activity shows sexual dimorphism , and this is thought to be a mechanism underlying sex-specific disease incidence .
Evidence is scarce on whether these sex differences are also present in childhood .
In a meta- analysis , we recently found that basal ( non-stimulated ) cortisol in saliva and free cortisol in 24-h urine follow sex-specific patterns .
We explored whether these findings could be extended with sex differences in HPA axis reactivity . | Levels of the stress-sensitive hormone cortisol increase dramatically in the first 30 - 40min after waking , an effect known as the cortisol awakening response ( CAR ) . There is considerable cross-sectional evidence that psychosocial stress is associated with an increased CAR , and the CAR has been found to be altered in the presence of stress-related diseases , including major depressive disorder ( MDD ) . To date , no prospect i ve longitudinal studies have examined whether individual differences in the CAR serve as a premorbid risk factor for MDD . In a sample of 230 late adolescents , clinical diagnoses of MDD were predicted from the CAR as well as other indicators of basal cortisol functioning gathered 1 year earlier , including : waking cortisol levels , bedtime cortisol levels , the size of the CAR , average cortisol , and the slope of the diurnal cortisol rhythm across the waking day . Age and gender , health and health behaviors , baseline neuroticism , exposure to stressful life events and past episodes of mood and anxiety disorders were included as covariates , to help ensure effects are attributable to the CAR rather than related variables . A higher baseline CAR was associated with a significantly increased risk of developing MDD by follow-up , even when excluding individuals with baseline MDD . No other baseline cortisol measures were significant prospect i ve predictors of MDD . In summary , the CAR is a significant prospect i ve risk factor for the development of MDD in young adults , providing some support for the possibility that a heightened CAR may play a role in the etiology of major depressive disorder BACKGROUND Sex differences in stress responses may be one mechanism underlying gender differences in depression . We hypothesized that men and women would show different adrenocortical responses to different stressors . In particular , we predicted that women would show greater responses to social rejection stressors , whereas men would demonstrate greater responses to achievement stressors . METHODS Following a rest session in which they habituated to the laboratory , 50 healthy volunteers ( 24 men and 26 women , mean age 19.1 , SD = 1.13 ) were r and omly assigned to achievement or rejection stress conditions . The achievement condition involved a mathematical and a verbal challenge ; the rejection condition involved two social interaction challenges . Self-reported affect and salivary cortisol were measured throughout each stress session ( baseline , stress , and poststress periods ) . RESULTS There were no sex differences in mood ratings following the stressors ; however , cortisol responses showed the predicted gender by condition by time interaction . Men showed significantly greater cortisol responses to the achievement challenges , but women showed greater cortisol responses to the social rejection challenges . CONCLUSIONS Women appear more physiologically reactive to social rejection challenges , but men react more to achievement challenges . Women 's greater reactivity to rejection stress may contribute to the increased rates of affective disorders in women The current cross-sectional study investigated basal and stress-challenged hypothalamic-pituitary-adrenocortical ( HPA ) system function in 102 five-year old kindergarten children ( 59 boys , 43 girls ) who had been assessed by a comprehensive psychological and behavioral test battery . Baseline HPA system activity was significantly increased in girls when compared to boys ( p<0.001 ) . Furthermore , basal HPA system activity predicted a high hormonal release during stress with -- again -- girls showing higher hormonal responses than boys ( p<0.01 ) . Importantly , increased HPA system activity ( baseline and stress-challenged ) was significantly associated with hyperactivity/impulsivity and emotional problems in boys and with positive emotions in girls ( p<0.05 ) . These results suggest an occurrence of neurobiological alterations early in development . The observed neurobiological changes are gender specific already at the age of 5 years . Prospect i ve long-term follow up of the identified subjects with HPA axis alterations will clarify if these markers are predictive for the onset of psychiatric disorders Estrogens are reported to provide protection against the development of cardiovascular disease in women , but the mechanisms underlying these effects are not well defined . We hypothesized that estrogen might affect the hormonal responses to stress . We therefore studied cortisol , ACTH , epinephrine , norepinephrine , and norepinephrine spillover and hemodynamic responses to a 10-min mental arithmetic test in 12 perimenopausal women r and omized to 8 weeks of estrogen supplementation ( estradiol valerate , 2 mg daily ; n = 7 ) or placebo ( n = 5 ) . Total body and forearm norepinephrine spillover were measured by radiotracer methodology . After supplementation with estradiol , the increases in both systolic and diastolic blood pressure in response to mental stress were reduced , and cortisol , ACTH , plasma epinephrine and norepinephrine , and total body norepinephrine spillover responses to stress were significantly attenuated ( P < 0.05 in each case ) . Forearm norepinephrine spillover was unchanged by estrogen , and there was no change in any of the responses after placebo . We conclude that estrogen supplementation in perimenopausal women attenuates blood pressure , glucocorticoid , and catecholamine responses to psychological stress The current study sought to examine whether children 's spontaneous use of the emotion regulation strategies suppression and re appraisal during a psychosocial stress task was related to their cortisol and alpha-amylase responses to that task . Salivary cortisol and alpha-amylase responses to a psychosocial stress task were assessed in 158 10-year-old children ( 83 girls ) . The children completed a self-report question naire measuring use of re appraisal and suppression during the task . Results showed overall increases in cortisol and alpha-amylase in response to the stressor , with higher cortisol reactivity in girls than in boys . With regard to emotion regulation , more use of suppression was related to lower cortisol reactivity in girls , and lower alpha-amylase reactivity and quicker alpha-amylase recovery in all children . The use of re appraisal was not related to the children 's cortisol or alpha-amylase responses . The current study is the first to investigate the relation between the spontaneous use of re appraisal and suppression , and physiological stress responses to a psychosocial stressor in children . Our results indicate that re appraisal and suppression are used and can be measured even in 10-year-olds . At this age re appraisal appears ineffective at down-regulating physiological responses , while suppression was related to lower physiological responses . For cortisol reactivity there was a sex difference in the relation with suppression , indicating the importance of including sex as a moderator variable in research study ing stress reactivity and its correlates in this age group Data from five independent studies were reanalyzed in order to investigate the impact of age and gender on HPA axis responses to an acute psychosocial laboratory stress task . The total sample consisted of 102 healthy subjects with 30 older adults ( mean age : 67.3 y ) , 41 young adults ( mean age : 23.5 y ) , and 31 children ( mean age : 12.1 y ) . All participants were exposed to the Trier Social Stress Test ( TSST ) . The stress protocol caused highly significant ACTH and total plasma cortisol responses in older and younger male and female adults ( all p<0.0001 ) as well as salivary free cortisol responses in all six age and gender groups ( all p<0.0001 ) . Three-way ANOVAs for repeated measurement were applied to investigate the impact of age and gender on ACTH and cortisol responses . Results showed that the ACTH response to stress was higher in younger adults compared to older adults ( main effect : p=0.009 , interaction : p=0.06 ) . Post hoc analyses revealed that there was no age effect in the subgroup of women ( p = n.s . ) , while younger men had higher ACTH responses compared to older men ( p=0.01 ) . For total plasma cortisol , ANOVA results showed that the pattern of reactivity did not differ between age and gender groups ( all interactional effects p = n.s . ) , although older females had hightened overall cortisol levels compared to the other groups , as proofed in post hoc analyses ( all p<0.05 ) . For free salivary cortisol , a significant main effect of gender ( p=0.05 ) and an almost significant three-way-interaction ( p=0.09 ) emerged . Post hoc analyses showed an elevated overall free salivary cortisol response in elderly men compared to elderly women ( p=0.006 ) , while no gender differences emerged in neither young adults nor children ( both p = n.s . ) . In sum , the stressor induced significant HPA axis responses in all age and gender groups . The observed ACTH response patterns in young and elderly adults may suggest that a heightened hypothalamic drive in young men decreases with age , result ing in similar ACTH responses in elderly men and women . Alternative interpretations are also discussed . The data also supports the idea of a greater adrenal cortex sensitivity to ACTH signals in young females . Free salivary cortisol responses were elevated in elderly men compared to elderly women , an effect which can not be explained by gender differences in perceived stress responses to the TSST . It can be speculated if corticosteroid binding globulin ( CBG ) and /or sex steroids are important modulators of these effects Sex differences in rates of internalizing disorders have been attributed in part to heightened sensitivity to stress in females . While the sex difference in disorder rates becomes most pronounced in adolescence , developmental research suggests that stress reactivity in girls may be related to elevated internalizing symptoms even in childhood . We therefore examined whether child sex moderated associations between symptoms of psychopathology and cortisol reactivity to a st and ardized stress task in 409 three-year-old community-dwelling children . Anxious symptoms were associated with elevated cortisol reactivity , but only in girls . Externalizing symptoms were unrelated to baseline cortisol or cortisol reactivity , and no evidence for moderation by child sex was found . Results suggest that cortisol reactivity to stress in early childhood has a sex-specific association with girls ' internalizing symptoms This study investigates basal levels of cortisol and dehydroepi and rosterone ( DHEA ) , and their relation to gender and pubertal development , in healthy children and adolescents . Salivary cortisol and DHEA levels were examined in 129 normally developing subjects aged eight to 16 years . Subjects provided morning ( 08:00 h ) and evening ( 20:00 h ) saliva sample s over four consecutive days . Pubertal stage was assessed using Tanner stage sketches , and subjects were grouped according to their general status of pubertal development ( pre-early puberty : Tanner stageII ) . Results showed that morning salivary cortisol in mid-postpubertal girls was greater than in mid-postpubertal boys , but not pre-early pubertal girls and boys . Mean levels of salivary DHEA were greater in mid-postpubertal boys and girls than in pre-early pubertal boys and girls . Changes in hypothalamic-pituitary-adrenal ( HPA ) axis function that occur during puberty may have implication s for immediate and long-term adolescent health OBJECTIVE Our purpose was to determine the pattern of reactivity to stress in premenopausal and postmenopausal women and to assess the effects of estrogen . STUDY DESIGN A behavioral stress test was given to premenopausal ( n = 13 ) and postmenopausal women ( n = 36 ) . Biophysical and neuroendocrine responses were measured during and on completion of the stress test . The postmenopausal women were then r and omized to placebo or transdermal estradiol treatment for 6 weeks , at which time another behavioral stress test was given . RESULTS Stress reactivity to math and speech tasks elicited significantly greater systolic blood pressure responses in postmenopausal women compared with premenopausal women ( p < 0.05 ) . On retesting , significant biophysical responses that were present during the initial stress testing were still present ( p < 0.05 ) in the placebo group but were blunted with estrogen treatment . Plasma corticotropin , cortisol , and rostenedione , and norepinephrine increased during testing to a similar degree in premenopausal and postmenopausal women ; this response was maintained after placebo treatment . Postmenopausal women treated with estrogen had blunted responses . CONCLUSION Significant differences in responses to psychologic stress exist in premenopausal and postmenopausal women . The lack of adaptation may account in part for the increased risk of cardiovascular disease in postmenopausal women . Estrogen appears to blunt the stress-induced response OBJECTIVE Consistent sex differences in regulation of the hypothalamic pituitary adrenocortical ( HPA ) axis have been shown in animal models and emerge over puberty . However , parallel work in humans is lacking despite implication s for elucidating the emergence of sex differences in depression over puberty . We investigated sex differences in HPA response to corticotropin releasing hormone ( CRH ) challenge over puberty in a carefully screened normative sample . METHODS Participants were 68 healthy children ( 41 % girls ) , ages 6 - 16 , with no personal or family history of psychiatric disorder . Pubertal maturation was determined by Tanner staging . Following 24h of adaptation , 9 - 10 plasma cortisol sample s were collected over 30 - 40 min pre-infusion baseline , 1 μg/kg CRH infusion , and 90 - 180 min post-infusion recovery . Thirty-seven participants completed 2 + CRH challenges allowing inclusion of cross-sectional and longitudinal data in all analyses . The influence of gender and pubertal maturation on parameters of cortisol response to CRH challenge was investigated using nonlinear mixed model methodology . RESULTS Girls showed increasing total cortisol output following CRH challenge over puberty , while boys showed little change in total cortisol output over puberty . Increased cortisol output in girls was explained by slower reactivity and recovery rates leading to prolonged time to reach peak cortisol and delayed return to baseline over puberty . Girls also showed increasing baseline cortisol over puberty , while boys showed declining baseline over puberty . CONCLUSION Results reveal subtle normative sex differences in the influence of pubertal maturation on HPA regulation at the pituitary level . This normative shift may tip the balance towards stress response dysregulation in girls at high risk for depression , and may represent one potential mechanism underlying elevated rates of depression among pubescent girls & NA;Globally , the health disparity of hypertension is disproportionately greater within the African American population and develops at an earlier age . Elevated and continuous interaction of biologic measures during adolescence may be precursors and indicators of risk for blood pressure changes and the subsequent development of adult essential hypertension . The purpose of this study was to describe ( 1 ) the prevalence of biologic measures of risk of hypertension , specifically family history of hypertension , prehypertension , elevated salivary cortisol , and hyperresponsive cortisol and cardiovascular reactivity , and ( 2 ) the gender difference in the prevalence of biologic risk factors of hypertension . Subjects and Method : This was an exploratory descriptive design with a nonr and om purposive sample . Participants ( N = 106 ) were high school , African American adolescents , aged 14 to 18 years . Data , including family history of hypertension , resting blood pressure , and blood pressure and cortisol levels before and after induced physiologic stress by cold water h and immersion , were measured . Results : One hundred six African American participants ( 49 males and 57 females ) completed the study . Data described that 71 % had a positive family history of hypertension . Overall , the resting blood pressures were 120 mm Hg for systolic and 68 mm Hg for diastolic . Forty-one percent of the patients had prehypertensive blood pressures ; 86 % had elevated cortisol ; 49 % had hyperresponsive blood pressure reactivity ; and 35 % had cortisol hyperresponsivity . Excluding ethnicity , 65 % had 3 or more biologic measures of risk of hypertension . Statistically significant gender differences included male systolic pressure and number of males with prehypertension . Conclusion : This study provides evidence of the high prevalence of multiple physiologic biologic measures of risk of hypertension factors within a vulnerable population . The continuous interaction of biologic measures over time may increase the susceptibility and risk of essential hypertension development and supports the development of appropriate physiologically based behavioral interventions Sex differences in stress hormone functions are presumed to depend on sex hormones . And yet , surprisingly few psychoneuroendocrine studies actually assess within-sex variations of testosterone , estradiol , and progesterone when investigating sex-specific activities of the hypothalamic-pituitary-adrenal axis . In this method ological study of 204 healthy adults ( 60 men ) , we assessed whether cortisol profiles would differ between the sexes when unadjusted or adjusted for basal sex hormones among both sexes . Reactive cortisol was sample d using 6 saliva sample s measured every 10-min as part of the Trier Social Stress Test that generally activates cortisol among men more than women . Diurnal cortisol was sample d over two days at ( 1 ) awakening , ( 2 ) 30-min thereafter , ( 3 ) 1400 h , ( 4 ) 1600 h , and ( 5 ) bedtime . Sex hormones were collected at baseline before the psychosocial stressor and on two occasions during diurnal cortisol assessment . Repeated- measures analysis of covariance controlled for key covariates in analyses unadjusted or adjusted for sex hormones . Results revealed that men had higher reactive cortisol than women in unadjusted analysis , but this sex difference was attenuated when adjusting for sex hormones . While diurnal cortisol showed no sex differences in unadjusted models , adjusting for sex hormones revealed that women have higher morning cortisol . Correlations using area under the curve formulae revealed intriguing sex-specific associations with progesterone in men and testosterone in women that we propose have implication s for social and affective neuroscience . In summary , our results reveal that adjusting for sex hormones alters " sex-specific " reactive and diurnal cortisol profiles Evidence from animal as well as human studies has suggested that significant sex differences exist in hypothalamus-pituitary-adrenal axis ( HPA ) activity . As gonadal steroids could be important modulators of HPA sex differences , stress responses were investigated in subjects of advanced age after dehydroepi and rosterone ( DHEA ) or placebo treatment . After a 2-week treatment with 50 mg DHEA daily or placebo , 75 men and women ( mean age , 67.6 yr ) were exposed to the Trier Social Stress Test ( TSST ) . The TSST is a brief psychosocial stress that consists of a free speech and mental arithmetic task in front of an audience . The results show that the TSST induced significant increases in ACTH , salivary free cortisol , total plasma cortisol , norepinephrine , and heart rates ( all P < 0.0001 ) as well as decreased positive affect in the elderly ( P = 0.0009 ) . Men showed larger stress responses in ACTH ( P = 0.004 ) , salivary free cortisol ( P = 0.044 ) , and plasma total cortisol ( P = 0.076 ) compared to women . No sex differences were observed in norepinephrine , epinephrine , or heart rate responses . In contrast to ACTH and cortisol response differences , women reported that they were significantly more stressed by the TSST than men ( P = 0.0051 ) . Women treated with DHEA showed ACTH stress responses similar to those of men , but significantly enhanced compared to those of women taking placebos ( P < 0.009 ) . No other stress response differences emerged between DHEA and placebo groups . Finally , DHEA treatment did not result in an improvement of subjective well-being . We conclude that elderly men show larger HPA responses than women to psychosocial stress , as studied in the TSST . Estrogen effects on hypothalamic CRF-producing neurons might be responsible for these sex differences Previous research has suggested that women may have greater and more prolonged hypothalamic-pituitary-adrenal response to challenge at older ages . Data on patterns of ACTH and cortisol responses to a " naturalistic " driving simulation challenge were examined to test the hypothesis that older women ( aged 70 - 79 years ) would show greater response than a comparable group of older men . Analyses of mean ACTH or cortisol responses in terms of maximal increase , area under the curve and repeated measures ANOVA did not reveal significant gender differences . By contrast , analyses of the joint occurrence of ACTH and cortisol responses above the respective sample medians indicated that women were significantly more likely to respond to the challenge with elevated ACTH and cortisol responses . The lack of significant gender difference in the analyses of mean scores result ed from the sensitivity of this measure of typically ( or average response ) to outliers in the data , thereby substantially distorting the report of typical ( or average ) responses for the male population . Analyses of the temporal patterns of ACTH and cortisol response in terms of the stability of the subject 's relative rank at each sampling time indicated that : ( 1 ) there was considerable stability of rankings based on the initial cortisol response ( though not ACTH ) through the recovery period ; and ( 2 ) women exhibited greater instability than men , being more likely to exhibit shifts in rank from high to low over time . These findings suggest that : ( 1 ) as a group , older women are more likely to show larger responses than comparably healthy older men to a " naturalistic " driving simulation challenge ; ( 2 ) there is considerable stability in patterns of cortisol response from initial response at 20 min through the recovery period , indicating that those showing greater initial response continue to experience higher levels of cortisol during the post-challenge recovery period ; and ( 3 ) instability is more common among women than men Evidence from animal studies and clinical observations suggest that the activity of the pituitary-adrenal axis is under significant influence of sex steroids . The present study investigated how a short term elevation of estradiol levels affects ACTH , cortisol , norepinephrine , and heart rate responses to mental stress in healthy men . In a double blind study , 16 men received a patch delivering 0.1 mg estradiol/day transdermally , and age- and body mass index-matched control subjects received a placebo patch . Twenty-four to 48 h later , they were exposed to a brief psychosocial stressor ( free speech and mental arithmetic in front of an audience ) . In response to the psychosocial stressor , ACTH , cortisol , norepinephrine , and heart rate were increased in both experimental groups ( all P < 0.0001 ) . However , the estradiol-treated subjects showed exaggerated peak ACTH ( P < 0.001 ) and cortisol ( P < 0.002 ) responses compared to the placebo group . Also , the norepinephrine area under the response curve was greater in the estradiol group ( P < 0.05 ) . Although heart rate responses differences failed to reach statistical significance , they , too , tended to be larger in the estradiol group . Neither mood ratings before or after the stressor , nor ratings of the perception of the stressor could explain the observed endocrine response differences . In conclusion , short term estradiol administration result ed in hyperresponses of the pituitary-adrenal axis and norepinephrine to psychosocial stress in healthy young men independent of psychological effects , as assessed in this study The hormonal responses to surgical stress in adults are well characterized . We hypothesized that children have age-related differences in the " stress responses " to surgery . To test this hypothesis we prospect ively studied 98 children ( aged 2 to 20 years ) undergoing elective surgical procedures under general anesthesia . Preoperative and postoperative ( 1 hour postoperation ) blood sample s were obtained and serum prolactin and cortisol concentrations were measured . Patient data were stratified by patient age and length of operation . All patients had significant ( P < .05 ) increases in serum cortisol and prolactin concentrations 1 hour postoperatively as compared with preoperative values . However , there were no significant differences in prolactin and cortisol responses to surgery based on the age , anesthetic technique , or length of operation . Females had higher mean ( + /- SD ) serum prolactin concentrations ( 78.41 + /- 62.23 micrograms/L ) as compared with males postoperatively ( 39.8 + /- 21.75 micrograms/L ) ( P < .05 ) . We conclude the following : ( 1 ) children have significant increases in circulating prolactin and cortisol concentrations following surgery and anesthesia , and that those increases are not affected by age , length of surgery , or anesthetic technique ; and ( 2 ) females have greater prolactin responses to surgery and anesthesia than males Studies on the influence of sex hormones on cortisol responses to awakening and stress have mainly been conducted in adults , while reports on adolescents are scarce . We studied the effects of gender , menstrual cycle phase and oral contraceptive ( OC ) use on cortisol responses in a large sample of adolescents . Data come from TRAILS ( TRacking Adolescents ' Individual Lives Survey ) , a prospect i ve population study of Dutch adolescents . This study uses data of 644 adolescents ( age 15 - 17 years , 54.7 % boys ) who participated in a laboratory session including a performance-related social stress task ( public speaking and mental arithmetic ) . Free cortisol levels were assessed by multiple saliva sample s , both after awakening and during the laboratory session . No significant effects of gender and menstrual phase on cortisol responses to awakening were found , while girls using OC displayed a slightly blunted response ( F(1 , 244)=5.30 , p=.02 ) . Cortisol responses to social stress were different for boys and free-cycling girls ( F(3 , 494)=9.73 , p<.001 ) , and OC users and free-cycling girls ( F(3 , 279)=15.12 , p<.001 ) . Unexpectedly , OC users showed no response at all but displayed linearly decreasing levels F(1 , 279)=19.03 , p<.001 ) of cortisol during the social stress test . We found no effect of menstrual cycle phase on cortisol responses to social stress ( F(3 , 157)=0.58 , p=.55 ) . The absence of a gender difference in the adolescents ' cortisol awakening response found in this study is consistent with previous reports . Our results further suggest that adolescent OC users display slightly blunted cortisol responses after awakening , and that gender differences in cortisol responses to social stress during adolescence are comparable to those described for adult population s , that is , stronger responses in men than in women . Whereas previous work in adults suggested blunted stress responses in OC users compared to men and free-cycling women , adolescent OC users showed no cortisol response . Effects of type of OC could not be studied because of low numbers of OC that were only progestin based |
11,864 | 22,071,809 | There was no evidence of a difference between highly permeable polyurethane dressings and other polyurethane dressings in the prevention of catheter-related bloodstream infection ( low quality evidence ) . | BACKGROUND Central venous catheters ( CVCs ) facilitate venous access , allowing the intravenous administration of complex drug treatments , blood products and nutritional support , without the trauma associated with repeated venepuncture .
However , CVCs are associated with a risk of infection .
Some studies have indicated that the type of dressing used with them may affect the risk of infection .
Gauze and tape , transparent polyurethane film dressings such as Tegaderm ® and Opsite ® , and highly vapour-permeable transparent polyurethane film dressings such as Opsite IV3000 ® , are the most common types of dressing used to secure CVCs .
Currently , it is not clear which type of dressing is the most appropriate .
OBJECTIVES To compare gauze and tape with transparent polyurethane CVC dressings in terms of catheter-related infection , catheter security , tolerance to dressing material and dressing condition in hospitalised adults and children . | Recent developments in dressings for intravenous access sites include a transparent dressing which does not retain moisture . This article describes a r and omised controlled trial to compare the new dressing with a st and ard dressing . There was no difference in sepsis rates between the two groups , and both methods had advantages and disadvantages . The authors suggest that cost may be a factor in choice of dressing The objective of this study was to assess the risk of bacteremia , estimate the cost and evaluate the quality of life by using a transparent dressing ( TD ) versus ( vs ) a dry gauze ( DG ) on the exit site of long term central I.V. catheters ( LTCC ) of hemodialysis patients . This 6-months preliminary study was conducted on 58 patients ( pts ) r and omized to receive DG replaced 3 times/week ( 29 pts ) or TD replaced every 7 days ( 29 pts ) . Data on patients , conditions of the exit site , local infection , bacteremia , quality of life and cost related to each type of dressing were collected . Two pts in the DG group experienced bacteremia related to their LTCC vs 1 pt in the group TD . A total of 7 ( DG ) vs 13 ( TD ) pts experienced skin condition changes at the catheter exit site . Some skin reactions , erythema and pruritus , did occur initially in the group TD and was due in part to insufficient drying time of the skin preparation solution . The estimated individual , weekly costs for using the DG was $ 7.60 vs $ 4.72 Canadian dollars for the TD . The SF-36 ™ scores did not show a significant difference between the 2 groups during the study ( 3.8 ( PCS ) , 6.4 ( MCS ) at study end ) . Although this study was statistically underpowered , it suggests that the incidence of bacteremia was not increased with the use of a TD . Moreover , the use of a TD allowed fewer dressing changes , lowered total treatment costs , with no observed unfavorable impact on the quality of life and without significant local complications of the exit site . Based on the positive results observed in this pilot study , further study is warranted to examine the cost effectiveness of long-term use of TD dressings on dialysis catheter exit sites A prospect i ve r and omized clinical trial has been conducted to compare the clinical performance , with prolonged use , of two film-type transparent dressings used over subclavian and jugular single-lumen venous catheters . ' OpSite ' , a traditional dressing with a moderate moisture vapour permeability was compared with a new dressing of high moisture vapour permeability , ' OpSite IV3000 ' . Information was collected daily to assess the nature and incidence of complications , dressing durability and the ease of application and removal . One hundred and one patients provided two well-matched population s receiving a total of 153 dressings for a total of 780 catheter-days . No differences between the two dressings were noted with respect to the incidence of complications , such as moisture accumulation or lifting , and dressing durability . The low incidence of catheter-related sepsis ( ' OpSite ' group three episodes and ' OpSite IV3000 ' group one episode ) suggests that transparent dressings do not increase this risk . This clinical study demonstrated the new ' OpSite IV3000 ' to be easier to h and le , leading to better application , improved catheter fixation and easy removal A comparative study of ' Op-site ' and ' Nobecutan-gauze ' dressings for central venous lines was performed . Seventy-seven long antebrachial and 68 infraclavicular subclavian catheters were studied . A statistically significant reduction in the incidence of positive cultures from the catheter tip and from the skin puncture site was found with the ' Nobecutan-gauze ' dressing . No difference in the incidence of catheter-related septicaemia was found . The theoretical advantage of being able to observe signs of inflammation when ' Op-site ' was used did not reduce the incidence of local infection at the skin puncture site . In conclusion we found that a ' Nobecutan-gauze ' dressing was a satisfactory alternative to an ' Op-site ' dressing The incidence of catheter-related sepsis associated-with the use of Tegaderm or Opsite IV3000 dressings on 100 critically ill patients with liver disease was studied . All the patients had central venous catheters in situ and they were r and omly assigned to one of the two dressings . In this study the sites of insertion were assessed at each dressing change , together with any fluid under the dressing . No statistically significant difference between the two dressings was found in accumulation of fluid , skin microbial colonization , local infection or systemic infection of patients in our sample . There was no apparent advantage to using the more permeable Opsite IV3000 dressing The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . 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 . Patients having central venous catheters for three or more days were prospect ively r and omized to receive a transparent ( n = 58 ) or gauze ( n = 57 ) dressing to compare the incidence of insertion site colonization , local catheter-related infection , and catheter-related sepsis . Quantitative cultures of the catheter insertion site ( 25 cm2 ) revealed significantly greater colonization ( P less than or equal to .009 ) after 48 h in the transparent versus the gauze dressing group . Local catheter-related infection occurred significantly more often ( P = .002 ) in the transparent ( 62 % ) than in the gauze group ( 24 % ) . Seven episodes of catheter-related bacteremia occurred in the transparent group ( 16.6 % ) and none in the gauze group ( P = .015 ) . Stepwise logistic regression analysis revealed that cutaneous colonization at the insertion site of greater than or equal to 10(3 ) cfu/mL ( relative risk , 13.16 ) and difficulty of insertion ( relative risk , 5.39 ) were significant factors for catheter-related infection . These data suggest that transparent dressings are associated with significantly increased rates of insertion site colonization , local catheter-related infection , and systemic catheter-related sepsis in patients with long-term central venous catheters PURPOSE / OBJECTIVES To determine the effect of two central venous catheter ( CVC ) dressing protocol s on catheter-related infections in hospitalized patients with long-term tunneled catheters undergoing an autologous bone marrow transplant ( BMT ) , to determine the prevalence of long-term CVC-related infections in this population , and to identify other factors in the study sample related to long-term CVC infection . DESIGN Experimental . SETTING BMT unit of a regional oncology center in a tertiary care hospital . SAMPLE The sample consisted of 101 adult patients with cancer with long-term , tunneled CVCs inserted in the operating room on admission for autologous BMT . METHODS Patients r and omly were assigned to one of two dressing-change procedure groups . The control group received the current st and ard of care for patients receiving BMT -- a dry , sterile gauze dressing ( DSGD ) changed every 24 hours . The experimental group received Opsite 3000TM ( Smith + Nephew Ltd. , Massilon , OH ) transparent moisture vapor permeable dressings ( MVPD ) changed weekly . MAIN RESEARCH VARIABLES CVC infection rates , frequency of IV tubing changes , immune status , duration of catheter use , occurrence and outcome of catheter occlusion , and use of a catheter for total parenteral nutrition . FINDINGS Research ers determined the difference in CVC-related infections between the two groups and the impact of select variables on CVC-related infection . When all categories of CVC-related infection ( i.e. , suspected , sepsis , tunnel ) were considered , no statistical difference was found in the likelihood of the groups remaining infection-free ( p = 0.76 ) over time . CVC sepsis occurred in one patient in the DSGD group and five patients in the MVPD group ; however , this difference was not statistically significant over time ( p = 0.067 ) . CONCLUSIONS Development of CVC sepsis or tunnel infection in close proximity to the time of CVC surgical placement suggests that factors other than the assigned dressing were associated with the occurrence of CVC-related infection in three cases . Although the MVPD group required dressing changes more frequently than every seven days ( as specified by the protocol ) because of exit-site drainage and nonocclusiveness , transparent dressings were more cost-effective than daily gauze dressings in this population . IMPLICATION S FOR NURSING PRACTICE For adults undergoing autologous BMT , either DSGD or transparent CVC dressing can be used safely based on patient preference and skin tolerance to the dressing material Patients undergoing bone marrow transplant ( BMT ) are at great risk of infection and sepsis . Long-term central catheters ( LTCCs ) , required for IV therapy , can be a portal of entry for infectious agents . This r and omized , prospect i ve study compared two types of catheter dressings in 98 patients undergoing BMT : a dry sterile gauze dressing ( DSGD ) changed daily and a transparent adherent dressing ( TAD ) changed every four days . Study outcomes included incidence and severity of local and systemic complications , patient assessment of comfort , and calculation of nursing time . One case of catheter-related infection occurred during the study . No significant differences existed between the two dressings in the incidence of positive skin cultures or local complications with the exception of skin irritation . The TAD caused less skin irritation , was preferred by patients , cost less , and required less nursing time . The findings indicate that TADs provide a safe , comfortable , and cost-effective alternative to DSGDs for patients undergoing BMT and receiving antibiotic support during aplasia A prospect i ve , r and omized study compared the use of Opsite and st and ard gauze/tape dressings in 261 patients receiving parenteral nutrition . Eighty-four patients had a source of external drainage and were evaluated as a separate group . Catheter-related sepsis was assessed by blood culture , catheter tip culture , clinical sepsis , and clinical defervescence of fever after catheter removal . Although no statistically significant difference between Opsite and st and ard dressings could be identified , Opsite-treated patients consistently had increased parameters of catheter-related sepsis in all comparisons . As used here , Opsite is probably not a suitable catheter dressing system for parenteral nutrition Central venous lines are now common in children who need a permanent form of intravenous access . These lines frequently become infected . This study compared the effects of different antiseptics ( Hibiclens [ chlorhexadine 4 % ; Stuart Pharmaceutical , Wilmington , DE ] and Betadine [ povidone-iodine , Clini Pad Corp , Guilford , CT ] ) used to clean the skin as well as the dressings used to cover the exit site ( Tegaderm [ 3-M Medical-Surgical Division , St Paul , MN ] and gauze ) on microorganism growth on the skin in a pediatric oncology population . Sixty subjects were recruited from the oncology and bone marrow transplant units of Children 's Hospital in Boston , MA . The subjects were r and omly assigned to one of four dressing groups . These included : 1 , Betadine and Tegaderm ; 2 , Betadine and gauze ; 3 , Hibiclens and Tegaderm ; and 4 , Hibiclens and gauze . Dressings were done on a Monday-Wednesday-Friday basis . Quantitative cultures were obtained before the first and after the fifth dressing changes . There were no significant differences in incidence of bacterial growth between dressing groups ( F = 1.05 , P = .377 ) . Redness ( F = 3.01 , P = .037 ) and swelling ( F = 2.75 , P = .051 ) were more frequently seen in Betadine groups . Boys were more often infected than girls . ( χ 2 = 4.075 , P = .044 Abstract Central venous catheterization is one of the important sepsis reasons in surgical patients . In this r and omized controlled study , the effect of the frequency and type of catheter site care , as well as age , coexisting malignancy or diabetes mellitus , total parenteral nutrition administration and antibiotics use , on central venous catheter infection was investigated . Seventy-two single-lumen polyurethane catheters were included . In group I ( n : 33 ) , a transparent occlusive dressing was applied to the insertion site and not removed for 7 days unless there were signs of local infection . In group II ( n : 39 ) , daily site care was done with povidone-iodine 10 % solution and a new sterile gauze was applied . Chi-square , linear correlation and multiple regression tests were used for statistical analysis . Mean duration of catheters was 8 ±4 days . There was no catheter-related sepsis . Ten ( 13.9 % ) patients had positive catheter tip cultures of whom three had site infection as well . The incidence of site and tip infections were not significantly different in group I and II ( p > 0.05 ) . Site infection and age younger than 60 years significantly increased the rate of tip infection ( p : 0.004 and p : 0.02 respectively ) . Total parenteral nutrition administration was associated with higher rate of tip infection ( p : 0.06 ) . Coexisting malignancy or diabetes mellitus , duration of catheter and antibiotics use did not have any significant effect on the rate of central venous catheter infections ( p > 0.05 ) . In conclusion , we observed that the frequency of insertion site care and the type of dressing applied to the site had no significant effect on the rate of CVC infection . Insertion site infection was the most significant factor increasing the incidence of catheter tip infection . The use of the CVC for total parenteral nutrition facilitated tip infection as well A prospect i ve controlled study of the safety of various catheter dressing protocol s was carried out in 168 patients receiving parenteral nutrition via an infraclavicular central venous catheter . Four protocol s were compared : 36 patients received gauze dressings changed three times per week ; 31 received OpSite dressings changed every 7th day ( OpS-7 ) , 32 received OpSite changed every 10th day ( OpS-10 ) , and 69 received OpSite changed twice weekly ( OpS-ICU ) . Mean duration of parenteral nutrition was approximately 2 weeks and all groups were well matched except that OpS-ICU patients suffered more frequently from an acute illness . Catheter-related sepsis was identified by clinical signs of systemic sepsis , positive peripheral venous blood and catheter-tip cultures and /or defervescence of fever after catheter removal . Catheter-related sepsis rates were low in all groups : 1/36 for Gauze , 0/31 for OpS-7 , 1/32 for OpS-10 , and 2/69 for OpS-ICU . Septicemia attributable to causes apart from catheter sepsis occurred in two , two , three , and four patients , respectively . Bacterial colonization of skin beneath OpSite was no more common in the OpS-10 than in the other groups . Signs of inflammation at catheter insertion sites were common in all groups but did not relate closely to skin colonization . OpSite can be safely applied to central venous catheters inserted under strict aseptic conditions , even in patients with open septic drainage . Dressings can be left in place for 7 days with a margin of safety lasting to 10 days , thus saving on cost of material s and nursing time BACKGROUND Although many catheter-related bloodstream infections ( CRBSIs ) are preventable , measures to reduce these infections are not uniformly implemented . OBJECTIVE To up date an existing evidence d-based guideline that promotes strategies to prevent CRBSIs . DATA SOURCES The MEDLINE data base , conference proceedings , and bibliographies of review articles and book chapters were search ed for relevant articles . STUDIES INCLUDED Laboratory-based studies , controlled clinical trials , prospect i ve interventional trials , and epidemiologic investigations . OUTCOME MEASURES Reduction in CRBSI , catheter colonization , or catheter-related infection . SYNTHESIS The recommended preventive strategies with the strongest supportive evidence are education and training of healthcare providers who insert and maintain catheters ; maximal sterile barrier pre caution s during central venous catheter insertion ; use of a 2 % chlorhexidine preparation for skin antisepsis ; no routine replacement of central venous catheters for prevention of infection ; and use of antiseptic/antibiotic-impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies ( ie , education and training , maximal sterile barrier pre caution s , and 2 % chlorhexidine for skin antisepsis ) . CONCLUSION Successful implementation of these evidence -based interventions can reduce the risk for serious catheter-related infection 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 |
11,865 | 30,895,735 | FINDINGS Both observational and interventional studies showed considerable agreement that supervised regular moderate to vigorous physical activity ( MVPA ) is more effective on adiposity and cardiorespiratory fitness than habitual PA .
Further , it was reported that PA of different intensities improves insulin sensitivity and decreases daily insulin dosage .
Results of glycemic control were equivocal .
A consistent agreement among the studies revealed a considerable benefit of regular habitual PA of light to moderate intensity on blood glucose regulation and lipid profile . | PURPOSE In this systematic review we aim ed to evaluate the effects of physical activity ( PA ) and exercise on biochemical and physiological outcomes in children and adolescents with type 1 diabetes ( T1D ) . | CONTEXT There is a paucity of data regarding the association between glycosylated hemoglobin ( HbA1c ) variability and risk of microvascular complications in adolescents with type 1 diabetes ( T1D ) . OBJECTIVE To investigate the association between HbA1c variability and risk of microvascular complications in adolescents with T1D . DESIGN Prospect i ve cohort study from 1990 to 2014 ( median follow-up , 8.1 y ) . SETTING Tertiary pediatric hospital . PARTICIPANTS A total of 1706 adolescents ( aged 12 - 20 minimum diabetes duration 5 y ) with median age of 15.9 years ( interquartile range , 14.3 - 17.5 ) and diabetes duration of 8.1 years ( 6.3 - 10.8 ) . MAIN OUTCOME MEASURES Glycemic variability was computed as the SD of all HbA1c measurements ( SD-HbA1c ) after diagnosis . Retinopathy was detected using 7-field fundal photography , renal function assessed using albumin excretion rate , peripheral neuropathy detected using thermal and vibration threshold testing , and cardiac autonomic neuropathy ( CAN ) detected using time- and frequency-domain analyses of electrocardiogram recordings . Generalized estimating equations were used to examine the relationship between complications outcomes and HbA1c variability , after adjusting for known risk factors , including HbA1c , diabetes duration , blood pressure , and lipids . RESULTS In multivariable analysis , SD-HbA1c was associated with early retinopathy ( odds ratio [ OR ] 1.32 ; 95 % confidence interval , 1.00 - 1.73 ) , albuminuria ( OR 1.81 ; 1.04 - 3.14 ) , increased log10 albumin excretion rate ( OR 1.10 ; 1.05 - 1.15 ) and CAN ( OR 2.28 ; 1.23 - 4.21 ) but not peripheral neuropathy . CONCLUSIONS Greater HbA1c variability predicts retinopathy , early nephropathy , and CAN , in addition to established risk factors , in adolescents with T1D . Minimizing long term fluctuations in glycemia may provide additional protection against the development of microvascular complications INTRODUCTION Osteoporosis is a growing health problem in patients with type 1 diabetes mellitus ( T1DM ) . The aim of this study was to determine the effects of a 9-month weight-bearing physical activity program on bone mineral density ( BMD ) and bone biomarkers in T1DM compared with healthy children . METHODS This was a r and omized controlled trial including 27 diabetic and 32 healthy children ( mean age = 10.5 ± 2.5 yr ) . Both T1DM and healthy participants were r and omized to either an exercise or a control group ( i.e. , four groups ) . At baseline and 9 months , total body ( TB ) , lumbar spine ( LS2-LS4 ) , femoral neck , and greater trochanter areal BMD ( aBMD ) and serum bone biomarkers ( osteocalcin , type 1 collagen cross-linking ) were measured . The intervention consisted of two 90-min sessions per week of weight-bearing physical activity ( ball games , jumping , rope skipping , and gymnastics ) . RESULTS Baseline variables were similar among groups . At 9 months , changes in TB ( T1DM = 0.035 ± 0.022 g·cm(-2 ) , healthy = 0.031 ± 0.017 g·cm(-2 ) ) and LS2-LS4 ( T1DM = 0.046 ± 0.038 g·cm(-2 ) , healthy = 0.063 ± 0.034 g·cm(-2 ) ) aBMD were statistically significant in the intervention groups and of similar magnitude between T1DM and healthy subjects . The level of type 1 collagen cross-linking ( T1DM = -0.12 ± 0.32 ng·mL(-1 ) , healthy = -0.36 ± 0.11 ng·mL(-1 ) ) decreased in the intervention groups but was not associated with TB aBMD changes . CONCLUSIONS Regular weight-bearing physical activity ( 180 min·wk(-1 ) , including ball games , jumping activities , and gymnastics ) improves total and LS2-LS4 bone mineral accretion in children with T1DM , in a similar magnitude to healthy subjects . We conclude that children with T1DM should be encouraged to practice regular physical activity to enhance peak bone mass and prevent osteoporosis later in life OBJECTIVES To evaluate the evolution of subcutaneous glucose ( SG ) after a st and ardized aerobic exercise in children and adolescents treated with continuous subcutaneous insulin infusion ( CSII ) or multiple daily injection ( MDI ) regimen before and after adaptation of insulin doses . RESEARCH DESIGN AND METHODS Eleven CSII- and 13 MDI-treated patients performed 2 30-minute sessions of moderate to vigorous ( 70 % of age-based maximal heart rate ) exercise on a treadmill under continuous glucose monitoring ( CGM ) . First sessions were scheduled without insulin modification ( TT#1 ) while patients performed second sessions ( TT#2 ) after preemptive algorithm-based insulin dose modifications . RESULTS While insulin adaptations did not modify immediate postexercise drops in blood glucose during TT#2 in either group , CSII-treated patients had their glucose control improved during TT#2 ( mean of 141 ± 56 mg/dL vs 144 ± 80 mg/dL in TT#1 ; P < .05 ) with up to 86 % of SG levels within targets during 16 hours postexercise . Contrarily , SG levels did not normalize during TT#2 in MDI-treated patients who experienced higher rates of hyperglycemia during the afternoon snack . As compared with TT#1 , CSII-treated patients had reduced rates of hypoglycemia during 4 hours post-TT#2 ( from 19.5 % to 2.1 % ; P < .01 ) and had shorter duration of nocturnal hypoglycemia ( 35.5 ± 12.8 vs 204.7 ± 165 minutes ; P = .04 ) whereas in the MDI group no changes in percentages of hypoglycemia were observed during TT#2 . CONCLUSION In our pediatric cohort , algorithmic adaptations of insulin doses were associated with better outcomes in terms of postexercise glucose control in patients with CSII therapy but not with MDI treatment This paper describes PEDro , the Physiotherapy Evidence Data base . PEDro is a web-based data base of r and omized controlled trials and systematic review s in physiotherapy . It can be accessed free of charge at http://ptwww.cchs.usyd.edu.au/pedro . The data base contains bibliographic details and abstract s of most English- language r and omized trials and systematic review s in physiotherapy , and of many trials and review s in other language s. Trials on the data base are rated on the basis of their method ological quality so that users of the data base can quickly identify trials of high quality . Trials and systematic review s are extensively indexed to facilitate search ing . PEDro provides an important information re source to support evidence -based clinical practice BACKGROUND Patients with type 1 diabetes mellitus ( T1DM ) may experience poor muscle health as a result of chronic hyperglycemia . Despite this , muscle function in children with T1DM with good or poor glycemic control has yet to be examined in detail . OBJECTIVE To assess differences in muscle-related fitness variables in children with T1DM with good glycemic control ( T1DM-G ) , as well as those with poor glycemic control ( T1DM-P ) , and non-diabetic , healthy controls . SUBJECTS Eight children with T1DM-G [ glycosylated hemoglobin ( HbA1c ) ≤ 7.5 % for 9 months ] , eight children with T1DM-P ( HbA1c ≥ 9.0 % for 9 months ) , and eight healthy controls completed one exercise session . METHODS Anaerobic and aerobic muscle functions were assessed with a maximal isometric grip strength test , a Wingate test , and an incremental continuous cycling test until exhaustion . Blood sample s were collected at rest to determine HbA1c at the time of testing . Physical activity was monitored over 7 d using accelerometry . RESULTS Children with T1DM-P displayed lower peak oxygen consumption ( VO2peak ) values ( mL/kg/min ) compared to healthy controls ( T1DM-P : 33.2 ± 5.6 , controls : 43.5 ± 6.3 , p < 0.01 ) , while T1DM-G ( 43.5 ± 6.3 ) had values similar to controls and T1DM-P. There was a negative relationship between VO2peak and HbA1c% ( r = -0.54 , p < 0.01 ) . All groups were similar in all other fitness variables . There were no group differences in physical activity variables . CONCLUSION Children with T1DM-G did not display signs of impaired muscle function , while children with T1DM-P have signs of altered aerobic muscle capacity |
11,866 | 26,461,263 | For aspirin 1000 mg and diflunisal 1000 mg , opioids , or fixed-dose combination drugs containing opioids , participants typically experienced significantly more adverse events than with placebo .
Studies of combinations of ibuprofen and paracetamol reported significantly fewer adverse events .
Serious adverse events were rare , occurring a rate of about 1 in 3200 participants .Most review s did not report specific adverse events .
AUTHORS ' CONCLUSIONS Despite ongoing problems with the measurement , recording , and reporting of adverse events in clinical trials and in systematic review s , the large amount of information available for single oral doses of analgesics provides evidence that adverse events rates are generally similar with active drug and placebo in these circumstances , except at higher doses of some drugs , and in combinations including opioids | BACKGROUND This is an up date of a Cochrane overview published in Issue 9 , 2011 ; that overview considered both efficacy and adverse events .
This overview considers adverse events , with efficacy dealt with in a separate overview .
Thirty-nine Cochrane review s of r and omised trials have examined the adverse events associated with individual drug interventions in acute postoperative pain .
This overview brings together the results of those individual review s. OBJECTIVES To provide an overview of adverse event rates associated with single-dose oral analgesics , compared with placebo , for acute postoperative pain in adults . | & NA ; Adverse events in r and omized controlled trials of noninvasive , pharmacologic analgesics are frequently incompletely or inconsistently reported . A comprehensive reporting checklist is proposed to improve disclosure of adverse effects . & NA ; The development of valid and informative treatment risk – benefit profiles requires consistent and thorough information about adverse event ( AE ) assessment and participants ’ AEs during r and omized controlled trials ( RCTs ) . Despite a 2004 extension of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement recommending the specific AE information that investigators should report , there is little evidence that analgesic RCTs adequately adhere to these recommendations . This systematic review builds on prior recommendations by describing a comprehensive checklist for AE reporting developed to capture clinical ly important AE information . Using this checklist , we coded AE assessment methods and reporting in all 80 double‐blind RCTs of noninvasive pharmacologic treatments published in the European Journal of Pain , Journal of Pain , and PAIN ® from 2006 to 2011 . Across all trials , reports of AEs were frequently incomplete , inconsistent across trials , and , in some cases , missing . For example , > 40 % of trials failed to report any information on serious adverse events . Trials of participants with acute or chronic pain conditions and industry‐sponsored trials typically provided more and better‐ quality AE data than trials involving pain‐free volunteers or trials that were not industry sponsored . The results of this review suggest that improved AE reporting is needed in analgesic RCTs . We developed an ACTTION ( Analgesic , Anesthetic , and Addiction Clinical Trial Translations , Innovations , Opportunities , and Networks ) AE reporting checklist that is intended to assist investigators in thoroughly and consistently capturing and reporting these critically important data in publications Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Postoperative pain can have a significant effect on patient recovery . An underst and ing of patient attitudes and concerns about postoperative pain is important for identifying ways health care professionals can improve postoperative care . To assess patients ’ postoperative pain experience and the status of acute pain management , we conducted a national study by using telephone question naires . A r and om sample of 250 adults who had undergone surgical procedures recently in the United States was obtained from National Family Opinion . Patients were asked about the severity of postsurgical pain , treatment , satisfaction with pain medication , patient education , and perceptions about postoperative pain and pain medications . Approximately 80 % of patients experienced acute pain after surgery . Of these patients , 86 % had moderate , severe , or extreme pain , with more patients experiencing pain after discharge than before discharge . Experiencing postoperative pain was the most common concern ( 59 % ) of patients . Almost 25 % of patients who received pain medications experienced adverse effects ; however , almost 90 % of them were satisfied with their pain medications . Approximately two thirds of patients reported that a health care professional talked with them about their pain . Despite an increased focus on pain management programs and the development of new st and ards for pain management , many patients continue to experience intense pain after surgery . Additional efforts are required to improve patients ’ postoperative pain experience OBJECTIVE To assess how information about adverse events is included in systematic review s. STUDY DESIGN AND SETTING We included all new Cochrane review s published in the Cochrane Data base of Systematic Review s ( CDSRs ) and all new review s ( 2003 - -2004 ) in the Data base of Abstract s of Review s of Effects ( DAREs ) in Issue 1 2005 of The Cochrane Library . RESULTS More than half of Cochrane ( 44/78 ) and DARE ( 46/79 ) review s assessed drug interventions . The rest assessed surgery ( Cochrane [ 12 ] ; DARE [ 10 ] ) , psychosocial , educational , or physiotherapy interventions ( 22 ; 23 ) . Seventy-six percent ( 59/78 ) of Cochrane review s mentioned adverse events as an outcome compared with 48 % ( 38/79 ) of DARE review s. Most review s mentioning adverse events were of drug interventions ( Cochrane [ 41/59 ] ; DARE review s [ 29/38 ] ) . Considering review s that mentioned adverse events , 95 % ( 56/59 ) of Cochrane review s included only r and omized trials and 73 % ( 43/59 ) included an analysis of adverse events . For 10 Cochrane review s , adverse events had not been reported by the included trials . In contrast , 58 % ( 22/38 ) of DARE review s mentioning adverse events included only r and omized trials , the rest included both r and omized and nonr and omized studies . CONCLUSIONS Most Cochrane review s of drug interventions considered adverse events . This was not the case for DARE review s and for Cochrane review s of nondrug interventions . This could be improved The nocebo effect is the onset of untoward reactions following the administration of an indifferent substance . The oral challenge with alternative drugs plays a central role in the management of drug allergy and the use of inert substances is part of this procedure . We evaluated the occurrence and clinical characteristics of nocebo effect in patients with adverse drug reactions . Six hundred patients , seen in three different centres ( Genoa , Naples and Verona ) with a history of reactions to drugs , underwent a blind oral challenge with the administration of an indifferent substance and active drugs . The administration of an inert substance provoked untoward reactions in 54 patients ( 27 % ) in Verona , 60 ( 30 % ) in Naples and 48 ( 24 % ) in Genoa . The overall occurrence of nocebo effect was 27 % . The majority of reactions were subjective symptoms ( itching , malaise , headache etc ) , perceived as troublesome by all subjects . The occurrence was significantly higher in women than in men . Our data , collected in a large population , confirm that the nocebo effect occurs frequently in clinical practice . In managing adverse drug reactions through oral challenge the nocebo effect is m and atory to recognize false positive responses Objectives To compare the efficacy and safety of single versus combination non-prescription oral analgesics in community-derived people aged 40 years and older with chronic knee pain . Methods A r and omised , double-blind , four-arm , parallel-group , active controlled trial investigating short-term ( day 10 ) and long-term ( week 13 ) benefits and side-effects of four regimens , each taken three times a day : ibuprofen ( 400 mg ) ; paracetamol ( 1000 mg ) ; one fixed-dose combination tablet ( ibuprofen 200 mg/paracetamol 500 mg ) ; two fixed-dose combination tablets ( ibuprofen 400 mg/paracetamol 1000 mg ) . Results There were 892 participants ( mean age 60.6 , range 40–84 years ) ; 63 % had radiographic knee osteoarthritis and 85 % fulfilled American College of Rheumatology criteria for osteoarthritis . At day 10 , two combination tablets were superior to paracetamol ( p<0.01 ) for pain relief ( determined by mean change from baseline in WOMAC pain ; n=786 ) . At 13 weeks , significantly more participants taking one or two combination tablets rated their treatment as excellent/good compared with paracetamol ( p=0.015 , p=0.0002 , respectively ; n=615 ) . The frequency of adverse events was comparable between groups . However , by 13 weeks , decreases in haemoglobin ( ≥1 g/dl ) were observed in some participants in all groups . Twice as many participants taking two combination tablets had this decrease compared with those on monotherapy ( p<0.001 ; paracetamol , 20.3 % ; ibuprofen , 19.6 % ; one or two combination tablets , 24.1 % , 38.4 % , respectively ) . Conclusions Ibuprofen/paracetamol combination analgesia , at non-prescription doses , confers modest short-term benefits for knee pain/osteoarthritis . However , in this population , paracetamol 3 g/day may cause similar degrees of blood loss as ibuprofen 1200 mg/day , and the combination of the two appears to be additive . Study no IS RCT CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , generalizable data on drug safety reporting are sparse . OBJECTIVE To scrutinize the completeness of safety reporting in r and omized trials . DESIGN , SETTING , AND PATIENTS Survey of safety reporting in 192 r and omized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm ( N = 130074 patients ) . Trial reports were identified from comprehensive meta-analyses in 7 medical areas . MAIN OUTCOME MEASURES Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects ; article space allocated to safety reporting and predictors of such reporting . RESULTS Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39 % and 29 % of trial reports , respectively . Only 46 % of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity . For these 3 parameters , there was significant heterogeneity in rates of adequate reporting across topics ( P = .003 , P<.001 , and P = .02 , respectively ) . Overall , the median space allocated to safety results was 0.3 page . A similar amount of space was devoted to contributor names and affiliations ( P = .16 ) . On average , the percentage of space devoted to safety in the results section was 9.3 % larger in trials involving dose comparisons than in those that did not ( P<.001 ) and 3.8 % smaller in trials reporting statistically significant results for efficacy outcomes ( P = .047 ) . CONCLUSIONS The quality and quantity of safety reporting vary across medical areas , study design s , and setting s but they are largely inadequate . Current st and ards for safety reporting in r and omized trials should be revised to address this inadequacy Background Although the methods for conducting systematic review s of efficacy are well established , there is much less guidance on how systematic review s of adverse effects should be performed . Methods In order to determine where method ological research is most needed to improve systematic review s of adverse effects of health care interventions , we conducted a descriptive analysis of systematic review s published between 1994 and 2005 . We search ed the Data base of Abstract s of Review s of Effects ( DARE ) and The Cochrane Data base of Systematic Review s ( CDSR ) to identify systematic review s in which the primary outcome was an adverse effect or effects . We then extracted data on many of the elements of the systematic review process including : types of interventions studied , adverse effects of interest , re sources search ed , search strategies , data sources included in review s , quality assessment of primary data , nature of the data analysis , and source of funding . Results 256 review s were included in our analysis , of which the majority evaluated drug interventions and pre-specified the adverse effect or effects of interest . A median of 3 re sources were search ed for each review and very few review s ( 13/256 ) provided sufficient information to reproduce their search strategies . Although more than three quarters ( 185/243 ) of the review s sought to include data from sources other than r and omised controlled trials , fewer than half ( 106/256 ) assessed the quality of the studies that were included . Data were pooled quantitatively in most of the review s ( 165/256 ) but heterogeneity was not always considered . Less than half ( 123/256 ) of the review s reported on the source of funding . Conclusion There is an obvious need to improve the methodology and reporting of systematic review s of adverse effects . The methodology around identification and quality assessment of primary data is the main concern For many of us working in the field of pain medicine , 2003 represented a turning point . For a decade a more liberal approach to opioid prescribing , supported in part by a steady stream of short-term , r and omised controlled trials and facilitated by a tide of educational initiatives sponsored by pharmaceutical companies selling the next best thing , had put pain specialists ahead of the pack . We thought we had at our fingertips the newly acquired knowledge to open the floodgates and deploy our most potent weapon , strong opioids , in the battle to manage persistent pain . But then a distant warning bell was heard . Jane Ballantyne and Jianren Mao published a paper in the New Engl and Journal of Medicine in which they sounded a number of caution ary notes.1 They pointed out that opioids are not all good news when used in the long term and , in particular , the way that opioids are used in clinical practice can not be justified from the information we derive from clinical trials . A year later there were more loud noises off . An editorial in Pain described a developing epidemic of opioid misuse in parallel with the marked and progressive rise in opioid prescribing.2 The debate shifted from ‘ Why not prescribe opioids ? ’ to ‘ Why not to prescribe opioids ? ’ Data from the USA are unambiguous . The increase in prescription of opioids for pain has been accompanied by an increase in prescription drug misuse and additional risk of morbidity and mortality.3–10 The prescribing statistics from other developed countries , including the UK , show a similar rate of rise in opioid use , so it is no surprise to read dire warnings of the storm of misuse and opioid-related deaths that is about to hit us.11–13 It is also unsurprising that the mix of a good story about the man in the street becoming addicted and a dig at doctors has made its way into our daily newspapers.14–16 For certain , every patient who becomes an addict as a result of irresponsible prescribing or marketing is a patient too many . Addiction destroys the lives of sufferers and their families and is a barrier to successful pain management . Support groups representing patients who have run into trouble with opioids and other drugs have recently found a voice in the UK , and this has led to both a parliamentary inquiry and a coordinated Department of Health work stream to address the problem.17,18 As part of this work stream , the situation with regard to addiction and mortality in the UK is becoming clearer . There may be limitations in the way that data regarding addiction to prescribed and over-the-counter ( OTC ) drugs are collected and it is likely that addiction to medicinal opioids is somewhat under-reported . The National Drug Treatment Monitoring System data show that addiction to prescribed and OTC opioids does occur but the numbers of patients presenting for support in relation to addiction to prescribed opioids has remained stable over a 5-year period.18 The Office for National Statistics records data on all drug-related deaths . A review of the 2010 data show unchanged or falling death rates in relation to co-codamol , co-dydramol and dihydrocodeine ; a steady increase in deaths from tramadol since 2003 ( 87 tramadol-related deaths in 2009 and 132 deaths in 2010 ) ; and a rise in codeine-related deaths from 2006 to 2009 , which now seems to have stabilised.19 So what does all this mean ? As far as we know , we do not , in the UK , have an epidemic of addiction and opioid-related mortality as a result of increased opioid prescribing – or at least not yet . We have only really just started looking properly . We might speculate that the inability of pharmaceutical companies to market opioids directly to patients , the current primary care set-up in which most patients still have a family doctor who has a pretty good grip on who , apart from themselves , is giving what to patients , and a culture in which patients , on the whole , believe that doctors know best , might act as brakes on the addiction and mortality juggernaut . However , this is no time for complacency . What the addiction and mortality data do not tell us is the enormous clinical challenge and healthcare burden in relation to patients with persistent pain on unhelpful and very-high-dose opioids who , in some cases for years , are burdened by all the harms and none of the benefits of opioid treatment . We do not know what the scale of the opioid-related harms is , but all of us see patients in this trap in almost every clinic . We must remain vigilant and diligent in our efforts to improve what we know about safe prescribing of opioids and opioid-related harms . Caution ary guidance exists , but given the lack of a large enough data set to give us the answers we so badly need in relation to long-term opioid therapy , such guidance is still heavily weighted by professional opinion . It may be that we have a real opportunity here in the UK to somehow head off the impending storm by getting the message about safe prescribing to everyone who needs to know it , and to support the victims who have been already hit by the opioid problem with improved recognition and management of opioid burdens . If we could get it right it would be a public health triumph . If we do not , and the UK ends up in the undoubted opioid chaos seen in the USA , it will be as bad for those who do not need opioids as for those who do We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials Abstract Objectives : To investigate the cost effectiveness of intravenous ketorolac compared with intravenous morphine in relieving pain after blunt limb injury in an accident and emergency department . Design : Double blind , r and omised , controlled study and cost consequences analysis . Setting : Emergency department of a university hospital in the New Territories of Hong Kong . Participants : 148 adult patients with painful isolated limb injuries ( limb injuries without other injuries ) . Main outcome measures : Primary outcome measure was a cost consequences analysis comparing the use of ketorolac with morphine ; secondary outcome measures were pain relief at rest and with limb movement , adverse events , patients ' satisfaction , and time spent in the emergency department . Results : No difference was found in the median time taken to achieve pain relief at rest between the group receiving ketorolac and the group receiving morphine , but with movement the median reduction in pain score in the ketorolac group was 1.09 per hour ( 95 % confidence interval 1.05 to 2.02 ) compared with 0.87 ( 0.84 to 1.06 ) in the morphine group ( P=0.003 ) . The odds of experiencing adverse events was 144.2 ( 41.5 to 501.6 ) times more likely with morphine than with ketorolac . The median time from the initial delivery of analgesia to the participant leaving the department was 20 ( 4.0 to 39.0 ) minutes shorter in the ketorolac group than in the morphine group ( P=0.02 ) . The mean cost per person was $ HK44 ( £ 4 ; $ 5.6 ) in the ketorolac group and $ HK229 in the morphine group ( P<0.0001 ) . The median score for patients ' satisfaction was 6.0 for ketorolac and 5.0 for morphine ( P<0.0001 ) . Conclusion : Intravenous ketorolac is a more cost effective analgesic than intravenous morphine in the management of isolated limb injury in an emergency department in Hong Kong , and its use may be considered as the dominant strategy 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 Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale Abstract Healthy university students and hospital staff taking no medications were surveyed by question naire to obtain data on the occurrence of many symptoms often listed as side effects of drugs AIMS To assess hospital admission rates for gastrointestinal ( GI ) or cardiovascular ( CV ) events in real-life use of nonsteroidal anti-inflammatory drugs ( NSAIDs ) . METHODS CADEUS is a real-life population -based cohort study of 23 535 coxib ( celecoxib or rofecoxib ) and 22 919 traditional NSAID ( tNSAID ) users . Each hospitalization reported between index day ( NSAID delivery ) and question naire su bmi ssion ( median = 75 days ) was explored using hospital discharge summaries . An expert committee vali date d blindly serious GI and CV events according to predefined criteria . RESULTS Coxib users were older and had more GI history than tNSAID users . There were 21 hospitalizations for GI events , 12 in the coxib cohort and nine in the tNSAID cohort ( respectively one and three upper GI haemorrhages and no ulcer perforations ) . Rates of GI events were 0.39 per 1000 patients [ 95 % confidence interval ( CI ) 0.18 , 0.75 ] for tNSAID users and 0.51 per 1000 patients ( 95 % CI 0.26 , 0.89 ) for coxib users . There were 21 hospitalizations for CV events , 13 in the coxib cohort and eight in the tNSAID cohort . None was fatal . Rates of CV events were , respectively , 0.59 ( 95 % CI 0.24 , 1.22 ) , 0.51 ( 95 % CI 0.19 , 1.11 ) and 0.35 ( 95 % CI 0.15 , 0.69 ) per 1000 patients for celecoxib , rofecoxib and tNSAIDs . GI or CV event rates were not different between products even for patients > 60 years old . CONCLUSIONS Hospitalization rates for GI bleeding were 10 - 20 times lower than expected from published r and omized clinical trials , probably because of differences in drug usage and concomitant gastroprotection . CV event rates conformed to those expected from general population data . These results emphasize the necessity of developing population healthcare data bases to explore such low event rates Abstract Objective : To survey patients ' opinions of their experiences in hospital in order to produce data that can help managers and doctors to identify and solve problems . Design : R and om sample of 36 NHS hospitals , stratified by size of hospital ( number of beds ) , area ( north , midl and s , south east , south west ) , and type of hospital ( teaching or non-teaching , trust or directly managed ) . From each hospital a r and om sample of , on average , 143 patients was interviewed at home or the place of discharge two to four weeks after discharge by means of a structured question naire about their treatment in hospital . Subjects : 5150 r and omly chosen NHS patients recently discharged from acute hospitals in Engl and . Subjects had been patients on medical and surgical wards apart from paediatric , maternity , psychiatric , and geriatric wards . Main outcome measures : Patients ' responses to direct questions about preadmission procedures , admission , communication with staff , physical care , tests and operations , help from staff , pain management , and discharge planning . Patients ' responses to general questions about their degree of satisfaction in hospitals . Results : Problems were reported by patients , particularly with regard to communication with staff ( 56 % ( 2824/5020 ) had not been given written or printed information ) ; pain management ( 33 % ( 1042/ 3162 ) of those suffering pain were in pain all or most of the time ) ; and discharge planning ( 70 % ( 3599/ 5124 ) had not been told about warning signs and 62 % ( 3177/5119 ) had not been told when to resume normal activities ) . Hospitals failed to reach the st and ards of the Patient 's Charter — for example , in explaining the treatment proposed and giving patients the option of not taking part in student training . Answers to questions about patient satisfaction were , however , highly positive but of little use to managers . Conclusions : This survey has highlighted several problems with treatment in NHS hospitals . Asking patients direct questions about what happened rather than how satisfied they were with treatment can eluci date the problems that exist and so enable them to be solved |
11,867 | 25,712,470 | There was wide variation in methods , the joints able to be tested , and the population s sample d. The predominant construct was active or passive joint position detection , followed by passive motion detection and motion direction discrimination .
The Rivermead Assessment of Somatosensory Perception was generally considered to be a valid and reliable tool but with low precision ; other tools with higher precision are potentially not clinical ly feasible . | Proprioception is a vital aspect of motor control and when de grade d or lost can have a profound impact on function in diverse clinical population s. This systematic review aim ed to identify clinical ly related tools to measure proprioceptive acuity , to classify the construct(s ) underpinning the tools , and to report on the clinimetric properties of the tools . | Background : Sensory assessment to estimate spread and effectiveness of a peripheral nerve block is difficult because no clinical test is specific for small sensory fibers . Occurrence of a swelling illusion ( SI ) during a peripheral nerve block corresponds to the impairment of small sensory fibers . The authors investigated the usefulness of SI in predicting successful peripheral nerve block by assessing the temporospatial correlation between progression of sensory impairment in cutaneous distributions anesthetized and localization of SI during peripheral nerve block installation . Methods : Interscalene , infracoracoid , or sciatic nerve blocks were performed using a nerve stimulator and 1.5 % mepivacaine in 53 patients , with a total of 201 nerves to be anesthetized . Pinprick , cold , warm , touch , and proprioception were assessed every 3 min , while patients were asked to describe their perception of size and shape of their anesthetized limb and localization of these illusions . Data are presented as mean ± SD and percentage ( 95 % confidence interval ) . Results : Failure occurred in 12 cutaneous distributions out of a total of 201 theoretically blocked nerves . SI appeared earlier than warmth impairment ( 4.3 ± 2.7 vs. 6.2 ± 2.0 min ; P < 0.05 ) , always corresponding to successfully anesthetized cutaneous distributions , with the exception of 1 patient , who developed SI in 2 cutaneous distributions while sensory testing indicated failure in 1 distribution . SI successfully predicted the blockade of a cutaneous distribution with a sensitivity of 1.00 ( 0.98–1.00 ) , a specificity of 0.92 ( 0.65–0.99 ) , and an accuracy of 0.99 ( 0.97–1.00 ) . Conclusions : Swelling illusion may provide an early assessment of the success of a peripheral nerve block in unse date d patients Objective : To characterize the nature of sensory impairments after stroke , identify associated factors , and assess the relationships between sensory impairment , disability , and recovery . Methods : Prospect i ve cross-sectional survey of 102 people with hemiparesis following their first stroke . Tactile and proprioceptive sensation in the affected arm and leg were measured using the Rivermead Assessment of Somatosensory Perception 2 - 4 weeks post-stroke . Demographics , stroke pathology , weakness , neglect , disability , and recovery were documented . Results : Tactile impairment was more common than proprioceptive ( P < .000 ) , impairment of discrimination was more common than detection ( P < .000 ) , and tactile sensation was more severely impaired in the leg than the arm ( P < .000 ) . No difference in proprioception between the arm and leg ( P = .703 ) or between proximal and distal joints ( P = .589 , P = .705 ) was found . The degree of weakness and the degree of stroke severity were significantly associated with sensory impairment ; demographics , stroke side and type , and neglect were not associated . All the sensory modalities were significantly related to independence , mobility , and recovery ( r = 0.287 [ P < .011 ] to r = 0.533 [ P < .000 ] ) . Conclusion : Sensory impairments of all modalities are common after stroke , although tactile impairment is more frequent than proprioceptive loss , especially in the leg . They are associated with the degree of weakness and the degree of stroke severity but not demographics , stroke pathology , or neglect , and they are related to mobility , independence in activities of daily living , and recovery The role of proprioception as a protective mechanism has gained interest in recent years . From the clinical st and point , several studies have dealt with ways to enhance proprioception following surgery and during rehabilitation . If kinesthesia ( ability to detect passive motion ) can be enhanced as a consequence of long-term athletic training , such training must be included as a part of the rehabilitation process to protect the patient from reinjury . Consequently , the purpose of this study was to compare the kinesthetic knee pattern between trained gymnasts and healthy nongymnasts . The proprioception testing device ( PTD ) was used to evaluate knee kinesthesia . From 45 ° of flexion , the knee was passively extended with the PTD . The device was stopped by the subject when this passive motion was detected . Fifteen healthy college-age female gymnasts ( mean age 19.3 years ) and 30 normal volunteers ( mean age 20.7 years ) comprised our study sample . A one-way analysis of variance ( ANOVA ) was used to compare the mean values of the dominant gymnastic knee to the dominant knee in the control group . Results revealed statistically significant mean differences between the trained gymnastic group and the untrained control group ( F1.34 (.95)=7.17.P=0.011 ) . The results of this study suggest that extensive training has a positive influence on knee kinesthesia in addition to increasing muscle tone . According to the findings of this and other studies , highly trained athletes possess enhanced neurosensory pathways which are speculated to develop as a result of long-term athletic training . Although definite conclusions can not be made from our investigation , prospect i ve studies can determine the true role of athletic training in proprioceptive patterns The effect of glenohumeral arthritis and subsequent total shoulder arthroplasty ( TSA ) on shoulder proprioception has not been evaluated previously . A prospect i ve analysis of 20 consecutive patients with unilateral advanced glenohumeral arthritis who underwent TSA was undertaken . Shoulder proprioception testing for passive position sense and detection of motion was performed 1 week before surgery and 6 months after TSA . The presence of glenohumeral arthritis had a significant effect on position sense for all 3 planes tested ( flexion , abduction , and external rotation ) . There were significant differences ( P < .05 ) compared with the uninvolved shoulder and with a group of 20 age- and gender-matched subjects without a history of shoulder problems . Six months after TSA , position sense was significantly improved ( P < .05 ) and was not significantly different from that in the contralateral shoulder or the comparison group . Detection of motion was also significantly worse in the arthritic group compared with that in the uninvolved contralateral side ( P < .05 ) . Six months after TSA , the sensitivity to detection of motion improved ( P < .01 ) and was not significantly different than that in the uninvolved contralateral shoulder . In addition , the postoperative values for the involved shoulder were not significantly different than those in the age- and gender-matched comparison group . This study demonstrates a significant decrease in proprioceptive function in patients with advanced glenohumeral arthritis . After TSA , there was a marked improvement in proprioception STUDY DESIGN A cross-sectional study in patients with recurrent/chronic low back trouble and healthy control subjects . OBJECTIVE To evaluate the effect of paraspinal muscle fatigue on the ability to sense a change in lumbar position . SUMMARY OF BACKGROUND DATA Protection against spinal injury requires proper anticipation of events , appropriate sensation of body position , and reasonable muscular responses . Lumbar fatigue is known to delay lumbar muscle responses to sudden loads . It is not known whether the delay is because of failure in the sensation of position , output of the response , or both . METHODS Altogether , 106 subjects ( 57 patients with low back trouble [ 27 men and 30 women ] and 49 healthy control subjects [ 28 men and 21 women ] ) participated in the study . Their ability to sense a change in lumbar position while seated on a special trunk rotation unit was assessed . A motor rotated the seat with an angular velocity of 1 degree per second . The task in the test involved reacting to the perception of lumbar movement ( rotation ) by releasing a button with a finger movement . The test was performed twice , before and immediately after a fatiguing procedure . During the endurance task , the participants performed upper trunk repetitive extensions against a resistance , with a movement amplitude adjusted between 25 degrees flexion and 5 degrees extension , until exhaustion . RESULTS Patients with chronic low back trouble had significantly poorer ability than control subjects on the average to sense a change in lumbar position ( P = 0.007 ) , which was noticed before and after the fatiguing procedure . Lumbar fatigue induced significant impairment in the sensation of position change ( P < 0.000001 ) . CONCLUSIONS Lumbar fatigue impairs the ability to sense a change in lumbar position . This feature was found in patients and control subjects , but patients with low back trouble had poorer ability to sense a change in lumbar position than control subjects even when they were not fatigued . There seems to be a period after a fatiguing task during which the available information on lumbar position and its changes is inaccurate Study Design . A clinical trial comparing a back pain group with a pain‐free group . Objectives . To investigate whether proprioceptive deficits existed in a group of individuals reporting low back pain . Summary of Background Data . Little work has so far been conducted on the measurement of proprioception in the spine . Those studies that have been carried out , however , have failed to identify proprioceptive deficits in individuals with back pain . Previous work on peripheral joints has revealed that proprioception is affected with muscular or joint injury or degeneration . Methods . Forty individuals took part in the study , 20 with back pain and 20 with no pain . Participants were required to reproduce a predetermined target position , in st and ing and four‐point kneeling , 10 times in 30 seconds . A computer screen was used to provide visual feedback on position . A mean deviation from the target position was obtained for each individual . A measurement of left elbow position sense was conducted in five individuals from each group to establish differences in short‐term motor memory between the groups . Results . There were no differences between the subject groups in terms of short‐term motor memory ( P > 0.05 ) . A two‐way analysis of variance between subject groups and position to identify differences in accuracy ( deviation from the target ) found that there were differences between subject groups in either position ( P < 0.05 ) . There was no significant difference in accuracy between the positions used ( P > 0.05 ) . Conclusions . Differences in proprioception do exist between individuals with back pain and those free from back pain . Further research needs to be undertaken on proprioceptive exercise programs and their effect on back pain Objective : To develop a st and ardized , clinical ly relevant , quantitative assessment of somatosensory performance in patients with stroke . Design : Prospect i ve observational study and test evaluation . Setting : Local Oxford hospitals and a regional neurological rehabilitation centre . Subjects : Stroke patients with a ” rst , lateralized acute stroke in hospital , and age-matched control subjects . Method : Each patient was assessed in a structured way using a new battery of formal tests of somatosensory performance . Results : A total of 100 patients and 50 controls were fully investigated . Control subjects performed at or near ceiling on all tests , but patients showed impaired performance on all tests . The Rivermead Assessment of Somatosensory Performance ( RASP ) showed good intra-rater and inter-rater reliability for all subtests . There were however only weak relationships between scores of sensory impairment and scores of motor impairment or mobility and dependence . Conclusions : The RASP provides a practical and reliable assessment of sensory loss , which provides the clinician with a comprehensive picture of the patient ’s performance and can be used to inform and monitor rehabilitation and recovery OBJECTIVES To identify a battery of tests that predicts safe and unsafe performance on an on-road assessment of driving . DESIGN Prospect i ve cohort study . SETTING University laboratory assessment and an on-road driving test . PARTICIPANTS Two hundred seventy community-living adults aged 70 to 88 recruited through the electoral roll . MEASUREMENTS Performance on a battery of multidisciplinary tests and on a st and ardized measure of on-road driving performance . RESULTS A combination of three tests from the vision , cognitive , and motor domains , including motion sensitivity , color choice reaction time , postural sway on a compliant foam rubber surface , and a self-reported measure of driving exposure , was able to classify participants into safe and unsafe driver groups with sensitivity of 91 % and specificity of 70 % . CONCLUSION In a sample of licensed older drivers , a short battery of tests and a self-reported measure of driving exposure were able to accurately predict driving safety Background Female athletes are at significantly greater risk of anterior cruciate ligament ( ACL ) injury than male athletes in the same high-risk sports . Decreased trunk ( core ) neuromuscular control may compromise dynamic knee stability . Hypotheses ( 1 ) Increased trunk displacement after sudden force release would be associated with increased knee injury risk ; ( 2 ) coronal ( lateral ) , not sagittal , plane displacement would be the strongest predictor of knee ligament injury ; ( 3 ) logistic regression of factors related to core stability would accurately predict knee , ligament , and ACL injury risk ; and ( 4 ) the predictive value of these models would differ between genders . Study Design Cohort study ( prognosis ) ; Level of evidence , 2 . Methods In this study , 277 collegiate athletes ( 140 female and 137 male ) were prospect ively tested for trunk displacement after a sudden force release . Analysis of variance and multivariate logistic regression identified predictors of risk in athletes who sustained knee injury . Results Twenty-five athletes ( 11 female and 14 male ) sustained knee injuries over a 3-year period . Trunk displacement was greater in athletes with knee , ligament , and ACL injuries than in uninjured athletes ( P < .05 ) . Lateral displacement was the strongest predictor of ligament injury ( P = .009 ) . A logistic regression model , consisting of trunk displacements , proprioception , and history of low back pain , predicted knee ligament injury with 91 % sensitivity and 68 % specificity ( P = .001 ) . This model predicted knee , ligament , and ACL injury risk in female athletes with 84 % , 89 % , and 91 % accuracy , but only history of low back pain was a significant predictor of knee ligament injury risk in male athletes . Conclusions Factors related to core stability predicted risk of athletic knee , ligament , and ACL injuries with high sensitivity and moderate specificity in female , but not male , athletes 1 . The purpose of these experiments was to determine the accuracy with which human subjects could discriminate proprioceptive ( nonretinotopic ) targets during movement . The targets were located at either a specified angle in joint space , or a specified angular distance from an initial joint angle . 2 . In these experiments the right elbows of normal human subjects were passively extended from either predictable or unpredictable starting angles . The subjects were instructed to open the right h and to indicate that the elbow was passing through a target joint angle or a target angular distance . The subjects were not given visual information about the location of the elbow , so they had to rely on proprioceptive input to perform this task . The target ( criterion joint angle or angular distance ) was learned by the use of proprioception during 8 - 15 practice trials . 3 . Four experiments were conducted . In three experiments the target was located at a constant joint angle , and in the fourth experiment the target was located at a constant angular distance from the starting angle . The starting angle in all four experiments was pseudor and omly varied from trial to trial . 4 . On the basis of an analysis of constant errors , subjects were more accurate at discriminating angular distance than joint angle . The slope of the relationship between the starting position and the constant errors was dictated by the task requirement . 5 . In the distance discrimination experiment , when the starting angle was more flexed than the intermediate ( i.e. , central ) position , the subjects slightly overshot the target distance . Conversely , when the starting angle was more extended than the intermediate position , the subjects slightly undershot the target distance . 6 . In the joint angle discrimination experiments , the opposite results were obtained . Subjects overshot the target when the starting position of the elbow was more extended than the intermediate starting position , and they undershot the target when the starting position was more flexed than the intermediate starting position . The amplitude of these systematic errors increased when the subjects were unaware that the initial angle of their elbow was variable . 7 . It is concluded that , in kinesthetic tasks of this type , the discrimination of angular distance is more accurate than the discrimination of joint angle . We hypothesize that the nervous system extracts kinematic information related to both joint angle and angular distance from proprioceptors , and that the encoding and or decoding of angular distance is more accurate than that of absolute joint angle . ( ABSTRACT TRUNCATED AT 400 WORDS Proprioception was quantified in a group of patients who had documented complete ACL tears . Threshold to detection of passive change in position of the knee was measured using a well-described test . Eleven pa tients with arthroscopically proven complete ACL tears and findings consistent with moderate to severe anter olateral rotatory instability were tested . Testing was done within the 30 ° to 40 ° range of knee flexion . Patients were blindfolded and the injured and uninjured knees were tested in r and om sequence so that the normal knee could serve as an internal control . Testing was also done in a blind manner , i.e. , the examiner did not know which knee had been injured . An age- matched control group underwent identical testing . Po tentially significant variables such as age , time from injury , and degree of rehabilitation as measured by thigh circumference and isokinetic testing of the knee were included in a multivariate analysis . Control subjects demonstrated virtually identical threshold values between their two knees , the mean variation being less than 2 % . The test group , however , showed a significantly higher mean threshold value for the injured versus the noninjured knee ( P < 0.01 ) , the mean variation being over 25 % . Multivariate analysis demonstrated that changes recorded in the propriocep tion of the injured knee were attributable to the loss of the ACL rather than to other variables . Patients who have complete ACL tears and moderate to severe rotatory instability may also experience a decline in proprioceptive function of their knee 1 . Recent studies have shown that the CNS uses proprioceptive information to coordinate multijoint movement sequences ; proprioceptive input related to the kinematics of one joint rotation in a movement sequence can be used to trigger a subsequent joint rotation . In this paper we adopt a broad definition of " proprioception , " which includes all somatosensory information related to joint posture and kinematics . This paper addresses how the CNS uses proprioceptive information related to the velocity and position of joints to coordinate multijoint movement sequences . 2 . Normal human subjects sat at an experimental apparatus and performed a movement sequence with the right arm without visual feedback . The apparatus passively rotated the right elbow horizontally in the extension direction with either a constant velocity trajectory or an unpredictable velocity trajectory . The subjects ' task was to open briskly the right h and when the elbow passed through a prescribed target position , similar to backh and throwing in the horizontal plane . The r and omization of elbow velocities and the absence of visual information was used to discourage subjects from using any information other than proprioceptive input to perform the task . 3 . Our results indicate that the CNS is able to extract the necessary kinematic information from proprioceptive input to trigger the h and opening at the correct elbow position . We estimated the minimal sensory conduction and processing delay to be 150 ms , and on the basis of this estimate , we predicted the expected performance with different degrees of reduced proprioceptive information . These predictions were compared with the subjects ' actual performances , revealing that the CNS was using proprioceptive input related to joint velocity in this motor task . To determine whether position information was also being used , we examined the subjects ' performances with unpredictable velocity trajectories . The results from experiments with unpredictable velocity trajectories indicate that the CNS extracts proprioceptive information related to both the velocity and the angular position of the joint to trigger the h and movement in this movement sequence . 4 . To determine the generality of proprioceptive triggering in movement sequences , we estimated the minimal movement duration with which proprioceptive information can be used as well as the amount of learning required to use proprioceptive input to perform the task . The temporal limits for proprioceptive processing in this movement task were established by determining the minimal movement time during which the task could be performed . ( ABSTRACT TRUNCATED AT 400 WORDS DESIGN Prospect i ve cohort study . SETTING Population -based cohort . PARTICIPANTS InCHIANTI ( " Invecchiare in Chianti " or aging in the Chianti area ) study participants ( N=960 ; age , 21 - 91 y , 51.8 % women ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES The Cumulative Somatosensory Impairment Index was derived from baseline performance on clinical tests of pressure sensitivity , vibration sensitivity , proprioception , and graphesthesia . Global postural control was assessed using Frailty and Injuries Cooperative Studies of Intervention Techniques ( FICSIT ) balance test , time to complete 5 repeated chair st and s , and fast walking speed , at baseline and at 3-year follow-up . RESULTS In participants without neurologic conditions ( n=799 ) , the Cumulative Somatosensory Impairment Index was significantly different in age groups classified by decades ( P<.001 ) . Compared with participants without prevalent conditions , the Cumulative Somatosensory Impairment Index was significantly higher in persons with diabetes ( P=.017 ) , peripheral arterial disease ( P=.006 ) , and a history of stroke ( P<.001 ) . In the overall population ( N=960 ) , in the fully adjusted multiple regression models , the Cumulative Somatosensory Impairment Index independently predicted deterioration in FICSIT scores ( P=.002 ) , time for 5 repeated chair st and s ( P<.001 ) , and fast gait speed ( P=.003 ) at 3-year follow-up . CONCLUSIONS The Cumulative Somatosensory Impairment Index is a valid measure that detects relevant group differences in lower limb somatosensory impairment and is an independent predictor of decline in postural control over 3 years OBJECTIVE To determine the effects of a sensory retraining protocol on sensation , postural control , and gait in acute stroke subjects . DESIGN R and omized controlled pilot trial . SETTING Inpatient rehabilitation hospital . PARTICIPANTS Twenty-one subjects with sensory deficits in the feet , undergoing rehabilitation for stroke . INTERVENTION Sensory retraining of the more affected lower limb versus relaxation ( sham intervention ) . MAIN OUTCOME MEASURES Light touch at the sole of the foot ( Semmes-Weinstein monofilaments ) , proprioception ( Distal Proprioception Test ) , postural control ( Berg Balance Scale ) , and gait ( timed , Iowa Level of Assistance Scale ) . RESULTS Significant improvements ( P<.05 ) over time were found in light touch at 3 points of the feet and in postural control , timed gait , and walking aid . No significant time effects were observed in proprioception or amount of assistance required to walk . No significant differences were detected between groups in any of the outcome variables , apart from light touch at the first metatarsal . The study had poor power ( 13 % ) to detect group effects due to the small sample size . CONCLUSIONS Results of this pilot study are unable to support or refute the routine use of sensory retraining of the lower limb for people during inpatient rehabilitation after stroke . Further research with a larger sample size is required |
11,868 | 31,817,943 | While the included publications had a moderate risk of bias score , which may inflate reported weight loss outcomes , the published data to date suggest that severely energy-restricted diets , delivered via diets of varying composition , effectively produce clinical ly relevant weight loss ( ≥10 % of initial body weight ) when used for 6 weeks or more in people with class III obesity | Severely energy-restricted diets are used in obesity management , but their efficacy in people with class III obesity ( body mass index ≥40 kg/m2 ) is uncertain .
The aims of this systematic review and meta- analysis were to determine the effectiveness and characteristics of severely energy-restricted diets in people with class III obesity . | OBJECTIVE : In epidemiological studies , weight loss is usually associated with increased mortality rate . Contrarily , among obese people , weight loss reduces other risk factors for disease and death . We hypothesised that this paradox could exist because weight is used as an implicit adiposity index . No study has considered the independent effects of weight loss and fat loss on mortality rate . We studied mortality rate as a function of weight loss and fat loss . DESIGN : Analysis of ‘ time to death ’ in two prospect i ve population -based cohort studies , the Tecumseh Community Health Study ( 1890 subjects ; 321 deaths within 16 y of follow-up ) and the Framingham Heart Study ( 2731 subjects ; 507 deaths within 8 y of follow-up ) , in which weight and fat ( via skinfolds ) loss were assessable . RESULTS : In both studies , regardless of the statistical approach , weight loss was associated with an increased , and fat loss with a decreased , mortality rate ( P<0.05 ) . Each st and ard deviation ( s.d . ) of weight loss ( 4.6 kg in Tecumseh , 6.7 kg in Framingham ) was estimated to increase the hazard rate by 29 % ( 95 % confidence interval CI ) , ( 14 % , 47 % , respectively ) and 39 % ( 95 % CI , 25 % , 54 % respectively ) , in the two sample s. Contrarily , each s.d . of fat loss ( 10.0 mm in Tecumseh , 4.8 mm in Framingham ) was estimated to reduce the hazard rate 15 % ( 95 % CI , 4 % , 25 % ) and 17 % ( 95 % CI , 8 % , 25 % ) in Tecumseh and Framingham , respectively . Generalisability of these results to severely ( that is , body mass index BMI ) ≥34 ) obese individuals is unclear . CONCLUSIONS : Among individuals that are not severely obese , weight loss is associated with increased mortality rate and fat loss with decreased mortality rate Binge eating disorder ( BED ) is associated with high levels of obesity and psychological suffering , but little is known about 1 ) the distribution of features of BED in the general population and 2 ) their consequences for weight development and psychological distress in young adulthood . We investigated the prevalence of features of BED and their association with body mass index ( BMI ) and psychological distress among men ( n = 2423 ) and women ( n = 2825 ) from the longitudinal community-based FinnTwin16 cohort ( born 1975 - 1979 ) . Seven eating-related cognitions and behaviors similar to the defining features of BED were extracted from the Eating Disorder Inventory-2 and were assessed at a mean age of 24 . BMI and psychological distress , measured with the General Health Question naire , were assessed at ages 24 and 34 . We assessed prevalence of the features and their association with BMI and psychological distress cross-sectionally and prospect ively . More than half of our participants reported at least one feature of BED ; clustering of several features in one individual was less common , particularly among men . The most frequently reported feature was ' stuffing oneself with food ' , whereas the least common was ' eating or drinking in secrecy ' . All individual features of BED and their clustering particularly were associated with higher BMI and more psychological distress cross-sectionally . Prospect ively , the clustering of features of BED predicted increase in psychological distress but not additional weight gain when baseline BMI was accounted for . In summary , although some features of BED were common , the clustering of several features in one individual was not . The features were cumulatively associated with BMI and psychological distress and predicted further increase in psychological distress over ten years of follow-up Aims : To compare effectiveness of a 1-year weight loss program in moderately and severely obese patients . Methods : The study sample included 311 obese patients participating in a weight loss program , which comprised a 12-week weight reduction phase ( low-calorie formula diet ) and a 40-week weight maintenance phase . Body weight and glucose and lipid values were determined at the beginning of the program as well as after the weight reduction and the weight maintenance phase . Participants were analyzed according to their BMI class at baseline ( 30 - 34.9 kg/m2 ; 35 - 39.9 kg/m2 ; 40 - 44.9 kg/m2 ; 45 - 49.9 kg/m2 ; ≥50 kg/m2 ) . Furthermore , moderately obese patients ( BMI < 40 kg/m2 ) were compared to severely obese participants ( BMI ≥ 40 kg/m2 ) . Results : Out of 311 participants , 217 individuals completed the program . Their mean baseline BMI was 41.8 ± 0.5 kg/m2 . Average weight loss was 17.9 ± 0.6 % , result ing in a BMI of 34.3 ± 0.4 kg/m2 after 1 year ( p < 0.001 ) . Overall weight loss was not significantly different in moderately and severely obese participants . Yet , severely obese participants achieved greater weight loss during the weight maintenance phase than moderately obese participants ( -3.1 ± 0.7 % vs. -1.2 ± 0.6 % ; p = 0.04 ) . Improvements in lipid profiles and glucose metabolism were found throughout all BMI classes . Conclusion : 1-year weight loss intervention improves body weight as well as lipid and glucose metabolism not only in moderately , but also in severely obese individuals Background Behavioral lifestyle interventions during pregnancy can prevent excessive gestational weight gain ( GWG ) in women with normal weight ; however , effective interventions to reduce GWG in ethnically diverse women with obesity are lacking . Objective A r and omized controlled trial was conducted to test whether a behavioral lifestyle intervention with partial meal replacement reduces GWG rate in Hispanic and non-Hispanic women with overweight or obesity relative to enhanced usual care . Design Participants ( n = 257 ) were recruited in San Luis Obispo , California , and Providence , Rhode Isl and , between November 2012 and May 2016 . Participants were pregnant ( mean ± SD : 13.6 ± 1.8 wk of gestation ) with overweight or obesity and had a mean age of 30.3 y ; 41.6 % of participants were Hispanic . Women were r and omly assigned within site and by ethnicity to enhanced usual care ( n = 128 ) or to a behavioral lifestyle intervention with partial meal replacement ( n = 129 ) . The primary outcome was GWG per week of observation . Secondary outcomes were proportions exceeding Institute of Medicine ( IOM ) guidelines for total GWG , changes in weight-control behaviors and cardiovascular disease risk factors , and incidence of pregnancy complications . Study retention was 99.6 % ( 256 of 257 ) . Results The intervention compared with usual care result ed in less mean ± SD weekly GWG ( 0.33 ± 0.25 compared with 0.39 ± 0.23 kg/wk ; P = 0.02 ) and total GWG ( 9.4 ± 6.9 compared with 11.2 ± 7.0 kg ; P = 0.03 ) and reduced the proportion of women who exceeded IOM guidelines for total GWG ( 41.1 % compared with 53.9 % ; P = 0.03 ) . No significant group × time × demographic subgroup ( ethnicity , BMI , age , parity , and income ) interactions were observed . Among intervention participants , greater meal replacement intake was related to reduced GWG rate ( β = -0.07 ; 95 % CI:-0.12 , -0.03 ; P = 0.002 ) . The intervention compared with usual care increased weight-control strategies ( P < 0.0001 ) and cognitive restraint ( P < 0.0001 ) and reduced triglycerides ( P = 0.03 ) . Conclusion Prenatal behavioral intervention with partial meal replacement significantly reduced GWG in Hispanic and non-Hispanic women with overweight or obesity . This trial was registered at www . clinical trials.gov as NCT01545934 Background We evaluated the effectiveness of a sequential diet regimen termed the obese preoperative diet ( OPOD ) in morbidly obese patients with and without type 2 diabetes mellitus ( T2DM ) scheduled for laparoscopic bariatric surgery . Methods Fifty patients ( body mass index 53.5 ± 8.4 kg/m2 ) scheduled for bariatric surgery , including 14 with T2DM , were prospect ively enrolled and followed the OPOD regimen : a very low-calorie ketogenic diet for 10 days , followed by a very low-calorie diet for 10 days , and then a low-calorie diet for 10 days . Patients were evaluated at baseline ( T0 ) and after 10 days ( T1 ) , 20 days ( T2 ) , and 30 days ( T3 ) . Results Body weight , body mass index , waist circumference , and neck circumference were significantly lower at T1 , T2 , and T3 than at T0 in the 48 patients who completed the OPOD . Two patients discontinued the OPOD after 4–7 days . In patients with T2DM , fasting plasma glucose levels decreased significantly , enabling reduction of diabetic medications . Plasma and urine ketone levels increased at T1 but were all < 1 mmol/L , and hunger decreased during the diet period . Conclusions OPOD , including 10 days of a VLCKD , was safe and effective in morbidly obese patients , and it seems to be promising in morbidly obese patients with and without T2DM scheduled for laparoscopic bariatric surgery Objective Attrition rates of up to 77 % have been reported in conservative weight-reduction programs for the treatment of obesity . In view of the cost of such programs to the health system , there is a need to identify the variables that predict premature discontinuation of treatment . Previous studies have focused mainly on somatic and sociodemographic parameters . The prospect i ve influence of psychological factors has not been systematic ally investigated to date . Methods A total of 164 patients ( 138 of whom were women ) with a mean age of 45 years and a mean body mass index of 39.57 participated in a 1-year outpatient weight-reduction program at the Charité – Universitätsmedizin Berlin University Hospital . The program included movement therapy , dietary advice , psychoeducational and behavioral interventions , relaxation procedures , and consultations with a specialist in internal medicine and a psychologist . Patients also underwent regular laboratory and psychological testing . The results were evaluated using a t-test , χ2-test , and logistic regression analysis . Results Seventy-one of the 164 patients ( 61 women , mean age = 43 years , mean body mass index = 39.53 ) withdrew before the end of the program ( attrition rate = 43.3 % ) . While there were no differences between the somatic and metabolic characteristics of those who withdrew and those who remained , the sociodemographic and psychological factors had some relevance . In particular , “ expectation of self-efficacy ” ( Fragebogen zu Selbstwirksamkeit , Optimismus und Pessimismus [ SWOP ] ) , “ not working , ” “ tiredness ” ( Berliner Stimmungsfragebogen [ BSF ] ) , “ pessimism ” ( SWOP ) and “ positive reframing ” ( Brief-COPE ) were found to play a role in whether participants subsequently dropped out of the treatment . “ Support coping ” ( Brief-COPE ) and “ older age ” prior to the start of treatment were identified as variables that promoted treatment adherence . Conclusion The results are discussed in light of previous findings and with regard to whether the modules of the weight-reduction program should be adapted Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies OBJECTIVE To estimate the effect of intentional weight loss on mortality in overweight individuals with diabetes . RESEARCH DESIGN AND METHODS We performed a prospect i ve analysis with a 12-year mortality follow-up ( 1959 - 1972 ) of 4,970 overweight individuals with diabetes , 40 - 64 years of age , who were enrolled in the American Cancer Society 's Cancer Prevention Study I. Rate ratios ( RRs ) were calculated , comparing overall death rates , and death from cardiovascular disease ( CVD ) or diabetes in individuals with and without reported intentional weight loss . RESULTS Intentional weight loss was reported by 34 % of the cohort . After adjustment for initial BMI , sociodemographic factors , health status , and physical activity , intentional weight loss was associated with a 25 % reduction in total mortality ( RR = 0.75 ; 95 % CI 0.67 - 0.84 ) , and a 28 % reduction in CVD and diabetes mortality ( RR = 0.72 ; 0.63 - 0.82 ) . Intentional weight loss of 20 - 29 lb was associated with the largest reductions in mortality ( approximately 33 % ) . Weight loss > 70 lb was associated with small increases in mortality CONCLUSIONS Intentional weight loss was associated with substantial reductions in mortality in this observational study of overweight individuals with diabetes BACKGROUND Effective primary care practice ( PCP ) treatments are needed for extreme obesity . The Louisiana Obese Subjects Study ( LOSS ) tested whether , with brief training , PCPs could effectively implement weight loss for individuals with a body mass index ( BMI ) ( calculated as weight in kilograms divided by height in meters squared ) of 40 to 60 . METHODS The LOSS , a 2-year ( July 5 , 2005 , through January 30 , 2008 ) r and omized , controlled , " pragmatic clinical trial " trained 7 PCPs and 1 research clinic in obesity management . Primary outcome measure was year-2 percentage change from baseline weight . Volunteers ( 597 ) were screened and r and omized to intensive medical intervention ( IMI ) ( n = 200 ) or usual care condition ( UCC ) ( n = 190 ) . The UCC group had instruction in an Internet weight management program . The IMI group recommendations included a 900-kcal liquid diet for 12 weeks or less , group behavioral counseling , structured diet , and choice of pharmacotherapy ( sibutramine hydrochloride , orlistat , or diethylpropion hydrochloride ) during months 3 to 7 and continued use of medications and maintenance strategies for months 8 to 24 . RESULTS The mean age of participants was 47 years ; 83 % were women , and 75 % were white . Retention rates were 51 % for the IMI group and 46 % for the UCC group ( P = .30 ) . After 2 years , the results were as follows : ( 1 ) among 390 r and omized participants , 31 % in the IMI group achieved a 5 % or more weight loss and 7 % achieved a 20 % weight loss or more , compared with 9 % and 1 % of those in the UCC group . ( 2 ) The mean + /- SEM baseline observation carried forward analysis showed a weight loss of -4.9 % + /- 0.8 % in IMI and -0.2 + /- 0.3 % in UCC . ( 3 ) Last observation carried forward analysis showed a weight loss of -8.3 % + /- 0.79 % for IMI , whereas UCC was -0.0 % + /- 0.4 % . ( 4 ) A total of 101 IMI completers lost -9.7 % + /- 1.3 % ( -12.7 + /- 1.7 kg ) , whereas 89 UCC completers lost -0.4 % + /- 0.7 % ( -0.5 + /- 0.9 kg ) ; ( P < .001 for all group differences ) . Many metabolic parameters improved . CONCLUSION Primary care practice s can initiate effective medical management for extreme obesity ; future efforts must target improving retention and weight loss maintenance . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00115063 We sought to evaluate the effect of weight loss on echocardiographic epicardial fat thickness , as index of visceral adiposity , and whether epicardial fat change after the weight loss can be proportionally different from overall body weight changes and related to cardiac parameters changes in severely obese subjects . This was an interventional study in 20 severely obese subjects ( 12 women , 8 men , BMI 45+/-5 kg/m(2 ) , 35+/-10 years ) who underwent 6-month very low calorie diet weight loss program . Baseline and after 6-month weight loss anthropometrics , echocardiographic epicardial fat thickness , left ventricular mass ( LVM ) , and diastolic function parameters were assessed . Subjects lost 20 % of original body weight , BMI reduced by 19 % of original BMI , waist circumference decreased by 23 % of initial waist circumference . Epicardial fat thickness decreased from 12.3+/-1.8 to 8.3+/-1 mm P<0.001 after the 6-month very low calorie diet , as -32 % of baseline epicardial fat thickness . LVM and diastolic function changes were better correlated with epicardial fat changes . We showed that significant weight loss can be associated with significant reduction in the epicardial fat thickness , marker of visceral adiposity in severely obese subjects . Epicardial fat decrease , therefore visceral fat decrease , can be proportionally higher than overall adiposity decrease . Epicardial fat changes are significantly associated with obesity-related cardiac morphological and functional changes during weight loss . Measurement of echocardiographic epicardial fat thickness may provide an additional tool in underst and ing the metabolic risk associated with variation in fat distribution BACKGROUND Very-low-energy diets ( VLEDs ) together with behavior therapy ( BT ) are widely used in the treatment of morbid obesity , but there is no evidence of their long-term effectiveness as compared with behavior therapy alone . METHODS Fifty-nine morbidly obese patients ( 25 men and 34 women ; mean weight , 132.8 + /- 20.7 kg ; mean age , 43.1 + /- 9.2 years ) were treated with combined therapy of VLED and BT or BT alone . No maintenance program was used . Eighty-seven percent of eligible patients were contacted 4.8 to 6.2 years after the program . RESULTS During treatment , 56 % of patients dropped out of the VLED + BT group and 28 % from the BT group ( P = .03 ) . High scores on the Symptom Checklist-90R before treatment predicted dropout from the VLED+BT group , but not from BT . At the end of therapy , mean weight change was -22.9 kg in the VLED+BT group and -8.9 kg in the BT group ( P < .001 ) . The overall weight change from pretreatment to the 5-year follow-up was greater in the VLED+BT group than in the BT group ( -16.9 kg vs -4.9 kg , respectively ; P = .03 ) . Men succeeded better in the VLED+BT group than in BT . Among the dropouts , the mean weight change from baseline was + 5.2 kg in the VLED+BT group and + 13.0 kg in the BT group . CONCLUSIONS Our data suggest that in the treatment of morbid obesity , VLED combined with BT may produce a better 5-year maintenance than BT alone , especially among men . A satisfactory weight loss can be achieved without a maintenance program Although it is generally agreed that both ketogenic and nonketogenic very low calorie diets promote weight reduction , there is no consensus on a preference of one diet over the other in regard to protein sparing . In the present study , we compared the effects of isocaloric ( 600 kcal/d ) and isonitrogenous ( 8 g nitrogen/d ) ketogenic ( low carbohydrate ) and nonketogenic diets on parameters of protein and amino acid metabolism , in 16 morbidly obese women maintained on these diets for 4 weeks while confined to a metabolic ward . Cumulative urinary nitrogen excretion ( g/4 wk ) was significantly ( P less than .01 ) greater ( 248 + /- 6 v 207 + /- 12 , mean + /- SEM , n = 8) , and cumulative nitrogen balance significantly ( P less than .02 ) more negative ( -50.4 + /- 4.4 v -18.8 + /- 5.7 ) , during treatment with the ketogenic than with the nonketogenic diet . Plasma leucine concentration ( mumol/L ) was significantly higher ( P less than .05 ) during treatment with the ketogenic than with the nonketogenic diet at day 14 ( 210 + /- 17 v 150 + /- 8) , but not at day 28 ( 174 + /- 9 v 148 + /- 8) . Whole-body rates of leucine oxidation ( mmol/h ) were significantly higher ( P less than .05 ) during treatment with the ketogenic than with the nonketogenic diet at day 14 ( 1.29 + /- 0.20 v 0.92 + /- 0.10 ) and at day 28 ( 1.00 + /- 0.16 v 0.75 + /- 0.10 ) . Conversely , proteolysis , as measured by leucine turnover rate and urinary excretion of 3-methylhistidine , was not significantly different between the diets . ( ABSTRACT TRUNCATED AT 250 WORDS We examined the dose‐response relationship between weight reduction and pain/functional improvement in persons with symptomatic knee osteoarthritis ( KOA ) participating in a community‐based weight loss program OBJECTIVE Evaluate the relationship between low social support ( SS ) and adherence to diet in a cardiovascular disease ( CVD ) lifestyle intervention trial . DESIGN Prospect i ve sub study . SETTING AND PARTICIPANTS Blood relatives/cohabitants of hospitalized cardiac patients in a r and omized controlled trial ( n=458 ; 66 % female , 35 % nonwhite , mean age 50 years ) . MAIN OUTCOME MEASURES Non-adherence to diet using MEDFICTS ( Meats , Eggs , Dairy , Fried foods , fat In baked goods , Convenience foods , fats added at the Table , and Snacks ) tool ; SS using the Enhancing Recovery in Coronary Heart Disease Patients Social Support Instrument . ANALYSIS Logistic regression models adjusted for confounders . RESULTS Significant predictors ( P<.05 ) of non-adherence to diet recommendations at 1 year included low SS , increased body mass index and waist size , lower physical activity , depression , pre-action stages of change , control group assignment , and being male . Those with low SS at baseline 2.7 greater odds of being non-adherent to diet at 1 year vs those with higher SS ( 95 % confidence interval=1.1 - 6.4 ) ; there was no interaction by group assignment . CONCLUSION AND IMPLICATION S Low SS at baseline was independently associated with non-adherence to diet at 1 year , suggesting that family members with low SS may be at heightened CVD risk as a result of poor dietary adherence Short sleep appears to be strongly associated with obesity and altered metabolic function , and sleep and growth hormone ( GH ) secretion seems interlinked . In obesity , both the GH-insulin-like-growth-factor-I ( GH-IGF-I ) axis and sleep have been reported to be abnormal , however , no studies have investigated sleep in relation to the GH-IGF-I axis and weight loss in obese subjects . In this study polygraphic sleep recordings , 24-h GH release , 24-h leptin levels , free-IGF-I , total-IGF-I , IGF-binding protein-3 ( IGFBP-3 ) , acid-labile subunit ( ALS ) , cortisol and insulin sensitivity were determined in six severely obese subjects ( BMI : 41+/-1 kg/m(2 ) , 32+/-2 years of age ) , cross-sectional at baseline , and longitudinal after a dramatically diet-induced weight loss ( 36+/-7 kg ) . Ten age- and gender-matched nonobese subjects served as controls . Sleep duration ( 360+/-17 vs. 448+/-15 min/night ; P<0.01 ) , 24-h GH ( 55+/-9 vs. 344+/-55 mU/l.24 h ; P<0.01 ) , free-IGF-I ( 2.3+/-0.42 vs. 5.7+/-1.2 microg/l ; P<0.01 ) , and total-IGF-I ( 186+/-21 vs. 301+/-18 microg/l ; P<0.01 ) were significantly decreased and 24-h leptin levels were increased ( 35+/-5 vs. 12+/-3 microg/l ; P<0.01 ) in obese subjects at pre-weight loss compared with nonobese subjects After diet-induced weight loss the differences in GH , free IGF-I , and leptin were no longer present between previously obese and nonobese subjects , whereas a significant difference in sleep duration and total IGF-I levels persisted . Rapid eye movement ( REM ) sleep , non-REM sleep , IGFBP-3 , ALS , and cortisol levels were similar in obese and nonobese subjects . Sleep duration , 24-h GH , and IGF-I levels were decreased and 24-h leptin levels were increased in obese subjects . We conclude that hyposomatotropism and hyperleptinemia in obesity are transient phenomena reversible with weight loss , whereas short sleep seems to persist after weight has been reduced dramatically BACKGROUND Type 2 diabetes is a chronic disorder that requires lifelong treatment . We aim ed to assess whether intensive weight management within routine primary care would achieve remission of type 2 diabetes . METHODS We did this open-label , cluster-r and omised trial ( DiRECT ) at 49 primary care practice s in Scotl and and the Tyneside region of Engl and . Practice s were r and omly assigned ( 1:1 ) , via a computer-generated list , to provide either a weight management programme ( intervention ) or best- practice care by guidelines ( control ) , with stratification for study site ( Tyneside or Scotl and ) and practice list size ( > 5700 or ≤5700 ) . Participants , carers , and research assistants who collected outcome data were aware of group allocation ; however , allocation was concealed from the study statistician . We recruited individuals aged 20 - 65 years who had been diagnosed with type 2 diabetes within the past 6 years , had a body-mass index of 27 - 45 kg/m2 , and were not receiving insulin . The intervention comprised withdrawal of antidiabetic and antihypertensive drugs , total diet replacement ( 825 - 853 kcal/day formula diet for 3 - 5 months ) , stepped food re introduction ( 2 - 8 weeks ) , and structured support for long-term weight loss maintenance . Co- primary outcomes were weight loss of 15 kg or more , and remission of diabetes , defined as glycated haemoglobin ( HbA1c ) of less than 6·5 % ( < 48 mmol/mol ) after at least 2 months off all antidiabetic medications , from baseline to 12 months . These outcomes were analysed hierarchically . This trial is registered with the IS RCT N registry , number 03267836 . FINDINGS Between July 25 , 2014 , and Aug 5 , 2017 , we recruited 306 individuals from 49 intervention ( n=23 ) and control ( n=26 ) general practice s ; 149 participants per group comprised the intention-to-treat population . At 12 months , we recorded weight loss of 15 kg or more in 36 ( 24 % ) participants in the intervention group and no participants in the control group ( p<0·0001 ) . Diabetes remission was achieved in 68 ( 46 % ) participants in the intervention group and six ( 4 % ) participants in the control group ( odds ratio 19·7 , 95 % CI 7·8 - 49·8 ; p<0·0001 ) . Remission varied with weight loss in the whole study population , with achievement in none of 76 participants who gained weight , six ( 7 % ) of 89 participants who maintained 0 - 5 kg weight loss , 19 ( 34 % ) of 56 participants with 5 - 10 kg loss , 16 ( 57 % ) of 28 participants with 10 - 15 kg loss , and 31 ( 86 % ) of 36 participants who lost 15 kg or more . Mean bodyweight fell by 10·0 kg ( SD 8·0 ) in the intervention group and 1·0 kg ( 3·7 ) in the control group ( adjusted difference -8·8 kg , 95 % CI -10·3 to -7·3 ; p<0·0001 ) . Quality of life , as measured by the EuroQol 5 Dimensions visual analogue scale , improved by 7·2 points ( SD 21·3 ) in the intervention group , and decreased by 2·9 points ( 15·5 ) in the control group ( adjusted difference 6·4 points , 95 % CI 2·5 - 10·3 ; p=0·0012 ) . Nine serious adverse events were reported by seven ( 4 % ) of 157 participants in the intervention group and two were reported by two ( 1 % ) participants in the control group . Two serious adverse events ( biliary colic and abdominal pain ) , occurring in the same participant , were deemed potentially related to the intervention . No serious adverse events led to withdrawal from the study . INTERPRETATION Our findings show that , at 12 months , almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs . Remission of type 2 diabetes is a practical target for primary care . FUNDING Diabetes UK The aim of this study was to determine the effect of weight loss induced by 6 weeks very-low-calorie-diet ( VLCD ) and behavioural intervention on pulmonary gas exchange during exercise in non-smoking morbid obese ( BMI > 40 kg/m2 ) otherwise healthy patients . Seven obese patients underwent a maximal bicycle ergometer test with continuous analysis of expired air and arterial blood sampling before and after a mean weight loss of 18 % ( 25.7 kg , range : 10 - 50 kg ) . Body mass index ( BMI ) decreased with weight loss from 46.6 ( 6.3 ) kg/m2 to 38.0 ( 4.7 ) kg/m2 ( P<0.01 ) . Oxygen consumption ( VO2 ) at low and submaximal exercise levels decreased after weight reduction , but the change was not statistically significant . The peak oxygen consumption related to body weight ( VO2/kg ) increased 22 % from the initial 16.2 ( 3.6 ) ml/min/kg to 19.8 ( 3.1 ) ml/min/kg ( P<0.05 ) . Decrease in VCO2 was significant at submaximal exercise level . Ventilatory equivalent for CO2 increased significantly after weight reduction ( P<0.05 ) . St and ing up and light exercise result ed in a significant increase in the mean arterial oxygen tension ( PaO2 ) ( P<0.05 ) and a significant decrease in the mean alveolar-arterial difference P(A-a)O2 ( P<0.05 ) when compared to supine values . The mean increase in PaO2 with weight loss was not significant . The peak P(A-a)O2 decreased significantly after weight reduction . In conclusion , weight reduction induced by VLCD and behavioural intervention without exercise therapy can improve gas exchange during exercise in morbid obesity . Increased wasted ventilation , and a tendency to alveolar hyperventilation , after weight loss may reflect a delay in the adaptation of regulation of breathing to rapid weight loss Background Safe and effective weight control strategies are needed to stem the current obesity epidemic . The objective of this one-year study was to document and compare the macronutrient and micronutrient levels in the foods chosen by women following two different weight reduction interventions . Methods Ninety-six generally healthy overweight or obese women ( ages 25–50 years ; BMI 25–35 kg/m2 ) were r and omized into a Traditional Food group ( TFG ) or a Meal Replacement Group ( MRG ) incorporating 1–2 meal replacement drinks or bars per day . Both groups had an energy-restricted goal of 5400 kJ/day . Dietary intake data was obtained using 3-Day Food records kept by the subjects at baseline , 6 months and one-year . For more uniform comparisons between groups , each diet intervention consisted of 18 small group sessions led by the same Registered Dietitian . Results Weight loss for the 73 % ( n = 70 ) completing this one-year study was not significantly different between the groups , but was significantly different ( p ≤ .05 ) within each group with a mean ( ± st and ard deviation ) weight loss of -6.1 ± 6.7 kg ( TFG , n = 35 ) vs -5.0 ± 4.9 kg ( MRG , n = 35 ) . Both groups had macronutrient ( Carbohydrate : Protein : Fat ) ratios that were within the ranges recommended ( 50:19:31 , TFG vs 55:16:29 , MRG ) . Their reported reduced energy intake was similar ( 5729 ± 1424 kJ , TFG vs 5993 ± 2016 kJ , MRG ) . There was an improved dietary intake pattern in both groups as indicated by decreased intake of saturated fat ( ≤ 10 % ) , cholesterol ( < 200 mg/day ) , and sodium ( < 2400 mg/day ) , with increased total servings/day of fruits and vegetables ( 4.0 ± 2.2 , TFG vs 4.6 ± 3.2 , MRG ) . However , the TFG had a significantly lower dietary intake of several vitamins and minerals compared to the MRG and was at greater risk for inadequate intake . Conclusion In this one-year university-based intervention , both dietitian-led groups successfully lost weight while improving overall dietary adequacy . The group incorporating fortified meal replacements tended to have a more adequate essential nutrient intake compared to the group following a more traditional food group diet . This study supports the need to incorporate fortified foods and /or dietary supplements while following an energy-restricted diet for weight loss BACKGROUND The DiRECT trial assessed remission of type 2 diabetes during a primary care-led weight-management programme . At 1 year , 68 ( 46 % ) of 149 intervention participants were in remission and 36 ( 24 % ) had achieved at least 15 kg weight loss . The aim of this 2-year analysis is to assess the durability of the intervention effect . METHODS DiRECT is an open-label , cluster-r and omised , controlled trial done at primary care practice s in the UK . Practice s were r and omly assigned ( 1:1 ) via a computer-generated list to provide an integrated structured weight-management programme ( intervention ) or best- practice care in accordance with guidelines ( control ) , with stratification for study site ( Tyneside or Scotl and ) and practice list size ( > 5700 or ≤5700 people ) . Allocation was concealed from the study statisticians ; participants , carers , and study research assistants were aware of allocation . We recruited individuals aged 20 - 65 years , with less than 6 years ' duration of type 2 diabetes , BMI 27 - 45 kg/m2 , and not receiving insulin between July 25 , 2014 , and Aug 5 , 2016 . The intervention consisted of withdrawal of antidiabetes and antihypertensive drugs , total diet replacement ( 825 - 853 kcal per day formula diet for 12 - 20 weeks ) , stepped food re introduction ( 2 - 8 weeks ) , and then structured support for weight-loss maintenance . The co primary outcomes , analysed hierarchically in the intention-to-treat population at 24 months , were weight loss of at least 15 kg , and remission of diabetes , defined as HbA1c less than 6·5 % ( 48 mmol/mol ) after withdrawal of antidiabetes drugs at baseline ( remission was determined independently at 12 and 24 months ) . The trial is registered with the IS RCT N registry , number 03267836 , and follow-up is ongoing . FINDINGS The intention-to-treat population consisted of 149 participants per group . At 24 months , 17 ( 11 % ) intervention participants and three ( 2 % ) control participants had weight loss of at least 15 kg ( adjusted odds ratio [ aOR ] 7·49 , 95 % CI 2·05 to 27·32 ; p=0·0023 ) and 53 ( 36 % ) intervention participants and five ( 3 % ) control participants had remission of diabetes ( aOR 25·82 , 8·25 to 80·84 ; p<0·0001 ) . The adjusted mean difference between the control and intervention groups in change in bodyweight was -5·4 kg ( 95 % CI -6·9 to -4·0 ; p<0·0001 ) and in HbA1c was -4·8 mmol/mol ( -8·3 to -1·4 [ -0·44 % ( -0·76 to -0·13 ) ] ; p=0·0063 ) , despite only 51 ( 40 % ) of 129 patients in the intervention group using anti-diabetes medication compared with 120 ( 84 % ) of 143 in the control group . In a post-hoc analysis of the whole study population , of those participants who maintained at least 10 kg weight loss ( 45 of 272 with data ) , 29 ( 64 % ) achieved remission ; 36 ( 24 % ) of 149 participants in the intervention group maintained at least 10 kg weight loss . Serious adverse events were similar to those reported at 12 months , but were fewer in the intervention group than in the control group in the second year of the study ( nine vs 22 ) . INTERPRETATION The DiRECT programme sustained remissions at 24 months for more than a third of people with type 2 diabetes . Sustained remission was linked to the extent of sustained weight loss . FUNDING Diabetes UK PURPOSE The purpose of this study is to compare the efficacy of a portion-controlled meal replacement diet ( PCD ) to a st and ard diet ( SD ) based on recommendations by the American Diabetes Association in achieving and maintaining weight loss among obese participants with type 2 diabetes . METHODS This study is a university-based , controlled clinical trial . Participants were 119 men and women with diabetes with a body mass index between 25 and 40 kg/m(2 ) , assigned r and omly to one of two 34-week , 75 % of predicted energy need diets ( portion controlled or st and ard , self-selected , food based ) and then followed by 1-year maintenance . RESULTS Using intention-to-treat analyses , weight loss at 34 weeks and weight maintenance at 86 weeks was significantly better on PCD versus SD . Approximately 40 % of the PCD participants lost > or = 5 % of their initial weight compared with 12 % of those on the SD . Significant improvements in biochemical and metabolic measures were observed at 34 weeks in both groups . The retention rate and self-reported ease of adherence in the PCD group were significantly higher throughout the study . CONCLUSIONS A diet using portion-controlled meal replacements yielded significantly greater initial weight loss and less regain after 1 year of maintenance than a st and ard , self-selected , food-based diet . As PCDs may help obese patients with type 2 diabetes adhere to a weight control program , diabetes educators may consider recommending them as part of a comprehensive approach to weight control |
11,869 | 20,921,236 | Results : For secondary progressive MS , immunoablative therapy with autologous bone marrow/peripheral blood stem cell transplantation was associated with higher progression-free survival ( up to 3 years following treatment ) when using intermediate-intensity conditioning regimens compared with high-intensity conditioning regimens .
Conclusions : Patients with secondary progressive MS refractory to conventional medical treatment have longer progression-free survival following autologous stem cell transplantation with intermediate-intensity conditioning regimens than with high-intensity conditioning regimens | Background and objectives : The purpose of this systematic review was to evaluate the safety and efficacy of autologous hematopoietic cell transplantation in patients with progressive multiple sclerosis ( MS ) refractory to conventional medical treatment . | High-dose immunosuppressive therapy ( HDIT ) with autologous hematopoietic stem cell transplantation ( auto-HSCT ) is a new and promising approach to the treatment of multiple sclerosis ( MS ) patients because currently there are no effective treatment methods for this disease . In this article , we present results of a prospect i ve clinical study of efficacy of HDIT + auto-HSCT in MS patients . The following treatment strategies were employed in the study : " early , " " conventional , " and " salvage/late " transplantation . Fifty patients with various types of MS were included in this study . No toxic deaths were reported among 50 MS patients ; transplantation procedure was well-tolerated by the patients . The efficacy analysis was performed in 45 patients . Twenty-eight patients achieved an objective improvement of neurological symptoms , defined as at least 0.5-point decrease in the Exp and ed Disability Status Scale ( EDSS ) score as compared to the baseline and confirmed during 6 months , and 17 patients had disease stabilization ( steady EDSS level as compared to the baseline and confirmed during 6 months ) . The progression-free survival at 6 years after HDIT + auto-HSCT was 72 % . Magnetic resonance imaging data were available in 37 patients before transplantation showing disease activity in 43.3 % . No active , new , or enlarging lesions were registered in patients without disease progression . In conclusion , HDIT + auto-HSCT suggests positive results in management of patients with different types of MS . Identification of treatment strategies based on the level of disability , namely " early , " " conventional , " and " salvage/late " transplantation , appears to be feasible to improve treatment outcomes Based on the good results of experimental transplantation in animal models of multiple sclerosis and of other autoimmune diseases , we have treated 24 patients suffering from chronic progressive multiple sclerosis with high-dose chemotherapy ( BEAM regimen ) followed by autologous blood stem cell rescue and antithymocyte globulin . Blood stem cells were mobilised with cyclophosphamide at 4g/m2 and G- ( or GM- ) CSF . In 9 cases , additional CD34 + cell- selection of the graft was performed . Here we up date previously published results of this novel treatment , mainly with regard to clinical efficacy , as the median follow-up time has reached 40 months ( range , 21–51 ) . Infections were the principal toxicity early after the procedure , with death of a patient from aspergillosis 65 days post stem cell infusion . No serious late events occurred apart from a case of autoimmune thyroiditis that developed 11 months after transplant in a patient who had received a CD34 + cell-depleted graft . Mild and transient neurotoxicity was observed in 10 patients ( 42 % ) , most probably associated with fever and infections . Eighteen patients ( 18/23 ; 78 % ) responded to the treatment , i.e. , they were improved or stabilized , while five patients progressed , of which 4 had primary progressive disease . Of those improved or stabilised ( 18 ) , 9 patients have maintained stable condition whereas 9 developed relapses or they slowly resumed progression , although their disability scores have not gotten worse than they were before transplantation . The probability of progression-free survival ( compared to entry status ) at 3 years is 92 % for patients with secondary progressive disease and 39 % for the primary progressive type . CD34 + cell- selection did not seem to yield better results except for a delay in progression or in relapse after transplantation . These results appear better than those achieved by any other treatment of progressive multiple sclerosis , including beta-interferon , but they need to be confirmed by other open or controlled studies in view of the well-known difficulty of judging objective ly the effect of a treatment in patients with this disease There were 26 patients enrolled in a pilot study of high-dose immunosuppressive therapy ( HDIT ) for severe multiple sclerosis ( MS ) . Median baseline exp and ed disability status scale ( EDSS ) was 7.0 ( range , 5.0 - 8.0 ) . HDIT consisted of total body irradiation , cyclophosphamide , and antithymocyte globulin ( ATG ) and was followed by transplantation of autologous , granulocyte colony-stimulating factor (G-CSF)-mobilized CD34-selected stem cells . Regimen-related toxicities were mild . Because of bladder dysfunction , there were 8 infectious events of the lower urinary tract . One patient died from Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disorder ( PTLD ) associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen . An engraftment syndrome characterized by noninfectious fever with or without rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurologic symptoms . There were 2 significant adverse neurologic events that occurred , including a flare of MS during mobilization and an episode of irreversible neurologic deterioration after HDIT associated with fever . With a median follow-up of 24 ( range , 3 - 36 ) months , the Kaplan-Meier estimate of progression ( > /= 1.0 point EDSS ) at 3 years was 27 % . Of 12 patients who had oligoclonal b and s in the cerebrospinal fluid at baseline , 9 had persistence after HDIT . After HDIT , 4 patients developed new enhancing lesions on magnetic resonance imaging of the brain . The estimate of survival at 3 years was 91 % . Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified ; however , modifications of the initial approaches appear to reduce treatment risks . This was a heterogeneous high-risk group , and a phase 3 study is planned to fully assess efficacy Aggressive forms of multiple sclerosis ( MS ) represent a limited group of demyelinating diseases that rapidly progress to severe disability . Currently available therapies are poorly effective against these clinical entities . Recently , it has been demonstrated that intense immunosuppression followed by autologous haematopoietic stem cell transplantation ( AHSCT ) can affect the clinical course of individuals with severe MS and completely abrogate the inflammatory activity detected by MRI . We report the result of the Italian phase 2 GITMO study , a multicentre study in which 21 MS patients , who were rapidly deteriorating and not responding to the usual therapeutic strategies , were treated with this procedure . The clinical effect of the treatment is long lasting , with a striking abrogation of inflammation detected by MRI findings . These results support a role for intense immunosuppression followed by ASCT as treatment in rapidly evolving MS cases unresponsive to conventional therapies There were 21 patients with rapidly progressive multiple sclerosis ( MS ) treated on a phase 1/2 study of intense immune suppressive therapy and autologous hematopoietic stem cell ( HSC ) support with no 1-year mortality . Following transplantation , one patient had a confirmed acute attack of MS . Neurologic progression defined by the exp and ed disability status scale ( EDSS ) did not increase in disability by 1.0 or more steps in any of 9 patients with a pretransplantation EDSS of 6.0 or less . In 8 of 12 patients with high pretransplantation disability scores ( EDSS > 6.0 ) , progressive neurologic disability as defined by at least a 1-point increase in the EDSS has occurred and was manifested as gradual neurologic deterioration . There were 2 patients with a pretransplantation EDSS of 7.0 and 8.0 who died from complications of progressive disease at 13 and 18 months following treatment . Our experience suggests that intense immune suppression using a total body irradiation (TBI)-based regimen and hematopoietic stem cell transplantation ( HSCT ) are not effective for patients with progressive disease and high pretransplantation disability scores . Further studies are necessary to determine the role of intense immune suppressive therapy and HSC support in ambulatory patients with less accumulated disability and more inflammatory disease activity . Specifically , more patients and longer follow-up would be required in patients with an EDSS of 6.0 or less before drawing conclusions on this subgroup RATIONALE Phase I/II studies of autologous hematopoietic stem cell transplantation ( HSCT ) for multiple sclerosis ( MS ) were initiated , based on results of experimental transplantation in animal models of multiple sclerosis and clinical observations in patients treated concomitantly for malignant disease . PATIENTS Eighty-five patients with progressive MS were treated with autologous HSCT in 20 centers and reported to the autoimmune disease working party of the European Group for Blood and Marrow Transplantation ( EBMT ) . 52 ( 61 % ) were female , median age was 39 [ 20 - 58 ] years . The median interval from diagnosis to transplant was 7 [ 1 - 26 ] years . Patients suffered from severe disease with a median EDSS score of 6.5 [ 4.5 - 8.5 ] . Active disease prior to transplant was documented in 79 of 82 evaluable cases . RESULTS The stem cell source was bone marrow in 6 and peripheral blood in 79 , and stem cells were mobilized into peripheral blood using either cyclophosphamide combined with growth factors or growth factors alone . Three patients experienced transient neurological complications during the mobilization phase . The high dose regimen included combination chemotherapy , with or without anti-lymphocyte antibodies or , with or without , total body irradiation . The stem cell transplants were purged of lymphocytes in 52 patients . Median follow-up was 16 [ 3 - 59 ] months . There were 7 deaths , 5 due to toxicity and infectious complications , 2 with neurological deterioration . The risk of death of any cause at 3 years was 10 (+/-7)% ( 95 % confidence interval ) . Neurological deterioration during transplant was observed in 22 patients ; this was transient in most but was associated with MS progression in 6 patients . Neurological improvement by > or = 1 point in the EDSS score was seen in 18 ( 21 % ) patients . Confirmed progression-free survival was 74 (+/-12)% at 3 years being 66 (+/-23)% in patients with primary progressive MS but higher in patients with secondary progressive or relapsing-remitting MS , 78 (+/-13)% ; p = 0.59 . The probability of confirmed disease progression was 20 (+/-11)% . MRI data were available in 78 patients before transplant showing disease activity ( gadolinium enhancing , new or enlarging lesions ) in 33 % . Posttransplant MRI showed activity at any time in 5/61 ( 8 % ) evaluable cases . CONCLUSION Autologous HSCT suggest positive early results in the management of progressive MS and is feasible . These multicentre data suggest an association with significant mortality risks especially in some patient groups and are being utilised in the planning of future trials to reduce transplant related mortality AUTOIMMUNE DISEASES ( AD ) have a high prevalence and cause significant morbidity , health care expense , and mortality . The treatment of certain patients suffering from severe AD , refractory to conventional therapies , is unsatisfactory . Theoretical considerations , pre clinical animal models , and recently published clinical experience support the concept that the natural course of AD may be altered by intensive immunoablation and autologous stem cell transplantation ( ASCT ) . Eradication of autoreactive cells by the conditioning regimen and redistribution of an altered cellular and humoral immunological network , or thymic reeducation , are potential mechanisms for response . On this basis , ASCT is a promising experimental therapy for AD resistant to conventional treatments . We report the preliminary results of the Spanish experience in this field BACKGROUND AND OBJECTIVES Autologous stem cell transplantation ( ASCT ) is currently being evaluated as a therapy for patients with multiple sclerosis ( MS ) . We report the results of a phase II trial to evaluate feasibility and toxicity of CD34 + selected ASCT ( CD34+/ASCT ) and treatment results at one year of follow-up . DESIGN AND METHODS Patients with advanced secondary progressive ( SP ) or relapsing-remitting ( RR ) MS and confirmed worsening of the extended disability status scale ( EDSS ) in the previous year despite interferon or other immunotherapies were included . Peripheral blood stem cells were obtained by leukaphereses after mobilization with cyclophosphamide ( Cy ) and granulocyte colony-stimulating factor ( G-CSF ) . CD34 + selection was performed by means of an Isolex 300 or CliniMACS device . BCNU , Cy and antithymocyte globulin ( ATG ) were administered as conditioning regimen . RESULTS Fifteen patients ( 9 SPMS and 6 RRMS ) with a median EDSS of 6.0 ( 4.5 - 6.5 ) and a median of 3 ( 1 - 7 ) relapses in the previous year were included . Mobilization was unsuccessful in one patient . During mobilization , one patient had a transient neurologic deterioration . The main complication during ASCT were engraftment syndrome , which developed in three patients , CMV reactivation in one , and neurologic deterioration in two patients coinciding with high-fever related to ATG . Hematologic recovery was fast and complete in all cases . At 12 months , the EDSS had improved in three patients , worsened in two and remained stable in nine . Despite withdrawal of all immunosuppressive therapy only two patients had relapses . Magnetic resonance imaging showed disappearance of enhanced T1 lesions but oligoclonal b and s persisted in the cerebrospinal fluid of all evaluated cases . INTERPRETATION AND CONCLUSIONS CD34+/ASCT using BCNU , Cy and ATG as conditioning regimen has an acceptable toxicity and clearly reduces the progression of MS . Further follow-up is necessary to establish the real impact of this procedure on the long-term evolution of the disease Background During the last 15 years , high-dose chemotherapy with autologous hematopoietic stem cell transplantation ( HSCT ) has globally been performed for severe multiple sclerosis ( MS ) . Most patients have been in progressive phase with long disease duration . As a rule , treatment effect has been minor or moderate . Patients Since 2004 , we have performed HSCT in nine young patients with “ malignant ” relapsing – remitting MS . Criteria for treatment were short duration of disease ; very frequent , severe relapses ; recent improvement periods indicating potential for recovery after strong immunosuppression . Findings Median age at treatment was 27 ( range 9–34 ) years , MS duration 26 ( 4–100 ) months , and annualized relapse rate 10 ( 4–12 ) . Median Disability Status Scale ( extended disability status scale , EDSS ) at HSCT was 7.0 ( 3.5–8.0 ) . Median follow-up time April 2008 is 29 ( 23–47 ) months . Median EDSS improvement is 3.5 ( 1.0–7.0 ) , clearly surpassing most previous reports . One patient relapsed mildly with rapid recovery 7 months after HSCT . All patients are otherwise stable , median EDSS being 2.0 ( 0–6.0 ) . Before HSCT , 61 relapses occurred in 82 patient months ; during follow-up , one relapse in 289 patient months . Conclusion This small series of patients with “ malignant ” relapsing – remitting MS suggests HSCT to be an effective treatment option for this relatively rare disease course . It further suggests that future criteria for HSCT in MS should be close to the present ones |
11,870 | 28,806,588 | Javed noted that patients with ID were less likely to report side effects than patients without ID , especially in regard to cognitive adverse events [ 5 ] .
A recent Cochrane review concluded that side effects in the ID population are similar to the | The prevalence of epilepsy in adults with an intellectual disability ( ID ) is up to 20 times greater than in the general population [ 1 ] .
A recent survey of carers and professionals showed considerable concern over presence and impact of side effects from anti-epileptic drug ( AED ) treatment in people with ID ( in particular drowsiness , memory problems , depression ) [ 2 ] .
The term side effect typically relates to any secondary undesirable effect of a treatment or drug .
Physical , cognitive , behavioural or emotional side effects can cause significant impact on the quality of life of an individual .
Monitoring side effects in adults with ID and epilepsy is challenging due to the commonly co-existing occurrence of behaviour and communication disorders [ 3 ] .
The incidence of side effects is estimated to be as high as 58 % in the wider population receiving treatment ( i.e. adults with epilepsy without ID ) [ 4 ] . | This prospect i ve , open-label study evaluated the efficacy and safety of adjunctive levetiracetam ( LEV ) in Korean adults with uncontrolled partial epilepsy . Study patients had to have an average of at least 1 and not more than 14 partial seizures per month ( averaged over a 3-month historical baseline ) despite the use of one or two AEDs . Patients initially received LEV 1000 mg/day ( administered bid ) and could increase to 2000 mg/day after 2 weeks , and to 3000 mg/day after another 2 weeks , to obtain adequate seizure control . During the 12-week maintenance period , the dose of LEV could be increased or decreased once if seizure control was insufficient or tolerability warranted , respectively . Seizure count and adverse events ( AEs ) were recorded by patients . Global evaluation scale ( GES ) and quality of life ( QOLIE-31 ) were also evaluated . A total of 100 patients were enrolled and 92 patients completed the study . The median percent reduction in weekly seizure frequency over the treatment period was 43.2 % . The > or=50 % and > or=75 % responder rates were 45.4 % and 36.1 % , respectively . Seizure freedom throughout the 16-week treatment period was observed in 17 patients . On investigator 's GES , 81 patients were considered improved , with 41 patients showing marked improvement . Most QOLIE-31 scales improved significantly . Treatment-emergent AEs were reported in 59 patients . Three most common AEs were somnolence ( 36 % ) , dizziness ( 12 % ) , and headache ( 8 % ) . Adjunctive LEV therapy was effective and well-tolerated in Korean adults with refractory partial epilepsy CONTEXT Despite reported success , surgery for pharmacoresistant seizures is often seen as a last resort . Patients are typically referred for surgery after 20 years of seizures , often too late to avoid significant disability and premature death . OBJECTIVE We sought to determine whether surgery soon after failure of 2 antiepileptic drug ( AED ) trials is superior to continued medical management in controlling seizures and improving quality of life ( QOL ) . DESIGN , SETTING , AND PARTICIPANTS The Early R and omized Surgical Epilepsy Trial ( ERSET ) is a multicenter , controlled , parallel-group clinical trial performed at 16 US epilepsy surgery centers . The 38 participants ( 18 men and 20 women ; aged ≥12 years ) had mesial temporal lobe epilepsy ( MTLE ) and disabling seizues for no more than 2 consecutive years following adequate trials of 2 br and -name AEDs . Eligibility for anteromesial temporal resection ( AMTR ) was based on a st and ardized presurgical evaluation protocol . Participants were r and omized to continued AED treatment or AMTR 2003 - 2007 , and observed for 2 years . Planned enrollment was 200 , but the trial was halted prematurely due to slow accrual . INTERVENTION Receipt of continued AED treatment ( n = 23 ) or a st and ardized AMTR plus AED treatment ( n = 15 ) . In the medical group , 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery . MAIN OUTCOME MEASURES The primary outcome variable was freedom from disabling seizures during year 2 of follow-up . Secondary outcome variables were health-related QOL ( measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 [ QOLIE-89 ] overall T-score ) , cognitive function , and social adaptation . RESULTS Zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure free during year 2 of follow-up ( odds ratio = ∞ ; 95 % CI , 11.8 to ∞ ; P < .001 ) . In an intention-to-treat analysis , the mean improvement in QOLIE-89 overall T-score was higher in the surgical group than in the medical group but this difference was not statistically significant ( 12.6 vs 4.0 points ; treatment effect = 8.5 ; 95 % CI , -1.0 to 18.1 ; P = .08 ) . When data obtained after surgery from participants in the medical group were excluded , the effect of surgery on QOL was significant ( 12.8 vs 2.8 points ; treatment effect = 9.9 ; 95 % CI , 2.2 to 17.7 ; P = .01 ) . Memory decline ( assessed using the Rey Auditory Verbal Learning Test ) occurred in 4 participants ( 36 % ) after surgery , consistent with rates seen in the literature ; but the sample was too small to permit definitive conclusions about treatment group differences in cognitive outcomes . Adverse events included a transient neurologic deficit attributed to a magnetic resonance imaging-identified postoperative stroke in a participant who had surgery and 3 cases of status epilepticus in the medical group . CONCLUSIONS Among patients with newly intractable disabling MTLE , resective surgery plus AED treatment result ed in a lower probability of seizures during year 2 of follow-up than continued AED treatment alone . Given the premature termination of the trial , the results should be interpreted with appropriate caution . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00040326 The objective of this study was to compare the relative cost-effectiveness of two AEDs by a prospect i ve clinical audit . Patients starting on the adjunctive therapies lamotrigine and topiramate were recruited from the out-patient epilepsy clinics at Queen Square . Three interview were scheduled : baseline ; three months follow-up and six months from baseline . Of the 81 patients recruited , a total of 73 patients completed all three interviews . An intention to treat analysis was performed on the data . Seizure severity and frequency were assessed using the National Hospital Seizure Severity Scale . Side-effects , adverse events and reasons for stopping medication were also recorded . At the third interview , a total of 47/73 ( 64 % ) were still on the prescribed adjunctive drug . Outcome was assessed by two methods : the > 50 % seizure reduction cited in the literature and a more stringent assessment of patient ' satisfaction ' which we defined operationally on clinical criteria . Using this definition , a total of 10/73 ( 14 % ) patients were ' satisfied ' . The relative costs of starting patients on each of the two AEDs were calculated , both drug costs and the costs of adverse events ( the latter were defined as events requiring urgent medical attention ) . The costs of the two drugs were compared . A number of method ological issues relating to cost comparison are discussed . Outcome and pharmaco-economic studies need to assess more than reduction in number of seizures . They should take into account variables important for quality of life including side-effects and adverse events PURPOSE In this prospect i ve study , we compared the long-term cognitive and behavioral effects of lamotrigine ( LTG ) and carbamazepine ( CBZ ) in patients with newly diagnosed or untreated partial epilepsy . METHODS This was a multicenter , open-label , r and omized study that compared monotherapy with LTG and CBZ in newly diagnosed or untreated patients with partial epilepsy . We employed an 8-week titration period and a 40-week maintenance period . Neuropsychological tests , Symptom Check List-90 , and QOLIE-31 were assessed at baseline , 16 weeks , and 48 weeks after drug treatment . A group-by-time interaction was the primary outcome measure and was analyzed by use of the linear mixed model . RESULTS A total of 110 patients were eligible and 73 completed the 48-week study ( LTG , n=39 ; CBZ , n=34 ) . Among the cognitive tests , significant group-by-time interaction was identified only in phonemic fluency of Controlled Oral Word Association Task ( p=0.0032 ) and Stroop Color-Word Interference ( p=0.0283 ) , with a significant better performance for LTG group . All other neuropsychological tests included did not show significant group-by-time interactions . Among the subscales of Symptom Check List-90 , significant group-by-time interactions were identified in Obsessive-Compulsive ( p=0.0005 ) , Paranoid Ideation ( p=0.0454 ) , Global Severity Index ( p=0.0194 ) , and Positive Symptom Total ( p=0.0197 ) , with a significant improvement for CBZ group . QOLIE-31 did not show significant group-by-time interactions . CONCLUSION Our data suggest that epilepsy patients on LTG have better performance on phonemic fluency and the task of Stroop Color-Word Interference than do patients on CBZ , whereas patients on CBZ had more favorable behavioral effects on two subscales and two global scores of Symptom Check List-90 than did patients on LTG Twenty-four patients with refractory epilepsy on one or more antiepileptic drugs were given additional vigabatrin ( 1 g twice daily for six weeks , followed by 1.5 g twice daily for a further six weeks ) and matched placebo in a double blind , r and omised , crossover study . A battery of neuropsychological tests was administered at baseline and at weeks two , six and 12 of both treatment periods . No significant differences were found between vigabatrin and placebo at any time point for any of the objective tests of cognitive function . Patients , however , reported a greater degree of sedation after two and six weeks on vigabatrin than during the equivalent placebo phase ( p < 0.01 ) , although no such difference was apparent at 12 weeks . Follow up over a mean of 14.75 months in 12 responders , who continued on vigabatrin , revealed a significant improvement ( all p < 0.01 ) on each of three composite scales ( three psychomotor tests , four memory tests , three self rating scales ) compared with their scores during the double blind trial . Vigabatrin did not cause cognitive impairment either acutely or in the long term . Phased introduction , however , seems a prudent policy to allow tolerance to early subjective sedation Lamotrigine is a broad-spectrum antiepileptic drug that blocks sodium channels , thereby inhibiting the pre-synaptic release of excitatory neurotransmitters . The primary aim of the study was to evaluate lamotrigine add-on therapy and consecutive monotherapy in patients with epilepsy whose seizures were not controlled by carbamazepine or valproate . One hundred and twenty six epilepsy patients at 18 centres in Pol and were recruited into a lamotrigine substitution study . In all patients , existing seizures were poorly controlled with valproate ( n= 63 ) or carbamazepine ( n= 63 ) monotherapy . The study consisted of four phases : ( 1 ) a 4-week lamotrigine dose-escalation phase , ( 2 ) an 8-week lamotrigine add-on phase , ( 3 ) an 8-week carbamazepine/valproate withdrawal phase , and ( 4 ) an 8-week lamotrigine monotherapy phase . Of 126 patients recruited into the study , 107 ( 85 % ) completed dose-escalation and add-on therapy with lamotrigine and 85 ( 68 % ) completed lamotrigine monotherapy . Fifty percent of patients during add-on therapy and 53 % during lamotrigine monotherapy experienced at least 50 % reduction in total seizures ( responders ) compared to the pre- study period . Approximately 20 % of patients during add-on therapy and 27 % during lamotrigine monotherapy were seizure free . Total well-being was assessed using a Visual Analogue Scale with 62 % of patients during add-on therapy and 60 % in lamotrigine monotherapy reporting improvement in scores . Lamotrigine was generally well tolerated . Treatment was discontinued in 7 % because of adverse events . In conclusion , lamotrigine is an effective AED in add-on therapy and monotherapy , it is safe and well tolerated , and successful conversion from add-on to monotherapy can be achieved in many cases . An additive effect between lamotrigine and valproate was observed Several specific and general measures are available for the assessment of overall health related quality of life in epilepsy . Few of the commonly used measures provide utility weights for use in cost-utility analyses . This study compares four methods for measuring utility weights : time trade-off ( TTO ) , st and ard gamble ( SG ) , 15D , end the EuroQol visual analog scale . All patients aged 18 - 67 years with a diagnosis of epilepsy , who had been admitted to or attended the outpatient clinic at a large county hospital 1987 - 1994 , received a comprehensive question naire . From 397 respondents , 82 patients were r and omly selected . Most of the 57 patients completing the study generally had well-controlled epilepsy , but were still on anti-epileptic medication . Mean age was 44 years . Fourty-one percent were male and 59 % female . The result ing utility weights differed considerably between the measures , both with regard to central tendency and dispersion . Median utility scores : EuroQol visual analog scale 0.75 , 15D 0.90 , TTO 0.98 , SG 0.99 . There was a good association between the EuroQol rating scale and the 15D , and a moderate association between SG and TTO . These preference instruments measure different aspects of health-related quality of life and thus yield different results . Caution should be taken when interpreting cost-utility studies , as results will depend on the choice of utility instrument OBJECTIVES The goals of this study were to observe behavioral changes in patients receiving levetiracetam ( LEV ) , a newer antiepileptic drug ( AED ) , and to answer the question of whether LEV exerts a specific effect on impulse control and aggression . METHODS We asked 288 consecutive patients with epilepsy on LEV ( 90 % polytherapy , mean dose=2689 mg ) and 135 relatives whether LEV caused a positive or negative behavioral change . Forty-three patients on other AEDs served as a control group . Ratings were related to patient characteristics , efficacy , dose , drug load , bidirectional ratings of change in behavioral domains , and question naires on personality ( Fragebogens zur Persönlichkeit bei zerebralen Erkrankungen ) and impulsivity ( Barratt Impulsiveness Scale-11 ) . RESULTS LEV was rated as very effective by 40 % of the patients . In contrast to only 9 % of the controls , a considerable number of patients reported a behavioral change while taking LEV ( 12 % very negative , 25 % negative , 16 % positive , 6 % very positive ) . Negative ratings were due to loss of self-control , restlessness , sleep problems , and , most importantly , aggression . Positive ratings were due to increased energy , vigilance , and activation . Increases in psychomotor speed , concentration , and remote memory indicated subjectively experienced positive effects on cognition . The proxy reports indicated reliable self-reports . Reported change was not related to type of epilepsy , co-therapy , dose , drug load , or psychiatric history . Negative effects were , however , associated with poorer seizure control , mental retardation , indicators of an organic psychosyndrome , and nonplanning impulsiveness . CONCLUSION The results indicate that LEV exerts a dose-independent stimulating effect that can be positive or negative . Aggression is a prominent feature . Lack of efficacy , mental retardation , and presumably also pre-intake disposition ( organic psychosyndrome , impulsivity ) may be helpful in predicting whether additional activation under LEV will be positive or negative We examined the effects of adjunctive lacosamide ( LCM ) on mood and quality of life ( QOL ) in adult patients with partial-onset seizures in a prospect i ve , controlled , single-blind study . Patients in whom LCM was added to their AED regimen for clinical indications comprised the LCM group ( n=18 ) , while the control group ( n=32 ) comprised patients on ≥2 AEDs with anticipated stable dosing for the duration of the study . Profile of Mood States ( POMS ) and QOLIE-89 were used to assess mood and QOL at enrollment and 12 - 16weeks later . Adherence to LCM was measured electronically with the Medication Event Monitoring System ( MEMS ) and using a self-report measure . There were no significant between-group differences in age , AED load , side-effects ( A-B Neurotoxicity Scale ) , MoCA mental status , or seizure-related factors . LCM adherence ( measured by MEMS ) was 70.7 % . There was a significant decrease in negative mood states in the LCM group ( estimated marginal mean at baseline=49.4 , at follow-up=29.7 ; p=0.02 ) , after controlling for seizure freedom . Based on previously reported benchmarks , clinical ly significant change on the POMS occurred in 7 ( 38 % ) LCM patients . The effect of LCM on the overall QOL was not significant ( p=0.078 ) . Correlation between POMS Total Mood Distress and Emotional-Wellbeing on the QOLIE-89 was significant ( r=-0.783 ; p=0.01 ) . These results suggest that LCM may have a favorable impact on mood RATIONALE Achievement of maximum seizure control with preservation or even improvement of patient 's cognitive capabilities is the major aim of epilepsy therapy . EpiTrack is a brief screening tool for the tracking of cognitive side effects of antiepileptic drugs . Test selection was based on recent studies on the effects of topiramate on cognition and retrospective inspection of results from patients with antiepileptic drug ( AED ) side effects . METHODS The 15-minute screening tool comprises six subtests : the Trail-Making Test ( parts A and B ) , a test of response inhibition , digit span backward , written word fluency , and a maze test . These tests were st and ardized in 220 healthy subjects , 100 of whom were reevaluated after 5.3 months to obtain information on reliability and practice effects . Criterion validity was determined by correlation to other neuropsychological measures . For a first clinical evaluation , the impact of epilepsy ( seizures ) and medication on EpiTrack scores was evaluated cross-sectionally in 184 consecutive in patients with chronic epilepsy . RESULTS According to the normative data , we developed an easy scoring scheme assigning test scores on a 7-point scale . The EpiTrack is suitable for patients between 18 and 60 years of age . Age corrections were included for patients between 40 and 60 years . EpiTrack scores on subtests for both controls and patients were su bmi tted to principal component analysis . VARIMAX rotation yielded a two-factor solution ( verbal/visuo-spatial ) that accounted for 63.8 % of the total variance in controls . In the patient group , only one factor emerged accounting for 54.7 % of variance . EpiTrack correlates with global scores of attention ( r=0.85 ) and language ( r=0.67 ) ( P's<0.001 ) . At a cutoff score of 25 , only 2.7 % of the controls were classified as impaired , while impairment was indicated in 48.4 % of the patients . The score is sensitive to monthly frequency of complex partial seizures and to number of AEDs . It shows negative cognitive effects of valproate and topiramate given in mono/polytherapy . CONCLUSION EpiTrack is a promising 15-minute screening tool for the detection and tracking of cognitive side effects of AEDs and adverse effects of seizures in patients with epilepsy . Future application will show its value in prospect i ve follow-up studies on AED side effects We conducted a prospect i ve , observational study to verify the efficacy , tolerability and impact on quality of life , mood and global neurocognitive performances of oxcarbazepine monotherapy in patients with brain tumor-related epilepsy ( BTRE ) . Patients were followed for 12 months . We recruited 25 patients ( 11 females 14 males ; mean age 49.7 ) affected with BTRE ( 17 de novo patients and 7 in monotherapy with other antiepileptics ) and introduced oxcarbazepine monotherapy because of uncontrolled seizures and /or side effects . At first visit , patients underwent neurological examination , Qolie 31P V2 , EORTC QLQC30 , Zung self-depression rating scale ( ZSDRS ) and adverse events profile . A seizure diary was given to each patient . Follow-up duration was 1–12 months ( mean 7.1 months , 5 patients died and 10 dropped out ) . Totals of 16 patients underwent both chemotherapy and radiotherapy , 4 chemotherapy only , 1 radiotherapy only , and 4 did not undergo any systemic therapy . Mean dosage of oxcarbazepine was 1,230 mg/day ( min 600 , max 2,100 mg/day ) . McNemar ’s test showed a significant difference in seizure freedom rate ( P = 0.002 ) between baseline and final follow-up in the intent-to-treat population . Six patients ( 24 % ) had serious side effects and one patient ( 4 % ) mild . Logistic regression revealed that , in our study , chemotherapy and radiotherapy did not affect the efficacy of OXC in seizure outcome ( P = 0.658 ) . The test evaluation at final follow-up showed a significant improvement in ZSDRS ( P = 0.011 ) and no change over time . Oxcarbazepine seems to be efficacious in controlling seizures and in improving mood in patients with BTRE , but special caution should be taken when it is administered during radiotherapy The aim of this prospect i ve , multicenter , open-label study was to investigate the efficacy of levetiracetam ( LEV ) and determine its effects on cognitive and neuropsychological function . Sixty-nine patients were evaluated for effects of LEV on seizure control , cognitive ( Mini-Mental State Examination [ MMSE ] ) and neuropsychological ( Symptom Checklist-90 Revised [ SCL-90-R ] ) functions , and quality of life ( Quality of Life in Epilepsy--10 [ QOLIE-10 ] ) assessment s at 3 and 12 months of follow-up . Thirty-nine percent of patients achieved seizure freedom , and 68 % had a > or = 50 % seizure frequency reduction after 1 year of LEV ( 1235.5+/-392.7 mg/day ) . There were also significant improvements in mean MMSE score and in the recall and language items of MMSE . There were modest improvements in interpersonal sensitivity and paranoid ideation scales of the SCL-90-R , and improvements in cognition and medication effect items of the QOLIE-10 . The results demonstrate that LEV not only effectively reduces seizure frequency , but also possibly contributes to improvements in neuropsychological functions such as recall , language , interpersonal sensitivity , and paranoid ideation An open-label retrospective study was conducted to assess the effectiveness and tolerability of topiramate in children and adolescents with pervasive developmental disorders ( PDD ) . Topiramate is a novel antiepileptic drug approved as an adjunctive treatment for seizure disorders . A retrospective chart review was conducted in an outpatient clinic specialized in treating individuals with developmental disabilities , to identify all children and adolescents with PDD who received topiramate . Patients were included if concomitant medications remained unchanged . Treatment response was assessed using the Global Improvement item of the Clinical Global Impressions scale ( CGI-GI ) , based on a review of medical records and the Conners Parent Scale ( CPS ) , as completed by parents . Fifteen patients were identified ( 12 male , 3 female ; age = 14.7 + /- 3.3 years ) , including 11 patients with autistic disorder , 2 patients with Asperger 's disorder , and 2 patients with PDD not otherwise specified ( PDD , NOS ) . Eight patients ( 4 patients with autistic disorder , 2 patients with Asperger 's disorder , and 2 patients with PDD , NOS ) were judged to be responders , as defined by a score of 1 or 2 on the CGI-GI . Treatment duration was 25 + /- 16 weeks , and the mean dose was 235 + /- 88 mg . Differences between baseline and the end-of-trial period were observed in the following CPS subscales : conduct , hyperactivity , and inattention . No differences were noted in the psychosomatic , learning , and anxiety subscales . Three patients discontinued topiramate because of side effects , with 2 patients experiencing cognitive difficulties and 1 patient a skin rash . Topiramate may be beneficial for treating secondary symptoms of PDD , and prospect i ve openlabel studies and double-blind , placebo-controlled studies to assess its efficacy and safety are needed We conducted a prospect i ve , long-term audit of lamotrigine and topiramate as add-on treatment for refractory epilepsy . A total of 55 patients participated in the study . Five years after starting the drug 7/20 patients remained on lamotrigine and 13/35 on topiramate . The patients still on the study drugs showed an improvement in seizure frequency , with 5/7 patients being seizure free on lamotrigine and 4/13 on topiramate . Furthermore , we assessed quality of life using the quality of life assessment schedule and found a significant improvement for the patients still on the study drugs . These data suggest that about one third of the patients on lamotrigine or topiramate as add-on therapy stay on the drug in the long term . These patients are likely to benefit with respect to objective and subjective outcome measures OBJECTIVE To assess the course of sexual function in epilepsy patients treated with lamotrigine . MATERIAL AND METHODS This open study included 141 patients treated with lamotrigine for a period of 8 months : 79 patients initiated treatment with lamotrigine monotherapy , and 62 were switched to lamotrigine because of lack of efficacy or adverse events to a previous antiepileptic drug ( AED ) . Patients were assessed at baseline and after 4 and 8 months of treatment . In the baseline and final visits the Changes in Sexual Functioning Question naire ( CSFQ ) was applied . Analysis was performed in an intent-to-treat population . RESULTS In women who started treatment with lamotrigine , a significant improvement was observed , both in total CSFQ score ( increase of 5.39 + /- 6.95 points ; p < 0.05 ) , and in the five dimensions of the scale ( desire/frequency , desire/interest , pleasure , arousal/excitement and orgasm ) . In men , a significant improvement was only observed in the pleasure dimension . In the group of patients in whom a previous AED was substituted by lamotrigine , significant improvement was recorded in the dimensions of pleasure and orgasm in men and desire/frequency in women , whilst in women the desire/interest dimension showed a decrease . CONCLUSIONS In this observational study , an improvement in sexual dysfunction was observed in association with lamotrigine . This could have been the result of improvement of the epilepsy , changes in quality of life , elimination of side effects from other AEDs , or a mood-stabilizing effect of lamotrigine PURPOSE Antiepileptic drugs ( AEDs ) are frequently used for their beneficial psychoactive effects on affective disorders . We sought to demonstrate a psychoactive effect of gabapentin ( GBP ) when used as add-on AED therapy . METHODS Forty adult patients with partial epilepsy were studied in a prospect i ve , non-r and omized fashion with interviewer-rated and self-rated scales of mood and anxiety : the Cornell Dysthymia Rating Scale ( CDRS ) , Beck Depression Inventory ( BDI ) , and Hamilton Depression ( Ham-D ) and Anxiety ( Ham-A ) Scales . After completion of baseline mood and anxiety scales ( time 1 ) , 20 of the 40 patients were prescribed add-on GBP ( treated group ) . The remaining 20 patients served as a control group . Both groups were similar in age and sex distribution . Follow-up mood and anxiety scales were performed in all patients approximately 3 months later ( time 2 ) . The average GBP dose at time 2 was 1,615 mg/day . All patients were taking stable doses of one to four AEDs at baseline and throughout the study . Seizure frequency was monitored throughout . Statistical significance was assessed by analysis of variance ( ANOVA ) by using a two-factor repeated- measures model . RESULTS The GBP-treated group had a significant decrease in CDRS score over time compared with the control group ( p = 0.04 ) . No significant differences between the control and the treated groups were found for any of the remaining mood scales ( BDI , p = 0.58 ; Ham-D , p = 0.59 ; Ham-A , p = 0.93 ) . There was no significant difference or change in seizure frequency between groups . CONCLUSIONS GBP treatment is associated with mood improvement as measured by the CDRS . This improvement was not accounted for by seizure improvement This r and omized , double-blind , placebo-controlled UK trial evaluated the effect of topiramate as add-on therapy on seizure frequency , seizure severity , and quality of life in patients with epilepsy and intellectual disability . There were three phases : 4 weeks baseline , 18 weeks titration to 200 - 400 mg topiramate/day ( adults ) or 5 - 9 mg/kg/day ( children ) , 12 weeks maintenance . Recruitment was low ( 88/120 ) ; analyses were underpowered . Seizure frequency varied enormously ( median 17.7 , maximum 1706.2 ) . There was no significant difference in reduction in mean total seizure frequency or number of responders between the groups . Topiramate reduced seizure frequency by > 30 % from baseline ( placebo 1 % ) ; post hoc analyses showed a trend toward significance ( R ratio , P=0.052 ) . There were no significant differences between the groups with respect to mean seizure severity or other outcome measures . Topiramate was generally well tolerated ; body weight ( P=0.015 ) and systolic blood pressure ( P=0.043 ) were reduced . The study suggests that topiramate reduces seizure frequency in patients with epilepsy and intellectual disability without the added burden of behavior effects , and was potentially advantageous to physical well-being This study evaluated the effects of lamotrigine as adjunctive therapy for refractory epilepsy in patients with mental retardation . Patients with epilepsy and mental retardation having uncontrolled seizures despite treatment with other antiepileptic drugs were eligible ( n=67 ) . The open-label study comprised a Baseline Phase , an Escalation Phase during which lamotrigine was titrated to a target dose , an 8-week Maintenance Phase during which doses of lamotrigine and concomitant antiepileptic drugs were maintained , and a 12-week Optimization Phase during which doses of lamotrigine and other antiepileptic drugs could be adjusted . Almost half ( 44 % ) of patients experienced a 50 % reduction in seizure frequency during the Maintenance Phase after addition of lamotrigine ; 15 % of patients became seizure-free . A similar pattern of results was reported for the Optimization Phase . Investigator-rated clinical status was improved relative to baseline in 66 and 74 % of patients at the end of the Maintenance and Optimization Phases , respectively . Most patients experienced improvements in seizure frequency , duration , and intensity during the Maintenance Phase ( 62 to 72 % ) and the Optimization Phase ( 65 to 74 % ) . Many patients were rated as having improved social functioning during the Maintenance Phase ( 42 % ) and the Optimization Phase ( 46 % ) . The Aberrant Behavior Checklist score for lethargy and the mean Habilitative Improvement Scale score were improved at the ends of the Maintenance and Optimization Phases relative to baseline ( P < or = 0.04 ) . One limitation of this study is its open-label design , which limits the ability definitively to attribute the clinical improvements to lamotrigine . Adjunctive lamotrigine in patients with refractory epilepsy and mental retardation appears to decrease seizure frequency and improve behavior while permitting a reduction in dose of concomitant antiepileptic drugs PURPOSE There is relatively little known about the effects of new antiepileptic drugs ( AEDs ) on sleep . This study was done to evaluate the effect of levetiracetam ( LEV ) on subjective sleep quality and sleep architecture in patients with epilepsy , and the results were compared with the effects of carbamazepine-CR ( CBZ-CR ) . METHODS This is a longitudinal r and omized controlled trial using two different treatments , LEV ( 1000 mg/day ) or CBZ-CR ( 400mg/day ) . Thirty-one subjects ( 16 LEV and 15 CBZ-CR ) had partial epilepsy and were tested with an overnight polysomnography ( PSG ) with full 10 - 20 electrodes . Sleep question naires and National Hospital Seizure severity Scale ( NHS3 ) were evaluated . PSG and the question naires were repeated after 4 - 6 weeks of treatment . RESULTS In the LEV group , when treatment PSG findings were compared with baseline , there was a significant increase in sleep efficiency ( p=0.039 ) but no changes in subjective sleep parameters . In the CBZ-CR group , there was a significant increase in the percentage of slow wave sleep ( p=0.038 ) while other sleep parameters were not significantly changed after treatment . There were no significant differences in effects on sleep between the LEV and CBZ-CR groups . CONCLUSION LEV may increase sleep efficiency without major effects on sleep structure with an overall effect on sleep parameters comparable to CBZ-CR Drowsiness is a common complaint among patients with epilepsy taking antiepileptic drugs ( AEDs ) and may be of particular importance because of the potential effects on cognitive abilities . We used a novel EEG‐based measure ( the Awake Maintenance Task , AMT ) to determine objective ly whether patients on chronic , stable AED therapy had impaired ability to maintain wakefulness . Thirty patients receiving AEDs [ carbamazepine ( CBZ ) , phenytoin ( PHT ) , phenobarbital ( PB ) , valproate ( VPA ) ] were compared to 35 healthy controls , 12 seizure patients not taking AEDs , and 16 patients with multiple sclerosis . A structured EEG recording was conducted under controlled conditions , and subjects were tested to determine their ability to maintain wakefulness during a 6‐min unstimulated trial . Testing also included Digit Symbol , auditory reaction time , and subjective measures of fatigue or sleepiness [ Profile of Mood States ( POMS ) , Stanford Sleepiness Scale ( SSS ) ] . Patients receiving AEDs had a mean total drowsiness score of 101 s compared with ≤ 12 s for each of the three control groups ( p < 0.001 ) . One third of the AED‐treated patients had > 120 s of drowsiness , in contrast to only 1 of 63 controls ( p < 0.001 ) . Among patients receiving AEDs , objective EEG drowsiness did not correlate with AED levels or performance measures . Untreated seizure patients had significantly greater complaints of lack of vigor despite a near absence of objective drowsiness on the AMT . These results suggest that epilepsy patients receiving chronic AED therapy have impaired ability to maintain wakefulness . Patient self‐reports of AED‐related sleepiness may not accurately represent this problem OBJECTIVE To evaluate the efficacy and safety of adjunctive zonisamide ( ZNS ) therapy in Korean adults with uncontrolled partial epilepsy . METHODS Study patients had an average of at least one seizure per 4-week ( averaged over a 12-week historical baseline ) despite the use of one to three antiepileptic drugs . The starting dose of ZNS was 100mg/day , and was increased to 200mg/day after 2weeks . During the 12-week maintenance period , the dose of ZNS was adjusted to 200 - 400mg/day based on the physicians ' discretion . The global evaluation scale ( GES ) and quality of life ( QOLIE-31 ) were also evaluated . RESULTS A total of 121 patients were enrolled , of which 88 patients completed the study . The median percent reduction in weekly seizure frequency over the treatment period was 59.0 % . The ≥50 % and ≥75 % responder rates were 57.3 % and 38.5 % , respectively . Seizure freedom over the treatment period was observed in 25 patients , but seizure freedom throughout the 16-week treatment period was attained in only 16 patients . On investigator 's GES , 84 patients were considered improved , with 33 patients showing marked improvement . In QOLIE-31 scale , seizure worry improved significantly but emotional well-being deteriorated . Treatment-emergent adverse events ( AEs ) were reported in 80 patients . The most common AEs were dizziness ( 28.1 % ) , somnolence ( 24.0 % ) , anorexia ( 18.2 % ) , headache ( 14.0 % ) , nausea ( 13.2 % ) , and weight loss ( 10.7 % ) . Twenty-two patients discontinued the trial due to drug-related AEs . CONCLUSIONS Our results suggest that adjunctive ZNS therapy for the treatment of refractory partial epilepsy , though efficacious , is associated with significant tolerability problems INTRODUCTION Pregabalin efficacy and safety as an adjunctive treatment for partial seizures was evaluated using an open-label , flexible-dose . STUDY DESIGN In 98 adults with refractory partial epilepsy taking 1 - 3 anti-epileptic drugs with ≥2 seizures during an 8-week baseline period . METHODS Pregabalin was increased to ≤600 mg/day during a 9-week dose optimization period with dosage maintained for 12 additional weeks . Primary endpoint was the percentage change in partial seizure frequency between the 8-week baseline and 12-week observation period . RESULTS Pregabalin treatment was associated with a significant reduction in partial seizure frequency : median percent change in partial seizure frequency from baseline to 12 weeks was -33 % and -22 % in patients with a baseline seizure frequency of ≤3 and > 3 per 28 days , respectively . The 50 % and 75 % responder rates were 41.94 % ( 95 % CI : 31.91 - 51.96 ) and 30.11 % ( 95 % CI : 20.78 - 39.43 ) , respectively . Nineteen percent of subjects were seizure-free throughout the last 12 weeks . Pregabalin administration result ed in a significant reduction in anxiety ( mean reduction in Hospital Anxiety and Depression Scale scores of 1.68 units , 95 % CI : -2.60 to -0.76 ) . Most patients were much improved or very much improved on Patient Global Impression of Change ( 53.8 % ) and Clinical Global Impression of Change ( 53.8 % ) . The most frequently self-reported adverse events ( AEs ) were mild or moderate somnolence ( 20.4 % ) and dizziness ( 5.1 % ) with a low AE discontinuation rate ( 5.1 % ) . CONCLUSIONS The efficacy and side-effect profile of pregabalin were similar to previous pregabalin double-blind , controlled studies . Additionally , pregabalin , as an add-on treatment for partial epilepsy , exhibits significant anti-anxiety properties The aim of this study was to evaluate the efficacy and safety of gabapentin in patients with learning disabilities and resistant epilepsy , comparing the effects of gabapentin with lamotrigine on efficacy , behaviour and mood . An open-label , r and omized , parallel group , multicentre add-on study comparing gabapentin with lamotrigine in 109 patients with drug-resistant localization-related epilepsy and learning disabilities was conducted : 39 patients were r and omized to gabapentin and 44 to lamotrigine . The study population had a range of learning disabilities and severe partial epilepsy . The percentage of patients achieving a greater than or equal to 50 % reduction in seizure frequency on gabapentin was 50 % , ( mean reduction in seizures was 51 % ) . Compared to 48.6 % of lamotrigine patients , no statistically significant treatment differences could be identified . The safety profile of both drugs was consistent with that seen in previous clinical trials . Carer-rated visual analogue scales detected significant improvements ( P < 0.05 ) for the gabapentin-treated patients in seizure severity , attention , general health and sleeping pattern , while for lamotrigine seizure severity improved significantly . For learning disabled patients with resistant epilepsy , gabapentin and lamotrigine provide safe and effective treatment , with positive benefits on behaviour Background Epilepsy is a devastating disorder that impacts on patients ’ quality of life , irrespective of use of anti epileptic drugs ( AEDs ) . This study estimates the health-related quality of life ( HRQOL ) and its associated predictors among epilepsy patients receiving AEDs . Methods A total of 175 epilepsy patients already receiving AED for at least 3 months were r and omly selected and interviewed from mental clinics at Mulago and Butabika national referral hospitals in Ug and a between May - July 2011 . A HRQOL index , the primary outcome , was constructed using items from Quality Of Life in Epilepsy Inventory ( QOLIE-31 ) and the Hospital Anxiety and Depression Scale ( HADS ) question naires . The internal consistency and adequacy of these items was also computed using Cronbach 's alpha and Kaiser-Meyer-Olkin tests . Partial correlations were used to evaluate the contribution of the health dimensions ( mental , psychological , social , physical functioning and emotional well being ) and , multiple linear regressions to determine factors independently associated with HRQOL . Results Just about half of the respondents ( 54 % ) were males , and nearly two thirds ( 62 % ) had received AEDs for at least 12 months . The average age was 26.6 years ( SD = 11.1 ) . The overall HRQOL mean score was 58 ( SD = 13 ) on a scale of 0–100 . The average scores of different dimensions or subscales ranged from 41 ( physical ) to 65 ( psychological ) . At least three quarters ( 75 % ) of all subscales had good internal consistency and adequacy . The largest variations in the overall HRQOL were explained by social and mental functioning ; each accounting for about 30 % of the difference in the HRQOL but seizure control features explained a little ( 6 % ) variation . Factors negatively associated with HRQOL were poly-therapy ( -1.16 , p = 0.01 ) and frequency of seizures ( -2.29 , p = 0.00 ) . Other factors associated with overall HRQOL included drug side effects , sex , marital status and education . Duration on AEDs was not a significant predictor of HRQOL . Conclusion The HRQOL for epilepsy patients on AEDs is very low . The predictors of low HRQOL were socio factors ( marital status , education ) and drug side effects , frequency of seizure , and type of therapy OBJECTIVE : To assess the effect of different doses of gabapentin ( GBP ) on cognitive function in treated epileptic patients . METHODS : Twenty seven patients with refractory partial seizures commenced a double blind , dose ranging , placebo controlled , crossover study of adjuvant GBP . Each treatment phase lasted three months , during which the dose of GBP or matched placebo was increased stepwise at intervals of four weeks ( 1200 mg/day , 1800 mg/day , and 2400 mg/day in three daily doses ) . Psychomotor and memory testing was carried out at the end of each four week period , at which time the patient also completed subjective measures of cognition , fatigue , worry , temper , and dysphoria . A visual analogue scale was used to assess drowsiness and a question naire was employed to gauge the severity of side effects . RESULTS : In the 21 patients completing the study , GBP produced a significant reduction in median monthly seizure frequency from 7 to 4.3 ( P = 0.02 ) , the decrease being most pronounced for secondarily generalised seizures ( from 1.0 to 0.3 , P = 0.01 ) . Forty three per cent of patients reported a reduction in seizure frequency of at least 50 % throughout all GBP doses . Mean ( SD ) plasma concentrations of GBP at 1200 , 1800 , and 2400 mg/day were 4.7 ( 2.6 ) , 6.8 ( 3.8 ) , and 8.6 ( 3.3 ) mg/l respectively . The drug had no effect on composite psychomotor and memory scores ; nor was there alteration in any self assessment subscore . The mean drowsiness ( P = 0.03 ) score was higher during treatment with 2400 mg GBP daily compared with matched placebo . Composite psychomotor ( r = -0.47 , P < 0.01 ) , tiredness ( r = 0.42 , P < 0.01 ) , and side effect ( r = 0.61 , P < 0.001 ) scores correlated significantly with seizure frequency but not with GBP dose . CONCLUSION : GBP is a well tolerated and effective antiepileptic drug which had no measurable effect on cognition but did produce sedation at the highest dose . This study also supports the suggestion that seizures can cause cognitive impairment The aim of this study was to compare the effect of treatment with lamotrigine ( LTG ) or carbamazepine ( CBZ ) on health-related quality of life ( HRQOL ) and to demonstrate the use of the SEALS Inventory as a comparative tool in clinical trials . Two hundred and sixty patients with newly diagnosed epilepsy were r and omized to 48 weeks of treatment with LTG ( n = 131 ) or CBZ ( n = 129 ) . HRQOL was measured at baseline and weeks 4 , 12 , 24 , and 48 using the modified Side Effect and Life Satisfaction ( SEALS ) Inventory-a 38-item question naire divided into five subscales : Worry , Temper , Cognition , Dysphoria , and Tiredness . Overall , SEALS scores in the LTG group decreased ( improved ) significantly from baseline ( P = 0.001 ) . The LTG group had improvement in all five subscales over the 48 weeks of the study . CBZ patients had significantly worse SEALS scores than LTG patients at week 4 ( P < 0.038 ) . There was no significant change ( positive or negative ) in subsequent SEALS assessment s. Analysis of SEALS data by subscale showed that the the CBZ group experienced more cognitive side-effects in general and more general changes in energy levels and affect during the first 4 weeks of treatment . These changes may help explain the difference in study completion rate : LTG 65 % , CBZ 51 % ( P = 0.018 ) . LTG offers the patient with newly diagnosed epilepsy significant benefits of greater tolerability and better health-related quality of life compared with CBZ . The SEALS Inventory is an effective tool for use in clinical trials of AEDs ; it was a better predictor of trial completion than seizure counts , and used as a covariate enabled better detection of treatment effects . In general practice , the use of the SEALS Inventory to assess HRQOL has the potential to improve quality of care for people with epilepsy The objective of this study was to assess the psychiatric effects of the antiepileptic drug ( AED ) felbamate ( FBM ) in patients with epilepsy . FBM is a new AED with a novel putative ( antiglutaminergic ) mechanism . Older AEDs such as carbamazepine and valproate have psychotropic properties , but the psychiatric effects of FBM and other new antiglutamatergic AEDs remain to be determined . Thirty in patients with refractory epilepsy were openly tapered off all AEDs in conjunction with intensive presurgical monitoring prior to a two week r and omized double-blind parallel trial of FBM monotherapy versus placebo , followed by open FBM therapy . Psychopathology was rated with weekly psychiatric rating scales . Anxiety , depression and seizures increased significantly with AED discontinuation . Acute blind FBM monotherapy yielded antiepileptic and stimulant-like effects ( insomnia , anorexia , and anxiety ) , but failed to influence AED withdrawal-emergent psychopathology . Restarting original AEDs resolved such pathology in FBM drop outs . Chronic open FBM also had stimulant-like effects , with half of the patients displaying psychiatric deterioration and the other half modest improvement compared to baseline therapies . Baseline insomnia and anxiety may be markers for poorer psychiatric responses to chronic open FBM . FBM had stimulant-like effects , lacked anxiolytic effects , and failed to attenuate AED withdrawal-emergent psychopathology . Baseline insomnia or anxiety may predict poorer psychiatric responses to FBM . Further studies are required to assess whether the novel psychiatric effects observed with FBM also occur with other new antiglutamatergic AEDs OBJECTIVE To evaluate the efficacy , safety , and cognitive effects of initial vigabatrin monotherapy compared with initial carbamazepine monotherapy in patients with newly diagnosed epilepsy . DESIGN Open , r and omized , controlled design . Follow-up period of 12 months . SETTING University hospital with an epilepsy center . PATIENTS A total of 100 patients , aged 15 to 64 years , classified as suffering from partial seizures and /or generalized tonic-clonic seizures were r and omized to either vigabatrin or carbamazepine monotherapy . Fifty-nine patients with a single epileptic seizure and no antiepileptic drug treatment served as a control population for objective safety measures . OUTCOME MEASURES To evaluate the comparative efficacy and toxicity of vigabatrin and carbamazepine , the drug success rate ( ie , the proportion of patients continuing successful treatment with the r and omly assigned drug ) after 12 months of steady-state treatment was used . To evaluate the safety of the drugs in addition to reported side effects , visual evoked potential recordings and neuropsychological evaluation were performed during follow-up . RESULTS During the 12-month follow-up period , 60 % of patients receiving vigabatrin and carbamazepine were treated successfully . Vigabatrin caused fewer side effects that required discontinuation of therapy . However , vigabatrin had to be discontinuated more often owing to lack of efficacy , and fewer of the successfully treated patients receiving vigabatrin achieved total freedom from seizures . Vigabatrin had no detrimental effects on cognitive functions . Retrieval from both episodic and semantic memory and flexibility of mental processing improved significantly in patients successfully treated with vigabatrin . CONCLUSION Vigabatrin seems to be an effective and safe antiepileptic drug as primary monotherapy for epilepsy with fewer cognitive side effects than carbamazepine In this investigation , the effects of lamotrigine versus placebo on depressive symptoms in patients with epilepsy were prospect ively assessed . This investigation was a secondary analysis of a r and omized , double-blind , placebo-controlled , parallel-group study in which adult patients received adjunctive lamotrigine ( n=32 ) or placebo ( n=38 ) for a 7-week dose escalation phase , followed by a 12-week maintenance phase , for primary generalized tonic-clonic ( PGTC ) seizures . Mood symptoms were assessed with the Beck Depression Inventory , second edition ( BDI-II ) , the Profile of Mood States ( POMS ) , and the Cornell Dysthymia Rating Scale-Self-Report ( CDRS ) . Mean ( SD ) BDI-II scores at screening reflected mild depressive symptoms and were similar between groups ( lamotrigine 18.3 ( 12.1 ) , placebo 16.8 ( 12.0 ) ) . At the end of the maintenance phase , mean ( SD ) improvement from baseline was greater with lamotrigine than placebo with respect to BDI-II score ( lamotrigine 8.9 ( 7.6 ) , placebo 1.7 ( 8.5 ) , P=0.01 ) and POMS total score ( lamotrigine 32.0 ( 30.4 ) , placebo 6.5 ( 32.3 ) , P=0.03 ) and numerically greater with lamotrigine than placebo for CDRS score ( lamotrigine 7.3 ( 7.8 ) , placebo 4.1 ( 13.9 ) , P=0.50 ) . Among the subset of patients with at least mild depression ( BDI-II score10 ) , mean improvement from baseline was numerically , but not statistically significantly , greater with lamotrigine ( 11.5 , n=13 ) than placebo ( 3.1 , n=18 ) ( P=0.054 ) . Median percentage reductions in seizure frequency were significantly greater with lamotrigine than placebo during the escalation phase , the maintenance phase , and the escalation and maintenance phases combined for PGTC seizures and all generalized seizures . However , improvement in seizure frequency was not correlated with improvement in mood ( r=0.1 , P = ns ) . Compared with placebo , lamotrigine improved mood symptoms independently of seizure reduction in patients with generalized seizures . Lamotrigine may be useful in treating patients with epilepsy and comorbid depressive symptoms BACKGROUND AND PURPOSE Complaints about side-effects of antiepileptic drugs ( AEDs ) may be overlooked in clinical practice . We assessed the value and risks of an active intervention policy for reported complaints in a r and omized controlled pragmatic trial . METHODS This r and omized controlled pragmatic trial included 111 adults treated for epilepsy in seven general hospitals . They were considered well-managed by their treating physician , but reported moderate to severe complaints on a question naire ( SIDAED , assessing SIDe effects in AED treatment ) . The intervention was adjustment of AED treatment ( 53 patients ) , either reduction of dose or switch of AED , versus continuation of treatment unchanged ( 58 control patients ) during 7 months . Primary outcomes were quality of life ( Qolie-10 ) and complaints score . Secondary outcome measures were the occurrence of seizures or adverse events . RESULTS After 7 months , the relative risk ( RR ) for improvement in quality of life was 1.80 ( 1.04 - 3.12 ) for the intervention group compared to control and the RR of decrease in complaints was 1.34 ( 0.88 - 2.05 ) . In 58 % of patients r and omized to adjustment , the medication had indeed been changed . DISCUSSION In conclusion , despite a possible risk of seizure recurrence , adjustment of drug treatment in well-managed patients with epilepsy , who report considerable complaints , improves the quality of life Second generation antiepileptics lamotrigine ( LTG ) and tiagabine ( TGB ) were primarily licensed for adjunctive treatment of simple and complex partial seizures with/without secondary generalisation as similarly effective drugs . Reduction of seizures frequency is the most important index of drug efficacy , but overall therapeutic benefit estimated as a quality of life is nowadays the target goal of management . In this study efficacy and tolerability of LTG or TGB as short-term add-on treatment in patients with refractory complex partial seizures were assessed by the use of both physician-rated measures ( mean monthly seizure frequency , responders rate , adverse events , clinical biochemistry ) and patients perceived change in their own quality of life estimation ( descriptive scale and visual analogue scale-VAS ) . Comparable efficacy of LTG ( n-22 , 378 mg/day ) and TGB ( n-26 , 43 mg/g ) was assessed as 41 and 35 % of responders and above half of patients with noticeable improvement . 25 % of patients in both groups reported reduction of seizures severity in 4-points descriptive scale . Biochemistry values did not show clinical ly significant changes after treatment . 13 % of patients on LTG reported adverse events ( headache , asthenia , irritability , insomnia ) . This coefficient was greater for TGB-35 % ( asthenia , headache , sleepiness , vertigo ) . However , no case of discontinuation as a result of adverse events was reported for either of the tested drugs . Even if efficacy of LTG and TGB was comparable in objective measurements , only patients on LTG reported a significant quality of life improvement in VAS . This might be the consequence of more frequent adverse events and treatment schedule of TGB ( triple dosing/day ) . This trial confirmed that VAS might be used as an easy additional test in evaluation of antiepileptic drug for individual patient in everyday clinical practice We explored factors that may predispose patients to adverse mood effects during treatment with vigabatrin ( gamma-vinyl GABA ; VGB ) : mood disorders before VGB treatment , type of epilepsy , seizure type and seizure frequency , type and number of comedication , and VGB dose . The clinical relevance of such a study is that it may help identify circumstances in which VGB should be administered with caution . Seventy-three patients ( 40 males , 33 females ) , all with refractory epilepsies , who received VGB as add-on therapy , were assessed by the Amsterdamse Stemmingslyst ( ASL ) , a mood-rating scale , before the start of treatment , and demographic and clinical data were recorded . The patients were followed for 6 months after the start of VGB treatment . Treatment with VGB had to be discontinued in 38 patients ( 52 % of the total sample ) . Mood problems were the main reason for discontinuation in 9 ( 12.3 % of the total sample ) . In 6 other patients , mood problems were mentioned as the reason for discontinuing treatment , in combination with lack of drug efficacy . Development of adverse mood effects could not be predicted by a specific mood profile on the ASL . Before treatment , the " mood problems discontinuation group " did not show extreme scores for any assessed areas of mood and no significant differences from other patients were noted on the mood scales . Neither did clinical or demographic data show statistically confirmed specific characteristics for the mood problems discontinuation group , though the patients tended to use more antiepileptic drugs ( AEDs ) as cotherapy , to have a slightly lower daily dose of VGB , to be slightly older , and were mostly female . ( ABSTRACT TRUNCATED AT 250 WORDS We sought to examine the impact of depression upon antiepileptic drug ( AED ) adherence in patients with epilepsy . We administered the Center for Epidemiologic Studies Depression Scale ( CES-D ) , Neurological Disorders Depression Inventory for Epilepsy ( NDDI-E ) , Seizure Severity Question naire ( SSQ ) , and Quality of Life in Epilepsy-10 ( QOLIE-10 ) and measured AED adherence by utilizing the medication possession ratio ( MPR ) in adult patients with epilepsy identified through a pharmacy cl aims data base . From a sampling frame of over 10,000 patients identified in cl aims , 2750 were r and omly selected and contacted directly by mail to participate in the cross-sectional survey . A total of 465 eligible patients completed a survey . Survey data were combined with administrative cl aims data for analysis . We conducted a path analysis to assess the relationships between depression , adherence , seizure severity , and quality of life ( QOL ) . Patients with depression scored significantly worse on measures of seizure severity ( p=.003 ) , QOL ( p<.001 ) , and adherence ( p=.001 ) . On path analysis , depression and QOL and seizure severity and QOL were related , but only the NDDI-E scores had a significant relationship with medication adherence ( p=.001 ) . Depression as measured by the NDDI-E was correlated with an increased risk of AED nonadherence . Depression or seizure severity adversely impacted QOL . These results demonstrate yet another important reason to screen for depression in epilepsy OBJECTIVE In view of the conflicting results of cognitive and behavioral consequences of PB , the present study was planned to analyze its efficacy , serial neuropsychological functions and its impact on psychosocial functioning in adults with epilepsy while on phenobarbitone ( PB ) . METHODOLOGY This prospect i ve multi-centric study carried out across 4 centers in India included 75 adult patients of ≥18 years ( M : F=52:23 ; age : 27.3 ± 8.5 years ) with epilepsy who were prescribed phenobarbitone and underwent serial st and ardized neuropsychological assessment ( NIMHANS battery for adults ) at baseline , 1 month , 3 months , 6 months and 12 months . The demographic , seizure details and outcome measures were recorded . RESULTS Of the 75 patients , 63 had completed clinical and neuropsychological assessment , i.e. visit 1 ( baseline ) , visit 4 ( 6 months ) and visit 5 ( 12 months ) . There was no deterioration rather an improvement during the follow visits in all the neuropsychological functions . The results indicate that 16 neuropsychological variables changed significantly , viz . mental speed ( p<0.001 ) , sustained attention ( p<0.001 ) , focused attention ( p<0.002 ) , planning ( p<0.001 ) , concept formation ( p<0.05 ) , set shifting ( p<0.001 ) , verbal learning ( p<0.0001 ) , verbal memory ( p<0.0001 ) , visual memory ( p<0.0001 ) and intelligence ( p<0.001 ) . The scales measuring the outcome of psychosocial functioning significantly changed during follow up included happiness ( p<0.002 ) , Impact of Epilepsy on patient 's life ( p<0.02 ) , A-B Neuropsychological Assessment ( p<0.015 ) , HADS anxiety ( p<0.001 ) and emotional disorder ( p<0.006 ) . There was a significant reduction in seizure severity as measured by Liverpool Seizure Severity Scale ( p<0.002 ) and seizure freedom was maintained . CONCLUSIONS This study demonstrated that phenobarbitone is effective , well tolerated AED and do not have cognitive impairment over one year . There was variable but distinct improvement in cognition and psychosocial functioning , and effective seizure control could be one of the factor for it BACKGROUND Interictal depression is common in patients with epilepsy and it significantly impacts quality of life . Some studies indicate that levetiracetam ( LEV ) may have mood stabilizing properties . METHODS Twenty-five adults with uncontrolled partial seizures and concomitant depressive symptoms were treated with LEV . Patients were evaluated for depression and anxiety with several psychometric measures , including : Montgomery and Asberg Depression Rating Scale ( MADRS ) , Hamilton Depression Rating Scale ( HDRS ) , Zung Self-rating Scale for Depression ( Z-SDS ) , Hamilton Anxiety Rating Scale ( HARS ) , Zung Self-rating Scale for Anxiety ( Z-SAS ) . RESULTS Evaluations after 5 weeks and after 3 months of LEV treatment demonstrated significant improvement in depression and anxiety . CONCLUSIONS This uncontrolled study suggests that treatment with LEV may also improve depression and anxiety in patients with partial seizures . However , the sample of patients is limited and the possibility of a placebo effect can not be excluded . These findings must be considered preliminary and should be replicated under placebo-controlled conditions The Portl and Neurotoxicity Scale ( PNS ) is a brief patient-based survey of neurotoxicity complaints commonly encountered with the use of antiepileptic drugs ( AEDs ) . The authors present data on the validity of this scale , particularly when used in longitudinal studies . Participants included 55 healthy controls , 23 epilepsy patient controls , and 86 healthy volunteers who took various AEDs or placebos for 12 weeks as part of r and omized , double-blind studies of AED effects on cognitive abilities . Test-retest reliability in the control groups averaged .80 ( total score ) . Test-retest changes in the PNS were sensitive to AED usage in general ( p < .001 ) and to each of the five AEDs tested but not to placebo . Test-retest changes in the PNS were strongly correlated with several scales of the Profile of Mood States but only weakly correlated with objective cognitive test measures . The PNS has satisfactory psychometric properties and is sensitive to AED usage in test-retest studies Summary : The efficacy of an antiepileptic drug ( AED ) is determined at present by the drug‐elicited reduction in seizure frequency . Reduction of seizure frequency as the sole measure of efficacy does not account for treatment‐induced reductions in seizure severity and positive psychological effects experienced by the patient . A clinical trial was undertaken in which seizure frequency was the primary and seizure severity and psychological well‐being were the secondary measures of efficacy . Psychological assessment and seizure frequency were monitored in patients whose epilepsy was treated with lamotrigine ( LTG ) or placebo . The results indicate that LTG is an effective AED , causing reductions in seizure frequency and severity and improvements in mood and mastery . In addition , the study demonstrated that the use of seizure severity scales , especially the Ictal subscale , may enhance the sensitivity of assessment of trials of AED treatments OBJECTIVES To evaluate the effects of adjunctive pregabalin 300 mg/day versus placebo on polysomnographic ( PSG ) variables in patients with well controlled partial seizures and subjectively reported sleep disturbance . METHODS An exploratory , 4-week , double-blind , r and omized study in patients with well controlled partial seizures on AED monotherapy and subjective sleep disturbance over the previous 6 months . Mean changes from baseline to endpoint in PSG and subjective sleep variables ( MOS Sleep Scale , Groningen Sleep Question naire ) in patients on adjunctive pregabalin 300 mg/day ( n=8 ) were compared with patients on placebo ( n=7 ) . RESULTS Baseline PSGs showed sleep fragmentation . Mean sleep efficiency improved significantly in both treatment groups in the mean baseline to endpoint change ; there was no significant between-group difference . Pregabalin treatment was associated with a significant reduction in number of awakenings ( p = 0.02 ) , and improvement in wake time after sleep onset approached significance ( p = 0.055 ) , suggesting improvement in sleep continuity that was not observed in the placebo group . Pregabalin was also associated with significant improvements in the MOS sleep disturbance and sleep quantity subscales compared with placebo ( p < or = 0.03 ) . There were no changes in self-reported seizure control . CONCLUSIONS This exploratory pilot study suggests that pregabalin may improve sleep continuity in patients with clinical ly relevant sleep disturbance . The effect on disturbed sleep appears independent of seizure control . The effects of pregabalin on disturbed sleep and seizures and their interrelationships warrant further study Summary : The need for new antiepileptic drugs ( AEDs ) and more sensitive methods of assessing their efficacy is well recognized . This study was design ed to evaluate the efficacy and safety of lamotrigine ( LTG ) , a potential new AED and to develop and test new outcome measures . A health‐related quality of life ( HRQL ) model was developed which contains previously vali date d measures of anxiety , depression , happiness , overall mood , self‐esteem , and mastery and a specifically design ed seizure severity scale with patient‐ and caregiver‐based components . This HRQL model was used in a r and omized , placebo‐controlled , double‐blind , cross‐over study of LTG in 81 patients with refractory partial seizures . Seizure frequency was the primary measure and seizure severity and the HRQL were secondary measures of efficacy . The reduction in seizure frequency with LTG , relative to placebo , was 29.7 % [ 95 % confidence interval ( CI ) 17.8 % , 39.9 % ] for total seizure count , 33.4 % ( 95 % CI 14.8 % , 47.9 % ) for complex partial seizures ( CPS ) and 20.3 % ( 95 % CI 0.3 % , 36.2 % ) for secondarily generalized tonic‐clonic seizures ( GTCS ) . However , although 41 patients elected to continue with LTG , only 11 experienced at least 50 % reduction in total seizures , indicating that other factors influenced their decision . The score with LTG , relative to placebo , was significantly lower for the ictal ( p = 0.017 ) and caregivers ( p = 0.035 ) subscales of the seizure severity scale and significantly higher for happiness ( p = 0.003 ) and mastery ( p = 0.003 ) . Simple correlation and multiple‐regression analyses indicate that the effects on seizure frequency , seizure severity , and psychological variables appear to be independent of each other . This study indicates that LTG is effective in reducing seizure frequency and has additional favorable effects on seizure severity , mood , and perceived internal control . Some of the scales used indicate the potential of secondary measures of efficacy to enhance the sensitivity of trials of new AEDs The development and st and ardisation of an inventory for measuring anti-epileptic drug effects on cognition and affect is described . The Side Effect and Life Satisfaction inventory ( SEALS ) was derived from symptoms and side-effects reported by a patient population . It was administered to 45 patients on two occasions and test-retest reliability was demonstrated . It was administered to 923 patients with epilepsy . An underlying factor structure was produced by principal components analysis , consisting of five sub-scales which were stable when data from males and females were analysed separately or together . Validity was evaluated by comparing inventory scores of patients undergoing a number of treatment trials to show that the inventory was sensitive to treatment differences when other variables were controlled . Patients taking two or more anti-epileptic drugs had poorer SEALS scores than those taking a single drug . Patients taking vigabatrin and one other AED had poorer scores than those taking lamotrigine ( LTG ) and one other AED . A comparison of changes from baseline to week 4 of a double blind comparison of carbamazepine ( CBZ ) and LTG showed significantly greater improvement in SEALS scores for patients taking LTG , and significantly poorer scores in those patients taking CBZ who dropped out of the study , than in those who continued . It is concluded that SEALS is a valid and reliable tool for use in anti-epileptic drug trials AIM To evaluate the behavioral effects of lamotrigine as add-on therapy in treatment-resistant epilepsy . METHODS An open , prospect i ve , long-term study of lamotrigine as adjuvant therapy was performed in 56 patients with drug-resistant epilepsy ( female/male ratio 35/21 , age range 16 - 51 years ) . All the patients kept seizure diaries , and electroencephalograms were recorded at baseline and during 24 months of the treatment . Quality of life question naire , Hamilton depression scale ( HMD ) , Beck depression scale ( BDI ) , and Hamilton anxiety scale ( HMA ) were used before and during lamotrigine therapy . Comparative assessment s were made in an age- and sex-matched control group treated with other antiepileptic drugs . RESULTS Overall , seizure control was improved in 55.3 % of the patients , remained unchanged in 39.3 % , and deteriorated in 5.4 % . Improvement in some quality of life measures occurred in 50 % of the patients . The HMD subscales and BDI scale showed significant improvement in lamotrigine treated patients compared to the control group ( ANOVA , p < 0.01 ) . Negative behavioral effects occurred in 10.7 % of the patients . CONCLUSION Lamotrigine demonstrated significant antiepileptic long-term efficacy , and its positive effects on the mood and quality of life , which surpassed the negative behavioral effects , and contributed highly to the favorable treatment outcome OBJECTIVE Whereas the efficacy of the newer antiepileptic drugs ( AEDs ) is well established , there remain questions regarding their cognitive side effects . Therefore , we performed a comparative open r and omized trial with TPM and TGB as add-on therapy , with particular consideration of cognition , mood , and health-related quality of life ( HRQOL ) . METHODS Forty-one patients with refractory epilepsy were r and omly assigned to one of the two treatment groups ( TPM vs TGB ) and received neuropsychological testing at baseline ( T1 ) , after titration ( 3 months , T2 ) , and during the maintenance phase ( another 3 months , T3 ) . Tests included measures of intelligence , attention , working memory , episodic memory , language , and self-report question naires regarding mood and HRQOL . Twenty patients ( 8 TPM , 12 TGB ) discontinued the trial for different reasons ( no group difference ) . RESULTS Seizure outcome ( intention-to-treat analysis ) was comparably good in both groups ( 8.1 % seizure free , 29.7 % seizure reduction>50 % ) . From baseline to after the titration paired sample t tests revealed significant deterioration in verbal fluency , language comprehension , working memory , and visual block tapping under TPM and a deterioration in verbal memory ( delayed free recall ) in the TGB group . These functions remained stable in the maintenance phase . Self-report measures initially indicated concerns about AED side effects in both groups and concerns about worse cognitive functioning and depression under TPM . In the maintenance phase the TGB group reported feeling a lack of energy , whereas patients on TPM demonstrated improvement on all QOLIE scales on a descriptive level . CONCLUSION This study demonstrates the comparable efficacy of TPM and TGB . Consistent with previous reports , TPM but not TGB appears to be associated with persistent negative cognitive side effects on frontal lobe-associated functions , the degree of which may be estimated by the fact that this effect was observed with a very small sample size . In contrast , in patients taking TPM , initially negatively affected HRQOL returns to baseline in the long run on a descriptive level . The latter finding may be interpreted in accordance with the observation that objective performance and subjective self-report under TPM can be dissociated This study prospect ively examined whether continued add-on treatment with oxcarbazepine ( OXC ) is associated with quantitative improvement in mood and anxiety symptoms in adult patients with partial epilepsy . Depressive symptoms and anxiety were assessed by clinical interview using the Hamilton Depression Rating Scale ( HDRS ) , the Cornell Dysthymia Rating Scale ( CDRS ) , the Beck Depression Inventory ( BDI ) , and the Hamilton Anxiety Rating Scale ( HARS ) . Forty controls ( patients with epilepsy treated with antiepileptic drugs other than OXC ) and 40 OXC-treated patients were enrolled and completed the study . In our study , a significant improvement in affect , as measured by the CDRS , was demonstrated during the course of OXC treatment for 3 months . HDRS and BDI scores also declined in the OXC-treated group , but these decreases did not reach statistical significance . In addition , 28 of 40 OXC-treated subjects who were dysthymic by CDRS criteria on study entry ( score > or = 20 ) demonstrated affective improvement consistent with a treatment-related antidepressant effect ( score < 20 ) . Although our results do not provide conclusive evidence supporting the specific use of OXC as an antidepressant , the significant decline in dysthymic symptoms in OXC-treated subjects compared with controls lends support to the hypothesis that OXC improves mood OBJECTIVE To determine whether patients who fail their first antiepileptic drug ( AED ) have better neuropsychiatric and quality -of-life ( QOL ) outcomes if substituted to levetiracetam monotherapy compared with a second older AED . DESIGN R and omized comparative trial . Participants with partial epilepsy who had failed monotherapy with phenytoin sodium , carbamazepine , or valproate sodium were r and omized to substitution monotherapy with levetiracetam or a different older AED . Assessment s were performed at baseline , 3 months , and 12 months using question naires measuring neuropsychiatric , QOL , seizure control , AED adverse effects , and neurocognitive outcomes . SETTING Epilepsy service of a teaching hospital . PATIENTS Fifty-one patients were r and omized to levetiracetam and 48 were r and omized to a second older AED ( 25 to valproate and 23 to carbamazepine ) . MAIN OUTCOME MEASURES Proportions showing improvements in depression ( on the Hospital Anxiety and Depression Scale ) and QOL scores ( on the 89-item Quality of Life in Epilepsy Inventory ) at 3 months . RESULTS There were no differences between the groups in depression scores at 3 months ( improvement in 17 of 43 patients [ 39.5 % ] in the levetiracetam group and 15 of 44 patients [ 34.1 % ] in the older AED group ; P = .60 ) , but a greater proportion of the older AED group improved on the 89-item Quality of Life in Epilepsy Inventory compared with the levetiracetam group ( 27 of 38 patients [ 71.1 % ] vs 21 of 43 patients [ 48.8 % ] , respectively ; P = .04 ) . The QOL , anxiety , and AED adverse effects scores were improved in both groups at 3 and 12 months after r and omization . CONCLUSIONS Substitution monotherapy in a patient experiencing ongoing seizures or tolerability issues is associated with sustained improvements in measures of QOL , psychiatric , and adverse events outcomes . Patients switched to levetiracetam do not have better outcomes than those switched to a second older AED . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12606000102572 OBJECTIVES To compare clinicians ' choice of one of the st and ard epilepsy drug treatments ( carbamazepine or valproate ) versus appropriate comparator new drugs . DESIGN A clinical trial comprising two arms , one comparing new drugs in carbamazepine and the other with valproate . SETTING A multicentre study recruiting patients with epilepsy from hospital outpatient clinics . PARTICIPANTS Patients with an adequately documented history of two or more clinical ly definite unprovoked epileptic seizures within the last year for whom treatment with a single antiepileptic drug represented the best therapeutic option . INTERVENTIONS Arm A was carbamazepine ( CBZ ) versus gabapentin ( GBP ) versus lamotrigine ( LTG ) versus oxcarbazepine ( OXC ) versus topiramate ( TPM ) . Arm B valproate ( VPS ) versus LTG versus TPM . MAIN OUTCOME MEASURES Time to treatment failure ( withdrawal of the r and omised drug for reasons of unacceptable adverse events or inadequate seizure control or a combination of the two ) and time to achieve a 12-month remission of seizures . Time from r and omisation to first seizure , 24-month remission of seizures , incidence of clinical ly important adverse events , quality of life ( QoL ) outcomes and health economic outcomes were also considered . RESULTS Arm A recruited 1721 patients ( 88 % with symptomatic or cryptogenic partial epilepsy and 10 % with unclassified epilepsy ) . Arm B recruited 716 patients ( 63 % with idiopathic generalised epilepsy and 25 % with unclassified epilepsy ) . In Arm A LTG had the lowest incidence of treatment failure and was statistically superior to all drugs for this outcome with the exception of OXC . Some 12 % and 8 % fewer patients experienced treatment failure on LTG than CBZ , the st and ard drug , at 1 and 2 years after r and omisation , respectively . The superiority of LTG over CBZ was due to its better tolerability but there is satisfactory evidence indicating that LTG is not clinical ly inferior to CBZ for measures of its efficacy . No consistent differences in QoL outcomes were found between treatment groups . Health economic analysis supported LTG being preferred to CBZ for both cost per seizure avoided and cost per quality -adjusted life-year gained . In Arm B for time to treatment failure , VPS , the st and ard drug , was preferred to both TPM and LTG , as it was the drug least likely to be associated with treatment failure for inadequate seizure control and was the preferred drug for time to achieving a 12-month remission . QoL assessment s did not show any between-treatment differences . The health economic assessment supported the conclusion that VPS should remain the drug of first choice for idiopathic generalised or unclassified epilepsy , although there is a suggestion that TPM is a cost-effective alternative to VPS . CONCLUSIONS The evidence suggests that LTG may be a clinical and cost-effective alternative to the existing st and ard drug treatment , CBZ , for patients diagnosed as having partial seizures . For patients with idiopathic generalised epilepsy or difficult to classify epilepsy , VPS remains the clinical ly most effective drug , although TPM may be a cost-effective alternative for some patients . Three new antiepileptic drugs have recently been licensed in the UK for the treatment of epilepsy ( levetiracetam , zonisamide and pregabalin ) , therefore these drugs should be compared in a similarly design ed trial Objective : To determine the effectiveness of systematic screening with a brief 19-item self-report instrument , the Adverse Events Profile ( AEP ) , to reduce adverse effects of antiepileptic drugs ( AEDs ) and improve subjective health status . Methods : The authors performed a prospect i ve r and omized trial comparing the use of the AEP with usual care without the AEP . Sixty-two patients with an AEP score of ≥45 were enrolled from a consecutive group of 200 consenting adults with epilepsy . Results : The mean percent improvement in AEP scores was greater in the patient group for which clinicians received the AEP compared with the usual care group ( 25 % vs 5 % ; p < 0.01 ) . Mean change in Quality of Life in Epilepsy Inventory (QOLIE)-89 total scores was not different between groups , but for the entire sample QOLIE-89 change was greater for patients having a 15-point improvement in AEP scores than for those with a 0- to 15-point improvement or a worsened score ( 24 vs 12 vs 3 ; analysis of variance , p < 0.008 ) . More patients in the AEP group had a > 15-point improvement in QOLIE-89 score ( p < 0.03 ) . Use of the AEP was associated with a 2.8-fold increase ( 95 % CI , 1.7 to 4.8 ) in AED modifications . No difference in seizure rates was observed . Conclusions : Systematic screening for antiepileptic drug side effects may increase identification of toxicity and guide medication changes to reduce adverse effects and possibly improve subjective health status The present study was design ed to reveal changes of cognitive processes in epilepsy ( EP ) patients with Topiramate ( TPM ) or Valproate ( VPA ) treatment using Wechsler Adult Intelligence Scale ( WAIS-CR ) and event-related potential ( ERP ) . Thirty untreated epilepsy patients were r and omly divided into two groups receiving TPM or VPA , respectively . Fifteen healthy volunteers were included as controls . All the patients were examined by WAIS-CR and ERP before and 3 months after drug treatment . Controls were examined by ERP at the time recruited into the study and 3 months later . Unfamiliar grey-scale photographs of faces ( front view ) were used as stimuli . ERP were recorded at the same time . Mean Intelligence Quotient ( IQ ) in TPM group decreased after the 3-month treatment ( 90.40 vs. 81.00 , P<0.05 ) . One component of ERP-P300 was smaller in epilepsy patients than controls ( P<0.05 ) , but remained unchanged after TPM or VPA treatment ( P>0.05 ) . A delayed and smaller N270 was detected in patients compared to controls ( P<0.05 ) . After 3 months TPM treatment , it decreased further compared to before treatment ( P<0.05 ) . N170 was lower in patient groups , and it became lower after TPM treatment than before . Our results demonstrate that in all epilepsy patients with mild cognitive impairment ERP changes were found . TPM affected the cognitive functions in epilepsy patients reflected by the decreased full-scale intelligence quotient ( FIQ ) . The imperative effects of TPM on visual perception function reflected by N170 were more obvious than that of VPA . Attention reflected by N270 was impaired after TPM treatment AIM The aim of this study was to evaluate the impact of two different therapeutic strategies in patients with partial seizures who were intractable to the first prescribed antiepileptic drug ( AED ) ; alternative monotherapy vs early add-on treatment . METHODS We conducted an open , cluster-r and omised , prospect i ve , controlled trial in patients with persistent partial seizures , despite treatment with one AED , who were never administered any other AEDs . Neurologists were r and omised to two strategies : in group A , an alternative monotherapy with a second AED was employed ; in group B , add-on treatment with a second AED was employed . The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment . The secondary outcomes were : ( i ) the percentage of patients achieving a 50 % reduction in the number of seizures at six months ; ( ii ) the quality of life based on the Quality Of Life In Epilepsy scale ; and ( iii ) tolerability . RESULTS A total of 143 neurologists were included and r and omised , and 264 patients were evaluated . At six months , the primary outcome was 51 % in group A and 45 % in group B ( p=0.34 ) . The percentage of patients achieving a 50 % reduction in the number of seizures at six months was 76 % in group A and 84 % in group B ( p=0.53 ) . The quality of life and the tolerability did not significantly differ between the two groups . CONCLUSIONS Alternative monotherapy or early treatment initiation with another AED drug result ed in similar efficacy , and the side effects associated with monotherapy and combined therapies were similar , which suggests that individual susceptibility is more important than the number and burden of AEDs used Abstract Background : Both epilepsy and depressive symptoms are more prevalent in older individuals than in any other age group . Furthermore , depressive symptoms are among the most common interictal psychiatric co-morbid disorders in people with epilepsy . For these reasons , pharmacological treatment of epilepsy that might also confer antidepressant effects may be particularly beneficial in older patients . In this respect , lamotrigine is of considerable interest amongst antiepileptic drugs ( AEDs ) because it has proven thymoleptic activity . Objective : These analyses , conducted on a data set drawn from a previously reported , open-label , multicentre , prospect i ve study , examined the effect of lamotrigine on mood in adults aged ≥50 years with epilepsy and co-morbid depressive symptoms . All subjects were receiving background AED therapy at baseline . Methods : Of the 158 subjects enrolled in the initial study , 40 adults ( 24 women , 16 men ) met the age criterion for these analyses . The study consisted of a screening/baseline phase and four treatment phases over 36 weeks : lamotrigine escalation phase ( 7 weeks ) ; lamotrigine maintenance or adjunctive therapy phase ( 12 weeks ) ; concomitant AED withdrawal phase ( 5 weeks ) ; and lamotrigine monotherapy phase ( 12 weeks ) . Psychometric evaluation of mood utilized the Beck Depression Inventory ( BDI-II ) , Center for Epidemiological Studies Depression Scale ( CES-D ) , the Neurological Disorders Depression Inventory in Epilepsy ( NDDI-E ) and the Profile of Mood States ( POMS ) . Scores at the end of the adjunctive and monotherapy phases were compared with baseline scores . Lower scores on these scales indicate less depressive symptomatology . Results : Mean baseline scores for the BDI-II , CES-D , NDDI-E and POMS were 15.8 , 24.3 , 13.8 and 57.7 , respectively . Change scores were statistically significant ( p < 0.01 ) compared with baseline at the end of the adjunctive and monotherapy phases for all four psychometric measures of mood , with the exceptions of BDI-II and NDDI-E at the end of the adjunctive phase . Conclusions : The older adults in these analyses presented with low to moderate levels of depressive symptoms . Addition of lamotrigine to background AED therapy demonstrated antidepressant activity similar to that for the whole sample in the initial study . Given that the onset and prevalence of epilepsy are higher in older adults than in any other age group , pharmacological treatment for epilepsy in older patients that might also confer antidepressant therapy may be particularly beneficial |
11,871 | 26,914,267 | However , low intraday reliability was reported for the theoretical maximum horizontal force ( ICC 0.64 ) within adolescent athletes , and low validity was reported for velocity during the initial 5 m of a sprint acceleration ( bias up to 0.41 m/s ) measured with a laser device .
There have been no reports to date of criterion validity of kinetic measures of sprint acceleration performance on NMT and TT , and only limited results regarding acceptable concurrent validity of radar-derived kinetic data .
Conclusions Radar , laser , NMT and TT technologies can be used to reliably measure sprint acceleration performance and to provide insight into the determinants of sprinting speed .
Radar and laser technology may not be suitable for measuring the first few steps of a sprint acceleration | Background Advanced testing technologies enable insight into the kinematic and kinetic determinants of sprint acceleration performance , which is particularly important for field-based team-sport athletes .
Establishing the reliability and validity of the data , particularly from the acceleration phase , is important for determining the utility of the respective technologies .
Objective The aim of this systematic review was to explain the utility , reliability , validity and limitations of ( 1 ) radar and laser technology , and ( 2 ) non-motorised treadmill ( NMT ) and torque treadmill ( TT ) technology for providing kinematic and kinetic measures of sprint acceleration performance . | The effects of high-intensity , short- duration , re-warm-ups on team-sport-related performance were investigated . In a r and omised , cross-over study , participants performed 2 × 26-min periods of an intermittent activity protocol ( IAP ) on a non-motorized treadmill , interspersed by 15-min of passive recovery ( CON ) ; 3-min small-sided game ( SSG ) ; or a 5RM leg-press . Measures included counter-movement jump , repeated-sprint , the Loughborough soccer passing test ( LSPT ) , blood lactate concentration , heart-rate , and perceptual measures . Data were analyzed using effect size ( 90 % confidence intervals ) , and percentage change ; determining magnitudes of effects . A 5RM re-warm-up improved flight-time to contraction-time ratio when compared to SSG ( 9.8 % , ES ; 0.5±0.3 ) and CON ( ES : 9.4 % , 0.7±0.5 ) re-warm-ups , remaining higher following the second IAP ( 8.8 % , ES ; 0.5±0.3 and 10.2 % , ES ; 0.6±0.6 , respectively ) . Relative-maximum rate-of-force development was greater in the 5RM condition following the second IAP compared to SSG ( 29.3 % , ES ; 0.7±0.5 ) and CON ( 16.2 % , ES ; 0.6±0.6 ) . Repeated-sprint ability during the second IAP improved in the 5RM re-warm-up ; peak velocity , mean velocity , and acceleration were 4 , 3 , and 18 % greater , respectively . Within groups , the SSG re-warm-up improved LSPT performance post-intervention ; 6.4 % ( ES : 0.6±0.8 ) and following the second IAP 6.2 % ( ES : 0.6±0.6 ) , compared to pre-intervention . A 5RM leg-press re-warm-up improved physical performance , while a SSG re-warm-up enhanced skill execution following st and ardized intermittent exercise Sweeney , KM , Wright , GA , Brice , AG , and Doberstein , ST . The effect of β-alanine supplementation on power performance during repeated sprint activity . J Strength Cond Res 24(1 ) : 79 - 87 , 2010-The dipeptide carnosine has been shown to contribute to the buffer capacity of hydrogen ions ( H+ ) during intense exercise . Increasing skeletal muscle carnosine levels through β-alanine ( BA ) supplementation has been shown to maintain acid-base balance , delay fatigue , and improve exercise performance . We design ed this study to examine the effect of 5 weeks of BA supplementation on repeat high-intensity sprint performance . Nineteen , physically active , college men were divided into 2 groups ( control [ C ] , n = 10 or BA , n = 9 ) . We performed double-blind placebo-controlled study where subjects ingested 4 g per day during the first week and 6 g per day over the next 4 weeks of a placebo ( rice flour ) or a BA supplement . Subjects completed 2 sets of 5 5-second sprints with 45-second recovery separated by 2 minutes of active recovery . All tests were conducted on a non-motorized treadmill against a resistance of 15 % of the participant 's body weight . We recorded horizontal power ( HP ) of the running sprint . Post-exercise capillary blood sample s were analyzed for lactate to determine the metabolic dem and s. There were no significant between-group differences ( p > 0.05 ) in HPpeak or HPmean for the repeat sprint protocol . No significant between-group differences were found for performance decrement ( % fatigue ) for HPpeak or HPmean . In addition , no significant interactions were observed . Post-exercise blood lactate values were similar pre and post supplementation in both groups . The results of this study clearly indicate that 5 weeks of BA supplementation provides no benefit for repeat sprint performance We investigated the acute and chronic responses to multiple sets of repeated-sprint exercise ( RSE ) , focusing on changes in acceleration , intermittent running capacity and physiological responses . Ten healthy young adults ( 7 males , 3 females ) performed an incremental test , a Yo-Yo intermittent recovery test level1 ( Yo-Yo IR1 ) , and one session of RSE . RSE comprised three sets of 5 × 4-s maximal sprints on a non-motorised treadmill , with 20 s of passive recovery between repetitions and 4.5 min of passive recovery between sets . After ten repeated-sprint training sessions , participants repeated all tests . During RSE , performance was determined by measuring acceleration , mean and peak power/velocity . Recovery heart rate ( HR ) , HR variability , and finger-tip capillary lactate concentration ( [ Lac− ] ) were measured . Performance progressively decreased across the three sets of RSE , with the indices of repeated-sprint ability being impaired to a different extent before and after training . Training induced a significant increase ( p < 0.05 ) in all indices of performance , particularly acceleration ( 21.9 , 14.7 and 15.2 % during sets 1 , 2 and 3 , respectively ) . Training significantly increased Yo-Yo IR1 performance by 8 % and decreased Δ[Lac−]/work ratio ( −15.2 , −15.5 , −9.4 % during sets 1 , 2 and 3 , respectively ) and recovery HR during RSE . There were strong correlations between Yo-Yo IR1 performance and indices of RSE performance , especially acceleration post-training ( r = 0.88 , p = 0.004 ) . Repeated-sprint training , comprising only 10 min of exercise overall , effectively improved performance during multiple-set RSE . This exercise model better reflects team-sport activities than single-set RSE . The rapid training-induced improvement in acceleration , quantified here for the first time , has wide applications for professional and recreational sport activities Abstract Reliability refers to the reproducibility of values of a test , assay or other measurement in repeated trials on the same individuals . Better reliability implies better precision of single measurements and better tracking of changes in measurements in research or practical setting s. The main measures of reliability are within-subject r and om variation , systematic change in the mean , and retest correlation . A simple , adaptable form of within-subject variation is the typical ( st and ard ) error of measurement : the st and ard deviation of an individual ’s repeated measurements . For many measurements in sports medicine and science , the typical error is best expressed as a coefficient of variation ( percentage of the mean ) . A biased , more limited form of within-subject variation is the limits of agreement : the 95 % likely range of change of an individual ’s measurements between 2 trials . Systematic changes in the mean of a measure between consecutive trials represent such effects as learning , motivation or fatigue ; these changes need to be eliminated from estimates of within-subject variation . Retest correlation is difficult to interpret , mainly because its value is sensitive to the heterogeneity of the sample of participants . Uses of reliability include decision-making when monitoring individuals , comparison of tests or equipment , estimation of sample size in experiments and estimation of the magnitude of individual differences in the response to a treatment . Reasonable precision for estimates of reliability requires approximately 50 study participants and at least 3 trials . Studies aim ed at assessing variation in reliability between tests or equipment require complex design s and analyses that research ers seldom perform correctly . A wider underst and ing of reliability and adoption of the typical error as the st and ard measure of reliability would improve the assessment of tests and equipment in our disciplines Despite the exp and ing use of Whole Body Vibration training among athletes , it is not known whether adding Whole Body Vibration training to the conventional training of sprint-trained athletes will improve speed-strength performance . Twenty experienced sprint-trained athletes ( 13 male symbol , 7 female symbol , 17 - 30 years old ) were r and omly assigned to a Whole Body Vibration group ( n=10 : 6 male symbol and 4 female symbol ) or a Control group ( n=10 : 7 male symbol , 3 female symbol ) . During a 5-week experimental period all subjects continued their conventional training program , but the subjects of the Whole Body Vibration group additionally performed three times weekly a Whole Body Vibration training prior to their conventional training program . The Whole Body Vibration program consisted of unloaded static and dynamic leg exercises on a vibration platform ( 35 - 40 Hz , 1.7 - 2.5 mm , Power Plate ) . Pre and post isometric and dynamic ( 100 degrees/s ) knee-extensor and -flexor strength and knee-extension velocity at fixed resistances were measured by means of a motor-driven dynamometer ( Rev 9000 , Technogym ) . Vertical jump performance was measured by means of a contact mat . Force-time characteristics of the start action were assessed using a load cell mounted on each starting block . Sprint running velocity was recorded by means of a laser system . Isometric and dynamic knee-extensor and knee-flexor strength were unaffected ( p>0.05 ) in the Whole Body Vibration group and the Control group . As well , knee-extension velocity remained unchanged ( p>0.05 ) . The duration of the start action , the result ing start velocity , start acceleration , and sprint running velocity did not change ( > 0.05 ) in either group . In conclusion , this specific Whole Body Vibration protocol of 5 weeks had no surplus value upon the conventional training program to improve speed-strength performance in sprint-trained athletes The literature contains some hypotheses regarding the most favorable ground reaction force ( GRF ) for sprint running and how it might be achieved . This study tested the relevance of these hypotheses to the acceleration phase of a sprint , using GRF impulse as the GRF variable of interest . Thirty-six athletes performed maximal-effort sprints from which video and GRF data were collected at the 16-m mark . Associations between GRF impulse ( expressed relative to body mass ) and various kinematic measures were explored with simple and multiple linear regressions and paired t-tests . The regression results showed that relative propulsive impulse accounted for 57 % of variance in sprint velocity . Relative braking impulse accounted for only 7 % of variance in sprint velocity . In addition , the faster athletes tended to produce only moderate magnitudes of relative vertical impulse . Paired t-tests revealed that lower magnitudes of relative braking impulse were associated with a smaller touchdown distance ( p < 0.01 ) and a more active touchdown ( p < 0.001 ) . Also , greater magnitudes of relative propulsive impulse were associated with a high mean hip extension velocity of the stance limb ( p < 0.05 ) . In conclusion , it is likely that high magnitudes of propulsion are required to achieve high acceleration . Although there was a weak trend for faster athletes to produce lower magnitudes of braking , the possibility of braking having some advantages could not be ruled out . Further research is required to see if braking , propulsive , and vertical impulses can be modified with specific training . This will also provide insight into how a change in one GRF component might affect the others The aim of the study was to assess the reliability of sprint performance in both field and laboratory conditions . Twenty-one male ( mean ± s : 19 ± 1 years , 1.79 ± 0.07 m , 77.6 ± 7.1 kg ) and seventeen female team sport players ( mean ± s : 21 ± 4 years , 1.68 ± 0 . 07 m , 62.7 ± 4.7 kg ) performed a maximal 20-metre sprint running test on eight separate occasions . Four trials were conducted on a non-motorised treadmill in the laboratory ; the other four were conducted outdoors on a hard-court training surface with time recorded by single-beam photocells . Trials were conducted in r and om order with no familiarisation prior to testing . There was a significant difference between times recorded during outdoor field trials ( OFT ) and indoor laboratory trials ( ILT ) using a non-motorised treadmill ( 3.47 ± 0.53 vs. 6.06 ±1.17s ; p < 0.001 ) . The coefficient of variation ( CV ) for time was 2.55 - 4.22 % for OFT and 5.1 - 7.2 % for ILT . During ILT peak force ( 420.9 ± 87.7N ) , mean force ( 147.2 ± 24.7N ) , peak power ( 1376.8 ± 451.9W ) and mean power ( 514.8 ± 164.4W ) , and were measured . The CV for all ILT variables was highest during trial 1 - 2 comparison . The CV ( 95 % confidence interval ) for the trial 3 - 4 comparison yielded : 9.4 % ( 7.7 - 12 . 1 % ) , 7.9 % ( 6.4 - 10.2 % ) , 10.1 % ( 8.2 - 13.1 % ) and 6.2 % ( 5.1 - 8.0 % ) for PF , MF , PP and MP and respectively . The results indicate that reliable data can be derived for single maximal sprint measures , using fixed distance protocol s. However , significant differences in time/speed over 20-m exist between field and laboratory conditions . This is primarily due to the frictional resistance in the non- motorised treadmill . Measures of force and power during ILT require at least 3 familiarisations to reduce variability in test scores . Key pointsReliable data can be derived from single maximal sprint measures in both indoor and outdoor environments using fixed distance protocol s . There may be significant time differences to complete fixed distance trials between the two environments . Measures of mean force , peak force and peak power during indoor trials may require multiple trials to reduce variability in test scores & NA ; Lakomy , J. , and D.T. Haydon . The effects of enforced , rapid deceleration on performance in a multiple sprint test . J. Strength Cond . Res . 18(3):579–583 . 2004.—The nature of multiple sprint sports such as soccer , hockey , and rugby is such that deceleration plays an important part in the movement patterns of players during a game and training . The purpose of this study was to investigate the effect of deceleration on fatigue during repeated sprint efforts . A group of 18 elite field hockey players ( all men ) performed a running repeated sprint ability test ( 6 × 40 m using maximal effort and departing every 30 seconds ) . In one condition , there was no deceleration zone , and in the second condition , the test had a deceleration component ( rapid deceleration to a stop within 6 m of the end of each sprint ) . Sprint times under each condition were compared using a repeated measures analysis of variance . No significant difference was seen between the 2 conditions for mean sprint times ( p > 0.05 ) or for the mean fatigue index ( p > 0.05 ) . However , results showed a divergent trend , and further analysis extrapolating the data for an increased number of sprints showed that a significant difference ( p < 0.05 ) would have been seen at the 11th sprint . Although this study found that the deceleration zone had little effect on the 6‐sprint protocol , it was clear that the deceleration component would have shown an effect , giving rise to greater fatigue and slower sprint times , if the number of sprints had been increased . The implication s are that deceleration training should be introduced into general fitness training programs for those competing in multiple sprint sports The objective was to estimate the contribution of experience , body size and maturity status to variation in the functional capacities of adolescent football ( soccer ) players . The sample included 69 players 13.2–15.1 years of age from three clubs which competed in the highest division for their age group in the first Portuguese national division . Height and weight were measured and stage of pubic hair development was assessed at clinical examination . The number of years of experience in football was obtained at interview . Three tests of functional capacity were administered : 30-m dash ( running speed ) , vertical jump ( explosive power ) and a yo-yo intermittent endurance test ( aerobic resistance ) . Multiple linear regression analysis was used to estimate the relative contributions of age , stage of sexual maturity , height , weight and years of formal training in football to the three indicators of functional capacity . Stage of puberty , body size and years of training accounted for 21 % to 50 % of the variance in the three tasks . Sexual maturity status was the primary contributor to the variance in the intermittent shuttle run , whereas weight and height were the primary contributors to the explained variance in the 30-m dash and vertical jump , respectively . In conclusion , biological maturity status significantly influences the functional capacity of adolescent football players 13–15 years of age . Training is a significant contributor to aerobic resistance , whereas weight and height are significant contributors to the sprint and vertical jump , respectively We investigated the differences in performance between 100-m sprints performed on a sprint treadmill recently vali date d versus on a st and ard track . To date , studies comparing overground and treadmill running have mainly focused on constant and not maximal “ free ” running speed , and compared running kinetics and kinematics over a limited number of steps , but not overall sprint performance . Eleven male physical education students including two sprinters performed one 100-m on the treadmill and one on a st and ard athletics track in a r and omized order , separated by 30 min . Performance data were derived in both cases from speed – time relationships measured with a radar and with the instrumented sprint treadmill , which allowed subjects to run and produce speed “ freely ” , i.e. with no predetermined belt speed imposed . Field and treadmill typical speed – distance curves and data of maximal and mean speed , 100-m time and acceleration/deceleration time constants were compared using t tests and field – treadmill correlations were tested . All the performance parameters but time to reach top speed and deceleration time constant differed significantly , by about 20 % on average , between field and treadmill ( e.g. top speed of 8.84 ± 0.51 vs. 6.90 ± 0.39 m s−1 ) . However , significant correlations were found ( r > 0.63 ; P < 0.05 ) for all the performance parameters except time to reach top speed . Treadmill and field 100-m sprint performances are different , despite the fact that subjects could freely accelerate the belt . However , the significant correlations found make it possible to investigate and interpret inter-individual differences in field performance from treadmill measurements This study determined mechanical power during movements specific to maximal walking and running using a non-motorized treadmill in 38 elderly [ 69.4 ( 5.0 ) years ] and 50 young [ 24.3 ( 3.4 ) years ] men . The mean mechanical power over a period of time covering six steps , during which the belt velocity peaked and then kept almost plateau , was determined as a performance score in each of maximal walking ( WP ) and running ( RP ) . In terms of the value relative to body mass , the relative difference between the two age groups was greater for RP ( 61.7 % ) than for WP ( 21.4 % ) or isometric knee extension ( 34.1 % ) and flexion torque ( 43.8 % ) . In the two groups , WP was significantly ( P<0.05 ) correlated to knee extension ( r=0.582 for the elderly and r=0.392 for the young ) and flexion torque ( r=0.524 for the elderly and r=0.574 for the young ) . Similarly , RP was also significantly ( P<0.05 ) correlated to knee extension ( r=0.627 for the elderly and r=0.478 for the young ) and flexion torque ( r=0.500 for the elderly and r=0.281 for the young ) . In these relationships , the WP adjusted statistically by thigh muscle torque was similar in the two age groups . However , the corresponding value for RP was significantly higher in the young than in the elderly . The findings here indicate that : ( 1 ) the difference between the young and elderly men in mechanical power is greater during maximal running than maximal walking , and ( 2 ) although the thigh muscle torque contributes to the power production during the two maximal exercise modes in the two age groups , the RP is greater in the young than in the elderly regardless of the difference in the thigh muscle torque Abstract Kawamori , N , Newton , RU , Hori , N , and Nosaka , K. Effects of weighted sled towing with heavy versus light load on sprint acceleration ability . J Strength Cond Res 28(10 ) : 2738–2745 , 2014—Weighted sled towing is used by athletes to improve sprint acceleration ability . The typical coaching recommendation is to use relatively light loads , as excessively heavy loads are hypothesized to disrupt running mechanics and be detrimental to sprint performance . However , this coaching recommendation has not been empirically tested . This study compared the effects of weighted sled towing with 2 different external loads on sprint acceleration ability . Twenty-one physically active men were r and omly allocated to heavy- ( n = 10 ) or light-load weighted sled towing ( n = 11 ) groups . All subjects participated in 2 training sessions per week for 8 weeks . The subjects in the heavy and light groups performed weighted sled towing using external loads that reduced sprint velocity by approximately 30 and 10 % , respectively . Before and after the training , the subjects performed a 10-m sprint test , in which split time was measured at 5 and 10 m from the start . The heavy group significantly improved both the 5- and 10-m sprint time by 5.7 ± 5.7 and 5.0 ± 3.5 % , respectively ( P < 0.05 ) , whereas only 10-m sprint time was improved significantly by 3.0 ± 3.5 % ( P < 0.05 ) in the light group . No significant differences were found between the groups in the changes in 5-m and 10-m sprint time from pre- to posttraining . These results question the notion that training loads that induce greater than 10 % reduction in sprint velocity would negatively affect sprint performance and point out the potential benefit of using a heavier load for weighted sled towing Seven high school boys ( 16.4 + /- 0.5 y , mean + /- SD ) and 7 girls ( 16.4 + /- 0.5 y ) , who specialized in track and field events , performed ten 5-s maximal sprint runs with an interval of 10s between each sprint on a non-motorized running ergometer . In each sprint , the mean mechanical power ( MP ) from the start until the belt velocity of the ergometer ( i. e. , running velocity ) peaked was calculated . The boys showed significantly higher MP than the girls in all sprints . However , when MP was expressed as the ratio to the total volume of muscles located in the right lower limb ( MP x MV(-1 ) ) , estimated using a bioelectrical impedance analysis , significant gender effect was limited to the values at the 1 st and 2 nd sprints . The decline of MP over the ten sprints , expressed as a relative value to that at the 1 st sprint , was greater in boys ( 46.2 + /- 7.6 % ) than in girls ( 33.9 + /- 8.6 % ) , and significantly correlated with MP x MV(-1 ) at the 1st sprint ( r = 0.568 , p < 0.05 ) . However , no significant difference between the boys and girls was found in the relative difference between MP values at the 3rd and 10th sprints , where the gender difference in MP x MV(-1 ) at every sprint was insignificant . The findings here indicate that , for trained teenage boys and girls , ( 1 ) significant gender difference in mechanical power developed during repeated bouts of maximal running exists only in the initial phase of the task , when the difference in the volume of the lower limb muscles is normalized , and ( 2 ) it may be a reason for a greater decline of mechanical power developed during the bout in boys compared to girls The purpose of this study was to determine the effects of body mass-based squat training on body composition , muscular strength and motor fitness in adolescent boys . Ninety-four boys ( 13.7 ± 0.6 yrs , 1.60 ± 0.09 m , 50.2 ± 9.6 kg ) participated in this study and were r and omly assigned to training ( n = 36 ) or control ( n = 58 ) groups . The training group completed body mass-based squat exercise training ( 100 reps/day , 45 sessions ) for 8 weeks . Body composition and muscle thickness at the thigh anterior were determined by a bioelectrical impedance analyzer and ultrasound apparatus , respectively . Maximal voluntary knee extension strength and sprint velocity were measured using static myometer and non-motorized treadmill , respectively . Jump height was calculated using flight time during jumping , which was measured by a matswitch system . The 8-wk body mass-based squat training significantly decreased percent body fat ( 4.2 % ) and significantly increased the lean body mass ( 2.7 % ) , muscle thickness ( 3.2 % ) and strength of the knee extensors ( 16.0 % ) , compared to control group . The vertical jump height was also significantly improved by 3.4 % through the intervention . The current results indicate that body mass-based squat training for 8 weeks is a feasible and effective method for improving body composition and muscular strength of the knee extensors , and jump performance in adolescent boys . Key pointsAn 8-wk body mass-based squat exercise training decreased percent body fat in adolescent boys . The body mass-based squat exercise training increased muscle size and strength capability of the knee extensors in adolescent boys . The squat exercise training improves vertical jump height in adolescent boys This study aim ed to determine the measurement error associated with estimates of velocity from a laser-based device during different phases of a maximal athletic sprint . Laser-based displacement data were obtained from 10 sprinters completing a total of 89 sprints and were fitted with a fifth-order polynomial function which was differentiated to obtain instantaneous velocity data . These velocity estimates were compared against criterion high-speed video velocities at either 1 , 5 , 10 , 30 or 50 m using a Bl and -Altman analysis to assess bias and r and om error . Bias was highest at 1 m ( + 0.41 m/s ) and tended to decrease as the measurement distance increased , with values less than + 0.10 m/s at 30 and 50 m. R and om error was more consistent between distances , and reached a minimum value ( ±0.11 m/s ) at 10 m. Laser devices offer a potentially useful time-efficient tool for assessing between-subject or between-session performance from the mid-acceleration and maximum velocity phases ( i. e. , at 10 m and beyond ) , although only differences exceeding 0.22 - 0.30 m/s should be considered genuine . However , laser data should not be used during the first 5 m of a sprint , and are likely of limited use for assessing within-subject variation in performance during a single session Spring-mass model properties of eight non-specialized male runners were measured during four straight 100-m sprints on an athletics track . A recently developed simple measurement method allowed to calculate leg and vertical stiffness , vertical displacement of the center of mass , and stride temporal characteristics . Changes in these mechanical parameters were studied and correlated with those of sprint performance . During the first 100 m , forward velocity showed significant variations ( mean value of 8.10 + /- 0.31 m x s(-1 ) over the entire 100-m ) , while leg and vertical stiffnesses ( 19.5 + /- 4.3 kN x m(-1 ) and 93.9 + /- 12.4 kN x m(-1 ) , respectively ) remained constant . No significant link was found between mechanical and performance parameters over this first sprint . During the following three sprints , vertical stiffness , step frequency , and contact time significantly decreased ( 20.6 + /- 7.9 % , 8.03 + /- 3.34 % , and 14.7 + /- 7.2 % of the first 100-m value , respectively ) with decreasing maximal and mean velocities ( 10.9 + /- 2.0 % and 7.30 + /- 5.23 % , respectively ) , whereas leg stiffness and maximal force remained constant . Furthermore , changes between these mechanical and performance parameters were significantly related , showing the clear relationship between impairment in spring-mass model properties of the runners ' lower limbs and the decrease in performance in fatigue conditions induced by the repetition of these all-out efforts |
11,872 | 28,042,882 | CONCLUSIONS This systematic review reveals a lack of evidence to determine whether early mobilisation interventions are beneficial to this vulnerable patient group .
Nevertheless , ambulation from the first postoperative day with temporary prosthesis is possible among the heterogeneous population of dysvascular lower limb-amputated patients if the necessary interdisciplinary team is dedicated to the task . | AIMS AND OBJECTIVES To assess the effect of early mobilisation of patients after dysvascular lower limb amputation and to compare the effectiveness of different mobilisation regimens .
BACKGROUND Patients who have undergone dysvascular major lower limb amputations are at high risk of postoperative complications , which include loss of basic functions , and early mobilisation interventions might prevent these complications .
RELEVANCE TO CLINICAL PRACTICE Mobilisation is a fundamental care task often missed for several reasons . | Amputations of the lower extremity are still a common problem in diabetic feet and peripheral vasculopathies . The presented paper introduces a new device for an easier and faster mobilization of below-the-knee amputees . It is based on a new modular prostheses with individual inflatable air bladders . The compliance rate is higher with this device and it could be used from the day of surgery until the definitive prostheses is made . A biomechanical cadaver study with the prostheses will also be presented BACKGROUND Perioperative treatment of patients with colorectal cancer according to the Enhanced Recovery After Surgery ( ERAS ) protocol has proven to reduce complications and duration of stay . However , strict adherence remains a challenge and the benefits may decrease with lower adherence . In this study , we report on 8 years of adherence to the ERAS protocol and its effect on postoperative outcome in patients with colon cancer . METHODS In 2006 , the ERAS protocol was introduced for treatment of colon cancer patients in the Medical Center Alkmaar , a large teaching hospital . Patients scheduled for elective colon cancer resection were included in this study . Adherence to ERAS items was monitored and along with clinical data prospect ively gathered in a data base . In 2011 , several measures to improve adherence were implemented . RESULTS In total , 816 patients were included . Mean adherence rate was 73 % in 2006 and 2007 , 66 % in 2008 and 2009 , 63 % in 2010 and 2011 , and 82 % in 2012 and 2013 . There was a shorter duration of stay in the years with high adherence ( 5.7 days ) compared with the years with low adherence ( 7.3 days ; P < .001 ) . The ERAS items that were the strongest predictors for a shorter duration of stay were no nasogastric tube , early mobilization , early oral nutrition , early removal of epidural , early removal of catheter , and nonopioid oral analgesia . CONCLUSION It is possible to improve adherence to the ERAS protocol and related outcomes with specific measures . Adherence to the ERAS protocol was related inversely to duration of stay . Only postoperative items of the ERAS protocol were predictive for a shorter duration of stay . Keeping adherence optimal remains an ongoing challenge that requires repeated training and dedicated personnel To evaluate the use of an immediate postoperative prosthesis ( IPOP ) for transtibial amputees , we compared patient outcomes from a prospect i ve clinical study of 19 patients managed with an IPOP with those of a retrospective review of a matched historic control group of 23 patients managed with st and ard soft dressings . Data were analyzed with the Student 's t-test , and significance was set at P=0.05 . The IPOP patients had no surgical revisions , whereas the patients with st and ard soft dressings had 11 . This was a significant difference . IPOP patients also had significantly fewer postoperative complications and shorter times to custom prosthesis than did controls Eighty lower-extremity amputation patients were r and omly divided into two groups : one that ambulated ( A ) early ( 48 to 72 hours ) and one that did not ( NA ) . Group A patients used an immediate , post-operative , pneumatic splinting device . The two groups were compared as to the incidence of wound and constitutional post-operative complications , with the A group showing significantly fewer . As in previous studies , the A group continued toward quicker and more successful rehabilitation OBJECTIVES To estimate the prevalence of different levels of mobility in a hospitalized older cohort , to measure the degree and rate of adverse outcomes associated with different mobility levels , and to examine the physician activity orders and documented reasons for bedrest in the lowest mobility group . DESIGN A prospect i ve cohort study . SETTING An 800-bed university teaching hospital . PARTICIPANTS Four hundred ninety-eight hospitalized medical patients , aged 70 and older . MEASUREMENTS Using average mobility level , scored from 0 to 12 , the low-mobility group was defined as having a score of 4 or less , intermediate as a score of higher than 4 to 8 , and high as higher than 8 . Outcomes were functional decline , new institutionalization , death , and death or new institutionalization . RESULTS Low and intermediate levels of mobility were common , accounting for 80 ( 16 % ) and 157 ( 32 % ) study patients , respectively . Overall , any activity of daily living ( ADL ) decline occurred in 29 % , new institutionalization in 13 % , death in 7 % , and death or new institutionalization in 22 % of patients in this cohort . When compared with the high mobility group , the low and intermediate groups were associated with the adverse outcomes in a grade d fashion , even after controlling for multiple confounders . The low-mobility group had an adjusted odds ratio ( OR ) of 5.6 ( 95 % confidence interval (CI)=2.9 - 11.0 ) for ADL decline , 6.0 ( 95 % CI=2.5 - 14.8 ) for new institutionalization , 34.3 ( 95 % CI=6.3 - 185.9 ) for death , and 7.2 ( 95 % CI=3.6 - 14.4 ) for death or new institutionalization . The intermediate group had adjusted ORs of 2.5 ( 95 % CI=1.5 - 4.1 ) , 2.9 ( 95 % CI=1.4 - 6.0 ) , 10.1 ( 95 % CI=1.9 - 52.9 ) , and 3.3 ( 95 % CI=1.8 - 5.9 ) for ADL decline , new institutionalization , death , and death or new institutionalization , respectively . Bedrest was ordered at some point during hospitalization in 165 ( 33 % ) patients . For most patients , mobility was limited involuntarily ( bedrest orders ) , and almost 60 % of bedrest episodes in the lowest mobility group had no documented medical indication . CONCLUSION Low mobility and bedrest are common in hospitalized older patients and are important predictors of adverse outcomes . This study demonstrated that the adverse outcomes associated with low mobility and bedrest may be viewed as iatrogenic events leading to complications , such as functional decline It is common practice to keep those patients with lower extremity autografts immobile until post-operative day ( POD ) 5 . There is however inherent risks associated with even short periods of immobility . As of now there are no r and omized controlled trials looking at early ambulation of patients with lower extremity autografts in the burn community . The objective of this study was to show that patients who begin ambulation within 24 hours of lower extremity autografting will have no increased risk of graft failure than those patients who remain immobile until POD 5 . Thirty-one subjects who received autografts to the lower extremity were r and omized after surgery into either the early ambulation group ( EAG;17 subjects ) or the st and ard treatment group ( STG;14 subjects ) . Those subjects r and omized to the EAG began ambulating with physical therapy on POD 1 . Subjects in the STG maintained bed rest until POD 5 . There was no difference in the number of patients with graft loss in either the EAG or STG on POD 5 , and during any of the follow-up visits . No subjects required regrafting . There was a significant difference in the mean minutes of ambulation , with the EAG ambulating longer than the STG ( EAG 23.4 minutes [ SD 12.03 ] , STG 14.1 [ SD 9.00 ] , P=.0235 ) on POD 5 . Burn patients with lower extremity autografts can safely ambulate on POD 1 without fear of graft failure compared with those patients that remain on bed rest for 5 days |
11,873 | 17,989,084 | CONCLUSIONS Comprehensive interventions with at least physical activity , dietary intervention and health education may be effective in reducing obesity in Chinese children . | BACKGROUND Overweight and obesity pose a challenge to public health in China .
According to Chinese definition , 303 million Chinese are overweight ( body mass index , BMI > or= 24 kg m(-2 ) ) .
Among them , 73 million are clinical ly obese ( BMI > or= 28 kg m(-2 ) ) .
In line with the global trend , the rate of obesity in China continues to increase , with associated morbidity and mortality .
This study was to identify interventions , which are effective in Mainl and Chinese society . | To evaluate the efficacy of a community-based adult obesity intervention in Angang . The intervention included health education activities among residents in a community in Anyang . 2400 and 1200 individual were r and omly selected as intervention group and control group respectively from a community in Anyang . The question nairing survey and body weight measuring were conducted and repeated at the end of the study for one year . The results showed that the awareness on the prevention of obesity was enhanced(P < 0.05 ) and mean weight of target population decreased . The community-based intervention for obesity was effective as well as feasible Background : Childhood obesity has become a nutritional problem in China since the 1990s . Aims : A family based behavioural treatment was developed and tested , to see if its use was feasible in China and to evaluate its impact on obese schoolchildren . Methods : In a single school in Beijing , 33 obese children were r and omly assigned to a treatment group and 35 to a control group . The treatment group participated in a family based behavioural treatment programme for two years . Height and weight were measured every six months for all participants . Blood pressure , cholesterol , and triglyceride levels were measured at baseline and after two years of programme implementation . Results : Body mass index ( BMI , kg/m2 ) was significantly reduced in the treatment group ( from 26.6 ( 1.7 ) to 24.0 ( 0.9 ) , 95 % CI 2.06 to 3.18 ) but not in the control group ( from 26.1 ( 1.5 ) to 26.0 ( 1.6 ) ) . Total cholesterol decreased 5.5 % and triglycerides 9.7 % in the treatment group . There was a significant correlation between change in BMI and change in triglycerides . There were no significant changes in plasma lipids in the controls . Blood pressure values also decreased significantly in the treatment , but not the control group . Conclusions : A family based behavioural intervention was feasible to use in treating obesity in schoolchildren in Beijing , China . After two years of implementation , it successfully decreased the degree of obesity , reduced levels of blood pressure , and decreased serum lipids in treatment ; there were no significant changes among control children OBJECTIVE To examine the effect of community-based health education and health promotion on body mass index ( BMI ) , overweight and obesity . METHODS We separately selected 100,000 population in Beijing , Shanghai and Changsha Cities during 1991 - 2000 . Each of the cities was then r and omly separated intervention and control community of 500,000 population . In the intervention community various kinds of health education and health promotion had been carried out . The level of knowledge , attitude and behavior ( KAB ) and body mass index ( BMI ) were evaluated . RESULTS The net increases of KAB level and regularly exercising rate in three city and different target population were statistically differences in comparison with baseline survey of 1992 , and the net decreases of the BMI , overweight rate and obesity rate of the whole population were statistically differences . CONCLUSION Health education and health promotion can effectively control the rising of population BMI , and have great meaningful for population preventing from cardio-cerebro-vascular diseases |
11,874 | 20,576,004 | None of the interventions had an effect in preventing overweight and obesity . | The objective of this study was to analyse interventions for the prevention of overweight and obesity in children under 5 years of age . | BACKGROUND The prevalence of obesity in the United States is a significant public health problem . Many obesity-related risk factors are more prevalent in minority population s. Given the recalcitrant nature of weight loss interventions for adults , prevention of overweight and obesity has become a high priority . The present study reports baseline data from an obesity prevention intervention developed for minority preschool children . METHODS Hip-Hop to Health Jr. is a 5-year r and omized controlled intervention that targets 3- to 5-year-old minority children enrolled in 24 Head Start programs . Our primary aim is to test the effect of the intervention on change in body mass index . Data were collected on sociodemographic , anthropometric , behavioral , and cognitive variables for the children and parents at baseline . RESULTS Participants included 416 black children , 337 black parents , 362 Latino children , and 309 Latino parents . Using body mass index for age and sex > or = the 95th percentile as the definition of overweight , 15 % of the black children and 28 % of the Latino children were overweight . More than 75 % of the parents were either overweight or obese . DISCUSSION The development of interventions to effectively prevent or control obesity early in life is crucial . These data highlight the escalating problem of weight control in minority population Context : Recent data indicate a marked increase in the prevalence of obesity among school-aged children . Thus , efficacious programmes that prevent overweight development in children are urgently needed . Objective : To evaluate the impact of repeatedly given , individualised dietary and lifestyle counselling on the prevalence of overweight during the first 10 years of life . Design and participants : This study was a part of the Special Turku Coronary Risk Factor Intervention Project for Children ( STRIP ) , which is a prospect i ve , r and omised trial aim ed at reducing the exposure of the intervention children to the known risk factors of atherosclerosis . At the child 's age of 7 months , 1062 children were assigned to an intervention group ( n=540 ) or to a control group ( n=522 ) . The intervention children received individualised counselling focused on healthy diet and physical activity biannually . Height and weight of the children were measured at least once a year . Main outcome measure : Prevalence of overweight and obesity among the intervention and control children by sex and age . Children were classified as overweight or obese if their weight for height was > 20 % or ⩾40 % above the mean weight for height of healthy Finnish children , respectively . Results : After the age of 2 years , there were continuously fewer overweight girls in the intervention group than in the control group . At the age of 10 years , 10.2 % of the intervention girls and 18.8 % of the control girls were overweight ( P=0.0439 ) , whereas 11.6 % of the intervention boys and 12.1 % of the control boys were overweight ( P≈1.00 ) . Only three children in the intervention group were obese at some age point , whereas 14 control children were classified as obese at some age point . Conclusion : Individualised dietary and lifestyle counselling given twice a year since infancy decreases prevalence of overweight in school-aged girls even without any primary energy restrictions BACKGROUND The evidence that breastfeeding protects against obesity and a variety of chronic diseases comes almost entirely from observational studies , which have a potential for bias due to confounding , selection bias , and selective publication . OBJECTIVE We assessed whether an intervention design ed to promote exclusive and prolonged breastfeeding affects children 's height , weight , adiposity , and blood pressure at age 6.5 y. DESIGN The Promotion of Breastfeeding Intervention Trial ( PROBIT ) is a cluster-r and omized trial of a breastfeeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative . A total of 17,046 healthy breastfed infants were enrolled from 31 Belarussian maternity hospitals and their affiliated clinics ; of those infants , 13,889 ( 81.5 % ) were followed up at 6.5 y with duplicate measurements of anthropometric variables and blood pressure . Analysis was based on intention to treat , with statistical adjustment for clustering within hospitals or clinics to permit inferences at the individual level . RESULTS The experimental intervention led to a much greater prevalence of exclusive breastfeeding at 3 mo in the experimental than in the control group ( 43.3 % and 6.4 % , respectively ; P < 0.001 ) and a higher prevalence of any breastfeeding throughout infancy . No significant intervention effects were observed on height , body mass index , waist or hip circumference , triceps or subscapular skinfold thickness , or systolic or diastolic blood pressure . CONCLUSIONS The breastfeeding promotion intervention result ed in substantial increases in the duration and exclusivity of breastfeeding , yet it did not reduce the measures of adiposity , increase stature , or reduce blood pressure at age 6.5 y in the experimental group . Previously reported beneficial effects on these outcomes may be the result of uncontrolled confounding and selection bias Exercise has been found to be effective for prevention of weight gain and maintenance of a stable weight in adults . The objective of this study was to evaluate the effect of a school-based aerobic exercise program on the obesity indexes of preschool children . Subjects were 292 second-year elementary school pupils from 2 kindergartens in Hat Yai municipality , Songkhla province , southern Thail and . A specially design ed exercise program , including a 15-min walk before beginning the morning class and a 20-min aerobic dance session after the afternoon nap , 3 times a week , was conducted for 29.6 wk . Weight , height , and triceps skinfold thickness were measured 4 times . At the end of the study , the prevalence of obesity , using 95th percentile National Center for Health Statistics triceps-skinfold-thickness cutoffs , of both the exercise and control groups decreased . That of the exercise group decreased from 12.2 % at baseline to 8.8 % ( Wilcoxon signed-rank test , P = 0.058 ) , whereas that of the control group decreased from 11.7 % to 9.7 % ( Wilcoxon signed-rank test , P = 0.179 ) . A sex difference in the response of body mass index ( BMI ) to exercise was observed . Girls in the exercise group had a lower likelihood of having an increasing BMI slope than the control girls did ( odds ratio : 0.32 ; 95 % CI : 0.18 , 0.56 ) . In conclusion , our study suggests that a 29.6-wk school-based exercise program can prevent BMI gain in girls and may induce a remission of obesity in preschool-age children The evidence that breast-feeding protects against obesity is based on observational studies , with potential for confounding and selection bias . This article summarizes a previously published study in which we assessed whether an intervention design ed to promote exclusive and prolonged breast-feeding affects children 's height , weight , adiposity , and blood pressure ( BP ) at age 6.5 y. The Promotion of Breastfeeding Intervention Trial ( PROBIT ) is a cluster-r and omized trial of a breast-feeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative . A total of 17,046 healthy breast-fed infants were enrolled from 31 Belarussian maternity hospitals and affiliated clinics , of whom 13,889 ( 81.5 % ) were followed up at 6.5 y with duplicate measurements of height , weight , waist circumference , triceps and subscapular skinfold thicknesses , systolic and diastolic BP . Analysis was based on intention to treat , with statistical adjustment for clustering within hospitals/clinics to permit inferences at the individual level . The experimental intervention led to a large increase in exclusive breast-feeding at 3 mo ( 43.3 % vs. 6.4 % , P < 0.001 ) and a significantly higher prevalence of any breast-feeding throughout infancy . No significant intervention effects were observed on height , BMI , adiposity measures , or BP . The breast-feeding promotion intervention result ed in substantial increases in the duration and exclusivity of breast-feeding yet did not reduce measures of adiposity at age 6.5 y. Previous reports of protective effects against obesity may reflect uncontrolled bias caused by confounding and selection Objective To assess whether a physical activity intervention reduces body mass index in young children . Design Cluster r and omised controlled single blinded trial over 12 months . Setting Thirty six nurseries in Glasgow , Scotl and . Participants 545 children in their preschool year , mean age 4.2 years ( SD 0.2 ) at baseline . Intervention Enhanced physical activity programme in nursery ( three 30 minute sessions a week over 24 weeks ) plus home based health education aim ed at increasing physical activity through play and reducing sedentary behaviour . Main outcome measure Body mass index , expressed as a st and ard deviation score relative to UK 1990 reference data . Secondary measures were objective ly measured physical activity and sedentary behaviour ; fundamental movement skills ; and evaluation of the process . Results Group allocation had no significant effect on the primary outcome measure at six and 12 months or on measures of physical activity and sedentary behaviour by accelerometry . Children in the intervention group had significantly higher performance in movement skills tests than control children at six month follow-up ( P=0.0027 ; 95 % confidence interval 0.3 to 1.3 ) after adjustment for sex and baseline performance . Conclusions Physical activity can significantly improve motor skills but did not reduce body mass index in young children in this trial . Trial registration Current Controlled Trials IS RCT N36363490 OBJECTIVE To investigate whether dietary counseling design ed for primary prevention of atherosclerosis and given repeatedly since infancy had an effect on prepubertal children 's body satisfaction . DESIGN R and omized controlled trial . PARTICIPANTS At the age of 7 months , 1062 infants were r and omized to an intervention group ( n = 540 ) or a control group ( n = 522 ) . At the age of 8 years , body satisfaction of 217 children in the intervention group and 218 in the control group was evaluated . Intervention Since the children were 8 months old , families in the intervention group had regularly received individualized health education and dietary advice aim ed at decreasing the children 's intake of saturated fat and cholesterol . MAIN OUTCOME MEASURES A pictorial instrument was used in measuring estimated current and desired body sizes ; a difference between the 2 indicated body dissatisfaction . Weight and height were measured . RESULTS When adjusted for relative weight , there were no differences in the mean values of estimated current size , desired size , or body dissatisfaction between the girls in the intervention and control groups ( P = .62 , P = .72 , and P = .39 , respectively ) , or between the boys in the intervention and control groups ( P = .21 , P = .64 , and P = .53 , respectively ) . The proportions of children who were satisfied with their size , who wished to be thinner , or who wished to look heavier did not differ between the intervention and control groups in either girls ( P = .65 ) or boys ( P = .85 ) . CONCLUSION Long-term , individualized dietary counseling since infancy with the focus on dietary fat did not enhance body dissatisfaction or desire to be thinner in 8-year-old children OBJECTIVE To determine whether maternal participation in an obesity prevention plus parenting support ( OPPS ) intervention would reduce the prevalence of obesity in high-risk Native-American children when compared with a parenting support (PS)-only intervention . RESEARCH METHODS AND PROCEDURES Forty-three mother/child pairs were recruited to participate . Mothers were 26.5 + /- 5 years old with a mean BMI of 29.9 + /- 3 kg/m(2 ) . Children ( 23 males ) were 22 + /- 8 months old with mean weight-for-height z ( WHZ ) scores of 0.73 + /- 1.4 . Mothers were r and omly assigned to a 16-week OPPS intervention or PS alone . The intervention was delivered one-on-one in homes by an indigenous peer educator . Baseline and week 16 assessment s included weight and height ( WHZ score and weight-for-height percentile for children ) , dietary intake ( 3-day food records ) , physical activity ( measured by accelerometers ) , parental feeding style ( Child Feeding Question naire ) , and maternal outcome expectations , self-efficacy , and intention to change diet and exercise behaviors . RESULTS Changes in WHZ scores showed a trend toward significance , with WHZ scores decreasing in the PS condition and increasing among the OPPS group ( -0.27 + /- 1.1 vs. 0.31 + /- 1.1 , p = 0.06 ) . Children in the OPPS condition also significantly decreased energy intake ( -316 + /- 835 kcal/d vs. 197 + /- 608 kcal/d , p < 0.05 ) . Scores on the restriction subscale of the Child Feeding Question naire decreased significantly in the OPPS condition ( -0.22+/- 0.42 vs. 0.08+/- 0.63 , p < 0.05 ) , indicating that mothers in the OPPS group were engaging in less restrictive child feeding practice s over time . DISCUSSION A home-visiting program focused on changing lifestyle behaviors and improving parenting skills showed promise for obesity prevention in high-risk Native-American children OBJECTIVE . Our goal was to study childhood growth patterns and development of overweight in children who were overweight or normal weight at 13 years of age . PARTICIPANTS AND METHODS . This study is part of a prospect i ve atherosclerosis-prevention trial Special Turku Coronary Risk Factor Intervention Project for Children ) . At 7 months of age , 1062 children were r and omly assigned to an intervention group ( n = 540 ) receiving biannual fat-oriented dietary counseling or to a control group ( n = 522 ) . Height and weight of the children and their parents were monitored annually . Our study group comprised those children who participated in the 13-year study visit ( n = 541 ) . At 13 years of age , the child was classified as overweight ( n = 84 ) if his or her BMI exceeded the international age- and gender-specific overweight criteria . RESULTS . In overweight girls , the annual weight gain increased from 2.8 kg during the third and fourth year of life to 7.5 kg during the 12th year of life , whereas the annual weight gain of the girls who were normal weight ranged from 2.1 to 4.8 kg during the same period . The annual weight gain was similar of overweight boys and in their normal-weight peers until the age of 5 years , but after that it increased from 3.5 to 7.9 kg in overweight and from 2.6 to 5.5 kg in normal-weight boys . The BMI of the girls and boys who were overweight at the age of 13 exceeded the international cutoff point for overweight from the age of 5 and 8 years onward , respectively . The mean BMI s of the mothers and fathers of the overweight children were higher than those of the parents of the normal-weight children . The STRIP intervention had no effect on the examined growth parameters or on parental BMI . CONCLUSIONS . The children who were overweight at 13 years of age gained more weight than their normal-weight peers by the age of 2 or 3 years onward . The girls became overweight by the age of 5 years , whereas the boys only after 8 years of age . Parental BMI and steep weight gain in early childhood indicate markedly increased risk for becoming overweight OBJECTIVE To evaluate the impact of individualized and repeatedly given dietary counseling on fat intake and nutrient intake of children aged 8 months to 4 years . DESIGN Prospect i ve r and omized clinical trial . PARTICIPANTS Children ( N = 1062 ) from 1054 families were r and omized to an intervention ( n = 540 ) or a control ( n = 522 ) group when each child participant was 6 months old . INTERVENTIONS The children in the intervention group were counseled to reduce their intake of saturated fat and cholesterol but to ensure their adequate energy intake . Dietary issues were discussed with the families of the children in the control group only briefly according to the current practice of well-baby clinics . MAIN OUTCOME MEASURES Food consumption was evaluated by using 3- and 4-day food records that were kept at 5- to 12-month intervals , and nutrient intakes were analyzed with a Micro Nutrica computer program ( Social Insurance Institution , Turku , Finl and ) . RESULTS The intake of fat ( 29 % of the energy intake ) and cholesterol ( 70 mg ) showed no differences between the groups of children at 8 months of age . The fat intake in the children in the intervention group was then continuously 2 % of the energy intake below that of the children in the control group ( P < .001 ) . After the age of 13 months , the cholesterol intake of the children in the control group exceeded that of the children in the intervention group by 20 mg ( P < .001 ) . The children in the intervention group consumed 3 % ( of the energy intake ) less saturated ( P < .001 ) and 1 % ( of the energy intake ) more polyunsaturated fats ( P < .001 ) than did the children in the control group at age 13 months and older . The carbohydrate intake was slightly higher in the children in the intervention group than in the children in the control group . Intakes of vitamins , minerals , and trace elements showed no differences between the 2 groups . CONCLUSIONS The intakes of fat by the children in the intervention and control groups were markedly below values that were recommended for the first 2 years of life . Despite the low intake of fat , the intake of other nutrients fulfilled current recommendations , except for vitamin D and iron . Individualized dietary counseling that led to clear changes in the type of fat intake had a minimal effect on vitamin or mineral intakes Objectives . We examined recent overweight and obesity trends in a multiethnic population of low-income preschool children . Methods . We defined overweight as sex-specific body mass index ( BMI ) -for-age ≥85th and < 95th percentile and obesity as sex-specific BMI -for-age ≥95th percentile , and calculated them using demographic data and r and omly selected height and weight measurements that were recorded while 2- to < 5-year-old children were enrolled in the New York State ( NYS ) Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) during 2002–2007 . Results . Obesity prevalence peaked at 16.7 % in 2003 , declined from 2003 through 2005 , and stabilized at 14.7 % through 2007 . Among both boys and girls , the downward trend in annual prevalence of obesity was evident only among Hispanic children ( 22.8 % boys and 20.9 % girls in 2002 vs. 19.3 % boys and 17.5 % girls in 2007 ) and non-Hispanic black children ( 15.6 % boys and 14.2 % girls in 2002 vs. 13.6 % boys and 12.4 % girls in 2007 ) . In contrast , the annual prevalence estimate for overweight showed an increasing trend from 2002 through 2007 . Conclusions . These results showed a slight decline in prevalence of childhood obesity and a continuing rise in prevalence of childhood overweight among children enrolled in the NYS WIC program during 2002–2007 . Future research should investigate the extent to which the slight decline in childhood obesity prevalence may be attributable to population -based and high-risk obesity prevention efforts in NYS OBJECTIVE Hip-Hop to Health Jr. was a diet/physical activity intervention design ed to reduce gains in BMI ( kilograms per meter squared ) in preschool minority children . RESEARCH METHODS AND PROCEDURES Twelve predominantly Latino Head Start centers participated in a group-r and omized trial conducted between Fall 2001 and Winter 2003 . Six centers were r and omized to a culturally proficient 14-week ( three times weekly ) diet/physical activity intervention . Parents participated by completing weekly homework assignments . The children in the other six centers received a general health intervention that did not address either diet or physical activity . The primary outcome was change in BMI , and secondary outcomes were changes in dietary intake and physical activity . Measures were collected at baseline , post-intervention , and at Years 1 and 2 follow-up . RESULTS There were no significant differences between intervention and control schools in either primary or secondary outcomes at post-intervention , Year 1 , or Year 2 follow-ups . DISCUSSION When Hip-Hop to Health Jr. was conducted in predominantly black Head Start centers , it was effective in reducing subsequent increases in BMI in preschool children . In contrast , when the program was conducted in Latino centers , it was not effective . Although the intervention did not prevent excessive weight gain in Latino children , it was very well received . Future interventions with this population may require further cultural tailoring and a more robust parent intervention OBJECTIVE To evaluate the longitudinal impact of dietary counseling on children 's nutrient intake . DESIGN A prospect i ve , r and omized , clinical trial . PARTICIPANTS Children were recruited to the study between December 1 , 1989 , and May 30 , 1992 . At the age of 7 months , children were r and omized to the intervention group ( n = 540 ) or the control group ( n = 522 ) and were followed up until the age of 10 years . Intervention Families in the intervention group have , since r and omization , received regularly individualized counseling about how to modify the quality and quantity of fat in the child 's diet , the goal being an unsaturated-saturated fat ratio of 2:1 . MAIN OUTCOME MEASURES Nutrient intakes between the ages of 4 and 10 years based on annual 4-day food records . RESULTS The fat intake of the intervention children was constantly around 30 % of the calorie ( energy ) intake , while that of the control children was 2 to 3 calorie percentage units higher ( P<.001 ) . The intervention children received 2 to 3 calorie percentage units less saturated fats and 0.5 to 1.0 calorie percentage unit more polyunsaturated fats than the control children ( P<.001 for both ) . However , neither group reached the 2:1 goal set for the unsaturated-saturated fatty acid ratio . The vitamin and mineral intakes of the intervention and control children closely resembled each other despite the marked differences in fat intake . CONCLUSION Individualized , biannually given , fat intake-focused dietary counseling that began at the child 's age of 8 months continued to influence favorably the diet of 4- to 10-year-old intervention children without disadvantageous dietary effects , but the 2:1 goal for unsaturated-saturated fat ratio was not reached CONTEXT Current evidence that breastfeeding is beneficial for infant and child health is based exclusively on observational studies . Potential sources of bias in such studies have led to doubts about the magnitude of these health benefits in industrialized countries . OBJECTIVE To assess the effects of breastfeeding promotion on breastfeeding duration and exclusivity and gastrointestinal and respiratory infection and atopic eczema among infants . DESIGN The Promotion of Breastfeeding Intervention Trial ( PROBIT ) , a cluster-r and omized trial conducted June 1996-December 1997 with a 1-year follow-up . SETTING Thirty-one maternity hospitals and polyclinics in the Republic of Belarus . PARTICIPANTS A total of 17 046 mother-infant pairs consisting of full-term singleton infants weighing at least 2500 g and their healthy mothers who intended to breastfeed , 16491 ( 96.7 % ) of which completed the entire 12 months of follow-up . INTERVENTIONS Sites were r and omly assigned to receive an experimental intervention ( n = 16 ) modeled on the Baby-Friendly Hospital Initiative of the World Health Organization and United Nations Children 's Fund , which emphasizes health care worker assistance with initiating and maintaining breastfeeding and lactation and postnatal breastfeeding support , or a control intervention ( n = 15 ) of continuing usual infant feeding practice s and policies . MAIN OUTCOME MEASURES Duration of any breastfeeding , prevalence of predominant and exclusive breastfeeding at 3 and 6 months of life and occurrence of 1 or more episodes of gastrointestinal tract infection , 2 or more episodes of respiratory tract infection , and atopic eczema during the first 12 months of life , compared between the intervention and control groups . RESULTS Infants from the intervention sites were significantly more likely than control infants to be breastfed to any degree at 12 months ( 19.7 % vs 11.4 % ; adjusted odds ratio [ OR ] , 0.47 ; 95 % confidence interval [ CI ] , 0.32 - 0.69 ) , were more likely to be exclusively breastfed at 3 months ( 43.3 % vs 6.4 % ; P<.001 ) and at 6 months ( 7.9 % vs 0.6 % ; P = .01 ) , and had a significant reduction in the risk of 1 or more gastrointestinal tract infections ( 9.1 % vs 13.2 % ; adjusted OR , 0.60 ; 95 % CI , 0.40 - 0.91 ) and of atopic eczema ( 3.3 % vs 6.3 % ; adjusted OR , 0.54 ; 95 % CI , 0.31 - 0.95 ) , but no significant reduction in respiratory tract infection ( intervention group , 39.2 % ; control group , 39.4 % ; adjusted OR , 0.87 ; 95 % CI , 0.59 - 1.28 ) . CONCLUSIONS Our experimental intervention increased the duration and degree ( exclusivity ) of breastfeeding and decreased the risk of gastrointestinal tract infection and atopic eczema in the first year of life . These results provide a solid scientific underpinning for future interventions to promote breastfeeding 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 Interventions to avoid atherosclerosis might be more successful if launched early in life when eating and life-style patterns are formed , but dietary interventions have been limited by fears of diet-induced growth failure . We investigated the effects of a diet low in saturated fat and cholesterol on serum lipid concentrations and growth in 1062 healthy 7-month-old infants in a r and omised study . Every 1 - 3 months , families in the intervention group received dietary advice aim ed at adequate energy supply , with low fat intake ( 30 - 35 % energy , polyunsaturated/monounsaturated/saturated fatty acid ratio 1/1/1 , and cholesterol intake < 200 mg daily ) . Infants in control families consumed an unrestricted diet . 3-day food records were collected at ages 8 and 13 months . Growth was carefully monitored . Between 7 and 13 months serum cholesterol and non-high-density-lipoprotein cholesterol concentrations did not change significantly in the intervention group ( mean change -0.03 [ SD 0.72 ] mmol/L and 0.01 [ 0.67 ] mmol/L ) but increased substantially in the control group ( 0.24 [ 0.64 ] mmol/L and 0.23 [ 0.60 ] mmol/L ; p for difference in mean changes between groups < 0.001 ) . Daily intakes of energy and saturated fat were lower in the intervention than in the control group at 13 months ( 4065 [ 796 ] vs 4370 [ 748 ] kJ , p = 0.033 , and 9.3 [ 3.5 ] vs 14.5 [ 4.8 ] g , p < 0.001 , respectively ) , and intake of polyunsaturated fat was higher ( 5.8 [ 2.2 ] vs 4.4 [ 1.4 ] g , p < 0.001 ) . Growth did not differ between the groups and was as expected for children at this age . Serum cholesterol concentrations fell significantly in parents of intervention-group infants . The increases in serum cholesterol and non-high-density-lipoprotein cholesterol concentration that occur in infants between the ages of 7 and 13 months can be avoided by individualised diets , with no effect on the children 's growth This paper summarizes the objectives , design , follow-up , and data validation of a cluster-r and omized trial of a breastfeeding promotion intervention modeled on the WHO/UNICEF Baby-Friendly Hospital Initiative ( BFHI ) . Thirty-four hospitals and their affiliated polyclinics in the Republic of Belarus were r and omized to receive BFHI training of medical , midwifery , and nursing staffs ( experimental group ) or to continue their routine practice s ( control group ) . All breastfeeding mother-infant dyads were considered eligible for inclusion in the study if the infant was singleton , born at > or = 37 weeks gestation , weighed > or = 2500 grams at birth , and had a 5-minute Apgar score > or = 5 , and neither mother nor infant had a medical condition for which breastfeeding was contraindicated . One experimental and one control site refused to accept their r and omized allocation and dropped out of the trial . A total of 17,795 mothers were recruited at the 32 remaining sites , and their infants were followed up at 1 , 2 , 3 , 6 , 9 , and 12 months of age . To our knowledge , this is the largest r and omized trial ever undertaken in area of human milk and lactation . Monitoring visits of all experimental and control maternity hospitals and polyclinics were undertaken prior to recruitment and twice more during recruitment and follow-up to ensure compliance with the r and omized allocation . Major study outcomes include the occurrence of > or = 1 episode of gastrointestinal infection , > or = 2 respiratory infections , and the duration of breastfeeding , and are analyzed according to r and omized allocation ( " intention to treat " ) . One of the 32 remaining study sites was dropped from the trial because of apparently falsified follow-up data , as suggested by an unrealistically low incidence of infection and unrealistically long duration of breastfeeding , and as confirmed by subsequent data audit of polyclinic charts and interviews with mothers of 64 r and omly-selected study infants at the site . Smaller r and om audits at each of the remaining sites showed extremely high concordance between the PROBIT data forms and both the polyclinic charts and maternal interviews , with no evident difference in under- or over-reporting in experimental vs control sites . Of the 17,046 infants recruited from the 31 participating study sites , 16,491 ( 96.7 % ) completed the study and only 555 ( 3.3 % ) were lost to follow-up . PROBIT 's results should help inform decision-making for clinicians , hospitals , industry , and governments concerning the support , protection , and promotion of breastfeeding OBJECTIVES To assess the impact of a culturally proficient dietary/physical activity intervention on changes in body mass index ( BMI ) ( kg/m 2 ) . STUDY DESIGN R and omized controlled trial ( Hip-Hop to Health Jr. ) conducted between September 1999 and June 2002 in 12 Head Start preschool programs in Chicago , Illinois . RESULTS Intervention children had significantly smaller increases in BMI compared with control children at 1-year follow-up , 0.06 vs 0.59 kg/m 2 ; difference -0.53 kg/m 2 ( 95 % CI -0.91 to -0.14 ) , P = .01 ; and at 2-year follow-up , 0.54 vs 1.08 kg/m 2 ; difference -0.54 kg/m 2 ( 95 % CI -0.98 to -0.10 ) , P = .02 , with adjustment for baseline age and BMI . The only significant difference between intervention and control children in food intake/physical activity was the Year 1 difference in percent of calories from saturated fat , 11.6 % vs 12.8 % ( P = .002 ) . CONCLUSIONS Hip-Hop to Health Jr. was effective in reducing subsequent increases in BMI in preschool children . This represents a promising approach to prevention of overweight among minority children in the preschool years UNLABELLED BACKGROUND ; The increasing prevalence of overweight among children in the United States presents a national health priority . Higher rates of overweight/obesity among minority women place their children at increased risk . Although increased rates of overweight are observed in 4- to 5-year-old children , they are not observed in 2- to 3-year-old children . Therefore , early prevention efforts incorporating families are critical . METHODS The primary aim of Hip-Hop to Health Jr. is to alter the trajectory toward overweight/obesity among preschool African-American and Latino children . This 5-year r and omized intervention is conducted in 24 Head Start programs , where each site is r and omized to either a 14-week dietary/physical activity intervention or a general health intervention . RESULTS This paper presents the rationale and design of the study . Efficacy of the intervention will be determined by weight change for the children and parent/caretaker . Secondary measures include reductions in dietary fat and increases in fiber , fruit/vegetable intake , and physical activity . Baseline data will be presented in future papers . CONCLUSIONS The problem of overweight/obesity is epidemic in the United States . Behaviors related to diet and physical activity are established early in life and modeled by family members . Early intervention efforts addressing the child and family are needed to prevent obesity later in life . This paper describes a comprehensive , family-oriented obesity prevention program for minority preschool children |
11,875 | 28,698,483 | However , considering the available evidence , the use of VR in the assessment of those conditions showed some promise in identifying : ( 1 ) how those patients experienced their body image ; and ( 2 ) environments or specific kinds of foods that may trigger binge-purging cycle .
Some studies using VR-based environments associated to cognitive behavioral techniques showed their potential utility in improving motivation for change , self-esteem , body image disturbances and in reducing binge eating and purging behavior | Several lines of evidence suggest that Virtual Reality ( VR ) has a potential utility in eating disorders .
The objective of this study is to review the literature on the use of VR in bulimia nervosa ( BN ) and binge eating disorder ( BED ) . | CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs Background Recent research identifies unhealthful weight-control behaviors ( fasting , vomiting , or laxative abuse ) induced by a negative experience of the body , as the common antecedents of both obesity and eating disorders . In particular , according to the allocentric lock hypothesis , individuals with obesity may be locked to an allocentric ( observer view ) negative memory of the body that is no longer up date d by contrasting egocentric representations driven by perception . In other words , these patients may be locked to an allocentric negative representation of their body that their sensory inputs are no longer able to up date even after a dem and ing diet and a significant weight loss . Objective To test the brief and long-term clinical efficacy of an enhanced cognitive-behavioral therapy including a virtual reality protocol aim ed at unlocking the negative memory of the body ( ECT ) in morbidly obese patients with binge eating disorders ( BED ) compared with st and ard cognitive behavior therapy ( CBT ) and an inpatient multimodal treatment ( IP ) on weight loss , weight loss maintenance , BED remission , and body satisfaction improvement , including psychonutritional groups , a low-calorie diet ( 1200 kcal/day ) , and physical training . Methods 90 obese ( BMI > 40 ) female patients with BED upon referral to an obesity rehabilitation center were r and omly assigned to conditions ( 31 to ECT , 30 to CBT , and 29 to IP ) . Before treatment completion , 24 patients discharged themselves from hospital ( 4 in ECT , 10 in CBT , and 10 in IP ) . The remaining 66 in patients received either 15 sessions of ECT , 15 sessions of CBT , or no additional treatment over a 5-week usual care inpatient regimen ( IP ) . ECT and CBT treatments were administered by 3 licensed psychotherapists , and patients were blinded to conditions . At start , upon completion of the inpatient treatment , and at 1-year follow-up , patients ' weight , number of binge eating episodes during the previous month , and body satisfaction were assessed by self-report question naires and compared across conditions . 22 patients who received all sessions did not provide follow-up data ( 9 in ECT , 6 in CBT , and 7 in IP ) . Results Only ECT was effective at improving weight loss at 1-year follow-up . Conversely , control participants regained on average most of the weight they had lost during the inpatient program . Binge eating episodes decreased to zero during the inpatient program but were reported again in all the three groups at 1-year follow-up . However , a substantial regain was observed only in the group who received the inpatient program alone , while both ECT and CBT were successful in maintaining a low rate of monthly binge eating episodes . Conclusions Despite study limitations , findings support the hypothesis that the integration of a VR-based treatment , aim ed at both unlocking the negative memory of the body and at modifying its behavioral and emotional correlates , may improve the long-term outcome of a treatment for obese BED patients . As expected , the VR-based treatment , in comparison with the st and ard CBT approach , was able to better prevent weight regain but not to better manage binge eating episodes . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 59019572 ; http://www.controlled-trials.com/IS RCT N59019572 ( Archived by WebCite at http://www.webcitation.org/6GxHxAR2 G Body image ( BI ) disturbances are considered to be central in eating disorders ( ED ) psychopathology . There are few studies focused on the treatment of BI disturbances in ED , and most of them have used " traditional methods . " The purpose of the present study was to probe the effectiveness of one specific component in the assessment and treatment of BI in ED by means of virtual reality ( VR ) . Two treatment conditions were applied : ( a ) The St and ard Body Image Treatment Condition ( SBIT ) and ( b ) the VR Condition . Thirteen eating disordered patients were r and omly assigned to one of those conditions . No differences between both conditions were found in general ED measures , but patients treated in the VR condition showed a greater significant improvement in specific BI measures . These results suggest that BI treatment with VR could be more targeted to its disturbances . than traditional techniques are The aim of this article was to study the effect of virtual-reality exposure to situations that are emotionally significant for patients with eating disorders ( ED ) on the stability of body-image distortion and body-image dissatisfaction . A total of 85 ED patients and 108 non-ED students were r and omly exposed to four experimental virtual environments : a kitchen with low-calorie food , a kitchen with high-calorie food , a restaurant with low-calorie food , and a restaurant with high-calorie food . In the interval between the presentation of each situation , body-image distortion and body-image dissatisfaction were assessed . Several 2 x 2 x 2 repeated measures analyses of variance ( high-calorie vs. low-calorie food x presence vs. absence of people x ED group vs. control group ) showed that ED participants had significantly higher levels of body-image distortion and body dissatisfaction after eating high-calorie food than after eating low-calorie food , while control participants reported a similar body image in all situations . The results suggest that body-image distortion and body-image dissatisfaction show both trait and state features . On the one h and , ED patients show a general predisposition to overestimate their body size and to feel more dissatisfied with their body image than controls . On the other h and , these body-image disturbances fluctuate when participants are exposed to virtual situations that are emotionally relevant for them Binge eating is often preceded by reports of negative affect , but the mechanism by which affect may lead to binge eating is unclear . This study evaluated the effect of negative affect on neural response to anticipation and receipt of palatable food in women with bulimia nervosa ( BN ) versus healthy controls . We also evaluated connectivity between the amygdala and reward-related brain regions . Females with and without BN ( n=26 ) underwent functional magnetic resonance imaging ( fMRI ) during receipt and anticipated receipt of chocolate milkshake and a tasteless solution . We measured negative affect just prior to the scan . Women with BN showed a positive correlation between negative affect and activity in the putamen , cau date , and pallidum during anticipated receipt of milkshake ( versus tasteless solution ) . There were no significant relations between negative affect and receipt of milkshake . Connectivity analyses revealed a greater relation of amygdala activity to activation in the left putamen and insula during anticipated receipt of milkshake in the bulimia group relative to the control group . The opposite pattern was found for the taste of milkshake ; the control group showed a greater relation of amygdala activity to activation in the left putamen and insula in response to milkshake receipt than the bulimia group . Results show that as negative affect increases , so does responsivity of reward regions to anticipated intake of palatable food , implying that negative affect may increase the reward value of food for individuals with bulimia nervosa or that negative affect has become a conditioned cue due to a history of binge eating in a negative mood Background Many research ers and clinicians have proposed using virtual reality ( VR ) in adjunct to in vivo exposure therapy to provide an innovative form of exposure to patients suffering from different psychological disorders . The rationale behind the ' virtual approach ' is that real and virtual exposures elicit a comparable emotional reaction in subjects , even if , to date , there are no experimental data that directly compare these two conditions . To test whether virtual stimuli are as effective as real stimuli , and more effective than photographs in the anxiety induction process , we tested the emotional reactions to real food ( RF ) , virtual reality ( VR ) food and photographs ( PH ) of food in two sample s of patients affected , respectively , by anorexia ( AN ) and bulimia nervosa ( BN ) compared to a group of healthy subjects . The two main hypotheses were the following : ( a ) the virtual exposure elicits emotional responses comparable to those produced by the real exposure ; ( b ) the sense of presence induced by the VR immersion makes the virtual experience more ecological , and consequently more effective than static pictures in producing emotional responses in humans . Methods In total , 10 AN , 10 BN and 10 healthy control subjects ( CTR ) were r and omly exposed to three experimental conditions : RF , PH , and VR while their psychological ( Stait Anxiety Inventory ( STAI-S ) and visual analogue scale for anxiety ( VAS-A ) ) and physiological ( heart rate , respiration rate , and skin conductance ) responses were recorded . Results RF and VR induced a comparable emotional reaction in patients higher than the one elicited by the PH condition . We also found a significant effect in the subjects ' degree of presence experienced in the VR condition about their level of perceived anxiety ( STAI-S and VAS-A ) : the higher the sense of presence , the stronger the level of anxiety . Conclusions Even though preliminary , the present data show that VR is more effective than PH in eliciting emotional responses similar to those expected in real life situations . More generally , the present study suggests the potential of VR in a variety of experimental , training and clinical context s , being its range of possibilities extremely wide and customizable . In particular , in a psychological perspective based on a cognitive behavioral approach , the use of VR enables the provision of specific context s to help patients to cope with their diseases thanks to an easily controlled stimulation Body-image dissatisfaction is a problem that affects a substantial minority ofwomen and cuts across various diagnostic groups . College women with a significant level ofbody-image dissatisfaction were r and omly assigned to either a cognitive-behavioral treatment ( CBT ) program ( n = 15 ) or to a waiting-list control group ( n = 16 ) . The CBT program consisted of six structured , individual sessions that applied cognitive-behavioral procedures to the problem of negative body image . At pretest , posttest , and 7-week foUow-up , multiple aspects of body image and other areas of psychosocial functioning were assessed . Relative to the control condition , the CBT program successfully improved affective body image , weakened maladaptive body-image cognitions , and enhanced social self-esteem and feelings about physical fitness and sexuality . Treatment effects were largely maintained at followup . After posttest , the control group received a 3-week treatment with immediate effects that generally replicated those obtained in the 6-wer program Treating binge eating disorders is not easy : the disordered eating is usually combined with a patient who is overweight and often obese . As underlined by the current literature , treatment outcome must focus , at a minimum , on the binge eating characterizing this disorder , on weight changes , and preferably also changes in co-morbid psychopathology . To address these issues , cognitive behavioral therapy ( CBT ) is still considered the best approach . However , if we check the results of follow-up studies , different authors reported some relapse in the frequency of binge eating and small weight gains over the follow-up period . This paper describes the 6-month follow-up outcome of the Experiential Cognitive Therapy ( ECT ) , a multi factorial treatment for binge eating disorders , including virtual reality therapy . These results are compared in a r and omized controlled trial ( n = 36 ) with the ones obtained by CBT and nutritional groups only . The results showed that 77 % of the ECT group quit binging after 6 months versus 56 % for the CBT sample and 22 % for the nutritional group sample . Moreover , the ECT sample reported better scores in most psychometric tests including EDI-2 and body image scores The main goal of this paper is to preliminarily evaluate the efficacy of a virtual-reality (VR)-based multidimensional approach in the treatment of body image attitudes and related constructs . The female binge eating disorder ( BED ) patients ( n=20 ) , involved in a residential weight control treatment including low-calorie diet ( 1200 cal/day ) and physical training , were r and omly assigned either to the multidimensional VR treatment or to psychonutritional groups based on the cognitive-behavior approach . Patients were administered a battery of outcome measures assessing eating disorders symptomathology , attitudes toward food , body dissatisfaction , level of anxiety , motivation for change , level of assertiveness , and general psychiatric symptoms . In the short term , the VR treatment was more effective than the traditional cognitive-behavioral psychonutritional groups in improving the overall psychological state of the patients . In particular , the therapy was more effective in improving body satisfaction , self-efficacy , and motivation for change . No significant differences were found in the reduction of the binge eating behavior . The possibility of inducing a significant change in body image and its associated behaviors using a VR-based short-term therapy can be useful to improve the body satisfaction in traditional weight reduction programs . However , given the nature of this research that does not include a followup study , the obtained results are preliminary only This article explores the efficacy of virtual environments representing situations that are emotionally significant to patients with eating disorders ( ED ) to modify depression and anxiety levels both in these patients and in controls . Eighty-five ED patients and 108 students were r and omly exposed to five experimental virtual environments ( a kitchen with low-calorie food , a kitchen with high-calorie food , a restaurant with high-calorie food , a restaurant with low-calorie food , and a swimming-pool ) and to one neutral environment . In the interval between the presentation of each situation , anxiety and depressed mood were assessed . Results of several repeated measures analyses demonstrated that patients show higher levels of anxiety and a more depressed mood after eating , especially high-calorie food , and after visiting the swimming pool than in the neutral room . In contrast , controls only show higher levels of anxiety in the swimming pool . In the rest of the situations they presented a similar mood state as in the neutral room . We concluded that virtual reality is a useful vehicle for eliciting similar emotional reactions to those one would expect in real life situations . Thus , this technology seems well suited for use in experimental studies as well as in evaluative and therapeutic context It is well known that obesity has a multifactorial etiology , including biological , environmental , and psychological causes . For this reason , obesity treatment requires a more integrated approach than the st and ard behavioral treatment based on dietary and physical activity only . To test the long-term efficacy of an enhanced cognitive-behavioral therapy ( CBT ) of obesity , including a virtual reality ( VR ) module aim ed at both unlocking the negative memory of the body and to modify its behavioral and emotional correlates , 163 female morbidly obese in patients ( body mass index > 40 ) were r and omly assigned to three conditions : a st and ard behavioral inpatient program ( SBP ) , SBP plus st and ard CBT , and SBP plus VR-enhanced CBT . Patients ' weight , eating behavior , and body dissatisfaction were measured at the start and upon completion of the inpatient program . Weight was assessed also at 1 year follow-up . All measures improved significantly at discharge from the inpatient program , and no significant difference was found among the conditions . However , odds ratios showed that patients in the VR condition had a greater probability of maintaining or improving weight loss at 1 year follow-up than SBP patients had ( 48 % vs. 11 % , p = 0.004 ) and , to a lesser extent , than CBT patients had ( 48 % vs. 29 % , p = 0.08 ) . Indeed , only the VR-enhanced CBT was effective in further improving weight loss at 1 year follow-up . On the contrary , participants who received only the inpatient program regained back , on average , most of the weight they had lost . Findings support the hypothesis that a VR module addressing the locked negative memory of the body may enhance the long-term efficacy of st and ard CBT |
11,876 | 26,207,706 | FINDINGS The only method for obtaining reliable coagulation test results from central venous access devices is the flush then waste/discard method . | BACKGROUND Central venous access devices are used for chemotherapy and other medication administration , blood product administration , parenteral nutrition , and for obtaining blood sample s in patients where the vasculature is difficult to access .
Patients may need additional blood sample s prior to invasive procedures and when clinical situations arise during cancer care .
In addition , monitoring coagulability through ongoing blood testing is common in patients with cancer and requires repeated sampling to adjust anticoagulant medications .
OBJECTIVES The purpose of this review of the literature is to determine the best practice s for collecting coagulation test sample s from central venous access devices . | The purpose of this study was to test agreement in blood values obtained from a discard method and a push-pull method in sample s from central venous catheters in pediatric patients . The discard method causes blood loss beyond what is necessary for blood testing and increases potential for infection each time the central venous catheter is entered . Twenty-eight children ranging in age from 6 months to 12 years were enrolled in the study . A research protocol was developed to pair the 2 methods of blood collection for each sample . The Bl and -Altman method was used to test agreement on each blood value for each paired sample . Of the 438 pairs of measured blood values , 420 ( 95.9 % ) fell within the limits of agreement . Nurses reported no difficulty in using the push-pull technique to obtain any sample s. The push-pull method of obtaining blood specimens from pediatric central venous catheters should be considered . It can eliminate blood loss through discard and can reduce infection because it reduces the number of times a catheter is entered Purpose / Objective : The purpose of this study was to test an evidence -based procedure of drawing blood sample s for coagulation testing from heparinized peripherally inserted central catheter ( PICC ) by comparing results with blood drawn from venipuncture ( VP ) . Design : A prospect i ve , quasi-experimental design using purposive sampling was used . Setting : The setting was a 230-bed community hospital located in the Southwest . The hospital is part of a 15-hospital system . Sample : The sample was composed of 30 hospitalized patients with heparinized PICCs . Methods : Informed consent was obtained . Using aseptic technique , sample s of blood were drawn via VP and from the PICC using the evidence -based procedure . Data were analyzed using Pearson product moment correlations and Bl and -Altman analysis . Findings : For 5 coagulation tests studied , correlations between PICC values and VP values ranged from 0.990 to 0.998 , indicating almost perfect correlations . In Bl and -Altman analyses , mean biases and SDs were small to moderate for prothrombin time , 0.13 seconds ( −0.55 to 0.81 seconds ) ( P = 0.0484 ) ; international normalized ratio , 0.010 ( −0.050 to 0.070 ) ( P = 0.085 ) ; partial thromboplastin time , 2.16 seconds ( −5.10 to 9.43 seconds ) ( P = 0.0033 ) ; and fibrinogen , −18.2 mg ( −70.4 to 34.1 mg ) ( P = 0.0033 ) and 0.52 ( −0.73 to 1.77 ) seconds ( P = 0.0003 ) . Correlations of absolute difference versus average ranged from 0.18 to 0.49 . Only the paired international normalized ratio sample s had P values suggesting nonagreement . Conclusions : Drawing blood sample s from heparinized PICCs for coagulation tests using the evidence -based procedure developed for this study result ed in accurate coagulation test results in 4 of the 5 tests : prothrombin time , partial thromboplastin time , and fibrinogen in seconds and in milligrams PURPOSE / OBJECTIVES Determine the blood volume that must be wasted to obtain a clinical ly useful prothrombin time ( PT ) , activated partial thromboplastin time ( APTT ) , and fibrinogen concentration for blood drawn from a heparinized ( 2.5 ml of 100 units/ml ) , double-lumen venous catheter . DESIGN Prospect i ve , nonr and omized study comparing test results obtained from blood sample s drawn through the catheters with those obtained via peripheral venipuncture . Patients acted as their own control . SETTING Inpatient and outpatient units of a cancer research center located in a mid-Atlantic city in the United States . SAMPLE Twenty double-lumen 10 Fr . Hickman catheters ( Bard Access Systems , Salt Lake City , UT ) were studied in 20 adult patients with cancer who had no history of coagulation disorders . METHODS Sample s were collected from the red lumen of 20 heparinized , double-lumen Hickman catheters after 5 , 10 , 15 , 20 , and 25 ml of blood first were discarded . PTs , APTTs , and fibrinogen concentrations were measured on each sample . The results were compared with those derived from a simultaneously obtained peripheral blood sample . MAIN RESEARCH VARIABLES PT , APTT , and fibrinogen values of blood sample s after 5 , 10 , 15 , 20 , and 25 ml discards and PT , APTT , and fibrinogen of peripheral blood sample s. FINDINGS The coagulation results using peripheral blood were always within the normal range except for one slightly elevated APTT . After 25 ml of discard , all of the PTs and fibrinogen concentrations and 95 % of the APTTs of catheter blood were within the normal range and therefore clinical ly useful . CONCLUSIONS Clinical ly useful PTs , APTTs , and fibrinogen concentrations often can be derived with catheter-drawn blood when the objective is to confirm normal coagulation . However , because it is very difficult to obtain heparin-free sample s through heparinized , double-lumen Hickman catheters , peripheral blood should be drawn for coagulation testing when a totally heparin-free sample is needed to make a critical clinical decision . IMPLICATION S FOR NURSING PRACTICE These findings provide important information for practice when nurses have to decide whether to draw coagulation tests through a heparinized catheter . Further research is needed with larger sample s in varied population s ( e.g. , pediatrics ) to study catheters made of different material s and of different calibers |
11,877 | 26,507,078 | In addition , the implication s of adding either the PCA3 assay or the phi to clinical assessment were not clear .
Furthermore , the addition of the PCA3 assay or the phi to clinical assessment plus magnetic resonance imaging was not found to improve discrimination .
The results from the cost-effectiveness analyses indicated that using either the PCA3 assay or the phi in the NHS was not cost-effective .
The clinical benefit of using the PCA3 assay or the phi in combination with existing tests , scans and clinical judgement has not yet been confirmed .
The results from the cost-effectiveness analyses indicate that the use of these tests in the NHS would not be cost-effective . | BACKGROUND There is no single definitive test to identify prostate cancer in men .
Biopsies are commonly used to obtain sample s of prostate tissue for histopathological examination .
However , this approach frequently misses cases of cancer , meaning that repeat biopsies may be necessary to obtain a diagnosis .
The PROGENSA ( ® ) prostate cancer antigen 3 ( PCA3 ) assay ( Hologic Gen-Probe , Marlborough , MA , USA ) and the Prostate Health Index ( phi ; Beckman Coulter Inc. , Brea , CA , USA ) are two new tests ( a urine test and a blood test , respectively ) that are design ed to be used to help clinicians decide whether or not to recommend a repeat biopsy .
OBJECTIVE To evaluate the clinical effectiveness and cost-effectiveness of the PCA3 assay and the phi in the diagnosis of prostate cancer . | PURPOSE In patients with a negative prostate biopsy and persistent suspicion of prostate cancer , additional analyses such as the PCA3 score , PHI and multiparametric magnetic resonance imaging have been proposed to reduce the number of unnecessary repeat biopsies . In this study we evaluate the diagnostic accuracy of PCA3 , PHI , multiparametric magnetic resonance imaging and various combinations of these tests in the repeat biopsy setting . MATERIAL S AND METHODS A total of 170 patients with an initial negative prostate biopsy and persistent suspicion of prostate cancer were enrolled in this prospect i ve study . The patients underwent measurements of the total prostate specific antigen and free prostate specific antigen rate , along with PHI , PCA3 tests and multiparametric magnetic resonance imaging before st and ard repeat biopsy that was performed by urologists blinded to the multiparametric magnetic resonance imaging results . Multivariate logistic regression models with various combinations of PCA3 , PHI and multiparametric magnetic resonance imaging were used to identify the predictors of prostate cancer with repeat biopsy , and the performance of these models was compared using ROC curves , AUC analysis and decision curve analysis . RESULTS In the ROC analysis the most significant contribution was provided by multiparametric magnetic resonance imaging ( AUC 0.936 ) , which was greater than the contribution of the PHI+PCA3 model ( p < 0.001 ) . In the multivariate logistic regression analysis only multiparametric magnetic resonance imaging was a significant independent predictor of prostate cancer diagnosis with repeat biopsy ( p < 0.001 ) . The results of the decision curve analysis confirmed that the most significant improvement in the net benefit was provided by multiparametric magnetic resonance imaging . CONCLUSIONS Multiparametric magnetic resonance imaging provides high diagnostic accuracy in identifying patients with prostate cancer in the repeat biopsy setting compared with PCA3 and PHI PURPOSE We tested the hypothesis that serum isoform [-2]proPSA derivatives % p2PSA and Prostate Health Index are accurate predictors of prostate cancer in men scheduled for repeat biopsy . MATERIAL S AND METHODS The study was an observational prospect i ve evaluation of a clinical cohort of men with 1 or 2 previous negative prostate biopsies , with persistent suspicion of prostate cancer . They were enrolled in the study to determine the diagnostic accuracy of % p2PSA using the formula , ( p2PSA pg/ml)/(free prostate specific antigen ng/ml × 1,000)] × 100 , and Beckman-Coulter Prostate Health Index using the formula , ( p2PSA/free prostate specific antigen ) × √total prostate specific antigen ) , and to compare it with the accuracy of established prostate cancer serum tests ( total prostate specific antigen , free prostate specific antigen and percent free prostate specific antigen ) . Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis . RESULTS Prostate cancer was found in 71 of 222 ( 31.9 % ) subjects . % p2PSA and Prostate Health Index were the most accurate predictors of disease . % p2PSA significantly outperformed total prostate specific antigen , free prostate specific antigen , percent free prostate specific antigen and p2PSA in the prediction of prostate cancer ( p ≤0.01 ) , but not Prostate Health Index ( p = 0.094 ) . Prostate Health Index significantly outperformed total prostate specific antigen and p2PSA ( p ≤0.001 ) but not free prostate specific antigen ( p = 0.109 ) and free/total prostate specific antigen ( p = 0.136 ) . In multivariable logistic regression models % p2PSA and Prostate Health Index achieved independent predictor status , and significantly increased the accuracy of multivariable models including prostate specific antigen and prostate volume with or without percent free prostate specific antigen and prostate specific antigen density by 8 % to 11 % ( p ≤0.034 ) . At a % p2PSA cutoff of 1.23 , 153 ( 68.9 % ) biopsies could have been avoided , missing prostate cancer in 6 patients . At a Prostate Health Index cutoff of 28.8 , 116 ( 52.25 % ) biopsies could have been avoided , missing prostate cancer in 6 patients . CONCLUSIONS Serum % p2PSA and Prostate Health Index are more accurate than st and ard reference tests in predicting repeat prostate biopsy outcome , and could avoid unnecessary repeat biopsies Study Type – Diagnosis ( exploratory cohort ) Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men . In the United States , 90 % of men with prostate cancer are more than age 60 years , diagnosed by early detection with the prostate-specific antigen ( PSA ) blood test , and have disease believed confined to the prostate gl and ( clinical ly localized ) . Common treatments for clinical ly localized prostate cancer include watchful waiting ( WW ) , surgery to remove the prostate gl and ( radical prostatectomy ) , external-beam radiation therapy and interstitial radiation therapy ( brachytherapy ) , and and rogen deprivation . Little is known about the relative effectiveness and harms of treatments because of the paucity of r and omized controlled trials . The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study # 407:Prostate Cancer Intervention Versus Observation Trial ( PIVOT ) , initiated in 1994 , is a multicenter r and omized controlled trial comparing radical prostatectomy with WW in men with clinical ly localized prostate cancer . We describe the study rationale , design , recruitment methods , and baseline characteristics of PIVOT enrollees . We provide comparisons with eligible men declining enrollment and men participating in another recently reported r and omized trial of radical prostatectomy vs WW conducted in Sc and inavia . We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment . From these , 5023 met initial age , comorbidity , and disease eligibility criteria , and a total of 731 men agreed to participate and were r and omized . The mean age of enrollees was 67 years . Nearly one-third were African American . Approximately 85 % reported that they were fully active . The median PSA was 7.8ng/mL ( mean 10.2ng/mL ) . In three-fourths of men , the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise . Using previously developed tumor risk categorizations incorporating PSA levels , Gleason histologic grade , and tumor stage , it was found that approximately 40 % had low-risk , 34 % had medium-risk , and 21 % had high-risk prostate cancer based on local histopathology . Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Sc and inavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Sc and inavian trial . PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States . Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinical ly localized prostate cancer BACKGROUND The Prostate CAncer gene 3 ( PCA3 ) assay has shown promise as an aid in prostate cancer ( pCA ) diagnosis in identifying men with a high probability of a positive ( repeat ) biopsy . OBJECTIVE This study evaluated the clinical utility of the PROGENSA PCA3 assay . DESIGN , SETTING , AND PARTICIPANTS This European prospect i ve , multicentre study enrolled men with one or two negative biopsies scheduled for repeat biopsy . MEASUREMENTS After digital rectal examination ( DRE ) , first-catch urine was collected to measure PCA3 mRNA concentration and to calculate the PCA3 score . The PCA3 score was compared to biopsy outcome . The diagnostic accuracy of the PCA3 assay was compared to percent of free prostate-specific antigen ( % fPSA ) . RESULTS AND LIMITATIONS In 463 men , the positive repeat biopsy rate was 28 % . The higher the PCA3 score , the greater the probability of a positive repeat biopsy . The PCA3 score ( cut-off of 35 ) had a greater diagnostic accuracy than % fPSA ( cut-off of 25 % ) . The PCA3 score was independent of the number of previous biopsies , age , prostate volume , and total prostate-specific antigen ( PSA ) level . Moreover , the PCA3 score was significantly higher in men with high- grade prostate intraepithelial neoplasia ( HGPIN ) versus those without HGPIN , clinical stage T2 versus T1 , Gleason score > or=7 versus < 7 , and " significant " versus " indolent " ( clinical stage T1c , PSA density [ PSAD ] < 0.15ng/ml , Gleason score in biopsy < or=6 , and percent positive cores < or=33 % ) pCA . CONCLUSIONS The probability of a positive repeat biopsy increases with rising PCA3 scores . The PCA3 score was superior to % fPSA for predicting repeat prostate biopsy outcome and may be indicative of clinical stage and significance of pCa Background : Identification of men harbouring insignificant prostate cancer ( PC ) is important in selecting patients for active surveillance . Tools have been developed in PSA-screened population s to identify such men based on clinical and biopsy parameters . Methods : Prospect ively collected case series of 848 patients was treated with radical prostatectomy between July 2007 and October 2011 at an English tertiary care centre . Tumour volume was assessed by pathological examination . For each tool , receiver operator characteristics were calculated for predicting insignificant disease by three different criteria and the area under each curve compared . Comparison of accuracy in screened and unscreened population s was performed . Results : Of 848 patients , 415 had Gleason 3 + 3 disease on biopsy . Of these , 32.0 % had extra-prostatic extension and 50.2 % were up grade d. One had positive lymph nodes . Two hundred and six ( 24 % of cohort ) were D’Amico low risk . Of these , 143 had more than two biopsy cores involved . None of the tools evaluated has adequate discriminative power in predicting insignificant tumour burden . Accuracy is low in PSA-screened and -unscreened population s. Conclusions : In our unscreened population , tools design ed to identify insignificant PC are inaccurate . Detection of a wider size range of prostate tumours in the unscreened may contribute to relative inaccuracy BACKGROUND After 11 years of follow-up , the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) reported a 29 % reduction in prostate-cancer mortality among men who underwent screening for prostate-specific antigen ( PSA ) levels . However , the extent to which harms to quality of life result ing from overdiagnosis and treatment counterbalance this benefit is uncertain . METHODS On the basis of ERSPC follow-up data , we used Microsimulation Screening Analysis ( MISCAN ) to predict the number of prostate cancers , treatments , deaths , and quality -adjusted life-years ( QALYs ) gained after the introduction of PSA screening . Various screening strategies , efficacies , and quality -of-life assumptions were modeled . RESULTS Per 1000 men of all ages who were followed for their entire life span , we predicted that annual screening of men between the ages of 55 and 69 years would result in nine fewer deaths from prostate cancer ( 28 % reduction ) , 14 fewer men receiving palliative therapy ( 35 % reduction ) , and a total of 73 life-years gained ( average , 8.4 years per prostate-cancer death avoided ) . The number of QALYs that were gained was 56 ( range , -21 to 97 ) , a reduction of 23 % from unadjusted life-years gained . To prevent one prostate-cancer death , 98 men would need to be screened and 5 cancers would need to be detected . Screening of all men between the ages of 55 and 74 would result in more life-years gained ( 82 ) but the same number of QALYs ( 56 ) . CONCLUSIONS The benefit of PSA screening was diminished by loss of QALYs owing to postdiagnosis long-term effects . Longer follow-up data from both the ERSPC and quality -of-life analyses are essential before universal recommendations regarding screening can be made . ( Funded by the Netherl and s Organization for Health Research and Development and others . ) BACKGROUND In 2008 , we reported that radical prostatectomy , as compared with watchful waiting , reduces the rate of death from prostate cancer . After an additional 3 years of follow-up , we now report estimated 15-year results . METHODS From October 1989 through February 1999 , we r and omly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy . Follow-up was complete through December 2009 , with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death . Relative risks , with 95 % confidence intervals , were estimated with the use of a Cox proportional-hazards model . RESULTS During a median of 12.8 years , 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died ( P=0.007 ) . In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting , death was due to prostate cancer . This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6 % and 20.7 % , respectively ( a difference of 6.1 percentage points ; 95 % confidence interval [ CI ] , 0.2 to 12.0 ) , and a relative risk with surgery of 0.62 ( 95 % CI , 0.44 to 0.87 ; P=0.01 ) . The survival benefit was similar before and after 9 years of follow-up , was observed also among men with low-risk prostate cancer , and was confined to men younger than 65 years of age . The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age . Among men who underwent radical prostatectomy , those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth ( relative risk , 6.9 ; 95 % CI , 2.6 to 18.4 ) . CONCLUSIONS Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer . Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment . ( Funded by the Swedish Cancer Society and the National Institutes of Health . ) PURPOSE The identification of clinical ly insignificant prostate cancer could help avoid overtreatment . Current criteria for insignificant prostate cancer use a tumor volume threshold of less than 0.5 ml for the index tumor . In this study we reassess this tumor volume threshold for clinical ly insignificant prostate cancer using an independent data set . MATERIAL S AND METHODS The rate of insignificant prostate cancer was calculated by modeling lifetime risk estimates of prostate cancer diagnosis in screened and nonscreened participants in a r and omized prostate cancer screening trial . Using lifetime risk estimates 50.8 % of screen detected prostate cancer was calculated to be clinical ly insignificant and the 49.2 % largest tumor volume of 325 prostatectomy specimens was used to determine the threshold tumor volume for insignificant prostate cancer . Because stage and grade represent the strongest determinants of cancer aggressiveness , we also calculated the tumor volume threshold for insignificant cancer after the selection of patients with organ confined prostate cancer without Gleason pattern 4/5 . The analyses were performed for total tumor volume and for index tumor volume . RESULTS The minimum threshold tumor volume of the index tumor and total tumor was 0.55 and 0.70 ml , respectively . After accounting for tumor stage and grade we obtained a threshold volume for the index tumor and total tumor of 1.3 and 2.5 ml , respectively . CONCLUSIONS We confirmed the original value of the index tumor volume threshold of 0.5 ml for insignificant prostate cancer , and we demonstrated that clinical ly insignificant prostate cancer may include index Gleason score 6 , pT2 tumors with volumes up to at least 1.3 ml . These results suggest a reconsideration of current methods and nomograms used for pretreatment risk assessment OBJECTIVE To overcome the well-known prostate-specific antigen limits , several new biomarkers have been proposed . Since its introduction in clinical practice , the urinary prostate cancer gene 3 ( PCA3 ) assay has shown promising results for prostate cancer ( PC ) detection . Furthermore , multiparametric magnetic resonance imaging ( mMRI ) has the ability to better describe several aspects of PC . METHODS A prospect i ve study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC . All patients underwent the PCA3 test and mMRI before a second transrectal ultrasound-guided prostate biopsy . The accuracy and reliability of PCA3 ( 3 different cutoff points ) and mMRI were evaluated . Four multivariate logistic regression models were analyzed , in terms of discrimination and the cost benefit , to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome . A decision curve analysis was also plotted . RESULTS Repeated transrectal ultrasound-guided biopsy identified 68 new cases ( 41.7 % ) of PC . The sensitivity and specificity of the PCA3 test and mMRI was 68 % and 49 % and 74 % and 90 % , respectively . Evaluating the regression models , the best discrimination ( area under the curve 0.808 ) was obtained using the full model ( base clinical model plus mMRI and PCA3 ) . The decision curve analysis , to evaluate the cost/benefit ratio , showed good performance in predicting PC with the model that included mMRI and PCA3 . CONCLUSION mMRI increased the accuracy and sensitivity of the PCA3 test , and the use of the full model significantly improved the cost/benefit ratio , avoiding unnecessary biopsies AIM To compare the prostate antigen 3 ( PCA3 ) test with (1)H-magnetic resonance spectroscopic imaging ( (1)H-MRSI ) and dynamic contrast-enhanced magnetic resonance imaging ( DCEMR ) combined examination in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen ( PSA ) levels and prior negative r and om transrectal ultrasound (TRUS)-guided biopsy . PATIENTS AND METHODS Forty-three patients with a first r and om biopsy negative for prostate adenocarcinoma , persistent elevated PSA and negative digital rectal examination were recruited . All the patients were su bmi tted to MRSI examination ( MRSI-DCEMR ) and were su bmi tted to an attentive prostate massage in order to perform PCA3 assay . Afterwards , 10-core laterally-directed r and om TRUS-guided prostate biopsy was performed . RESULTS The overall sensitivity and specificity of a PCA3 score ≥35 for positive biopsy were 76.9 % and 66.6 % , respectively , with a positive predictive value ( PPV ) of 80 % and a negative predictive value ( NPV ) of 62.5 % ; as for MRSI sensitivity and specificity were , respectively , 92.8 % and 86.6 % with a PPV of 92.8 % and a NPV of 86.6 % . Receiver operating characteristic ( ROC ) analysis rates were 0.755 for PCA3 and 0.864 for MRSI . CONCLUSION Combined MRSI/DCEMR can better improve the cancer detection rate in patients with prior negative TRUS-guided biopsy and altered PSA serum levels than PCA3 . Optimization of MRSI will allow more precise diagnosis of local invasion and improved bioptical procedures BACKGROUND The most beneficial number and the location of prostate biopsies remain matters of debate , especially after an initial negative biopsy . OBJECTIVE To identify the optimal combination of sampling sites ( number and location ) to detect prostate cancer ( PCa ) in patients previously su bmi tted to an initial negative prostatic biopsy . DESIGN , SETTING , AND PARTICIPANTS A transrectal ultrasound-guided systematic 24-core prostate biopsy ( 24PBx ) was performed prospect ively in 340 consecutive patients after a first negative biopsy ( at least 12 cores ) . MEASUREMENTS We relied on a classification and regression tree analysis to identify three clinical ly different subgroups of patients at dissimilar risk of harboring PCa at second biopsy . Subsequently , we set the cancer-positive rate of the 24PBx at 100 % and calculated PCa detection rates for 255 possible combinations of sampling sites . We selected the optimal biopsy scheme ( defined as the combination of sampling sites that detected 95 % of all the cancers with the minimal number of biopsy cores ) for each patient subgroup . RESULTS AND LIMITATIONS After an initial negative biopsy , cancer was detected at rebiopsy in 95 men ( 27.9 % ) . At a given number of cores , the cancer detection rates varied significantly according to the different combination of sites considered . Three different PCa risk groups were identified : ( 1 ) previous report of atypical small acinar proliferation of the prostate ( ASAP ) , ( 2 ) no previous ASAP and ratio of free prostate-specific antigen ( fPSA ) to total PSA ( % fPSA ) ≤10 % , and ( 3 ) no previous ASAP and % fPSA > 10 % . For patients with previous ASAP or patients with no previous ASAP and % fPSA ≤10 % , two schemes with different combinations of 14 cores were most favorable . The optimal sampling in patients with no previous ASAP and % fPSA > 10 % was a scheme with a combination of 20 cores . CONCLUSIONS Both the number and the location of biopsy cores taken affect cancer detection rates in a repeated biopsy setting . We developed an internally vali date d flowchart to identify the most advantageous set of sampling sites according to patient characteristics BACKGROUND Prostate cancer antigen 3 ( PCA3 ) holds promise in diagnosing prostate cancer ( PCa ) , but no consensus has been reached on its clinical use . Multivariable predictive models have shown increased accuracy over individual risk factors . OBJECTIVE To compare the performance of the two available risk estimators incorporating PCA3 in the detection of PCa in the " grey area " of prostate-specific antigen ( PSA ) < 10 ng/ml : the up date d Prostate Cancer Prevention Trial ( PCPT ) calculator and Chun 's nomogram . DESIGN , SETTING , AND PARTICIPANTS Two hundred eighteen patients presenting with an abnormal PSA ( excluding those with PSA > 10 ng/ml ) and /or abnormal digital rectal examination were prospect ively enrolled in a multicentre Italian study between October 2008 and October 2009 . All patients underwent ≥12-core prostate biopsy . MEASUREMENTS PCA3 scores were assessed using the Progensa assay ( Gen-Probe , San Diego , CA , USA ) . Comparisons between the two models were performed using tests of accuracy ( area under the receiver operating characteristic curve [ AUC-ROC ] ) , calibration plots , and decision curve analysis . Biopsy predictors were identified by univariable and multivariable logistic regression . In addition , performance of PCA3 was analysed through AUC-ROC and predictive values . RESULTS AND LIMITATIONS PCa was detected in 73 patients ( 33.5 % ) . Among predictors included in the models , only PCA3 , PSA , and prostate volume retained significant predictive value . AUC-ROC was higher for the up date d PCPT calculator compared to Chun 's nomogram ( 79.6 % vs 71.5 % ; p=0.043 ) ; however , Chun 's nomogram displayed better overall calibration and a higher net benefit on decision curve analysis . Using a probability threshold of 25 % , no high- grade cancers would be missed ; the PCPT calculator would save 11 % of biopsies , missing no cancer , whereas Chun 's nomogram would save 22 % of avoidable biopsies , although missing 4.1 % non-high- grade cancers . The small number of patients may account for the lack of statistical significance in the predictive value of individual variables or model comparison . CONCLUSIONS Both Chun 's nomogram and the PCPT calculator , by incorporating PCA3 , can assist in the decision to biopsy by assignment of an individual risk of PCa , specifically in the PSA levels < 10 ng/ml OBJECTIVES The aim of this prospect i ve study was to evaluate the sensitivity of the sextant biopsy protocol compared with a more extensive procedure for the detection of prostate cancer and to define a biopsy model with the minimal number of biopsies necessary to maintain diagnostic accuracy . METHODS A total of 512 consecutive patients with suspected prostate cancer were examined with transrectal ultrasound ( TRUS ) and underwent TRUS-guided core biopsy . All patients had 8 or 10 st and ardized biopsy sample s taken , with the number depending on the size of the gl and . Additional biopsy sample s were taken from hypoechoic or hyperechoic lesions located outside the predetermined location for the st and ardized biopsies ( ie , target biopsies ) . The sensitivity of the detection of cancer for different combinations of biopsy sample s was analyzed and compared with that of our model with 8 to 10 biopsies . RESULTS In all , 276 cancers were detected , of which 88 ( 32 % ) had an isoechoic appearance . Sensitivity was 59 % for focal lesions detected by TRUS , 85 % to 97 % for different combinations of systematic biopsy sample s , and 93 % to 98 % for a combination of systematic and target biopsy sample s. The sensitivity for the st and ard sextant protocol was 85 % . By adding target biopsies , the sensitivity increased to 93 % . CONCLUSIONS The st and ard sextant protocol leaves 15 % of cancers undetected compared with results obtained from a more extensive biopsy procedure . By combining systematic and target sampling , the sensitivity increases ; however , a major concern is that the clinical importance of cancers detected by multiple biopsies needs to be evaluated INTRODUCTION Prostate Cancer Gene 3 ( PCA3 ) is a recently described and highly specific urinary marker for prostate cancer ( CaP ) . Its introduction in clinical practice to supplement low specificity of prostate specific antigen ( PSA ) can improve CaP diagnosis and follow-up . However , before its introduction , it is necessary to vali date the method of PCA3 detection in distinct geographic population s. OBJECTIVES Our aim was to describe for the first time in Latin America , the application of the PROGENSA PCA3 assay for PCA3 detection in urine in Chilean men and its utility for CaP diagnosis in men with an indication of prostate biopsy . MATERIAL S AND METHODS Sixty-four Chilean patients ( mean age , 64 years ) with indication of prostate biopsy because of elevated PSA and /or suspicious digital rectal examination ( DRE ) were prospect ively recruited . PCA3 scores were assessed from urine sample s obtained after DRE , before biopsy , and compared with PSA levels and biopsy outcome . RESULTS The median PSA value and mean PCA3 score were 5.8 ng/ml and 31.7 , respectively . Using a cutoff PCA3 score of 35 , the sensitivity and specificity for detecting CaP were 52 % and 87 % , respectively . The receiver operating characteristic ( ROC ) curve analysis showed an area under the curve of 0.77 for PCA3 and 0.57 for PSA , for the same group of patients . In patients with previous negative biopsy , PCA3 specificity increased by 2.2 % . CONCLUSIONS This is the first report in Latin America on the use of PCA3 in diagnosing CaP. Our results are comparable to those reported in other population s in the literature , demonstrating the reproducibility of the test . PCA3 score was highly specific and we specially recommend its use in patients with persistent elevated PSA and prior negative biopsies PURPOSE Due to the limited specificity of prostate specific antigen for prostate cancer screening , there is an ongoing search for adjunctive biomarkers . Retrospective studies have suggested that an isoform of proenzyme prostate specific antigen called [-2]proenzyme prostate specific antigen may enhance the specificity of prostate specific antigen based screening . We examined the usefulness of this isoform in a prospect i ve prostate cancer screening study . MATERIAL S AND METHODS From a population of 2,034 men undergoing prostate cancer screening we examined the relationship between the measurement of the [-2]isoform of proenzyme prostate specific antigen ( p2PSA ) and prostate cancer detection . Specifically we compared the usefulness of total prostate specific antigen , the ratio of free-to-total prostate specific antigen , the ratio of p2PSA-to-free prostate specific antigen , and a formula combining prostate specific antigen , free prostate specific antigen and p2PSA ( the Beckman Coulter prostate health index or phi ) to predict prostate cancer in men from the study undergoing prostate biopsy with a prostate specific antigen of 2.5 to 10 ng/ml and nonsuspicious digital rectal examination . RESULTS Despite similar total prostate specific antigen ( p = 0.88 ) , percent free prostate specific antigen ( p = 0.02 ) and % p2PSA ( p = 0.0006 ) distinguished between positive and negative biopsy results . On ROC analysis % p2PSA ( AUC 0.76 ) outperformed prostate specific antigen ( AUC 0.50 ) and percent free prostate specific antigen ( AUC 0.68 ) for differentiating between prostate cancer and benign disease . Setting the sensitivity at 88.5 % , p2PSA led to a substantial improvement in specificity as well as positive and negative predictive values . The Beckman Coulter prostate health index ( AUC 0.77 ) had the best overall performance characteristics . CONCLUSIONS This is the first prospect i ve study to our knowledge to demonstrate that p2PSA provides improved discrimination between prostate cancer and benign disease in screened men with a prostate specific antigen of 2.5 to 10 ng/ml and a negative digital rectal examination Study Type – Clinical ( prospect i ve trial ) BACKGROUND Prediction models need external validation to assess their value beyond the setting where the model was derived from . OBJECTIVE To assess the external validity of the European R and omized study of Screening for Prostate Cancer ( ERSPC ) risk calculator ( www.prostatecancer-riskcalculator.com ) for the probability of having a positive prostate biopsy ( P(posb ) ) . DESIGN , SETTING AND PARTICIPANTS The ERSPC risk calculator was based on data of the initial screening round of the ERSPC section Rotterdam and vali date d in 1825 and 531 men biopsied at the initial screening round in the Finnish and Swedish sections of the ERSPC respectively . P(posb ) was calculated using serum prostate specific antigen ( PSA ) , outcome of digital rectal examination ( DRE ) , transrectal ultrasound and ultrasound assessed prostate volume . MEASUREMENTS The external validity was assessed for the presence of cancer at biopsy by calibration ( agreement between observed and predicted outcomes ) , discrimination ( separation of those with and without cancer ) , and decision curves ( for clinical usefulness ) . RESULTS AND LIMITATIONS Prostate cancer was detected in 469 men ( 26 % ) of the Finnish cohort and in 124 men ( 23 % ) of the Swedish cohort . Systematic miscalibration was present in both cohorts ( mean predicted probability 34 % versus 26 % observed , and 29 % versus 23 % observed , both p<0.001 ) . The areas under the curves were 0.76 and 0.78 , and substantially lower for the model with PSA only ( 0.64 and 0.68 respectively ) . The model proved clinical ly useful for any decision threshold compared with a model with PSA only , PSA and DRE , or biopsying all men . A limitation is that the model is based on sextant biopsies results . CONCLUSIONS The ERSPC risk calculator discriminated well between those with and without prostate cancer among initially screened men , but overestimated the risk of a positive biopsy . Further research is necessary to assess the performance and applicability of the ERSPC risk calculator when a clinical setting is considered rather than a screening setting Objectives To measure the effect of the adverse events within 35 days of transrectal ultrasound guided biopsy from the perspective of asymptomatic men having prostate specific antigen ( PSA ) testing ; to assess early attitude to re-biopsy ; to estimate healthcare re source use associated with adverse events due to biopsy ; and to develop a classification scheme for reporting adverse events after prostate biopsy . Design Prospect i ve cohort study ( Prostate Biopsy Effects : ProBE ) nested within Prostate Testing for Cancer and Treatment ( ProtecT ) study . Participants Between 1999 and 2008 , 227 000 community dwelling men aged 5069 years were identified at 352 practice s and invited to counselling about PSA testing . 111 148 attended a nurse led clinic in the community , and 10 297 with PSA concentrations of 3 - 20 ng/mL were offered biopsy within ProtecT. Between February 2006 and May 2008 , 1147/1753 ( 65 % ) eligible men ( mean age 62.1 years , mean PSA 5.4 ng/mL ) having 10 core transrectal ultrasound guided biopsy under antibiotic cover in the context of ProtecT were recruited to the ProBE study . Outcome measures Purpose design ed question naire administered at biopsy and 7 and 35 days after the procedure to measure frequency and effect of symptoms related to pain , infection , and bleeding ; patients ’ attitude to repeat biopsy assessed immediately after biopsy and 7 days later ; participants ’ healthcare re source use within 35 days of biopsy evaluated by question naire , telephone follow-up , and medical note review ; each man ’s adverse event profile grade d according to symptoms and healthcare use . Results Pain was reported by 429/984 ( 43.6 % ) , fever by 172/985 ( 17.5 % ) , haematuria by 642/976 ( 65.8 % ) , haematochezia by 356/967 ( 36.8 % ) , and haemoejaculate by 605/653 ( 92.6 % ) men during the 35 days after biopsy . Fewer men rated these symptoms as a major/moderate problem—71/977 ( 7.3 % ) for pain , 54/981 ( 5.5 % ) for fever , 59/958 ( 6.2 % ) for haematuria , 24/951 ( 2.5 % ) for haematochezia , and 172/646 ( 26.6 % ) for haemoejaculate . Immediately after biopsy , 124/1142 ( 10.9 % , 95 % confidence interval 9.2 to 12.8 ) men reported that they would consider further biopsy a major or moderate problem : seven days after biopsy , this proportion had increased to 213/1085 ( 19.6 % , 17.4 % to 22.1 % ) . A negative attitude to repeat biopsy was associated with unfavourable experience after the first biopsy , particularly pain at biopsy ( odds ratio 8.2 , P<0.001 ) and symptoms related to infection ( 7.9 , P<0.001 ) and bleeding ( 4.2 , P<0.001 ) ; differences were evident between centres ( P<0.001 ) . 119/1147 ( 10.4 % , 8.7 % to 12.3 % ) men reported consultation with a healthcare professional ( usually their general practitioner ) , most commonly for infective symptoms . Complete data for all index symptoms at all time points were available in 851 participants . Symptoms and healthcare use could be used to grade these men as follows : grade 0 ( no symptoms/contact ) 18 ( 2.1 % , 1.3 % to 3.3 % ) ; grade 1 ( minor problem/no contact ) 550 ( 64.6 % , 61.4 % to 67.8 % ) ; grade 2 ( moderate/major problem or contact ) 271 ( 31.8 % , 28.8 % to 35.1 % ) ; grade 3 ( hospital admission ) 12 ( 1.4 % , 0.8 % to 2.4 % ) ; and grade 4 ( death ) 0 . Grade of adverse event was associated with an unfavourable attitude to repeat biopsy ( Kendall ’s τ-b ordinal by ordinal 0.29 , P<0.001 ) . Conclusion This study with a high response rate of 89 % at 35 days in men undergoing biopsy in the context of a r and omised controlled trial has shown that although prostate biopsy is well tolerated by most men , it is associated with significant symptoms in a minority and affects attitudes to repeat biopsy and primary care re source use . These findings will inform men who seek PSA testing for detection of prostate cancer and assist their physicians during counselling about the potential risks and effect of biopsy . Variability in the adverse event profile between centres suggests that patients ’ outcomes could be improved and healthcare use reduced with more effective administration of local anaesthetic and antibiotics . Trial registration Current Controlled Trials IS RCT N20141297 |
11,878 | 22,672,340 | The Mimic dV-Trainer ( ® ) , ProMIS ( ® ) , SimSurgery Educational Platform ( ® ) ( SEP ) and Intuitive systems have shown face , content and construct validity .
The Robotic Surgical SimulatorTM system has only been face and content vali date d. All of the simulators except SEP have shown educational impact .
Virtual reality simulators were shown to be effective training tools for junior trainees .
Simulation training holds the greatest potential to be used as an adjunct to traditional training methods to equip the next generation of robotic surgeons with the skills required to operate safely .
There is no evidence to suggest one type of simulator provides more effective training than any other . | To analyse studies validating the effectiveness of robotic surgery simulators .
There are five different robotic surgery simulation platforms available on the market . | Background Laparoscopic surgery challenges both the surgical novice and experienced open surgeon with unique psychomotor adaptations . Surgical skills assessment has historically relied on subjective opinion and case experience . Objective performance metrics have stimulated much interest in surgical education over the last decade and proficiency-based simulation has been proposed as a paradigm shift in surgical skills training . New assessment tools must be subjected to scientific validation . This study examined the construct validity of a hybrid laparoscopic simulator with in-built motion tracking technology . Methods Volunteers were recruited from four experience groups ( consultant surgeon , senior trainee , junior trainee , medical student ) . All subjects completed question naires and three tasks on the ProMIS laparoscopic simulator ( laparoscope orientation , object positioning , sharp dissection ) . Motion analysis data was obtained via optical tracking of instrument movements . Objective metrics included time , path length ( economy of movement ) , smoothness ( controlled h and ling ) and observer-recorded penalty scores . Results One hundred and sixty subjects completed at least one of the three tasks . Significant group differences were confirmed for number of years qualified , age and case experience . Significant differences were found between experts and novices in all three tasks . Sharp dissection was the strongest discriminator of four recognised laparoscopic skill groups : consultants outperformed students and juniors in all three performance metrics and objective penalty score ( p < 0.05 ) , and only accuracy of dissection did not distinguish them from senior trainees ( p = 0.261 ) . Seniors dissected faster , more efficiently and more accurately than juniors and students ( p < 0.05 ) . Conclusions ProMIS provides a construct valid laparoscopic simulator and is a feasible tool to assess skills in a cross-section of surgical experience groups . ProMIS has the potential to objective ly measure pre-theatre dexterity practice until an agreed proficiency level of dexterity is achieved . Future work should now examine whether training to expert criterion levels on ProMIS correlates with actual operative performance Background : To vali date the usefulness of virtual reality surgical simulators , we investigated the transfer of skills achieved by their use to real tasks . Methods : Thirty medical students underwent a pretest using a real laparoscopic trainer . They were then r and omized to the following three groups : group I received no training ; group II received training using the Minimal Invasive Surgical Trainer in Virtual Reality ( MIST-VR ) ; and group III received training using conventional training exercises . Each group then underwent a posttest . Using the Imperial College Surgical Assessment Device ( ICSAD ) , scores were generated for time taken , distance traveled , number of movements made , and speed of instrument movement . Results : Significant changes between the MIST-VR group ( group II ) and the conventionally trained group ( group III ) , were observed in the speed of movement of the left h and and the numbers of movements taken by each h and , when compared to the untrained group ( group I ) . Conclusion : The training of novices using MIST-VR yields quantifiable changes in skill that are transferable to a simple real task and are similar to the results achieved with conventional training Objective : To determine if prior training on the LapMentor ™ laparoscopic simulator leads to improved performance of basic laparoscopic skills in the animate operating room environment . Summary Background Data : Numerous influences have led to the development of computer-aided laparoscopic simulators : a need for greater efficiency in training , the unique and complex nature of laparoscopic surgery , and the increasing dem and that surgeons demonstrate competence before proceeding to the operating room . The LapMentor ™ simulator is expensive , however , and its use must be vali date d and justified prior to implementation into surgical training programs . Methods : Nineteen surgical interns were r and omized to training on the LapMentor ™ laparoscopic simulator ( n = 10 ) or to a control group ( no simulator training , n = 9 ) . Subjects r and omized to the LapMentor ™ trained to expert criterion levels 2 consecutive times on 6 design ated basic skills modules . All subjects then completed a series of laparoscopic exercises in a live porcine model , and performance was assessed independently by 2 blinded review ers . Time , accuracy rates , and global assessment s of performance were recorded with an interrater reliability between review ers of 0.99 . Results : LapMentor ™ trained interns completed the 30 ° camera navigation exercise in significantly less time than control interns ( 166 ± 52 vs. 220 ± 39 seconds , P < 0.05 ) ; they also achieved higher accuracy rates in identifying the required objects with the laparoscope ( 96 % ± 8 % vs. 82 % ± 15 % , P < 0.05 ) . Similarly , on the two-h and ed object transfer exercise , task completion time for LapMentor ™ trained versus control interns was 130 ± 23 versus 184 ± 43 seconds ( P < 0.01 ) with an accuracy rate of 98 % ± 5 % versus 80 % ± 13 % ( P < 0.001 ) . Additionally , LapMentor ™ trained interns outperformed control subjects with regard to camera navigation skills , efficiency of motion , optimal instrument h and ling , perceptual ability , and performance of safe electrocautery . Conclusions : This study demonstrates that prior training on the LapMentor ™ laparoscopic simulator leads to improved resident performance of basic skills in the animate operating room environment . This work marks the first prospect i ve , r and omized evaluation of the LapMentor ™ simulator , and provides evidence that LapMentor ™ training may lead to improved operating room performance OBJECTIVES To assess the face , content , and construct validity of the dV-Trainer . The dV-Trainer is a virtual reality simulator for the da Vinci Surgical System that is in beta development . METHODS Medical students , residents , and attending surgeons were enrolled in a prospect i ve , institutional review board-approved study . The subjects were prospect ively categorized as novice or experienced . Each subject completed 2 EndoWrist modules and 2 needle-driving modules . The performance was recorded using a built-in scoring algorithm . Each subject completed a question naire after finishing the modules . RESULTS The novice group ( n = 19 ) consisted of 3 students ( 16 % ) , 11 residents ( 58 % ) , and 5 attending surgeons ( 26 % ) . The novices had operated an average of 1.3 + /- 2.2 hours at the da Vinci console before using the simulator . The experienced subjects ( n = 7 ) had performed an average of 140 robotic cases ( range 30 - 320 ) . Experienced robotic surgeons outperformed novices in nearly all variables , including total score , total task time , total instrument motion , and number of instrument collisions ( P < .01 ) . All experienced surgeons ranked the simulator as useful for training and agreed with incorporating the simulator into a residency curriculum . The virtual reality and instrumentation achieved acceptability . The needle-driving modules did not exceed the acceptability threshold . CONCLUSIONS The results of the present study have shown that the dV-Trainer has face , content , and construct validity as a virtual reality simulator for the da Vinci Surgical System . The needle-driving modules need to be refined . Studies are underway to assess the concurrent and predictive criterion validity . The dV-Trainer could become a beneficial training simulator for robotic surgery OBJECTIVES : Computer-based colonoscopy simulation ( CBCS ) is being utilized in endoscopy training without supporting evidence that it improves patient-based colonoscopy performance . The goal of this pilot study was to determine if CBCS training improves gastroenterology ( GI ) fellows ' patient-based colonoscopy skills . METHODS : Competency at colonoscopy among 4 novice GI fellows who completed a 6-h CBCS curriculum was compared with 4 novice fellows who were not CBCS-trained . Measurements of competency were rendered by supervising faculty by recording “ insertion time,”“depth of unassisted insertion,”“independent procedure completion,”“ability to identify endoscopic l and marks,”“inserts in a safe manner,”“adequately visualizes mucosa on withdrawal , ” and “ responds appropriately to patient discomfort ” with each colonoscopy . RESULTS : Simulator-trained fellows outperformed traditionally trained fellows during their initial 15 colonoscopies in all performance aspects except “ insertion time ” ( pp < 0.05 ) . Simulator-trained fellows inserted the endoscope significantly further and reached the cecum independently nearly twice as often during this early training period . Three parameters ( “ depth of insertion,”“independent completion , ” and “ ability to identify l and marks ” ) demonstrated a continued advantage out to 30 colonoscopies . Beyond 30 procedures , there was no difference in the performance of the two groups . CONCLUSION : In this pilot study , a 6-h CBCS curriculum provides an early training advantage by enhancing competency at the early stages of patient-based colonoscopy . These advantages are negligible after approximately 30 patient-based procedures . CBCS-enhanced training may allow faculty to be more efficient with their colonoscopy practice This research represents a r and omized blinded pilot study to evaluate the acceptability and validity of a da Vinci robotic virtual reality simulator platform tested during a pediatric robotic surgery post-graduate course during the annual American Urological Association meeting in June 2007 . Course enrollees performed robotic skills tasks on the da Vinci robot and on an offline dV-Trainer and course participant demographic and performance data were analyzed . The majority of learners believed that VR simulation is useful for teaching robotic skills , they believed that the offline trainer can teach robotic skills comparable to a dry lab robotics skills station , and the offline trainer was able to discriminate between experts and novices of robotic surgery , thereby meeting criteria for face , content , and construct validities . This is the first reported acceptability study of a VR robotic surgery simulator as compared to the da Vinci robot system |
11,879 | 28,694,152 | RESULTS : Study quality ranged from good to poor and addressed only oral contraceptive pills , emergency contraception pills , and the combined vaginal ring .
No differences in ovulation suppression or breakthrough bleeding were observed in any study that combined hormonal contraceptives with any antibiotic .
No significant decreases in any progestin pharmacokinetic parameter occurred during co‐administration with any antibiotic .
: Evidence from clinical and pharmacokinetic outcomes studies does not support the existence of drug interactions between hormonal contraception and non‐rifamycin antibiotics .
Most women can expect no reduction in hormonal contraceptive effect with the concurrent use of non‐rifamycin antibiotics | OBJECTIVE : The purpose of this study was to determine whether interactions between non‐rifamycin antibiotics and hormonal contraceptives result in decreased effectiveness or increased toxicity of either therapy . | BACKGROUND We evaluated the effects of cytochrome P450 3A4 ( CYP3A4 ) induction and inhibition on steady-state pharmacokinetics of the components of a novel oral contraceptive ( OC ) containing estradiol valerate ( E₂V ) and dienogest ( DNG ) . STUDY DESIGN CYP3A4 induction was assessed in an open-label , one-arm study . Sixteen healthy postmenopausal women received E₂V 2 mg/DNG 3 mg ( days 1 - 17 ) and concomitant rifampicin ( 600 mg , days 12 - 16 ) . Ratios of the area under the serum concentration-time curve between 0 and 24 h [ AUC(0 - 24 h ) ] and maximum serum concentration ( C(max ) ) of E₂ and DNG on days 17 and 11 ( after and before rifampicin intervention ) are presented . CYP3A4 inhibition was investigated in an open-label , parallel-group study in 24 healthy postmenopausal women receiving E₂V 2 mg/DNG 3 mg ( days 1 - 14 ) and concomitant ketoconazole ( 400 mg , n=12 ) or erythromycin ( 500 mg three times daily , n=12 ) on days 8 - 14 . Mean ratios of AUC(0 - 24 h ) and C(max ) of E₂ and DNG on days 7 and 14 are presented . RESULTS Concomitant administration of rifampicin decreased systemic drug exposure and yielded geometric mean ratios for E₂C(max ) and AUC(0 - 24 h ) of 75 % and 56 % , respectively . Corresponding mean ratios for DNG were 48 % and 17 % , respectively . Ketoconazole coadministration increased systemic drug exposure and yielded ratios of E₂ of 165 % and 157 % , respectively , and ratios of DNG of 194 % and 286 % , respectively . Erythromycin coadministration also result ed in increased mean C(max ) and AUC(0 - 24 h ) of both E₂ and DNG . Geometric mean ratios of C(max ) and AUC(0 - 24 h ) for E₂ were 151 % and 133 % , respectively . Corresponding ratios for DNG were 133 % and 162 % , respectively . CONCLUSIONS Significant drug-drug interactions are apparent when CYP3A4 modulators are coadministered with the components of a novel OC containing E₂V/DNG . Coadministration of CYP3A4 modulators should be avoided where possible , and another type of contraception should be used when coadministration of CYP3A4 inducers like rifampicin is unavoidable The effect of ciprofloxacin , a new broad-spectrum quinolone derivative , on concomitant oral contraceptive steroids has been studied in a double-blind cross-over placebo-controlled r and omized trial . Ten healthy women using long-term oral contraceptive steroids received either ciprofloxacin 500 mg BID or placebo during two consecutive cycles . Therapy was continued for seven days from the first day of contraceptive treatment . FSH , LH and oestradiol blood levels were repeatedly determined to monitor contraceptive steroid efficacy . A seven-day treatment with ciprofloxacin did not affect steroid treatment outcome and appears to be safe in women using this contraceptive method The possibility of escape ovulation in women using a fluoroquinolone ofloxacin for antibacterial treatment at a dose of 200 mg twice daily for 7 days when taking a combined oral contraceptive ( Microgynon , 150 μg levonorgestrel and 30 μg ethinyl estradiol ) was studied in 20 women . By using a placebocontrolled , rendomized , cross-over design 6 contraceptive pill cycles were followed . Follicle-stimulating hormone and estradiol concentrations were measured on tablet days 5–8 , 19–21 ; progesterone was assayed on days 19–21 during treatment with ofloxacin or placebo . Ultrasonographical investigations for measurements of the number and diameter of ovarian follicles were performed on one of days 5–10 , 11–17 , 18–24 , 25–28 . No indications of ovulation during ofloxacin medication were detected . It is concluded that alternative contraceptive pre caution s should not be needed when ofloxacin is prescribed for patients taking oral contraceptives . ResuméOn a étudié la possibilité d'une ovulation fortuite chez une vingtaine de femmes utilisant la fluoroquinoline ofloxacine pour un traitement antibactérien , selon une dose de 200 mg deux fois par jour pendant 7 jours , en même temps que le contraceptif oral Microgynon ( 150 μg de lévonorgestrel et 30 μg d'éthinyl oestradiol ) . A l'aide d'un contrôle croisé , r and omisé avec placebo , on a suivi 6 cycles pendant lesquels la pilule avait été utilisée . On a mesuré les concentrations de gonadostimuline ( FSH ) et d'oestradiol aux jours 5–8 et 19–21 de la prise des pilules , et on a analysé la progestérone aux jours 19–21 soit durant le traitement à l'ofloxacine soit durant la prise du placebo . Par explorations échographiques , on a mesuré le nombre et le diamètre des follicules ovariens au cours de l'un des jours 5 à 10 , 11 à 17 , 18 à 24 , 25 à 28 . Aucune indication d'ovulation n'a été décelée pendant l'administration de l'ofloxacine . On peut en conclure qu'il ne devrait pas être nécessaire de prendre d'autres pré caution s contraceptives lorsque l'ofloxacine est prescrit à des femmes utilisant les contraceptifs orauxResumenSe estudió en 20 mujeres la posibilidad de ovulación de escape en mujeres a las que se administró una fluoroquinolona , ofloxacin , como tratamiento antibacteriano a una dosis de 200 mg dos veces al día durante 7 días al tomar un anticonceptivo oral combinado , Microgynon ( 150 μg de levonorgestrel y 30 μg de etinilestradiol ) . Utiliz and o un diseño cruzado , aleatorizado y controlado por placebo , se examinaron 6 ciclos con píldora anticonceptiva . Se midieron las concentraciones de folicoestimulina y estradiol en los días de píldora 5–8 , 19–21 ; la progesterona se examinó en los días 19–21 durante et tratamiento con ofloxacin o placebo . Se realizaron investigaciones ecográficas para medir el número y tamaño de los folículos ováricos en uno de los días 5–10 , 11–17 , 18–24 , 25–28 . No se detectó ninguna indicación de ovulación durante la medicación con ofloxacin . Se llegó a la conclusión de que no se necesitan precauciones anticonceptivas adicionales cu and o a las pacientes que toman anticonceptivos orales se les prescribe ofloxacin In view of the considerable debate concerning the possible failure of contraception in women taking broad spectrum antibiotics , we have examined a group of 12 women aged 22 - 32 in a controlled study . Each woman had been on long-term therapy with oral contraceptive steroids ( OCS ) containing ethynylestradiol ( EE2 ) and levonorgestrel ( Ng ) for at least 6 months and all were in good general health . Blood sample s were taken about 11.0 hours after dosing with their OCS on days 5 , 6 , 7 and 8 of their contraceptive cycle , for measurement of EE2 , Ng , FSH and LH by radioimmunoassay . In addition blood sample s were taken on days 19 , 20 and 21 of the contraceptive cycle for assay of progesterone concentrations in plasma . The study was repeated in the next cycle of use of their OCS during which they took temafloxacin , a broad spectrum quinolone antibiotic in a dose of 600 mg twice daily for 7 days starting on day 1 of the cycle . All women completed the study satisfactorily as judged by diary cards , tablet counts and plasma temafloxacin concentrations . In the early part of the study some nausea and headaches were seen due to taking temafloxacin on an empty stomach but these effects were not seen when the antibiotic was later given with food . There was no evidence of any interaction between temafloxacin and the OCS . The plasma concentration of EE2 was 61.4 + /- 21.1 pg/ml in the control cycle and 68.5 + /- 26.6 pg/ml in the temafloxacin cycle . ( ABSTRACT TRUNCATED AT 250 WORDS Objective To use a novel , sensitive study design to detect a potential oral contraceptive ( OC ) and dirithromycin drug interaction by assessing the pharmacokinetics of the ethinyl estradiol ( E2 ) component of a common OC and the potential failure of OC effectiveness . Methods In this nonblinded study , 20 healthy women using Ortho Novum 7/7/7 - 28 were selected for a three-OC-cycle study . Baseline measures included E2 and progesterone serum levels on days 21 , 23 , 25 , and 27 of cycle one and days 1 , 3 , 5 , and 7 of cycle two . During cycle two , 24-hour blood sampling and radioimmunoassay analysis for ethinyl E2 pharmacokinetics were performed on day 8 and pelvic ultrasound on day 13 . Oral dirithromycin 500 mg/day for 14 days began on day 21 of cycle 2 . After starting dirithromycin , cycle two and three serum E2 , progesterone , and serial ethinyl E2 levels and pelvic ultrasound replicated the baseline schedule . Ovulation was assumed if E2 concentration was greater than 50 pg/mL , progesterone concentration was greater than 3 ng/mL , or if an ovarian cyst greater than 10 mm was present on ultrasound . Results Pharmacokinetic analysis demonstrated a small ( 7.6 % ) but statistically significant decrease ( P = .03 ) in the mean ethinyl E2 24-hour area under the curve and an increase in apparent oral clearance . No woman ovulated , based on E2 levels and progesterone concentrations or ultra sound . Conclusion Dirithromycin increased the apparent oral clearance of ethinyl E2 . The clinical importance of the interaction may be negligible because no woman ovulated or had compromised OC effectiveness in this small series WHAT IS KNOWN AND OBJECTIVE Ulipristal acetate ( UPA ) is a novel selective progesterone receptor modulator for the treatment of benign gynaecological conditions such as uterine myoma . In vitro , it is mainly metabolized by the cytochrome P450 isoenzyme CYP3A4 and to a small extent by CYP1A2 and CYP2D6 . Erythromycin , a macrolide antibiotic , has been shown to be a moderate CYP3A4 inhibitor . Thus , the aim of this study was to determine the effects of erythromycin at steady-state concentrations on the pharmacokinetics of UPA . Effects on the pharmacokinetics of the mono-demethylated metabolite of UPA ( PGL4002 ) were also evaluated . METHODS This was a non-r and omized , single-sequence , two-period , open , single-dose study in 18 healthy female subjects . Subjects received oral UPA ( 20 mg ) once daily on days 1 and 13 and twice-daily erythromycin propionate administrations ( 500 mg ) from days 9 through 17 . RESULTS Geometric mean Cmax and AUCs of UPA were increased by 24 % [ geometric mean ratio point estimate ( 90 % CI ) : 1·24 ( 1·01 - 1·52 ) ] and + 224 % and + 227 % [ geometric mean ratio point estimates ( 90 % CI ) : AUC0-t 3·24 ( 2·75 - 3·83 ) and AUC0-∞ ( 3·27 ( 2·79 - 3·83 ) ] , respectively , with no effect on median tmax or t1/2 . Geometric mean Cmax of PGL4002 was decreased by 47 % [ geometric mean ratio point estimate ( 90 % CI ) : 0·523 ( 0·44 - 0·62 ) ] , but AUCs were increased by + 62 % and + 66 % [ geometric mean ratio point estimates ( 90 % CI ) : AUC0-t 1·62 ( 1·43 - 1·85 ) and AUC0-∞ by 1·66 ( 1·47 - 1·88 ) ] , respectively , with no effect on median tmax . However , geometric mean t1/2.doubled from 24 h to 48 h. No subject was discontinued from the study due to adverse events . WHAT IS NEW AND CONCLUSION Concomitant use of ulipristal acetate with erythromycin at therapeutic concentrations led to a limited increase in Cmax and a 3-fold increase in AUCs for UPA and to a decrease in Cmax and an increase in AUCs and prolonged elimination for PGL4002 . This indicates that inhibition of CYP3A4 impacted rate and extent of absorption of UPA and also its metabolism by slowing the elimination of its metabolite PGL4002 Doxycycline and other antibiotics have been implicated in oral contraceptive ( OC ) failure , but information is sparse and studies of a doxycycline-OC interaction are nonexistent . Because an interaction between doxycycline and OCs , especially those containing low-dose estrogen , could result in an unplanned and unwanted pregnancy , a controlled clinical trial of the effects of doxycycline on OC hormone concentrations was performed . Twenty-four women aged 18 - 35 years were recruited as volunteers from among the patients seen in a University-based family planning clinic . While they were on a steady dose of the OC Ortho-Novum 1/35 , serum concentrations of ethinyl estradiol , norethindrone , and endogenous progesterone were measured on days 18 , 19 , and 20 of the menstrual cycle ( control phase ) . These measurements were repeated on days 18 , 19 , and 20 of the following menstrual cycle while the patient was taking doxycycline , 100 mg twice daily ( treatment phase ) . No statistically significant differences in serum levels of ethinyl estradiol , norethindrone , or endogenous progesterone were seen between the control and treatment phases . However , there was large inter-patient and intra-patient variability in ethinyl estradiol and norethindrone levels . No elevations of endogenous progesterone occurred to suggest ovulation during antibiotic administration in either phase . It is not known what effects longer or earlier administration of doxycycline during the OC cycle would have on serum hormone concentrations or ovulation . Pregnancies attributed to failure of OCs because of tetracycline use could in fact be due to other causes or could represent a true interaction that only manifests itself in a small proportion of women at ABSTRACT Several antibiotics have been reported to lessen the ovarian suppression produced by oral contraceptive agents , as a result of drug interactions . The present investigation was design ed to study the likelihood of the occurrence of any such interaction between the fluoroquinolone antibiotic ciprofloxacin ( Ciproxin ) at a dosage of 500 mg twice a day and the “ low-dose ” oral contraceptive Marvelon ( 30 μg of ethinyl estradiol [ EE ] plus 150 μg of desogestrel ) . Twenty-four healthy female volunteers were studied in a double-blind , placebo-controlled , r and omized crossover trial . There were no significant differences between measurements of the area under the concentration-time curve of EE up to 24 h after oral contraceptive intake during placebo and ciprofloxacin administration on days 11 and 16 of the cycles , indicating the absence of pharmacokinetic interaction . Similarly , no clinical ly significant differences in the levels of sex hormone binding globulin were found between the placebo and ciprofloxacin cycles , indicating no major variation in EE levels during ciprofloxacin and placebo treatment . Ten subjects in each of the placebo and ciprofloxacin groups had early-follicular-phase levels of 17-β estradiol ( < 184 ng/liter ) at one or more points during their cycles , but none had values above the early-follicular-phase range , indicating no significant ovarian activity . In addition , all subjects had progesterone levels of < 2 ng/ml , indicating the absence of ovulation . Only two subjects , who received the placebo , had evidence of sustained follicular growth to a potentially ovulatory follicle ( ∼18 mm ) . We conclude that ciprofloxacin does not interfere with the ovarian suppression produced by the low-dose oral contraceptive Marvelon ABSTRACT Women of childbearing age commonly receive azithromycin for the treatment of community-acquired infections , including during pregnancy . This study determined azithromycin pharmacokinetics in pregnant and nonpregnant women and identified covariates contributing to pharmacokinetic variability . Plasma sample s were collected by using a sparse-sampling strategy from pregnant women at a gestational age of 12 to 40 weeks and from nonpregnant women of childbearing age receiving oral azithromycin for the treatment of an infection . Pharmacokinetic data from extensive sampling conducted on 12 healthy women were also included . Plasma sample s were assayed for azithromycin by high-performance liquid chromatography . Population data were analyzed by nonlinear mixed-effects modeling . The population analysis included 53 pregnant and 25 nonpregnant women . A three-compartment model with first-order absorption and a lag time provided the best fit of the data . Lean body weight , pregnancy , ethnicity , and the coadministration of oral contraceptives were covariates identified as significantly influencing the oral clearance of azithromycin and , except for oral contraceptive use , intercompartmental clearance between the central and second peripheral compartments . No other covariate relationships were identified . Compared to nonpregnant women not receiving oral contraceptives , a 21 % to 42 % higher dose-adjusted azithromycin area under the plasma concentration-time curve ( AUC ) occurred in non-African American women who were pregnant or receiving oral contraceptives . Conversely , azithromycin AUCs were similar between pregnant African American women and nonpregnant women not receiving oral contraceptives . Although higher levels of maternal and fetal azithromycin exposure suggest that lower doses be administered to non-African American women during pregnancy , the consideration of azithromycin pharmacodynamics during pregnancy should guide any dose adjustments Background Two pharmacokinetic studies were performed to investigate whether there is any interaction between etonogestrel or ethinylestradiol released from the combined contraceptive vaginal ring NuvaRing ® and concomitant treatment with orally administered amoxicillin or doxycycline . Methods In one study , healthy women were r and omised to receive either NuvaRing ® alone for 21 days or NuvaRing ® for 21 days plus amoxicillin on days 1–10 . After a 7-day ring-free washout period , women were crossed over to the alternate regimen for a further 21-day treatment period . The other study used an identical design except that women received doxycycline instead of amoxicillin . The amoxicillin study measured serum etonogestrel and ethinylestradiol levels and area under the serum concentration-time curve ( AUC ) values over the initial 12 hours on days 1 ( AUC12 ) and 10 ( AUCrr216 - 228 ) and the whole of days 1–11 ( AUC240 ) and 1–22 ( AUC504 ) . The doxycycline study measured AUC values over the initial 24 hours on days 1 ( AUCrr24 ) and 10 ( AUCrr216 - 240 ) and the whole of days 1–11 ( AUC240 ) and 1–22 ( AUCrr504 ) . Results No differences in etonogestrel or ethinylestradiol serum concentrations were observed between subjects using NuvaRing ® alone versus those receiving the ring plus either of the antibiotics . Calculation of etonogestrel and ethinylestradiol interaction/control ratios confirmed the absence of pharmacokinetic interactions . Conclusion The results from these studies demonstrate the absence of pharmacokinetic interactions between etonogestrel and ethinylestradiol released from NuvaRing ® and the oral antibiotics amoxicillin and doxycycline , suggesting that contraceptive efficacy would also be unaffected The effectiveness of oral contraceptives with concomitant use of ampicillin has been question ed . Eleven volunteer subjects were studied during 2 consecutive menstrual cycles ; they were given Demulen with placebo or ampicillin during each of the cycles . Serum estradiol ( E2 ) , progesterone ( P4 ) , luteinizing hormone ( LH ) , and follicle-stimulating hormone ( FSH ) were evaluated on days 13 and 19 of each cycle . Testosterone-binding globulin ( TeBG ) capacity and ferning of cervical mucus were evaluated on day 13 of each cycle . Subjective symptoms were recorded . All cycles appeared to be anovulatory . Steroid suppression was present in 10 of 11 patients during both cycles . Estrogendependent TeBG was not affected by ampicillin . It is possible that cervical mucus ferning was improved by concurrent ampicillin administration . Ampicillin appears unlikely to diminish the effectiveness of the oral contraceptive studied |
11,880 | 22,696,318 | Multivariable meta-regression indicated that feedback may be more effective when baseline performance is low , the source is a supervisor or colleague , it is provided more than once , it is delivered in both verbal and written formats , and when it includes both explicit targets and an action plan .
In addition , the effect size varied based on the clinical behaviour targeted by the intervention .
Audit and feedback generally leads to small but potentially important improvements in professional practice .
The effectiveness of audit and feedback seems to depend on baseline performance and how the feedback is provided . | BACKGROUND Audit and feedback is widely used as a strategy to improve professional practice either on its own or as a component of multifaceted quality improvement interventions .
This is based on the belief that healthcare professionals are prompted to modify their practice when given performance feedback showing that their clinical practice is inconsistent with a desirable target .
Despite its prevalence as a quality improvement strategy , there remains uncertainty regarding both the effectiveness of audit and feedback in improving healthcare practice and the characteristics of audit and feedback that lead to greater impact .
OBJECTIVES To assess the effects of audit and feedback on the practice of healthcare professionals and patient outcomes and to examine factors that may explain variation in the effectiveness of audit and feedback . | BACKGROUND Increasing clinician awareness of racial disparities and improving communication may enhance diabetes care among black patients . OBJECTIVE To evaluate the effect of cultural competency training and performance feedback for primary care clinicians on diabetes care for black patients . DESIGN Cluster r and omized , controlled trial conducted between June 2007 and May 2008 . ( Clinical Trials.gov registration number : NCT00436176 ) SETTING : 8 ambulatory health centers in eastern Massachusetts . PARTICIPANTS 124 primary care clinicians caring for 2699 ( 36 % ) black and 4858 ( 64 % ) white diabetic patients . INTERVENTION INTERVENTION clinicians received cultural competency training and monthly race-stratified performance reports that highlighted racial differences in control of hemoglobin A(1c ) ( HbA(1c ) ) and low-density lipoprotein ( LDL ) cholesterol levels and blood pressure . MEASUREMENTS Clinician awareness of racial differences in diabetes care and rates of achieving clinical control targets among black patients at 12 months . RESULTS White and black patients differed significantly in baseline rates of achieving an HbA(1c ) level less than 7 % ( 46 % vs. 40 % ) , an LDL cholesterol level less than 2.59 mmol/L ( < 100 mg/dL ) ( 55 % vs. 43 % ) , and blood pressure less than 130/80 mm Hg ( 32 % vs. 24 % ) ( all P < 0.050 ) . At study completion , intervention clinicians were significantly more likely than control clinicians to acknowledge the presence of racial disparities in the 8 health centers as a whole ( 82 % vs. 59 % ; P = 0.003 ) , within their local health center ( 70 % vs. 51 % ; P = 0.020 ) , and among their own patients ( 63 % vs. 43 % ; P = 0.037 ) . Black patients of clinicians in the intervention and control groups did not differ at 12 months in rates of controlling HbA(1c ) level ( 48 % vs. 45 % ; P = 0.24 ) , LDL cholesterol level ( 48 % vs. 49 % ; P = 0.40 ) , or blood pressure ( 23 % vs. 25 % ; P = 0.47 ) . LIMITATION 11 % of primary care teams did not attend cultural competency training sessions . CONCLUSION The combination of cultural competency training and race-stratified performance reports increased clinician awareness of racial disparities in diabetes care but did not improve clinical outcomes among black patients BACKGROUND Complete diagnostic evaluation or CDE ( i.e. , colonoscopy or combined flexible sigmoidoscopy plus barium enema X-ray ) is often not performed for persons with an abnormal screening fecal occult blood test ( FOBT+ ) result . METHOD This study evaluated the impact of a reminder-feedback and educational outreach intervention on primary care practice CDE recommendation and performance rates . Four hundred seventy primary care physicians ( PCPs ) in 318 practice s participated in the study . Patients were mailed an FOBT kit annually as part of a screening program . Practice s were r and omly assigned to a Control Group ( N = 198 ) or an Intervention Group ( N = 120 ) . During an 18-month pre-r and omization period and a 9-month post-r and omization period , 2992 screening FOBT+ patients were identified . Intervention practice s received the screening program and the intervention . Control practice s received only the screening program . Study outcomes were baseline-adjusted CDE recommendation and performance rates . RESULTS At baseline , about two-thirds of FOBT+ patients received a CDE recommendation , and about half had a CDE performed . At endpoint , CDE recommendation and performance rates were both significantly higher for the Intervention as compared to the Control practice s ( OR = 2.28 ; 95 % CI : 1.37 , 3.78 , and OR = 1.63 ; 95 % CI : 1.06 , 2.50 , respectively ) . CONCLUSIONS The reminder-feedback plus educational outreach intervention significantly increased CDE recommendation and performance We performed a r and omized , prospect i ve study to evaluate the use of a written feedback system in reducing the intraoperative costs of drugs and supplies used by anesthesiologists . Over 6 mo , 27 anesthesiology residents were r and omized to feedback and control groups for their rotations in neurosurgical anesthesia . We recorded the cost of drugs and supplies for three procedures : carotid endarterectomy , lumbar decompression , and cervical decompression . For each study case , members of the feedback group received a written cost analysis showing their performance relative to the departmental average . Members of the feedback group had significantly lower costs for carotid endarterectomies ( $ 79.98 + /- $ 15.20 vs $ 97.59 + /- $ 21.53 ) and for lumbar decompressions ( $ 56.72 + /- $ 16.49 vs $ 76.05 + /- $ 20.11 ) . The source of savings included lower use rates for propofol and etomi date and for patient warming devices . Analysis of data from recovery areas revealed a trend toward lower patient temperature in lumbar procedures performed by the feedback group . Three months after the feedback period , we collected a follow-up data set in the absence of feedback . This revealed a significant rebound in overall cost by the feedback group for both carotid endarterectomies and lumbar surgery . Implication s : This is the first r and omized , prospect i ve evaluation of a cost management system in anesthesia . Using resident anesthesiologists , we showed that the written feedback of individualized performance data can be used to lower the overall cost of intraoperative drugs and supplies used for an anesthetic in the absence of m and ated clinical guidelines . ( Anesth Analg 1998;86:510 - 5 Although numerous utilization review s of serum digoxin assays have demonstrated the positive impact of therapeutic drug monitoring , to our knowledge , the question of whether the withdrawal of such a program would reverse the effect has not been addressed . The current study employed a prospect i ve , r and omized , crossover design to evaluate this question and document the cost savings . There were 196 serum digoxin assays performed in the 207 patients . It was found that a continuous therapeutic drug-monitoring program was warranted since , after its withdrawal , there was a deterioration in audit criteria performance . Reimplementation of the therapeutic drug-monitoring program result ed in a significant decrease in the average number of assays requested per patient ( from 1.41 to 0.73 ) and an improvement in audit criteria performance OBJECTIVE : To determine whether residents perceived oral , face-to-face feedback about their continuity clinic performance as better than a similar , written version . DESIGN : Single-blind , r and omized controlled trial . SETTING : Two university-based , internal medicine residency clinics . PARTICIPANTS : All 68 internal medicine and combined program ( medicine-pediatrics , medicine-psychiatry , medicine-neurology , and preliminary year ) residents and their clinic preceptors . MEASUREMENTS AND MAIN RESULTS : Residents at each program were separately r and omized to oral or written feedback sessions with their clinic preceptors . The oral and written sessions followed similar , structured formats . Both groups were later sent question naires about aspects of the clinic . Sixty-five ( 96 % ) of the residents completed the question naire . Eight of the 19 questions dealt with aspects of feedback . A feedback scale was developed from the survey responses to those eight questions ( α=.86 ) . There were no significant differences in the responses to individual questions or in scale means ( p>.20 ) between the two feedback groups . When each university was analyzed separately , one had a higher scale mean ( 3.10 vs 3.57 , p=.047 ) , but within each university , there were no differences between the oral and written feedback groups ( p>.20 ) . CONCLUSIONS : No differences were observed between the oral and written feedback groups . In attempting to provide better feedback to their residents , medical educators may better apply their efforts to other aspects , such as the frequency of their feedback , rather than the form of its delivery Due to possible method ological and practical problems , many research ers refrain from using a r and omized controlled trial design to evaluate procedures already embedded in routine health care . We performed a r and omized controlled trial on the effects of routine individual feedback on test ordering behavior of family physicians . The trial started after 4 years of feedback and lasted for 2.5 years . With some adaptations a r and omized trial proved to be possible . In evaluating health-care procedures that can not be blinded in a traditional way , asking full and study -specific informed consent may conflict with the validity of the design . In such studies , an alternative procedure is to be considered . Our trial , with doctors as study subjects , was held on an already accepted routine procedure ( feedback ) . This made it possible to refrain from obtaining study -specific informed consent . Consequently , a Hawthorne effect and contamination of the trial arms through information leakage could be avoided . Justification and general criteria for not obtaining full and study -specific informed consent are worked out . In health-care research on the performance of doctors or on interventions into the quality of care , obtaining a general informed consent in advance is an acceptable alternative approach OBJECTIVE To evaluate the impact of systematic patient evaluation and patient and provider feedback on the processes and intermediate outcomes of diabetes care in Independent Practice Association model internal medicine practice s. RESEARCH DESIGN AND METHODS Nine practice s providing care to managed care patients were r and omly assigned as intervention or comparison sites . Intervention-site subjects had Annual Diabetes Assessment Program ( ADAP ) assessment s ( HbA(1c ) , blood pressure , lipids , smoking , retinal photos , urine microalbumin , and foot examination ) at years 1 and 2 . Comparison-site subjects had ADAP assessment s at year 2 . At Intervention sites , year 1 ADAP results were review ed with subjects , mailed to providers , and incorporated into electronic medical records with guideline -generated suggestions for treatment and follow-up . Medical records were evaluated for both groups for the year before both the year 1 and year 2 ADAP assessment s. Processes and intermediate outcomes were compared using linear and logistic mixed hierarchical models . RESULTS Of 284 eligible subjects , 103 of 173 ( 60 % ) at the Intervention sites and 71 of 111 ( 64 % ) at the comparison sites participated ; 83 of 103 ( 81 % ) of the intervention-site subjects returned for follow-up at year 2 . Performance of the six recommended assessment s improved in intervention-site subjects at year 2 compared with year 1 ( 5.8 vs. 4.3 , P = 0.0001 ) and compared with comparison-site subjects at year 2 ( 4.2 , P = 0.014 ) . No significant changes were noted in intermediate outcomes . CONCLUSIONS The ADAP significantly improved processes of care but not intermediate outcomes . Additional interventions are needed to improve intermediate outcomes OBJECTIVE To assess the effects of a facilitator enhanced multifaceted intervention to implement a locally adapted guideline on the shared care for people with type 2 diabetes . METHODS During 1 year a cluster-r and omized trial was performed in 30 general practice s. In the intervention group , nurse facilitators enhanced guideline implementation by analysing barriers to change , introducing structured care , training practice staff and giving performance feedback . Targets for HbA1c% , systolic blood pressure as well as indications for angiotensin converting enzyme/angiotensin receptor blocking agent prescription differed from the national guidelines . In the control group , GPs were asked to continue the care for people with diabetes as usually . Generalized estimating equations were used to control for the clustered design of the study . RESULTS In the intervention group , more people were seen on a 3-monthly basis ( 88 % versus 69 % , P < 0.001 ) and more blood pressure and bodyweight measurements were performed every 3 months ( blood pressure 83 % versus 66 % , P < 0.001 and bodyweight 78.9 % versus 48.5 % , P < 0.001 ) . Apart from a marginal difference in mean cholesterol , differences in HbA1c% , blood pressure , body mass index and treatment satisfaction were not significant . CONCLUSION Multifaceted implementation of locally adapted shared care guidelines did improve the process of diabetes care but hardly changed intermediate outcomes . In the short term , local adaptation of shared care guidelines does not improve the cardiovascular risks of people with type 2 diabetes Improved pneumococcal vaccine ( PPV ) immunization for seniors is a national goal of the Medicare program . This study examined whether adding a simple telephone follow-up to an existing mailed physician performance feedback under the Medicare program would increase the impact on billed pneumococcal immunizations . Medicare fee-for-service cl aims data were used to select New York primary care physicians with high volume ( n = 732 ) or African-American serving ( n = 329 ) practice s. All practice s received mailed feedback on their 1999 Medicare practice specific PPV coverage rates , along with educational material s and offers of assistance . Practice s were also r and omized to receive telephone calls directing attention to the mailing and further promoting improvements in PPV coverage or no active follow-up . Physicians r and omized to telephone follow-up showed significantly higher rates of practice specific PPV coverage in 2000 than those receiving the routine mailing only , and 27 % vs. 17 % ( p = 0.01 ) of high volume physicians and 34 % vs. 22 % ( p = .052 ) of African American serving physicians achieved at least a 5 % increase in their cumulative PPV cl aims coverage . This study concludes that telephone follow-up is an effective and straightforward method to enhance the impact of practice specific feedback to promote improvements in Medicare PPV immunization . However , improved methods may be needed to induce a large percentage of physicians to change In an academic general medicine clinic , we performed a r and omized , controlled trial to compare ( 1 ) the effects of supplying monthly feedback reports of compliance with preventive care protocol s by 135 internal medicine house staff with ( 2 ) the effects of specific reminders given to them at the time of patient visits . The protocol s were r and omly divided into two groups , A and B , and half the house staff were given feedback for Group A and half for Group B. Thus , each group served as a control for the other . Each feedback group was also r and omly assigned to receive reminders for either Group A or B protocol s. House staff receiving feedback more often complied with fecal occult blood testing , mammography , pneumococcal vaccination , use of metronidazole , and combined Group A and B protocol s than did controls ( P < 0.01 ) . There was also significantly more compliance with the same protocol s by house staff receiving reminders , but the increase for fecal occult blood testing , pneumococcal vaccination , and combined Group A protocol s was twice that seen in physicians given feedback alone . In addition , reminders alone increased compliance with oral calcium supplementation . Overall compliance with the preventive care protocol s was low : 10 - 15 % in physicians receiving neither feedback nor reminders , increasing to 15 - 30 % in those receiving reminders . Physician compliance with suggested preventive care protocol s can be increased by both delayed feedback and immediate reminders , but reminders have a greater effect BACKGROUND In the future , primary care groups ( PCGs ) will have to consider how best to apply audit and education to fulfil their commitment to clinical governance and to facilitate the implementation of research findings . AIM To establish whether an exploration of ' barriers to change ' can enhance the effectiveness of an educational intervention design ed to improve the management of hypertension in the elderly . METHOD A parallel-arm , r and omized , single-blind , controlled trial of practice -based educational visits in 18 practice s. These practice s had previously taken part in a multi practice audit of the management of hypertension in the elderly . Both groups received outreach visits in their own practice , during which they received the results of the previous audit . The nine ' intervention ' practice s were encouraged to explore barriers that would prevent them from implementing pertinent research findings . The control group was not encouraged to do this . The main outcome measure of the trial was determined in advance as ' the stated management of systolic hypertension in patients aged 70 to 79 ' . A secondary endpoint was the stated management of a specific patient scenario . The endpoints were tested by question naire before and after the educational intervention . RESULTS For the primary endpoint , there was a statistically significant difference in the stated threshold for treating systolic hypertension between intervention and control groups after the visits ( 161.8 mmHg versus 167.2 mmHg ; P = 0.007 ) . For the secondary endpoint , there was also a statistically significant difference between the two groups , after the visits , in their willingness to treat a 70-year-old male with mild hypertension ( 89 % of doctors would treat in the intervention group versus 57 % in the control group ; P = 0.047 ) . CONCLUSION The effectiveness of an educational intervention is significantly improved by addressing the barriers preventing practitioners from implementing the findings of research BACKGROUND A multistate r and omized study conducted under the Health Care Financing Administration 's ( HCFA 's ) Health Care Quality Improvement Program ( HCQIP ) offered the opportunity to compare the effect of a written feedback intervention ( WFI ) with that of an enhanced feedback intervention ( EFI ) on improving the anticoagulant management of Medicare beneficiaries who present to the hospital with venous thromboembolic disease . METHODS Twenty-nine hospitals in five states were r and omly assigned to receive written hospital-specific feedback ( WFI ) of feedback enhanced by the participation of a trained physician , quality improvement tools , and an Anticoagulant Management of Venous Thrombosis ( AMVT ) project liaison ( EFI ) . Differences in the performance of five quality indicators between baseline and remeasurement were assessed . Quality managers were interviewed to determine perceptions of project implementation . RESULTS No significant differences in the change from baseline to remeasurement were found between the two intervention groups . Significant improvement in one indicator and significant decline in two indicators were found for one or both groups . Yet 59 % of all quality managers perceived the AMVT project as being successful to very successful , and more EFI quality managers perceived success than did WFI managers ( 71 % versus 40 % ) . In the majority of EFI hospitals , physician liaisons played an important role in project implementation . CONCLUSION Study results indicated that the addition of a physician liaison , quality improvement tools , and a project liaison did not provide incremental value to hospital-specific feedback for improving quality of care . Future studies with larger sample sizes , lengthier follow-up periods , and interventions that include more of the elements shown to affect practice behavior change are needed to identify an optimal feedback model for use by external quality management organizations Feedback can be described as a way to provide information on doctors ' performance to enable changes in future behaviour . Feedback is used with the aim of changing test-ordering behaviour . It can lead to reductions in test usage and cost savings . It is not sufficiently clear , however , whether feedback leads to more appropriate test use . Since 1985 , the Diagnostic Coordinating Center Maastricht has been giving feedback on diagnostic tests as a routine health care activity to all family doctors in its region . Both quantity and quality of requests are discussed . In a r and omised , controlled trial over 2.5 years , discussion of tests not included previously was added to the existing routine feedback . One group of family doctors ( n = 39 ) received feedback on test-group A ( electrocardiography , endoscopy , cervical smears , and allergy tests ) , the other ( n = 40 ) on test-group B ( radiographic and ultrasonographic tests ) . Thus , each group of doctors acted as a control group for the other . Changes in volume and rationality of requests were analysed . The number of requests decreased during the trial ( p = 0.036 ) . Request numbers decreased particularly for test-group A ( p = 0.04 ) . The proportion of requests that were non-rational decreased more in the intervention than in the control groups ( p = 0.009 ) . Rationality improved predominantly for test-group B ( p = 0.043 ) . Thus , routine feedback can change the quantity and quality of requests Background The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting . Methods Twenty facilities took part in a r and omized controlled trial with a seven month follow-up period . Two outreach visits were delivered by a pharmacist . At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates , psychotropic drug prescribing and stroke risk reduction practice s ( BP monitoring , aspirin and warfarin use ) for the facility relevant to the physician . The effect of the interventions was determined via pre- and post-intervention case note audit . Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications . Chi-square tests , independent sample s t-test , and logistic regression were used in the analysis . Results Data were available from case notes at baseline ( n = 897 ) and seven months follow-up ( n = 902 ) , 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits . Pre- and post-intervention data were available for 715 participants . There were no differences between the intervention and control groups for the three month fall rate . We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention . The exception was significantly greater use of " as required " antipsychotics in the intervention group compared with the control group after the pharmacy intervention ( RR = 4.95 ; 95%CI 1.69–14.50 ) . There was no statistically significant difference between groups for the numbers of patients " at risk of stroke " on aspirin at follow-up . Conclusions While the strategy was well received by the physicians involved , there was no change in prescribing patterns . Patient care in residential setting s is complex and involves contributions from the patient 's physician , family and residential care staff . The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained OBJECTIVE : To determine the impact of printed patient-specific feedback regarding potential misprescribing of antiulcer agents ( AUAs ) . Measures of impact included improvements in patients ’ dispensing profiles , assessed according to predetermined criteria , and decreases in cost and quantity of AUAs dispensed . DESIGN : Controlled study . After evaluation for compliance with predetermined criteria , prescribers identified as having one or two patient profiles with potential errors were assigned alternatively to control or experimental groups . An intervention was mailed to the experimental group . SETTING : Outpatient setting in the New Mexico Medicaid population . PARTICIPANTS : Patients and prescribers identified as having potential misprescribing of AUAs . INTERVENTION : The intervention consisted of a cover letter describing the purpose of the drug utilization review program , an educational fact sheet regarding prescribing AUAs , patient profiles with potential misprescribing , and physician response forms . MEASUREMENTS AND MAIN RESULTS : There were greater improvements in dispensing to patients in the intervention group ( x2 , p<.001 ) . Significant odds ratios for the intervention group were 2.29 for AUAs discontinued , 1.98 for all improvements combined , 13.13 for improvement in listing of proper diagnosis for AUAs , and 2.84 for appropriate indication when prescribing the higher acute daily dosage . Using data from 3 months before and after the intervention , we found greater decreases in mean monthly costs ( p=.044 ) and mean monthly quantity of AUAs dispensed ( p=.049 ) in the intervention group . CONCLUSIONS : This intervention significantly decreased AUA dispensing to patients whose prescribers were mailed the patient-specific feedback intervention Abstract Problem : Inhabitants of Torres Strait Isl and s have the highest prevalence of diabetes in Australia and many preventable complications . In 1999 , a one year r and omised cluster trial showed improved diabetes care processes and reduced admissions to hospital when local indigenous health workers used registers , recall and reminder systems , and basic diabetes care plans , supported by a specialist outreach service . This study looked at whether those improvements were sustained two years after the end of the trial . Design : Three year follow up clinical audit of 21 primary healthcare centres , and review of admissions to hospital in the previous 12 months . Background and setting : Remote indigenous communities in far north east Australia , population about 9600 , including 921 people with diabetes . Key measures for improvement Number of people on registers , care processes ( regular measures of weight , blood pressure , haemoglobin A 1c , urinary protein concentration , and concentrations of serum lipids and creatinine ) , appropriate clinical interventions ( drug treatment and vaccinations ) , and intermediate patient outcome measures ( weight , blood pressure , and glycaemic control ) . Admissions to hospital . Strategies for change : Audit and feedback to clinicians and managers ; provision of clinical guidelines and a clear management structure ; workshops and training . Effects of change : The number of people on registers increased from 555 in 1999 to 921 in 2002 . Most care processes and clinical interventions improved . The proportion of people with good glycaemic control ( haemoglobin A 1c ≤ 7 % ) increased from 18 % to 25 % in line with increased use of insulin ( from 7 % to 16 % ) . The proportion of those with well controlled hypertension ( < 140/90 ) increased from 40 % to 64 % . The proportion admitted to hospital with a diabetes related condition fell from 25 % to 20 % . Mean weight increased from 87 kg to 91 kg . Lessons learnt : In remote setting s , appropriate management structures and clinical support for people with diabetes can lead to improvements in care processes , control of blood pressure , and preventable complications that result in admission to hospital . Control of weight and glycaemia are more difficult and requires more active community engagement . Priorities now include increasing the availability and affordability of good food , achieving weight loss , and increasing appropriate use of hypoglycaemic agents , including insulin OBJECTIVE To assess the impact of diverse continuing medical education ( CME ) interventions on physician performance and health care outcomes . DATA SOURCES Using continuing medical education and related phrases , we performed regular search es of the indexed literature ( MEDLINE , Social Science Index , the National Technical Information Service , and Educational Research Information Clearinghouse ) from 1975 through 1991 . In addition , for these years , we used manual search es , key informants , and requests to authors to locate other indexed articles and the nonindexed literature of adult and continuing professional education . STUDY SELECTION From the result ing data base we selected studies that met the following criteria : r and omized controlled trials ; educational programs , activities , or other interventions ; studies that included 50 % or more physicians ; follow-up assessment s of at least 75 % of study subjects ; and objective assessment s of either physician performance or health care outcomes . DATA EXTRACTION Studies were review ed for data related to physician specialty and setting . Continuing medical education interventions were classified by their mode(s ) of activity as being predisposing , enabling , or facilitating . Using the statistical tests supplied by the original investigators , physician performance outcomes and patient outcomes were classified as positive , negative , or inconclusive . DATA SYNTHESIS We located 777 CME studies , of which 50 met all criteria . Thirty-two of these analyzed physician performance ; seven evaluated patient outcomes ; 11 examined both measures . The majority of the 43 studies of physician performance showed positive results in some important measures of re source utilization , counseling strategies , and preventive medicine . Of the 18 studies of health care outcomes , eight demonstrated positive changes in patients ' health care outcomes . CONCLUSION Broadly defined CME interventions using practice -enabling or reinforcing strategies consistently improve physician performance and , in some instances , health care outcomes This paper describes how the quality of medical care provided by general practitioners for patients suffering from cardiac failure was assessed . A peer group of general practitioners provided the criteria of adequate process and outcome of care . The impact of a flow sheet design of medical record on the quality of care was tested in a controlled study . Although there were significant improvements in the process measures as a result of the new medical record , there was no measurable benefit in terms of outcome . The particular problems of defining criteria of care in general practice are described and the usefulness of methods of measuring quality whose validity is in doubt is question ed BACKGROUND Although high blood pressure is associated with significant morbidity and mortality , the proportion reaching the goal blood pressures as outlined in the Seventh Report of the Joint National Committee on Prevention , Detection , Evaluation , Treatment of High Blood Pressure ( JNC 7 ) is low . We conducted a r and omized trial in primary care practice s of a multifactorial intervention targeted to improve providers ' adherence to hypertension guidelines . METHOD A total of 61 primary care practice s in North Carolina were r and omized to receive either a multifactorial intervention ( guideline dissemination via a continuing medical education session , academic detailing sessions , audit and feedback on preintervention rates of adherence , and automated blood pressure machines ) or an attention control of similar magnitude but targeted at a different guideline . Outcomes were determined through review of patient charts conducted by an independent masked quality assurance organization . RESULTS We found no difference between the 2 groups in any of the adherence measures including no difference in the percentage of patients at goal ( intervention 49.2 % , control 50.6 % ) , with undiagnosed hypertension ( 18.1 % vs 13.6 % ) , average systolic ( 126 vs 125.1 mm Hg ) , or diastolic blood pressure ( 73.1 vs 73.4 mm Hg ) . Similarly , there was no difference in provider adherence to treatment recommendations ( use of thiazide-type diuretic as first-line therapy : 32 % vs 29.5 % ; use of 2-drug therapy in stage 2 hypertension : 11.3 % vs 10.4 % ) . CONCLUSION An intensive , multifactorial intervention did not improve adherence to national hypertension guidelines among community-based primary care . Efforts should be focused on other types of interventions to improve rates of control of hypertension Introduction We aim ed to assess whether hypertension management with a structured physician information program and a feedback system leads to improved blood pressure ( BP ) control and cardiovascular outcomes . Methods Cluster r and omized ( 3 : 1 ) , open , monitored , multicenter trial in Germany . Primary care-based physicians in the information group ( IG ) received detailed training on hypertension guidelines , feedback on target-level attainment , and a reminder to intensify treatment after each patient visit , whereas the observation/control group ( CG ) did not receive any such measures . A three-level mixed model was developed . Time-independent level differences between groups , group-independent changes , and nonparallel group-specific changes over time were tested . Results A total of 15 041 ( 78.1 % ) hypertensive patients were in the IG and 4213 ( 21.9 % ) in the CG . By 1-year follow-up , 82.9 % of patients in the IG and 81.5 % in the CG remained in the study . The guideline -oriented BP target was attained by 56.8 % in the IG and 52.5 % in the CG ( + 4.3 % , P = 0.03 ) , whereas the individual BP target was attained by 57.0 % in the IG and 51 % in the CG ( P = NS ) . BP control in the IG was achieved 2 months earlier on average . Clinical inertia , defined as the absence of medication changes , despite noncontrol of BP , occurred significantly less often in the IG group . One-year cardiovascular outcomes did not differ between groups . Conclusion The delivery of systematic information in connection with a feedback system reduces clinical inertia and improves guideline adherence . Although compared with earlier studies , the hypertension control rates obtained are higher , there is still considerable room for improvement . Eur J Cardiovasc Prev Rehabil 17:271 - 279 © 2010 The European Society of AIMS In Belgium , general practitioners ( GPs ) mainly manage oral anticoagulation therapy . To improve the quality of oral anticoagulation management by GPs and to compare different models and interventions , a r and omized clinical trial was performed . METHODS AND RESULTS Stratified r and omization divided 66 GP- practice s into four groups . A 6-month retrospective analysis assessed the baseline quality . In the prospect i ve study , each group received education on oral anticoagulation , anticoagulation files , and patient information booklets ( groups A , B , C , and D ) . Group B additionally received feedback every 2 months on their anticoagulation performance ; group C determined the international normalized ratio ( INR ) with a CoaguChek device in the doctor 's office or at the patient 's home ; and group D received Dawn AC computer assisted advice for adapting oral anticoagulation . For the different groups , the time spent in target INR range ( Rosendaal 's method ) and adverse events related to anticoagulation were determined and compared with the same quality indicators at baseline . There was a significant increase in per cent of time within 0.5 INR from target , from 49.5 % at baseline to 60 % after implementing the different interventions . However , neither the per cent in target range nor the event rates differed among the four groups . CONCLUSION The interventions significantly improved the quality of management of oral anticoagulation by Belgian GPs , mainly as a result of an education and support programme Objective To investigate the effectiveness and cost-effectiveness of different guideline implementation strategies , using the Scottish Intercollegiate Guidelines Network ( SIGN ) Guideline 42 ' Management of unerupted and impacted third molar teeth ' ( published 2000 ) as a model . Design A pragmatic , cluster RCT ( 2 × 2 factorial design ) .Subjects Sixty-three dental practice s across Scotl and . Clinical records of all 16—24-year-old patients over two , four-month periods in 1999 ( pre-intervention ) and 2000 ( post-intervention ) were search ed by a clinical research er blind to the intervention group . Data were also gathered on the costs of the interventions . Interventions Group 1 received a copy of SIGN 42 Guideline and had an opportunity to attend a postgraduate education course ( PGEC ) . In addition to this , group 2 received audit and feedback ( A and F ) . Group 3 received a computer aided learning ( CAL ) package . Group 4 received A and F and CAL.Principal outcome measurement The proportion of patients whose treatment complied with the guideline . Results The weighted t-test for A and F versus no A and F ( P=0.62 ) and CAL versus no CAL ( P=0.76 ) were not statistically significant . Given the effectiveness results ( no difference ) the cost effectiveness calculation became a cost-minimisation calculation . The minimum cost intervention in the trial consisted of providing general dental practitioners ( GDPs ) with guidelines and the option of attending PGEC courses . Routine data which subsequently became available showed a Scotl and -wide fall in extraction s prior to data collection . Conclusion In an environment in which pre-intervention compliance was unexpectedly high , neither CAL nor A and F increased the dentists ' compliance with the SIGN guideline compared with mailing of the guideline and the opportunity to attend a postgraduate course . The cost of the CAL arm of the trial was greater than the A and F arm . Further work is required to underst and dental professionals ' behaviour in response to guideline implementation strategies A r and omized controlled trial of several strategies design ed to reduce the use of laboratory tests by house staff was performed in two parts . Part 1 compared cost education , cost audits , and both methods combined , all after a baseline observation period . Significant reductions were achieved only in the combination group for the categories of total tests ( 9.4 % ) and Sequential Multiple Analysis (SMA)-12 ( 10.8 % ) , but not for charges , SMA-6 , or complete blood cell counts ( CBCs ) . Part 2 compared a group subjected to faculty chart review with a control group . Significant reductions in total charges ( 9.8 % ) , total tests ( 15.1 % ) , SMA-12s ( 20.6 % ) , SMA-6s ( 12.5 % ) , and CBCs ( 18.5 % ) were observed in the intervention group , as compared with the control group . Among the methods examined , faculty chart review seems to be the most effective method of reducing the amount of laboratory testing performed by house staff BACKGROUND The extent of use of antibiotics for upper respiratory tract infection ( URTI ) prompted a previous study of an educational intervention based on prescriber feedback and management guidelines . This study demonstrated a reduction in antibiotic prescribing for URTI and a more appropriate choice of antibiotic for tonsillitis/streptococcal pharyngitis . There are few long-term follow-up studies of educational programmes of this kind . OBJECTIVES This follow-up study aim ed to examine if the reduction in antibiotic prescribing observed in the intervention group of the original study remained present after 5 years , and how the prescribing behaviour of the GPs involved in the follow-up differed from a large national survey of GP prescribing . METHODS Attempts were made to contact the 157 GPs involved in the original study . Of these , 121 were both located and currently working in general practice . Ninety-six consented to take part and , of these , 79 completed a morbidity and treatment survey of 100 patient encounters ( response rate 65.3 % ) . RESULTS The intervention group ( n = 37 ) maintained their pattern of prescribing of antibiotics for URTI and choice of antibiotic for tonsillitis/streptococcal pharyngitis , with no significant change between the completion of the original study and the 5-year follow-up . The control group ( n = 42 ) showed a downward trend in antibiotic prescribing for URTI , with the effect that no significant differences remained between groups at the 5-year follow-up . At the 5-year follow-up , both groups prescribed significantly fewer antibiotics for URTI and showed greater adherence to prescribing guidelines for tonsillitis/streptococcal pharyngitis than participants in a large national GP survey ( n = 984 ) . CONCLUSION This study demonstrated maintenance of prescribing behaviour in the intervention group in the long term . However , the changes in prescribing observed in the control group and the power limitations of the study make it uncertain whether this was the result of a sustained effect of the educational intervention . The differences in both groups from the large national GP survey suggest that other influences on prescribing ( such as participation in vocational training for general practice ) were also having an important effect BACKGROUND Family physicians ( FPs ) in Australia underutilize effective strategies to help patients stop smoking . We conducted a cluster r and omization trial to evaluate a multifaceted , practice -based intervention involving audit , feedback , and academic detailing to improve FP smoking cessation advice . METHODS Sixty FPs in 39 practice s participated . FPs ' provision of smoking cessation advice was measured by patient recall , medical record audit , and FP self-report . Logistic regression analysis using generalized estimating equations was performed to assess improvements in practice , after adjustment for clustering by practice . RESULTS Improvements between baseline and posttest in patient recall of FP advice about nicotine replacement patches and gum were significantly greater in the intervention than in the control group ( P = 0.0056 and P = 0.0002 , respectively ) . While there were substantial increases in patient recall of assessment of smoking status and FP use of " quit date s , " behavioral advice , and written material s in the intervention group , these changes were not significantly greater than those in the control group . Notation of patients ' smoking status and smoking cessation advice in medical records remained suboptimal in both groups . CONCLUSIONS This multifaceted intervention was successful only in promoting FPs ' use of nicotine replacement therapy . While the use of other effective cessation strategies appeared to increase , a larger trial is needed for further evaluation Although low dose aspirin reduces risk in patients with heart disease , many such patients do not receive daily prophylactic aspirin.1 We report a trial of feedback of general practitioners ' data on aspirin prescribing aim ed at increasing coded aspirin prescribing in patients with heart disease . Computerised practice s were r and omised to receive feedback on their prescribing , either of aspirin for patients with ischaemic heart disease or of hormone replacement therapy for women who had had hysterectomies . We approached 48 practice s in north London ; nine refused , and 11 were excluded . Of the 28 ( 58 % ) practice s in the study , seven were single h and ed and six had five or more partners . All participating practice s used the emis computer system except two that used Paradoc ; both systems yielded sufficiently reliable and comparable data . Eligible practice s had to have computerised information on hysterectomies and ischaemic heart disease and use their systems for repeat prescribing . Practice s were then r and omised by using sealed envelopes to Abstract Objective : To test the effectiveness of two programmes to improve the treatment of acute depression in primary care . Design : R and omised trial . Setting : Primary care clinics in Seattle . Patients : 613 patients starting antidepressant treatment . Intervention : Patients were r and omly assigned to continued usual care or one of two interventions : feedback only and feedback plus care management . Feedback only comprised feedback and algorithm based recommendations to doctors on the basis of data from computerised records of pharmacy and visits . Feedback plus care management included systematic follow up by telephone , sophisticated treatment recommendations , and practice support by a care manager . Main outcome measures : Blinded interviews by telephone 3 and 6 months after the initial prescription included a 20 item depression scale from the Hopkins symptom checklist and the structured clinical interview for the current DSM-IV depression module . Visits , antidepressant prescriptions , and overall use of health care were assessed from computerised records . Results : Compared with usual care , feedback only had no significant effect on treatment received or patient outcomes . Patients receiving feedback plus care management had a higher probability of both receiving at least moderate doses of antidepressants ( odds ratio 1.99 , 95 % confidence interval 1.23 to 3.22 ) and a 50 % improvement in depression scores on the symptom checklist ( 2.22 , 1.31 to 3.75 ) , lower mean depression scores on the symptom checklist at follow up , and a lower probability of major depression at follow up ( 0.46 , 0.24 to 0.86 ) . The incremental cost of feedback plus care management was about $ 80 ( £ 50 ) per patient . Conclusions : Monitoring and feedback to doctors yielded no significant benefits for patients in primary care starting antidepressant treatment . A programme of systematic follow up and care management by telephone , however , significantly improved outcomes at modest cost Abstract Objective : To assess the effect of a multifaceted intervention directed at general practitioners on six year mortality , morbidity , and risk factors of patients with newly diagnosed type 2 diabetes . Design : Pragmatic , open , controlled trial with r and omisation of practice s to structured personal care or routine care ; analysis after 6 years . Setting : 311 Danish practice s with 474 general practitioners ( 243 in intervention group and 231 in comparison group ) . Participants : 874 ( 90.1 % ) of 970 patients aged ≥40 years who had diabetes diagnosed in 1989 - 91 and survived until six year follow up . Intervention : Regular follow up and individualised goal setting supported by prompting of doctors , clinical guidelines , feedback , and continuing medical education . Main outcome measures : Predefined clinical non-fatal outcomes , overall mortality , risk factors , and weight . Results : Predefined non-fatal outcomes and mortality were the same in both groups . The following risk factor levels were lower for intervention patients than for comparison patients ( median values ) : fasting plasma glucose concentration ( 7.9 v 8.7 mmol/l , P=0.0007 ) , glycated haemoglobin ( 8.5 % v 9.0 % , P<0.0001 ; reference range 5.4 - 7.4 % ) , systolic blood pressure ( 145 v 150 mm Hg , P=0.0004 ) , and cholesterol concentration ( 6.0 v 6.1 mmol/l , P=0.029 , adjusted for baseline concentration ) . Both groups had lost weight since diagnosis ( 2.6 v 2.0 kg ) . Metformin was the only drug used more frequently in the intervention group ( 24 % ( 110/459 ) v 15 % (61/415)).Intervention doctors arranged more follow up consultations , referred fewer patients to diabetes clinics , and set more optimistic goals . Conclusions : In primary care , individualised goals with educational and surveillance support may for at least six years bring risk factors of patients with type 2 diabetes to a level that has been shown to reduce diabetic complications but without weight gain . What is already known on this topic Evidence is increasing that control of hyperglycaemia , hypertension , and dyslipidaemia may postpone the development of diabetic complications in patients with type 2 diabetes Maintaining good control over a long period can be difficult What this study adds Structured individualised personal care with educational and surveillance support for general practitioners reduced levels of risk factors in type 2 diabetic patients after six years Risk factors were reduced to a level that has been shown to have a beneficial effect on diabetic complications Participants also showed modest weight Abstract Objective : To determine whether locally developed guidelines on asthma and diabetes disseminated through practice based education improve quality of care in non-training , inner city general practice s. Design : R and omised controlled trial with each practice receiving one set of guidelines but providing data on the management of both conditions . Subjects:24 inner city , non-training general practice s. Setting : East London . Main outcome measures : Recording of key variables in patient records ( asthma : peak flow rate , review of inhaler technique , review of asthma symptoms , prophylaxis , occupation , and smoking habit ; diabetes : blood glucose concentration , glycaemic control , funduscopy , feet examination , weight , and smoking habit ) ; size of practice disease registers ; prescribing in asthma ; and use of structured consultation “ prompts . ” Results : In practice s receiving diabetes guidelines , significant improvements in recording were seen for all seven diabetes variables . Both groups of practice s showed improved recording of review of inhaler technique , smoking habit , and review of asthma symptoms . In practice s receiving asthma guidelines , further improvement was seen only in recording of review of inhaler technique and quality of prescribing in asthma . Sizes of disease registers were unchanged . The use of structured prompts was associated with improved recording of four of seven variables on diabetes and all six variables on asthma . Conclusions : Local guidelines disseminated via practice based education improve the management of diabetes and possibly of asthma in inner city , non-training practice s. The use of simple prompts may enhance this improvement Abstract Objective To test a multifaceted collaborative quality improvement intervention design ed to promote evidence based surfactant treatment for preterm infants of 23 - 29 weeks ' gestation . Design Cluster r and omised controlled trial Setting and participants 114 neonatal intensive care units ( which treated 6039 infants of 23 - 29 weeks gestation born in 2001 ) . Main outcome measures Process of care measures : proportion of infants receiving first surfactant in the delivery room , proportion receiving first surfactant more than two hours after birth , and median time from birth to first dose of surfactant . Clinical outcomes : death before discharge home , and pneumothorax . Intervention Multifaceted collaborative quality improvement advice including audit and feedback , evidence review s , an interactive training workshop , and ongoing faculty support via conference calls and email . Results Compared with those in control hospitals , infants in intervention hospitals were more likely to receive surfactant in the delivery room ( adjusted odds ratio 5.38 ( 95 % confidence interval 2.84 to 10.20 ) ) , were less likely to receive the first dose more than two hours after birth ( adjusted odds ratio 0.35 ( 0.24 to 0.53 ) ) , and received the first dose of surfactant sooner after birth ( median of 21 minutes v 78 minutes , P < 0.001 ) . The intervention effect on timing of surfactant was larger for infants born in the participating hospitals than for infants transferred to a participating hospital after birth . There were no significant differences in mortality or pneumothorax . Conclusion A multifaceted intervention including audit and feedback , evidence review s , quality improvement training , and follow up support changed the behaviour of health professionals and promoted evidence based practice BACKGROUND Benzodiazepine use by elderly patients is associated with adverse outcomes including increased risk of falls and fractures , motor vehicle accidents and cognitive impairment . Recent studies suggest that individualized feedback and education to physicians may improve drug prescribing . In this study , we evaluated an intervention to address the inappropriate prescribing of benzodiazepines for elderly patients . METHODS We identified 1624 primary care physicians who wrote at least 10 prescriptions for the target drugs in a 2-month period and r and omly assigned these physicians to the intervention group or the control group . We obtained data from the Ontario Drug Benefit cl aims data base , which covers all Ontario residents aged 65 years and over for drugs selected from a minimally restrictive formulary . Every 2 months for 6 months , confidential profiles of benzodiazepine prescription use coupled with evidence -based educational bulletins were mailed to the intervention group . The control group received feedback and educational bulletins about first-line antihypertension drug prescribing for elderly patients . Our main outcome measures were reductions in the proportion of each physician 's total benzodiazepine prescriptions for long-acting agents , combinations of benzodiazepines with other psychoactive medications ( including other benzodiazepines ) and long-term benzodiazepine therapy . RESULTS After r and omization , 168 physicians agreed to be in the intervention group and 206 in the control group . Their demographic and prescribing characteristics were similar . Although the proportion of long-acting benzodiazepine prescriptions decreased by 0.7 % in the intervention group between the baseline period and the end of the intervention period ( from 20.3 % , or a mean of 29.5 prescriptions , to 19.6 % , or a mean of 27.7 prescriptions ) and increased by 1.1 % in the control group ( from 19.8 % , or a mean of 26.4 prescriptions , to 20.9 % , or a mean of 27.7 prescriptions ) ( p = 0.036 ) , this difference was not clinical ly significant . There was no significant difference over the study period in either combination prescribing of benzodiazepines or in prescriptions for long-term benzodiazepine therapy . INTERPRETATION We did not find that a program of confidential feedback and educational material offered to Ontario primary care physicians had a clinical ly significant impact on their benzodiazepine prescribing To determine whether continuing medical education affects the quality of clinical care , we r and omly allocated 16 Ontario family physicians to receive or not receive continuing-education packages covering clinical problems commonly confronted in general practice . Over 4500 episodes of care , provided before and after study physicians received continuing education , were compared with preset clinical criteria and classified according to quality . Although objective tests confirmed that the study physicians learned from the packages , there was little effect on the overall quality of care . When the topics were of relatively great interest to the physicians , the control group ( who did not receive the packages ) showed as much improvement as did the study group . When the topics were not preferred , however , the documented quality of care provided by study physicians rose ( P less than 0.05 ) and differed from that provided by control physicians ( P = 0.01 ) . Finally , there was no spillover effect on clinical problems not directly covered by the program . In view of the trend toward m and atory continuing education and the re sources expended , it is time to reconsider whether it works OBJECTIVE To evaluate the feasibility and implementation needs of a cholesterol guideline by assessing the effectiveness of simple dissemination as well as extensive implementation of this guideline on actual performance of general practitioners ( GPs ) . DESIGN R and omized controlled trial . SETTING AND SUBJECTS Thirty-two Dutch GPs in 20 general practice s , 3950 patient records . INTERVENTIONS Guideline dissemination to all 32 GPs , and a 5-month programme for improvement in the intervention group . This programme was developed after barriers to working according to the guideline had been investigated , and consisted of group education , desktop supportive material s , feedback on performance , and face-to-face instruction on location . MAIN OUTCOME MEASURES The outcome parameters were defined as quality of selective case finding and quality of diagnostic procedures , and were measured by chart audit . RESULTS The quality of selective case finding , especially the targeting of cholesterol testing to those with positive cardiovascular risk profiles , did not improve following intervention . Performance of the procedure necessary to diagnose hypercholesterolaemia even deteriorated . The quantity of cholesterol testing increased in both groups , but this was probably explained by the increased availability of desktop cholesterol analysers . CONCLUSIONS Neither simple dissemination nor an intensive programme for improvement had measurable impact on actual performance on working according to the cholesterol guideline . Both the validity and the opinion about feasibility of the guideline in daily practice deserve more attention during guideline development Background Our professional development plan aim ed to improve the primary care management of acute asthma , which is known to be suboptimal . Methods We invited 59 general practice s in Grampian , Scotl and to participate . Consenting practice s were r and omised to early and delayed intervention groups . Practice s undertook audits of their management of all acute attacks ( excluding children under 5 years ) occurring in the 3 months preceding baseline , 6-months and 12-months study time-points . The educational programme [ including feedback of audit results , attendance at a multidisciplinary interactive workshop , and formulation of development plan by practice teams ] was delivered to the early group at baseline and to the delayed group at 6 months . Primary outcome measure was recording of peak flow compared to best/predicted at 6 months . Analyses are presented both with , and without adjustment for clustering . Results 23 consenting practice s were r and omised : 11 to early intervention . Baseline practice demography was similar . Six early intervention practice s withdraw before completing the baseline audit . There was no significant improvement in our primary outcome measure ( the proportion with peak flow compared to best/predicted ) at either the 6 or 12 month time points after adjustment for baseline and practice effects . However , the between group difference in the adjusted combined assessment score , whilst non-significant at 6 months ( Early : 2.48 ( SE 0.43 ) vs. Delayed 2.26 ( SE 0.33 ) p = 0.69 ) reached significance at 12 m ( Early:3.60 ( SE 0.35 ) vs. Delayed 2.30 ( SE 0.28 ) p = 0.02 ) . Conclusion We demonstrated no significant benefit at the a priori 6-month assessment point , though improvement in the objective assessment of attacks was shown after 12 months . Our practice development programme , incorporating audit , feedback and a workshop , successfully engaged the healthcare team of participating practice s , though future r and omised trials of educational interventions need to recognise that effecting change in primary care practice s takes time . Monitoring of the assessment of acute attacks proved to be a feasible and responsive indicator of quality care Abstract Objective : To develop a working model with which prescribing behaviour among general practitioners might be influenced . Design : Intervention based on feedback on prescribing rates and problem-oriented educational outreach visits , using educational material and local opinion leaders . R and omised study with three parallel intervention groups of general practitioners , which also served as controls for each other . The pharmacotherapeutic fields chosen were hypertension , peptic ulcer/dyspepsia and depression . Prescription data were retrieved from the electronic patient records for periods of 1 year before and after the intervention . Setting : Six health care centres and three continuing medical education groups in Stockholm . Subjects : Forty general practitioners . Main outcome measures : Drug prescribing rates and patterns before and after the intervention . Results : In the hypertension field , desired trends in fractional prescribing ( favouring diuretics and beta blocking agents ) were recorded , with a significant ( P<0.05 ) effect on prescriptions for agents acting on the renin – angiotensin system , despite a pre-existing prescribing behaviour already much in line with the goals . In the peptic ulcer/dyspepsia field , desired trends were recorded for both types of therapies addressed . The fractional prescribing rates for proton-pump inhibitors decreased from 61.0 % to 52.6 % in the intervention arm and increased from 68.1 % to 76.0 % in the control arm ( not significant due to low power ) . The depression group focused on better general attention to the disease and only minor changes were registered . Conclusion : Feedback of individual prescribing rates , combined with problem-oriented educational outreach visits , is a promising model for the improvement of prescribing behaviour . Data from the electronic patient record were feasible for feedback on prescribing rates OBJECTIVE . We tested whether NICU teams trained in benchmarking and quality improvement would change practice s and improve rates of survival without bronchopulmonary dysplasia in inborn neonates with birth weights of < 1250 g. METHODS . A cluster-r and omized trial enrolled 4093 inborn neonates with birth weights of < 1250 g at 17 centers of the National Institute of Child Health and Human Development Neonatal Research Network . Three centers were selected as best performers , and the remaining 14 centers were r and omized to intervention or control . Changes in rates of survival free of bronchopulmonary dysplasia were compared between study year 1 and year 3 . RESULTS . Intervention centers implemented potentially better practice s successfully ; changes included reduced oxygen saturation targets and reduced exposure to mechanical ventilation . Five of 7 intervention centers and 2 of 7 control centers implemented use of high-saturation alarms to reduce oxygen exposure . Lower oxygen saturation targets reduced oxygen levels in the first week of life . Despite these changes , rates of survival free of bronchopulmonary dysplasia were all similar between intervention and control groups and remained significantly less than the rate achieved in the best-performing centers ( 73.3 % ) . CONCLUSIONS . In this cluster-r and omized trial , benchmarking and multimodal quality improvement changed practice s but did not reduce bronchopulmonary dysplasia rates OBJECTIVE To assess the practice -level effects of ( 1 ) a physician peer leader intervention and ( 2 ) peer leaders in combination with the introduction of asthma education nurses to facilitate care improvement . And , to compare findings with previously reported patient-level outcomes of trial enrollees . STUDY SETTING Data were included on children 5 - 17 years old with asthma in 40 primary care practice s , affiliated with managed health care plans enrolled in the Pediatric Asthma Care Patient Outcomes Research Team ( PORT ) r and omized trial . STUDY DESIGN Primary care practice s were r and omly assigned to one of two care improvement arms or to usual care . Automated cl aims data were analyzed for 12-month periods using a repeated cross-sectional design . The primary outcome was evidence of at least one controller medication dispensed among patients with persistent asthma . Secondary outcomes included controller dispensing among all identified asthmatics , evidence of chronic controller use , and the dispensing of oral steroids . Health service utilization outcomes included numbers of ambulatory visits and hospital-based events . PRINCIPAL FINDINGS The proportion of children with persistent asthma prescribed controllers increased in all study arms . No effect of the interventions on the proportion receiving controllers was detected ( peer leader intervention effect 0.01 , 95 percent confidence interval [ CI ] : -0.07 , 0.08 ; planned care intervention effect -0.03 , 95 percent CI : -0.09 , 0.02 ) . A statistical trend was seen toward an increased number of oral corticosteroid bursts dispensed in intervention practice s. Significant adjusted increases in ambulatory visits of 0.08 - 0.10 visits per child per year were seen in the first intervention year , but only a statistical trend in these outcomes persisted into the second year of follow-up . No differences in hospital-based events were detected . CONCLUSIONS This analysis showed a slight increase in ambulatory asthma visits as a result of asthma care improvement interventions , using automated data . The absence of detectable impact on medication use at the practice level differs from the positive intervention effect observed in patient self-reported data from trial enrollees . Analysis of automated data on nonenrollees adds information about practice -level impact of care improvement strategies . Benefits of practice -level interventions may accrue disproportionately to the subgroup of trial enrollees . The effect of such interventions may be less apparent at the level of practice s or health plans OBJECTIVE To determine whether audit/feedback and educational material s improve adherence to recommendations for laboratory monitoring and cytoprotective agents to detect and prevent adverse events caused by nonsteroidal anti-inflammatory agents ( NSAIDs ) . STUDY DESIGN Controlled , cluster-r and omized trial . METHODS Physicians commonly prescribing NSAIDs were identified within a large managed care organization and r and omized to a control or an intervention group ( audit/feedback with peer-derived benchmarks and continuing medical education ) . Medical records were examined 10 months before and after the intervention for clinical data and receipt of complete blood count ( CBC ) , creatinine testing , and cytoprotective agents ( process measures ) . Primary analysis compared intervention versus control physicians among those who initially performed below a peer-derived benchmark . General estimating equations accounted for patient clustering . RESULTS Of 101 physicians initially r and omized , 85 remained eligible ( 38 internists , 36 family physicians , 11 rheumatologists ) postintervention . Mean percent change in performance between intervention and control physicians for CBC monitoring was 16 % versus 10 % ; for creatinine monitoring , 0 % versus 17 % ; and use of cytoprotective agents , -3 % versus -1 % . None of these changes were significant . Rheumatology specialty , number of NSAID prescriptions and physician visits , and patient risk factors for NSAID-related toxicity were more strongly associated with improved safety practice s than the intervention . CONCLUSIONS Audit/feedback and educational material s had no observed effect on improving NSAID-related safety practice s. Potentially contributing factors include high baseline performance ( ceiling effect ) , dilution of the intervention effect by case mix and provider factors , nonreceipt of intervention material s , and diverse indications for lab tests Ondansetron has had a major impact on the prevention of emesis in patients receiving chemotherapy . However , the high cost and potential for inappropriate prescribing of this agent warranted a closer examination of its utilization . Hospital guidelines regarding the use of ondansetron were prepared by the Pharmacy and Therapeutics Committee and approved by the Medical Advisory Committee . The guidelines were then distributed to all physicians . Physicians were r and omized into an intervention or non-intervention group . A prospect i ve drug use evaluation was then conducted for a 10-week period where pharmacists monitored ondansetron prescribing and compared each order against hospital guidelines . For orders deemed inappropriate , only the intervetion-group physicians were contacted for therapy modification . The control of nausea and vomiting was then assessed for all patients 24 h and 72 h after chemotherapy via a simple patient question naire . There were no significant differences with respect to the control of nausea and vomiting between patients who received ondansetron according to guidelines and those who did not . A total of 76 % ( 48/63 ) of the prescriptions met hospital guidelines in the intervention group compared to 51.6 % ( 33/64 ) in the control ( P=0.007 ) . During the study period , physicians in the intervention group prescribed $ Can 757 worth of ondansetron inappropriately compared to $ 1814 in the control . Drug use evaluation with pharmacist intervention was an effective method of controlling unnecessary hospital costs and contributed towards the appropriate use of on-dansetron without compromising patient care Background : Colorectal cancer ( CRC ) screening is recommended for all adults 50 to 75 years old , yet only slightly more than one-half of eligible people are current with screening . Because CRC screening is usually initiated upon recommendations of primary care physicians , interventions in these setting s are needed to improve screening . Objectives : To assess the impact of a quality improvement intervention combining electronic medical record based audit and feedback , practice site visits for academic detailing and participatory planning , and “ best- practice ” dissemination on CRC screening in primary care practice . Research Design : Two-year group r and omized trial . Subjects : Physicians , midlevel providers , and clinical staff members in 32 primary care practice s in 19 States caring for 68,150 patients 50 years of age or older . Measures : Proportion of active patients up-to- date ( UTD ) with CRC screening ( colonoscopy within 10 years , sigmoidoscopy within 5 years , or at home fecal occult blood testing within 1 year ) and having screening recommended within past year among those not UTD . Results : Patients 50 to 75 years in intervention practice s exhibited significantly greater improvement ( from 60.7 % to 71.2 % ) in being UTD with CRC screening than patients in control practice s ( from 57.7 % to 62.8 % ) , the adjusted difference being 4.9 % ( 95 % confidence interval , 3.8%–6.1 % ) . Recommendations for screening also increased more in intervention practice s with the adjusted difference being 7.9 % ( 95 % confidence interval , 6.3%–9.5 % ) . There was wide inter practice variation in CRC screening throughout the intervention . Conclusions : A multicomponent quality improvement intervention in practice s that use electronic medical record can improve CRC screening OBJECTIVE To investigate the effectiveness of a quality improvement educational program in rural hospitals . DESIGN Hospital-r and omized controlled trial . SETTING PARTICIPANTS A total of 47 rural and small community hospitals in Texas that had previously received a web-based benchmarking and case- review tool . INTERVENTION The 47 hospitals were r and omized either to receive formal quality improvement educational program or to a control group . The educational program consisted of two 2-day didactic sessions on continuous quality improvement techniques , followed by the design , implementation and reporting of a local quality improvement project , with monthly coaching conference calls and annual follow-up conclaves . MAIN OUTCOME MEASURES Performance on core measures for community-acquired pneumonia and congestive heart failure were compared between study groups to evaluate the impact of the educational program . RESULTS No significant differences were observed between the study groups on any measures . Of the 23 hospitals in the intervention group , only 16 completed the didactic program and 6 the full training program . Similar results were obtained when these groups were compared with the control group . CONCLUSIONS While the observed results suggest no incremental benefit of the quality improvement educational program following implementation of a web-based benchmarking and case- review tool in rural hospitals , given the small number of hospitals that completed the program , it is not conclusive that such programs are ineffective . Further research incorporating supporting infrastructure , such as physician champions , financial incentives and greater involvement of senior leadership , is needed to assess the value of quality improvement educational programs in rural hospitals 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 BACKGROUND Many studies have suggested that general practitioners fail to detect a substantial minority of their patients who are psychologically distressed , and there is concern about the possible sequelae of this . Individual patients may suffer unresolved problems , and there are potential costs to the health service in consequent recurrent consultations , inappropriate referrals or treatment . Educational interventions based on small groups led by facilitators have been shown to alter the consultation behaviours of general practitioners that are known to be related to accurate detection of psychological distress . AIM This controlled study aim ed to show that , by utilizing a brief self-directed educational intervention focusing on detection of psychological distress , general practitioners can improve their performance significantly . For this purpose , a new educational intervention was design ed : the second aim of the study was thus to assess the effectiveness of this specific intervention . METHOD An educational intervention was design ed which focused on skills relevant to detecting psychological distress , using the principles of reflection on general practitioner performance and consultation skill work . It was design ed to be used by individual general practitioners without outside support , using a combination of written background material , feedback on performance and analysis of video material . The effectiveness of the intervention was tested by comparing a trial and control cohort of general practitioners , using detection rates as an outcome measure . RESULTS The detection rate of the general practitioners who underwent the intervention improved significantly compared with their performance before intervention and with that of the control group . CONCLUSION General practitioners can improve their ability to detect psychological distress in their patients utilizing this self-directed educational approach Purpose To assess the effectiveness of supplying occupational physicians ( OPs ) with targeted and stage-matched information or with feedback on reporting occupational diseases to the national registry in the Netherl and s. Methods In a r and omized controlled design , 1076 OPs were divided into three groups based on previous reporting behaviour : precontemplators not considering reporting , contemplators considering reporting and actioners reporting occupational diseases . Precontemplators and contemplators were r and omly assigned to receive stage-matched , stage-mismatched or general information . Actioners were r and omly assigned to receive personalized or st and ardized feedback upon notification . Outcome measures were the number of OPs reporting and the number of reported occupational diseases in a 180-day period before and after the intervention . Results Precontemplators were significantly more male and self-employed compared to contemplators and actioners . There was no significant effect of stage-matched information versus stage-mismatched or general information on the percentage of reporting OPs and on the mean number of notifications in each group . Receiving any information affected reporting more in contemplators than in precontemplators . The mean number of notifications in actioners increased more after personalized feedback than after st and ardized feedback , but the difference was not significant . Conclusions This study supports the concept that contemplators are more susceptible to receiving information but could not confirm an effect of stage-matching this information on reporting occupational diseases to the national registry AIM To determine the impact and cost-effectiveness of telephone versus written access to magnetic resonance imaging ( MRI ) , and of different strategies for disseminating locally produced guidelines , upon requests by general practitioners ( GPs ) for knee and lumbar spine investigation . MATERIAL AND METHODS Two sequential pragmatic open cluster-r and omized trials were conducted within 39 general practice s. The outcome measure in each trial was concordance of request with local guidelines . Trial 1 : practice s requested MRI by telephone or in writing . Trial 2 : all practice s received guidelines , plus either : a practice -based seminar , practice -specific audit feedback , both seminar and feedback , or neither . RESULTS A total of 414 requests were assessed in the two trials . Trial 1 : telephone access cost pound4.86 more per request but rates of concordant requests were equivalent ( 65%/64 % : telephone/written ) . Trial 2 : compared to the control group , costs per practice were pound1911 higher in seminar group , pound1543 higher in feedback group and pound3578 higher for those receiving both . Concordance was greater following the intervention ( 74 % vs 65 % ; P < 0.05 ) , but there was no difference between the four study groups . CONCLUSIONS Method of access did not affect concordance . Written access was more cost-effective . Seminars and feedback were no more effective in modifying practice than guidelines alone , which was thus the most cost-effective option BACKGROUND Postnatal morbidity is high , and many GPs lack the confidence and knowledge to deal with common postnatal problems . There is a high consultation rate , but few women disclose common health problems . OBJECTIVE The aim of the present study was to increase the knowledge and skills of GPs to enable them to identify and manage common health problems experienced by women in the year following childbirth . METHODS An educational programme [ Guidelines for Assessing Postnatal Problems ( GAPP ) ] embedded within a large r and omized community intervention trial [ Program of Re sources , Information and Support for Mothers ( PRISM ) ] with a before/after evaluation was undergone by Australian GPs working in four metropolitan and four rural communities . The programme comprised audit , interactive workshops , role-play and evidence -based guidelines , and was evaluated at baseline and 6 months through written question naires and a surgery consultation with a trained simulated patient evaluator . RESULTS A total of 68 ( 86 % ) GPs took part in the full GAPP programme . The odds of a GP improving on the knowledge items ranged from 1.0 to 16 , with the greatest change occurring in knowledge about the effectiveness of cognitive behavioural therapy for maternal depression . Of the GPs with an incorrect response at baseline , the percentage demonstrating improved knowledge at follow-up ranged from 22 to 100 % . Around half of the GPs demonstrated excellent communication skills at baseline . Of the remaining GPs , more than half demonstrated greatly improved skills to detect common postnatal problems at follow-up . At baseline simulated patient visit , 70 % of GPs inquired about sexual problems yet none inquired about the possibility of abuse , whereas at follow-up 94 % inquired about sexual problems and 51.5 % facilitated the disclosure of physical and emotional abuse . Anonymous feedback on the programme by participating GPs showed that 89 % believed the programme positively influenced their actual practice . Interestingly , GPs demonstrated greater knowledge and skills in the simulated setting than on the written question naire . CONCLUSIONS This relatively brief multifaceted educational programme assisted many participants in improving their knowledge and the skills required to improve both physical and emotional health after birth . Despite being experienced clinicians and participating actively in a programme on interviewing skills , half of the GPs did not facilitate disclosure of the underlying sensitive issue ( abuse ) during the follow-up consultation and could benefit from further in-depth training in effective communication skills OBJECTIVE Investigating whether and how the prescribing behaviour of general practitioners ( GPs ) can be changed by the pharmacist 's feedback . DESIGN R and omised , prospect i ve . SETTING Residential home ' Bernlef ' , Groningen , the Netherl and s. METHOD In the period 2 February-18 March 1993 the effect of different ways of sending prescriptions by the pharmacist on medication use was investigated . The 43 GPs of the inhabitants were r and omly divided in 3 groups . Group A formed the control group and was requested to send their prescriptions as before , group B moreover received a list with the medication used by their patients , group C also got a list with the actual medication of their patients as well as recommendations by the pharmacist . Effects on medication use were determined after 4 weeks . RESULTS The 196 inhabitants used an average of 6.5 drugs ( range 0 - 19 ) . No difference was found between group A and group B , but there was a difference with group C. In all three groups the number of added drugs increased by 5 % , but the number of deleted drugs was 7 % in group C , as against only 3 % in groups A and B ( p < 0.05 ) . The feedback of the pharmacist that for 44 % of GPs contained new information result ed 9 times in the ending of medication and 4 times in decreasing of the dose . CONCLUSION Pharmacist 's feedback by means of remarks on prescribed medication positively influences prescription behaviour of the GP Objective . Immunizations and other cost-effective preventive services remain underused by many children , especially those living in poverty . Given the effectiveness of provider-based tracking systems and the widespread use by managed care organizations of financial incentives to influence physician practice patterns , we design ed and tested an intervention combining these strategies . We studied whether a system of semiannual assessment and feedback , coupled with financial incentives , could improve pediatric preventive care in a Medicaid health maintenance organization ( HMO ) . Methodology . We r and omly assigned primary care sites serving children in a Medicaid HMO to one of three groups : a feedback group ( where physicians received written feedback about compliance scores ) , a feedback and incentive group ( where physicians received feedback and a financial bonus when compliance criteria were met ) , and a control group . We evaluated compliance with pediatric preventive care guidelines through semiannual chart audits during the years 1993 to 1995 . Results . Compliance with pediatric preventive care improved dramatically in the study period . Repeated measures ANOVA demonstrated a significant increase in all three study groups throughout the time in total compliance scores ( from 56%–73 % ) , as well as scores for immunizations ( from 62%–79 % ) and other preventive care ( from 54%–71 % ) . However , no significant differences were observed between either intervention group and the control group , nor were there any interaction ( group-by-time ) effects . Conclusions . Feedback to physicians , with or without financial incentives , did not improve pediatric preventive care in this Medicaid HMO during a time of rapid , secular improvements in care . Possible explanations include the context and timing of the intervention , the magnitude of the financial incentives , and lack of physician awareness of the intervention Background : The number of inappropriate prescriptions for sexually transmitted infections ( STIs ) in Sudan is suspected to be high . Simple multifaceted interventions directed at prescribers may improve prescribing patterns in the Sudan . Objective : To evaluate the effect of multifaceted interventions on prescribing for STIs in the White Nile State , Sudan . Methods : The study involved 20 health centres r and omly assigned to four different multifaceted interventions to improve prescribing . Results : Prescriber targeted interventions involving audit and feedback together with academic detailing and practice guidelines reduced the number of inappropriate prescriptions by 50 % ( p<0.001 ) . Audit and feedback together with seminars and practice guidelines reduced inappropriate prescriptions by 43 % ( p<0.001 ) . Audit and feedback alone reduced inappropriate prescriptions by 16 % ( p = 0.127 ) . Conclusion : Prescribing for STIs in the White Nile State of Sudan needs improving . Multifaceted interventions appear effective in improving prescribing CONTEXT Hospital report cards are increasingly being implemented for quality improvement despite lack of strong evidence to support their use . OBJECTIVE To determine whether hospital report cards constructed using linked hospital and prescription administrative data bases are effective for improving quality of care for acute myocardial infa rct ion ( AMI ) . DESIGN The Administrative Data Feedback for Effective Cardiac Treatment ( AFFECT ) study , a cluster r and omized trial . SETTING AND PATIENTS Patients with AMI who were admitted to 76 acute care hospitals in Quebec that treated at least 30 AMI patients per year between April 1 , 1999 , and March 31 , 2003 . INTERVENTION Hospitals were r and omly assigned to receive rapid ( immediate ; n = 38 hospitals and 2533 patients ) or delayed ( 14 months ; n = 38 hospitals and 3142 patients ) confidential feedback on quality indicators constructed using administrative data . MAIN OUTCOME MEASURES Quality indicators pertaining to processes of care and outcomes of patients admitted between 4 and 10 months after r and omization . The primary indicator was the proportion of elderly survivors of AMI at each study hospital who filled a prescription for a beta-blocker within 30 days after discharge . RESULTS At follow-up , adjusted prescription rates within 30 days after discharge were similar in the early vs late groups ( for beta-blockers , odds ratio [ OR ] , 1.06 ; 95 % confidence interval [ CI ] , 0.82 - 1.37 ; for angiotensin-converting enzyme inhibitors , OR , 1.17 ; 95 % CI , 0.90 - 1.52 ; for lipid-lowering drugs , OR , 1.14 ; 95 % CI , 0.86 - 1.50 ; and for aspirin , OR , 1.05 ; 95 % CI , 0.84 - 1.33 ) . In addition , adjusted mortality was similar in both groups , as were length of in-hospital stay , physician visits after discharge , waiting times for invasive cardiac procedures , and readmissions for cardiac complications . CONCLUSIONS Feedback based on one-time , confidential report cards constructed using administrative data is not an effective strategy for quality improvement regarding care of patients with AMI . A need exists for further studies to rigorously evaluate the effectiveness of more intensive report card interventions CONTEXT Performance feedback and benchmarking , common tools for health care improvement , are rarely studied in r and omized trials . Achievable Benchmarks of Care ( ABCs ) are st and ards of excellence attained by top performers in a peer group and are easily and reproducibly calculated from existing performance data . OBJECTIVE To evaluate the effectiveness of using achievable benchmarks to enhance typical physician performance feedback and improve care . DESIGN Group-r and omized controlled trial conducted in December 1996 , with follow-up through 1998 . SETTING AND PARTICIPANTS Seventy community physicians and 2978 fee-for-service Medicare patients with diabetes mellitus who were part of the Ambulatory Care Quality Improvement Project in Alabama . INTERVENTION Physicians were r and omly assigned to receive a multimodal improvement intervention , including chart review and physician-specific feedback ( comparison group ; n = 35 ) or an identical intervention plus achievable benchmark feedback ( experimental group ; n = 35 ) . MAIN OUTCOME MEASURE Preintervention ( 1994 - 1995 ) to postintervention ( 1997 - 1998 ) changes in the proportion of patients receiving influenza vaccination ; foot examination ; and each of 3 blood tests measuring glucose control , cholesterol level , and triglyceride level , compared between the 2 groups . RESULTS The proportion of patients who received influenza vaccine improved from 40 % to 58 % in the experimental group ( P<.001 ) vs from 40 % to 46 % in the comparison group ( P = .02 ) . Odds ratios ( ORs ) for patients of achievable benchmark physicians vs comparison physicians who received appropriate care after the intervention , adjusted for preintervention care and nesting of patients within physicians , were 1.57 ( 95 % confidence interval [ CI ] , 1.26 - 1.96 ) for influenza vaccination , 1.33 ( 95 % CI , 1.05 - 1.69 ) for foot examination , and 1.33 ( 95 % CI , 1.04 - 1.69 ) for long-term glucose control measurement . For serum cholesterol and triglycerides , the achievable benchmark effect was statistically significant only after additional adjustment for physician characteristics ( OR , 1.40 [ 95 % CI , 1.08 - 1.82 ] and OR , 1.40 [ 95 % CI , 1.09 - 1.79 ] , respectively ) . CONCLUSION Use of achievable benchmarks significantly enhances the effectiveness of physician performance feedback in the setting of a multimodal quality improvement intervention Background The increasing prevalence of type 2 diabetes poses a major public health challenge . Population -based screening and early treatment for type 2 diabetes could reduce this growing burden . However , the benefits of such a strategy remain uncertain . Methods and design The ADDITION-Cambridge study aims to evaluate the effectiveness and cost-effectiveness of ( i ) a stepwise screening strategy for type 2 diabetes ; and ( ii ) intensive multifactorial treatment for people with screen-detected diabetes in primary care . 63 practice s in the East Anglia region participated . Three undertook the pilot study , 33 were allocated to three groups : no screening ( control ) , screening followed by intensive treatment ( IT ) and screening plus routine care ( RC ) in an unbalanced ( 1:3:3 ) r and omisation . The remaining 27 practice s were r and omly allocated to IT and RC . A risk score incorporating routine practice data was used to identify people aged 40–69 years at high-risk of undiagnosed diabetes . In the screening practice s , high-risk individuals were invited to take part in a stepwise screening programme . In the IT group , diabetes treatment is optimised through guidelines , target-led multifactorial treatment , audit , feedback , and academic detailing for practice teams , alongside provision of educational material s for newly diagnosed participants . Primary endpoints are modelled cardiovascular risk at one year , and cardiovascular mortality and morbidity at five years after diagnosis of diabetes . Secondary endpoints include all-cause mortality , development of renal and visual impairment , peripheral neuropathy , health service costs , self-reported quality of life , functional status and health utility . Impact of the screening programme at the population level is also assessed through measures of mortality , cardiovascular morbidity , health status and health service use among high-risk individuals . Discussion ADDITION-Cambridge is conducted in a defined high-risk group accessible through primary care . It addresses the feasibility of population -based screening for diabetes , as well as the benefits and costs of screening and intensive multifactorial treatment early in the disease trajectory . The intensive treatment algorithm is based on evidence from studies including individuals with clinical ly diagnosed diabetes and the education material s are informed by psychological theory . ADDITION-Cambridge will provide timely evidence concerning the benefits of early intensive treatment and will inform policy decisions concerning screening for type 2 diabetes . Trial registration Current Controlled trials IS RCT 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 < 0.02 ) ; changes were smaller with feedback only and reminders only ( P = NS vs. control ) . Trends were similar but not significant with 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 < 0.001 ) . CONCLUSIONS Feedback on performance aim ed at overcoming clinical inertia and given to 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 We investigated success factors for the introduction of a guideline on recognition of Lynch syndrome in patients recently diagnosed with colorectal cancer ( CRC ) below age 50 or a second CRC below age 70 . Pathologists were asked to start microsatellite instability ( MSI ) testing and report to surgeons with the advice to consider genetic counselling when MSI test or family history was positive . A multicentre cluster-r and omised controlled trial ( Clinical Trials.gov , number NCT00141466 ) was performed in 12 pathology laboratories ( clusters ) , serving 29 community hospitals . All received an introduction to the new guideline . In the intervention group , surgeons received education and tumour test result reminders ; pathologists were provided with inclusion criteria cards , an electronic patient inclusion reminder system and feedback on inclusion . Two hundred sixty-six CRC patients were eligible for recognition as at risk for Lynch syndrome . The actual recognition was 18 % more successful in the intervention as compared to the control arm ( 77 % ( 120 of 156 ) compared to 59 % ( 65 of 110 ) ) , with an adjusted odds ratio ( OR ) = 2.8 ( 95 % confidence interval ( CI ) 1.1–7.0 ) . The electronic reminder system for pathologists was most strongly associated with recognition of high-risk patients , OR = 4.2 ( 95 % CI 1.7–10.1 ) . An electronic reminder system for pathologists appeared effective for adherence to a new complex guideline and will enhance the recognition of Lynch syndrome BACKGROUND This paper describes a collaborative Medicare cl aims data linkage and sharing effort between the Baylor Health Care System ( BHCS ) and Texas Medical Foundation ( TMF , the Texas Quality Improvement Organization ) design ed to assess the effect of three quality improvement interventions on care delivered to elderly patients with diabetes . The r and omized controlled trial is being conducted among a network of primary care physician practice s owned by BHCS and focuses on measures of care process and outcome . METHODS Cohort definition and baseline measurement took place between January 1 and December 31 , 2000 . BHCS administrative data and TMF-supplied Medicare enrollment data were used to define the January 1 , 2001 prevalence cohort of Medicare diabetic beneficiaries meeting study inclusion criteria . A total of 22 practice s ( with 92 physicians and 2,158 patients ) were r and omized to one of three interventions , each of which involved performance measurement feedback on three cl aims -based measures of care process . Physician profiles , generated by TMF using Medicare utilization files , were reported to study physicians via academic detailing sessions with a BHCS physician educator . RESULTS The January 1 - December 31 , 2000 baseline Medicare cl aims for the January 1 , 2001 prevalence cohort were provided to HTPN by TMF in October 2001 , representing a ten-month lag in the ability of Quality Improvement Organizations to provide Part B data relative to a specific episode of care time frame . Overall baseline rates for the cl aims -based process measures were : annual HbA1c testing ( 86.1 % ) , annual eye examination ( 60.8 % ) , and annual lipid profile ( 72.5 % ) . As anticipated , medical-record based rates of annual eye examination were significantly underrepresented . Agreement between cl aims -based and medical record-based measures was very close for annual HbA1c and annual lipid profile . CONCLUSIONS The use of Medicare cl aims data , through collaboration with a QIO , can help health care providers overcome a significant barrier associated with quality improvement initiatives . Limitations associated with the use of Medicare cl aims can impact implementation of intervention strategies , but do not prevent them from being a practical tool for improving care Purpose To evaluate the effect of a combined or a single educational intervention on the prescribing behaviour of general practitioners ( GPs ) . The primary endpoint was effect on inappropriate prescribing according to the Medication Appropriateness Index ( MAI ) . Methods General practitioners were r and omised to either ( 1 ) a combined intervention consisting of an interactive educational meeting plus feedback on participating patients ’ medication , ( 2 ) a single intervention with an interactive educational meeting or ( 3 ) a control group ( no intervention ) . Elderly ( > 65 years ) patients exposed to polypharmacy ( ≥5 medications ) were identified and approached for inclusion . Data on medications prescribed over a 3-month period were collected , and the GPs provided detailed information on their patients before and after the intervention . A pre- and post-MAI were scored for all medications . Results Of the 277 GPs invited to participate ; 41 ( 14.8 % ) volunteered . Data were obtained from 166 patients before and after the intervention . Medication appropriateness improved in the combined intervention group but not in the single intervention group . The mean change in MAI and number of medications was −5 [ 95 % confidence interval ( CI ) −7.3 to −2.6 ] and −1.03 ( 95 % CI −1.7 to −0.30 ) in the combined intervention group compared with the group with the educational meeting only and the no intervention group . Conclusions A combined intervention consisting of an interactive educational meeting plus recommendations given by clinical pharmacologists/pharmacists concerning specific patients can improve the appropriateness of prescribing among elderly patients exposed to polypharmacy . This study adds to the limited number of well-controlled , r and omised studies on overall medication appropriateness among elderly patients in primary care . Important limitations to the study include variability in data provided by participating GPs and a low number of GPs volunteering for the study A project to improve physician performance in colorectal cancer screening was evaluated as part of an ambulatory quality assurance program . A minimum st and ard was adopted requiring a digital examination and stool test for occult blood at annual check-ups of patients aged 40 years and older . During a 3½-year period , three different intervention strategies for improved compliance with the st and ard were sequentially implemented and assessed : educational meeting , retrospective feedback of group compliance rate , and retrospective feedback of individual compliance rate compared with that of peers . A pretest/posttest design was employed in evaluating the first two intervention strategies . Neither strategy result ed in significant improvement in compliance . Monthly feedback of individual performance ranked with that of peers was then implemented in a r and omized clinical trial utilizing a crossover design . During the first 6-month period , the physicians receiving feedback ( group 1 ) improved from 66.0 % to 79.9 % ( P < 0.001 ) , while the control group ( group 2 ) also improved , from 67.5 % to 76.6 % ( P < 0.001 ) , suggesting a spillover effect . During the second 6-month period , group 2 received feedback and group 1 did not . Group 1 stabilized at approximately 80 % while group 2 continued to improve from 76.6 % to 84.0 % ( P < 0.001 ) . Behavior changes persisted at 6 and 12 months after intervention Our aim was to evaluate effects on prescribing for urinary tract infection ( UTI ) and asthma , of an education with messages based on national guidelines , aim ed at improving prescribing in primary care in Sweden . The study is part of the European Drug Education Project . A r and omized controlled trial , with groups of general practitioners ( GPs ) allocated to education on UTI ( 18 groups , 104 GPs ) or asthma ( 18 groups , 100 GPs ) , the two parallel intervention arms being controls for each other . Feedback was provided on the GP 's judgments of simulated cases and prescribing . Prescribing indicators were developed and measured before and after the intervention . Analysis was performed by multi-level technique . Prescribing of first choice UTI drugs increased in the intervention arm from 52 % to 70 % and remained constant in the control arm ( P < 0.001 ) . The proportion of patients receiving an inhaled corticosteroid increased insignificantly in both study arms . The educational model can be used to improve prescribing . Further studies are needed to define when the model is effective OBJECTIVE To assess the effectiveness of an intervention targeting both physicians and nurses vs. physicians only in improving venous thromboprophylaxis for older patients . DESIGN Cluster r and omized trial . SETTING Fifty hospital-based post-acute care departments in France . PARTICIPANTS Patients aged 65 years or older . INTERVENTION A multifaceted intervention to implement a clinical practice guideline addressing venous thromboprophylaxis . MAIN OUTCOME MEASURES The effectiveness outcomes were elastic stocking use , ambulation or mobilization under the supervision of a physical therapist and anticoagulant-based prophylaxis . Patient outcomes included deep vein thrombosis and anticoagulant-related adverse events . RESULTS One department allocated to the intervention targeted at physicians only and seven departments allocated to the intervention targeted at both physicians and nurses dropped out of the study . Compared with the intervention targeted at physicians only ( n = 497 patients ) , the intervention targeted at both physicians and nurses ( n = 315 patients ) was associated with a higher rate of mobilization ( 62 vs. 37 % , P < 0.001 ) and comparable levels of elastic stocking ( 32 vs. 39 % , P = 0.74 ) and anticoagulant ( 55 vs. 48 % , P = 0.36 ) use . The rates of deep vein thrombosis ( 15 vs. 13 % , P = 0.50 ) , bleeding ( 1 vs. 1 % , P = 0.99 ) and thrombocytopaenia ( 0 vs. 0.2 % , P = 0.99 ) did not differ between the two groups . CONCLUSIONS A multifaceted intervention targeting nurses in addition to physicians can increase the frequency of mobilization of older patients to prevent venous thromboembolism but does not alter the use of elastic stockings and anticoagulant . A differential drop-out of departments might have contributed to creating imbalances in baseline characteristics and outcomes in this study To determine effective methods of promoting routine cancer screening , we r and omly assigned 62 internal medicine residents to receive cancer screening reminders ( computer-generated lists of overdue tests at patients ' visits ) , audit with feedback ( monthly seminars about screening , with feedback about their performance rates ) , or no intervention ( controls ) . Half of the residents in each group also were r and omized to receive patient education ( patients received literature and notices of overdue tests ) . We review ed a sample of each physician 's medical records to assess performance of seven tests during 9-month periods before and after initiating the interventions . Cancer screening reminders increased performance of six of seven tests ; audit with feedback , four of seven tests ; and patient education , one of two targeted breast cancer screening tests . The results indicate that the cancer screening reminders strategy was the most effective in promoting the performance of routine cancer screening tests The purpose of this study was to compare the effect of 2 feedback strategies on the adherence to congestive heart failure ( CHF ) guidelines . Thirty-two hospitals in 4 states were r and omized to receive either a written feedback intervention ( low-intensity intervention [ LII ] ) or an intervention involving feedback , a physician liaison , and quality improvement tools ( high-intensity intervention [ HII ] ) . CHF quality indicators were assessed , and quality managers were interviewed at baseline and remeasurement . No significant changes in quality indicators were found as a result of either intervention . Seventy-eight percent of quality managers indicated that hospital project implementation had not begun until shortly before remeasurement . HII quality managers perceived the CHF project as significantly more successful compared with LII quality managers ( 63 % versus 13 % , P < .01 ) . Evaluation of the effects of external feedback on practice behavior requires sufficient time for organizational and individual clinician change to occur . Physician liaisons may play a role in facilitating this change OBJECTIVES The authors estimate separately contributions of each component intervention to overall effectiveness of quality assurance cycles used to improve practice performance . METHODS In a r and omized , controlled trial , experimental cycles of quality assurance were conducted for eight patient-care guidelines , with two experimental cycles assigned to each of 16 group practice s. For three separate interventions per cycle , practitioners : ( 1 ) were notified of the name of the experimental guideline , ( 2 ) discussed criteria of conformance to the guideline , and ( 3 ) received feedback on performance . Actions taken in response to interventions were documented . Using medical records data for a baseline year and for 3 months after each intervention and an additional 9 months , the authors scored each practice for conformance to two experimental guidelines and to control guidelines . RESULTS For all patient-care guidelines combined , and for four of five guidelines showing improvement , knowledge of guidelines and review criteria alone produced no change . After feedback , performance improved and improvement persisted for at least 9 months . The number of corrective actions implemented contributed significantly to effectiveness of quality assurance . CONCLUSIONS Feedback to providers of data on their performance is a more powerful stimulus for quality improvement than is knowledge of guidelines or discussion of review criteria In a 1 year prospect i ve study we evaluated the effect of feedback of laboratory data on the requesting behaviour of physicians in general medicine . Data on within-hours and out-of-hours clinical chemistry laboratory usage and revenue expenditure for in patients and out patients , expressed in terms of clinical workload , were supplied monthly to a group of three consultant physicians in general medicine . With these data the physician could monitor his performance over a period of time and compare it with that of his peers . Two consultants in general medicine who received no information served as controls . Over a period of 6 months , there was a 25 % , 13 % and 18 % decrease in tests ( P < 0·01 ) , requests ( P < 0·05 ) and revenue expenditure ( P < 0·01 ) per outpatient visit , respectively , in the intervention group of physicians following the introduction of feedback when compared to their baseline period and to the control group . The decrease ( P < 0·01 ) was in the commonly requested and ‘ seemingly cheap ’ tests . There was no significant change in laboratory use and expenditure on in patients . The feedback of laboratory data was acceptable to the physicians , raised their awareness of laboratory usage and costs and decreased laboratory workload and expenditure OBJECTIVE To assess the impact of a quality improvement ( QI ) intervention on the quality of diabetes care at primary care clinics . RESEARCH DESIGN AND METHODS Twelve primary care medical practice s were matched by size and location and r and omized to intervention or control conditions . Intervention clinic staff were trained in a seven-step QI change process to improve diabetes care . Surveys and medical record review s of 754 patients , surveys of 329 clinic staff , interviews with clinic leaders , and analysis of training session videotapes evaluated compliance with and impact of the intervention . Mixed-model nested analyses compared differences in the quality of diabetes care before and after intervention . RESULTS All intervention clinics completed at least six steps of the seven-step QI change process in an 18-month period and , compared with control clinics , had broader staff participation in QI activities ( P = 0.04 ) , used patient registries more often ( P = 0.03 ) , and had better test rates for HbA(1c ) ( A1C ) , LDL , and blood pressure ( P = 0.02 ) . Other processes of diabetes care were unchanged . The intervention did not improve A1C ( P = 0.54 ) , LDL ( P = 0.46 ) , or blood pressure ( P = 0.69 ) levels or a composite of these outcomes ( P = 0.35 ) . CONCLUSIONS This QI change process was successfully implemented but failed to improve A1C , LDL , or blood pressure levels . Data suggest that to be successful , such a QI change process should direct more attention to specific clinical actions , such as drug intensification and patient activation PURPOSE Underst and ing the transformation of primary care practice s to patient-centered medical homes ( PCMHs ) requires making sense of the change process , multilevel outcomes , and context . We describe the methods used to evaluate the country ’s first national demonstration project of the PCMH concept , with an emphasis on the quantitative measures and lessons for multi method evaluation approaches . METHODS The National Demonstration Project ( NDP ) was a group-r and omized clinical trial of facilitated and self-directed implementation strategies for the PCMH . An independent evaluation team developed an integrated package of quantitative and qualitative methods to evaluate the process and outcomes of the NDP for practice s and patients . Data were collected by an ethnographic analyst and a research nurse who visited each practice , and from multiple data sources including a medical record audit , patient and staff surveys , direct observation , interviews , and text review . Analyses aim ed to provide real-time feedback to the NDP implementation team and lessons that would be transferable to the larger practice , policy , education , and research communities . RESULTS Real-time analyses and feedback appeared to be helpful to the facilitators . Medical record audits provided data on process-of-care outcomes . Patient surveys contributed important information about patient-rated primary care attributes and patient-centered outcomes . Clinician and staff surveys provided important practice experience and organizational data . Ethnographic observations supplied insights about the process of practice development . Most practice s were not able to provide detailed financial information . CONCLUSIONS A multi method approach is challenging , but feasible and vital to underst and ing the process and outcome of a practice development process . Additional longitudinal follow-up of NDP practice s and their patients is needed Background —It is difficult to put research findings into clinical practice by either guidelines or prescription feedback . Aim —To study the effect on the quality of prescribing by a combined intervention of providing individual feedback and deriving quality criteria using guideline recommendations in peer review groups . Methods —199 general practitioners in 32 groups were r and omised to participate in peer review meetings related to either asthma or urinary tract infections . The dispensing by the participating doctors of antiasthmatic drugs and antibiotics during the year before the intervention period provided the basis for prescription feedback . The intervention feedback was design ed to describe the treatment given in relation to recommendations in the national guidelines . In each group the doctors agreed on quality criteria for their own treatment of the corresponding diseases based on these recommendations . Comparison of their prescription feedback with their own quality criteria gave each doctor the proportion of acceptable and unacceptable treatments . Main outcome measure — Difference in the prescribing behaviour between the year before and the year after the intervention . Results —Before intervention the mean proportions of acceptably treated asthma patients in the asthma group and urinary tract infection ( control ) group were 28 % and 27 % , respectively . The mean proportion of acceptably treated patients in the asthma group was increased by 6 % relative to the control group ; this difference was statistically significant . The mean proportions of acceptable treatments of urinary tract infection before intervention in the urinary tract infection group and asthma ( control ) group were 12 % for both groups which increased by 13 % in the urinary tract infection group relative to the control group . Relative to the mean pre-intervention values this represented an improvement in treatment of 21 % in the asthma group and 108 % in the urinary tract infection group . Conclusions —Deriving quality criteria of prescribing by discussing guideline recommendations gave the doctors a basis for judging their treatment of individual patients as acceptable or unacceptable . Presented with feedback on their own prescribing , they learned what they did right and wrong . This provided a foundation for improvement and the process thus instigated result ed in the doctors providing better quality patient care OBJECTIVE To evaluate the implementation of clinical guidelines for hypertension in general practice by use of a computer-based clinical decision support system ( CDSS ) and a specific implementation strategy . Evaluation of patient outcome . DESIGN R and omised study with health centres as units . The intervention group had the CDSS installed and made ready for use , doctors and assistants were trained and received a user-manual , the doctors were offered telephone repetitions , a seminar in risk intervention and , at the same seminar , further demonstration of the CDSS . The doctors received baseline registration s with information of how they treated their own hypertensive patients , and use of the CDSS was checked repeatedly . SETTING General practice in Sør- and Nord-Trøndelag counties in Norway , 380,000 inhabitants . PARTICIPANTS Seventeen health centres with 24 doctors and 984 patients in the intervention group . Data from 879 patients used in the final analyses . Twelve health centres with 29 doctors and 1255 patients in the control group . Data from 1119 patients used in the final analyses . MAIN OUTCOME MEASURES After an intervention period of 18 months , group differences in level of systolic and diastolic blood pressure , serum cholesterol , body mass index , and risk score for myocardial infa rct ion were calculated , as well as group differences in fractions of smokers . RESULTS Significant group difference in favour of intervention group : diastolic blood pressure 1 mmHg ( 95 % CI -1.89 , -0.17 ) . However , a significant baseline difference in systolic blood pressure in favour of control group of 2.7 mmHg ( 95 % CI 1.0 , 4.5 ) had been reduced to 1.2 mmHg ( 95 % CI -0.6 , 3.0 ) after intervention . CONCLUSION Implementation of clinical guidelines in the treatment of hypertensive patients in general practice by means of a CDSS and several other procedures for implementation did not affect patient outcome in any clinical ly significant way PURPOSE We wanted to evaluate the added value of small peer-group quality improvement meetings compared with simple feedback as a strategy to improve test-ordering behavior . Numbers of tests ordered by primary care physicians are increasing , and many of these tests seem to be unnecessary according to established , evidence -based guidelines . METHODS We enrolled 194 primary care physicians from 27 local primary care practice groups in 5 health care regions ( 5 diagnostic centers ) . The study was a cluster r and omized trial with r and omization at the local physician group level . We evaluated an innovative , multifaceted strategy , combining written comparative feedback , group education on national guidelines , and social influence by peers in quality improvement sessions in small groups . The strategy was aim ed at 3 specific clinical topics : cardiovascular issues , upper abdominal complaints , and lower abdominal complaints . The mean number of tests per physician per 6 months at baseline and the physicians ’ region were used as independent variables , and the mean number of tests per physician per 6 months was the dependent variable . RESULTS The new strategy was executed in 13 primary care groups , whereas 14 groups received feedback only . For all 3 clinical topics , the decrease in mean total number of tests ordered by physicians in the intervention arm was far more substantial ( on average 51 fewer tests per physician per half-year ) than the decrease in mean number of tests ordered by physicians in the feedback arm ( P = .005 ) . Five tests considered to be inappropriate for the clinical problem of upper abdominal complaints decreased in the intervention arm , with physicians in the feedback arm ordering 13 more tests per 6 months ( P = .002 ) . Interdoctor variation in test ordering decreased more in the intervention arm . CONCLUSION Compared with only disseminating comparative feedback reports to primary care physicians , the new strategy of involving peer interaction and social influence improved the physicians ’ test-ordering behavior . To be effective , feedback needs to be integrated in an interactive , educational environment OBJECTIVE : The effect of clinical guidelines on re source utilization for complex conditions with substantial barriers to clinician behavior change has not been well studied . We report the impact of a multifaceted guideline implementation intervention on primary care clinician utilization of radiologic and specialty services for the care of acute low back pain . DESIGN : Physician groups were r and omized to receive guideline education and individual feedback , supporting patient education material s , both , or neither . The impact on guideline adherence and re source utilization was evaluated during the 12-month period before and after implementation . PARTICIPANTS : Fourteen physician groups with 120 primary care physician and associate practitioners from 2 group model HMO practice s. INTERVENTIONS : Guideline implementation utilized an education/audit/feedback model with local peer opinion leaders . The patient education component included written and videotaped material s on the care of low back pain . MAIN RESULTS : The clinician intervention was associated with an absolute increase in guideline -consistent behavior of 5.4 % in the intervention group versus a decline of 2.7 % in the control group ( P=.04 ) . The patient education intervention produced no significant change in guideline -consistent behavior , but was poorly adopted . Patient characteristics including duration of pain , prior history of low back pain , and number of visits during the illness episode were strong predictors of service utilization and guideline -consistent behavior . CONCLUSIONS : Implementation of an education and feedback-supported acute low back pain care guideline for primary care clinicians was associated with an increase in guideline -consistent behavior . Patient education material s did not enhance guideline effectiveness . Implementation barriers could limit the utility of this approach in usual care setting BACKGROUND Most studies of interventions to reduce laboratory test utilization have occurred in academic hospital setting s , used historical controls , or have had short post intervention follow-up . Interventions with the greatest impact use multiple approaches , are repeated regularly , include comparisons with physician peers , and have a personal approach . We determined whether laboratory test utilization by community physicians could be reduced by a multifaceted program of education and feedback . METHODS We identified 200 physicians who ordered the largest number of common laboratory tests during 1 year in a nonhospital , commercial community ( reference ) laboratory . They were assigned to intervention and control groups ( 100 each ) . Intervention physicians were visited individually up to three times by laboratory representatives over a 2-year period . At each visit , educational material and the physician 's personal laboratory test utilization data were presented and discussed briefly in general terms , with the latter compared with utilization data for the physician 's peers . Overall test utilization rates 1 year before , during , and 2 years after the intervention were measured using population -based data bases . Time-series analysis was used to determine the effect of the intervention on laboratory test utilization . RESULTS The two groups began with similar test utilization : control group , 4.06 x 10(6 ) tests in 1.48 x 10(6 ) visits ( 2.73 tests/visit ) ; intervention group , 3.90 x 10(6 ) tests in 1.41 x 10(6 ) visits ( 2.77 tests/visit ) . During the 2-year intervention , intention-to-treat analysis showed that utilization decreased significantly in the intervention group compared with the controls [ relative reduction of 7.9 % ( P < 0.0001 ) ; absolute reduction of 0.22 tests/visit ( 95 % confidence interval , 0.20 - 0.24 ) ] . This difference persisted until the end of study observation , or more than 2 years after the intervention ended . CONCLUSION A multifaceted education and feedback strategy can significantly and persistently decrease laboratory utilization by practicing community physicians Four similar teams of physicians associated with similar inpatient units and r and omly assigned patients were used to study the effect of providing physicians with cost information about their use of lab tests and x-rays . Two teams received information about lab test costs , and two teams received x-ray test costs . Test usage fell during the experimental conditions and continued to fall after the experimental period ended in teams in which there was an interested leader Background Because the ultimate purpose of new medical knowledge is to achieve improved health outcomes , physicians need to possess and use this knowledge in their practice . The authors introduced enhanced education and individualized feedback to reduce postoperative nausea and vomiting ( PONV ) . The primary objective was to increase anesthesiologists ' use of preventive measures to reduce PONV , and the secondary objective was to determine whether patient outcomes were improved . Methods After obtaining hospital ethics committee approval , the effect of education and feedback on anesthesiologist performance and the rate of PONV in major surgery elective in‐ patients during a 2‐yr period was assessed . After baseline data collection ( 6 months ) , anesthesiologists at the study hospital received enhanced education ( 8 months ) and individualized feedback ( 10 months ) . Parallel data collection was performed at a control hospital at which practice was continued as usual . The education promoted preventive measures ( antiemetic premedication , nasogastric tubes , droperidol , metoclopramide ) . Individualized feedback provided the number of patients receiving promoted measures and the rate of PONV . The mean percentage of anesthesiologists ' patients receiving at least one promoted measure and the rate of PONV were compared with baseline levels . Results At the study hospital , there was a significant increase in the mean percentage of the anesthesiologists ' female patients receiving a preventive measure as well as a significant increase in the use of droperidol greater or equal to 1 mg ( P < 0.05 ) for all patients . The use of other promoted measures was unaffected . Absolute rates of PONV were unaffected at the study hospital until the postfeedback period ( decrease of 8.8 % between baseline and postfeedback ( P = 0.015 ) ) . Conclusion It was demonstrated that enhanced education and individualized feedback can change anesthesiologists ' practice patterns . The actual benefit to patients from use of preventive measures was limited when used in the everyday clinical situation . Therefore , only modest decreases in PONV were achieved , despite the use of preventive measures A prospect i ve , controlled trial to reduce polypharmacy in patients 65 years or older was carried out in the residents ' clinic of a teaching hospital . Of 272 elderly patients surveyed , 89 ( 33 % ) were taking five or more prescription drugs . Recommendations to discontinue medications or to simplify regimens were formulated for 79 polypharmacy patients . Compared to 41 controls , the 38 patients whose physicians were informed of the recommended changes demonstrated a small but significant reduction in the mean number of drugs , the complexity , and the cost of their regimens . Physicians complied with eight ( 100 % ) of eight recommendations to simplify a dosage schedule , eight ( 62 % ) of 13 recommendations to substitute a new drug for the old one , and only eight ( 40 % ) of 20 recommendations to stop a medication ( P = .04 ) . Noncompliance usually result ed from patient refusal or from medications being prescribed by another provider . Whereas feedback to the primary physician is beneficial , more substantial reductions in outpatient polypharmacy may require overcoming patient barriers and limiting the number of prescribing physicians CONTEXT Antenatal corticosteroids for fetal maturation have been underused , despite evidence for their benefits in cases of preterm birth . OBJECTIVE To evaluate dissemination strategies aim ed at increasing appropriate use of this therapy . DESIGN AND SETTING Twenty-seven tertiary care institutions were r and omly assigned to either usual dissemination of practice recommendations ( n = 14 ) or usual dissemination plus an active , focused dissemination effort ( n = 13 ) . SUBJECTS Obstetricians and their preterm delivery cases at participating hospitals . INTERVENTION Recommendations by a National Institutes of Health ( NIH ) Consensus Conference held in late February-early March 1994 were disseminated in early May 1994 . Usual dissemination was publication of the recommendations and endorsement by the American College of Obstetricians and Gynecologists . Active dissemination was a year-long educational effort led by an influential physician and a nurse coordinator at each facility , consisting of gr and rounds , a chart reminder system , group discussion of case scenarios , monitoring , and feedback . MAIN OUTCOME MEASURE Use or nonuse of antenatal corticosteroids was abstract ed from medical records of eligible women delivering at the participating hospitals in the 12 months immediately prior to release of the NIH recommendations ( average number of records abstract ed , 130 ) and in the 12 months following their release ( average number of records abstract ed , 122 ) . RESULTS Active dissemination significantly increased the odds of corticosteroid use after the conference . Use increased from 33.0 % of eligible patients receiving corticosteroids to 57.6 % , or by 75 % over baseline , in usual dissemination hospitals . Use increased from 32.9 % to 68.3 % , oran 108 % increase , in active dissemination hospitals . Gestational age and maternal diagnosis affected use of the therapy in complex ways . CONCLUSION An active , focused dissemination effort increased the effectiveness of usual dissemination methods when combined with key principles to change physician practice OBJECTIVE To assess whether providing customized clinical information to patients and physicians improves safety or quality of diabetes care . RESEARCH DESIGN AND METHODS Study subjects included 123 primary care physicians and 3,703 eligible adult diabetic patients with elevated A1C or LDL cholesterol , who were r and omly assigned to receive customized feedback of clinical information as follows : 1 ) patient only , 2 ) physician only , 3 ) both the patient and physician , or 4 ) neither patient nor physician . In the intervention groups , patients received customized mailed information or physicians received printed , prioritized lists of patients with recommended clinical actions and performance feedback . Hierarchical models were used to accommo date group r and om assignment . RESULTS Study interventions did not improve A1C test ordering ( P = 0.35 ) and negatively affected LDL cholesterol test ordering ( P < 0.001 ) in the 12 months postintervention . Interventions had no effect on LDL cholesterol values ( P = 0.64 ) , which improved in all groups over time . Interventions had a borderline unfavorable effect on A1C values among those with baseline A1C ≥7 % ( P = 0.10 ) and an unfavorable effect on A1C values among those with baseline A1C ≥8 % ( P < 0.01 ) . Interventions did not reduce risky prescribing events or increase treatment intensification . Time to next visit was longer in all intervention groups compared with that for the control group ( P < 0.05 ) . CONCLUSIONS Providing customized decision support to physicians and /or patients did not improve quality or safety of diabetes care and worsened A1C control in patients with baseline A1C ≥8 % . Future research ers should consider providing point-of-care decision support with re design of office systems and /or incentives to increase appropriate actions in response to decision-support information OBJECTIVES : To assess the effects of outreach visits by trained nurse facilitators on the organisation of services used to prevent cardiovascular disease . To identify the characteristics of general practice s that determined success . DESIGN : A non-r and omised controlled trial of two methods of implementing guidelines to organise prevention of cardiovascular disease : an innovative outreach visit method compared with a feedback method . The results in both groups were compared with data from a control group . SETTING AND SUBJECTS : 95 general practice s in two regions in The Netherl and s. INTERVENTIONS : Trained nurse facilitators visited practice s , focusing on solving problems in the organisation of prevention . They applied a four step model in each practice . The number of visits depended on the needs of the practice team . The feedback method consisted of the provision of a feedback report with advice specific to each practice and st and ardised instructions . MAIN OUTCOME MEASURES : The proportion of practice s adhering to 10 different guidelines . Guidelines were on the detection of patients at risk , their follow up , the registration of preventive activities , and teamwork within the practice . RESULTS : Outreach visits were more effective than feedback in implementing guidelines to organise prevention . Within the group with outreach visits , the increase in the number of practice s adhering to the guidelines was significant for six out of 10 guidelines . Within the feedback group , a comparison of data before and after intervention showed no significant differences . Partnerships and practice s with a computer changed more . CONCLUSION : Outreach visits by trained nurse facilitators proved to be effective in implementing guidelines within general practice s , probably because their help was practical and design ed for the individual practice , guided by the wishes and capabilities of the practice team BACKGROUND Diabetes mellitus continues to result in substantial morbidity and mortality despite receiving much attention from health care providers . Automated clinician reminder systems have been developed to improve adherence to diabetes care guidelines , but these reminder systems do not always provide actionable information and may be unable to detect relevant , subjective patient information that affects clinical decision making . Face-to-face visits with pharmacists , who have knowledge of care guidelines and medication management strategies , may assist in improving diabetes care . It is unknown if the combination of pharmacist chart review and clinician reminders could improve diabetes care without requiring face-to-face visits . OBJECTIVE To assess the effects of a comprehensive , pharmacistdelivered , primary care , physician-focused intervention in a large hospital based primary care practice to improve the quality of care for patients with diabetes including rates of semiannual hemoglobin A1c testing and other biomarker and process measures . METHODS This was a prospect i ve , r and omized , controlled study conducted in a hospital-based , primary care practice , composed of 37 faculty primary care physicians ( PCPs ) and 95 internal medicine residents . The initial sample included 346 patients with diabetes and 72 PCPs caring for them . PCPs were r and omized to receive either a personalized letter from a practicing pharmacist containing treatment recommendations for patients with upcoming primary care visits ( intervention , n = 33 ) or to usual care without the letters ( control , n = 39 ) . The letter included patient-specific recommendations regarding overdue testing as well as drug therapy to achieve diabetes-related treatment targets . The intervention included addition of the letter to the electronic medical record ( EMR ) and presentation of the letter to the PCP at the time of the index primary care visit that occurred between November 2003 and August 2004 . Follow-up chart review was performed after the primary care visit to determine changes in 5 process and 3 biomarker outcome measures of diabetes care within 30 days of the index visit . The primary study outcome was a process measure , change in rates of semiannual A1c testing from baseline to 30-day follow-up . Baseline differences were tested for statistical significance using Pearson chisquare . The statistical significance of the intervention 's effect was tested using logistic regression models predicting achievement of each study outcome , with r and omization status ( intervention vs. control ) as the predictor variable of interest , controlling for baseline performance for each measure . RESULTS 171 patients were in the 4 medical clinic suites with 33 PCPs who received the intervention , and 175 patients were in the 4 suites with 39 PCPs in usual care . 30-day outcomes were analyzed for 301 patients ( 87.0 % ) who attended their scheduled index primary care visit . Of these 301 patients , 44.5 % were black , 65.8 % were female , and the mean age was 63 years . At baseline , there were no significant differences between the intervention group ( n = 150 ) and the usual care ( control ) group ( n = 151 ) in the 3 biomarker measures ( proportion with A1c less than 7 % , proportion with low-density lipoprotein cholesterol [ LDL-C ] less than 100 milligrams per deciliter [ mg per dL ] , or blood pressure less than 130/80 millimeters mercury [ mm Hg ] ) . There were no significant baseline differences in 4 of the 5 process measures ; however , the rate of annual LDL-C testing was significantly higher for the intervention than for the control group at baseline ( 86.0 % vs. 74.8 % , respectively , P = 0.015 ) . In logistic regression analysis , rates of semiannual A1c testing were not significantly different between the intervention and control groups , increasing from baseline to follow-up by 16 % in the intervention group and 9 % in the control group ( P = 0.146 ) . The proportion of patients with A1c less than 7 % at follow-up was 43.3 % in the intervention group versus 37.7 % in the control group ( intervention effect P = 0.099 ) . The only statistically significant difference between the 2 groups in the 8 outcome measures was a higher proportion with an annual eye exam at follow-up in the intervention group ( 60.0 % ) versus the usual care group ( 50.3 % , intervention effect P = 0.017 ) . CONCLUSIONS Pharmacist-generated recommendations delivered by letter to PCPs in an academic medical practice were not associated with statistically significant improvements in most quality measures for diabetes care assessed at 30 days following the intervention . Further research is needed with more patients and a longer follow-up time to determine how best to improve the quality of care of patients with diabetes using focused recommendations for therapy changes and reminder notices to clinicians BACKGROUND Physician adherence to National Cholesterol Education Program clinical practice guidelines has been poor . METHODS We recruited 68 primary care family and internal medicine practice s ; 66 were r and omly allocated to a study arm ; 5 practice s withdrew , result ing in 29 receiving the Third Adult Treatment Panel ( ATP III ) intervention and 32 receiving an alternative intervention focused on the Seventh Report of the Joint National Committee on the Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC-7 ) . The ATP III providers received a personal digital assistant providing the Framingham risk scores and ATP III-recommended treatment . All practice s received copies of each clinical practice guideline , an introductory lecture , 1 performance feedback report , and 4 visits for intervention-specific academic detailing . Data were abstract ed at 61 practice s from r and om sample s of medical records of patients treated from June 1 , 2001 , through May 31 , 2003 ( baseline ) , and from May 1 , 2004 , through April 30 , 2006 ( follow-up ) . The proportion screened with subsequent appropriate decision making ( primary outcome ) was calculated . Generalized estimating equations were used to compare results by arm , accounting for clustering of patients within practice s. RESULTS We examined 5057 baseline and 3821 follow-up medical records . The screening rate for lipid levels increased from 43.6 % to 49.0 % ( ATP III practice s ) and from 40.1 % to 50.8 % ( control practice s ) ( net difference , -5.3 % [ P = .22 ] ) . Appropriate management of lipid levels decreased slightly ( 73.4 % to 72.3 % ) in ATP III practice s and more markedly ( 79.7 % to 68.9 % ) in control practice s. The net change in appropriate management favored the intervention ( + 9.7 % ; 95 % confidence interval [ CI ] , 2.8%-16.6 % [ P < .01 ] ) . Appropriate drug prescription within 4 months decreased in both arms ( 38.8 % to 24.8 % in ATP III practice s and 45.3 % to 24.1 % in control practice s ; net change , + 7.2 % [ P = .37 ] ) Overtreatment declined from 6.6 % to 3.9 % in ATP III and rose from 4.2 % to 6.4 % in control practice s ( net change , -4.9 % [ P = .01 ] ) . CONCLUSIONS A multifactor intervention including personal digital assistant-based decision support may improve primary care physician adherence to the ATP III guidelines . Trial Registration clinical trials.gov Identifier : NCT00224848 BACKGROUND Improvement in the delivery of influenza and pneumococcal vaccinations to high-risk groups is an important aspect of preventive care for primary healthcare teams . AIM To investigate the effect of an educational outreach visit to primary healthcare teams on influenza and pneumococcal vaccination uptake in high-risk patients . DESIGN Cluster r and omised controlled trial . SETTING Thirty general practice s in the Trent region , UK . METHODS Fifteen practice s were r and omised to intervention and 15 to the control group after stratifying for baseline vaccination rate . All intervention practice s were offered and received an educational outreach visit to primary healthcare teams , in addition to audit and feedback directed at improving influenza and pneumococcal vaccination rates in high-risk groups . Control practice s received audit and feedback alone . All practice s measured influenza and pneumococcal vaccination rates in high-risk groups . Primary outcomes were improvements in vaccination rates in patients aged 65 years and over , and patients with coronary heart disease ( CHD ) , diabetes and a history of splenectomy . RESULTS Improvements in pneumococcal vaccination rates in the intervention practice s were significantly greater compared with controls in patients with CHD , 14.8 % versus 6.5 % ( odds ratio [ OR ] = 1.23 , 95 % confidence interval [ CI ] = 1.13 to 1.34 ) and diabetes , 15.5 % versus 6.8 % ( OR = 1.18 , 95 % CI = 1.08 to 1.29 ) but not splenectomy , 6.5 % versus 4.7 % ( OR = 0.96 , 95 % CI = 0.65 to 1.42 ) . Improvements for influenza vaccination were also usually greater in intervention practice s but did not reach statistical significance . The increases for influenza vaccination in intervention versus control practice s were for CHD , 18.1 % versus 13.1 % ( OR = 1.06 , 95 % CI = 0.99 to 1.12 ) ; diabetes , 15.5 % versus 12.0 % ( OR = 1.07 , 95 % CI = 0.99 to 1.16 ) , splenectomy 16.1 % versus 2.9 % ( OR = 1.22 , 95 % CI = 0.78 to 1.93 ) ; and those over 65 years 20.7 % versus 25.4 % ( OR = 0.99 , 95 % CI = 0.96 to 1.02 ) . CONCLUSION Practice s where primary care teams received an educational outreach visit demonstrated a significantly greater improvement in uptake in high-risk groups for pneumococcal but not influenza vaccine Rationale and aims Quality circles ( QCs ) are well established as a means of aiding doctors . New quality improvement strategies include benchmarking activities . The aim of this paper was to evaluate the efficacy of QCs for asthma care working either with general feedback or with an open benchmark . Methods Twelve QCs , involving 96 general practitioners , were organized in a r and omized controlled trial . Six worked with traditional anonymous feedback and six with an open benchmark ; both had guided discussion from a trained moderator . Forty-three primary care practice s agreed to give out question naires to patients to evaluate the efficacy of QCs . Results A total of 256 patients participated in the survey , of whom 185 ( 72.3 % ) responded to the follow-up 1 year later . Use of inhaled steroids at baseline was high ( 69 % ) and self-management low ( asthma education 27 % , individual emergency plan 8 % , and peak flow meter at home 21 % ) . Guideline adherence in drug treatment increased ( P = 0.19 ) , and asthma steps improved ( P = 0.02 ) . Delivery of individual emergency plans increased ( P = 0.008 ) , and unscheduled emergency visits decreased ( P = 0.064 ) . There was no change in asthma education and peak flow meter usage . High medication guideline adherence was associated with reduced emergency visits ( OR 0.24 ; 95 % CI 0.07–0.89 ) . Use of theophylline was associated with hospitalization ( OR 7.1 ; 95 % CI 1.5–34.3 ) and emergency visits ( OR 4.9 ; 95 % CI 1.6–14.7 ) . There was no difference between traditional and benchmarking QCs . Conclusions Quality circles working with individualized feedback are effective at improving asthma care . The trial may have been underpowered to detect specific benchmarking effects . Further research is necessary to evaluate strategies for improving the self-management of asthma patients OBJECTIVE To investigate the effectiveness of an educational Quality Use of Medicines program , delivered at the level of general practice , on medicines use , falls and quality of life in people aged > or = 65 years . DESIGN Cluster r and omised controlled trial conducted in 2002 . SETTING General practice s in the Hunter Region , New South Wales , Australia . PARTICIPANTS Twenty general practitioners recruited 849 patients to participate in the study . INTERVENTION Education ( academic detailing , provision of prescribing information and feedback ) ; medication risk assessment ; facilitation of medication review ; financial incentives . MAIN OUTCOME MEASURES PRIMARY MEASURES a composite score reflecting use of benzodiazepines , non-steroidal anti-inflammatory drugs ( NSAIDs ) and thiazide diuretics ; secondary measures : use of medication review s , occurrence of falls , quality of life ( as assessed by SF-12 and EQ-5D survey scores . RESULTS Compared with the control group , participants in the intervention group had increased odds of having an improved medication use composite score ( odds ratio [ OR ] , 1.86 ; 95 % CI , 1.21 - 2.85 ) at 4-month follow-up but not at 12 months . At 4-month follow-up , the intervention group had reduced odds of using NSAIDs ( OR , 0.62 ; 95 % CI , 0.39 - 0.99 ) and showed a non-significant reduction in use of benzodiazepines ( OR , 0.51 ; 95 % CI , 0.20 - 1.30 ) and thiazide diuretics ( OR , 0.70 ; 95 % CI , 0.48 - 1.01 ) . Changes in drug use were not significant at 12-month follow-up . At 12 months , intervention-group participants had lower adjusted ORs ( AORs ) for having a fall ( AOR , 0.61 ; 95 % CI , 0.41 - 0.91 ) , injury ( AOR , 0.56 ; 95 % CI , 0.32 - 0.96 ) , and injury requiring medical attention ( AOR , 0.46 ; 95 % CI , 0.30 - 0.70 ) . Quality -of-life scores were unaffected by the intervention . CONCLUSION Education and systems for medication review conducted by GPs can be used to improve use of medicines . These interventions are associated with a reduction in falls among older people , without adverse effects on quality of life PURPOSE The purpose of the study was to determine if simply providing nursing facilities with comparative quality performance information and education about quality improvement would improve clinical practice s and subsequently improve resident outcomes , or if a stronger intervention , expert clinical consultation with nursing facility staff , is needed . DESIGN AND METHODS Nursing facilities ( n = 113 ) were r and omly assigned to one of three groups : workshop and feedback reports only , workshop and feedback reports with clinical consultation , and control . Minimum Data Set ( MDS ) Quality Indicator ( QI ) feedback reports were prepared and sent quarterly to each facility in intervention groups for a year . Clinical consultation by a gerontological clinical nurse specialist ( GCNS ) was offered to those in the second group . RESULTS With the exception of MDS QI 27 ( little or no activity ) , no significant differences in resident assessment measures were detected between the groups of facilities . However , outcomes of residents in nursing homes that actually took advantage of the clinical consultation of the GCNS demonstrated trends in improvements in QIs measuring falls , behavioral symptoms , little or no activity , and pressure ulcers ( overall and for low-risk residents ) . IMPLICATION S Simply providing comparative performance feedback is not enough to improve resident outcomes . It appears that only those nursing homes that sought the additional intensive support of the GCNS were able to effect enough change in clinical practice to improve resident outcomes significantly BACKGROUND Antibiotics are a medication class for which inappropriate prescribing is frequently described . We sought to assess the effectiveness of a mailed intervention combining confidential prescribing feedback with targeted educational bulletins in increasing the use of less expensive , first-line antibiotics by practising physicians . METHODS The participants were 251 r and omly selected primary care physicians from southern Ontario who consented to participate ( 135 in the feedback group and 116 in the control group ) . Prescribing data were obtained from the cl aims data base of the Ontario Drug Benefit program , which covers all Ontarians over age 65 years for drugs selected from a minimally restrictive formulary . Confidentially prepared profiles of antibiotic prescriptions coupled with guidelines -based educational bulletins were mailed to the intervention group every 2 months for 6 months . The control group received no intervention until after completion of the study . The main outcome measures were change from baseline in physician 's median antibiotic cost and proportion of episodes of care in which a prespecified first-line antibiotic was used first . RESULTS The median prescription cost of about $ 11 remained constant in the feedback group but rose in the control group ( change of $ 0.05 v. $ 3.37 , p < 0.002 ) . First-line drug use increased in the feedback group but decreased in the control group ( change of 2.6 % v. -1.7 % , p < 0.01 ) . In a mailed survey of 100 feedback recipients ( response rate 76 % ) , 82 % indicated that they would participate readily in another , similar program . INTERPRETATION A simple program of confidential feedback and educational material s blunted cost increases , increased the use of first-line antibiotics and was highly acceptable to Ontario primary care physicians OBJECTIVE : To evaluate and compare the effects of two programmes of assessment of practice management in a practice visit : mutual visits and feedback by peers compared with visits and feedback by non-physician observers . DESIGN : Prospect i ve , r and omised intervention study , with follow up after one year . SETTING : General practice s in the Netherl and s in 1993 and 1994 . SUBJECTS : A total of 90 general practitioners ( GPs ) in 68 practice s ; follow up after one year comprised 81 GPs in 62 practice s. MAIN MEASURES : Scores on indicators and dimensions of practice management in the visit instrument to assess practice management and organisation ( a vali date d Dutch method to assess practice management in a practice visit ) . Change was defined as the difference in score between the first visit and the visit after one year on 208 indicators and on 33 dimensions of practice management . RESULTS : Data of 44 mutual visits by peers were compared with data of 46 visits by non-physician observers . After a year both programmes showed improvements on many aspects of practice management , but different aspects changed in each of the two programmes . After mutual practice visits , GPs scored significantly higher on content of the doctor 's bag , on collaboration with colleagues , on collaboration with other care providers , and on accessibility of patient information than after a visit by a non-physician observer . The visits by non-physician observers result ed in a higher score on extent of use of records and on assessment on outcome and year report . CONCLUSION : Change after mutual practice visits and feedback by peers is more marked than after a visit and feedback by a non-physician observer OBJECTIVE To determine the costs and cost reductions of an innovative strategy aim ed at improving test ordering routines of primary care physicians , compared with a traditional strategy . DESIGN Multicenter r and omized controlled trial with r and omization at the local primary care physicians group level . SETTING Primary care : local primary care physicians groups in five regions of the Netherl and s with diagnostic centers . STUDY PARTICIPANTS Twenty-seven existing local primary care physicians groups , including 194 primary care physicians . INTERVENTION The test ordering strategy was developed systematic ally , and combined feedback , education on guidelines , and quality improvement sessions in small groups . In regular quality meetings in local groups , primary care physicians discussed each others ' test ordering behavior , related it to guidelines , and made individual and /or group plans for change . Thirteen groups engaged in the entire strategy ( complete intervention arm ) , while 14 groups received feedback only ( feedback arm ) . MAIN OUTCOME MEASURE Running costs , development costs , and research costs were calculated for the intervention period per primary care physician per 6 months . The mean costs of tests ordered per primary care physician per 6 months were assessed at baseline and follow-up . RESULTS The new strategy was found to cost 702.00 , while the feedback strategy cost 58.00 . When including running costs only , the intervention was found to cost 554.70 , compared with 17.10 per primary care physician per 6 months in the feedback arm . When excluding opportunity costs for the physicians ' time spent , the intervention was found to cost 92.70 per physician per 6 months in the complete intervention arm . The mean costs reduction that physicians in that arm achieved by reducing unnecessary tests was 144 larger per physician per 6 months than the physicians in the feedback arm ( P = 0.048 ) . CONCLUSION On the basis of our findings , including the expected non-monetary benefits , we recommend further long-term effect and cost-effect studies on the implementation of the quality strategy BACKGROUND No single quality improvement instrument has proved consistently effective , but multifaceted interventions are believed to have the greatest impact . However , only little is known regarding what combinations are likely to be successful . OBJECTIVE To evaluate the impact of a multifaceted intervention strategy combining GP registration s , outreach visits and feedback , targeting secondary prevention of ischemic heart disease in general practice . METHODS A r and omised controlled trial including 28 GPs in Ringkjøbing County , Denmark . Half of the GPs received outreach visits and feedback on their prescribing of heart disease drugs . Evaluation was based on registration of consultations with patients suffering from ischemic heart disease . RESULTS The intervention had a statistically significant impact on prescribing of lipid lowering drugs [ odds ratio 1.59 ; 95 % confidence interval ( CI ) 1.00 to 2.53 ] and acetylsalicylic acid ( odds ratio 2.54 ; 95 % CI 1.21 to 5.31 ) . CONCLUSION An intervention strategy combining outreach visits , feedback and GP registration s is a promising way of improving the quality of preventive treatment in general practice Abstract Objectives To assess the effectiveness of a multiple intervention aim ed at reducing antibiotic prescription rates for symptoms of the respiratory tract in primary care . Design R and omised controlled trial . Subjects Twelve peer review groups including 100 general practitioners with their collaborating pharmacists in the region of Utrecht , Netherl and s. Intervention The intervention consisted of group education meetings , with a consensus procedure on indication for and type of antibiotics and with training in communication skills ; monitoring and feedback on prescribing behaviour ; group education for assistants of general practitioners and pharmacists ; and educational material for patients . The control group did not receive any of these elements . Main outcome measures Antibiotic prescription rates for acute symptoms of the respiratory tract and patients ' satisfaction . Results 89 general practitioners completed the study ( 89 % ) . At baseline , prescription rates for antibiotics for respiratory tract symptoms did not differ between intervention and control group ( 27 % v 29 % , respectively ) . After nine months , the prescription rates in the intervention group fell to 23 % , whereas the control group 's rose to 37 % ( mean difference in change −12 % , 95 % confidence interval −18.9 % to −4.0 % ) . Multilevel analysis confirmed the results of the unadjusted analysis ( intervention effect −10.7 % , −20.3 % to −1.0 % ) . Patients ' satisfaction was high and did not differ in the two groups at baseline or after the intervention . Conclusions A multiple intervention reduced prescribing rates of antibiotics for respiratory tract symptoms while maintaining a high degree of satisfaction among patients . Further research should focus on the sustainability and cost effectiveness of this intervention Objective : To evaluate the effects of feedback reports combined with outreach visits from trained non-physicians on the clinical decision making of general practitioners ( GPs ) in cardiovascular care . Design : Pragmatic cluster controlled trial with r and omisation of practice s to support ( intervention group ) or no special attention ( control group ) ; analysis after 2 years . Setting : 124 general practice s in The Netherl and s. Participants : 185 GPs . Main outcome measures : Compliance rates for 12 evidence -based indicators for the management of patients with hypertension , hypercholesterolaemia , angina pectoris , or heart failure . The evaluation relied on the prospect i ve recording of patient encounters by the participating GPs . Results : The GPs reported 30 101 clinical decisions at baseline and 22 454 decisions after the intervention . A significant improvement was seen for five of the 12 indicators : assessment of risk factors in patients with hypercholesterolaemia ( odds ratio 2.04 ; 95 % CI 1.44 to 2.88 ) or angina pectoris ( 3.07 ; 1.08 to 8.79 ) , provision of information and advice to patients with hypercholesterolaemia ( 1.58 , 1.17 to 2.13 ) or hypertension ( 1.55 , 1.35 to 1.77 ) , and checking for clinical signs of deterioration in patients with heart failure ( 4.11 , 2.17 to 7.77 ) . Single h and ed practice s , non-training practice s , and practice s with older GPs gained particular benefit from the intervention . Conclusions : Intensive support from trained non-physicians can alter certain aspects of the clinical decision making of GPs in cardiovascular care . The effect is small and the strategy needs further development Abstract Objectives : To establish the effect of an educational intervention for general practitioners on the health behaviours and wellbeing of elderly patients . Design : R and omised controlled trial with 1 year follow up . Setting : Metropolitan general practice s in Melbourne , Australia . Subjects : 42 general practitioners and 267 of their patients aged over 65 years . Intervention : Educational and clinical practice audit programme for general practitioners on health promotion for elderly people . Main outcome measures : Patients ' physical activity , functional status , self rated health , immunisation status , social contacts , psychological wellbeing , drug usage , and rate of influenza vaccination . Primary efficacy variables were changes in outcome measures over 1 year period . Results : Patients in the intervention group had increased ( a ) walking by an average of 88 minutes per fortnight , ( b ) frequency of pleasurable activities , and ( c ) self rated health compared with the control group . No change was seen in drug usage , rate of influenza vaccination , functional status , or psychological wellbeing as a result of the intervention . Extrapolations of the known effect of these changes in behaviour suggest mortality could be reduced by 22 % if activity was sustained for 5 years . Conclusions : Education of the general practitioners had a positive effect on health outcomes of their elderly patients . General practitioners may have considerable public health impact in promotion of health for elderly patients . Key messages Few educational interventions for doctors have shown benefit to the health of patients Elderly people were identified in the UK health initiatives as in need of additional attention , and levels of health protective behaviours were low in community surveys A multifaceted educational intervention for general practitioners was effective in improving walking behaviour , self rated health status , and the frequency of social contacts in elderly patients General practitioners are effective in improving health and health behaviours in their elderly Background — Despite evidence supporting the use of aspirin , & bgr;-blockers , angiotensin-converting enzyme inhibitors , and lipid-lowering therapies in eligible patients , adoption of these secondary prevention measures after coronary artery bypass grafting has been inconsistent . We sought to rigorously test on a national scale whether low-intensity continuous quality improvement interventions can be used to speed secondary prevention adherence after coronary artery bypass grafting . Methods and Results — A total of 458 hospitals participating in the Society of Thoracic Surgeons National Cardiac Data base and treating 361 328 patients undergoing isolated coronary artery bypass grafting were r and omized to either a control or an intervention group . The intervention group received continuous quality improvement material s design ed to influence the prescription of the secondary prevention medications at discharge . The primary outcome measure was discharge prescription rates of the targeted secondary prevention medications at intervention versus control sites , assessed by measuring preintervention and postintervention site differences . Prer and omization treatment patterns and baseline data were similar in the control ( n=234 ) and treatment ( n=224 ) groups . Individual medication use and composite adherence increased over 24 months in both groups , with a markedly more rapid rate of adherence uptake among the intervention hospitals and a statistically significant therapy hazard ratio in the intervention versus control group for all 4 secondary prevention medications . Conclusions — Provider-led , low-intensity continuous quality improvement efforts can improve the adoption of care processes into national practice within the context of a medical specialty society infrastructure . The findings of the present trial have led to the incorporation of study outcome metrics into a medical society rating system for ongoing quality improvement BACKGROUND There is increasing evidence that clinical guidelines can lead to improvements in clinical care . However , they are not self-implementing . Outreach visits may improve prescribing behaviour . METHODS Within a before- and -after pragmatic r and omized controlled trial , involving all general practice s in one health district , routine methods were used to distribute guidelines for management of Helicobacter pylori eradication . Intervention practice s were offered a visit and the conduct of an audit by a pharmacist trained in the techniques of outreach visiting . The intervention was evaluated using level three Prescribing Analysis and Cost ( PACT ) data for metronidazole and omeprazole for the two 12 month periods around the introduction of the guidelines . RESULTS Of the 38 intervention practice s 19 accepted an outreach visit and three accepted the offer of an audit . There was a significant increase in omeprazole use during the study of 0.24 [ 95 per cent confidence interval ( CI ) + 0.19 to + 0.29 ] dose units per year but no effect from the offer [ -0.02 ( 95 per cent CI -0.12 to + 0.08 ) dose units ] or acceptance of a visit [ -0.03 ( 95 per cent CI -0.15 to + 0.08 ) dose units ] . The results for metronidazole were similar , with an increase in use of 0.028 ( 95 per cent CI + 0.018 to + 0.038 ) dose units per year . The effect of the intervention was a non-significant change in prescribing of -0.005 ( 95 per cent CI -0.025 to + 0.015 ) dose units . Accepting a visit had little effect on prescribing : a change of 0.003 ( 95 per cent CI -0.021 to + 0.027 ) dose units . CONCLUSIONS The routine use of untargeted outreach visiting is probably not a worthwhile strategy Abstract Objective : To assess the effectiveness of three different methods of promoting secondary prevention of coronary heart disease in primary care . Design : Pragmatic , unblinded , cluster r and omised controlled trial . Setting : Warwickshire . Subjects : 21 general practice s received intervention ; outcome measured in 1906 patients aged 55 - 75 years with established coronary heart disease . Interventions : Audit of notes with summary feedback to primary health care team ( audit group ) ; assistance with setting up a disease register and systematic recall of patients to general practitioner ( GP recall group ) ; assistance with setting up a disease register and systematic recall of patients to a nurse led clinic ( nurse recall group ) . Main outcome measures : At 18 months ' follow up : adequate assessment ( defined ) of 3 risk factors ( blood pressure , cholesterol , and smoking status ) ; prescribing of hypotensive agents , lipid lowering drugs , and antiplatelet drugs ; blood pressure , serum cholesterol level , and plasma cotinine levels . Results : Adequate assessment of all 3 risk factors was much more common in the nurse and GP recall groups ( 85 % , 76 % ) than the audit group ( 52 % ) . The advantage in the nurse recall compared with the audit group was 33 % ( 95 % confidence interval 19 % to 46 % ) ; in the GP recall group compared with the audit group 23 % ( 10 % to 36 % ) , and in the nurse recall group compared with the GP recall group 9 % ( −3 % to 22 % ) . However , these differences in assessment were not reflected in clinical outcomes . Mean blood pressure ( 148/80 , 147/81 , 148/81 mm Hg ) , total cholesterol ( 5.4 , 5.5 , 5.5 mmol/l ) , and cotinine levels ( % probable smokers 17 % , 16 % , 19 % ) varied little between the nurse recall , GP recall , and audit groups respectively , as did prescribing of hypotensive and lipid lowering agents . Prescribing of antiplatelet drugs was higher in the nurse recall group ( 85 % ) than the GP recall or audit groups ( 80 % , 74 % ) . After adjustment for baseline levels , the advantage in the nurse recall group compared with the audit group was 10 % ( 3 % to 17 % ) , in the nurse recall group compared with the GP recall group 8 % ( 1 % to 15 % ) and in the GP recall group compared with the audit group 2 % ( −6 % to 10 % ) . Conclusions : Setting up a register and recall system improved patient assessment at 18 months ' follow up but was not consistently better than audit alone in improving treatment or risk factor levels . Underst and ing the reasons for this is the key next step in improving the quality of care of patients with coronary heart disease . What is already known on this topic Effective preventive care of patients with any chronic disease requires planned and quality assured follow up on the basis of an up to date register Strategies for changing clinical practice in primary care have been of limited effectiveness What this study adds Setting up a coronary heart disease register for a practice substantially increases follow up and adequate assessment of patients at risk Improved assessment and follow up does not necessarily improve clinical outcome Follow up by nurses is as effective as , and may be more effective than , follow up by doctors Patients are being followed up and adequately assessed without the recommended preventive drugs being BACKGROUND Proper use of clinical practice guidelines can decrease variation in care between setting s. However , actual use of fertility guidelines is suboptimal and in need of improvement . Hence , a cluster-r and omized controlled trial was design ed to study the effects of two strategies to implement national Dutch guidelines on comprehensive fertility care . METHODS Sixteen fertility clinics participated in the trial . A minimal , professional-oriented implementation strategy of audit and feedback was tested versus a maximal multi-faceted strategy that was both professional and patient oriented . The extent of adherence to guideline recommendations , reflected in quality indicator scores , was the primary outcome measure . To gain an insight into unwanted side effects , patient anxiety and depression scores were gathered as secondary outcomes . Data collection encompassed medical record search , patient and professional question naires . RESULTS A total of 1499 couples were included at baseline and 1396 at the after-measurement . No overall significant improvement in indicator scores was found for either strategy [ odds ratios ranging from 0.23 ( 95 % confidence interval ( CI ) : 0.06 - 0.95 ) to 6.66 ( 95 % CI : 0.33 - 132.8 ] . Secondary outcomes did not differ significantly for both groups , although selected anxiety scores appeared lower in the maximal intervention group . Process evaluation of the trial revealed positive patient experiences with the intervention material [ e.g. an increased underst and ing of their doctor 's treatment policy ( 61 % ) , an increased ability to ask questions about the treatment ( 61 % ) ] . Professionals ' appreciation of intervention elements varied , and execution of the multi-faceted strategy appeared incomplete . DISCUSSION Absence of an intervention effect may be due to the nature of the strategies , incomplete execution or flaws in study design . Process evaluation data raise the question of whether professionals should be the only stakeholder responsible for guideline implementation . This study therefore contributes to an increased underst and ing of fertility guideline implementation in general , and the role of patients in particular Despite widely publicized hypertension treatment guidelines for physicians and lifestyle recommendations for patients , blood pressure control rates remain low . In community-based primary care clinics , we performed a nested , 2 × 2 r and omized , controlled trial of physician intervention versus control and /or patient intervention versus control . Physician intervention included internet-based training , self-monitoring , and quarterly feedback reports . Patient intervention included 20 weekly group sessions followed by 12 monthly telephone counseling contacts and focused on weight loss , Dietary Approaches to Stop Hypertension dietary pattern , exercise , and reduced sodium intake . The primary outcome was change in systolic blood pressure at 6 months . Eight primary care practice s ( 32 physicians ) were r and omized to physician intervention or control groups . Within those practice s , 574 patients were r and omized to patient intervention or control groups . Patient mean age was 60 years , 61 % were women , and 37 % were black . Blood pressure data were available for 91 % of patients at 6 months . The main effect of physician intervention on systolic blood pressure at 6 months , adjusted for baseline pressure , was 0.3 mm Hg ( 95 % CI : −1.5 to 2.2 ; P=0.72 ) . The main effect of the patient intervention was −2.6 mm Hg ( 95 % CI : −4.4 to −0.7 ; P=0.01 ) . The interaction of the 2 interventions was significant ( P=0.03 ) ; the largest impact was observed with the combination of physician and patient intervention ( −9.7±12.7 mm Hg ) . Differences between treatment groups did not persist at 18 months . Combined physician and patient interventions lowers blood pressure ; future research should focus on enhancing effectiveness and sustainability of these interventions Purpose : Despite the availability of clinical practice guidelines ( CPGs ) for cancer pain , consistent integration of these principles into practice has not been achieved . The optimal method for implementing CPGs and the impact of guidelines on healthcare outcomes remain uncertain . This study evaluated the effect of an audit and feedback ( A/F ) intervention on nurse practitioner ( NP ) implementation of cancer pain CPGs and on hospitalized patients ' self‐report of pain and satisfaction with pain relief . Data sources : Eight NPs and two groups of 96 patients were the sources of data . Eligible patients in both groups completed the Brief Pain Inventory‐Short Form ( BPI‐SF ) within 24 h of admission and every 48 h until discharge . During A/F , NPs received weekly feedback on pain scores and guideline adherence . Conclusions : Nurse practitioner adherence to CPGs increased during A/F. Pain intensity did not significantly differ between groups . Intervention group patients reported significantly less overall pain interference ( p < .0001 ) , interference with general activity ( p = .0003 ) , and sleep ( p = .006 ) . Satisfaction with pain relief increased from 68.4 % to 95.1 % during A/F ( p < .0001 ) . Implication s for practice : A/F is an effective strategy to promote CPG use . Improved functional status in the absence of decreased pain severity underscores the need to consider symptom clusters when study ing pain BACKGROUND Out reach facilitation is design ed to promote uptake of evidence -based guidelines . There is evidence indicating that outreach facilitation can be effective in improving implementation of preventive care in GPs ' offices . In this trial , we test a modified version of an outreach facilitation intervention . OBJECTIVE To evaluate whether a comprehensive preventive intervention program using outreach facilitators improves preventive care delivery . DESIGN Match-paired , cluster-r and omized controlled trial . SETTING Fee-for-service primary care practice s in Eastern Ontario , Canada , at a time of physician shortage . PARTICIPANTS Volunteer sample of 54 primary care practice s. MAIN OUTCOME MEASURES Mean difference between trial arms in practice s ' delivery of preventive manoeuvres , measured by preventive performance indices estimated from chart review s and patient survey data . RESULTS No difference was detected between the trial 's arms for the primary outcome 's overall prevention index [ 2.0 % ; 95 % confidence interval ( CI ) -3.2 to 7.3 ; P = 0.44 ] . A small significant difference between the arms was detected for the secondary outcome 's overall prevention index ( 2.8 % ; 95 % CI 0.7 - 4.8 ; P = 0.01 ) . CONCLUSION In contrast to similar facilitation trials , this outreach facilitation program did not produce improvements in the delivery of preventive care . This lack of effect may be due to differences in the intervention and context , or the practice 's limited capacity to change . Our intervention simultaneously facilitated a high number of manoeuvres , blinded facilitators and physicians to the targeted tests and had a relatively short intervention period and large number of practice s assigned per facilitator . Changes in the primary care service model in Ontario at the time of the trial could have also washed out the intervention effect BACKGROUND Although there is much room for improvement in the performance of recommended preventive manoeuvres , many inappropriate preventive interventions are being done . We evaluated a multifaceted intervention , delivered by nurses trained in prevention facilitation , to improve prevention in primary care . METHODS Forty-six health service organizations ( HSOs ) were recruited from 100 sites in Ontario . After baseline data were collected , we r and omly assigned the practice s to either an 18-month ( July 1997 to December 1998 ) multifaceted intervention delivered by 1 of 3 nurse facilitators ( 23 practice s ) or no intervention ( 23 practice s ) . The unit of intervention and analysis was the medical practice . The outcome measure was an overall index of preventive performance , which was calculated as the proportion of eligible patients who received 8 recommended preventive manoeuvres less the proportion of eligible patients who received 5 inappropriate preventive manoeuvres . RESULTS One HSO , in the intervention group , was lost to follow-up . Before the intervention , the index of preventive performance was similar for the intervention and control groups ( 31.9 % [ 95 % confidence interval ( CI ) 27.3%-36.5 % ] and 32.1 % [ 95 % CI 27.2%-37.0 % ] respectively ) . At follow-up the corresponding values were 43.2 % ( 95 % CI 38.4%-48.0 % ) and 31.9 % ( 95 % CI 26.8%-37.0 % ) , for an absolute improvement in the intervention group of 11.5 % ( p < 0.001 ) . The mean proportion of eligible patients who received the recommended manoeuvres was 62.3 % ( 95 % CI 58.2%-66.4 % ) in the intervention group , as compared with 57.4 % ( 95 % CI 54.1%-60.7 % ) in the control group , for an absolute improvement of 7.2 % ( p = 0.008 ) . The corresponding values for the inappropriate manoeuvres were 19.1 % ( 95 % CI 15.6%-22.6 % ) and 25.5 % ( 95 % CI 20.0%-31.0 % ) , for an absolute improvement of 4.4 % ( p = 0.019 ) . INTERPRETATION The tailored multifaceted intervention delivered by nurse facilitators was effective in modifying physician practice patterns and significantly improved preventive care performance Background A gap exists between evidence and practice regarding the management of cardiovascular risk factors . This gap could be narrowed if systematic ally developed clinical practice guidelines were effectively implemented in clinical practice . We evaluated the effects of a tailored intervention to support the implementation of systematic ally developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease . Methods and Findings We conducted a cluster-r and omized trial comparing a tailored intervention to passive dissemination of guidelines in 146 general practice s in two geographical areas in Norway . Each practice was r and omized to either the tailored intervention ( 70 practice s ; 257 physicians ) or control group ( 69 practice s ; 244 physicians ) . Patients started on medication for hypertension or hypercholesterolemia during the study period and all patients already on treatment that consulted their physician during the trial were included . A multifaceted intervention was tailored to address identified barriers to change . Key components were an educational outreach visit with audit and feedback , and computerized reminders linked to the medical record system . Pharmacists conducted the visits . Outcomes were measured for all eligible patients seen in the participating practice s during 1 y before and after the intervention . The main outcomes were the proportions of ( 1 ) first-time prescriptions for hypertension where thiazides were prescribed , ( 2 ) patients assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs , and ( 3 ) patients treated for hypertension or hypercholesterolemia for 3 mo or more who had achieved recommended treatment goals . The intervention led to an increase in adherence to guideline recommendations on choice of antihypertensive drug . Thiazides were prescribed to 17 % of patients in the intervention group versus 11 % in the control group ( relative risk 1.94 ; 95 % confidence interval 1.49–2.49 , adjusted for baseline differences and clustering effect ) . Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals . Conclusions Our tailored intervention had a significant impact on prescribing of antihypertensive drugs , but was ineffective in improving the quality of other aspects of managing hypertension and hypercholesterolemia in primary care BACKGROUND The Agency for Healthcare Research and Quality ( AHRQ ) Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit . METHODS We conducted a r and omized , controlled trial of the effectiveness of Guideline implementation at eight community-based primary care clinics in southern Wisconsin ( four test sites , four control sites ) among 2163 consecutively enrolled adult patients who smoked at least one cigarette per day and presented for nonemergency care during the baseline period ( June 16 , 1999 , to June 20 , 2000 ) or the intervention period ( from June 21 , 2000 , to May 3 , 2001 ) . After collecting baseline data , staff at test sites implemented the intervention over a 2-month period . The intervention included a tutorial for intake clinicians , group and individual performance feedback for intake clinicians , use of a modified vital signs stamp , an offer of free nicotine replacement therapy , and proactive telephone counseling . Staff at control sites received only general information about the AHRQ Guideline . Self-reported abstinence from smoking was determined by telephone interviews at 2- and 6-month follow-up assessment s. Hierarchical logistic regression models were used to estimate the odds ratios ( ORs ) for treatment assignment after adjustment for patient characteristics . All statistical tests were two-sided . RESULTS There were no statistically significant differences in smoking cessation rates between participants at test and control sites during the baseline period . Among participants treated during the intervention period , those at test sites were more likely than those at control sites to report being abstinent at the 2-month ( 16.4 % versus 5.8 % ; adjusted OR = 3.3 , 95 % confidence interval [ CI ] = 1.9 to 5.6 ; P<.001 ) and 6-month ( 15.4 % versus 9.8 % ; adjusted OR = 1.7 , 95 % CI = 1.2 to 2.6 ; P = .009 ) follow-up assessment s and to report continuous abstinence , that is , abstinence at both 2 and 6 months ( 10.9 % versus 3.8 % ; adjusted OR = 3.4 , 95 % CI = 1.8 to 6.3 ; P<.001 ) . CONCLUSION Implementation of a guideline -based smoking cessation intervention by intake clinicians in primary care is associated with higher abstinence among smokers BACKGROUND Traditional continuing medical education ( CME ) has not been successful in improving physicians ' practice . This project evaluated the use of e-mail to deliver evidence -based moderated case discussion s to family physicians . METHODS In a r and omized controlled trial , 58 southwestern Ontario physicians were recruited and r and omly assigned to receive two evidence -based cases ( type 2 diabetes , prevention ) or were put on a waiting list to receive the same . On-line discussion s took place about each case . Data were collected using two knowledge question naires , charts audits , and st and ardized patient visits for each of the two cases . RESULTS The two groups were similar except for rural/urban and solo versus group practice . The latter was related to outcomes , and analyses were controlled for this variable . The intervention group showed statistically significant improvements compared to the control group for knowledge and chart-audit scores for one of the two cases . CONCLUSIONS Using a r and omized control design , this e-mail CME method demonstrated mixed effectiveness AIM The aim of this study was to determine the effectiveness and relative cost of three forms of information feedback to general practice s -- graphical , graphical plus a visit by a medical facilitator and tabular . METHOD Routinely collected , central ly-held data were used where possible , analysed at practice level . Some non-routine practice data in the form of risk factor recording in medical notes , for example weight , smoking status , alcohol consumption and blood pressure , were also provided to those who requested it . The 52 participating practice s were stratified and r and omly allocated to one of the three feedback groups . The cost of providing each type of feedback was determined . The immediate response of practitioners to the form of feedback ( acceptability ) , ease of underst and ing ( intelligibility ) , and usefulness of regular feedback was recorded . Changes introduced as a result of feedback were assessed by question naire shortly after feedback , and 12 months later . Changes at the practice level in selected indicators were also assessed 12 and 24 months after initial feedback . RESULTS The result ing cost per effect was calculated to be 46.10 pounds for both graphical and tabular feedback , 132.50 pounds for graphical feedback plus facilitator visit and 773.00 pounds for the manual audit of risk factors recorded in the practice notes . The three forms of feedback did not differ in intelligibility or usefulness , but feedback plus a medical facilitator visit was significantly less acceptable . There was a high level of self-reported organizational change following feedback , with 69 % of practice s reporting changes as a direct result ; this was not significantly different for the three types of feedback . There were no significant changes in the selected indicators at 12 or 24 months following feedback . The practice characteristic most closely related to better indicators of preventive practice was practice size , smaller practice s performing significantly better . Separate clinics were not associated with better preventive practice . CONCLUSION It is concluded that feedback strategies using graphical and tabular comparative data are equally cost-effective in general practice with about two thirds of practice s reporting organizational change as a consequence ; feedback involving unsolicited medical facilitator visits is less cost-effective . The cost-effectiveness of manual risk factor audit is also called into question OBJECTIVE : To determine whether reminder cards in medical records enhance the effectiveness of audit with feedback in improving the care of patients taking long term benzodiazepine drugs . DESIGN : R and omised trial , practice s receiving feedback only in one group and practice s receiving feedback plus reminder cards in the other group . SETTING : 18 general practice s in Leicestershire . SUBJECTS : R and om sample s of patients who had been taking a benzodiazepine anxiolytic or hypnotic drug for four weeks or longer . MAIN OUTCOME MEASURES : Entries in medical records indicating compliance with five criteria of care : assessment of suitability for withdrawal ; being told about dependency ; withdrawal being recommended ; withdrawal or continuing medication ; and a consultation with the general practitioner in the past year . Data were collected before and after feedback or feedback plus reminders . RESULTS : Of a total population of 125,846 registered with the 18 practice s , 2409 ( 1.9 % ) had been taking a benzodiazepine for four weeks or longer . Of the 742 in the first sample s , 543 ( 73.2 % ) were women , the mean ( SD ) age was 68.7 ( 14.9 ) years , and they had been taking a benzodiazepine for 10.1 ( 6.7 ) years . The number of patients whose care complied with the criteria rose after the interventions to implement change . The increase was greater in practice s receiving feedback plus reminders for only two of the five criteria " told about dependency " increasing from 52 ( 11.1 % ) to 118 ( 25.8 % ) in the feedback only group , and from 27 ( 10.5 % ) to 184 ( 43.0 % ) in the feedback plus reminders group ; odds ratio ( OR ) 1.46 ( 95 % confidence interval ( 95 % CI ) 1.32 to 5.21 ) ; and " consulted in the past year " increasing from 434 ( 93.1 % ) to 411 ( 95.8 % ) in the feedback only group and 255 ( 96.6 % ) to 400 ( 99.8 % ) in the feedback plus reminders group , OR ( 95 % CI ) 13.5 ( 2.01 to 330.3 ) . CONCLUSIONS : Reminder cards had only a limited effect and can not be recommended for routine use . There were improvements in the care of patients of both groups of practice s and further studies are indicated to determine the impact of both systematic ally developed criteria and reminders embedded into restructured medical records We report here the results of a r and omized , controlled trial evaluating the efficacy of a semiautomated performance improvement system ( " patient feedback " ) that enables real-time monitoring of patient outcomes in outpatient substance abuse treatment clinics . The study involved 118 clinicians working at 20 community-based outpatient substance abuse treatment clinics in the northeast United States . Ten clinics received 12 weeks of the patient feedback performance improvement intervention , and 10 clinics received no intervention during the 12 weeks . More than 1,500 patients provided anonymous ratings of therapeutic alliance , treatment satisfaction , and drug/alcohol use . There was no evidence of an intervention effect on the primary drug and alcohol use scales . There was also no evidence of an intervention effect on secondary measures of therapeutic alliance . Clinician-rated measures of organizational functioning and job satisfaction also showed no intervention effect . Possible insights from these findings and alternative methods of utilizing feedback reports to enhance clinical outcomes are proposed BACKGROUND Although absolute risk of death associated with raised blood pressure increases with age , the benefits of treatment are greater in older patients . However , fewer patients in this group are identified , treated , and controlled . AIM To evaluate the impact of the provision of different levels of feedback on identification , treatment , and control of older patients with hypertension . DESIGN OF STUDY R and omised controlled trial . SETTING Fifty-two Scottish general practice s. METHOD Practice s were r and omly allocated to either control ( n = 19 ) , audit only feedback ( n = 16 ) , or audit plus risk feedback , prioritising patients by absolute risk ( n = 17 ) . Electronic data were extracted from practice computer systems annually from 1999 to 2001 and used to develop feedback . Data were collected for 30 345 patients aged 65 - 79 years . RESULTS The majority of known patients with hypertension in each group had an initial blood pressure recorded ( control = 89.6 % ; audit = 80.4 % ; risk = 96.1 % ) and this increased over the study period ( control = 92.3 % ; audit = 86.0 % ; risk = 96.6 % ) . Initially , more than 80 % of patients in each group were treated but many were uncontrolled ( blood pressure > /=160/ > /=90 mmHg ) ( control = 41.5 % ; audit = 41.3 % ; risk = 36.1 % ) . The numbers of untreated and uncontrolled patients in each group reduced ( control = 32.3 % ; audit = 38.3 % ; risk = 32.6 % ) . There was some evidence of a significant difference in mean systolic pressure between the audit plus risk and audit only groups : ( 149.6 versus 152.7 mmHg ; P = 0.019 ) and of significantly greater control in the audit plus risk group compared with the other groups 49.4 % ( versus audit only = 35.4 % ; versus control = 46.5 % ; odds ratio = 1.72 [ 95 % confidence interval = 1.09 to 2.70 ] ; P = 0.019 ) . CONCLUSIONS Levels of identification , treatment , and control improved in each group . Although there were still significant numbers of patients with uncontrolled hypertension , there is some evidence to suggest that providing patient-specific feedback may have a positive impact on identification and management of hypertension in older people and produce an increase in control Pharmaceuticals account for a significant portion of health care costs and are an important target for attempts at cost reductions . While many techniques have been shown effective , most are re source -intensive , have demonstrated fatigue after the intervention is ceased , and have been directed at specific items rather than total charges . The authors design ed a computerized program to feed back prescription charges . The intervention is easy to execute , inexpensive , and can be maintained indefinitely . The intervention was performed in a r and omized , prospect i ve , controlled trial with the medical residents of a large county hospital . The goal was to reduce total prescribing charges and produce a meaningful financial result . The intervention reduced the mean charge for a prescription by 6.7 % ( P < 0.025 ) , but with a long latent period and minimal impact on resident knowledge of drug charges . Significant differences were seen only at the end of the study . The program was viewed positively by the residents . The low cost of the intervention yielded a benefit-to-cost ratio in excess of 50:1 . Because of computerization and ongoing patient and resident r and omization at the study hospital , added costs of this r and omized trial in terms of computer time and research assistance were less than $ 1,000 BACKGROUND Although good medical records have been associated with good care , there is considerable room for their improvement in general practice . AIM To improve the quality of general practice medical records at minimal cost . METHOD A total of 150 r and omly sample d general practitioners ( GPs ) in suburban Brisbane , Australia , were r and omized in a controlled trial to receive or not receive an intervention . The intervention consisted of 6 to 12 one-hour monthly meetings when the pairs of GPs assessed sample s of each other 's medical records using a 12-item instrument . This was developed previously by a process of consensus of general practice teachers . Mean scores of 10 medical records selected at r and om from before the intervention started and one year later were compared . RESULTS After the intervention , the increase in the total score ( for which the maximum possible was 18 ) for the intervention GPs ( from a baseline of 11.5 to 12.3 ) was not significantly greater than for the controls ( from 11.4 to 11.7 ) . Legibility and being able to determine the doctor 's assessment of the consultation were significantly improved . The post-intervention increase of 1.06 ( 9.3 % ) of the total scores of the 47 % of intervention GPs who complied with the intervention was significantly greater than that for the controls . CONCLUSION The quality assurance activity improved some components of the quality of GPs ' clinical records . However , the improvement was small , and the search for activities for Australian GPs that demonstrate an improvement in the quality of their practice must continue Medical records of 150 medical ambulatory care patients r and omly assigned to groups in which screening for depression , physician sensitization about depression , and informational feedback to physicians were systemically varied were review ed for physician notations about depression and its treatment . Forty-two percent of the 100 patients screened with the Zung self-rating depression scale had scores outside the normal range . Chart notation about depression was effectively and appropriately increased by feedback and sensitization from 8 to 25 percent , but these procedures were less effective in increasing treatment interventions , which were noted for 12 percent of the entire sample . Physicians responded to patient information about depression presented to them in the format of a laboratory test , and such previsit screening devices may increase physician attention to psychological problems in general medical setting BACKGROUND Doctors ' communication with patients is commonly hampered by lack of training in this core skill . This study aim ed to assess the efficacy of an intensive 3-day training course on communication skills in a r and omised controlled trial with a two-by-two factorial design and several outcomes . METHODS 160 oncologists from 34 UK cancer centres were r and omly allocated to four groups : written feedback followed by course ; course alone ; written feedback alone ; and control . At each of two assessment periods , consultations with six to ten consecutive , consenting patients per doctor were videotaped . 2407 patients participated . Outcome measures included objective and subjective ratings made by research ers , doctors , and patients . The primary outcomes were objective improvements after the intervention in key communication skills . Course content included structured feedback , videotape review of consultations , role-play with simulated patients , interactive group demonstrations , and discussion led by a trained facilitator . FINDINGS In Poisson regression analysis of counts of communication behaviours , course attendance significantly improved key outcomes . The estimated effect sizes corresponded to higher rates of use of focused questions ( difference between course attenders [ n=80 ] and non-attenders [ n=80 ] 34 % , p=0.003 ) , focused and open questions ( 27 % , p=0.005 ) , expressions of empathy ( 69 % , p=0.003 ) , and appropriate responses to patients ' cues ( 38 % , p=0.026 ) , and a 24 % lower rate of use of leading questions ( p=0.11 ) . There was little evidence for the effectiveness of written feedback . INTERPRETATION The communication problems of senior doctors working in cancer medicine are not resolved by time and clinical experience . This trial shows that training courses significantly improve key communication skills . More re sources should be allocated to address doctors ' training needs in this vital area BACKGROUND The administration of many drugs concurrently to elderly patients is a well-known problem in geriatrics and involves numerous risks . One way to reduce polypharmacy is to provide information to physicians in order to modify their prescribing practice s. The main objective of this study was to evaluate the impact of an intervention program that targeted physicians with the aim of reducing the number of potentially inappropriate prescriptions ( PIPs ) given to elderly patients . METHODS A r and omized controlled trial was carried out among community-dwelling elderly people in Sherbrooke , Que . The participants were 266 patients over 75 years of age ( experimental group : n = 136 , control group : n = 130 ) . A team comprising 2 physicians , a pharmacist and a nurse review ed the list of drugs and the diagnoses of a subgroup of the experimental group in a case conference . Suggestions were formulated and mailed to the patients ' physicians together with relevant scientific documentation justifying the recommendations . The main outcome measure was the number of PIPs . RESULTS The mean number of PIPs per patient declined by 0.24 in the experimental group ( n = 127 ) and by 0.15 in the control group ( n = 116 ) . The decline in PIPs was even larger in the experimental group that had case conferences ( n = 80 ) , in which the mean number of PIPs per patient declined by 0.31 . However , this difference between the experimental group and the control group was not statistically significant in the intent-to-treat analysis . The number of drugs prescribed was not modified by the intervention , nor were the results of the global assessment of the patients ' drug profiles . INTERPRETATION This study suggests that the intervention program had no effect on the prescribing of PIPs Purpose : In 2004 only 68 % of women in Oklahoma over the age of 40 reported having a mammogram in the past 2 years , compared with 75 % nationally . Strategies to improve mammography rates have been numerous but have generally included single strategies , such as physician education , practice audit and feedback , and reminders ; flow sheets and results have been mixed . The purpose of this r and omized controlled trial was to determine the impact of a practice facilitator and “ best practice ” interventions on mammography rates in a practice -based research network . Methods : A total of 16 practice s participated ; 8 were assigned to intervention and 8 to usual care . Pre- and post-audits of mammography rates were conducted . Intervention practice s received feedback with benchmarking , academic detailing , and the assistance of a practice enhancement assistant to help with practice re design over a 9-month period . Results : The groups differed significantly for both the proportion of mammograms offered to eligible patients ( P = .043 ) and for the proportion of patients with current mammograms ( P < .015 ) . For the control group , 38 % of eligible women were offered a mammogram and 202 ( 35 % of those eligible ) actually did have documentation that a mammogram had been performed . Fifty-three percent of the eligible patients in the intervention group were offered a mammogram and 52 % of those eligible ( n = 332 ) did have documentation in the chart that the mammogram had been completed . Conclusion : The results suggest that these interventions can improve mammography rates in a range of practice setting s. These findings are consistent with other studies that have tested multicomponent interventions BACKGROUND Interventions to improve the fracture prevention in nursing homes are needed . METHODS Cluster-r and omized , single-blind , controlled trial of a multi-modal quality improvement intervention . Nursing homes ( n=67 ) with > or = 10 residents with a diagnosis of osteoporosis or recent hip fracture ( n=606 ) were r and omized to receive an early or delayed intervention consisting of audit and feedback , educational modules , teleconferences , and academic detailing . Medical record abstract ion and the Minimum Data Set were used to measure the prescription of osteoporosis therapies before and after the intervention period . Analysis was at the facility-level and Generalized Estimating Equation modeling was used to account for clustering . RESULTS No significant improvements were observed in any of the quality indicators . The use of osteoporosis pharmacotherapy or hip protectors improved by 8.0 % in the intervention group and 0.6 % in the control group , but the difference was not statistically significant ( P=.72 ) . Participation in the intervention activities was low , but completion of the educational module ( odds ratio [ OR ] 4.8 , 95 % confidence interval [ CI ] , 1.9 - 12.0 ) and direct physician contact by an academic detailer ( OR 4.5 , 95 % CI , 1.1 - 18.2 ) were significantly associated with prescription of osteoporosis pharmacotherapy or hip protectors in multivariable models . CONCLUSIONS Audit-feedback and education interventions were ineffective in improving fracture prevention in the nursing home setting , although results may have been tempered by low participation in the intervention activities CONTEXT Care of patients with depression in managed primary care setting s often fails to meet guideline st and ards , but the long-term impact of quality improvement ( QI ) programs for depression care in such setting s is unknown . OBJECTIVE To determine if QI programs in managed care practice s for depressed primary care patients improve quality of care , health outcomes , and employment . DESIGN R and omized controlled trial initiated from June 1996 to March 1997 . SETTING Forty-six primary care clinics in 6 US managed care organizations . PARTICIPANTS Of 27332 consecutively screened patients , 1356 with current depressive symptoms and either 12-month , lifetime , or no depressive disorder were enrolled . INTERVENTIONS Matched clinics were r and omized to usual care ( mailing of practice guidelines ) or to 1 of 2 QI programs that involved institutional commitment to QI , training local experts and nurse specialists to provide clinician and patient education , identification of a pool of potentially depressed patients , and either nurses for medication follow-up or access to trained psychotherapists . MAIN OUTCOME MEASURES Process of care ( use of antidepressant medication , mental health specialty counseling visits , medical visits for mental health problems , any medical visits ) , health outcomes ( probable depression and health-related quality of life [ HRQOL ] ) , and employment at baseline and at 6- and 12-month follow-up . RESULTS Patients in QI ( n = 913 ) and control ( n = 443 ) clinics did not differ significantly at baseline in service use , HRQOL , or employment after nonresponse weighting . At 6 months , 50.9 % of QI patients and 39.7 % of controls had counseling or used antidepressant medication at an appropriate dosage ( P<.001 ) , with a similar pattern at 12 months ( 59.2 % vs 50.1 % ; P = .006 ) . There were no differences in probability of having any medical visit at any point ( each P > or = .21 ) . At 6 months , 47.5 % of QI patients and 36.6 % of controls had a medical visit for mental health problems ( P = .001 ) , and QI patients were more likely to see a mental health specialist at 6 months ( 39.8 % vs 27.2 % ; P<.001 ) and at 12 months ( 29.1 % vs 22.7 % ; P = .03 ) . At 6 months , 39.9 % of QI patients and 49.9 % of controls still met criteria for probable depressive disorder ( P = .001 ) , with a similar pattern at 12 months ( 41.6 % vs 51.2 % ; P = .005 ) . Initially employed QI patients were more likely to be working at 12 months relative to controls ( P = .05 ) . CONCLUSIONS When these managed primary care practice s implemented QI programs that improve opportunities for depression treatment without m and ating it , quality of care , mental health outcomes , and retention of employment of depressed patients improved over a year , while medical visits did not increase overall BACKGROUND Previous interventions targeting primary care practitioners with the aim of increasing preventive care delivery have demonstrated limited effectiveness . The primary aim of this study was to assess the effectiveness of a computerized continuing medical education program to increase rates of three screening behaviors ( cholesterol , blood pressure , and cervical screening ) and to identify three risk behaviors ( smoking , alcohol consumption , benzodiazepine use ) in general practice . METHODS Nineteen general practitioners were r and omly allocated to intervention or control conditions . Those given the intervention received a computerized feedback system . The intervention was delivered using a touch-screen computer located in the surgery waiting area . The preventive behaviors of interest were patient smoking , alcohol use , benzodiazepine use , and blood pressure , cholesterol and cervical screening using the Papanicolou test . Differences in performance by group in each of the outcomes was measured at baseline and 3-month follow-up . Logistic regression analyses with generalized estimating equations were conducted as the main analyses . RESULT At 3-month follow-up , statistically significant differences were evident in the following outcome measures : accurate classification of benzodiazepine users ( z = 2.8540 , P < 0.05 ) ; accurate classification of non-benzodiazepine users ( z = 2.7339 , P < 0.05 ) ; accurate classification of hazardous or harmful alcohol drinkers ( z = 2.3079 , P < 0.02 ) ; blood pressure screening ( z = 3.4136 , P < 0.001 ) ; and cholesterol screening ( z = 6.6313 , P < 0.001 ) . CONCLUSION A computerized system of performance-specific feedback was effective at increasing some preventive care services in general practice BACKGROUND In light of widespread undertreatment for glucocorticoid-induced osteoporosis ( GIOP ) , we design ed a group r and omized controlled trial to increase bone mineral density ( BMD ) testing and osteoporosis medication prescribing among patients receiving long-term glucocorticoid therapy . METHODS Using administrative data bases of a large US health plan , we identified physicians who prescribed long-term glucocorticoid therapy to at least 3 patients . One hundred fifty-three participating physicians were r and omized to receive a 3-module Web-based GIOP intervention or control course . Intervention modules focused on GIOP management and incorporated case-based continuing medical education and personalized audit and feedback of GIOP management compared with that of the top 10 % of study physicians . In the year following the intervention , we compared rates of BMD testing and osteoporosis medication prescribing between intervention and control physicians . RESULTS Following the intervention , intent-to-treat analyses showed that 78 intervention physicians ( 472 patients ) vs 75 control physicians ( 477 patients ) had similar rates of BMD testing ( 19 % vs 21 % , P = .48 ; rate difference , -2 % ; 95 % confidence interval [ CI ] , -8 % to 4 % ) and osteoporosis medication prescribing ( 32 % vs 29 % , P = .34 ; rate difference , 3 % ; 95 % CI , -3 % to 9 % ) . Among 45 physicians completing all modules ( 343 patients ) , intervention physicians had numerically but not significantly higher rates of BMD testing ( 26 % vs 16 % , P = .04 ; rate difference , 10 % ; 95 % CI , 1%-20 % ) and bisphosphonate prescribing ( 24 % vs 17 % , P = .09 ; rate difference , 7 % ; 95 % CI , -1 % to 16 % ) or met a combined end point of BMD testing or osteoporosis medication prescribing ( 54 % vs 44 % , P = .07 ; rate difference , 10 % ; 95 % CI , -1 % to 21 % ) compared with control physicians . CONCLUSIONS In the main analysis , a Web-based intervention incorporating performance audit and feedback and case-based continuing medical education had no significant effect on the quality of osteoporosis care . However , dose-response trends showed that physicians with greater exposure to the intervention had higher rates of GIOP management . New cost-effective modalities are needed to improve the quality of osteoporosis care BACKGROUND The rapid increase of antibiotic resistance poses a significant threat to human health . Overuse of antibiotics has been linked to rates of antibiotic resistance . This study assessed the utility of two common interventions --1 ) practice profiling and feedback and 2 ) patient education material s -- implemented to decrease antibiotic prescribing for pediatric upper respiratory infections ( URIs ) . METHODS Based on Medicaid regions in Kentucky , primary care physicians managing pediatric respiratory infections in Medicaid were r and omized into four groups . Groups received either 1 ) performance feedback only , 2 ) patient education material s only , 3 ) both feedback and education material s , or 4 ) no intervention . Participating physicians had their antibiotic prescribing assessed for the period of July 1 , 1996 , to November 30 , 1997 , with an intervention in June 1997 . The study included 216 physicians and 124,092 episodes of care . RESULTS All groups increased in proportion of episodes with antibiotics between the pre-intervention and post-intervention periods . Prescribing in the patient education group and the patient education and feedback group increased at a significantly lower rate than in the control group . Physicians did not change their coding of illness to justify antibiotics after the intervention , and there was no significant generalization of effect of the pediatric intervention on prescribing for adult URIs . CONCLUSIONS These interventions demonstrate little if any impact on promoting appropriate antibiotic prescribing . Antibiotic prescribing for viral respiratory infections continues to increase , suggesting concomitant increases in antibiotic resistance Objective A major problem with inappropriate use of antibiotics is the emergence of resistance . Thus , cost-effective interventional strategies are required to improve their use . This study aim ed to evaluate the effect of multifaceted interventions on prescribing practice s of antibiotics in health centers of Khartoum State , Sudan . Methods Twenty health centers were r and omly assigned to receive : ( 1 ) no intervention ; ( 2 ) audit and feedback ; ( 3 ) audit and feedback + seminar ; or ( 4 ) audit and feedback + academic detailing . A total of 1,800 patient encounters , 30 from each health center , were r and omly collected . The total number of encounters with antibiotics prescribed were determined in each health center and they were evaluated with regard to antibiotic choice , dose and duration of therapy before the study and at 1 and 3 months post-intervention . Results In comparison to the control group , the prescriber targeted interventions involving audit and feedback , together with academic detailing ( 4 ) , reduced the mean number of encounters with an antibiotic prescribed by 6.3 and 7.7 ( p<0.001 ) at 1 and 3 months post-intervention , respectively . In addition , the mean number of encounters with an inappropriate antibiotic with respect to diagnosis , doses and / or duration of therapy was reduced by 5.3 and 5.9 ( p<0.001 ) at 1 and 3 months post-intervention , respectively . For audit and feedback together with seminars ( 3 ) and for audit and feedback alone ( 2 ) , the corresponding reductions were 5.3 , 7.1 , 4.4 and 5.1 ( p<0.001 ) and 1.4 , 2.8 , 1.8 and 1.9 ( p>0.05 ) , respectively . Conclusion Inappropriate prescribing patterns of antibiotics in health centers of Khartoum State , Sudan , are alarmingly high . Multifaceted interventions involving audit and feedback combined with either academic detailing or seminars appear more effective in changing prescribing practice s of antibiotics than audit and feedback alone Background : Although there is a great concern regarding rational use of drugs , the available evidence for the most appropriate strategies to improve prescribing is scarce . Goal : The goal of this study was to evaluate the effectiveness of the combination of feedback of individualized prescribing data and educational recommendations for improving the quality of prescribing in general practice . Method : A quasiexperimental intervention study was conducted in which prescribing rates of 282 family physicians before and after the intervention were compared . Physicians assigned to the individualized feedback group ( n = 195 ) received individual instruction with specific recommendations for improvement according to their baseline prescribing quality levels , whereas physicians in the minimal intervention group ( n = 87 ) only received st and ard nonindividualized prescribing data for the practice group as a whole . Results : A trend toward increasing high pharmacologic intrinsic value in both groups was observed . Overprescription of antibiotics showed a decrease in the individualized feedback group ( P = 0.006 ) and it did not change in the minimal intervention group . A different trend in the values in each group was observed with nonsteroidal antiinflammatory drugs , although it was not statistically significant . Overprescription of antiulcerative agents decreased among physicians in the individualized feedback group ( P = 0.003 ) ; however , there were not statistically significant differences as compared with the minimal intervention group . Changes in indicators of drug selection were more favorable for the group with individualized feedback , although no statistically significant differences were observed . Pharmaceutical expenditure increased significantly in the minimal intervention group as compared with the individualized feedback group , with an approximate difference of $ 7.87 per inhabitant and trimester ( P = 0.003 ) . Conclusion : The intervention showed that improving the quality of prescribing was feasible , particularly in overprescribing , and was associated with considerable savings in pharmaceutical costs BACKGROUND / OBJECTIVES Glycosylated hemoglobin ( HbA1C ) measurements in patients with diabetes mellitus contribute to glycemic control , and , therefore to lower diabetic complication rates . Determine if an intervention that includes cl aims -based feedback about patterns of HbA1C measurement results in more frequent monitoring of HbA1C in diabetic Medicare beneficiaries . SUBJECTS Primary care physicians in a single Southern state treating Medicare beneficiaries with diabetes mellitus . METHODS A group-r and omized evaluation of an intervention that included cl aims -based feedback about patterns of HbA1C measurement , educational material s , and practice aids . RESULTS Rates for each quality indicator increased from 1996 to 1998 for both the intervention and comparison groups , although increases were larger for intervention counties . HbA1C testing rates increased in intervention counties 16.8 % compared to 13.0 % in the comparison counties , an absolute difference of 4.0 % ( 95 % CI , 0.7 to 7.3 ) . Differences for other indicators were small , although positive and favoring the intervention , and lacked statistical significance . CONCLUSIONS Physician interventions that included practice -level feedback about monitoring of glycemic control successfully led to improved care of diabetic Medicare beneficiaries Abstract Objective : To test the effects of feedback of information about patients ' asthma to primary care teams . Design : Patients ' reports of morbidity , use of health services , and drug use on question naire was given to primary care teams . R and omised controlled trial with general practice s as the subject of the intervention was used to test effectiveness of supplying information . Setting : Primary care in district health authority , London . Subjects : 23 general practice s , each of which notified at least 20 asthmatic patients aged 15 - 60 years for each principal . Practice s were r and omly allocated to an intervention group ( receiving feedback of information on control of asthma ) or a control group ( no feedback ) . Intervention : Information on cards inserted in patients ' medical records ; booklet copies of information for team members ; formal presentation to primary care teams ; poster displays of data on patients in each practice . Main outcome measures : Type and frequency of asthma symptoms , use of health services , use of asthma drugs . Results : Reported morbidity at entry to the study was substantial : 45 % ( 818 ) patients reported breathlessness at least once a week . Less than half these patients were using inhaled steroids regularly . Intervention and control groups did not differ in practice or patient characteristics on entry to the study . In spite of the potential for improvement no differences were observed between the two practice groups at the end of the study —for example , breathlessness at least once a week in last six months was experienced by 36 % in intervention group v 35 % in control group ( t=−0.27 , P<0.79 ) ; surgery attendance in last six months by 48 % v 48 % ( t=−0.05 , P<0.96 ) ; regular use of inhaled steroids by 60 % v 58 % ( t=0.51 , P<0.62 ) . Conclusion : Feedback to general practitioners of information about patients ' asthma does not on its own lead to change in the outcome of clinical care A r and omized trial of substance abuse treatment programs tested whether “ enhanced profiles , ” consisting of feedback and coaching about performance indicators , improved the performance of residential , methadone , and detoxification programs . These enhanced profiles were review ed during quarterly on-site visits between October 2005 and July 2007 . The performance indicators were the percentage of clients completing referrals to a lower level of care , and the percentage of clients admitted to a higher level of care within 30 days of discharge . Control programs received only “ basic profiles , ” consisting of emailed quarterly printouts of these performance indicators . Effectiveness was evaluated using hierarchical linear models with client-level information nested within agencies and regions of the state . Treatment programs receiving enhanced profiles ( n = 74 ) did not perform significantly differently from those receiving only basic profiles ( n = 29 ) on either performance measure . To improve performance , interventions with greater scope and incentives may be needed Objective – To assess the effectiveness of feedback on the number of pathology tests ordered by general practice s. Design – R and omised controlled trial . Setting – General practice s in two primary care groups in Leicestershire , UK . Subjects – 58 general practitioners in 17 practice s received guidelines then feedback at 3-month intervals for 1 year about the numbers of thyroid function , rheumatoid factor tests and urine cultures they ordered , and 38 general practitioners in 16 practice s received guidelines then feedback about lipid and plasma viscosity tests . Main outcome measures – Numbers of tests requested per thous and patients registered with each practice . Results – There were no changes in the numbers of tests per thous and requested in either of the study groups for any of the tests . Conclusions – Feedback did not have an influence on test ordering by general practitioners in this study . More intensive strategies may be required to change the use of laboratory tests Purpose To determine whether a resident physician can be as effective as a faculty opinion leader in changing physicians ' compliance with a hypertension practice guideline . Method At a general internal medicine clinic associated with an internal medicine residency program , sequential charts were review ed for patients with uncontrolled or new-onset hypertension who were seen routinely during a two-week period . Subsequently , 23 providers were r and omly assigned to an academic intervention to implement a hypertension practice guideline led by a single second-year resident instructor ( RI ) , and 21 providers were assigned to the same intervention led by a single staff internist ( SI ) with an interest in hypertension . The intervention involved academic detailing , chart audit with feedback , and behavior reinforcement . Six weeks later , the chart audit was repeated to assess the change in practice patterns among providers taught by the RI compared with those taught by the SI . Results Overall , management consistent with the practice guideline improved from 32 % ( 51/157 ) to 45 % ( 56/123 ) ( p < .01 ) after the intervention . This change was due to improvement in the care provided by providers from the SI-led intervention : 28 % ( 17/60 ) to 57 % ( 26/46 ) ( p < .003 ) . Providers from the RI-led intervention showed no improvement : 35 % ( 34/97 ) to 39 % ( 30/77 ) ( p = NS ) . Conclusions This intervention was effective in improving providers ' compliance with a hypertension practice guideline , but only when led by a faculty opinion leader . A resident instructor using the same format was unable to change the providers ' behaviors The authors present a controlled evaluation of a rural adaptation of the assertive community treatment ( ACT ) model for clients with serious and persistent mental illness ( SPMI ) . Four community mental health setting s adopted an ACT model , while a fifth site blended ACT principles with those of the Rhinel and er model , another approach to case management for persons with SPMI . A broad array of client and system outcomes were evaluated at 6 , 12 , and 24 months into the intervention . Twelve-month findings alerted us to potential problems in implementing the treatment model in study year 1 ; the implementation was qualitatively evaluated and weaknesses were addressed at the beginning of the second treatment year . Small , positive findings at 24 months suggested that the mid- study course correction may have had an impact . We present these findings along with descriptive data on the challenges of implementing complex services models . We give particular attention to describing implementation barriers to mental health services provision that are uniquely rural Objective : To measure the impact of a population -based tracking system on influenza immunization rates . Design : Thirteen practice s with 45 physicians were r and omized to a control and two intervention groups . Setting : Private practice s. Patients : All patients aged 65 years and over who were seen in participating physicians ’ practice s within the preceding two years . Intervention : In both intervention groups influenza immunization rates for physicians were recorded weekly as cumulative percentages of their target population s , using a specially prepared poster . In addition , postcard reminders were sent to all the patients in one of the intervention groups . Measurements and main results : Immunization rates in the two intervention groups were 30 % higher than in the control group ; the control group immunized 50 % ( 2,405/4,772 ) of its target population , while the poster and poster/postcard groups immunized 66 % ( 1,420/2,149 ) and 67 % ( 2,427/3,604 ) , respectively . Conclusion : A population -based strategy that monitors performance can significantly improve rates of influenza immunization in private practice A model for improving physician prescribing that utilizes computerized feedback was studied in a family medicine residency practice . Resident and faculty physicians were stratified by level of experience and r and omized into two groups . For 9 months the experimental group received monthly printouts identifying drugs they had prescribed by br and name with estimates of cost savings that might have been realized by prescribing generic drugs . The control group received no feedback . Prescription monitoring of both groups continued for 12 months after all feedback had ceased . Median weighted rates of generic prescribing for the experimental physicians were 14 % for the baseline , 67 % for the feedback , and 54 % for the follow-up periods . Rates for the control physicians for the three periods were 32 % , 37 % and 31 % , respectively . The increase in generic prescribing by physicians in the experimental group was significantly greater than for control physicians ( P = 0.01 ) . The feedback model improved rates of generic prescribing but should be evaluated for broader areas of physician prescribing INTRODUCTION To determine if an evidence -based implementation ( EBI ) could lead to the successful implementation of evidence based care for adult asthma in small rural district hospitals . METHODS A controlled trial involving eight small rural hospitals ( four each in the study and control groups ) was conducted . Retrospective pre-intervention audits were conducted at all eight hospitals for 7 months ( 1 January 2004 to 31 July 2004 ) and evidence - practice gaps identified . An EBI was then used to implement established guidelines for the management of asthma in the study hospitals . Post-intervention audits were then performed over a period of 7 months ( 1 October 2004 to 31 April 2005 ) . RESULTS There were 52 presentations of asthma in the study hospitals in the pre-implementation phase and 47 post-implementation . The corresponding numbers for the control hospitals were 46 and 42 respectively . There were no statistically significant differences in the severity between the groups . Following the EBI there were significant improvements at the study hospitals for the documentation of severity ( 8 % to 62 % , p < 0.001 ) , use of spirometry ( 12 % to 62 % , p < 0.001 ) and the use of written short-term asthma plans ( 9 % to 26 % , p = 0.05 ) . There was a decrease in use of ipratropium in mild asthma ( 44 % to 30 % , p = 0.228 ) , an increase in the use of systemic steroids ( 61 % to 72 % , p = 0.255 ) and no change in prescribing antibiotics for afebrile patients with asthma ( 21 % to 21 % p = 0.956 ) . There was no significant change in practice at the control hospitals except for a decrease in the use of systemic steroids ( 48 % to 21 % , p = 0.011 ) . For the six clinical indicators aggregate there was a significant increase in compliance with guidelines at the study hospitals ( 36 % to 62 % , p < 0.001 ) but no change at the control hospitals ( 31 % to 31 % , p = 0.970 ) . CONCLUSION The pre-intervention audits demonstrated low levels of compliance with asthma guidelines across six clinical indicators . An EBI significantly improved compliance across these six indicators , and no improvement was noted in the control hospitals . This study demonstrates that an EBI can alter clinical practice in small rural district hospitals Background : Suboptimal medication treatment of asthma has been reported . More specifically , short-acting β 2-agonists are overused , while inhaled corticosteroids are underused . This can be related in part to poor adherence by patients to the prescribed regimen and to professionals ' failure to comply with practice guidelines . Feedback seems to have an effect on professional practice s related to medication use . Objective : To assess the impact of feedback letters to physicians and pharmacists on their patients ' appropriate use of asthma medication . Methods : Two r and omized trials were set up in the province of Quebec , Canada : one with physicians and another with pharmacists . A sample of voluntary physicians and pharmacists was r and omly assigned to either the experimental group or to the control group . Those in the experimental groups received three consecutive feedback letters over a 9-month period summarizing the asthma medications acquired by their patients over the preceding year . The feedback focused on short-acting β 2-agonists , long-acting β 2-agonists and antileukotrienes and provided information on compliance with five appropriate-use criteria . Pharmacists received aggregate profiles and individual profiles with patients ' names , while most physicians received aggregate profiles for all their eligible patients . Each mailing also included a pamphlet that summarized practice guidelines on asthma treatment . Results : Seventy-one physicians and 60 pharmacists participated in the study . Physicians who received the feedback letters did not differ from those in the control group in terms of their proportion of prescriptions compliant with the criteria , either before the feedback or after it ( p > 0.05 ) . The before-after difference was also similar between groups . The same was true for pharmacists . However , although the before-after difference for criteria 1 ( frequency of use of short-acting β 2-agonists ) and 2 ( frequency of use of long-acting β 2-agonists ) did not reach the usual statistical significance threshold of 0.05 , the p value was under 0.10 . Conclusions : As design ed in this study , feedback provided to physicians did not improve the appropriate use of asthma medication . However , feedback to pharmacists is promising , especially when including patients ' names so that pharmacists can intervene more specifically The British Geriatrics Society has described 16 training objectives for senior house officers ( SHOs ) in geriatric medicine . We have developed these into an audit st and ard , and in a controlled trial we consider the effectiveness of audit as a means of monitoring and improving SHO training . SHOs from three hospitals were sent a question naire asking about the adequacy of formal and informal training for each objective ; there was a response rate of 87 % . Results were presented at an audit meeting in one hospital , inadequacies of training identified and the hospital 's programme of teaching modified appropriately . Two control hospitals remained unaware of the audit findings and were therefore unable to modify their training programmes . Re-audit at six months completed the audit cycle ; the control hospitals showing no change between the two audits . In the intervention hospital the adequacy of training over the 16 objectives improved from 59 % at first audit to 73 % at re-audit . The initial audit had highlighted three target objectives as needing special attention ; here the improvement from 38 % to 69 % was even more impressive , and statistically significant at p < 0.05 on chi 2 test . Thus , although a question naire approach is inevitably subjective and affected by SHO satisfaction , the discipline of audit appeared effective in identifying and correcting deficiencies in an SHO training programme This study , conducted in four general hospitals , evaluates the effectiveness of feedback from utilization review coordinators in reducing the number of inappropriate hospital days . Experimental control was exerted over the type of feedback provided in the utilization review process to produce four treatment groups ( including a control group ) that vary according to 1 ) the channel used to inform an attending physician of a probable inappropriately located patient and 2 ) the amount of discretion permitted the nurse coordinator in deciding whether , when and to whom this information is provided . The results of the study indicate that physician and hospital performance in utilization review , measured both by inappropriate patient days and length of stay , are affected by the feedback strategy employed . For patients inappropriately located for a portion of their hospital stay , provision of concurrent feedback result ed in reduction of approximately two thirds of an inappropriate day and two and one half total days , compared with patients for whom no feedback was provided or for whom physician advisor involvement was required . In addition , the effect of reasons causing patients to be inappropriately located ( barriers ) was assessed . Barriers outside the realm of influence of the hospital or the physician were found to impede the effectiveness of the utilization review systems A consistent finding in health services research is the report of uneven uptake of research findings . Implementation trials have a variable record of success in effectively influencing clinicians ' behaviour . A more systematic approach may be to conduct Intervention Modelling Experiments before service-level trials , examining intervention effects on ' interim endpoints ' representing clinical behaviour , derived from empirically supported psychological theories . The objectives were to : ( 1 ) Design Intervention Modelling Experiments by backward engineering a ' real-world ' r and omised controlled trial ( NEXUS ) ; ( 2 ) examine the applicability of psychological theories to clinical decision-making ; ( 3 ) explore whether psychological theories can illuminate how interventions achieve their effects . A 2 x 2 factorial r and omised controlled trial was design ed with pre- and post-intervention data collection by postal question naire surveys . The first survey was used to generate feedback data and the interventions were delivered in the second survey . General medical practitioners ( GPs ) in Engl and and Scotl and participated . First survey respondents were r and omised twice to receive or not audit and feedback and educational reminder messages . The main outcome measures included behavioural intention ( general plan to refer for lumbar X-rays ) and simulated behaviour ( specific , scenario-based , decisions to refer for lumbar X-ray ) . Predictors were attitude , subjective norm , perceived behavioural control ( theory of planned behaviour ) , self-efficacy ( social cognitive theory ) and decision difficulty . Both interventions significantly influenced simulated behaviour , but neither influenced behavioural intention . There were no interaction effects . All theoretically derived cognitions significantly predicted simulated behaviour . Only subjective norm was not predictive of behavioural intention . The effect of audit and feedback on simulated behaviour was mediated through perceived behavioural control . The results of this study suggest that Intervention Modelling Experiments , using psychological models to help isolate mediators of clinical decision-making , may be a means of developing more potent interventions , and selecting implementation interventions with a greater likelihood of success in a service-level r and omised controlled trial OBJECTIVE To assess the effectiveness of a multifaceted intervention to improve the management of glucocorticoid-induced osteoporosis ( GIOP ) . METHODS Of 21 rheumatologists , 11 were r and omly assigned to a 3-part intervention consisting of a lecture and discussion regarding optimal management of GIOP , a confidential doctor-specific audit regarding management of GIOP , and a reminder mailing including concise pharmacologic recommendations . The remaining 10 rheumatologists received no special education . Patients with rheumatoid arthritis ( RA ) taking oral glucocorticoids seen in the 2 months after the intervention were followed for 6 months . Medical records were assessed to determine the proportion undergoing bone mineral density testing or receiving pharmacologic interventions for GIOP during the 6 months before and 6 months after the intervention . RESULTS There were 373 patients with RA taking oral glucocorticoids whose records were assessed . Patients in both arms of the trial were similar with respect to age , sex , menopausal status , glucocorticoid dosage and duration , duration of RA , disease-modifying antirheumatic drug use , and the proportion with comorbid conditions . At baseline , there was no significant difference between the patients with respect to osteoporosis medication use ( intervention 32 % versus control 34 % ) or bone densitometry use ( intervention 9 % versus control 5 % ) . After the intervention and a 6-month followup period , there were no differences in treatment ( intervention 33 % versus control 38 % ) or bone densitometry use ( intervention 8 % versus control 8 % ) . Adjusting for patient and physician characteristics did not significantly change these results . CONCLUSION A multifaceted intervention for GIOP , including doctor education , practice audit , and treatment suggestions , had no significant benefit on testing or treatment by rheumatologists over a 6-month followup period . Other intervention approaches need to be tested BACKGROUND The extent of use of antibiotics to treat upper respiratory infections in general practice is an area for concern due to the increasing problem of bacterial resistance . Effective educational strategies to promote rational prescribing are needed . OBJECTIVES We aim ed to examine the effectiveness of prescriber feedback and management guidelines in reducing antibiotics prescribing by GP trainees for undifferentiated upper respiratory tract infection , and in improving the choice of antibiotic for tonsillitis/streptococcal pharyngitis . The research tested a stepwise approach to targeting educational input to high prescribers . METHOD General Practice trainees in New South Wales ( n = 157 ) were r and omly allocated to a treatment group ( n = 78 ) which received an education intervention on antibiotic use , or to a control group ( n = 79 ) which received an intervention on an unrelated topic . Trainees completed three practice activity surveys , each of 110 consecutive patient encounters , with 6-month intervals between surveys . Prescriber feedback and management guidelines on use of antibiotics for URTI and choice of antibiotic for tonsillitis/streptococcal pharyngitis were delivered in a written form between surveys 1 and 2 . An educational outreach visit to high prescribers occurred between surveys 2 and 3 . Outcome measures were the rate of antibiotic prescribing for all indications , for URTI and prescribing of select antibiotics for tonsillitis/streptococcal pharyngitis . RESULTS Antibiotic prescribing by the intervention group declined over three occasions from 25.0 to 23.3 to 19.7 per 100 URTI problems , while the control group increased from 22.0 to 25.0 to 31.7 per 100 URTI problems ( P = 0.002 ) . Prescribing in agreement with accepted guidelines for tonsillitis/streptococcal pharyngitis increased over time in the intervention group from 55.6 to 69.8 to 73.0 per 100 problems , but decreased in the control group from 59.6 to 57.5 to 58.5 ( P = 0.05 ) . CONCLUSION Prescriber feedback and management guidelines were shown to influence antibiotic prescribing for URTI and choice of antibiotic for tonsillitis/streptococcal pharyngitis . This study provides a model for targeting educational input to those prescribers who most need to change their behaviour OBJECTIVES A r and omized controlled trial evaluated the impact of feedback and financial incentives on physician compliance with cancer screening guidelines for women 50 years of age and older in a Medicaid health maintenance organization ( HMO ) . METHODS Half of 52 primary care sites received the intervention , which included written feedback and a financial bonus . Mammography , breast exam , colorectal screening , and Pap testing compliance rates were evaluated . RESULTS From 1993 to 1995 , screening rates doubled overall ( from 24 % to 50 % ) , with no significant differences between intervention and control group sites . CONCLUSIONS Financial incentives and feedback did not improve physician compliance with cancer screening guidelines in a Medicaid HMO OBJECTIVE We developed AsthmaCritic , a non-inquisitive critiquing system integrated with the general practitioners ' electronic medical records . The system is based on the guidelines for asthma and chronic obstructive pulmonary disease ( COPD ) as issued by the Dutch College of General Practitioners . This paper assesses the effect of AsthmaCritic on monitoring and treatment of asthma and COPD by Dutch general practitioners in daily practice . METHODS A r and omized clinical trial in 32 practice s ( 40 Dutch general practitioners ) using electronic patient records . An intervention group was given the use of AsthmaCritic , a control group continued working in the usual manner . Both groups had the disposal of the asthma and COPD guidelines routinely distributed by the Dutch College of General Practitioners . We measured the average number of contacts , FEV 1 ( forced expiratory volume ) , and peak-flow measurements per asthma/ COPD patient per practice ; and , the average number of antihistamine , cromoglycate , deptropine , and oral bronchodilator prescriptions per asthma/ COPD patient per practice . RESULTS The number of contacts increased in the age group of 12 - 39 years . The number of FEV1 , peak-flow measurements , and the ratio of coded measurements increased , whereas the number of cromoglycate prescriptions decreased in the age group of 12 - 39 years . CONCLUSIONS Our study shows that the guideline -based critiquing system AsthmaCritic changed the manner in which the physicians monitored their patients and , to a lesser extent , their treatment behavior . In addition , the physicians changed their data -recording habits Group teaching in problem-based interviewing based on video and audiotape feedback of the doctor 's own consultations significantly improved the ability of experienced general practitioners to teach psychiatric skills to their trainees . When the GPs were r and omly allocated to one of three further training experiences -- video feedback of their tutorial sessions , discussion about how to teach and no further teaching , there were very few differences between the groups . The greatest impact on improving teaching skills was brought about by watching their own consultations in a group feedback setting Background : The AHRQ Clinical Practice Guideline for Treating Tobacco Use and Dependence recommends screening and treatment of all tobacco users . Effective methods to implement recommendations are needed because simple guideline dissemination does not necessarily result in changes in practice . Objectives : The Guideline Implementation for Tobacco ( GIFT ) study tested an organizational intervention to improve Guideline implementation . Research Design : GIFT r and omized 20 Veterans Affairs medical centers to intervention or control conditions . We trained prime movers at each site to improve identification of smoking status , promote primary care interventions and increase availability of smoking cessation medications . Sites and patients were evaluated before and after intervention . Subjects : GIFT included 20 Veterans Affairs medical centers and 5678 subjects . Measures : Data regarding smoking status , delivery of treatment , medication use , and smoking cessation were collected from participant surveys , medical record review , survey of site leaders , and Pharmacy Benefits Management . Results : The intervention did not increase participant report of being asked about smoking status or receipt of counseling . It did increase the rate of identification of smoking status in the medical record ( P = 0.0001 ) but did not increase the rate of counseling to stop smoking . Site level data showed no increase in the number of patients receiving smoking cessation medications or dollars spent on medications . Individual smoker data showed a significant increase in the use of medications for smoking cessation in intervention sites ( odds ratio = 6.89 , P < 0.0001 ) ; however , only a small minority of smokers received medication even after the intervention . There was no difference in smoking cessation rates between participants at the intervention and treatment sites . Conclusions : We conclude that improvements in smoking cessation rates are likely to require more intensive intervention in this population OBJECTIVES To examine the effectiveness of prescription-based counseling and self-monitoring in the promotion of physical activity in primary health care . METHODS The study was conducted in Finl and during 2003 - 2004 . Physicians from 24 health care units ( N = 67 ) were r and omized to a prescription or a non-prescription group . The patients ( N = 265 ) were assigned to the groups according to their physician . Every other patient of the non-prescription physicians received a pedometer and a physical activity log ( MON ) and feedback about their 5-day-recordings , the rest served as controls ( CON ) . PA was assessed prior and 2 and 6 months after the physician 's appointment with a question naire . RESULTS The mean increase in weekly overall physical activity at 2 months was 1.0 ( 95 % CI 0.0 to 2.0 ) session more in the prescription group than in controls . In at least moderate-intensity physical activity , the mean difference in changes was 0.8 ( 95 % CI 0.1 to 1.5 ) sessions at 2 months and 0.9 ( 95 % CI 0.2 to 1.5 ) sessions at 6 months for the favor of the prescription group . Compared to controls , self-monitoring increased the weekly duration of overall PA at 2 months on average by 217 min ( 95 % CI 23 to 411 ) . CONCLUSIONS Prescription can be recommended as a tool for primary health care physicians to promote physical activity . Self-monitoring with an expert feedback can be useful in increasing especially the weekly duration of overall physical activity in the short term Screening mammography is underutilized in many primary care practice s. We design ed a prospect i ve , controlled trial to evaluate two strategies for improving the utilization of mammography in an academic general medicine clinic . We assigned teams of house officers to ( 1 ) physician audit with periodic feedback , ( 2 ) a visit-based strategy directed at both patient and physician , or ( 3 ) a no intervention concurrent control arm . After 6 months , the percentage of 50- to 74-year-old women meeting the st and ard of an annual mammogram was 36 % for patients in the control arm , 62 % for patients of feedback residents , and 54 % for patients of the arm receiving the visit-based strategy . Patients of female providers were slightly more likely to meet the st and ard , but no effects were detected for patient race , new as opposed to follow-up patient , or higher frequency of clinic visits . We conclude that audit with feedback and a new visit-based strategy of a patient cue associated with a simplification of the ordering process each greatly improved the rate of utilization of screening mammography . Practitioners could reasonably choose the strategy most suited to their own situation Background : Previous research has found that wellness visits , recall and reminder systems , and st and ing orders are associated with higher rates of delivery of preventive services in primary care practice s. However , there is little information about how to help practice s implement these processes . Methods : A 6-month r and omized , controlled trial comparing a multicomponent quality improvement intervention to feedback and benchmarking . One clinician/nurse team from each of 24 practice s was r and omly assigned to one of 2 study arms . Intervention practice s received performance feedback , peer-to-peer education ( academic detailing ) , a practice facilitator , and computer ( information technology ) support . Implementation of the 3 targeted processes was determined by a blinded 3-clinician panel that review ed transcribed clinician interviews before and after intervention using performance definitions . Rates of delivery of selected preventive services were determined by chart audit . Results : Intervention practice s implemented more of the processes than control practice s overall ( P = .003 ) , for adults ( P = .05 ) , and for children ( P = .04 ) . They were also more likely to implement at least one of the processes for children ( P = .04 ) and to implement st and ing orders for either children or adults ( P = .02 ) . Mammography rates increased significantly . Neither clinician and practice characteristics nor clinician readiness to change predicted implementation . Conclusions : A multicomponent implementation strategy consisting of feedback , benchmarking , academic detailing , facilitation , and IT support increased implementation of evidence -based processes for delivering preventive services to a greater extent than performance feedback and benchmarking alone Purpose : To determine whether group academic detailing with performance feedback increases recommended laboratory monitoring among out patients dispensed medications . Methods : Thirty-eight primary care practice s in 3 states were r and omized to group academic detailing with physician-level performance feedback ( intervention ) or a control group . Adjusted differences in creatinine and potassium testing between intervention and control group patients with a new or continuing dispensing for angiotensin-converting enzyme ( ACE ) inhibitors/angiotensin receptor blockers ( ARBs ) , diuretics , or digoxin were evaluated using generalized estimating equation approaches . Results : Monitoring among patients with an initial ACE/ARB and diuretic dispensing significantly improved with the intervention [ odds ratio ( OR ) = 1.22 , 95 % confidence interval ( CI ) : 1.08–1.38 ; and OR = 1.25 , 95 % CI : 1.08–1.44 , respectively ) . The intervention also significantly improved monitoring among patients with a continuing dispensing for an ACE/ARB ( OR = 1.39 , 95 % CI : 1.11–1.74 ) or a diuretic ( OR = 1.28 , 95 % CI : 1.02–1.60 ) . Adjusted differences in testing rates between study arms were modest ( ranging from 2.5 % to 4.9 % ) . No significant differences in monitoring by study arm were detected among patients dispensed digoxin . Conclusions : The impact of a group academic detailing program with feedback on recommended laboratory monitoring among medication users was modest . Yet , given the numbers of out patients dispensed medications for which laboratory monitoring is recommended , group academic detailing may offer 1 method by which outpatient medication safety can be significantly improved The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested . Sixty family physicians were r and omised to two treatment strategies . " Test " physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing . Computer feedback on management was mailed to the doctors . This encouraged doctors to apply the " stepped care " protocol , supplied charts of diastolic blood pressure v time , and ranked patients ' diastolic blood pressures by percentile . Letters were mailed to patients to remind them of appointments . " Control " doctors filled out the same data collection forms as test physicians , but neither doctors nor patients received computer feedback . Physicians who used the computer saw more patients per practice than control doctors ( test 50 patients , control 40 ) . For all patients the length of follow up was significantly longer in test practice s ( test 199 days , control 167 ) , and a smaller percentage dropped out of active treatment in test practice s ( test 37.5 % , control 42.1 % ) . For patients with " moderate " hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practice s ( 88.5 mm Hg ) , but it failed to reach this goal in control practice s ( 93.3 mm Hg ) . A greater average reduction of diastolic pressure was achieved in test practice s ( test 21.7 mm Hg , control 16.7 mm Hg ) . Though patients with " moderate " hypertension were better controlled in test practice s than in control practice s , the patients in test practice s visited their doctors less often ( test 13.3 visits per patient-year , control 17.4 visits ) . Among patients with newly detected hypertension test practice s achieved a greater reduction in diastolic pressure than control practice s ( test 15.1 mm Hg v control 11.3 mm Hg ) and more sustained control of hypertension ( test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days ) BACKGROUND St and ard Treatment Guidelines were introduced to all prescribers at provincial hospitals in Lao PDR and treatment indicators were developed within the National Drug Policy programme to monitor compliance . OBJECTIVES To evaluate the effects of an educational intervention to improve treatment practice s of malaria , diarrhoea and pneumonia . METHODS R and omized controlled trial with prescribers at 24 departments at eight provincial hospitals , matched into four pairs . The three departments of internal medicine , paediatrics and out- patients in each pair were r and omized into intervention or control group . The 6-month intervention was conducted by members of the Drug and Therapeutics Committees , and comprised monthly audit sessions in the form of outcome feedback using indicator scores on recorded treatment of malaria , diarrhoea and pneumonia . We measured treatment indicator scores 6 months after the end of the intervention compared with baseline . RESULTS The aggregated mean scores for all diseases , and for malaria and diarrhoea , improved significantly . For pneumonia , improvement was seen in both the intervention and control groups . Record keeping was improved for all three diseases . For malaria , there were improvements in recording patients ' history , and in frequency of microscope testing ; for diarrhoea , regarding weight measurements , palpation of the fontanel for children under 2 years , and reduction of irrational use of anti-diarrhoeals and antibiotics ; for pneumonia , in recording respiratory count , and reducing irrational use of anti-histamines and anti-cough medications . CONCLUSIONS Audit-feedback systems to improve quality of care are feasible and effective also in hospital setting s in low-income countries OBJECTIVE : To examine whether feedback and treatment advice for depression presented to primary care physicians ( PCPs ) via an electronic medical record ( EMR ) system can potentially improve clinical outcomes and care processes for patients with major depression . DESIGN : R and omized controlled trial . SETTING : Academically affiliated primary care practice in Pittsburgh , PA . PATIENTS : Two hundred primary care patients with major depression on the Primary Care Evaluation of Mental Disorders ( PRIME-MD ) and who met all protocol - eligibility criteria .INTERVENTION : PCPs were r and omly assigned to 1 of 3 levels of exposure to EMR feedback of guideline -based treatment advice for depression : “ active care ” ( AC ) , “ passive care ” ( PC ) , or “ usual care ” ( UC ) . MEASUREMENTS AND MAIN RESULTS : Patients ’ 3- and 6-month Hamilton Rating Scale for Depression ( HRS-D ) score and chart review of PCP reports of depression care in the 6 months following the depression diagnosis . Only 22 % of patients recovered from their depressive episode at 6 months ( HRS-D ≤7 ) . Patients ’ mean HRS-D score decreased regardless of their PCPs ’ guideline -exposure condition ( 20.4 to 14.2 from baseline to 6-month follow-up ; P<.001 ) . However , neither continuous ( HRS-D ≤7 : 22 % AC , 23 % PC , 22 % UC ; P=.8 ) nor categorical measures of recovery ( P=.2 ) differed by EMR exposure condition upon follow-up . Care processes for depression were also similar by PCP assignment despite exposure to repeated reminders of the depression diagnosis and treatment advice ( e.g. , depression mentioned in ≥3 contacts with usual PCP at 6 months : 31 % AC , 31 % PC , 18 % UC ; P=.09 and antidepressant medication suggested/prescribed or baseline regimen modified at 6 months : 59 % AC , 57 % PC , 52 % UC ; P=.3 ) . CONCLUSIONS : Screening for major depression , electronically informing PCPs of the diagnosis , and then exposing them to evidence -based treatment recommendations for depression via EMR has little differential impact on patients ’ 3- or 6-month clinical outcomes or on process measures consistent with high- quality depression care Objective : To determine whether two different educational interventions would reduce polypharmacy in out patients receiving ten ( 10 ) or more active medications at the Denver Veterans Affairs Center . Design : 292 patients were r and omized into three ( 3 ) groups : Control ( n=88 ) ; simple notification of primary care provider ( n=102 ) ; intensive notification , provision of pharmacy profiles , compliance index , and chart review by senior clinician with recommendations ( n=104 ) . Setting : Veterans Affairs Medical Center affiliated with the University of Colorado Health Sciences Center . Patients / Participants : All patients receiving greater than ten ( 10 ) active medications who are followed by clinic staff at the Denver VAMC . The mean age was 62 years ( range 26–88 ) and 96 % were male . Interventions : The simple notification group received only a single letter recommending that the patient ’s number of medications be reduced . The intensive notification group received more sophisticated intervention with a chart review , two letters with calculation of patient compliance , and individualized suggestions for reduction in polypharmacy . The control group received no intervention . Measurements and main results : Control patients had significantly less reduction in polypharmacy then either the simple or intensive intervention groups at four months ( p=0.028 ) . There was no significant difference between the intervention groups ( p=0.189 ) . By six months the difference was no longer significant . Conclusions : A simple intervention can result in a significant reduction in the number of medications prescribed to patients with polypharmacy . The authors were unable to show that a more complex intervention result ed in a further reduction in polypharmacy STUDY OBJECTIVES To test whether a 34-item functional status question naire measuring physical , psychological , and social function can be used by physicians in practice to help improve their patients ' outcomes . DESIGN Prospect i ve r and omized trial . SETTING Community internal medicine practice s. PATIENTS Five hundred and ten continuing patients with functional disabilities who saw their physicians at least four times a year . PHYSICIANS : Seventy-six UCLA clinical volunteer faculty who are internists in community office practice s. INTERVENTIONS Physicians and their patients were r and omly assigned to the experimental or the control group . Experimental group physicians attended a 2-hour multimedia educational session and received four functional status reports on each of their study patients over a 1-year period . Control group physicians received no education and no functional status feedback . Control group and experimental group patients were tested for functional status with the functional status question naire every 4 months for 1 year . Both groups also completed monthly diaries that measured use of health services . Experimental group physicians answered an anonymous evaluation question naire at 6 months after study entry . MEASUREMENTS AND MAIN RESULTS Forty-three percent of experimental group physicians reported that they had used the functional status question naire to change therapy . Ninety-five percent reported that it was useful and accurate . Patient diaries did not show any difference between experimental group patients and control group patients in number of medications used , visits to physicians or other health professionals , equipment purchased , diet , or exercise programs . There were no significant differences between experimental and control group patients at exit from the study on any functional status or health outcome measure . CONCLUSION A more powerful intervention than a 2-hour educational session and the regular provision of functional status information is needed to help office-based internists improve patient outcomes The objectives of the study were to determine if a drug profile quantitatively and qualitatively influenced various aspects of drug utilization . A group of 1,632 medically indigent persons enrolled in the Kaiser Health Flan constituted the study population . This population received completely prepaid medical care including drug services from the Kaiser Medical Care Program . A computer-based chronological and monthly up date d listing of drugs ordered and prescriptions received was provided as the front page of the central ized outpatient medical chart for a r and omly selected half of the study population for a full year . Duplicate and bound copies of these patient drug profiles were also provided each outpatient pharmacy . The findings indicated the presence of the drug profile did not quantitatively or qualitatively affect prescription receipt of the group with the profile . Although the findings must be viewed in the context s of the population served and the medical care setting , the findings strongly indicate the need for additional research to assess additional forms of drug profiles and under conditions not addressed by this study The capacity of educational programs to improve physician performance remains doubtful despite many evaluative efforts . This is especially true for programs sponsored by the federal government . We tested the efficacy of an educational program conducted by Professional St and ards Review Organizations in reducing the inappropriate use of x-ray pelvimetry . This procedure may cause harm to the fetus , and there is little evidence that it is efficacious . We r and omly assigned 120 hospitals in six Professional St and ards Review Organizations to study and control groups . Physicians with delivery privileges at each study hospital participated in an educational program that discussed acceptable indications for x-ray pelvimetry . Pelvimetry use was similar in study and control hospitals before the program . However , after the program , pelvimetry was performed by physicians at study hospitals less than one third as often as by physicians at control hospitals . We conclude that educational programs can improve physician performance substantially and that such programs can be effectively conducted by federally sponsored physician organizations PURPOSE We sought to determine whether tailored educational interventions call improve the quality of care , as measured by the provision of preventive care services recommended by the US Preventive Services Task Force , as well as lead to better patient satisfaction . SUBJECT AND METHODS We performed a r and omized controlled study among 41 primary care physicians who cared for 1,810 r and omly selected patients aged 65 to 75 years old at Kaiser Permanente Woodl and Hills , a group-model health maintenance organization in southern California . All physicians received ongoing education . Physicians r and omly assigned to the comprehensive intervention group also received peer-comparison feedback and academic detailing . Baseline and postintervention ( 2 to 2.5 years later ) surveys examining the provision of preventive care and patient satisfaction were performed and medical records were review ed . RESULTS Based on the results of patient surveys , there were significant improvements over time in the provision of preventive care in both the education and the comprehensive intervention groups for influenza immunization ( 79 % versus 89 % , P < 0.01 , and 80 % versus 91 % , P < 0.01 ) , pneumococcal immunization ( 42 % versus 73 % , P < 0.01 and 34 % versus 73 % , P < 0.01 ) , and tetanus immunization ( 64 % versus 72 % , P < 0.01 , and 59 % versus 79 % , P < 0.01 ) . Mammography ( 90 % versus 80 % , P < 0.01 ) and clinical breast examination ( 85 % versus 79 % , P < 0.05 ) scores worsened in the education only group but not in the comprehensive intervention group . However , there were few differences in rates of preventive services between the groups at the end of the study , and the improvements in preventive care were not confirmed by medical record review . Patient satisfaction scores improved significantly in the comprehensive intervention group ( by 0.06 points on a 1 to 5 scale , P = 0.02 ) but not in the education only group ( by 0.02 points , P = 0.42 ) ; however , the improvement was not significantly greater in the comprehensive intervention group ( P = 0.20 ) . CONCLUSION A physician-targeted approach of education , peer-comparison feedback , and academic detailing has modest effects on patient satisfaction and possibly on the offering of selected preventive care services . The lack of agreement between patient reports and medical records review raises concerns about current methods of ascertaining compliance with guidelines for preventive care To test the feasibility and effects of incorporating concurrent quality assurance ( CQA ) into the concurrent utilization review s required by PSRO 's , adherence to essential criteria of medical care and attainment of expected immediate outcomes were monitored prospect ively in 5604 cases of seven conditions in 24 experimental and 26 control hospitals in five PSRO areas . CQA was not consistently associated with improved documentation in records , but was associated with slightly better adherence to treatment criteria in all five PSRO areas ( P less than 0.03 ) . Adherence to pooled documentation or treatment criteria was unrelated to outcomes . However , failure to adhere to disease-specific scientifically vali date d treatment criteria was associated with unsatisfactory outcomes in bacterial pneumonia ( P less than 0.01 ) and acute myocardial infa rct ion ( P less than 0.02 ) . CQA was professionally acceptable , technically feasible and compatible with PSRO review s. Given adequate physician support , CQA can produce slightly greater adherence to treatment criteria . If the criteria are valid , adherence may lead to improved immediate outcomes in some diseases OBJECTIVE To investigate the effect on immunization levels of retrospective written feedback to residents regarding missed immunization opportunities . DESIGN R and omized trial with control group . SETTING Pediatric resident continuity clinic in an urban hospital-based primary care clinic . PARTICIPANTS Thirty-two postgraduate level 2 and postgraduate level 3 pediatric residents . INTERVENTION Monthly retrospective written feedback mailed to residents detailing their missed immunization opportunities and appointment failure rates over a 12-month period beginning in February 1997 . MAIN OUTCOME MEASURES The immunization level of 2-year-old children in the resident clinic was the main outcome of interest . Secondary outcomes included missed immunization opportunity rates and appointment failure rates . RESULTS Postintervention immunization levels were 71.4 % ( 95 % confidence limits [ CLs ] : 63.2 % , 78.7 % ) for patients from the intervention group and 68.5 % ( 95 % CLs : 60.8 % , 75.4 % ) for patients from the control group . The immunization level for patients of both groups who had fewer than 2 visits during the second year of life was 47.2 % ( 95 % CLs : 38.2 % , 56.3 % ) . This compares with an immunization level of 78.1 % ( 95 % CLs : 66.0 % , 87.5 % ) for patients from both groups who had 2 visits during the second year of life , and with an immunization level of 88.2 % ( 95 % CLs : 81.0 % , 93.4 % ) for patients of both groups who had more than 2 visits during the second year of life ( P<.001 ) . CONCLUSIONS In this setting , written retrospective feedback to residents was an ineffective strategy for improving immunization levels . Adequate follow-up during the second year of life is critical in achieving high immunization levels OBJECTIVE The purpose of this study was to assess the impacts of individualized prescribing feedback and interactive small group education aim ed at encouraging evidence -based prescribing in family/general practice . METHODS A two-by-two factorial r and omized controlled trial was carried out involving 200 family physicians in British Columbia , Canada . The physicians met monthly in 28 peer learning groups within the Practice -Based Small Group ( PBSG ) learning programme . Personalized prescribing feedback related to hypertension was provided through ' prescribing portraits ' which graphically displayed comparative rates of individual and peer group prescribing , together with a concise guide for evidence -based prescribing . A case-based educational module , containing the same evidence -based message , was discussed in small groups . Groups were matched and r and omized into four arms of seven groups each : control ( n = 56 ) , prescribing portrait only ( n = 48 ) , educational module only ( n = 47 ) , both portrait and module ( n = 49 ) . The main outcome measure was changes in ' prescribing preferences ' to new patients among those medications used to treat hypertension ( i.e. probability that a patient would receive the evidence -based medication as first-line therapy ) . RESULTS Using data from the provincial pharmacy registry ( PharmaNet ) , prescribing preferences for antihypertensive agents were determined for all groups for a 6 month period before and after the interventions , based on 4394 patients receiving a first-line antihypertensive . Significant absolute increases in prescribing preference for thiazides were documented for both the module + 0.068 ( confidence interval [ CI ] 0.022 - 0.115 ) and the portrait + 0.065 ( CI 0.018 - 0.111 ) . Preference in the group receiving both module and portrait increased by + 0.115 ( CI 0.040 - 0.189 ) . CONCLUSIONS Evidence -based educational interventions combining personalized prescribing feedback with interactive group discussion can lead to modest but meaningful changes in physician prescribing . Clear messages , proper trial design and sensitive outcomes are necessary to demonstrate these changes Nurses with advanced training — diabetes re source nurses (DRNs)—can improve care for people with diabetes in capitated payment setting s. Their effectiveness in fee-for-service setting s has not been investigated . We conducted a 12-month practice -r and omized trial involving 22 practice s in a fee-for-service metropolitan network with 92 primary care physicians caring for 1891 Medicare patients ≥65 years with diabetes mellitus . Each practice was r and omized to one of three intervention groups : physician feedback on process measures using Medicare cl aims data ; Medicare cl aims feedback plus feedback on clinical measures from medical record ( MR ) abstract ion ; or both types of feedback plus a practice -based DRN . The primary endpoint investigated was hemoglobin A1c level . Other measures were low-density lipoprotein ( LDL ) cholesterol level , blood pressure , annual hemoglobin A1c testing , annual LDL screening , annual eye exam , annual foot exam , and annual renal assessment . Data were collected from medical chart abstract ion and Medicare cl aims . The number of patients with hemoglobin A1c < 9 % increased by 4 ( 0.9 % ) in the Cl aims group ; 9 ( 2.1 % ) in the Cl aims + MR group ( comparison with Cl aims : P = 0.97 ) ; and 16 ( 3.8 % ) in the DRN group ( comparison with Cl aims : P = 0.31 ) . Results were similar for the other clinical outcomes , with no differences significant at P = 0.10 . For process of care measures , decreases were seen in all groups , with no significant differences in change scores . Quality improvement strategies must be evaluated in the appropriate setting . Initiatives that have been effective in capitated systems may not be effective in fee-for-service environments RATIONALE , AIMS AND OBJECTIVES To assess the effectiveness of internal initiatives to improve quality as compared with external feedback , and as compared with a control group . METHOD Ten primary health centres were r and omly selected from the centres in the Murcia 's Region and were r and omly assigned into three groups : G1 committed themselves to the improvement ; G2 composed by two subgroups : with and without quality improvement ( QI ) activities - received external feedback ; G3 received no intervention . Quality of common cold management was measured in a r and om sample of 50 patients per centre before and after interventions . Effect was assessed comparing criteria compliance and the cost of treatments for common cold in the three groups . RESULTS G1 and G2 subgroup with internal QI improved significantly in all criteria , and in G1 average treatment cost decreased by 60 % ( P < 0.01 ) . G3 improved only in one criterion . Estimated yearly savings in treatment costs for common cold , for a centre with internal QI , were euro 12,193.83 and it would be euro 1,817 004.65 for the 30 centres in the Region . CONCLUSIONS Internally assumed QI activities were significantly more effective than external feedback . Besides , the high cost of deficient quality provides a wide margin to invest with benefits in the promotion of internal QI programmes A r and omized controlled trial with 76 physicians in 16 community hospitals evaluated audit and feedback and local opinion leader education as methods of encouraging compliance with a guideline for the management of women with a previous cesarean section . The guideline recommended clinical actions to increase trial of labor and vaginal birth rates . Charts for all 3552 cases in the study groups were audited . After 24 months the trial of labor and vaginal birth rates in the audit and feedback group were no different from those in the control group , but rates were 46 % and 85 % higher , respectively , among physicians educated by an opinion leader . Duration of hospital stay was lower in the opinion leader education group than in the other two groups . The overall cesarean section rate was reduced only in the opinion leader education group . There were no adverse clinical outcomes attributable to the interventions . The use of opinion leaders improved the quality of care In a r and omized controlled trial three methods of feedback of increasing intensity , directed at 183 doctors taking cervical smears , were compared with respect to their effects on the sampling quality of smears . Overall , feedback was found to have no influence on quality criteria in the crude data analysis . However , a significantly larger decrease in the percentage of smears lacking endocervical cells was found in the groups receiving monthly overviews of their results with peer comparison , when compared with the groups not receiving this type of feedback ( odds ratio 0.75 ) . Moreover , feedback appeared to have a clear effect on the presence of endocervical cells among doctors su bmi tting a substantial number of smears in the intervention period , as opposed to those who su bmi tted fewer smears . A positive correlation was also observed between the increase in the group mean of the proportions of smears containing pathological cells and the intensity of the feedback . However , this increase did not reach statistical significance . This study suggests that monthly feedback with peer comparison may have a positive relationship with some aspects of quality improvement in cervical screening OBJECTIVES . Reducing unnecessary antibiotic use , particularly among children , continues to be a public health priority . Previous intervention studies have been limited by size or design and have shown mixed results . The objective of this study was to determine the impact of a multifaceted , community-wide intervention on overall antibiotic use for young children and on use of broad-spectrum agents . In addition , we sought to compare the intervention 's impact on commercially and Medicaid-insured children . METHODS . We conducted a controlled , community-level , cluster-r and omized trial in 16 nonoverlapping Massachusetts communities , studied from 1998 to 2003 . During 3 years , we implemented a physician behavior-change strategy that included guideline dissemination , small-group education , frequent up date s and educational material s , and prescribing feedback . Parents received educational material s by mail and in primary care practice s , pharmacies , and child care setting s. Using health-plan data , we measured changes in antibiotics dispensed per person-year of observation among children who were aged 3 to < 72 months , resided in study communities , and were insured by a participating commercial health plan or Medicaid . RESULTS . The data include 223135 person-years of observation . Antibiotic-use rates at baseline were 2.8 , 1.7 , and 1.4 antibiotics per person-year among those aged 3 to < 24 , 24 to < 48 , and 48 to < 72 months , respectively . We observed a substantial downward trend in antibiotic prescribing , even in the absence of intervention . The intervention had no additional effect among children aged 3 to < 24 months but was responsible for a 4.2 % decrease among those aged 24 to < 48 months and a 6.7 % decrease among those aged 48 to < 72 months . The intervention effect was greater among Medicaid-insured children and for broad-spectrum agents . CONCLUSIONS . A sustained , multifaceted , community-level intervention was only modestly successful at decreasing overall antibiotic use beyond substantial secular trends . The more robust impact among Medicaid-insured children and for specific medication classes provides an argument for specific targeting of re sources for patient and physician behavior change 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 < 7.0 % , LDL cholesterol < 100 mg/dL , and blood pressure < 130/85 mmHg ) 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 In a cross-over design , three interventions were tested for their impact on the rate of use of 12 commonly ordered blood tests and roentgenograms among internists in a health maintenance organization . Overall use fell by 14.2 % in a 16-week period during which physicians received confidential feedback on their individual rates of use compared with peers ( cost feedback ) . Eleven of 12 tests showed some decrease . Similar feedback on rates of abnormal test results ( yield feedback ) and a program of test-specific education failed to show a consistent effect . Variability in rates of test use among physicians , as measured by the coefficient of variation , fell by 8.3 % with cost feedback , by 1.3 % with yield feedback , and by 2.3 % with education , but these changes were inconsistent across tests In a training programme to improve the accuracy with which family doctors rate psychiatric disturbances in their patients an agreement coefficient ( kappa ) was calculated for each of 45 trainees between their ratings of psychiatric disturbances and the symptom levels of their patients as reported on the General Health Question naire ( GHQ-28 ) . The 24 trainees with the lowest kappa cofficients were r and omly assigned to an index or a control group , and the index group received four sessions of individual instruction , based on videotaped feedback of their own interviews , aim ed at modifying their interview style . After the training sessions the index group had significantly improved the accuracy of their assessment BACKGROUND Radiological tests are often used by general practitioners ( GPs ) . These tests can be overused and contribute little to clinical management . We aim ed to assess two methods of reducing GP requests for radiological tests in accordance with the UK Royal College of Radiologists ' guidelines on lumbar spine and knee radiographs . METHODS We assessed audit and feedback , and educational reminder messages in six radiology departments and 244 general practice s that they served . The study was a before- and -after , pragmatic , cluster r and omised controlled trial with a 232 factorial design . A r and om subset of GP patients ' records were examined for concordance with the guidelines . The main outcome measure was number of radiograph requests per 1000 patients per year . Analysis was by intention to treat . FINDINGS The effect of educational reminder messages ( ie , the change in request rate after intervention ) was an absolute change of -1.53 ( 95 % CI -2.5 to -0.57 ) for lumbar spine and of -1.61 ( -2.6 to -0.62 ) for knee radiographs , both relative reductions of about 20 % . The effect of audit and feedback was an absolute change of -0.07 ( -1.3 to 0.9 ) for lumbar spine of 0.04 ( -0.95 to 1.03 ) for knee radiograph requests , both relative reductions of about 1 % . Concordance between groups did not differ significantly . INTERPRETATION 6-monthly feedback of audit data is ineffective but the routine attachment of educational reminder messages to radiographs is effective and does not affect quality of referrals . Any department of radiology that h and les referrals from primary care could deliver this intervention to good effect CONTEXT Numbers of diagnostic tests ordered by primary care physicians are growing and many of these tests seem to be unnecessary according to established , evidence -based guidelines . An innovative strategy that focused on clinical problems and associated tests was developed . OBJECTIVE To determine the effects of a multifaceted strategy aim ed at improving the performance of primary care physicians ' test ordering . DESIGN Multicenter , r and omized controlled trial with a balanced , incomplete block design and r and omization at group level . Thirteen groups of primary care physicians underwent the strategy for 3 clinical problems ( arm A ; cardiovascular topics , upper and lower abdominal complaints ) , while 13 other groups underwent the strategy for 3 other clinical problems ( arm B ; chronic obstructive pulmonary disease and asthma , general complaints , degenerative joint complaints ) . Each arm acted as a control for the other . SETTING Primary care physician groups in 5 regions in the Netherl and s with diagnostic centers recruited from May to September 1998 . STUDY PARTICIPANTS Twenty-six primary care physician groups , including 174 primary care physicians . INTERVENTION During the 6 months of intervention , physicians discussed 3 consecutive , personal feedback reports in 3 small group meetings , related them to 3 evidence -based clinical guidelines , and made plans for change . MAIN OUTCOME MEASURE According to existing national , evidence -based guidelines , a decrease in the total numbers of tests ordered per clinical problem , and of some defined inappropriate tests , is considered a quality improvement . RESULTS For clinical problems allocated to arm A , the mean total number of requested tests per 6 months per physician was reduced from baseline to follow-up by 12 % among physicians in the arm A intervention , but was unchanged in the arm B control , with a mean reduction of 67 more tests per physician per 6 months in arm A than in arm B ( P = .01 ) . For clinical problems allocated to arm B , the mean total number of requested tests per 6 months per physician was reduced from baseline to follow-up by 8 % among physicians in the arm B intervention , and by 3 % in the arm A control , with a mean reduction of 28 more tests per physician per 6 months in arm B than in arm A ( P = .22 ) . Physicians in arm A had a significant reduction in mean total number of inappropriate tests ordered for problems allocated to arm A , whereas the reduction in inappropriate test ordered physicians in arm B for problems allocated to arm B was not statistically significant . CONCLUSION In this study , a practice -based , multifaceted strategy using guidelines , feedback , and social interaction result ed in modest improvements in test ordering by primary care physicians The effect of medication profile review by a clinical pharmacist on prescribing in a general medicine clinic was studied . Patients who were receiving five or more prescription or nonprescription medications were r and omly assigned to an intervention group ( n = 315 ) or a control group ( n = 257 ) . A clinical pharmacist review ed the medication profile of each intervention group patient on the day before the patient 's clinic visit and attached a written profile review to the medical record for study by the physician during the visit . After each clinic day , the pharmacist obtained up date d records of patients in both groups and collected data on the number and cost of medications ordered before and after the visits . After the clinic visits , the average number of medications and the average monthly medication cost per patient decreased by 0.21 and $ 0.60 , respectively , for the intervention group , compared with increases of 0.48 and $ 3.31 for the control group . The net result of a single profile review was a decrease of 0.69 prescription per patient , for a monthly medication cost savings of $ 3.91 . The number and cost of medications that were discontinued were significantly higher in the intervention group . The intervention group also had significantly fewer drugs added for previously documented medical problems . Medication profile review by a clinical pharmacist reduced both the number and cost of drugs for patients receiving five or more medications In April 1989 , the Health Care Financing Administration stopped publishing the parameters that trigger review of Medicare cl aims because they thought that knowledge of the parameters would permit providers to schedule visits to avoid review . In this article , the authors report the results of an experimental study where previously unrevealed parameters were revealed to some providers of Medicare services and not to others . The authors find little evidence to suggest that providers schedule procedures to avoid review when they know the parameters . There is some evidence , however , that providers may be responding to the release of the parameters in other ways Abstract OBJECTIVE : To evaluate an innovative approach to continuing medical education , an outreach intervention design ed to improve performance rates of breast cancer screening through implementation of office systems in community primary care practice s. DESIGN : R and omized , controlled trial with primary care practice s assigned to either the intervention group or control group , with the practice as the unit of analysis . SETTING : Twenty mostly rural counties in North Carolina . PARTICIPANTS : Physicians and staff of 62 r and omly selected family medicine and general internal medicine practice s , primarily fee-for-service , half group practice s and half solo practitioners . INTERVENTION : Physician investigators and facilitators met with practice physicians and staff over a period of 12 to 18 months to provide feedback on breast cancer screening performance , and to assist these primary care practice s in developing office systems tailored to increase breast cancer screening . MEASUREMENTS AND MAIN RESULTS : Physician question naires were obtained at baseline and follow-up to assess the presence of five indicators of an office system . Three of the five indicators of office systems increased significantly more in intervention practice s than in control practice s , but the mean number of indicators in intervention practice s at follow-up was only 2.8 out of 5 . Cross-sectional review s of r and omly chosen medical records of eligible women patients aged 50 years and over were done at baseline ( n=2,887 ) and follow-up ( n=2,874 ) to determine whether clinical breast examinations and mammography , were performed . Results for mammography were recorded in two ways , mention of the test in the visit note and actual report of the test in the medical record . These review s showed an increase from 39 % to 51 % in mention of mammography in intervention practice s , compared with an increase from 41 % to 44 % in control practice s ( p=.01 ) . There was no significant difference , however , between the two groups in change in mammograms reported ( intervention group increased from 28 % to 32.7 % ; control group increased from 30.6 % to 34.0 % , p=.56 ) . There was a nonsignificant trend ( p=.06 ) toward a greater increase in performance of clinical breast examination in intervention versus control practice s. CONCLUSIONS : A moderately intensive outreach intervention to increase rates of breast cancer screening through the development of office systems was modestly successful in increasing indicators of office systems and in documenting mention of mammography , but had little impact on actual performance of breast cancer screening . At follow-up , few practice s had a complete office system for breast cancer screening . Outreach approaches to assist primary care practice s implement office systems are promising but need further development PURPOSE The aim of this study is to evaluate the effectiveness of academic detailing ( AD ) plus postal prescribing feedback versus postal prescribing feedback alone in reducing : ( i ) the overall rate of antibiotic ; and ( ii ) proportion of second-line antibiotic prescribing . In addition , the cost-effectiveness of an outreach prescriber adviser service versus a postal prescribing feedback service was evaluated . METHODS Volunteer general practitioner practice s ( n = 98 ) were r and omized to receive prescribing feedback via postal bulletin ( PB ) ( n = 50 ) or academic detailing plus postal bulletin ( AD ) ( n = 48 ) . Data analysis was based on the HSE- primary care reimbursement service ( HSE-PCRS ) prescribing data base . Regression ( beta ) coefficients , indicating proportion change in prescribing per month , and 95 % confidence intervals ( CIs ) are presented . The cost-effectiveness ratio was calculated from the total cost of the intervention divided by percentage change in antibiotic prescribing in AD versus PB group . RESULTS Immediately post intervention PB ( beta = -0.02 , 95 % CI -0.04 , -0.001 ) and AD ( beta = -0.02 , 95 % CI -0.03 , -0.001 ) practice s significantly decreased overall antibiotic prescribing . Second-line antibiotic prescribing was also significantly decreased by 2 - 3 % in both groups . However , there were no significant differences in antibiotic prescribing between the r and omized groups in the immediate or long-term post-intervention period . In the cost-effectiveness analysis a postal prescribing feedback service would cost euro 88 per percentage change in prescribing practice compared with euro 778 for a prescriber adviser service . CONCLUSION Prescribing feedback significantly reduced overall and second-line antibiotic prescribing , but academic detailing was not significantly more effective than postal bulletin in changing antibiotic prescribing practice Initial experience with one strategy to modify selection of empiric antibiotic therapy by medical residents in presented . New orders for parenteral antibiotics written by residents before receiving culture results were r and omly allocated to either a recommendation or a control group . Antibiotic orders from each group were compared with guidelines for antibiotic selection , and suggestions to change antibiotics were made only for orders from the recommendation group that did not match the guidelines . Recommendations for change appeared necessary for about 20 % of the orders within each group . At follow-up , 78 % of these orders had been changed as suggested in the recommendation group , whereas only 10 % of the orders in the control group were changed ( p less than 0.005 ) . The mean difference in daily cost per order was a savings of $ 27.40 in the recommendation group and only $ 1.11 in the control group ( p less than 0.01 ) AIMS To evaluate the effectiveness of a multifaceted intervention to improve the clinical decision making of general practitioners ( GPs ) for patients with diabetes . To identify practice characteristics which predict success . METHODS Cluster r and omized controlled trial with 124 practice s and 185 GPs in The Netherl and s. The intervention group received feedback reports and support from a facilitator ; the control group received no special attention . Outcome measures were the compliance rates with evidence -based recommendations pertaining to discussion of body weight control , discussion of problems with medication , blood pressure measurement , foot examination , eye examination , initiating anti-diabetic medication or increasing the dosage in cases of uncontrolled blood glucose , and scheduling a follow-up appointment . RESULTS The GPs reported on their clinical decision making in 1410 consultations with Type 2 diabetic patients at baseline and 1449 consultations after the intervention period . The intervention result ed in statistically significant improvement for two of the seven outcome measures : foot examination ( odds ratio 1.68 ; 95 % confidence interval 1.19 - 2.39 ) and eye examination ( 1.52 ; 1.07 - 2.16 ) . Discussion of problems with medication showed a near significant trend towards increased benefit for the intervention group ( 1.52 ; 0.99 - 2.32 ) . Practice characteristics were not found to be related to the success of the intervention . CONCLUSIONS Feedback reports with support from facilitators appear to increase rates of foot examination and eye examination in general practice . Alternative interventions should be explored to improve the pursuit of metabolic control by GPs Effective physician involvement in quality assurance in hospitals is necessary both to identify problems in patient care and to bring about problem resolution . This report describes a controlled , longitudinal study design ed to measure effects on physician performance of involving physicians in setting medical audit criteria , review ing audit results , and receiving concurrent reminders on a case-by- case basis . Unexpected low hemoglobin levels was the topic for audit . During phase 1 of the study , three r and omly composed physician groups were involved in criteria setting plus review of audit results , review of audit results alone , or no treatment . During phase 2 , 6 months later , the physicians in all three groups were exposed to 4 months of concurrent reminders . During phase 1 , the group involved in review of audit results only achieved 51 % compliance with the preset criteria compared with 26 % for the group involved in criteria setting and review of audit results ( P = 0.002 ) . During phase 2 , when concurrent reminders were provided , the group that was formerly the control group in phase 1 , achieved 77 % compliance as compared with 56 % for the group previously involved in criteria setting and review of audit results ( P = 0.004 ) . These findings challenge the common assumption that physicians should be involved in criteria setting . They also suggest that providing the individual physician with information concurrently on a case-by-case basis may be superior to review ing audit results for changing physician behavior BACKGROUND Low Chlamydia trachomatis screening rates create an opportunity to test innovative continuing medical education ( CME ) programs . Few studies of Internet-based physician learning have been evaluated with objective data on practice patterns . DESIGN This r and omized controlled trial tested a multicomponent Internet CME ( mCME ) intervention for increasing chlamydia screening of at-risk women aged 16 to 26 years . SETTING Eligible physician offices had > or = 20 patients at risk for chlamydia as defined by the Health Plan Employer Data and Information Set ( HEDIS ) , had at least one primary care physician ( internal medicine , family medicine/general practice , pediatrics ) with Internet access , and participated in the study managed care organization . The 191 r and omized primary care offices represented 20 states . INTERVENTION The intervention , available from February to December 2001 , consisted of four case-based learning modules , was tailored in real time to each physician based on theory of behavior change , and included office-level feedback of chlamydia screening rates . MAIN OUTCOME MEASURE HEDIS chlamydia screening rates for the pre-intervention ( 2000 ) and post-intervention ( 2002 ) periods . RESULTS Pre-intervention screening rates for the intervention and comparison offices were 18.9 % and 16.2 % ( p = 0.135 ) . Post-intervention screening rates for the intervention and comparison offices were 15.5 % and 12.4 % , respectively ( p = 0.044 , adjusting for baseline performance ) . CONCLUSIONS The substantial decline in chlamydia screening rates observed in the comparison offices was significantly attenuated for the intervention offices . The mCME favorably influenced chlamydia screening by primary care physicians The purpose of this study was to evaluate performance feedback delivered by on-site presentations compared to mailed feedback on improving acute myocardial infa rct ion ( AMI ) care . We used a r and omized trial including 18 hospitals nested within the Cooperative Cardiovascular Project . Patients comprised AMI Medicare patients admitted before ( n = 929 , 1994 and 1995 ) and after intervention ( n = 438 , 1996 ) . Control hospitals received written feedback by mail . The experimental intervention group received a presentation led by a cardiologist and a quality improvement specialist . We assessed the proportion of patients receiving appropriate AMI care before and after the intervention . Both univariate and multivariate analyses demonstrated no effect of the intervention in increasing the proportion of patients who received reperfusion , aspirin , beta-blockers , or angiotensin-converting enzyme in- hibitors . On-site feedback presentations were not associated with a larger improvement in AMI care compared to the mailed feedback . Other interventions , such as opinion leaders and patient-directed interventions , may be necessary in order to improve the care of AMI patients Background : In 1998 , the Health Re sources and Services Administration ’s Bureau of Primary Health Care began the Health Disparities Collaboratives ( HDC ) to improve chronic disease management in community health centers ( HCs ) nationwide . The HDC incorporates rapid quality improvement , a chronic care model , and best practice learning sessions . Objectives : To determine whether the HDC improves diabetes care in HCs over 4 years and whether more intensive interventions enhance care further . Subjects : Chart review of 2364 , 2417 , and 2212 r and omly selected patients with diabetes from 34 HCs in 17 states in 1998 , 2000 , and 2002 , respectively . Measures : American Diabetes Association st and ards . Research Design : We performed a r and omized controlled trial with an embedded prospect i ve longitudinal study . We r and omized 34 HCs that had undergone 1–2 years of the HDC . The st and ard-intensity arm continued the baseline HDC intervention . High-intensity arm centers received 4 additional learning sessions , provider training in behavioral change , and patient empowerment material s. To assess the impact of the HDC , we analyzed changes in clinical processes and outcomes in the st and ard-intensity centers . To determine the effect of more intensive interventions , we compared the st and ard- and high-intensity centers . Results : Between 1998 and 2002 , HCs undertaking the st and ard HDC improved 11 diabetes processes and lowered hemoglobin A1c [ −0.45 % ; 95 % confidence interval ( CI ) , −0.72 to −0.17 ] and low-density lipoprotein cholesterol ( −19.7 mg/dL ; 95 % CI , −25.8 to −13.6 ) . High-intensity intervention centers had greater use of angiotensin converting enzyme inhibitors [ adjusted odds ratio ( OR ) , 1.47 ; 95 % CI , 1.07–2.01 ] and aspirin ( OR , 2.20 ; 95 % CI , 1.28–3.76 ) , but lower use of dietary ( OR , 0.24 ; 95 % CI , 0.08–0.68 ) and exercise counseling ( OR , 0.34 ; 95 % CI , 0.15–0.75 ) . Conclusions : Diabetes care and outcomes improved in HCs during the first 4 years of the HDC quality improvement collaborative . More intensive interventions helped marginally & NA ; The authors evaluated the effect of an educational and feedback intervention on H2‐blocker prescribing patterns and determined , if such effects differed for network‐ versus group‐model health maintenance organization ( HMO ) physicians and in academic versus nonacademic setting s. Physicians were r and omized to receive an educational memor and um alone or combined with feedback regarding their individual prescribing behavior . The memo suggested preferred use of an H2‐blocker ( cimetidine ) that would be less expensive to the HMO . Prescribing was monitored during the 6 months before and after the intervention . The study was undertaken at the primary care practice s of a mixed group‐ and network‐model university‐affiliated HMO . Thirty group‐model ( at two academic and four nonacademic sites ) and 33 network‐model ( all in full‐time private practice ) primary care physicians participated in the study . The analysis utilized weighted and unweighted analysis of covariance of the change in physicians ' cimetidine‐prescribing rates between the baseline and study periods . A significant response to the intervention was noted among academic and nonacademic group‐model HMO physicians , but not among network physicians ( adjusted mean absolute prescribing changes of + 9.9 % and + 8.9 % versus ‐2.8 % , P = .02 ) . There was no difference in prescribing change based on ITYPE of intervention ( education versus feedback ) . The authors conclude that a simple passive educational intervention can be effective at changing group‐model HMO physician behavior OBJECTIVE To determine whether providing physicians with peer-comparison feedback can improve patient functional status . STUDY DESIGN R and omized , controlled , comparative study . METHODS Forty-eight primary care physicians at Kaiser Permanente Woodl and Hills , a group-model health maintenance organization in southern California , were r and omly assigned to an intervention group or a control group . All physicians were informed that their elderly patients ( r and omly selected patients aged 65 to 75 ) would be monitored . Physicians in the intervention group received aggregated peer-comparison feedback data ( physician " report cards " ) on the functional status of their elderly patients . Physicians in the control group received only general information that their patients ' functional status would be monitored . The effect of the intervention on patients ' functional status was determined by comparing responses to surveys completed by the patients at baseline and after the intervention . RESULTS Patients in both the control and intervention groups had a statistically significant decrease in functional status , including decreases in their ability to complete daily activities and increases in pain . In addition , patients in the control group reported a significant decrease in social activities , physical fitness , and feelings . In the intervention group , patients also experienced a significant decrease in social support . CONCLUSIONS Educational interventions , including peer-comparison feedback , did not result in improvements in patient functional status . Research is desperately needed to identify interventions that can lead to improved health for elderly patients BACKGROUND Older people in nursing and residential homes often have complex disabilities and behavioural disturbances . Recent publicity has highlighted the dangers of medication in this group , and controls over prescribing have been suggested . AIMS To investigate the effect of a review of medication by a pharmacist . METHOD An 8-month prospect i ve trial of an active medication review by a pharmacist was carried out on 330 residents in nursing homes in Manchester . RESULTS The intervention group experienced greater deterioration in cognitive function and behavioural disturbance than the control group , but the changes in depression and quality of life were similar for both groups . The number of drugs prescribed fell in the intervention group , but not in the control group , with a corresponding saving in drug costs . The number of deaths was significantly smaller in the intervention homes during the intervention period ( 4 v. 14 ) but not overall during the study period as a whole ( 26 v. 28 ) . CONCLUSION This clinical intervention reduced the number of medicines prescribed to elderly people in nursing homes , with minimal impact on their morbidity and mortality Quality assurance is required of all hospital outpatient clinics although there is little evidence documenting its value . The purpose s of this study were to assess the impact of quality assurance audits on physicians ’ ordering behavior and to learn whether doctors who actually performed audits behaved differently from physicians who passively received audit results . Baseline influenza vaccination and screening mammography ordering rates were established for the authors ’ residents ’ clinic in 1985 . In 1986 , residents were assigned r and omly to three groups . Residents in one group audited their own charts for 1985 influenza vaccination ordering ; the second group audited its own charts for 1985 screening mammography ordering ; and the third group performed no audit but received the other groups ’ results . Passive receipt of results improved ordering of vaccination from 40 % to 59 % and ordering of mammography from 8 % to 16 % . Actual performance of audits improved ordering of mammography from 16 % to 26 % but did not improve vaccination ordering . These quality assurance audits were effective in improving the performance of selected preventive health measures in a residents ’ clinic BACKGROUND A multisite , r and omized controlled trial was conducted from August 1994 through January 1996 to compare the impact of two strategies-academic detailing ( AD ) and continuous quality improvement ( CQI ) teams-on the implementation of national guidelines for the primary care of hypertension and depression . STUDY Twelve small groups of providers at four clinics-two at Group Health Cooperative of Puget Sound ( Seattle ) and two at academic medical centers-were r and omized in blocks along with their primary care patients to receive AD alone , AD plus CQI , or usual care . A detailing session conducted by a physician and two follow-up sessions conducted by a pharmacist lasted an average of 8 - 9 minutes . Each CQI team , which met , on average , 14 times in nine months , devised at least one intervention ( for example , weight loss counseling for hypertensives by nurse practitioners ) . RESULTS The detailing endeavors differed greatly across organizations . Although all teams generally worked well together , organizational factors such as staff layoffs and reorganizations competed for the teams ' attention . Team leaders differed in their ability to inspire members to " run with " ideas and to motivate personnel outside the team to implement interventions . SUMMARY AND CONCLUSIONS Surveys and semi-structured interviews suggest that both the AD and CQI interventions involved complex social interactions that result ed in varied implementation across the different organizations . Final analyses will need to focus on identifying factors associated with the relative success or failure of both clinical change techniques OBJECTIVE To evaluate the impact of a locally adapted evidence -based quality improvement ( EBQI ) approach to implementation of smoking cessation guidelines into routine practice . DATA SOURCES / STUDY SETTING We used patient question naires , practice surveys , and administrative data in Veterans Health Administration ( VA ) primary care practice s across five southwestern states . STUDY DESIGN In a group-r and omized trial of 18 VA facilities , matched on size and academic affiliation , we evaluated intervention practice s ' abilities to implement evidence -based smoking cessation care following structured evidence review , local priority setting , quality improvement plan development , practice facilitation , expert feedback , and monitoring . Control practice s received mailed guidelines and VA audit-feedback reports as usual care . DATA COLLECTION To represent the population of primary care-based smokers , we r and omly sample d and screened 36,445 patients to identify and enroll eligible smokers at baseline ( n=1,941 ) and follow-up at 12 months ( n=1,080 ) . We used computer-assisted telephone interviewing to collect smoking behavior , nicotine dependence , readiness to change , health status , and patient sociodemographics . We used practice surveys to measure structure and process changes , and administrative data to assess population utilization patterns . PRINCIPAL FINDINGS Intervention practice s adopted multifaceted EBQI plans , but had difficulty implementing them , ultimately focusing on smoking cessation clinic referral strategies . While attendance rates increased ( p<.0001 ) , we found no intervention effect on smoking cessation . CONCLUSIONS EBQI stimulated practice s to increase smoking cessation clinic referrals and try other less evidence -based interventions that did not translate into improved quit rates at a population level Evidence exists that some dentists may be failing to perform adequate periodontal diagnostic and preventive care for their patients . Continuing education ( CE ) is an avenue that is frequently employed as a strategy to alter the style of practice . This paper presents an evaluation of a year-long continuing education intervention " Periodontics in General Practice " , conducted among r and omly selected private general dental practice s in Adelaide , South Australia . The CE intervention featured a 1-day seminar , bi-monthly newsletters , individualised 3-monthly comparative feedback , and technical assistance . The study employed a longitudinal quasi-experimental design , which allowed for evaluation of the effectiveness of the intervention among practice s employing hygienists ( n = 12 ) and not employing dental hygienists ( n = 12 ) , taking into account the covariates of baseline level of provision of periodontal services , the practice 's level of participation in the intervention and attendance at other CE courses in periodontics over the year . A comparison group of practice ( n = 12 ) did not participate in the intervention over the year . Patient record audits , conducted at baseline and at 12 months , provided data for the evaluation of the effect of the intervention on the recording of periodontal diagnostic , preventive and treatment items . Practice s participating in the intervention showed increases in the percentage of records containing at least one periodontal diagnostic notation , and those practice s employing hygienists showed an increase in the percentage of records with at least one preventive notation and one treatment item . ( ABSTRACT TRUNCATED AT 250 WORDS Objective : To evaluate the effect on general practitioners ' prescribing of feedback on their levels of prescribing . Design : R and omised controlled trial . Setting : General practice in rural Australia . Participants : 2440 full time recognised general practitioners practising in non-urban areas . Intervention : Two sets of graphical displays ( 6 months apart ) of their prescribing rates for 2 years , relative to those of their peers , were posted to participants . Data were provided for five main drug groups and were accompanied by educational newsletters . The control group received no information on their prescribing . Main outcome measures : Prescribing rates in the intervention and control groups for the five main drug groups , total prescribing and potential substitute prescribing and ordering before and after the interventions . Results : The intervention and control groups had similar baseline characteristics ( age , sex , patient mix , practice s ) . Median prescribing rates for the two groups were almost identical before and after the interventions . Any changes in prescribing observed in the intervention group were also seen in the control group . There was no evidence that feedback reduced the variability in prescribing nor did it differentially affect the very high or very low prescribers . Conclusions : The form of feedback evaluated here — mailed , unsolicited , central ised , government sponsored , and based on aggregate data —had no impact on the prescribing levels of general practitioners We studied whether a hospital intervention utilizing medical opinion leaders and performance feedback reduced the proportion of women who reported that surgeons did not discuss options prior to surgery for early stage breast cancer . Opinion leaders provided clinical education to their peers using a variety of strategies and were selected for their ability to influence their peers . Performance feedback involved distributing performance reports that contained data on the outcomes of interest as well as on other treatment patterns . Twenty-eight hospitals in Minnesota were r and omized to the intervention or to a control group that received performance feedback only . The proportion of patients at intervention hospitals who said that their surgeon did not discuss options decreased significantly ( p<0.001 ) from 33 % to 17 % , but a similar decrease was observed among control hospitals . Using medical opinion leaders to intervene in hospitals appeared as effective as performance feedback The objective of this study was twofold , namely to evaluate the effectiveness of a dental clinical practice guideline on the management of asymptomatic impacted lower third molars ( i ) on referral rates and ( ii ) on dentists ' change in knowledge . A two-arm cluster r and omized controlled trial , with pre- and post-test assessment s , was conducted . A guideline was implemented by multifaceted interventions ( i.e. feedback , reminders , and an interactive meeting ) . The effect was evaluated after 1 yr by repeating the baseline question naire and by monitoring the number of patients who were referred for removal of their asymptomatic impacted m and ibular third molars . Instruments were question naires for detecting changes in knowledge , patient records , and panoramic radiographs . The knowledge of dentists regarding asymptomatic m and ibular third molar management was found to increase significantly in the intervention group as compared to the control group . There was no statistically significant difference between the groups in guideline -consistent patient referral rates at the post-test assessment . It was concluded that the methodology employed for dissemination and implementation of a clinical practice guideline on asymptomatic m and ibular third molar management improves dentists ' knowledge on this topic and is effective in improving decision-making in simulated cases ; however , no clinical effect was demonstrated OBJECTIVE To test whether a team training intervention in stroke rehabilitation is associated with improved patient outcomes . DESIGN A cluster r and omized trial of 31 rehabilitation units comparing stroke outcomes between intervention and control groups . SETTING Thirty-one Veterans Affairs medical centers . PARTICIPANTS A total of 237 clinical staff on 16 control teams and 227 staff on 15 intervention teams . Stroke patients ( N=487 ) treated by these teams before and after the intervention . INTERVENTION The intervention consisted of a multiphase , staff training program delivered over 6 months , including : an off-site workshop emphasizing team dynamics , problem solving , and the use of performance feedback data ; and action plans for process improvement ; and telephone and videoconference consultations . Control and intervention teams received site-specific team performance profiles with recommendations to use this information to modify team process . MAIN OUTCOME MEASURES Three patient outcomes : functional improvement as measured by the change in motor items of the FIM instrument , community discharge , and length of stay ( LOS ) . RESULTS For both the primary ( stroke only ) and secondary analyses ( all patients ) , there was a significant difference in improvement of functional outcome between the 2 groups , with the percentage of stroke patients gaining more than a median FIM gain of 23 points increasing significantly more in the intervention group ( difference in increase , 13.6 % ; P=.032 ) . There was no significant difference in LOS or rates of community discharge . CONCLUSIONS Stroke patients treated by staff who participated in a team training program were more likely to make functional gains than those treated by staff receiving information only . Team based clinicians are encouraged to examine their own team . ( Clinical Trials.gov identifier NCT00237757 ) Context Interventions to promote guideline -recommended care have met with limited success . Quality improvement experts believe that multicomponent interventions are more effective than simpler strategies , but this belief rests on limited evidence . Contribution In this r and omized trial of 20 primary care practice s , intervention practice s received quarterly site visits and 2 network meetings about quality improvement in addition to copies of practice guidelines and quarterly performance reports . Intervention practice s had greater improvement in providing guideline -recommended care for cardiovascular disease prevention and treatment than practice s that received only the guidelines and performance reports . Caution s The study involved a small number of practice s. The Editors Widespread evidence reveals inadequate implementation of evidence -based clinical practice guidelines for prevention and management of cardiovascular disease and stroke in primary care setting s ( 1 - 3 ) . Primary prevention deficiencies exist in the screening and management of dyslipidemia ( 4 ) and hypertension ( 5 ) . Secondary prevention deficiencies include inadequate treatment of dyslipidemia in patients with coronary heart disease ( CHD ) ( 6 ) and inadequate use of antiplatelet therapy in patients with CHD or cerebrovascular disease ( 7 ) , inadequate use of -blockers after myocardial infa rct ion ( 8) , inadequate use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers in patients with heart failure ( 9 ) , and inadequate use of oral anticoagulant therapy in patients with atrial fibrillation ( 10 ) . Finally , patients with diabetes mellitus who are at high risk for cardiovascular disease as well as microvascular disease infrequently receive recommended screening and adequate treatment for elevated glycosylated hemoglobin levels , hypertension , and dyslipidemia ( 11 ) . Published systematic review s point to the importance of multifaceted interventions in increasing adherence to practice guidelines and improving disease control ( 12 , 13 ) . Little is known , however , about the relative effectiveness of different implementation strategies . More research is needed to develop and vali date effective , theoretically sound , and practical strategies for improving the provision of evidence -based medicine in primary care . Particularly important are studies that address multiple common , chronic conditions , which together reflect a large proportion of the work of primary care providers ( 14 ) . This study was design ed as a pragmatic clinical trial ( 15 ) , intended to assess whether a multi method quality improvement intervention was more effective than a less intensive intervention for improving adherence to 21 quality indicators relevant to the primary and secondary prevention of cardiovascular disease and stroke . The multi method quality improvement intervention added practice site visits ( for academic detailing and quality improvement facilitation ) and network meetings ( for sharing best practice s ) to the approach of guideline dissemination and audit and feedback used in the less intensive intervention . The study was conducted in a practice -based research network ( PPRNet ) among users of a common electronic medical record ( Practice Partner Patient Records , Seattle , Washington ) , which historically provided audit and feedback to its practice members . Audit and feedback have already been shown to improve the practice of health care professionals , particularly in prescribing and test ordering ( 16 ) . Additional research is needed to assess the effect of audit and feedback in combination with other interventions . Methods Design The design was a cluster r and omized , controlled clinical trial , with the practice as the unit of r and omization . Twenty-three office-based primary care practice s in 15 states agreed to participate . The institutional review board at the Medical University of South Carolina approved the study . Study Indicators We derived the study indicators ( Table 1 ) from published sources ( 17 - 22 ) . Fourteen were process measures , which reflected whether recommended tests were done , appropriate diagnoses made , or appropriate medication prescribed . Seven were outcome measures , which reflected whether patients achieved recommended treatment goals . Some of the measures represented primary prevention , for example , screening for hypertension or dyslipidemia . Others represented secondary prevention , for example , reaching treatment goals for glycosylated hemoglobin levels , low-density lipoprotein ( LDL ) cholesterol levels , and blood pressure in patients with diabetes . An additional indicator , hormone replacement therapy for postmenopausal women , was included at the beginning of the study but was withdrawn in July 2002 when the results from the Women 's Health Initiative trial were published ( 23 ) . Table 1 . Study Indicators We determined practice performance for each study indicator at baseline and quarterly throughout the study . To determine performance , participating practice s ran a computer program to extract patient activity during the previous quarter from their electronic medical record . To protect patient confidentiality , the extract program assigned a unique , anonymous numerical identifier to each patient . The extract program obtained demographic information , such as age , race , and sex ; diagnoses ; medications ; laboratory data ; and vital signs . Text of progress notes , consultation reports , and discharge summaries were not extracted . The data were copied to a diskette and mailed to PPRNet or sent electronically via a secure server . In the PPRNet offices , the data were bridged to st and ard data dictionaries and converted to SAS data sets ( SAS Institute , Inc. , Cary , North Carolina ) on st and ard microcomputers for analyses . Interventions The intervention began on 1 January 2001 and was completed on 1 January 2003 . During the first quarter of 2001 , the medical director of each practice was sent printed copies of each practice guideline referenced in the study . Beginning in the first quarter of 2001 , the medical director was sent quarterly performance reports documenting the practice 's adherence to each of the 21 study indicators . Each report contained the practice 's current performance , calculated as the percentage of eligible patients who had received the recommended service , the number of patients who were receiving the recommended medication , or the number of patients who had achieved the treatment goal . The report also presented data on the practice s ' previous performance since the beginning of the study and the performance target , calculated as the 90th percentile at baseline among all practice s. In practice s with more than 1 clinician , individual provider data were not given because the study emphasized improvement at the practice level . The medical director was encouraged to share the reports with others in the practice in order to stimulate motivation for improvement . The 90th percentile was selected as the performance target because it reflected a bold but achievable goal ( at least 2 practice s were at this level of performance at baseline ) . Practice s in the control group received no other interventions during the study . An example of 1 page of a practice report is available in the Appendix Figure . Appendix Figure . Sample practice report for blood pressure in coronary heart disease . Practice s in the intervention group also participated in practice site visits and network meetings . Six or seven 1- or 2-day site visits were held at each practice approximately every 3 months during 2001 and 2002 . The practice site visit was led by 1 of the physician co authors , assisted during the first few visits in 2001 by a clinical pharmacist with expertise in academic detailing ( 24 ) , and at later visits by other co authors with expertise in quality improvement . Initial site visits focused on engaging clinicians and staff members in the project , through a formal presentation by the site visitors and group discussion with all members of the practice team , including providers , nurses , medical assistants , and reception and administrative personnel . Because of vacation or hospital coverage responsibilities , 1 or 2 providers were occasionally absent in the multiprovider practice s , and 1 practice involved only a few members of their staff . We placed detailed attention on the scientific justification for the chosen study indicators and on published frameworks for clinician behavior change ( 25 , 26 ) . Baseline practice performance on each study indicator was discussed , and previous evidence of the ability of PPRNet practice s to improve care was presented ( 27 ) . Practice s were encouraged to increase the use of quality improvement tools available in the electronic medical record , such as note templates with embedded practice guidelines , query functions , prompts , reminders , and messaging . At each visit , a participatory planning session was held in which practice members identified specific clinical indicators they wished to work on and improvement activities to conduct before the next site visit . Lessons from complexity theory were used in this exercisethe influence of each practice member on the system , the importance of replicating successful approaches and focusing on motivators for patients and staff , and the notion that simple changes are easiest to adopt and can have profound effects . In subsequent site visits , we focused on discussing the practice 's success in adopting its planned improvement activities , presenting up date d performance data , and planning additional practice -level interventions . The site visitors presented results from recently published studies relevant to the study indicators . Successful and unsuccessful approaches to improvement by other intervention sites were also presented . Two-day network meetings were held in Charleston , South Carolina , in May 2001 and May 2002 . The lead clinician from each intervention practice and the research team attended the first meeting . At this Clinical guidelines have been developed to assist with the management of patient care ; however , these guidelines are frequently neglected in clinical practice . Computer-generated reminders enhance guideline use , but these systems often fail to achieve high rates of guideline utilization . This study was design ed to test the hypothesis that computer-generated , individualized feedback regarding adherence to care guidelines will significantly improve clinician compliance with guideline recommendations presented through a computer-assisted management protocol . Half of the 45 primary care clinicians employed at a primary care clinic affiliated with an academic medical center , were r and omized to receive a biweekly electronic mail message consisting of a computer-generated report summarizing his/her response to care guideline recommendations for the diabetic patients seen during the previous 2 weeks . Clinician compliance with guideline recommendations was the primary outcome measure . This study demonstrated that the intervention significantly increased clinician compliance with the guideline recommendations without incurring high maintenance expenses . Median compliance among the intervention group was 35 % versus 6.1 % among the control group ( p < 0.01 ) . Electronically distributed , computer-generated , individualized feedback regarding clinician use of care guideline recommendations is an effective way to enhance compliance with a care guideline BACKGROUND The Royal College of Radiologists ( RCR ) have produced regularly up date d guidelines on radiological referrals since 1990 . A small study in 1992 showed postal distribution of guidelines reduced general practitioners ' referrals over the subsequent 9 weeks . However there have been no r and omized trials of the longer term effects of radiological guidelines and feedback on referral rates on X-ray requests from primary care . OBJECTIVES To see if the introduction of radiological guidelines into general practice s together with feedback on referral rates reduces the number of GP radiological requests over one year ; and to explore GPs'attitudes to the guidelines . METHODS Sixty-nine practice s referring patients to St George 's Healthcare Trust were r and omly allocated to intervention or control groups . In February 1995 a GP version of the RCR guidelines was sent to each GP in the 33 practice s in the intervention group . After 9 months intervention , practice s were sent revised guidelines with individual feedback on the number of examinations requested in the past 6 months . The total number of requests per practice was compared for the year before and the year after the introduction of the guidelines . Control practice s were sent the guidelines at the end of the study . All doctors were sent a question naire about the guidelines . RESULTS A total of 43 778 radiological requests were made during the two years 1994 - 1996 . In practice s receiving the guidelines there was a 20 % reduction in requests for spinal examinations compared with control practice s ( P < 0.05 ) . This corresponded to the effect reported by GPs . There was also a 10 % difference between the groups in the total number of requests made , but due to wide inter practice variation in referral rates this failed to reach statistical significance . CONCLUSIONS Introduction of radiological guidelines together with feedback on referral rates was effective in reducing the number of requests for spinal examinations over one year . Wider use of GP-orientated guidelines with regular updating and feedback might save costs and reduce unnecessary irradiation of patients Statistical process control ( SPC ) charts have previously been advocated for infection control quality improvement . To determine their effectiveness , a multicentre r and omised controlled trial was undertaken to explore whether monthly SPC feedback from infection control nurses ( ICNs ) to healthcare workers of ward-acquired meticillin-resistant Staphylococcus aureus ( WA-MRSA ) colonisation or infection rates would produce any reductions in incidence . Seventy-five wards in 24 hospitals in the UK were r and omised into three arms : ( 1 ) wards receiving SPC chart feedback ; ( 2 ) wards receiving SPC chart feedback in conjunction with structured diagnostic tools ; and ( 3 ) control wards receiving neither type of feedback . Twenty-five months of pre-intervention WA-MRSA data were compared with 24 months of post-intervention data . Statistically significant and sustained decreases in WA-MRSA rates were identified in all three arms ( P<0.001 ; P=0.015 ; P<0.001 ) . The mean percentage reduction was 32.3 % for wards receiving SPC feedback , 19.6 % for wards receiving SPC and diagnostic feedback , and 23.1 % for control wards , but with no significant difference between the control and intervention arms ( P=0.23 ) . There were significantly more post-intervention ' out-of-control ' episodes ( P=0.021 ) in the control arm ( averages of 0.60 , 0.28 , and 0.28 for Control , SPC and SPC+Tools wards , respectively ) . Participants identified SPC charts as an effective communication tool and valuable for disseminating WA-MRSA data The authors tested the effectiveness and estimated the cost of several interventions aim ed at reducing drug interactions in primary care by design ing a 15-month cluster-controlled trial . The trial involved 265 family physicians and their patients who were r and omized into 4 groups : control , report ( received feedback reports ) , session ( group sessions ) , and face-to-face ( personal interviews ) . The outcome was the mean of relevant interactions detected on electronic medical records . Cost-effectiveness was defined as the incremental cost to reduce drug interactions by 1 % . The authors detected a baseline mean of 6.7 interactions per 100 patients , which was reduced to 5.3 interactions after follow-up . No improvement was seen in the report group when compared with the control group , whereas progressive improvement in the other groups was noted ( P < .001 ) . Incremental cost was higher in the face-to-face group ( 69.4 vs 50.7 ) ; cost-effectiveness results were slightly better in the session group ( 4.2 vs 4.5 ) To determine the effect of two levels of educational intervention on benzodiazepine-prescribing behavior in an elderly population in a controlled prepaid group practice ( PPGP ) setting , we design ed a prospect i ve controlled trial , with six-month follow-up . Our setting was a 270,000 member group-model PPGP in Colorado , from 1990 to 1991 . Participants included 91 physicians , 62 men and 29 women ; median age was 38.7 years . Group 1 received a one-on-one educational presentation by a clinical pharmacist , written educational material s , a brief follow-up visit , and feedback with recommendations . Group 2 received only a face-to-face presentation , given to departmental groups , as well as the same written educational material s used in group 1 . Controls received no intervention . Our primary outcome measure was the benzodiazepine " on/off " status of the elderly PPGP members . The secondary outcome measure was the median change ( preintervention minus postintervention ) in a st and ardized amount of benzodiazepines prescribed per physician . Logistic regression analysis failed to show a significant effect on postintervention benzodiazepine on/off status between study groups , when controlling for preintervention on/off status , PPGP-member age , PPGP-member gender , and all possible interactions . Analysis of variance failed to demonstrate an effect of either intervention on the median change in st and ardized amount of benzodiazepines prescribed per physician , with groups 1 , 2 , and controls yielding values of -278 ( range : -4,137 , 2,844 ) , -330 ( -1,531 , 1,358 ) , and -541 ( range : -3,716 , 2,185 ) , respectively . We conclude that strategies effective in changing physician prescribing behavior in other setting s may not be effective in a PPGP setting with benzodiazepines in the elderly as the target for change Background : Current underst and ing of implementation methods is limited , and research has focused on changing doctors ’ behaviors . Aim : Our aim was to evaluate the impact of audit and feedback and educational outreach in improving nursing practice and patient outcomes . Methods : Using a factorial design , cluster r and omized controlled trial , we evaluated 194 community nurses in 157 family practice s and 1078 patients with diagnosis of urinary incontinence ( UI ) for nurses compliance with evidence -linked review criteria for the assessment and management of UI and impact on psychologic and social well-being and symptoms . In the outreach arms , nurses ’ self-reported barriers informed development of tailored strategies . Results : In comparison with educational material s alone , the implementation methods tested did not improve care at 6 months follow-up . Moderate rates of improvement ( 10–17 % of patients ) in performance for the assessment of UI and greater rates of improvement ( 20–30 % of patients ) for the management of care were found but effects were similar across arms . Improvement in patient outcomes was more consistently positive for educational outreach than for audit and feedback but differences were not significant . Adjustment for caseload size , severity or duration of UI and patients ’ age did not alter results . Conclusions : Printed educational material s alone may be as effective as audit and feedback and educational outreach in improving nurses ’ performance and outcomes of care for people with UI . Greater underst and ing of the underlying processes in improving performance within multidisciplinary teams through further , theory-driven studies with “ no intervention ” control groups and longer follow-up are needed OBJECTIVE To evaluate a health maintenance organization (HMO)-sponsored intervention to improve cancer screening in private physician practice s serving low-income , minority population s. DESIGN A r and omized controlled trial with preintervention and postintervention measurements . Measurements were obtained by abstract ing information from independent r and om sample s of medical charts ( N = 2316 at preintervention and 2238 at postintervention ) . SETTING Forty-seven primary care physician practice s located in low-income and minority urban neighborhoods in Chicago , Ill. INTERVENTION Practice s were encouraged to adopt an office chart reminder system and to use a patient health maintenance card . Activities to facilitate the adoption of these items and for compliance with cancer screening guidelines included on-site training and start-up assistance visits , a physician continuing medical education seminar , and quality assurance visits with feedback to physicians . MAIN OUTCOME MEASURES The proportions of patients with a chart-documented mammogram , clinical breast examination , Papanicolaou smear , or fecal occult blood slide test in the 2 years before preintervention and postintervention chart abstract ions . RESULTS Between baseline and postintervention , there was a net increase in the proportion of HMO members in the intervention , compared with the control practice s , who received in the preceding 2 years a Papanicolaou smear ( 11.9 % ) and a fecal occult blood slide test ( 14.1 % ) . There was a net increase in the proportion of non-HMO patients in the intervention compared with the control practice s who received a clinical breast examination ( 15.3 % ) and a fecal occult blood slide test ( 20.2 % ) . CONCLUSIONS Implementation of an HMO-mediated , multicomponent intervention to improve cancer screening was feasible and effective for the Papanicolaou smear , fecal occult blood slide test , and the clinical breast examination , but not for mammography OBJECTIVE To determine the effect of continuing medical education ( CME ) with and without a quality assurance component ( CME+QA ) on physician practice s in the prevention of venous thromboembolism . METHODS A communitywide study was performed in 15 short-stay hospitals in central Massachusetts . The study population included 3158 patients in acute-care hospitals with multiple risk factors for venous thromboembolism . Study hospitals were r and omly assigned to one of two educational strategies or to a control group that received no intervention . RESULTS The proportion of patients at high risk for venous thromboembolism who received effective methods of prophylaxis increased significantly from 29 % in 1986 to 52 % in 1989 ( P < .001 ) . This increase was seen in all study groups : control hospitals , 40 % to 51 % ( P < .001 ) ; CME hospitals , 21 % to 49 % ( P < .0001 ) ; and CME+QA hospitals , 27 % to 55 % ( P < .0001 ) . The increase in prophylaxis use from 1986 to 1989 was significantly greater among patients cared for in hospitals whose physicians participated in a formal CME program ( an increase of 28 % ) than in control hospitals ( an increase of 11 % ) ( P < .001 ) . There was no significant difference in the use of prophylaxis in hospitals whose physicians received CME+QA interventions compared with hospitals whose physicians received CME interventions alone ( identical increases of 28 % ) . CONCLUSION A formal CME program significantly increased the frequency with which physicians prescribed prophylaxis for venous thromboembolism . We believe the key factor in our CME interventions that motivated clinicians to change their practice s was the provision of hospital-specific data demonstrating a compelling need for improvement . Despite the substantial investment by hospitals in QA , traditional QA intervention appeared to provide no additional benefit . Even after extensive CME/QA interventions , prophylaxis for venous thromboembolism remained underutilized , suggesting the need to develop new approaches to changing clinical practice BACKGROUND Implementation of evidence -based obstetrical practice s remains a significant challenge . Effective strategies to disseminate and implement such practice s are needed . METHODS We r and omly assigned 19 hospitals in Argentina and Uruguay to receive a multifaceted behavioral intervention ( including selection of opinion leaders , interactive workshops , training of manual skills , one-on-one academic detailing visits with hospital birth attendants , reminders , and feedback ) to develop and implement guidelines for the use of episiotomy and management of the third stage of labor or to receive no intervention . The primary outcomes were the rates of prophylactic use of oxytocin during the third stage of labor and of episiotomy . The main secondary outcomes were postpartum hemorrhage and birth attendants ' readiness to change their behavior with regard to episiotomies and management of the third stage of labor . The outcomes were measured at baseline , at the end of the 18-month intervention , and 12 months after the end of the intervention . RESULTS The rate of use of prophylactic oxytocin increased from 2.1 % at baseline to 83.6 % after the end of the intervention at hospitals that received the intervention and from 2.6 % to 12.3 % at control hospitals ( P=0.01 for the difference in changes ) . The rate of use of episiotomy decreased from 41.1 % to 29.9 % at hospitals receiving the intervention but remained stable at control hospitals , with preintervention and postintervention values of 43.5 % and 44.5 % , respectively ( P<0.001 for the difference in changes ) . The intervention was also associated with reductions in the rate of postpartum hemorrhage of 500 ml or more ( relative rate reduction , 45 % ; 95 % confidence interval [ CI ] , 9 to 71 ) and of 1000 ml or more ( relative rate reduction , 70 % ; 95 % CI , 16 to 78 ) . Birth attendants ' readiness to change also increased in the hospitals receiving the intervention . The effects on the use of episiotomy and prophylactic oxytocin were sustained 12 months after the end of the intervention . CONCLUSIONS A multifaceted behavioral intervention increased the prophylactic use of oxytocin during the third stage of labor and reduced the use of episiotomy . ( Clinical Trials.gov number , NCT00070720 [ Clinical Trials.gov ] ; Current Controlled Trials number , IS RCT N82417627 [ controlled-trials.com ] . ) OBJECTIVES Adherence to h and hygiene among healthcare workers ( HCWs ) is widely believed to be a key factor in reducing the spread of healthcare-associated infection . The objective of this study was to evaluate the impact of a multifaceted intervention to increase rates of adherence to h and hygiene among HCWs and to assess the effect on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus ( MRSA ) colonization . DESIGN Cluster-r and omized controlled trial . SETTING Thirty hospital units in 3 tertiary care hospitals in Hamilton , Ontario , Canada . INTERVENTION After a 3-month baseline period of data collection , 15 units were r and omly assigned to the intervention arm ( with performance feedback , small-group teaching seminars , and posters ) and 15 units to usual practice . H and hygiene was observed during r and omly selected 15-minute periods on each unit , and the incidence of MRSA colonization was measured using weekly surveillance specimens from June 2007 through May 2008 . RESULTS We found that 3,812 ( 48.2 % ) of 7,901 opportunities for h and hygiene in the intervention group result ed in adherence , compared with 3,205 ( 42.6 % ) of 7,526 opportunities in the control group ( P < .001 ; independent t test ) . There was no reduction in the incidence of hospital-acquired MRSA colonization in the intervention group . CONCLUSION Among HCWs in Ontario tertiary care hospitals , the rate of adherence to h and hygiene had a statistically significant increase of 6 % with a multifaceted intervention , but the incidence of MRSA colonization was not reduced Objective : To evaluate a multifaceted intervention involving intensive academic detailing for general practitioners ( GPs ) to improve recruitment of women for cervical screening OBJECTIVE To evaluate the effectiveness of a health insurance company-initiated intervention strategy aim ed at optimizing acid-suppressing drug ( ASD ) prescriptions in primary care . METHODS In a cluster r and omized controlled trial design , 112 primary care physician ( PCP ) peer review groups ( 993 PCPs ) in the central region of the Netherl and s were r and omized . The PCPs in the intervention group received an ASD prescription optimization protocol , a list of their patients taking ASDs frequently on a long-term basis , and financial compensation for additional consultations with these patients . The PCPs in the control group did not receive any of these interventions . Prescription data on 23 433 patients were extracted from the data base of the regional health insurance company . The main outcome measures were the proportion of patients who reduced ASD consumption by more than 50 % and changes in annual volume and costs of ASD prescriptions . Differences in ASD reduction and in volume were analyzed applying multilevel regression analyses . RESULTS At baseline , 2.4 % of the patients ( n = 967 506 ) of the participating practice s used ASDs frequently on a long-term basis ( > 180 daily defined doses [ DDDs ] annually ) . During the 6-month intervention , 14.1 % of the patients in the intervention group reduced ASD consumption compared with 13.7 % in the control group ( adjusted relative risk , 1.04 ; 95 % confidence interval [ CI ] , 0.97 - 1.11 ) . Changes in intervention and control group in mean volume of ASD prescription per patient were similar ( beta = 0.33 for DDD ; 95 % CI -3.00 to 3.60 ) . CONCLUSIONS A health insurance company-initiated multifaceted intervention , including practical tools and financial incentives , did not alter ASD prescription practice in primary care . More tailored interventions , including patient-targeted initiatives , are required to optimize ASD prescription OBJECTIVES The Omnibus Budget Reconciliation Act of 1990 requires that Medicaid Agencies perform drug utilization review ( DUR ) . The Texas Medicaid Agency , in cooperation with the Texas DUR Board , have chosen to mail intervention letters to physicians with patient profiles that indicate possible inappropriate use of medications . The objective of this study was to assess the effect of intervention letters indicating duplicative anti-ulcer medications . METHODS Analysis of Medicaid prescription cl aims produced 335 patient profiles involving concurrent therapy . Physicians for 174 patients were selected r and omly to receive an intervention letter , a response form , and a stamped envelope . The remaining patients served as a control group . RESULTS A 71.2 % response rate was obtained . Of these responses , 48.9 % agreed with the letter and 19.1 % disagreed with the letter . Profiles generated 6 months after the letters were sent indicated that 47.7 % of the patients in the experimental group were still on concurrent therapy compared with 64.4 % of patients in the control group ( P = 0.007 ) . CONCLUSIONS The high response rate to the letter , the moderately high agreement with the letters , and the statistically significant reduction of duplicative therapy in the experimental group indicate that intervention letters can be an effective way to change prescribing . Future research is needed to assess the effects of educational intervention letters for other drug categories , for other population s , and for longer periods of time ; and the effect these changes may have on true patient outcomes Inappropriate prescribing for ARI and diarrhoea is a serious health problem in many developing countries including Bangladesh . A baseline retrospective prescribing survey for ARI and diarrhoea have been conducted in r and omly selected 60 thana health complexes ( THCs ) of Dhaka division of Bangladesh . In the 38 of 60 THCs , the prescribers did not comply with the st and ard treatment guidelines ( STG ) for ARI . They are marked as ' unsatisfactory performers ' . In these THCs unnecessary antibiotics were prescribed in more than 50 % of the encounters . The study further revealed that in 26 THCs , comprising 41.6 % of the 38 THCs , the situation was even worse regarding the indiscriminate use of antibiotics . In these THCs antibiotics were prescribed in > or = 72 % of the encounters . For diarrhoea , only in 8.3 % of the THCs antibiotics were prescribed in > or = 50 % of the encounters . Encouragingly , most of the prescribers prescribed ORS . So the diarrhoea cases were dropped from the intervention . The 24 out of 26 worse performing THCs for ARI management , were grouped into three groups : Group-I ( implementing STG+ Audit ) , Group-II ( STG ) and Group-III ( no intervention , control ) . The prescribers of the THCs belonging to Group-I and Group-II received STG+Audit and STG only respectively as intervention(s ) . On the contrary , the prescribers of the THCs of Group-III ( control ) did not receive any intervention . It was observed that after the implementation of interventions the use of the unnecessary antibiotics to treat ARI was significantly reduced ( p<0.01 ) compared to pre-intervention period in Group-I ( STG+Audit ) . In this group highly significant ( p<0.000 ) reduction in antibiotics use was achieved in 6 out of 8 THCs . The average reduction in antibiotic use in terms of encounters was 23.7 and 15.2 % in the Group-I and Group-II respectively owing to the intervention(s ) . Significant reduction in antibiotic use in terms of THCs was 3 ( out of 8 THCs ) and 2 ( out of 8 THCs ) belonging to the Group-II and Group-III respectively . When compensated for the change in the control group , the reduction of antibiotic use in terms of encounters was 15.2 and 6.9 % in the THCs of the Group-I and Group-II respectively due to introduction of the interventions . The study concludes that STG supported by prescription audit are highly effective interventions to change the prescribing behaviour of the prescribers for ARI in the THCs PURPOSE To evaluate the effect of sustained clinical pharmacist interventions involving elderly out patients with polypharmacy and their primary physicians . PATIENTS AND METHODS R and omized , controlled trial of 208 patients aged 65 years or older with polypharmacy ( > or = 5 chronic medications ) from a general medicine clinic of a Veterans Affairs Medical Center . A clinical pharmacist met with intervention group patients during all scheduled visits to evaluate their drug regimens and make recommendations to them and their physicians . Outcome measures were prescribing appropriateness , health-related quality of life , adverse drug events , medication compliance and knowledge , number of medications , patient satisfaction , and physician receptivity . RESULTS Inappropriate prescribing scores declined significantly more in the intervention group than in the control group by 3 months ( decrease 24 % versus 6 % , respectively ; P = 0.0006 ) and was sustained at 12 months ( decrease 28 % versus 5 % , respectively ; P = 0.0002 ) . There was no difference between groups at closeout in health-related quality of life ( P = 0.99 ) . Fewer intervention than control patients ( 30.2 % ) versus 40.0 % ; P = 0.19 ) experienced adverse drug events . Measures for most other outcomes remained unchanged in both groups . Physicians were receptive to the intervention and enacted changes recommended by the clinical pharmacist more frequently than they enacted changes independently for control patients ( 55.1 % versus 19.8 % ; P < 0.001 ) . CONCLUSIONS This study demonstrates that a clinical pharmacist providing pharmaceutical care for elderly primary care patients can reduce inappropriate prescribing and possibly adverse drug effects without adversely affecting health-related quality of life Objective : To assess the differential effectiveness of two methods of disseminating a smoking cessation programme to public hospital antenatal clinics . Design : Group r and omised trial . Setting : 22 antenatal clinics in New South Wales , Australia . Intervention : Clinics were allocated to a simple dissemination ( SD ) condition ( 11 clinics ) which received a mail-out of programme re sources or to an intensive dissemination ( ID ) condition ( 11 clinics ) which included the mail-out plus feedback , training , and ongoing support with midwife facilitator . Main outcome measures : Independent cross sectional surveys of women on a second or subsequent visit undertaken pre-dissemination and 18 months after dissemination . Outcomes were : ( 1 ) levels of smoking status assessment by clinic staff ; ( 2 ) proportion of women identifying as having been smokers at their first visit who reported receiving cessation advice ; ( 3 ) proportion of these women who had quit ( self report and expired air carbon monoxide ( CO ) ) ; and ( 4 ) smoking prevalence among all women ( self report and CO ) . Subjects : 5849 women pre-dissemination ( 2374 SD , 3475 ID ) and weighted sample of 5145 women post-dissemination ( 2302 SD , 2843 ID ) . Results : There were no significant differences between the groups on change on any outcome . Change in either group was minimal . In the post-dissemination survey , the cessation proportions were 6.4 % ( SD ) and 10.5 % ( ID ) . Conclusions : Relatively modest strategies for encouraging incorporation of smoking cessation activities into antenatal care were not effective in the long term . Alternative strategies should be implemented and evaluated . The findings reinforce the importance of a whole population approach to tobacco control Objective : We evaluated the effect of performance feedback on acute ischemic stroke care quality in Minnesota hospitals . Methods : A cluster-r and omized controlled trial design with hospital as the unit of r and omization was used . Care quality was defined as adherence to 10 performance measures grouped into acute , in-hospital , and discharge care . Following preintervention data collection , all hospitals received a report on baseline care quality . Additionally , in experimental hospitals , clinical opinion leaders delivered customized feedback to care providers and study personnel worked with hospital administrators to implement changes targeting identified barriers to stroke care . Multilevel models examined experimental vs control , preintervention and postintervention performance changes and secular trends in performance . Results : Nineteen hospitals were r and omized with a total of 1,211 acute ischemic stroke cases preintervention and 1,094 cases postintervention . Secular trends were significant with improvement in both experimental and control hospitals for acute ( odds ratio = 2.7 , p = 0.007 ) and in-hospital ( odds ratio = 1.5 , p < 0.0001 ) care but not discharge care . There was no significant intervention effect for acute , in-hospital , or discharge care . Conclusion : There was no definite intervention effect : both experimental and control hospitals showed significant secular trends with performance improvement . Our results illustrate the potential fallacy of using historical controls for evaluating quality improvement interventions . Classification of evidence : This study provides Class II evidence that informing hospital leaders of compliance with ischemic stroke quality indicators followed by a structured quality improvement intervention did not significantly improve compliance more than informing hospital leaders of compliance with stroke quality indicators without a quality improvement intervention Despite recommendations for voluntary HIV screening , few medical centres have implemented screening programmes . The objective of the study was to determine whether an intervention with computer-based reminders and feedback would increase screening for HIV in a Department of Veterans Affairs ( VA ) health-care system . The design of the study was a r and omized controlled trial at five primary care clinics at the VA Palo Alto Health Care System . All primary care providers were eligible to participate in the study . The study intervention was computer-based reminders to either assess HIV risk behaviours or to offer HIV testing ; feedback on adherence to reminders was provided . The main outcome measure was the difference in HIV testing rates between intervention and control group providers . The control group providers tested 1.0 % ( n = 67 ) and 1.4 % ( n = 106 ) of patients in the preintervention and intervention period , respectively ; intervention providers tested 1.8 % ( n = 98 ) and 1.9 % ( n = 114 ) , respectively ( P = 0.75 ) . In our r and om sample of 753 untested patients , 204 ( 27 % ) had documented risk behaviours . Providers were more likely to adhere to reminders to test rather than with reminders to perform risk assessment ( 11 % versus 5 % , P < 0.01 ) . Sixty-one percent of providers felt that lack of time prevented risk assessment . In conclusion , in primary care clinics in our setting , HIV testing rates were low . Providers were unaware of the high rates of risky behaviour in their patient population and perceived important barriers to testing . Low-intensity clinical reminders and feedback did not increase rates of screening Background : Medical record audits have been used to provide physicians with feedback about their compliance with preventive health and disease management recommendations . Purpose : To determine if report cards summarizing medicine residents ' preventive health and disease management practice s can be used as a feedback tool to improve practice performance . Methods : R and omized , blinded , controlled study of 44 internal medicine residents using an individualized 78-item report card based on outpatient record audits . Results : Four hundred ninety-seven charts were retrospectively audited at baseline and 284 charts in follow-up . There were no significant differences in baseline performance between the residents in the intervention and control group . There were no differences in performance scores between residents receiving report cards and those who had not in immunizations , counseling , total preventive health , diabetes , hypertension , and total disease management . Conclusions : Intensive data -based feedback using report cards may not be a successful way to improve ambulatory performance of medical house officers BACKGROUND Laboratory services play an important part in screening , diagnosis , and management of patients within primary care . However , unnecessary use of laboratory tests is increasing . Our aim was to assess the effect of two interventions on the number of laboratory tests requested by primary -care physicians . METHODS We did a cluster r and omised controlled trial using a 2x2 factorial design , involving 85 primary -care practice s ( 370 family practitioners ) that request all laboratory tests from one regional centre . The interventions were quarterly feedback of practice requesting rates for nine laboratory tests , enhanced with educational messages , and brief educational reminder messages added to the test result reports for nine laboratory tests . The primary outcome was the number of targeted tests requested by primary -care practice s during the 12 months of the intervention . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N06490422 . FINDINGS Practice s that received either or both the enhanced feedback and the reminder messages were significantly less likely than the control group to request the targeted tests in total ( enhanced feedback odds ratio 0.87 , 95 % CI 0.81 - 0.94 ; reminder messages 0.89 , 0.83 - 0.93 ) . The effect of the interventions varied across the targeted tests individually , although the number of tests requested for both interventions was generally reduced . Neither intervention was consistently better than the other . INTERPRETATION Enhanced feedback of requesting rates and brief educational reminder messages , alone and in combination , are effective strategies for reducing test requesting in primary care . Both strategies are feasible within most laboratory setting OBJECTIVE in an academic family practice clinic , we performed a controlled trial of a multifaceted intervention versus usual care for managing diabetes . Providers received didactic training and computerized compliance feedback to support staged diabetes management , an evidence d-based approach to diabetes care . RESEARCH DESIGN AND METHODS one firm of the clinic practice received the intervention , the other served as the control group during a 14-month baseline period and a 14-month study period . HbA1(c ) was the principal outcome measure . RESULTS there was a significant 0.71 % difference in change in HbA1(c ) values between the intervention and control firms ( P=0.02 ) . The subgroup with the greatest improvement in HbA1(c ) was those subjects who started the intervention with a HbA1(c ) above 8 % . The overall improvement in glycemic control could not be explained by differences in visit frequency or the aggressiveness of drug therapy . There were no changes in healthcare utilization or costs between the two firms . CONCLUSION in an academic family practice clinic , a multifaceted intervention in support of diabetes treatment guidelines modestly improved glycemic control without incurring additional costs . The improvement was mostly due to mitigation of the natural deterioration in control usually seen . Further efforts are required to involve all patients in co-managing their diabetes BACKGROUND Quality improvement collaboratives are used to improve health care quality , but their efficacy remains controversial . OBJECTIVE To assess the effects of a quality improvement collaborative on preoperative antimicrobial prophylaxis . DESIGN Longitudinal cluster r and omized trial , with the quality improvement collaborative as the intervention . SETTING United States . PARTICIPANTS 44 acute care hospitals , each of which r and omly sample d approximately 100 selected surgical cases ( cardiac , hip or knee replacement , and hysterectomy ) at both the baseline and remeasurement phases . INTERVENTION All hospitals received a comparative feedback report . Hospitals r and omly assigned to the intervention group ( n = 22 ) participated in a quality improvement collaborative comprising 2 in-person meetings led by experts , monthly teleconferences , and receipt of supplemental material s over 9 months . MEASUREMENTS Change in the proportion of patients receiving at least 1 antibiotic dose within 60 minutes of surgery ( primary outcome ) and change in the proportions of patients given any antibiotics , given antibiotics for 24 hours or less , given an appropriate drug , and given a single preoperative dose and receipt of any of the 5 measures ( secondary outcome ) . RESULTS The groups did not differ in the change in proportion of patients who received a properly timed antimicrobial prophylaxis dose ( -3.8 percentage points [ 95 % CI , -13.9 to 6.2 percentage points ] ) after adjustment for region , hospital size , and surgery type . Similarly , the groups did not differ in individual measures of antibiotic duration ; use of appropriate drug ; receipt of a single preoperative dose ; or an all-or-none measure combining timing , duration , and selection . LIMITATIONS Hospitals volunteered for the effort , thereby result ing in selection for participants who were motivated to change . Implementation of the surgical infection prevention measure reporting requirements by the Centers for Medicare & Medicaid Services and The Joint Commission may have motivated improvement in prophylaxis performance . CONCLUSION At a time of heightened national attention toward measures of antimicrobial prophylaxis performance , the trial did not demonstrate a benefit of participation in a quality improvement collaborative over performance feedback for improvement of these measures BACKGROUND Although clinical trials have shown that proper management of diabetes can improve outcomes , and treatment guidelines are widespread , glycated hemoglobin ( HbA1c ) levels in the United States are rising . Since process measures are improving , poor glycemic control may reflect the failure of health care providers to intensify diabetes therapy when indicated-- clinical inertia . We asked whether interventions aim ed at health care provider behavior could overcome this barrier and improve glycemic control . METHODS In a 3-year trial , 345 internal medicine residents were r and omized to be controls or to receive computerized reminders providing patient-specific recommendations at each visit and /or feedback on performance every 2 weeks . When glucose levels exceeded 150 mg/dL ( 8.33 mmol/L ) during visits of 4038 patients , health care provider behavior was characterized as did nothing , did anything ( any intensification of therapy ) , or did enough ( if intensification met recommendations ) . RESULTS At baseline , residents did anything for 35 % of visits and did enough for 21 % of visits when changes in therapy were indicated , and there were no differences among intervention groups . During the trial , intensification increased most during the first year and then declined . However , intensification increased more in the feedback alone and feedback plus reminders groups than for reminders alone and control groups ( P<.001 ) . After 3 years , health care provider behavior in the reminders alone and control groups returned to baseline , whereas improvement with feedback alone and feedback plus reminders groups was sustained : 52 % did anything , and 30 % did enough ( P<.001 for both vs the reminders alone and control groups ) . Multivariable analysis showed that feedback on performance contributed independently to intensification and that intensification contributed independently to fall in HbA1c ( P<.001 for both ) . CONCLUSIONS Feedback on performance given to medical resident primary care providers improved provider behavior and lowered HbA1c levels . Similar approaches may aid health care provider behavior and improve diabetes outcomes in other primary care setting STUDY OBJECTIVE We evaluate the effectiveness of an educational program in hospital emergency departments ( EDs ) targeting reduction in antibiotic overuse for acute respiratory tract infections . METHODS Sixteen hospitals participated in the cluster r and omized trial , selecting a Veterans Administration ( VA ) and non-VA hospital within each of 8 metropolitan regions . Intervention sites received performance feedback , clinician education , and patient educational material s , including an interactive computer kiosk located in the waiting room . Medical records were review ed at each site during the baseline year 1 and intervention year 2 . The primary measure of effect was the percentage of visits for upper respiratory tract infections and acute bronchitis that were treated with antibiotics . Secondary outcomes , including return visits and visit satisfaction , were assessed by follow-up telephone interviews of patients . Alternating logistic regression models were used to adjust for baseline treatment rates , case mix differences , and provider characteristics . RESULTS The adjusted antibiotic prescription level for upper respiratory tract infection/acute bronchitis visits was 47 % for control sites and 52 % for intervention sites in year 1 . Antibiotic prescriptions at control sites increased by 0.5 % between year 1 and year 2 ( 95 % confidence interval -3 % to 5 % ) and at intervention sites decreased by 10 % ( 95 % confidence interval -18 % to -2 % ) . There were no significant differences between control and intervention sites in the proportions of upper respiratory tract infection/bronchitis patients with return ED visits or in overall visit satisfaction . CONCLUSION Multidimensional educational interventions can reduce antibiotic overuse in the treatment of patients with upper respiratory tract infections and acute bronchitis in EDs . However , substantial antibiotic overuse persists despite this educational intervention PURPOSE Colorectal cancer screening is the most underused cancer screening tool in the United States . The purpose of this study was to test whether a health care provider-directed intervention increased colorectal cancer screening rates . PATIENTS AND METHODS The study was a r and omized controlled trial conducted at two clinic firms at a Veterans Affairs Medical Center . The records of 5,711 patients were review ed ; 1,978 patients were eligible . Eligible patients were men aged 50 years and older who had no personal or family history of colorectal cancer or polyps , had not received colorectal cancer screening , and had at least one visit to the clinic during the study period . Health care providers in the intervention firm attended a workshop on colorectal cancer screening . Every 4 to 6 months , they attended quality improvement workshops where they received group screening rates , individualized confidential feedback , and training on improving communication with patients with limited literacy skills . Medical records were review ed for colorectal cancer screening recommendations and completion . Literacy level was assessed in a subset of patients . RESULTS Colorectal cancer screening was recommended for 76.0 % of patients in the intervention firm and for 69.4 % of controls ( P = .02 ) . Screening tests were completed by 41.3 % of patients in the intervention group versus 32.4 % of controls ( P = .003 ) . Among patients with health literacy skills less than ninth grade , screening was completed by 55.7 % of patients in the intervention group versus 30 % of controls ( P < .01 ) . CONCLUSION A provider-directed intervention with feedback on individual and firm-specific screening rates significantly increased both recommendations and colorectal cancer screening completion rates among veterans This paper evaluates whether externally design ed , evidence -based interventions for improving care for depression can be locally implemented in managed care organizations . The interventions were carried out as part of a r and omized trial involving forty-six practice s within six diverse , nonacademic managed care plans . Based on evaluation of adherence to the intervention protocol , we determined that local practice leaders are able to implement pre design ed interventions for improving depression care . Adherence rates for most key intervention activities were above 70 percent , and many were near 100 percent . Three intervention activities fell short of the goal of 70 percent implementation and should be targets for future improvement BACKGROUND Patients with end-stage renal disease ( ESRD ) are at high risk of complications from influenza , but many dialysis centers report < 50 % influenza immunization coverage . STUDY DESIGN A group-r and omized evaluation of a multicomponent intervention to increase influenza vaccination rates in poorly performing dialysis centers in ESRD Networks 6 , 11 , and 15 . SETTING & PARTICIPANTS Facilities with the lowest immunization percentages in 2006 - 2007 were selected from each network and r and omly assigned to a st and ard ( n = 39 ) or intensive intervention ( n = 38 ) . INTERVENTION St and ard intervention included a feedback report with comparison to other centers in their network and educational material s for staff and patients . Intensive-intervention centers also received 3 educational seminars , assistance with and review of center-specific action plans , and monthly monitoring of vaccination plan and rates . OUTCOMES Change in vaccination rate in following year . MEASUREMENTS Dialysis center records of patient vaccination status . RESULTS There was an 8.9 % ( P = 0.04 ) adjusted mean absolute difference in improvement between intensive- and st and ard-intervention centers . LIMITATIONS Some vaccinations were self-reported by patients . The vaccination data form does not have an option for patient data unavailable , which may have caused patients without data to be coded as unvaccinated . CONCLUSIONS Multicomponent interventions may serve as a successful strategy to increase influenza vaccination rates at poorly performing centers , with a benefit beyond that provided by usual oversight and support Abstract Objective . To evaluate the effects of postal feedback with clinical ly relevant data on general practitioners ' prescribing compared with feedback with aggregate data on prescribing patterns of asthma drugs . Methods . The study was a r and omised , controlled trial . The general practitioners ( GPs ) in the County of Funen , Denmark ( 292 GPs representing 178 practice s ) were r and omised to one of three groups receiving different forms of prescriber feedback . The first group received detailed and clinical ly relevant data on asthma drug prescribing patterns and a guideline statement . These data included tables with counts of asthma patients following classification of each individual 's consumption of inhaled β2-agonists and use of inhaled steroids . The second group received aggregate data on asthma drug prescribing patterns and a guideline statement , and the third group received feedback on an unrelated subject and served as control for the other groups . Each GP received prescriber feedback three times within a 6-month period . The last two letters with prescriber feedback had up date d information with the purpose of showing changes in prescribing patterns . Effects were followed for a period of 1 year . The main outcome measures were change in fraction of asthmatics treated with inhaled steroids and incidence rate of treatment with inhaled steroids . Results . The three groups had similar baseline characteristics . None of the two types of feedback on prescribing of asthma drugs had a statistically significant impact on GPs ' prescribing patterns . Conclusion . Mailed prescriber feedback of detailed and clinical ly relevant data with a guideline statement , without revealing patient identities , has little or no impact on prescribing patterns BACKGROUND Despite national priorities in cancer control , the number of people with established ongoing medical care who do not receive indicated preventive services is substantial . Proven strategies to optimize preventive care in community practice are limited . METHODS In the Cancer Prevention in Community Practice Project ( CPCP ) , 50 primary care providers were r and omly assigned to receive an " office system " intervention . The intervention led to reorganization of office operations based on four functional core components : identifying patients ' needs for services ; monitoring their status over time ; providing positive reinforcement to patients ; and establishing an internal feedback component consisting of a brief audit to assess how the system is operating . Implementation of the CPCP system in each practice was accomplished using trained facilitators , and involved incorporating one or more tools developed to meet the functional components of the practice . RESULTS One hundred percent of the practice s were successful in implementing some changes in their office operations that met CPCP office system functional criteria . All study practice s implemented customized flow sheets , while use of other office system tools were incorporated at between 32 % to 75 % of study sites . Identifying patients in need of preventive services was performed most often by the clinical staff ( 39 % ) , whereas monitoring patients ' receipt of preventive services over time and reinforcing positive patient behavior were performed most often by physicians ( 63 % and 46 % , respectively ) . Changes made in practice s were maintained for at least 12 months . CONCLUSIONS Primary care practice s in community setting s can implement significant and lasting changes in their practice environment that will improve their performance of preventive activities . The functional components of the CPCP office system design proposed and tested here are applicable to a wide variety of practice setting BACKGROUND Effective therapies exist for reducing mortality in persons with coronary heart disease ( CHD ) , but they remain underused . OBJECTIVE To report the design and baseline results of a quality improvement project design ed to increase the use of hydroxymethyl glutaryl coenzyme A ( HMG-CoA ) reductase inhibitors , beta-adrenergic blocking agents , and angiotensin-converting enzyme ( ACE ) inhibitors in patients with CHD in a network-model managed care setting . METHODS Patients with CHD were identified by search ing a cl aims data base . Use of therapies was assessed by linkage with a pharmacy benefits data base . A survey was mailed to primary care physicians to collect information related to attitudes and behavioral intentions regarding aggressive management of CHD . An intervention , consisting of a guideline summary , performance feedback , and medical chart reminders , was evaluated in a r and omized , practice -based trial . RESULTS Among 1189 patients with CHD , the median prevalence of receipt of HMG-CoA reductase inhibitors , beta-adrenergic blocking agents , and ACE inhibitors across practice s at baseline ( the first 3 months of 1999 ) was 50.0 % , 35.0 % , and 18.8 % , respectively . Reported barriers included a perception that aggressive management of CHD is thought to be unimportant by support staff yet to require significant staff time . Aggressive management of CHD was perceived to incur non-reimbursable costs , to be unimportant in their patient population , to require a great deal of patient education and self-management , and to be limited because many patients do not adhere to therapy . CONCLUSIONS Opportunities exist for enhancing the quality of care provided to patients with CHD . Our experience to date supports the logistical feasibility of implementing network-level quality enhancement efforts in managed care networks To examine the effects of intensive patient and /or physician diabetes education on patient health outcomes , a controlled trial was conducted in which internal medicine residents and their 532 diabetic patients were r and omly assigned to : routine care ; patient education ; physician education ; or both patient and physician education . Patient outcome data were analyzed either by analysis of covariance on post intervention values ( 2-hour post-pr and ial plasma glucose [ PPG ] ; body weight [ BW ] ; blood pressure [ BP ] ; or analysis of variance conducted on change values ( fasting plasma glucose [ FPG ] and glycosylated hemoglobin [ A1Hgb ] ) . After patient education , significant improvements were observed in FPG , A1Hgb , BW , and systolic and diastolic BP . Physician education result ed in significant decreases in FPG , A1Hgb and BW . The combination of patient plus physician education result ed in the greatest improvements in patients ' health outcomes including FPG , A1Hgb , PPG , BW and diastolic BP . Adjusted systolic BPs were not significantly different in the two groups . While these physiologic improvements were statistically and probably clinical ly significant , hyperglycemia and obesity still persisted . Thus , achieving optimal patient outcomes for a chronic disease like diabetes mellitus may require a greater or more effective use of re sources than currently estimated Introduction : Formal didactic continuing medical education ( CME ) is relatively ineffective for changing physician behaviur . Diabetes mellitus is an increasingly prevalent disease , and interventions to improve adherence to clinical practice guidelines ( CPGs ) are needed . Methods : A stratified , cluster‐r and omized , controlled trial design was used to evaluate the effects of a teleconferenced educational detailing ( TED ) CME on glycemic control ( hemoglobin [ Hb ] A1c ) and family physician adherence to national diabetes guidelines . TED employed sequential , small‐group , case‐based education using CPGs delivered by a diabetes specialist . Medical record audit data from baseline through the end of a 12‐month postintervention period were compared for the control and intervention groups . Satisfaction with the intervention was evaluated . Results : Sixty‐one physicians provided 660 medical records . The intervention did not affect mean Hb A1c levels but did significantly ( p = .04 ) alter the distribution of patients by category of glycemic control , with fewer in the intervention group in inadequate control ( 15.8 % versus 23.9 % ) . More patients took insulin ( alone or with oral agents ) in the intervention group ( 21.2 % versus 12.0 % , p = .03 ) , and more took oral agents only in the control group ( 89.0 % versus 82.9 % , p = .005 ) . More patients in the intervention group had documentation of body mass index ( 7.8 % versus 1.9 % , p < .02 ) , eye exam ( 12.1 % versus 5.1 % , p = .02 ) , and treatment plan ( 43.5 % versus 23.6 % , p = .01 ) and used a flow sheet ( 14.6 % versus 7.7 % , p < .03 ) . Although there was general satisfaction with the teleconferencing format , specialist educators found the format more challenging than the family physicians . Discussion : CME delivered by teleconference was feasible , well attended , well received by participants , and improved some key diabetes management practice s and outcomes CONTEXT Publicly released report cards on hospital performance are increasingly common , but whether they are an effective method for improving quality of care remains uncertain . OBJECTIVE To evaluate whether the public release of data on cardiac quality indicators effectively stimulates hospitals to undertake quality improvement activities that improve health care processes and patient outcomes . DESIGN , SETTING , AND PATIENTS Population -based cluster r and omized trial ( Enhanced Feedback for Effective Cardiac Treatment [ EFFECT ] ) of 86 hospital corporations in Ontario , Canada , with patients admitted for acute myocardial infa rct ion ( AMI ) or congestive heart failure ( CHF ) . INTERVENTION Participating hospital corporations were r and omized to early ( January 2004 ) or delayed ( September 2005 ) feedback of a public report card on their baseline performance ( between April 1999 and March 2001 ) on a set of 12 process-of-care indicators for AMI and 6 for CHF . Follow-up performance data ( between April 2004 and March 2005 ) also were collected . MAIN OUTCOME MEASURES The co primary outcomes were composite AMI and CHF indicators based on 12 AMI and 6 CHF process-of-care indicators . Secondary outcomes were the individual process-of-care indicators , a hospital report card impact survey , and all-cause AMI and CHF mortality . RESULTS The publication of the early feedback hospital report card did not result in a significant systemwide improvement in the early feedback group in either the composite AMI process-of-care indicator ( absolute change , 1.5 % ; 95 % confidence interval [ CI ] , -2.2 % to 5.1 % ; P = .43 ) or the composite CHF process-of-care indicator ( absolute change , 0.6 % ; 95 % CI , -4.5 % to 5.7 % ; P = .81 ) . During the follow-up period , the mean 30-day AMI mortality rates were 2.5 % lower ( 95 % CI , 0.1 % to 4.9 % ; P = .045 ) in the early feedback group compared with the delayed feedback group . The hospital mortality rates for CHF were not significantly different . CONCLUSION Public release of hospital-specific quality indicators did not significantly improve composite process-of-care indicators for AMI or CHF . TRIAL REGISTRATION http:// clinical trials.gov Identifier : NCT00187460 In the international Drug Education Project , a new educational program for peer groups of doctors was developed and tested to improve the treatment of asthma patients in The Netherl and s , Norway , Sweden , and Slovakia . Individualized feedback on prescribing and the underlying decision strategy was presented and discussed within the group of doctors , in relation to existing guidelines . In a parallel , r and omized controlled design the effect on competence and actual prescribing was tested . Results were related to national guidelines . In general , the program improved the doctors ' attitudes as well as some of their prescribing behavior . The proportion of patients treated with inhaled corticosteroids significantly improved in The Netherl and s ( effect size 1.27 ) , and the proportion of oral corticosteroid use for exacerbation treatment increased both in The Netherl and s and in Norway ( effect sizes 1.99 and 0.87 , respectively ) . Overall attitudes of Dutch and Norwegian doctors also improved significantly ( effect sizes 1.06 and 0.87 , respectively ) , as did both knowledge ( effect size 1.06 ) and attitudes ( effect size 1.49 ) concerning exacerbation treatment in Slovakia . In Sweden no significant improvements could be measured . Conclusively , improvements in asthma treatment are possible with an educational program based on self-learning in small peer groups , although effects in one health care setting may not occur in another health care setting . Possible explaining factors may be different attitudes to and experiences with guidelines as well as with continuing medical education programs , and differences in the opportunities for change , including prevailing trends in prescribing behavior Introduction The medical literature describes disparity in colonoscopy performance . This r and omised , controlled study aim ed to characterise the impact of feedback on colonoscopy performance among gastroenterology ( GI ) trainees . Methods Gastroenterology trainees of similar experience levels who independently performed 581 colonoscopies over the study period were r and omised to receive feedback/no feedback on their colonoscopy performance . Results Baseline colonoscopy performance was similar in both groups . Following feedback , caecal intubation improved by 10.5 % ( from 72.9 to 83.4 % , p = 0.04 ) in the feedback group and declined by 6.1 % ( from 78 to 71.9 % , p = 0.2 ) in the control group ; polyp detection improved by 5.1 % ( from 12.9 to 18.0 % , p = 0.2 ) in the feedback group and by 2.9 % ( from 16.7 to 19.6 % , p = 0.5 ) in the control group . Conclusions Systematic feedback appears to enhance colonoscopy performance among GI trainees Background : Following surgery for rectal cancer , two unfortunate outcomes for patients are permanent colostomy and local recurrence of cancer . We tested whether a quality -improvement strategy to change surgical practice would improve these outcomes . Methods : Sixteen hospitals were cluster-r and omized to the intervention ( Quality Initiative in Rectal Cancer strategy ) or control ( normal practice ) arm . Consecutive patients with primary rectal cancer were accrued from May 2002 to December 2004 . Surgeons at hospitals in the intervention arm could voluntarily participate by attending workshops , using opinion leaders , inviting a study team surgeon to demonstrate optimal techniques of total mesorectal excision , completing postoperative question naires , and receiving audits and feedback . Main outcome measures were hospital rates of permanent colostomy and local recurrence of cancer . Results : A total of 56 surgeons ( n = 558 patients ) participated in the intervention arm and 49 surgeons ( n = 457 patients ) in the control arm . The median follow-up of patients was 3.6 years . In the intervention arm , 70 % of surgeons participated in workshops , 70 % in intraoperative demonstrations and 71 % in postoperative question naires . Surgeons who had an intraoperative demonstration provided care to 86 % of the patients in the intervention arm . The rates of permanent colostomy were 39 % in the intervention arm and 41 % in the control arm ( odds ratio [ OR ] 0.97 , 95 % confidence interval [ CI ] 0.63–1.48 ) . The rates of local recurrence were 7 % in the intervention arm and 6 % in the control arm ( OR 1.06 , 95 % CI 0.68–1.64 ) . Interpretation : Despite good participation by surgeons , the re source -intense quality -improvement strategy did not reduce hospital rates of permanent colostomy or local recurrence compared with usual practice . ( Clinical Trials.gov trial register no. NCT00182130 . A prospect i ve study employing a r and omly assigned control group was conducted to assess the usefulness of a chart audit in teaching paediatric residents the components of well child care . The charts of children less than 5 years of age were review ed and compared with audit criteria . Per cent compliance scores were calculated for five categories : present history ; behaviour-development ; family history ; past medical history ; and physical assessment . Five separate audits ( 10 charts per resident per audit ) were conducted -- two prior to giving the residents feedback , one after informing them that a study was being conducted , once a month after giving feedback , and one a year later . There was no significant difference between the baseline scores of the two groups . In addition , there were no significant changes in the experimental group 's scores during the first three audits or the control group 's scores over the whole 3-year course of the study . However , one month after receiving feedback , the scores of the experimental group improved significantly in present history , behaviour-development , and past history . One year later , the experimental group 's scores were lower in every category than in the preceding audit . However , their scores were higher than the control group and the difference reached statistical significance in present history . We conclude that regular chart audits with feedback are a valuable addition to the primary care curriculum in a paediatric residency programme OBJECTIVE To compare computer-based with manual health maintenance tracking systems to determine whether ( 1 ) a computer-based system will result in better provider compliance with the practice health maintenance protocol , ( 2 ) the incremental cost of operating a computer-based vs a manual health maintenance tracking system differs , and ( 3 ) inactive patients will respond to health maintenance reminders . DESIGN Two-year prospect i ve , r and omized , controlled trial . SETTING Rural , multiple-office , nonprofit , fee-for-service family practice . PATIENTS Adult members of families in which at least one member had been seen by the practice within the past 2 years . INTERVENTION A computer-based health maintenance tracking system that generated annual provider and patient reminders for all patients regardless of appointment status compared with a manual flowchart-based tracking system in which patient reminders were triggered by provider request . OUTCOME MEASURES Provider compliance with the health maintenance protocol determined by preintervention and postintervention chart audits , costs of computer-based tracking , and response of inactive patients to health maintenance reminders . RESULTS Overall provider compliance with the health maintenance protocol increased 15 percentage points in the computer-based tracking group and four percentage points in the manual group . The computer-based tracking group had significantly higher provider compliance than the manual group for eight of 11 procedures . The computer-based tracking system cost 78 cents per patient per year to operate . It was not associated with increased office visits or patient billings . CONCLUSIONS Computer-based health maintenance tracking improved provider health maintenance compliance compared with a manual system . The finding that health maintenance compliance improved without a significant increase in patient visits or billings requires confirmation in other setting s but suggests that considerable health maintenance can be incorporated into ongoing patient care Education is an effective tool for modifying physician use of the laboratory . We compared two interventions by assigning 56 medical house officers into four groups : control group ; feedback group , which received feedback concerning its use of tests ; manual group , which received a manual concerning cost-effective laboratory use ; and manual plus feedback group , which received both interventions . All intervention groups experienced significant decreases in test use . When we controlled for diagnosis , the manual plus feedback group had the most profound decrease ( 42 % ) in laboratory use , followed by the manual group . The feedback and control groups had no change . Attitudes and knowledge did not change . We conclude that one can , via simple techniques , modify house staff use of the outpatient laboratory . The less-expensive intervention was a cost-oriented manual , which may have a " sensitizing " rather than educational effect OBJECTIVES To assess the appropriateness of red blood cell ( RBC ) transfusions and the effectiveness of an intervention to reduce inappropriate RBC transfusions . DESIGN Medical record audit by hospital staff using a data form , before and after r and omly allocated interventions ( letter only or letter+visit ) . Criteria for assessing appropriateness of RBC transfusions were based on a systematic literature review . SETTING Ten major urban hospitals in Sydney , New South Wales , in 1998 and 1999 . SUBJECTS Medical records of up to 120 patients at each hospital ( n=1117 ) . INTERVENTIONS Letter-only ( 5 hospitals)-- results of first audit at the hospital mailed to chief executive officer of that hospital ; letter+visit ( 5 hospitals ) results of first audit at the hospital presented by the research team to a meeting of that hospital 's staff , and then mailed to the chief executive officer . MAIN OUTCOME MEASURE Proportion of RBC transfusions assessed as inappropriate . RESULTS At first audit , 35 % of RBC transfusions were assessed as inappropriate . Small reductions in inappropriate transfusions were found at the second audit , but the change was significant only for the hospitals receiving the letter-only intervention . About 5 % of patients received a single RBC unit ; 40 % of single-unit transfusions were inappropriate . More RBC transfusions were inappropriate in surgical patients than in those treated by other specialties . CONCLUSIONS About a third of RBC transfusions were assessed as inappropriate . The interventions had only a small effect on transfusion appropriateness This prospect i ve , r and omized , controlled trial , based in a Veterans Administration Hospital general medicine clinic , compared the cost effectiveness of two behaviorally oriented interventions design ed to reduce physicians ' drug prescribing costs . Clinical pharmacists visited one group of 11 physicians during weekly clinic sessions to counterdetail the prescribing of certain targeted drugs . A second group of 10 physicians were given data each week comparing their individual prescribing costs to those of their colleagues ( peer-comparison feedback ) . A control group of 10 physicians received neither intervention . Written patient-specific suggestions for cost-effective prescribing were employed in both intervention groups . Baseline prescribing costs were monitored through the hospital 's computer during a three-month , preintervention period and a seven-month intervention period . The 2026 written suggestions made by the doctors of pharmacy result ed in 613 ( 30.3 percent ) prescribing changes , including deletion , substitution , or change in dosage of targeted drugs . There were no intergroup differences in the response to written suggestions . However , the group receiving face-to-face visits from the clinical pharmacists achieved lower average prescription costs than the control group during seven of eight months . Intergroup differences were statistically significant ( p < 0.05 ) during three of the last five months of the study . The face-to-face meeting intervention was cost-effective , saving $ 478 per physician over seven months after accounting for Pharm . D. salary costs . There was no significant decrease in the number of prescriptions written by the face-to-face group compared with the control group , suggesting that drug substitution rather than deletion was the method used by physicians to lower drug costs . No savings result ed from the use of peer-comparison feedback . We conclude that personal visits by a Pharm . D. are a cost-effective technique for reducing physicians ' prescribing costs , and are superior to peer-comparison feedback Physicians endorse prevention but provide only low levels of screening , health counseling , and immunization . Between 1981 and 1986 , a r and omized controlled trial was conducted at the Seattle ( Wash ) Veterans Affairs Medical Center to assess the effectiveness of the following three methods of delivery of preventive services : ( 1 ) a physician-oriented model that includes education and motivation , a chart flowsheet listing recommended activities , and periodic feedback about performance ; ( 2 ) a patient education model in which patients were mailed an informative brochure advising them to ask physicians for preventive services as depicted in a patient-held pocket guide ; and ( 3 ) a health promotion clinic that patients were invited to attend . A control group received their usual care . A total of 1224 male out patients were enrolled in the trial . Baseline prevention rates for 12 age-specific prevention activities were below 25 % . Neither the control group rates during the 5-year trial nor the rates for the two educational models , either singly or as a combined intervention , changed . Only the health promotion clinic model was effective , tripling prevention rates in its first year and sustaining these levels for all 5 years . It is difficult to change the clinic roles of experienced physicians and their long-term patients in a specialized multiclinic setting . Providing a separate health promotion clinic option is popular with patients , bypasses gatekeeper barriers , is reasonable in cost , and warrants wider application PURPOSE Because limited audit/feedback of health status information has yielded mixed results , we evaluated the effects of a sustained program of audit/feedback on patient health and satisfaction . METHODS We conducted a group-r and omized effectiveness trial in which firms within Veterans Administration general internal medicine clinics served as units of r and omization , intervention , and analysis . Respondents to a baseline health inventory were regularly mailed the 36-Item Short Form ( SF-36 ) and , as relevant , question naires about six chronic conditions ( ischemic heart disease , diabetes , chronic obstructive pulmonary disease , depression , alcohol use , and hypertension ) and satisfaction with care . Data were reported to primary providers at individual patient visits and in aggregate during a 2-year period . RESULTS Baseline forms were mailed to 34,050 patients ; of the 22,413 respondents , 15,346 completed and returned follow-up surveys . Over the 2-year study , the difference between intervention and control groups ( as measured by difference in average slope ) was -0.26 ( 95 % confidence interval [ CI ] : -0.79 to 0.27 ; P=0.28 ) for the SF-36 Physical Component Summary score and -0.53 ( 95 % CI : -1.09 to 0.03 ; P=0.06 ) for the SF-36 Mental Component Summary score . No significant differences emerged after adjusting for deaths . There were no significant differences in condition-specific measures or satisfaction between groups after adjustment for provider type , panel size , and number of intervention visits , or after analysis of patients who completed all forms . CONCLUSION An elaborate , sustained audit/feedback program of general and condition-specific measures of health/satisfaction did not improve outcomes . To be effective , such data probably should be incorporated into a comprehensive chronic disease management program BACKGROUND Interventions to promote prescribing of preventive therapies in patients with cardiovascular disease ( CVD ) or diabetes have reported variable success . OBJECTIVE ( i ) To evaluate the effect of prescribing feedback on GP practice using academic detailing compared to postal bulletin on prescribing of CVD preventive therapies in patients with CVD or diabetes at 3 and 6 months post intervention and ( ii ) to evaluate the intervention from a GP 's perspective . METHODS Volunteer GP practice s ( n = 98 ) were r and omized to receive individualized prescribing feedback via academic detailing ( postal bulletin plus outreach visit ) ( n = 48 ) or postal bulletin ( n = 50 ) . The proportion of CVD or diabetic patients on statins and antiplatelet agents/warfarin pre- and post-intervention was calculated for each GP practice . Multivariate regression with a r and om effects model was used to compare differences between the groups adjusting for GP clustering and confounding factors . beta-Coefficients and 95 % confidence intervals ( CIs ) are presented . RESULTS There was a 3 % increase in statin prescribing in CVD patients at 6 months post-intervention for both r and omized groups , but there was no statistical difference between the groups ( beta = 0.004 ; 95 % CI = -0.01 to 0.02 ) . Statin and antiplatelet/warfarin prescribing also increased in the diabetic population ; there was no significant differences between the groups . GPs participating in the project expressed a high level of satisfaction with both interventions . CONCLUSION Prescribing of preventive therapies increased in both r and omized groups over the study period . But academic detailing did not have an additional effect on changing prescribing over the postal bulletin alone End-stage renal disease ( ESRD ) Networks are quality improvement organizations that collect , analyze , and report information to clinicians and allied health providers about discrepancies between observed patterns of care of ESRD patients and what has been recommended by clinical practice guidelines . The Networks facilitate response to this information by assisting ESRD treatment centers to develop quality improvement programs to redress inadequate care . The authors evaluated this process of quality improvement by selecting 42 treatment centers in a single ESRD Network with the lowest facility-specific mean urea reduction ratio ( URR ) . The treatment centers were r and omly assigned to two intervention strategies : ( 1 ) feedback alone ; ( 2 ) an intensive intervention that included feedback , workshops , distribution of educational material s and clinical practice guidelines , technical assistance with the development of quality improvement plans , and continued monitoring . The intensive intervention had greater improvement in the increased proportions of patients dialyzed with prescribed blood flow ( P = 0.02 ) and documented review of prescription ( P = 0.01 ) . Furthermore , the mean center URR increased nearly 3 % among intensive intervention centers ( from 68.1 to 70.9 ) but only 0.09 % among the feedback centers ( 68.2 to 69.1 ) ( P = 0.002 ) . Similarly , time on dialysis increased 7.5 min on average among patients in intervention centers but decreased 2 min for patients in comparison centers ( P = 0.03 ) . These results demonstrate that Network feedback , coupled with the intensive intervention , result ed in improvement in care that would otherwise not have occurred Background . It has not been demonstrated that the implementation of computerized quality improvement strategies can improve client-centered outcomes in public community based , long-term care ( CBLTC ) programs . Objectives . To test and evaluate 2 innovative computer-assisted , client-centered quality improvement strategies for public community-based , long-term care . The first strategy , the Normative Treatment Planning ( NTP ) program , assesses needs , prescribes services , and evaluates outcomes . The second strategy , the Client Feedback System ( CFS ) program , provides service vendors with feedback on client perceptions of services . Research Design . A 2 × 2 factorial design with the 2 strategies using cluster r and omization . Subjects . A total of 2222 clients ( 86 % of eligible program clients ) enrolled in Indiana ’s state case management program and /or the Medicaid home and community-based services waiver program for the aged and disabled as of January 1 , 1995 . Measures . Outcomes of needs met and client satisfaction were measured through telephone surveys every 6 months for 2 years . Results . A total of 1006 participants ( 45 % ) completed the 2-year evaluation study . For the group using only the NTP program , perception of needs met and client satisfaction were significantly better than the control group over the 2 years . During this period , the group using only the CFS program had significantly better client satisfaction than the control group . However , the effect sizes of the significant differences were small , and no statistically significant effects were found for the group using both programs . Conclusions . Client-centered quality improvement strategies can be implemented to enable public CBLTC programs to meet client needs better and increase client satisfaction The federally-m and ated nursing home survey and certification process has been criticized for focusing more on the potential of each facility to provide good care than on the demonstrated quality of care delivered or on result ant resident outcomes . This paper presents the results of an evaluation of the pilot of a new federal survey process ( Patient Care and Services , PaCS ) that concentrates surveyor time on the review of resident care , reduces surveyor time spent review ing policy and procedures , and , for the first time , m and ates personal interviews with a sample of facility residents . In Rhode Isl and , a r and omized control design was used to evaluate the impact of the survey on both the number and type of deficiencies cited , as well as on resident outcomes at six month follow-up . The PaCS team cited significantly more deficiencies , in total , than the traditional survey team , and significantly more patient-oriented deficiencies . However , no significant differences in resident outcomes were found when comparing nursing homes in which PaCS was administered and nursing homes in which only the traditional survey was administered BACKGROUND This 1-year r and omized trial tested the efficacy of behavioral techniques for increasing mammography referrals by primary care physicians in small , community practice s. METHODS Sixty-one practice s were r and omly assigned to one of three conditions : ( 1 ) education-only control , ( 2 ) education plus cue enhancement using mammography chart stickers , and ( 3 ) education plus cue enhancement plus feedback and token rewards . Quarterly chart audits of a defined sample ( N = 11,716 ) of women patients 50 years of age or older were conducted to document mammography referrals , completions , and compliance . RESULTS Referral and completion rates increased from baseline to first quarter and gradually declined thereafter . Overall , these rates were higher in the cuing conditions than in the control condition . In contrast , compliance rates in both experimental conditions increased over the year while remaining static in the control condition , demonstrating a strong and continuing effect for cue enhancement . Compliance increases were greatest for physicians who were older , nonwhite , with a second speciality , in solo practice , not members of the AMA , not residency trained , and not board certified . CONCLUSIONS Chart stickers can significantly increase mammography utilization in small , community practice s. These practice s are an efficient route to reaching large numbers of older women in need of mammography screening CONTEXT The effectiveness of recruiting local medical opinion leaders to improve quality of care is poorly understood . OBJECTIVE To evaluate a guideline -implementation intervention of clinician education by local opinion leaders and performance feedback to ( 1 ) increase use of lifesaving drugs ( aspirin and thrombolytics in eligible elderly patients , beta-blockers in all eligible patients ) for acute myocardial infa rct ion ( AMI ) , and ( 2 ) decrease use of a potentially harmful therapy ( prophylactic lidocaine ) . DESIGN R and omized controlled trial with hospital as the unit of r and omization , intervention , and analysis . SETTING Thirty-seven community hospitals in Minnesota . PATIENTS All patients with AMI admitted to study hospitals over 10 months before ( 1992 - 1993 , N=2409 ) or after ( 1995 - 1996 , N=2938 ) the intervention . INTERVENTION Using a vali date d survey , we identified opinion leaders at 20 experimental hospitals who influenced peers through small and large group discussion s , informal consultations , and revisions of protocol s and clinical pathways . They focused on ( 1 ) evidence ( drug efficacy ) , ( 2 ) comparative performance , and ( 3 ) barriers to change . Control hospitals received mailed performance feedback . MAIN OUTCOME MEASURES Hospital-specific changes before and after the intervention in the proportion of eligible patients receiving each study drug . RESULTS Among experimental hospitals , the median change in the proportion of eligible elderly patients receiving aspirin was + 0.13 ( 17 % increase from 0.77 at baseline ) , compared with a change of -0.03 at control hospitals ( P=.04 ) . For beta-blockers , the respective changes were + 0.31 ( 63 % increase from 0.49 at baseline ) vs + 0.18 ( 30 % increase from baseline ) for controls ( P=.02 ) . Lidocaine use declined by about 50 % in both groups . The intervention did not increase thrombolysis in the elderly ( from 0.73 at baseline ) , but nearly two thirds of eligible nonrecipients were older than 85 years , had severe comorbidities , or presented after at least 6 hours . CONCLUSIONS Working with opinion leaders and providing performance feedback can accelerate adoption of some beneficial AMI therapies ( eg , aspirin , beta-blockers ) . Secular changes in knowledge and hospital protocol s may extinguish out date d practice s ( eg , prophylactic lidocaine ) . However , it is more difficult to increase use of effective but riskier treatments ( eg , thrombolysis ) for frail elderly patients OBJECTIVES To improve end-of-life decision making and reduce the frequency of a mechanically supported , painful , and prolonged process of dying . DESIGN A 2-year prospect i ve observational study ( phase I ) with 4301 patients followed by a 2-year controlled clinical trial ( phase II ) with 4804 patients and their physicians r and omized by specialty group to the intervention group ( n = 2652 ) or control group ( n = 2152 ) . SETTING Five teaching hospitals in the United States . PATIENTS A total of 9105 adults hospitalized with one or more of nine life-threatening diagnoses ; an overall 6-month mortality rate of 47 % . INTERVENTION Physicians in the intervention group received estimates of the likelihood of 6-month survival for every day up to 6 months , outcomes of cardiopulmonary resuscitation ( CPR ) , and functional disability at 2 months . A specifically trained nurse had multiple contacts with the patient , family , physician , and hospital staff to elicit preferences , improve underst and ing of outcomes , encourage attention to pain control , and facilitate advance care planning and patient-physician communication . RESULTS The phase I observation documented shortcomings in communication , frequency of aggressive treatment , and the characteristics of hospital death : only 47 % of physicians knew when their patients preferred to avoid CPR : 46 % of do-not-resuscitate ( DNR ) orders were written within 2 days of death ; 38 % of patients who died spent at least 10 days in an intensive care unit ( ICU ) ; and for 50 % of conscious patients who died in the hospital , family members reported moderate to severe pain at least half the time . During the phase II intervention , patients experienced no improvement in patient-physician communication ( eg , 37 % of control patients and 40 % of intervention patients discussed CPR preferences ) or in the five targeted outcomes , ie , incidence or timing of written DNR orders ( adjusted ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.90 to 1.15 ) , physicians ' knowledge of their patients ' preferences not to be resuscitated ( adjusted ratio , 1.22 ; 95 % CI , 0.99 to 1.49 ) , number of days spent in an ICU , receiving mechanical ventilation , or comatose before death ( adjusted ratio , 0.97 ; 95 % CI , 0.87 to 1.07 ) , or level of reported pain ( adjusted ratio , 1.15 ; 95 % CI , 1.00 to 1.33 ) . The intervention also did not reduce use of hospital re sources ( adjusted ratio , 1.05 ; 95 % CI , 0.99 to 1.12 ) . CONCLUSIONS The phase I observation of SUPPORT confirmed substantial shortcomings in care for seriously ill hospitalized adults . The phase II intervention failed to improve care or patient outcomes . Enhancing opportunities for more patient-physician communication , although advocated as the major method for improving patient outcomes , may be inadequate to change established practice s. To improve the experience of seriously ill and dying patients , greater individual and societal commitment and more proactive and forceful measured may be needed BACKGROUND Diagnosis of domestic violence ( DV ) in primary care is low compared to its prevalence . Care for patients is deficient . Over a 1-year period , we tested the effectiveness of an intensive intervention to improve asking about DV , case finding , and management in primary care . The intervention included skill training for providers , environmental orchestration ( posters in clinical areas , DV questions on health question naires ) , and measurement and feedback . METHODS We conducted a group-r and omized controlled trial in five primary care clinics of a large health maintenance organization ( HMO ) . Outcomes were assessed at baseline and follow-up by survey , medical record review , and qualitative means . RESULTS Improved provider self-efficacy , decreased fear of offense and safety concerns , and increased perceived asking about DV were documented at 9 months , and also at 21 months ( except for perceived asking ) after intervention initiation . Documented asking about DV was increased by 14.3 % with a 3.9-fold relative increase at 9 months in intervention clinics compared to controls . Case finding increased 1.3-fold ( 95 % , confidence interval 0.67 - 2.7 ) . CONCLUSIONS The intervention improved documented asking about DV in practice up to 9 months later . This was mainly because of the routine use of health question naires containing DV questions at physical examination visits and the placement of DV posters in clinical areas . A small increase in case finding also result ed . System changes appear to be a cost-effective method to increase DV asking and identification Sc and J Prim Health Sci 2002;20:000 - 000 . ISSN 0281 - 3432 Objective - To evaluate the impact of feedback on the prescribing of antibiotics supplementary to clinical guidelines in the treatment of respiratory tract infections . Design - R and omised , controlled trial with GPs allocated to one of two groups . The first group received clinical guidelines on the treatment of respiratory tract infections plus postal feedback with aggregated data on their prescribing patterns for antibiotics . The second group served as controls for the first group and received the guidelines only . Setting - 299 GPs representing 181 practice s with 455 843 listed patients in the County of Funen , Denmark . Main outcome measures - Effects on GP prescribing patterns were measured by means of a prescription data base and followed for a period of 2 years with 2 outcome measures : 1 ) the antibiotic prescription rate and 2 ) the fraction of prescriptions for narrow-spectrum antibiotics . Results - The addition of feedback had no impact on GP prescribing patterns . Conclusion - Postal disseminated prescriber feedback in addition to a clinical guideline on the diagnosis and treatment of respiratory tract infections does not influence GP prescribing patterns . Interventions aim ed at improving performance in general practice should go beyond just giving GPs information on whether they are living up to st and ards RATIONALE Great emphasis is placed on the need to base assistance activities on efficacy evidence . Nevertheless , it is demonstrated that the mere knowledge of scientific recommendations is not sufficient to determine changes in practice . Many elements can influence the operators ' behaviour , so that comprehensive strategies are needed to change wrong or not evidence -based practice s. OBJECTIVES The aim was to compare the efficacy of two protocol implementation strategies : clinical -organizational integrated audits with feedback and presence of facilitators in the departments versus st and ard observation . METHODS Cluster-r and omized , controlled and open trial methods were used . Implementation was investigated for protocol s regarding the prevention of pressure lesions and the management of peripheral and central venous catheters . For both protocol s , a checklist with the indicators needed for the evaluation was created . The study was divided into five time points . For the initial and final investigation , evaluators filled-in the checklists for both study groups ; for the three intermediate investigations , the checklists were self-filled by the operators of the control group , while the operators of the experimental group received the intervention . RESULTS For almost all indicators , the data show an increment in the adoption of correct practice s. Nevertheless , the last investigation shows a significant ( P < 0.05 ) difference between the two groups in favour of the experimental group : 12 process indicators versus one for catheter management protocol and seven versus one for protocol on pressure lesions . CONCLUSIONS The main strong point of the study lies in carrying out an intervention aim ed at improving the operators ' adoption of two protocol s as a whole , rather than of single procedures . The audit intervention allowed to highlight some more subjective criticalities important in determining the success or failure of the implementation of effective practice OBJECTIVE To determine if written feedback improves the chart documentation and knowledge of physicians doing evaluations for child sexual abuse and to learn what other factors are associated with better documentation and knowledge . DESIGN R and omized , controlled trial . SETTING A statewide network of physicians performing child abuse evaluations . PARTICIPANTS All physicians who performed evaluations for sexual abuse during 1991 to 1992 . One hundred forty-seven physicians were r and omized to control ( n = 75 ) and intervention ( n = 72 ) groups , 122 ( 83 % ) remained at follow-up , and 87 of the 122 ( 71 % ) had done evaluations for child sexual abuse . INTERVENTIONS Tailored written feedback based on chart review s and relevant articles were sent to a r and omly selected one-half of the physicians during a 3-month period . MAIN OUTCOME MEASURES The quality of documentation and physician knowledge before and after the intervention . RESULTS Documentation by chart review of up to five r and omly chosen records per physician ( preintervention , n = 552 ; postintervention , n = 259 ) by review ers blinded to intervention status and physician knowledge was assessed by survey ( 78 % completion ) . Change in documentation and knowledge for physicians in the intervention group was not statistically significant compared with the control group . The risk ratio for a mean overall history rating of excellent/good was 0.89 ( 0.63 , 1.25 ) and for a mean overall physical examination rating of excellent/good was 1.03 ( 0.73 , 1.45 ) . Both groups improved significantly during the time period . The largest improvements in the time period were in documenting the history of where abuse occurred , in the physical examination position , hymenal description , penile findings , and knowing that chlamydia infection should be assessed by culture . A structured medical record , female physicians , and credits in continuing medical education were associated with better documentation . CONCLUSIONS Tailored feedback to the physician with directed educational material s did not seem to improve most aspects of documentation and knowledge of child sexual abuse , although notable improvement was seen during the time period studied . This study suggests that chart audits may not be the best use of re sources for trying to improve physician behavior ; credits in continuing medical education and use of structured records may be more likely to be beneficial OBJECTIVE To compare the effectiveness of group education and notification with that of notification alone in modifying prescribing of regulated analgesics . DESIGN R and omized controlled trial conducted from Dec. 1 , 1992 , to Dec. 31 , 1993 . SETTING Nonacademic primary care practice s in British Columbia . PARTICIPANTS Fifty-four physicians r and omly selected from a group of 100 physicians who had written a number of prescriptions for regulated drugs more than than two st and ard deviations above the mean number of prescriptions written for such drugs in 1992 . Any physician who was unable to participate was replaced from the original group of 100 before the study began . Five subjects did not complete the study and were not included in the analysis . INTERVENTIONS Participants were r and omly assigned to three groups : those in the first group received a written notification of excessive prescribing and attended a 1-day group-education activity , those in the second group received a written notification of excessive prescribing only and those in the third group were not subject to any intervention and were unaware that their prescribing had received special notice . OUTCOME MEASURE Mean number of prescriptions for regulated analgesics issued per physician in the 6 months before and the 6 months after the interventions . RESULTS Physicians in the group that attended the education intervention wrote , on average , 33 % fewer prescriptions after the intervention , whereas physicians in the group that received only written notification wrote 25 % fewer prescriptions , on average , after the intervention . No change in prescribing was shown in the control group . The differences in rates of prescribing of regulated analgesics between each intervention group and the control group were statistically significant ( p < 0.01 ) . The difference in the rate of prescribing between the two intervention groups was not significant . CONCLUSIONS Group education and notification of prescriber status as well as notification alone significantly reduced prescribing of regulated analgesics . Hence , feedback on a physician 's prescribing pattern may be a practical and less costly alternative to direct educational intervention in moderating the prescribing of regulated analgesics . The results do not , however , imply that notification is as effective as education in improving overall patient care . A follow-up study comparing the duration of the effect of the educational intervention with that of notification alone is warranted This study evaluated the economic impact of patient-focused pharmacist intervention in the community retail setting in patients with hypertension , diabetes , asthma , and /or hypercholesterolemia . Specially trained pharmacists intervened by providing targeted patient education , performing systematic patient monitoring , offering feedback and behavior modification , and communicating regularly with patients ' physicians to enable early intervention for drug-related problems . We evaluated prescription drug costs and total medical costs by comparing cl aims data from 188 patients enrolled in the program at three intervention pharmacies with data from 401 control patients at five nonparticipating pharmacies from the same retail chain . For all disease states , the average cost per prescription was significantly higher in the group receiving intervention than in the control group . Differences in total monthly prescription costs were significant only for patients with asthma , with higher monthly costs in the group receiving intervention . Substantial savings were demonstrated across all cost analyses for total monthly medical costs . Savings ranged from a conservative estimate of $ 143.95 per patient per month to $ 293.39 per patient per month when accounting for the possible influence of age , comorbid conditions , and disease severity . Our data indicate that pharmacist intervention in this community pharmacy-based disease management model substantially reduced monthly health care costs in patients with hypertension , hypercholesterolemia , diabetes , and asthma Two interventions design ed to help physicians manage hypertensive patients were evaluated in a controlled trial : 1 ) computer-generated feedback to facilitate identification of poorly controlled patients ; and 2 ) a physician education program on clinical management strategies , emphasizing patient compliance . Four physician practice teams received either computer feedback , the education program , both , or neither . Feedback team physicians received seven monthly listings of the latest visits and blood pressures of their hypertensive patients . The self-administered learning program included written clinical simulations and associated didactic material . Experimental and control physicians were similar in baseline knowledge , patient mix and level of training . All feedback team physicians requested appointments for listed patients , and their patients made twice as many visits as control patients during the intervention period ( p < 0.05 ) . Education team physicians showed significant gains on a content-specific post-intervention test : mean score 84 per cent compared with 74 per cent for the control group ( p < 0.005 ) . All patient groups showed improvement in blood pressure over the study period . However , no differences between intervention teams could be detected ( p > 0.20 ) . The probability of missing a 10 mm interteam difference in outcome diastolic pressure was 1 per cent ( power of 0.99 ) . Strategies for further improvement in outpatient hypertension management may need to come from outside the traditional medical model OBJECTIVE The aim of this project was to determine whether a tailored multifaceted intervention aim ed at site-specific barriers is more effective than audit feedback alone for improving adherence to inhospital stroke performance measures ( PMs ) : door to needle time of less than 1 hour for tissue plasminogen activator , dysphagia screening , deep venous thrombosis prophylaxis , and warfarin treatment for atrial fibrillation . METHODS Hospitals were paired on baseline adherence to dysphagia screening and quality improvement infrastructure and r and omized to receive audit feedback alone ( n=7 ) versus audit feedback plus site-specific interventions ( n=6 ) . Data were collected on all admitted patients with stroke seen in the neurology department before and after a 6-month implementation period . The primary end point was the difference in postintervention adherence rates for each PM , except tissue plasminogen activator because of low sample size . RESULTS Data were collected on 2071 preintervention patients and 1240 postintervention patients . Targeted site-specific interventions , such as st and ing orders and st and ardized dysphagia screens , were imperfectly implemented during the 6-month intervention period . For atrial fibrillation , the intervention group had an 11 % higher postintervention adherence rate beyond that of the control group ( 98 % v 87 % , P < .005 ) . No other statistically significant changes in PM adherence were observed . CONCLUSION Implementation of site-specific interventions for quality improvement of specific measures in stroke was difficult to achieve in a 6-month time frame and led to improved adherence for only one of 3 PMs . Studies with a longer intervention period and more sites are required to determine whether tailored interventions can enhance stroke improvement Objective To evaluate the effectiveness and efficiency of a tailored multifaceted strategy , delivered by a national clinical effectiveness programme , to implement a guideline on induced abortion OBJECTIVE To evaluate a project to implement guidelines on the management of patients with asthma or chronic obstructive pulmonany disease ( COPD ) in terms of the health outcomes of these patients . DESIGN A before- and -after study of 1 year with a non-r and omized but comparable reference group . SETTING General practice s in the Netherl and s. STUDY PARTICIPANTS Two-hundred and eighty patients from 14 practice s in the intervention group and 90 patients from five practice s in the reference group ( receiving usual care ) . INTERVENTION The project included a comprehensive implementation programme , involving identification of barriers , documentation of the care provided , specific education , feedback on compliance with the guidelines , and peer review . This project has been found to bring the process of care more in agreement with the guidelines . MAIN OUTCOME MEASURES Mean peak expiratory flow rate ( PEFR ) as a percentage of the predicted value , number of days with a diurnal variation in PEFR > or = 15 % , number of days with respiratory symptoms ( all recorded by patients for a period of 14 days ) , and perceived health status ( Nottingham Health Profile ) . RESULTS After 1 year , the intervention group showed statistically significant improvements with regard to the mean PEFR , the diurnal variation in PEFR , respiratory symptoms and the pain score of the Nottingham Health Profile . Comparing the changes within the intervention group with the changes within the reference group , only a positive effect of the intervention on the mean PEFR was found . CONCLUSION The comprehensive implementation programme improved the lung function and symptoms of asthma and COPD patients in the intervention group . However , in comparison with a reference group , the positive effect on the lung function was only small The objective of this study was to assess the effects of two brief training interventions to improve obstetricians ' and midwives ' explanations to patients of a routine prenatal screening test . Health professionals were r and omly allocated to one of two intervention groups or a control group . Information-giving about the test and communication skills were assessed at baseline , post-training and 3-month follow-up from audiotaped consultations . Both intervention groups received a 1-h training session involving small group discussion s focused around a video . In addition , one group received individual feedback on their baseline and post-training consultations . Twenty-six midwives and nine obstetricians completed the study according to the protocol . Changes between baseline and post-training , and between baseline and follow-up , were computed . Information-giving and communication skills improved significantly in subjects receiving training and feedback on their performance , with the greatest improvements occurring before feedback was given . Those receiving training without feedback significantly improved their communication skills and showed some improvement in information-giving . These results show that modest improvements in communication can be made with relatively brief training . Greater and more sustained improvements may be found if all staff were trained , and trained on a regular basis In the international Drug Education Project , an educational program involving auditing and feedback in peer groups to improve the treatment of asthma and urinary tract infections ( UTI ) was developed and tested in primary care . Individualized feedback was provided and discussed in 24 Dutch peer groups showing doctors their prescribing practice s and underlying reasons for treatment . A parallel , r and omized controlled design was used to test the effect on competence and actual prescribing ; in one study arm doctors received feedback on asthma treatment and in the other on UTI treatment . Especially the messages to treat asthma exacerbations with oral corticosteroids ( 17 % increase ) and to prescribe short courses for UTI ( decrease duration of 1.8 days ) brought about large improvements . Both messages concerned acute situations , and were clear and relatively easy for GPs to implement . GPs will experience more barriers when changing maintenance treatment of an asthma patient , which could explain the more limited success of this part of the educational program : the proportion of patients treated with inhaled corticosteroids increased 5 % . A ceiling effect was experienced regarding drug choice for UTI OBJECTIVE We aim ed to evaluate the effect of a medical audit on AIDS prevention in general practice . METHODS We conducted a prospect i ve r and omized controlled study performed as ' lagged intervention ' . At the time of comparison , the intervention group had completed 6 months of audit including a primary activity registration , feedback of own data and a meeting with colleagues and experts , and had received brief summaries of the meetings and reminders about the project ( a full ' audit circle ' ) . The participants were from general practice s in Copenhagen and the Counties of Funen and Vejle , Denmark . One hundred and thirty-three GPs completed the project . The main outcome measures were the number of consultations involving AIDS prevention and the number of talks about AIDS initiated by the GP , and some elements of the content were registered on a chart . RESULTS No statistically significant difference was observed in the frequency of consultations involving AIDS prevention between the intervention group ( 1.2 % of consultations ) and the control group ( 1.4 % ) . Furthermore , no significant differences were observed regarding the content of these consultations or regarding the fraction of such consultations initiated by the GPs . CONCLUSIONS Medical audit had no observed effect on AIDS prevention in general practice Concurrent charge feedback has gained widespread acceptance as a method of minimizing hospitals ' losses under the Medicare prospect i ve payment system despite the fact that its effect on patient outcomes , physician behavior , or charges has not been studied in depth . In a controlled trial on two medical wards in an academic medical center , the effect of daily charge feedback on charges was studied . Sixty-eight house staff and 16 teaching attending physicians participated during a 35-week period , taking care of 1057 eligible patients . No significant differences in charges were seen when all patients were included . Since 45 % of patients had planned protocol admissions ( diagnostic workups or protocol treatment ) on which the house staff had little change to impact , a subgroup analysis was performed , excluding these patients . In the remaining patients , a highly significant reduction in mean total charges ( 17 % ) , length of stay ( 18 % ) , room charges ( 18 % ) , and diagnostic testing ( 20 % ) was found . In-hospital mortality and preventable readmission within 30 days were similar on the two wards . It was concluded that charge feedback alone is effective in a teaching hospital for decreasing charges PURPOSE To examine the effects on process of care and patient well-being , of the regular collection and use of health-related quality -of-life ( HRQL ) data in oncology practice . PATIENTS AND METHODS In a prospect i ve study with repeated measures involving 28 oncologists , 286 cancer patients were r and omly assigned to either the intervention group ( regular completion of European Organization for Research and Treatment of Cancer-Core Quality of Life Question naire version 3.0 , and Hospital Anxiety and Depression Scale on touch-screen computers in clinic and feedback of results to physicians ) ; attention-control group ( completion of question naires , but no feedback ) ; or control group ( no HRQL measurement in clinic before encounters ) . Primary outcomes were patient HRQL over time , measured by the Functional Assessment of Cancer Therapy-General question naire , physician-patient communication , and clinical management , measured by content analysis of tape-recorded encounters . Analysis employed mixed-effects modeling and multiple regression . RESULTS Patients in the intervention and attention-control groups had better HRQL than the control group ( P = .006 and P = .01 , respectively ) , but the intervention and attention-control groups were not significantly different ( P = .80 ) . A positive effect on emotional well-being was associated with feedback of data ( P = .008 ) , but not with instrument completion ( P = .12 ) . A larger proportion of intervention patients showed clinical ly meaningful improvement in HRQL . More frequent discussion of chronic nonspecific symptoms ( P = .03 ) was found in the intervention group , without prolonging encounters . There was no detectable effect on patient management ( P = .60 ) . In the intervention patients , HRQL improvement was associated with explicit use of HRQL data ( P = .016 ) , discussion of pain , and role function ( P = .046 ) . CONCLUSION Routine assessment of cancer patients ' HRQL had an impact on physician-patient communication and result ed in benefits for some patients , who had better HRQL and emotional functioning The electronic health record ( EHR ) may be an effective tool to help clinicians address tobacco use more consistently . To evaluate the impact of EHR-generated practice feedback on rates of referral to a state-level tobacco quitline , we conducted a cluster r and omized clinical trial ( feedback versus no feedback ) within 19 primary care clinics in Oregon . Intervention clinics received provider-specific monthly feedback reports generated from EHR data . The reports rated provider performance in asking , advising , assessing , and assisting with tobacco cessation compared with a clinic average and an achievable benchmark of care . During 12 months of follow-up , EHR-documented rates of advising , assessing , and assisting were significantly improved in the intervention clinics compared with the control clinics ( p<.001 ) . A higher case-mix index and presence of a clinic champion were associated with higher rates of referral to a state-level quitline . EHR-generated provider feedback improved documentation of assistance with tobacco cessation . Connecting physician offices to a state-level quitline was feasible and well accepted CONTEXT Under routine hospital conditions h and washing compliance of health care workers including nurses , physicians , and others ( eg , physical therapists and radiologic technicians ) is unacceptably low . OBJECTIVES To investigate the efficacy of an education/ feedback intervention and patient awareness program ( cognitive approach ) on h and washing compliance of health care workers ; and to compare the acceptance of a new and increasingly accessible alcohol-based waterless h and disinfectant ( technical approach ) with the st and ard sink/soap combination . DESIGN A 6-month , prospect i ve , observational study . SETTING One medical intensive care unit ( ICU ) , 1 cardiac surgery ICU , and 1 general medical ward located in a 728-bed , tertiary care , teaching facility . PARTICIPANTS Medical caregivers in each of the above setting s. INTERVENTIONS Implementation of an education/ feedback intervention program ( 6 in-service sessions per each ICU ) and patient awareness program , followed by a new , increasingly accessible , alcohol-based , waterless h and antiseptic agent , initially available at a ratio of 1 dispenser for every 4 patients and subsequently 1 for each patient . MAIN OUTCOME MEASURE Direct observation of h and -washing for 1575 potential opportunities monitored over 120 hours r and omized for both time of day and bed locations . RESULTS Baseline h and washing compliance before and after defined events was 9 % and 22 % for health care workers in the medical ICU and 3 % and 13 % for health care workers in the cardiac surgery ICU , respectively . After the education/feedback intervention program , h and washing compliance changed little ( medical ICU , 14 % [ before ] and 25 % [ after ] ; cardiac surgery ICU , 6 % [ before ] and 13 % [ after ] ) . Observations after introduction of the new , increasingly accessible , alcohol-based , waterless h and antiseptic revealed significantly higher h and washing rates ( P<.05 ) , and h and washing compliance improved as accessibility was enhanced-before 19 % and after 41 % with 1 dispenser per 4 beds ; and before 23 % and after 48 % with 1 dispenser for each bed . CONCLUSIONS Education/feedback intervention and patient awareness programs failed to improve h and washing compliance . However , introduction of easily accessible dispensers with an alcohol-based waterless h and washing antiseptic led to significantly higher h and washing rates among health care workers There is an increasing drive to make nursing care evidence -based . High quality evidence from systematic review s relevant to postoperative pain relief exists , yet pain after surgery remains poorly controlled for many patients . This study aim ed to assess whether implementing evidence -based pain management improved postoperative pain outcomes . Pain on a 0 - 10 scale was the primary outcome and analgesic consumption a secondary outcome . A baseline audit was undertaken on four surgical wards to establish whether there was a need for the study . A r and omized-controlled trial was then design ed to assess the effects of implementing an evidence -based approach to postoperative pain management . The four wards were r and omized to receive the intervention or act as a control . Outcomes were assessed 3 months after the intervention on both intervention and control wards . The intervention ( implementation of an oral analgesic algorithm derived from systematic review s ) was then implemented on the control wards and outcomes reassessed after 3 months on the control wards . The intervention was design ed using an evidence -based approach to effective implementation . Four interactive sessions covered : ( 1 ) detailed feedback of baseline data and discussion ( utilizing audit and feedback ) , ( 2 ) why systematic review s , analgesic league tables and choice of drugs to develop an analgesic algorithm ( see Figure 1 ) , ( 3 ) principles of evidence based health care ( EBHC ) , including critical appraisal and ( 4 ) facilitation and change workshop . The findings revealed no significant differences in pain level or drug use between the intervention and control wards . However , the control wards also changed during the control period . Possible explanations for this are discussed . When looking at changes compared with baseline , both intervention and control wards increased their use of algorithm drugs and reduced use of non-algorithm drugs during the study . No effects were found on pain in the intervention wards . Pain ratings at rest since surgery , on movement since surgery and worst pain on movement were significantly reduced compared with baseline in the control wards . Although there are many pressures to utilize a r and omized-controlled trial study design in the culture of evidence -based health care , there will be times , especially when implementing complex changes in practice that other types of design should be considered Purpose Although clinical - practice guidelines ( CPGs ) are implemented on the assumption that they will improve the quality , efficiency , and consistency of health care , they generally have limited effect in changing physicians ’ behavior . The purpose of this study was to design and implement an effective program for formulating , promulgating , and implementing CPGs to foster the development of an evidence -based culture in an Israeli HMO . Method The authors implemented a four-stage program of stepwise collaborative efforts with academic institutions composed of developing quantitative tools to evaluate prescribing patterns , updating CPGs , collecting MDs ’ input via focus groups and quantitative surveys , and conducting a r and omized controlled trial of a two-stage , multipronged intervention . The test case for this study was the development , dissemination , and implementation of CPG for the treatment of acute uncomplicated cystitis in adult women . Interventions in the form of a lecture at a conference and a letter with personalized feedback were implemented , both individually and combined , to improve physicians ’ rates of prescribing the first-line drug , nitrofurantoin , and , in the absence of nitrofurantoin , adhering to the recommended duration of three days of treatment with ofloxacin . Results The tools and data -generating capabilities design ed and constructed in Stage I of the project were integral components of all subsequent stages of the program . Personalized feedback alone was sufficient to improve the rate of adherence to the guidelines by 19.4 % ( 95 % CI = 16.7 , 22.1 ) . Conclusions This study provides a template for introducing the component of experimentation essential for cultivating an evidence -based culture . This process , composed of collaborative efforts between academic institutions and a managed care organization , may be beneficial to other health care systems Objective . Under managed care , telephone management is crucial to pediatric practice , but an effective method is needed to teach residents telephone skills . Our objective was to design an interactive CD-ROM program to teach residents an organized , consistent approach to telephone complaints and to determine whether use of the program was associated with better subsequent telephone management than reading the same information . Setting . The general pediatric ambulatory center of a tertiary care children 's hospital . Participants . A total of 24 PL-2 and PL-3 pediatric residents . Design . A r and omized , prospect i ve , controlled comparison was conducted of resident management of two telephone calls : a 5-year-old with cough and trouble breathing , and a 7-year-old with fever . Thirteen residents were r and omized to the computer group and 11 to the reading control group . Intervention . Scripts , scoring , and feedback for 10 CD-ROM-simulated calls were developed from texts and pediatrician survey using a modified Delphi technique . Volunteers acted out the caller 's role in scenario scripts and were recorded onto a CD-ROM . The computer simulated calls by recognizing questions typed in a free-form format and answering with a voice response . Feedback was provided for omissions in history-taking and errors in assessment , triage , and home management . The computer group worked through the CD-ROM calls while the control group had equal time to read the same information . Evaluation Measures . A trained , st and ardized patient acted as the mother in pretest calls placed at the beginning of the month and posttest calls at the end . Calls were recorded and scored in a blinded manner using scoring templates and on interpersonal skills using the Patient Perception Question naire . Results . Pretest scores for the two calls were similar in the computer versus the control group ( cough , 70.33 % ± 8.36 vs 68.46 % ± 6.73 ; fever , 75.64 % ± 9.82 vs 73.59 % ± 9.06 ) . Posttest scores were significantly higher in the computer group than in the control group on both calls ( cough , 79.08 % ± 8.17 vs 69 ± 13.3 ; fever : 83.33 % ± 9.96 vs 70.35 % ± 9.66 ) . Interpersonal skills also were similar pretest ( 19 ± 3.4 vs 20 ± 2.7 ) . There was modest improvement in both groups without a statistically significant difference in posttest scores ( 24.2 ± 2.9 vs 22.5 ± 3.1 ) . Conclusions . Use of this CD-ROM telephone management program was associated with better postintervention telephone management . The program augments faculty instruction by teaching a consistent , general approach to telephone management OBJECTIVE A 1-year r and omized prospect i ve study was conducted to investigate the efficacy of feedback from split- sample testing as part of a capillary blood glucose quality assurance program . RESEARCH DESIGN AND METHODS A total of 124 nurses were r and omized to either group A ( quarterly comparisons with feedback ) or group B ( no feedback ) . The measure of nurse accuracy against the laboratory at 0 , 6 , and 12 months was determined by an additional five to seven split- sample tests without giving feedback to either group . Mean accuracy was determined in terms of percent absolute deviation from the laboratory result and a clinical consensus limit of ± 20 % deviation from the laboratory . RESULTS By 12 months , there was a significant effect of feedback on nurse agreement with the laboratory method ( P = 0.022 when agreement was scored as the mean percent absolute difference and P = 0.002 when agreement was scored in terms of the ± 20 % clinical consensus limit ) . Nurses in the group who had received no quarterly feedback from split- sample testing produced a 3.5 % greater mean percent absolute deviation from the laboratory method and 12 % fewer comparisons within the acceptable ± 20 % range . CONCLUSIONS Feedback received from split- sample testing has a significant effect in maintaining accuracy in capillary blood glucose monitoring Discrepancies between clinical guidelines and clinical practice call for practical implementation strategies . This study evaluates the implementation of clinical guidelines for hypertension in general practice with a specific computer-based clinical decision support system ( CDSS ) as part of the intervention . We carried out a r and omized study of general practice health centres in Sør- and Nord-Trøndelag counties in Norway ( population 380000 ) . A total of 17 health centres were included , with 24 doctors and 984 patients in the intervention group . Data from 887 patients was used in the analyses . There were 12 health centres with 29 doctors and 1255 patients in the control group . Data from 1127 control patients was used in the analyses . The main outcome measures were doctor 's behaviour , measured by adherence to registration of recommended variables in the Norwegian clinical guidelines for hypertension . The aim of the intervention was to lower the fractions of patients without registration s. However , there were no clinical ly significant differences between the intervention group and the control group for fractions of patients without registration of blood pressure ( intervention group 14.3 % , control group 14.2 % ) or serum cholesterol ( 62.3 % vs. 56.8 % ) during 12 months , nor , during 18 months , for fractions of patients without a registration of cigarette smoking ( 82.9 % vs. 87.1 % ) , cardiovascular inheritance ( 79.5 % vs. 73.4 % ) and body mass index ( 81.5 % vs. 89.2 % ) . One or several variables necessary for calculation of risk score for myocardial infa rct ion were missing in 91.7 % of patients in the intervention group and 91.9 % of patients in the control group . Large centre variations were shown for all variables . Implementation of clinical guidelines in the treatment of hypertensive patients in general practice , by means of a CDSS and several procedures for implementation did not result in clinical ly significant changes in the doctors ' behaviour . Of importance are both the lack of user-friendliness of the specific CDSS and problems in performing time-consuming multidimensional procedures BACKGROUND Despite progress in describing the problem of potentially inappropriate medication ( PIM ) use , there have been few prospect i ve studies demonstrating that interventions with specific medication criteria can make a difference in decreasing the use of problematic drugs in older adults . OBJECTIVE To design an intervention study to change physician behavior regarding PIM prescribing to older patients . STUDY DESIGN AND METHODS A prospect i ve r and omized block design was used during an 18-month period from January 2001 to June 2002 . The study population was primary care physicians ( n = 355 ) in the Medicare + Choice product line of a southeastern managed care organization and their patients 65 years and older . There were 170 physicians in the treatment group and 185 in the control group . Physicians were assigned to the treatment or usual-care , groups using a r and omization table , and each group included physicians who had and had not prescribed a PIM . RESULTS Approximately 71 % ( 84/118 ) of the physicians in the intervention group who prescribed a PIM completed and faxed back at least 1 potentially inappropriate medication form to the managed care organization . On 15.4 % ( 260/1692 ) of the medication forms , physicians made some change regarding PIM use . CONCLUSIONS Although many studies have addressed medication use among older adults , intervention studies aim ed at influencing physician prescribing in this population are limited . This study describes a low-cost , replicable method to contact and educate physicians on drug therapy issues in older adults Objective . To evaluate the effects of the introduction of an alcohol-based h and gel and multifaceted quality improvement ( QI ) interventions on h and hygiene ( HH ) compliance . Design . Interventional , r and omized cohort study with four study phases ( baseline ; limited intervention in two units ; full intervention in three units ; washout phase ) , performed in three intensive care units at a pediatric referral hospital . Methods . During 724 thirty-minute daytime monitoring sessions , a nonidentified observer witnessed 12 216 opportunities for HH and recorded compliance . Interventions . Introduction of an alcohol-based h and gel ; multifaceted QI interventions ( educational program , opinion leaders , performance feedback ) . Results . Baseline compliance decreased after the first 2 weeks of observation from 42.5 % to 28.2 % ( presumably because of waning of a Hawthorne effect ) , further decreased to 23.3 % in the limited intervention phase and increased to 35.1 % after the introduction of a h and gel with QI support in all three units ( P < 0.001 ) . The rise in compliance persisted in the last phase ( compliance , 37.2 % ) ; however , a gradual decline was observed during the final weeks . Except for the limited intervention phase , compliance achieved through st and ard h and washing and glove use remained stable around 20 and 10 % , respectively , whereas compliance achieved through gel use increased to 8 % ( P < 0.001 ) . After adjusting for confounding , implementation of the h and gel with QI support remained significantly associated with compliance ( odds ratio , 1.6 ; 95 % confidence interval , 1.4 to 1.8 ) . In a final survey completed by 62 staff members , satisfaction with the h and gel was modest ( 45 % ) . Conclusions . We noted a statistically significant , modest improvement in compliance after introduction of an alcohol-based h and gel with multifaceted QI support . When appropriately implemented , alcohol-based HH may be effective in improving compliance A crossover r and omized controlled trial of cycles of quality assurance in 16 primary care ( 8 medical , 8 pediatric ) group practice s was conducted . Of four medical and four pediatric tasks important to patient outcome , two were r and omly assigned to experimental intervention ( a quality assurance cycle ) , and two were also measured and used as blinded controls for each medical or pediatric group practice . Task performance was measured in each group for 12 months prior to , 9 months during , and 9 months after the experimental intervention , using as a performance score the percentage of evaluation criteria failed of those applicable to a case . As a result of quality assurance intervention , quality of performance was significantly improved in two of the tasks ( P<0.0001 , with 6.7 , and 9.8 percentage points improvement ) , and marginally improved in one task ( P=0.06 , 5.7 percentage points improvement ) . Surprisingly , tasks with lower perceived effect on patient health ( low physician motivation ) had greater improvement in quality . Unimproved tasks were associated with the perceived need for delivery system changes beyond the immediate control of the individual practitioner OBJECTIVE Despite the recommendations of numerous clinical practice guidelines , testing of at-risk women for Chlamydia trachomatis infection remains low . We evaluated an intervention to increase guideline -recommended chlamydia screening . METHOD In a two-by-two factorial design r and omized trial conducted in 2001 - 2002 , 23 primary care clinics at Group Health Cooperative in Washington State were r and omized to either control ( st and ard ) or intervention ( enhanced ) guideline implementation arms . Clinic-level intervention strategies included use of clinic-based opinion leaders , individual measurement and feedback , and exam room reminders . A second patient-level intervention , a chart prompt to screen for chlamydia , was delivered in a r and om sample of 3509 women . The outcome measure was post-intervention chlamydia testing rates among sexually active women ages 14 - 25 . RESULTS The clinic-level intervention did not significantly affect overall chlamydia testing ( odds ratio ( OR ) = 1.08 , 95 % confidence interval ( CI ) 0.92 - 1.26 , P = 0.31 ) . However , testing rates increased significantly among women making preventive care visits ( OR , Pap test visit = 1.23 , 95 % CI , 1.01 - 1.51 , P = 0.04 ; OR , physical exam visit = 1.22 , 95 % CI 1.06 - 1.42 , P = 0.009 , intervention vs. control clinics ) . The chart prompt intervention had no significant effect ( OR = 1.08 , 95 % CI 0.94 - 1.23 , P = 0.27 ) . CONCLUSIONS Interventions to improve guideline -recommended chlamydia testing increased testing among women making preventive care visits . Additional organizational change and /or patient activation strategies may improve plan-wide testing , particularly among asymptomatic women Dr A E Fletcher , Department of Epidemiology and Population Sciences , London School ofHygiene and Tropical Medicine , London WC1E 7HT . atenolol , but in an observational study we can not discount the possibility of confounding factors . Our model adjusted for the most obvious of these ( age and smoking ) , but there may be other unidentified factors . The strength of experimental studies is that r and omisation removes selection bias . In the Medical Research Council 's trial the relative risk of dying from cancer for men receiving atenolol was 1 9 compared with placebo ( 1 - 2 to 2 8) and 1 - 4 ( 0 9 to 2 2 ) compared with diuretic . In our study the 95 % confidence intervals of the relative risks for all cancers and for lung cancer excluded a twofold excess risk from atenolol . We can not exclude risks lower than this Background : Family physicians have an important clinical role in assessment and management of suspicious skin lesions . As a result of a previous needs assessment study , an educational intervention based on audit and feedback with opportunity for reflection on practice was introduced to 46 family physicians r and omly allocated to either an intervention ( 23 ) or control group ( 23 ) . As an educational tool , audit allows doctors to systematic ally review their practice and establish the quality of care they provide . When combined with feedback and comparison of clinical performance with peers or st and ards , it has been shown to increase learning and change behavior . Methods : Data based on their own patients , on the correlation between clinical and histologic diagnosis , and excisions of skin lesions were collated and reported to the intervention group . Results : Despite r and omization of the doctors , the patient population of doctors in the intervention and control groups were significantly different in key characteristics , including the types of skin lesions treated . The intervention group of doctors showed improved performance in providing clinical information on pathology requests and in adequate surgical excision of skin lesions . Diagnostic performance did not improve significantly , but physicians ' certainty of diagnosis did . Implication s : This study design has highlighted the difficulty in balancing the use of evidence ‐based educational strategies in an equivalent setting to normal practice with evaluation of performance using measures that include characteristics of practitioners ' patients that can not be controlled BACKGROUND Action research has been used successfully to promote change in disciplines other than medicine , but there are few examples of its use in primary care . OBJECTIVE We aim ed to discuss the benefits and difficulties of using action research in primary care using the example of child health surveillance provision in general practice . METHODS Twenty-eight general practice s were r and omly allocated into two groups . Action research was used to promote change in 14 practice s by facilitating practice meetings and by providing written feedback . The other 14 practice s received written feedback alone . The two groups of practice s were compared using the following : ( i ) semi-structured interviews with one health visitor and GP from each practice ; ( ii ) observation of baby clinics ; ( iii ) question naires to parents ; and ( iv ) return rates of child health surveillance review s from the personal child health record . RESULTS All 14 practice s in the action research arm of the study met as individual practice teams and decided to make changes to their provision of child health surveillance . Ten practice s audited their child health surveillance as a result . More health visitors in the action research practice s than in the comparison practice s reported changes to child health surveillance , audit , communication and use of the personal child health record . The majority of health visitors and GPs thought involvement in the action research process was beneficial . However , we were unable to show a statistically significant difference between the two groups of practice s in baby clinic provision , parent satisfaction or the return rate of child health surveillance review s. CONCLUSION Our study suggests that action research is a successful method of promoting change in primary care . However , measuring the impact of change is difficult Two annual cost-containment educational programs , featuring involvement of respected senior physicians , lectures , comparative feedback , chart review s , and small group discussion s , were design ed to reduce interns ’ generated costs in a private and a VA university hospital affiliated with Northwestern University Medical School . To evaluate the impact of this r and omized educational intervention , hospital data on inpatient charges and length of stay ( LOS ) were collected for 12 common medical diagnoses and adjusted by the Severity of Illness Index . Interns who were r and omized to the program were found to have significantly lower per patient costs and LOS than control group interns at both hospitals . These reductions in re source use and LOS were not associated with differences in patients ’ residual impairment on discharge , the incidence of inpatient complications , or the percentage of deaths and readmissions within 30 days . Our results suggest that the current hospital cost-containment environment may be far more conducive to physician cost-containment education than indicated by the earlier literature OBJECTIVES The purpose of this study was to evaluate the effect of clinical direct reports ( practice data with pertinent evidence from the literature ) on dialysis modality selection for patients with end-stage renal disease . METHODS A r and omized controlled clinical trial was conducted at five dialysis centers . Five of the 10 physician participants were assigned through central ized computerized r and omization to the intervention group ( who received 12 center-specific clinical direct reports encouraging the consideration of peritoneal dialysis ) , and five were assigned to the control group , who received usual information but no similar report . One hundred fifty-two patients were eligible for monitoring . RESULTS The number of patients allocated to peritoneal dialysis was significantly higher in the intervention group than in the control group ( 15.3 % versus 2.4 % ; P = 0.044 ) . Due to a need for transient initial hemodialysis by some patients , the percentage of patients receiving peritoneal dialysis further increased through the end of the 3-month follow-up ( 18.0 % versus 4.9 % , P = 0.041 ) . CONCLUSIONS There were no significant differences between the intervention and control groups in meeting patient preferences , metabolic status , and complication rates . The results of this study show that linking pertinent published evidence to actual practice data can support the implementation of practice recommendations and influence the selection of dialysis treatment for new patients OBJECTIVES The purpose of this study was to examine the effects on immunization coverage of 3 incentives for physicians -- a cash bonus for practice --wide increases , enhanced fee for service , and feedback . METHODS Incentives were applied at 4-month intervals over 1 year among 60 inner-city office-based pediatricians . At each interval , charts of 50 r and omly selected children between 3 and 35 months of age were review ed per physician . RESULTS The percentage of children who were up to date for diphtheria , tetanus , and pertussis and Haemophilus influenzae type b ; polio ; and measles-mumps-rubella immunization in the study 's bonus group improved by 25.3 percentage points ( P < .01 ) . No significant changes occurred in the other groups . However , percentage of immunizations received outside the participating practice also increased significantly in the bonus group ( P < .01 ) . Levels of missed opportunities to immunize were high in all groups and did not change over time . Physicians ' knowledge of contraindications was low . CONCLUSIONS Bonuses sharply and rapidly increased immunization cover-age in medical records . However , much of the increase was the result of better documentation . A bonus is a powerful incentive , but more structure or education may be necessary to achieve the desired results BACKGROUND The availability of clinical guidelines in isolation has generally failed to promote voluntary change in practice patterns . Accordingly , a r and omized controlled trial was conducted to determine the effectiveness of academic detailing ( AD ) techniques and continuous quality improvement ( CQI ) teams in increasing compliance with national guidelines for the primary care of hypertension and depression . METHODS Fifteen small group practice s at four Seattle primary care clinics were assigned to one of three study arms -- AD alone , AD plus CQI teams , or usual care . The activity of 95 providers and 4,995 patients was monitored from August 1 , 1993 , through January 31 , 1996 . Twelve-month baseline and study periods were separated by a six-month " wash-in " period during which training sessions were held . Changes in hypertension prescribing , blood pressure control , depression recognition , use of older tricyclics , and scores on the Hopkins Symptom Checklist depression scale were examined . RESULTS Clinics varied considerably in their implementation of both the AD and the CQI team interventions . Across all sites , AD was associated with change in a single process measure , a decline in the percentage of depressives prescribed first-generation tricyclics ( -4.7 percentage points versus control , p = 0.04 ) . No intervention effects were demonstrated for CQI teams across all sites for either disease condition . Within the clinic independently judged most successful at implementing both change strategies , the use of CQI teams and AD in combination did increase the percentage of hypertensives adequately controlled ( 17.3 percentage points versus control , p = 0.03 ) . SUMMARY AND CONCLUSIONS The AD techniques and the CQI teams evaluated were generally ineffective in improving guideline compliance and clinical outcomes regarding the primary care of hypertension and depression This study tests whether an outreach educational program tailored to institutional specific patient care practice s would improve the quality of care delivered to mechanically ventilated intensive care unit ( ICU ) patients in rural hospitals . The study was conducted as a r and omized control trial using 20 rural Iowa hospitals as the unit of analysis . Twelve r and omly selected hospitals received an outreach educational program . After review of the medical records of eligible patients , a multidisciplinary team of intensive care unit specialists from an academic medical center delivered an educational program with content specific to the findings and capacity of the hospital . The outcome measures included patient care processes , patient morbidity and mortality outcomes , and re source use . Results indicated that the outreach program significantly improved many patient care processes ( lab work , nursing , dietary management , ventilator management , ventilator weaning ) . The program marginally reduced hospital ventilator days . Both total length of stay and ICU length of stay fell markedly in the intervention group ( by an average of 3.2 and 2.1 d , respectively ) , while the control group fell only 0.6 and 0.3 d , respectively . However , these effects did not reach statistical significance . Unfortunately , the program had no detectable effects on the clinical outcomes of mortality or nosocomial events . We conclude that an outreach program of this type can effectively improve processes of care in rural ICUs . However , improving processes of care may not always translate into improvement of specific outcomes PURPOSE We undertook a study to assess the impact of comparative feedback vs general reminders on practice -based referrals to a tobacco cessation quit line and estimated costs for projected quit responses . METHODS We conducted a group-r and omized clinical trial comparing the impact of 6 quarterly ( 18 months ) feedback reports ( intervention ) with that of general reminders ( control ) on practice -based clinician referrals to a quit-line service . Feedback reports were based on an Achievable Benchmark of Care approach using baseline practice , clinician , and patient survey responses , and referrals per quarter . Comparable quit responses and costs were estimated . RESULTS Three hundred eight clinicians participated ( 171 family medicine , 88 internal medicine , 49 obstetrics-gynecology ) from 87 primary care practice s in Michigan . After 18 months , there were more referrals from the intervention than from the control practice s ( 484 vs 220 ; P < .001 ) . Practice facsimile ( fax ) referrals ( 84 % , n = 595 ) exceeded telephone referrals ( 16 % , n = 109 ) , but telephone referrals result ed in greater likelihood of enrollment ( 77 % telephone vs 44 % fax , P < .001 ) . The estimated number of smokers who quit based on the level of services utilized by referred smokers was 66 in the feedback and 36 in the gentle reminder practice s. CONCLUSION Providing comparative feedback on clinician referrals to a quit-line service had a modest impact with limited increased costs OBJECTIVE To test whether an educational outreach intervention for families and physicians , based on the Centers for Disease Control and Prevention ( CDC ) principles of judicious antibiotic use , decreases antimicrobial drug prescribing for children younger than 6 years old . Setting . Twelve practice s affiliated with 2 managed care organizations ( MCOs ) in eastern Massachusetts and northwest Washington State . Patients . All enrolled children younger than 6 years old . METHODS Practice s stratified by MCO and size were r and omized to intervention or control groups . The intervention included 2 meetings of the practice with a physician peer leader , using CDC-endorsed summaries of judicious prescribing recommendations ; feedback on previous prescribing rates were also provided . Parents were mailed a CDC brochure on antibiotic use , and supporting material s were displayed in waiting rooms . Automated enrollment , ambulatory visit , and pharmacy cl aims were used to determine rates of antibiotic courses dispensed ( antibiotics/person-year ) during baseline ( 1996 - 1997 ) and intervention ( 1997 - 1998 ) years . The primary analysis ( for children 3 to < 36 months and 36 to < 72 months ) assessed the impact of the intervention among children during the intervention year , controlling for covariates including patient age and baseline prescription rate . Confirmatory analyses at the practice level were also performed . RESULTS The practice s cared for 14 468 and 13 460 children in the 2 study years , respectively ; 8815 children contributed data in both years . Sixty-two percent of antibiotic courses were dispensed for otitis media , 6.5 % for pharyngitis , 6.3 % for sinusitis , and 9.2 % for colds and bronchitis . Antibiotic dispensing for children 3 to < 36 months old decreased 0.41 antibiotics per person-year ( 18.6 % ) in intervention compared with 0.33 ( 11.5 % ) in control practice s. Among children 36 to < 72 months old , the rate decreased by 0.21 antibiotics per person-year ( 15 % ) in intervention and 0.17 ( 9.8 % ) in control practice s. Multivariate analysis showed an adjusted intervention effect of 16 % in the younger and 12 % in the older age groups . The direction and approximate magnitude of effect were confirmed in practice -level analyses . CONCLUSIONS A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practice s , even in the setting of substantial secular trends toward decreased prescribing . Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse OBJECTIVES This study evaluated the effects of an intervention on rates of skin cancer prevention counseling by pharmacists . METHODS Fifty-four pharmacies were r and omly assigned to intervention or control conditions . Intervention consisted of training , feedback , and prompts . Counseling rates before and after the intervention were obtained from study confederates . RESULTS At pretest , the proportions of control and intervention sites providing counseling at least once were 7.4 % and 0 % , respectively ( NS ) . At posttest , these proportions were 3.7 % and 66.7 % , respectively ( P < .001 ) . CONCLUSIONS The results indicated that the intervention was successful and that pharmacists can play an important role in educating the public about skin cancer prevention strategies BACKGROUND Without protective practice s such as Universal Pre caution s , health care workers are at substantial risk for bloodborne infection , especially in areas such as Thail and with high prevalence of HIV infection . The purpose of this study was to evaluate the effectiveness of a peer feedback program ( PFP ) on h and washing and glove wearing ( HW/GW ) among Thai health care workers . METHODS Subjects ( N = 91 ) were r and omly assigned to receive PFP versus no treatment . By using a checklist , peer observers rated HW/GW compliance in their coworkers during patient care . For 1 month , the investigator posted a report of compliance behaviors from each 3 days of observations . HW/GW was also assessed by the investigator by direct observation at 1 month before the intervention , during the intervention period , and 1 month after the intervention . RESULTS Baseline HW/GW rates for the PFP and control groups were 49.2 % and 61.5 % , respectively . The PFP group had a significantly higher adjusted compliance rate than the control group during the intervention period ( P = .0001 ) . However , there was no significant difference in the compliance scores obtained 1 month after the intervention . CONCLUSIONS The PFP was effective during the intervention period , but there was no retention of effect . Therefore , adjunct methods should be sought to promote retention of effect OBJECTIVES The authors examined organizational characteristics of 16 primary care group practice s to determine their influence on quality or quality improvement . METHODS The authors used a data base compiled during a r and omized , controlled trial of quality assurance interventions consisting of measures of guideline -related performance for 630 practitioners . The authors distinguished performance under practitioners ' control from performance determined partly by systems of care within each practice . The authors conducted analyses for all criteria ( practitioner-controlled and system-dependent criteria ) before and after quality assurance interventions using analysis of variance models with adjustments in performance scores for patient and practitioner characteristics . Specifically , the authors used as covariates the full-time versus part-time status of practitioners , whether practice s were in hospitals or in health centers , and for practice s within health centers , the effect of size of practice in terms of the average number of practitioners on staff during a time period . RESULTS Full-time practitioners performed similarly before interventions but improved more after interventions overall and for practitioner-controlled criteria than did part-time practitioners . Health center practitioners performed better than did those in hospitals for system-dependent criteria before intervention . For system-dependent criteria , larger health centers performed better before interventions and improved more than did smaller health centers . CONCLUSIONS Organizational characteristics including practice size and location ( hospital-based or not ) and full- or part-time status of practitioners should be considered in measuring quality and planning quality improvements , particularly in relation to care that is predominantly under system versus practitioner control RATIONALE AND AIMS Clinical practice guidelines ( CPG ) reflect the evidence of effective pharmacotherapy of chronic ( systolic ) heart failure ( CHF ) which needs to be implemented . This study aim ed to evaluate the effect of a new , multifaceted intervention ( educational train-the-trainer course plus pharmacotherapy feedback = TTT ) compared with st and ard education on guideline adherence ( GA ) in general practice . METHOD Thirty-seven participating general practitioners ( GPs ) were r and omized ( 18 vs. 19 ) and included 168 patients with ascertained symptomatic CHF [ New York Heart Association ( NYHA ) II-IV ] . Groups received CPG , the TTT intervention consisted of four interactive educational meetings and a pharmacotherapy feedback , while the control group received a usual lecture ( St and ard ) . Outcome measure was GA assessed by prescription rates and target dosing of angiotensin converting enzyme ( ACE ) inhibitors ( ACE-I ) or angiotensin receptor blockers ( ARB ) , beta-blockers ( BB ) and aldosterone antagonists ( AA ) at baseline and 7-month follow-up . Group comparisons at follow-up were adjusted to GA , sex , age and NYHA stage at baseline . RESULTS Prescription rates at baseline ( n = 168 ) were high ( ACE-I/ARB 90 , BB 79 and AA 29 % ) in both groups . At follow up ( n = 146 ) , TTT improved compared with St and ard regarding AA ( 43 % vs. 23 % , P = 0.04 ) and the rates of reached target doses of ACE-I/ARB ( 28 % vs. 15 % , P = 0.04 ) . TTT group achieved significantly higher mean percentages of daily target dose ( 52 % vs. 42 % , mean difference 10.3 % , 95 % CI 0.84 - 19.8 , P = 0.03 ) . CONCLUSION Despite of pre-existing high GA in both groups and an active control group , the multifaceted intervention was effective in quality of care measured by GA . Further research is needed on the choice of interventions in different provider population AIMS To evaluate the effectiveness of a two-arm quality improvement program ( QIP ) to support general practice with limited tradition in chronic care on type 2 diabetes patient outcomes . METHODS During 18 months , we performed a cluster r and omized trial with r and omization of General Practice s. The usual QIP ( UQIP : 53 GPs , 918 patients ) merged st and ard interventions including evidence -based treatment protocol , annual benchmarking , postgraduate education , case-coaching for GPs and patient education . The advanced QIP ( AQIP : 67 GPs , 1577 patients ) introduced additional interventions focussing on intensified follow-up , shared care and patient behavioural changes . Main outcomes were HbA1c , systolic blood pressure ( SBP ) , and low density lipoprotein cholesterol ( LDL-C ) , analyzed by generalized estimating equations and linear mixed models . RESULTS In UQIP , endpoints improved significantly after intervention : HbA1c -0.4 % , 95 % CI [ -0.4 ; -0 . 3 ] ; SBP -3mmHg , 95 % CI [ -4 ; -1 ] ; LDL-C -13mg/dl , 95 % CI [ -15 ; -11 ] . In AQIP , there were no significant additional improvements in outcomes : HbA1c -0.4 % , 95 % CI [ -0.4 ; -0.3 ] ; SBP -4mmHg , 95 % CI [ -5 ; -2 ] ; LDL-C -14mg/dl , 95 % CI [ -15 ; -11 ] . CONCLUSIONS A multifaceted program merging st and ard interventions in support of general practice induced significant improvements in the quality of diabetes care . Intensified follow-up in AQIP with focus on shared care and patient behaviour changes did not yield additional benefit |
11,881 | 30,541,603 | Conclusions H and grip exercise is an effective modality for resting BP reduction result ing in clinical ly significant reductions for men and women of all ages . | Background The risk of developing cardiovascular disease can be directly correlated to one ’s resting blood pressure ( BP ) , age , and biological sex .
Resting BP may be successfully reduced using h and grip exercise training , although the impact of age and sex on training effectiveness has yet to be systematic ally evaluated .
The objective of this systematic review is to determine this impact of age and sex on h and grip-induced changes to resting BP . | Substantial progress has been made in the awareness , treatment , and prevention of cardiovascular disease ( CVD ) in women since the first women-specific clinical recommendations for the prevention of CVD were published by the American Heart Association ( AHA ) in 1999.1 The myth that heart disease is a “ man 's disease ” has been debunked ; the rate of public awareness of CVD as the leading cause of death among US women has increased from 30 % in 1997 to 54 % in 2009.2 The age-adjusted death rate result ing from coronary heart disease ( CHD ) in females , which accounts for about half of all CVD deaths in women , was 95.7 per 100 000 females in 2007 , a third of what it was in 1980.3,4 Approximately 50 % of this decline in CHD deaths has been attributed to reducing major risk factors and the other half to treatment of CHD including secondary preventive therapies.4 Major r and omized controlled clinical trials such as the Women 's Health Initiative have changed the practice of CVD prevention in women over the past decade.5 The investment in combating this major public health issue for women has been significant , as have the scientific and medical achievements . Despite the gains that have been made , considerable challenges remain . In 2007 , CVD still caused ≈1 death per minute among women in the United States.6 These represent 421 918 deaths , more women 's lives than were cl aim ed by cancer , chronic lower respiratory disease , Alzheimer disease , and accidents combined.6 Reversing a trend of the past 4 decades , CHD death rates in US women 35 to 54 years of age now actually appear to be increasing , likely because of the effects of the obesity epidemic.4 CVD rates in the United States are significantly higher for black females compared with their white counterparts ( 286.1/100 000 versus Introduction Isometric resistance training has repeatedly shown to be an effective exercise modality in lowering resting blood pressure ( BP ) , yet associated mechanisms and sex differences in the response to training remain unclear . Exploration into potential sex differences in the response to isometric resistance training is necessary , as it may allow for more optimal and sex-based exercise prescription , thereby maximizing the efficacy of the training intervention . Purpose Therefore , we investigated , in normotensives , whether sex differences exist in the response to isometric h and grip ( IHG ) training . Methods Resting BP and endothelium-dependent vasodilation ( brachial artery flow-mediated dilation ; FMD ) were assessed in 11 women ( 23 ± 4 years ) and 9 men ( 21 ± 2 years ) prior to and following 8 weeks of IHG training ( four , 2-min unilateral contractions at 30 % of maximal voluntary contraction ; 3 days per week ) . Results Main effects of time were observed ( all P < 0.05 ) , whereby IHG training reduced systolic BP ( Δ 8 ± 6 mmHg ) , diastolic BP ( Δ 2 ± 3 mmHg ) , mean arterial pressure ( Δ 4 ± 3 mmHg ) , and pulse pressure ( Δ 5 ± 7 mmHg ) , accompanied by increases in absolute ( Δ 0.09 ± 0.15 mm ) and relative ( Δ 2.4 ± 4.1 % ) brachial artery FMD ; however , no significant sex differences were observed in the magnitude of post-training change in any variable assessed ( all P > 0.05 ) . Conclusion IHG training effectively lowers resting BP and improves endothelium-dependent vasodilation in men and women , without significant sex differences in the magnitude of response Isometric HG ( h and grip ) training lowers resting arterial BP ( blood pressure ) , yet the mechanisms are elusive . In the present study , we investigated improved systemic endothelial function as a mechanism of arterial BP modification following isometric HG training in normotensive individuals . This study employed a within-subject repeated measures design primarily to assess improvements in BA FMD ( brachial artery flow-mediated dilation ; an index of endothelium-dependent vasodilation ) , with the non-exercising limb acting as an internal control . Eleven subjects performed four 2-min unilateral isometric HG contractions at 30 % of maximal effort , three times per week for 8 weeks . Pre- , mid- and post-training resting ABP and BA FMD ( exercised arm and non-exercised arm ) were measured via automated brachial oscillometry and ultrasound respectively . BA FMD ( normalized to the peak shear rate experienced in response to the reactive hyperaemic stimulus ) remained unchanged [ exercised arm , 0.029+/-0.003 to 0.026+/-0.003 to 0.029+/-0.004%/s(-1 ) ( pre- to mid- to post-training respectively ) ; non-exercised arm , 0.023+/-0.003 to 0.023+/-0.003 to 0.024+/-0.003%/s(-1 ) ( pre- to mid- to post-training respectively ) ; P=0.22 ] . In conclusion , improved systemic endothelial function is unlikely to be responsible for lowering arterial BP in this population Aerobic and isometric training have been shown to reduce resting blood pressure , but simultaneous aerobic and isometric training have not been studied . The purpose of this study was to compare the changes in resting systolic ( SBP ) , diastolic ( DBP ) , and mean arterial blood pressure ( MAP ) after 6 weeks of either ( i ) simultaneous walking and isometric h and grip exercise ( WHG ) , ( ii ) walking ( WLK ) , ( iii ) isometric h and grip exercise ( IHG ) , or control ( CON ) . Forty-eight healthy sedentary participants ( age 20.7 ± 1.7 yrs , mass 67.2 ± 10.2 kg , height 176.7 ± 1.2 cm , male n = 26 , and female n = 22 ) were r and omly allocated , to one of four groups ( n = 12 in each ) . Training was performed 4 × week−1 and involved either treadmill walking for 30 minutes ( WLK ) , h and grip exercise 3 × 10 s at 20 % MVC ( IHG ) , or both performed simultaneously ( WHG ) . Resting SBP , DBP , and MAP were recorded at rest , before and after the 6-week study period . Reductions in resting blood pressure were significantly greater in the simultaneous walking and h and grip group than any other group . These results show that simultaneous walking and h and grip training may have summative effects on reductions in resting blood pressure Aerobic endurance exercise ( AEX ) is an effective treatment in the prevention and management of high blood pressure ( BP ) . Growing evidence suggests potential benefits from isometric h and grip ( IHG ) exercise , which may promote similar or even larger reductions in BP than AEX . We compared the effects of home-based AEX and home-based IHG on BP . Sixty healthy individuals ( 31 men ; mean age , 33.1 years ; mean BP , 126.9 ± 1.6/84.7 ± 1.1 mm Hg ) were r and omized to IHG , AEX , or a control group . Both exercise interventions were performed in the home environment . The IHG group performed daily 4 × 2 minutes sustained grips at 30 % of maximal volitional contraction . Participants in the AEX group were advised to perform at least 150 min/wk of aerobic exercise at moderate intensity . Outcome measurements were assessed at baseline and 8 weeks of follow-up . Compared with the control group , AEX result ed in a larger reduction in ambulatory BP ; both AEX and IHG exercise tended to induce larger reductions in office systolic BP , and office diastolic BP was significantly more reduced after AEX but not IHG exercise . Responses to training were not significantly different between both the exercise interventions . Eight weeks of home-based AEX results in significant reductions in both ambulatory BP and office BP in healthy adults , whereas IHG reduces only office BP Introduction : Several established tools are available to assess study quality and reporting of r and omized controlled trials ; however , these tools were design ed with clinical intervention trials in mind . In exercise training intervention trials some of the traditional study quality criteria , such as participant or research er blinding , are extremely difficult to implement . Methods : We developed the Tool for the assEssment of Study qualiTy and reporting in EXercise ( TESTEX ) – a study quality and reporting assessment tool , design ed specifically for use in exercise training studies . Our tool is a 15-point scale ( 5 points for study quality and 10 points for reporting ) and addresses previously unmentioned quality assessment criteria specific to exercise training studies . Results : There were no systematic differences between the summated TESTEX scores of each observer [ H(2 ) = 0.392 , P = 0.822 ] . There was a significant association between the summated TESTEX scores of the three observers , with almost perfect agreement between observers 1 and 2 [ intra-class correlation coefficient ( ICC ) = 0.93 , 95 % confidence interval ( CI ) 0.82–0.97 , P < 0.001 ] , observers 1 and 3 ( ICC = 0.96 , 95 % CI 0.89–0.98 , P < 0.001 ) and observers 2 and 3 ( ICC = 0.91 , 95 % CI 0.75–0.96 , P < 0.001 ) . Conclusions : The TESTEX scale is a new , reliable tool , specific to exercise scientists , that facilitates a comprehensive review of exercise training trials OBJECTIVE A short-term isometric exercise protocol was tested in ten hypertensive individuals to determine its efficacy as a high blood pressure-reducing intervention . DESIGN The study was a prospect i ve case study of 10 hypertensive individuals ( 8 men , 2 woman , mean age = 52 + 5 years ) who underwent six weeks of isometric exercise training ( three sessions/week ) . METHODS Blood pressure , blood lipids and markers of oxidative stress were monitored before , during and following the isometric intervention . Electron spin resonance spectroscopy was used to directly measure radicals in the blood sample s. RESULTS After six weeks , systolic blood pressure decreased an average 13 mm Hg ( p < 0.05 ) from a mean blood pressure of 146 to 133 mm Hg , a level that is below the usual 140 mm Hg hypertension threshold . Blood lipids were unchanged , but markers of oxidative stress were affected , with a dramatic decrease in exercise-induced oxygen centered radicals ( -266 % ) , ( p < 0.05 ) and an increased resting whole blood glutathione : oxidized glutathione ( + 61 % ) in hypertensive adults following six weeks of isometric exercise . CONCLUSION Six weeks of isometric exercise training was effective in lowering systolic but not diastolic blood pressure in pre-hypertensive and hypertensive individuals , and enhanced antioxidant protection is a likely underlying mechanism Introduction : Hypertension is a major risk factor contributing to cardiovascular disease , which is the number one cause of deaths worldwide . Although antihypertensive medications are effective at controlling blood pressure , current first-line treatment for hypertension is nonpharmacological lifestyle modifications . Recent studies indicate that isometric resistance training ( IRT ) may also be effective for assisting with blood pressure management . The aim of this study was to determine the efficacy of IRT for blood pressure management and the suitability of a low-intensity working control group . Methods : Forty hypertensive individuals , aged between 36 and 65 years , conducted IRT for 8 weeks . Participants were r and omized into 2 groups , working at an intensity of either 5 % or 30 % of their maximum voluntary contraction . Participants performed 4 × 2 minute isometric h and grip exercises with their nondominant h and , each separated by a 3-minute rest period , 3 days a week . Results : Blood pressure measurements were conducted at baseline and at the end of the protocol using a Finometer . Eight weeks of isometric resistance training result ed in a 7-mmHg reduction of resting systolic blood pressure ( SBP ) ( 136 ± 12 to 129 ± 15 ; P = 0.04 ) in the 30 % group . Reductions of 4 mmHg were also seen in mean arterial pressure ( MAP ) ( 100 ± 8 to 96 ± 11 ; P = 0.04 ) in the 30 % group . There were no statistically significant reductions in diastolic blood pressure for the 30 % group , or any of the data for the 5 % group . Conclusion : Isometric resistance training conducted using h and grip exercise at 30 % of maximum voluntary contraction significantly reduced SBP and MAP . A lack of reduction in blood pressure in the 5 % group indicates that a low-intensity group may be suitable as a working control for future studies Objectives : Aerobic dynamic exercise reduces blood pressure ( BP ) and is broadly recommended by current American and European hypertension guidelines . Isometric exercise is currently not recommended , since data from only a few studies are available . We compare for the first time the effects of isometric h and grip training and aerobic exercise in a r and omized controlled trial . Methods : A total of 75 hypertensive patients were r and omized to one of the following 12-week programmes : Isometric h and grip training five times weekly ( two contractions of 2 min at 30 % of maximal power with each arm ) ; ‘ Sham-h and grip training ’ five times weekly ( two contractions of 2 min at 5 % of maximal power with each arm ) ; Aerobic exercise training of 30 min three to five times per week . All patients underwent office BP measurement , 24-h ambulatory BP measurement and noninvasive assessment of arterial compliance and systemic vascular resistance at baseline and after 12 weeks . Results : Baseline epidemiological and hemodynamic characteristics did not differ between groups . Aerobic exercise led to a significant reduction of systolic 24-h BP ( P = 0.025 ) , office SBP ( P = 0.03 ) , systemic vascular resistance ( P = 0.001 ) and small artery elasticity index ( P = 0.005 ) . There were no statistical significant changes of these parameters in the isometric exercise and the ‘ sham exercise ’ groups ( P > 0.05 each ) . Conclusion : Isometric h and grip training , performed according to a typical protocol , did not reduce BP in hypertensive patients . Aerobic exercise , even as an uncontrolled and unsupervised exercise regimen , led to a significant reduction of ambulatory and office BP The aim of this study was to determine whether a 4-wk h and grip training program would elicit changes in endothelium-dependent and endothelium-independent vasodilatation in resistance vessels of the human forearm . Minimum vascular resistance after a 10-min ischemic stimulus , an index of peak vasodilator capacity , was also determined . Forearm blood flow response to the endothelium-dependent vasodilator methacholine chloride did not change over the 4-wk-intervention period either in the group undertaking training ( n = 11 ) or in control subjects ( n = 6 ) . Similarly , the response to sodium nitroprusside was not influenced by the h and grip training program . Peak vasodilator capacity of the trained forearms significantly increased , whereas no change was evident in the untrained limbs . These results suggest that 4 wk of forearm exercise training enhances peak vasodilator capacity of the vasculature without influencing stimulated activity of the nitric oxide dilator system Previous work from our laboratory demonstrated that isometric h and grip ( IHG ) training improved local , endothelium-dependent vasodilation in medicated hypertensives [ McGowan CL ( PhD Thesis ) , 2006 ; McGowan et al. Physiologist 47 : 285 , 2004 ] . We investigated whether changes in the capacity of smooth muscle to dilate ( regardless of endothelial factors ) influenced this training-induced change , and we examined the acute vascular responses to a single bout of IHG . Seventeen subjects performed four 2-min unilateral IHG contractions at 30 % of maximal voluntary effort , three times a week for 8 wk . Pre- and posttraining , brachial artery flow-mediated dilation ( FMD , an index of endothelium-dependent vasodilation ) and nitroglycerin-mediated maximal vasodilation ( an index of endothelium-independent vasodilation ) were measured in the exercised arm by using ultrasound before and immediately after acute IHG exercise . IHG training result ed in improved resting brachial FMD ( P < 0.01 ) and no change in nitroglycerin-mediated maximal vasodilation . Pre- and posttraining , brachial artery FMD decreased following an acute bout of IHG exercise ( normalized to peak shear rate , pre- , before IHG exercise : 0.01 + /- 0.002 , after IHG exercise : 0.008 + /- 0.002%/s(-1 ) ; post- , before IHG exercise : 0.020 + /- 0.003 , after IHG exercise : 0.010 + /- 0.003%/s(-1 ) ; P < 0.01 ) . Posttraining , resting brachial artery FMD improved yet nitroglycerin-mediated maximal vasodilation was unchanged in persons medicated for hypertension . This suggests that the training-induced improvements in the resting brachial artery FMD were not due to underlying changes in the forearm vasculature . Acute IHG exercise attenuated brachial artery FMD , and although this impairment may be interpreted as hazardous to medicated hypertensives with already dysfunctional endothelium , the effects appear transient as repeated exposure to the IHG stimulus improved resting endothelium-dependent vasodilation Objectives Isometric h and grip ( IHG ) training ( four , 2-min sustained contractions at 30 % of maximal voluntary contraction , three times per week for 8–10 weeks ) lowers resting arterial blood pressure ( BP ) in hypertensive patients , including those receiving pharmacotherapy , although the mechanisms remain elusive . Ambulatory BP measurements are more efficacious in predicting cardiovascular disease-related events , yet the effects of IHG training on ambulatory BP are unknown . The objective of the current investigation was to test the hypotheses that 8 weeks of IHG training lowers resting and 24 h ambulatory BP concomitantly in medicated hypertensive patients , and may be the result of improved vagal modulation . Methods BP was assessed using brachial artery oscillometry , and coarse-graining spectral analysis was used to determine spectral power . Resting and 24 h ambulatory BP and heart rate variability ( HRV ) were measured pretraining , midtraining , and post-training in 11 medicated hypertensive patients ( mean±SD , resting BP : 113.9±12.7/60.7±11.6 mmHg ) , and in nine medicated hypertensive controls ( resting BP : 117.8±14.3/67.5±4.2 mmHg ) . Results Indices of BP and HRV were not significantly altered with IHG training ( all P>0.05 ) . Conclusion IHG training does not lower resting or ambulatory BP in hypertensive patients successfully treated with pharmacotherapy to within the normal range ( ⩽120/80 mmHg ) , nor does it improve HRV . Future studies should examine alternative IHG training protocol s in well-managed hypertensive patients and /or target poorly controlled medicated hypertensive patients Background The risk of developing cardiovascular disease is directly correlated to one ’s resting blood pressure ( BP ) , age , and biological sex . Resting BP can be reduced using h and grip exercise training , but the impact of age and sex on the effectiveness of training is not well documented . Methods / design A systematic search of the literature will be conducted for all experimental studies ( including r and omized controlled trials and prospect i ve experiments ) that report the influence of isometric h and grip exercise training on resting systolic blood pressure . The data bases Medline , Embase , Cochrane Review s , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) , SPORTD iscus , Web of Science , Allied and Complementary Medicine ( AMED ) , PubMed , and Scopus will be search ed until 1 December 2015 . Screening of potential articles , data abstract ion , and quality appraisal will be completed in duplicate independently . When necessary , corresponding authors will be contacted in order to facilitate the separation of pooled data into age and sex categories . Method ological quality will be determined using the Quality Assessment Framework developed by the Cochrane Collaboration and the Newcastle-Ottawa Quality Assessment Scale as appropriate . Any discrepancies will be resolved by a third author . Findings will be presented in accordance with the preferred reporting items for systematic review s and meta- analysis ( PRISMA ) guidelines . Discussion This systematic review will determine the overall effectiveness of h and grip exercise training in improving resting blood pressure . A novel , focused assessment will contrast effectiveness of h and grip training based on the age ( younger 18–54 years , older > 55 years ) and the sex ( men , women ) of study participants . This information is essential to consoli date before moving forward with the development and implementation of h and grip exercise training programmes which are design ed to best meet the needs of particular cohorts . Systematic review registration PROSPERO Background —Radial artery catheterization is associated with endothelial denudation and impaired vasodilator function , while postcatheterization exercise training may enhance artery function . The impact of catheterization and subsequent exercise training on low-flow mediated vasoconstriction ( L-FMC ) has not previously been studied . The aim of this study was to examine whether radial artery L-FMC is impaired by catheterization and consequent endothelial denudation . A further aim was to examine the effect of local h and grip exercise training on radial artery L-FMC and flow-mediated dilation ( FMD ) after transradial catheterization . Methods and Results —Thirty-two subjects undergoing transradial catheterization underwent assessment of L-FMC and FMD in the catheterized and contralateral radial artery before , and the day after , catheterization . A further 18 patients were recruited and r and omly assigned to either a 6-week h and grip exercise training program ( N=9 ) or a nonexercise control period ( N=9 ) . L-FMC was attenuated 1 day postcatheterization in the catheterized arm ( −2.07±0.84 to 0.35±0.83 ) , but unchanged in the noncatheterized arm ( −0.93±0.86 to −0.90±0.92 ; P<0.05 ) . In the training study , both FMD and L-FMC of the catheterized arm were preserved in the exercise group 7 weeks after catheterization ( FMD-pre , 6.84±0.79 ; FMD-post , 6.85±1.16 ; L-FMC-pre , −2.14±1.42 ; L-FMC-post , −3.58±1.04 % ) , but reduced in the control group ( FMD-pre , 8.27±1.52 ; FMD-post , 4.66±0.70 ; P=0.06 ; L-FMC-pre , −3.26±1.19 ; L-FMC-post , −1.34±1.27 % ; P<0.05 ) . Conclusions —Catheterization , and associated endothelial denudation , decreases L-FMC in the radial artery , suggesting that it is endothelium-dependent . Moreover , we demonstrate for the first time that exercise training has beneficial impacts on radial artery vasodilator and constrictor function We previously demonstrated that nonfatiguing rhythmic forearm exercise at 25 % maximal voluntary contraction ( 12 2-s contractions/min ) evokes sympathoexcitation without significant engagement of metabolite-sensitive muscle afferents ( B.A. Batman , J.C. Hardy , U.A. Leuenberger , M.B. Smith , Q.X. Yang and L.I. Sinoway . J. Appl . Physiol . 76 : 1077 - 1081 , 1994 ) . This is in contrast to the sympathetic nervous system responses observed during fatiguing static forearm exercise where metabolite-sensitive afferents are the key determinants of sympathetic activation . In this report we examined whether forearm exercise training would attenuate sympathetic nervous system responses to rhythmic forearm exercise . We measured heart rate , mean arterial blood pressure ( MAP ) , muscle sympathetic nerve activity ( microneurography ) , plasma norepinephrine ( NE ) , and NE spillover and clearance ( tritiated NE kinetics ) during nonfatiguing rhythmic forearm exercise before and after a 4-wk unilateral forearm training paradigm . Training had no effect on forearm mass , maximal voluntary contraction , or heart rate but did attenuate the increase in MAP ( increase in MAP : from 15.2 + /- 1.8 before training to 11.4 + /- 1.4 mmHg after training ; P < 0.017 ) , muscle sympathetic nerve activity ( increase in bursts : from 10.8 + /- 1.4 before training to 6.2 + /- 1.1 bursts/min after training ; P < 0.030 ) , and the NE spillover ( increases in arterial spillover : from 1.3 + /- 0.2 before training to 0.6 + /- 0.2 nmol.min-1.m-2 after training , P < 0.014 ; increase in venous spillover : from 2.0 + /- 0.6 before training to 1.0 + /- 0.5 nmol.min-1.m-2 after training , P < 0.037 ) seen in response to exercise performed by the trained forearm . Thus forearm training reduces sympathetic responses during a nonfatiguing rhythmic h and grip paradigm that does not engage muscle metaboreceptors . We speculate that this effect is due to a conditioning-induced reduction in mechanically sensitive muscle afferent discharge PURPOSE Research has demonstrated the efficacy of isometric h and grip ( IHG ) training to attenuate resting blood pressure . These studies have relied on the use of programmable digital h and grips for training . This study aim ed to determine the effectiveness of simple , inexpensive spring-loaded h and grip devices in producing hypotensive effects . METHODS The study was a r and omized controlled trial of 49 normotensive participants ( 66.4 ± 0.9 years ; 57 % women ) . Participants in the exercise group ( n = 25 ) trained and had blood pressure measured twice weekly for 8 weeks . Control participants ( n = 24 ) completed weekly blood pressure measurements . Pre- and posttraining measurements were each assessed over 3 visits . Statistical analysis of the pre-post data involved analyses of variance and hierarchical linear modeling was used to examine changes over time . RESULTS Following 8 weeks , IHG participants demonstrated significant reductions in resting blood pressure . Systolic and diastolic blood pressures were reduced from 122 ± 3 mm Hg to 112 ± 3 mm Hg ( P < .001 ) and from 70 ± 1 mm Hg to 67 ± 1 mm Hg ( P < .05 ) , respectively . Hierarchical linear modeling analysis also revealed a significant cross-level ( ie , group ÷ time ) interaction , with an estimated reduction in systolic blood pressure of 5.4 mm Hg ( P < .001 ) over the training period in the IHG group . CONCLUSIONS In agreement with previous studies , IHG training reduced resting arterial pressure following 8 weeks of training . Hypotensive effects linked to IHG training may be achieved using simple , inexpensive spring h and grip training devices and may provide a convenient and affordable therapeutic alternative or adjunctive therapy for lowering blood pressure BACKGROUND A neural linkage between peripheral abnormalities and the exaggerated exercise responses in chronic heart failure ( CHF ) was postulated . We studied the ergoreceptors ( afferents sensitive to skeletal muscle work ) in CHF and whether training can affect their activity . METHODS AND RESULTS In 12 stable CHF patients ( ejection fraction [ EF ] = 26.4 % ) and 10 control subjects ( EF = 55.3 % ) , we compared the responses to dynamic h and grip and during a 3-minute period of posth and grip regional circulatory occlusion ( PH-RCO ) . The ergoreflex contribution was quantified as the percentage responses to exercise maintained by PH-RCO compared with recovery without PH-RCO . Patients showed ergoreflex overactivation compared with control subjects in terms of ventilation ( 86.5 % versus 54.5 % ) , diastolic pressure ( 97.8 % versus 53.5 % ) , and leg vascular resistance ( 108.1 % versus 48.9 % ) ( all P < .05 ) . The contribution of the ergoreflex to vagal withdrawal ( high frequency of RR variability ) and sympathetic activation ( low frequency of RR , pressure variability ) was evident in both groups . Nine control subjects and nine CHF patients participated in 6 weeks of forearm training . Training reduced the ergoreflex contributions more in CHF than in control subjects : diastolic pressure ( -33.2 % versus -4.6 % ) , ventilation ( -57.6 % versus -24.6 % ) , and leg vascular resistance ( -59.9 % versus -8.0 % ) ( all P < .05 ) . CONCLUSIONS ( 1 ) The ergoreflex role has a larger effect on the responses to exercise in CHF than in control subjects . ( 2 ) Training may reduce this exaggerated ergoreflex activity , thereby improving the responses to exercise We examined the effects of unilateral , nondominant forearm training ( 4 wk ) on blood pressure and forearm metabolites during ischemic and nonischemic rhythmic h and grip ( 30 1-s contractions/min at 25 % maximal voluntary contraction ) . Contractions were performed by 10 subjects with the forearm enclosed in a pressurized Plexiglas tank to induce ischemic conditions . Training increased the endurance time in the nondominant arm by 102 % ( protocol 1 ) . In protocol 2 , tank pressure was increased in increments of 10 mmHg/min to + 50 mmHg . Training raised the positive-pressure threshold necessary to engage the pressor response . In protocol 3 , h and grip was performed at + 50 mmHg and venous blood sample s were analyzed . Training attenuated mean arterial pressure ( 109 + /- 5 and 98 + /- 4 mmHg pre- and posttraining , respectively , P < 0.01 ) , venous lactate ( 2.9 + /- 0.4 and 1.8 + /- 0.3 mmol/l pre- and posttraining , respectively , P < 0.01 ) , and the pH response ( 7.21 + /- 0.02 and 7.25 + /- 0.01 , pre- and posttraining , respectively , P < 0.01 ) . However , deep venous O2 saturation was unchanged . Training increased the positive-pressure threshold for metaboreceptor engagement , reduced metabolite concentrations , and reduced mean arterial pressure during ischemic exercise The aim of the present study was to investigate the effects of isometric-h and grip-induced PIT ( physical ischaemia training ) on remote coronary recruitment and growth . A total of 74 CAD ( coronary artery disease ) patients were r and omly assigned to either the IHG ( isometric h and grip group ) or NEG ( non-exercise group ) . Patients in the IHG performed isometric h and grip exercises during 1 min of coronary balloon occlusion , whereas patients in the NEG remained sedentary . CFI ( collateral flow index ) , HR ( heart rate ) , SBP ( systolic blood pressure ) and DBP ( diastolic blood pressure ) were evaluated before and at the end of occlusion . In a second study , 21 CAD patients were r and omly divided into the IHT ( isometric h and grip training ) group or the NTG ( non-training group ) . Patients in the IHT group performed 3 months of IHT , whereas patients in the control group remained sedentary . SPECT ( single-photon emission computed tomography ) was used to evaluate myocardial perfusion , and VEGF ( vascular endothelial growth factor ) levels were determined using ELISA . In the IHG , CFI was significantly higher than in the control group ( P<0.01 ) . HR , SBP and DBP in the IHG were significantly higher than in the NEG ( P<0.01 ) at the end of occlusion . In the second study , myocardial perfusion ( P<0.05 ) and left ventricular ejection fraction ( P<0.01 ) were significantly improved in the IHT group . VEGF levels in the IHT group were significantly increased ( P<0.01 ) . Levels of VEGF were negatively correlated with the summed rest score of SPECT ( r=-0.60 , P<0.01 ) . In conclusion , isometric h and grip exercise-induced PIT may promote remote collateral recruitment and growth in CAD patients BACKGROUND Exercise training improves endothelium-dependent vasodilation in animals . This study was design ed to determine whether forearm exercise training improves endothelium-dependent vasodilation in control subjects and patients with heart failure , a disease associated with abnormal endothelium-dependent vasodilation . METHODS AND RESULTS We used strain gauge plethysmography to assess the effects of short-term forearm exercise training on resistance vessel function in 11 control subjects and 7 patients with New York Heart Association class II and III heart failure . Subjects performed 30 minutes of h and grip exercise four times a week for 4 - 6 weeks . In the control subjects , exercise training increased forearm blood flow ( FBF ) responses to intra-arterial acetylcholine ( 20 microg/min ) from 6.9 + /- 3.1 to 12.2 + /- 3.0 mL/min/100 mL and peak reactive hyperemic FBF responses from 38.1 + /- 5.6 to 47.4 + /- 5.6 ( P < .05 ) . Basal FBF and responses to nitroprusside , L-N-monomethyl arginine and acute forearm exercise were not significantly changed . In the patients with heart failure , chronic forearm exercise did not significantly change any of the above-measured parameters . CONCLUSION Forearm exercise training improves endothelium-dependent vasodilation and peak hyperemic FBF in control subjects but not in patients with heart failure . These data suggest that resistance vessel abnormalities may not be as readily modifiable by exercise training in patients with heart failure compared with control subjects There exists no examination of what is the minimum anti-hypertensive threshold intensity for isometric exercise training . Twenty two normotensive participants were r and omly assigned to training intensities at either 5 % or 10 % of their maximal contraction . Twenty participants completed the study . Clinical meaningful , but not statistically significant , reductions in systolic blood pressure were observed in both 5 % and 10 % groups -4.04 mm Hg ( 95 % CI -8.67 to + 0.59 , p=0.08 ) and -5.62 mm Hg ( 95 % CI -11.5 to + 0.29 , p=0.06 ) respectively after 6 weeks training . No diastolic blood pressure reductions were observed in either 5 % -0.97 mm Hg ( 95 % CI -2.56 to + 0.62 , p=0.20 ) or 10 % MVC + 1.8 mm Hg ( 95 % CI -1.29 to + 4.89 , p=0.22 ) groups respectively after training . In those unable to complete isometric exercise at the traditional 30 % intensity , our results suggest there is no difference between 5 and 10 % groups and based on the principle of regression to the mean , this could mean both interventions induce a similar placebo-effect PURPOSE This study examined the effects of isometric h and grip training on resting arterial blood pressure , heart rate variability , and blood pressure variability in older adults with hypertension . METHODS Nine subjects performed four 2-min isometric h and grip contractions at 30 % of the maximum voluntary contraction force , 3 d.wk(-1 ) for 10 wk , and eight subjects served as controls . RESULTS After training , there was a significant reduction in resting systolic pressure and mean arterial pressure . In addition , power spectral analysis of heart rate variability demonstrated that the low frequency : high frequency area ratio tended to decrease . CONCLUSIONS It is concluded that isometric training at a moderate intensity elicits a hypotensive response and a simultaneous increase in vagal modulation in older adults with hypertension Background : Aerobic exercise reduces blood pressure ( BP ) on average 5–7 mmHg among those with hypertension ; limited evidence suggests similar or even greater BP benefits may result from isometric h and grip ( IHG ) resistance exercise . Method : We conducted a r and omized controlled trial investigating the antihypertensive effects of an acute bout of aerobic compared with IHG exercise in the same individuals . Middle-aged adults ( n = 27 ) with prehypertension and obesity r and omly completed three experiments : aerobic ( 60 % peak oxygen uptake , 30 min ) ; IHG ( 30 % maximum voluntary contraction , 4 × 2 min bilateral ) ; and nonexercise control . Study participants were assessed for carotid-femoral pulse wave velocity pre and post exercise , and left the laboratory wearing an ambulatory BP monitor . Results : SBP and DBP were lower after aerobic versus IHG ( 4.8 ± 1.8/3.1 ± 1.3 mmHg , P = 0.01/0.04 ) and control ( 5.6 ± 1.8/3.6 ± 1.3 mmHg , P = 0.02/0.04 ) over the awake hours , with no difference between IHG versus control ( P = 0.80/0.83 ) . Pulse wave velocity changes following acute exercise did not differ by modality ( aerobic increased 0.01 ± 0.21 ms , IHG decreased 0.06 ± 0.15 ms , control increased 0.25 ± 0.17 ms , P > 0.05 ) . A subset of participants then completed either 8 weeks of aerobic or IHG training . Awake SBP was lower after versus before aerobic training ( 7.6 ± 3.1 mmHg , P = 0.02 ) , whereas sleep DBP was higher after IHG training ( 7.7 ± 2.3 mmHg , P = 0.02 ) . Conclusion : Our findings did not support IHG as antihypertensive therapy but that aerobic exercise should continue to be recommended as the primary exercise modality for its immediate and sustained BP benefits Background There has been very little published work exploring the comparative effects of isometric resistance training ( IRT ) on blood pressure ( BP ) in men and women . Most of the previously published work has involved men and used resting BP as the primary outcome variable . Early evidence suggests that IRT is particularly effective in older women and has a positive influence on ambulatory BP , a better predictor of disease risk . Objectives With the WHO now placing global emphasis on the primary prevention of hypertension , the goals of this proof-of-concept study were to ( i ) examine whether sex differences exist in the ambulatory BP-lowering effects of IRT in young , normotensive men and women and ( ii ) determine whether these reductions can be predicted by simple laboratory stress tasks ( a 2-min sustained isometric contraction and a math task involving subtracting a two-digit number from a series of numbers ) . Results There were no differences in the IRT-induced reductions in 24-h ( men : & Dgr;4 mmHg , women : & Dgr;4 mmHg ) , daytime ( men : & Dgr;3 mmHg , women : & Dgr;4 mmHg ) , or night-time ( men : & Dgr;4 mmHg , women : & Dgr;3 mmHg ) ambulatory BP in men ( n=13 ) and women ( n=11 ) ( P<0.05 ) and these changes were not associated with systolic BP reactivity to either stress task ( all P>0.05 ) . Conclusion Our data suggest that lower ambulatory BP can be achieved , to a similar magnitude in young healthy women as well as men , with IRT ; however , the BP-lowering effectiveness can not be predicted by systolic BP reactivity . Taken together , this work heralds a potentially novel approach to the primary prevention of hypertension in both men and women and warrants further investigation in a larger clinical outcome trial |
11,882 | 30,946,371 | Conclusion : It will provide latest evidence to determine the efficacy and safety of CS for treatment of patients with NSCLC . | Background : Non-small cell lung cancer ( NSCLC ) is the most common lung cancer .
Numerous clinical studies have reported that the combination of carboplatin and S-1 ( CS ) can be used to treat NSCLC effectively .
However , no systematic review has been conducted to assess its efficacy and safety for NSCLC .
This systematic review aims to evaluate the efficacy and safety of CS for treatment of patients with NSCLC . | We conducted a phase II study of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small cell lung cancer ( NSCLC ) . Chemotherapy-naïve patients with advanced NSCLC were treated with S-1 and carboplatin . S-1 was administered orally twice daily for 14 days and carboplatin AUC 5 on day 1 of each cycle , and this was repeated every 4 weeks . Twenty-nine patients were enrolled in this study . The main grade 3 or 4 toxicities observed during the first cycle were neutropenia ( 10.3 % ) , thrombocytopenia ( 41 % ) , and transaminase elevation . Objective responses were seen in 9 patients ( response rate 31.0 % ) . The median survival time and median progression-free survival were 16.0 months ( 95 % CI , 12.1 - 19.0 months ) and 4.5 months ( 95 % CI , 3.2 - 6.1 months ) , respectively . Hematological adverse events reaching grade 3 or 4 were neutropenia ( 10.3 % ) , anemia ( 3.4 % ) , and thrombocytopenia ( 3.4 % ) . No febrile neutropenia was detected . Nonhematological toxicities were also mild . Although grade 3 infection was observed in 1 patient , the patient improved without intervention . The combination of S-1 plus carboplatin is an active and well-tolerated regimen for the treatment of patients with advanced NSCLC . Further investigations are required to confirm our results in r and omized trials Gefitinib , an epidermal growth factor receptor tyrosine kinase inhibitor ( EGFR-TKI ) , is an effective treatment for advanced non-small cell lung cancer ( NSCLC ) in patients with activating EGFR mutations . However , there have been little evidence -based studies of gefitinib in combination with platinum-doublet therapy in these patients . We performed a phase II trial to determine the efficacy and safety of triplet chemotherapy with gefitinib , carboplatin , and S-1 as a first-line treatment . This was a multicentre , single-arm , phase II trial of carboplatin , S-1 , and gefitinib in advanced NSCLC patients with activating EGFR mutations . Patients received four courses of these drugs in 3–4 week cycles . In each cycle , carboplatin ( area under curve = 5 ) was administered on day 1 , S-1 ( 80 mg/m2 ) on days 1–14 , and gefitinib ( 250 mg ) every day . Subsequently , the same regimen without carboplatin was administered until disease progression or unacceptable toxicity occurred . The 1-year progression-free survival ( PFS ) was the primary endpoint , while response rate ( RR ) , PFS , overall survival ( OS ) , and safety were secondary endpoints . Thirty-five patients were enrolled into this study . The 1-year PFS was 74.3 % and the overall RR was 85.7 % . The median PFS for all patients was 17.6 months ( 95 % confidence interval 15.5–∞ ) , but the median OS was not reached , because 28 patients were still alive after a median follow-up time of 21.4 months . Haematological adverse events ( grade 3 or higher ) included neutropaenia ( 17.1 % ) , thrombocytopenia ( 14.3 % ) , and anaemia ( 5.7 % ) , while non-haematological adverse events ( grade 3 or higher ) included elevated aminotransferase ( 20.0 % ) , diarrhoea ( 14.3 % ) , and febrile neutropaenia ( 2.9 % ) . No interstitial lung disease or treatment-related deaths occurred . Combination chemotherapy with carboplatin , S-1 , and gefitinib is efficacious and well tolerated as a first-line treatment in advanced NSCLC patients with activating EGFR mutations A previous phase 3 trial demonstrated noninferiority in terms of overall survival for combined S‐1 ( an oral fluoropyrimidine ) and carboplatin compared with combined paclitaxel and carboplatin as first‐line treatment for advanced non – small cell lung cancer ( NSCLC ) . In the current study , the authors evaluated the efficacy and safety of combined S‐1 , carboplatin , and bevacizumab followed by maintenance with S‐1 and bevacizumab in chemotherapy‐naive patients with advanced nonsquamous NSCLC The majority of patients with completely resected stage II or IIIA non-small-cell lung cancer ( NSCLC ) require adjuvant chemotherapy to improve survival following surgery . In the present trial , the 2-year disease-free survival ( DFS ) , and the feasibility and safety of S-1 as an adjuvant chemotherapy for advanced lung cancer were evaluated . A total of 40 patients with completely resected stage II or IIIA NSCLC were enrolled and r and omized to receive postoperative chemotherapy with either up to 4 cycles of paclitaxel plus carboplatin ( arm A ) or with up to 1 year of S-1 ( arm B ) . The primary endpoint was 2-year DFS . The secondary endpoints were feasibility and toxicity . A total of 40 patients were enrolled , but 3 were excluded in accordance with the exclusion criteria . The remaining 37 patients were analyzed . The 2-year DFS rate was 54.2 % in arm A and 84.2 % in arm B. Overall , 15/18 ( 83.3 % ) patients completed 4 cycles of paclitaxel plus carboplatin and 13/19 ( 68.4 % ) completed 1-year of S-1adjuvant chemotherapy . Of the 18 ( 16.7 % ) patients in arm A , 3 experienced grade 3 or 4 adverse events , while none in arm B experienced such events . Therefore , S-1 chemotherapy for patients with completely resected stage II or IIIA NSCLC was a feasible and safe regimen , and it may therefore be considered as a potential adjuvant chemotherapy option for advanced NSCLC The objective of this phase I/II study was to determine the recommended dose ( RD ) of S-1 and carboplatin ( CBDCA ) , and to evaluate the efficacy and safety of this combination in the treatment of patients with advanced non-small cell lung cancer ( NSCLC ) . Chemotherapy-naïve patients were treated with S-1 given orally on days 1 - 14 , and CBDCA infused intravenously on day 1 , repeated every 3 weeks . RD was AUC5 of CBDCA and 80 mg/m(2 ) of S-1 . Nineteen patients were treated at the RD . The overall response was 30.8 % ( 95 % confidence interval : 17.1 - 58.3 % ) . The response rate in the RD was 36.8 % ( 95 % CI : 16.3 - 61.6 % ) . The median overall survival time was 11.1 months ( 95 % CI : 8.1 - 15.3 months ) and the median progression-free survival time was 5.0 months ( 95 % CI : 3.6 - 6.0 months ) . Major grade s 3 - 4 toxicities were thrombocytopaenia ( 47 % ) , anaemia ( 26 % ) and infection ( 16 % ) . This is the first report to show promising activity of this combination in phase II , including survival data and manageable toxicity , especially in out patients receiving treatment for advanced NSCLC PURPOSE The primary goal of this open-label , multicenter , r and omized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival ( OS ) in chemotherapy-naive patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A total of 564 patients were r and omly assigned to receive either carboplatin ( area under the curve , 5 ) on day 1 plus oral S-1 ( 40 mg/m2 twice per day ) on days 1 to 14 or carboplatin ( area under the curve , 6 ) plus paclitaxel ( 200 mg/m2 ) on day 1 every 21 days . RESULTS At the planned interim analysis , with a total of 268 death events available , the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS ( hazard ratio , 0.928 ; 99.2 % CI , 0.671 to 1.283 ) . Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm , with 1-year survival rates of 57.3 % and 55.5 % , respectively . Rates of leukopenia or neutropenia of grade 3/4 , febrile neutropenia , alopecia , and neuropathy were more frequent in the carboplatin and paclitaxel arm , whereas thrombocytopenia , nausea , vomiting , and diarrhea were more common in the carboplatin and S-1 arm . The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm . CONCLUSION Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC , and is thus a valid treatment option Background : The purpose of this study was to evaluate the feasibility and compliance of adjuvant chemotherapy of S-1 plus carboplatin for patients with completely resected non-small cell lung cancer ( NSCLC ) of pathological stage IB-IIIB . Methods : S-1 was given orally at a dose of 80 mg/m2/day for 2 weeks , followed by a 2-week period of no treatment . Carboplatin was given intravenously on day 8 at an area under the curve of 6 . This regimen was repeated for four to six 28-day courses . Results : Seventeen patients were enrolled in this study . Fourteen of them completed at least 4 cycles of chemotherapy . Nine patients had grade 2 and three patients had grade 3 thrombocytopenia , respectively . Severe nonhematologic toxicities were uncommon . Treatment was delayed in a few patients because of prolonged thrombocytopenia . Conclusion : We concluded that the regimen was feasible and tolerable for patients with completely resected NSCLC as adjuvant chemotherapy BACKGROUND A phase III study ( Lung Cancer Evaluation of TS-1 ) previously demonstrated noninferiority in terms of overall survival ( OS ) at interim analysis for carboplatin-S-1 compared with carboplatin-paclitaxel for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A total of 564 patients were r and omly assigned to receive either carboplatin on day 1 plus oral S-1 on days 1 - 14 or carboplatin-paclitaxel on day 1 every 21 days . Up date d results and post hoc subgroup analysis according to tumor histology are presented . RESULTS The up date d analysis revealed a median OS of 15.2 months in the carboplatin-S-1 arm and 13.1 months in the carboplatin-paclitaxel arm , with a hazard ratio ( HR ) of 0.956 [ 95 % confidence interval ( CI ) 0.793 - 1.151 ] , consistent with the previous primary analysis . Median OS was 14.0 months in the carboplatin-S-1 arm and 10.6 months in the carboplatin-paclitaxel arm ( HR 0.713 ; 95 % CI 0.476 - 1.068 ) for patients with squamous cell carcinoma ( SCC ) , with corresponding values of 15.5 and 13.9 months ( HR 1.060 ; 95 % CI 0.859 - 1.308 ) for those with non-SCC . CONCLUSIONS These results establish the efficacy and safety of carboplatin-S-1 in patients with advanced NSCLC regardless of tumor histology Purpose There is no established st and ard regimen for non-small cell lung cancer ( NSCLC ) patients with interstitial lung disease ( ILD ) . For them , we performed a pilot study to evaluate the feasibility of chemotherapy with carboplatin and S-1 , which are known as cytotoxic drug with rare development of ILD as adverse event . Methods A total of 21 chemotherapy-naive NSCLC patients with ILD were prospect ively enrolled between March 2009 and September 2011 . Every 3 weeks , carboplatin at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m2 daily for 14 days were administered . Results The median age at initiating chemotherapy was 67 . Histological examination revealed 10 patients ( 48 % ) with adenocarcinoma . Before chemotherapy , partial pressure of arterial O2 ( PaO2 ) was low with a median of 71 Torr on room air . The median number of cycles administered was four , and the overall response rate and disease control rate were 33 and 67 % , respectively . At the time of data cut-off , all patients were deceased . The median progression-free survival ( PFS ) and median overall survival ( OS ) periods were 4.2 and 9.7 months . There was no significant difference of PFS and OS according to tumor histology . Acute exacerbation ( AE ) of ILD following S-1 plus carboplatin occurred in two patients ( 10 % , 2/21 ) within first course treatment . However , they were successfully managed with steroid therapy and survived for 7.0 and 8.8 months , respectively , after AE-ILD development . Conclusions This is the first prospect i ve study to evaluate the safety and efficacy of S-1 plus carboplatin treatment for NSCLC patients with ILD . This regimen could be a feasible option for NSCLC patients with ILD , regardless of tumor histology . Our results would support to carry out a large-scale clinical trial to confirm the feasibility of this regimen We conducted a phase I study to determine the maximum tolerated dose , the recommended dose and the safety profile of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small-cell lung cancer . Chemotherapy-naive patients with advanced non-small-cell lung cancer were treated with S-1 and carboplatin . S-1 was administered orally twice daily for 14 days and carboplatin on day 1 of each cycle , and this was repeated every 4 weeks . Doses of each drug were planned as follows : level 1 , 5/65 ; level 2 , 5/80 ; level 3 , 6/80 [ carboplatin ( area under the curve , mg/ml/min)/S-1 ( mg/m2/day ) ] . The dose-limiting toxicity of the regimen was assessed during the first chemotherapy cycle . Twelve patients were enrolled in this study . The main grade 3 or grade 4 toxicities observed during the first cycle were neutropenia ( 41 % ) , thrombocytopenia ( 41 % ) and transaminase elevation . Two of three patients in level 2 had dose-limiting toxicity and this level was considered the maximum tolerated dose . Level 1 was selected as the recommended dose . Objective responses were seen in four patients ( response rate 33 % ) . The combination of S-1 plus carboplatin is a feasible and well-tolerated regimen for the treatment of patients with advanced non-small-cell lung cancer INTRODUCTION S-1 is an oral fluoropyrimidine-based combination of tegafur , gimeracil , and oteracil potassium . Although the combination of S-1 with carboplatin is a first-line chemotherapy regimen for advanced non-small cell lung cancer ( NSCLC ) , the efficacy and safety of the regimen in the elderly remain unknown . METHODS The patient inclusion criteria were previously untreated advanced NSCLC , wild-type epidermal growth factor receptor , aged 70 years or more , and a performance status ( PS ) of 0 - 2 . The patients received oral S-1 ( 40mg/m2 , twice daily ) for 2 weeks and carboplatin ( area under the curve : 5 ) on day 1 every 4 weeks as induction treatment . After four induction cycles , S-1 alone ( 40mg/m2 , twice daily ) was administered for 2 weeks every 4 weeks as a maintenance therapy until disease progression . The primary endpoint was the overall response rate ( ORR ) , which was expected to exceed 20 % , and the secondary endpoints included the disease control rate ( DCR ) , progression-free survival ( PFS ) , overall survival ( OS ) , and the toxicity profile . The associations between clinical outcomes and expression of genes such as thymidylate synthase and thymidine phosphorylase in the tumors were evaluated . RESULTS Thirty-three patients were enrolled between March 2013 and June 2015 . The median age was 78 ( range 70 - 89 ) years , and 51.5 % had a PS of 0 . The ORR was 30.3 % ( 95 % confidence interval ( CI ) : 14.6 - 46.0 ) and the DCR 57.6 % ( 95 % CI : 40.7 - 74.4 ) . Grade 3/4 toxicities included thrombocytopenia ( 42.4 % ) , neutropenia ( 33.3 % ) , and anemia ( 27.3 % ) . There was one treatment-related death due to aspiration pneumonia following febrile neutropenia . The median PFS and OS were 134days ( 95 % CI : 79 - 173 ) and 479days ( 95 % CI : 250 - 571 ) , respectively . Low thymidine phosphorylase expression was associated with the DCR ( P<0.01 ) . CONCLUSION This study met the pre design ed primary endpoint , and the regimen seems to be a favorable treatment option OBJECTIVES The clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer ( NSCLC ) patients with interstitial lung disease ( ILD ) remain unclear . To fulfill this unmet medical need , we conducted a phase II study to eluci date the efficacy of S-1 in combination with carboplatin ( CBDCA ) in NSCLC patients with ILD . MATERIAL S AND METHODS A total of 33 advanced or recurrent NSCLC patients with ILD were prospect ively enrolled in this multicenter , open-label , phase II study . Every 4 weeks , CBDCA at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m2 daily for 14 days were administered . The primary endpoint was the investigator-assessed objective response rate . RESULTS The median age at initiating chemotherapy was 70 . Sixteen patients ( 48.5 % ) had squamous cell carcinoma histology . With respect to the types of ILD , the usual interstitial pneumonia pattern was dominant ( 66.7 % ) . The median number of cycles administered was 3 , and the overall response rate and disease control rate were 33.3 % and 78.8 % , respectively . The median progression-free survival , the median survival time and the 1-year survival rate were 4.8 months , 12.8 months and 51.4 % , respectively . Acute exacerbation of ILD caused by chemotherapy was noted in 2 patients ( 6.1 % ) . CONCLUSION This is the first prospect i ve study design ed to evaluate the efficacy of a specific chemotherapeutic regimen as the primary endpoint in patients with advanced NSCLC with ILD . The combination of S-1 with CBDCA may be a treatment option for advanced NSCLC patients with ILD ( The clinical trial registration number : UMIN000011046 ) |
11,883 | 28,707,404 | Sustained inflation was not better than intermittent ventilation for reducing mortality in the delivery room and during hospitalisation .
When considering secondary outcomes , such as need for intubation , need for or duration of respiratory support , or bronchopulmonary dysplasia , we found no evidence of relevant benefit for sustained inflation over intermittent ventilation .
The duration of mechanical ventilation was shortened in the SLI group . | BACKGROUND At birth , infants ' lungs are fluid-filled .
For newborns to have a successful transition , this fluid must be replaced by air to enable effective breathing .
Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation ( PPV ) .
Giving prolonged ( sustained ) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs .
OBJECTIVES To assess the efficacy of an initial sustained ( > 1 second duration ) lung inflation versus st and ard inflations ( ≤ 1 second ) in newly born infants receiving resuscitation with intermittent PPV . | BACKGROUND : Studies suggest that giving newly born preterm infants sustained lung inflation ( SLI ) may decrease their need for mechanical ventilation ( MV ) and improve their respiratory outcomes . METHODS : We r and omly assigned infants born at 25 weeks 0 days to 28 weeks 6 days of gestation to receive SLI ( 25 cm H2O for 15 seconds ) followed by nasal continuous positive airway pressure ( nCPAP ) or nCPAP alone in the delivery room . SLI and nCPAP were delivered by using a neonatal mask and a T-piece ventilator . The primary end point was the need for MV in the first 72 hours of life . The secondary end points included the need for respiratory supports and survival without bronchopulmonary dysplasia ( BPD ) . RESULTS : A total of 148 infants were enrolled in the SLI group and 143 in the control group . Significantly fewer infants were ventilated in the first 72 hours of life in the SLI group ( 79 of 148 [ 53 % ] ) than in the control group ( 93 of 143 [ 65 % ] ) ; unadjusted odds ratio : 0.62 [ 95 % confidence interval : 0.38–0.99 ] ; P = .04 ) . The need for respiratory support and survival without BPD did not differ between the groups . Pneumothorax occurred in 1 % ( n = 2 ) of infants in the control group compared with 6 % ( n = 9 ) in the SLI group , with an unadjusted odds ratio of 4.57 ( 95 % confidence interval : 0.97–21.50 ; P = .06 ) . CONCLUSIONS : SLI followed by nCPAP in the delivery room decreased the need for MV in the first 72 hours of life in preterm infants at high risk of respiratory distress syndrome compared with nCPAP alone but did not decrease the need for respiratory support and the occurrence of BPD Background Current neonatal resuscitation guidelines recommend 3:1 compression : ventilation ( C : V ) ratio . Recently , animal studies reported that continuous chest compressions ( CC ) during a sustained inflation ( SI ) significantly improved return of spontaneous circulation ( ROSC ) . The approach of CC during SI ( CC+SI ) has not been examined in the delivery room during neonatal resuscitation . Hypothesis It is a feasibility study to compare CC+SI versus 3:1 C : V ratio during neonatal resuscitation in the delivery room . We hypothesised that during neonatal resuscitation , CC+SI will reduce the time to ROSC . Our aim was to examine if CC+SI reduces ROSC compared with 3:1 C : V CPR in preterm infants <33 weeks of gestation . Study design R and omised feasibility trial . Method Once CC was indicated all eligible infants were immediately and r and omly allocated to either CC+SI group or 3:1 C : V group . A sequentially numbered , brown , sealed envelope contained a folded card box with the treatment allocation was opened by the clinical team at the start of CC . Study interventions Infants in the CC+SI group received CC at a rate of 90/min during an SI with a duration of 20 s ( CC+SI ) . After 20 s , the SI was interrupted for 1 s and the next SI was started for another 20 s until ROSC . Infants in the ‘ 3:1 group ’ received CC using 3:1 C : V ratio until ROSC . Primary outcome Overall the mean ( SD ) time to ROSC was significantly shorter in the CC+SI group with 31 ( 9 ) s compared with 138 ( 72 ) s in the 3:1 C : V group ( p=0.011 ) . Conclusion CC+SI is feasible in the delivery room . Trial registration number Clinical trials.gov NCT02083705 , pre- results Abstract Aim : To evaluate efficacy and safety of delivery room ( DR ) sustained lung inflation ( SLI ) in resuscitation of preterm neonates . Methods : R and omized Controlled Trial including 112 preterm infants r and omized to either SLI ( n = 57 ) using T-piece resuscitator [ maximum three inflations with maximum pressure of 30 cmH2O for 15 s followed by continuous positive airway pressure ( CPAP ) of 5–7 cmH2O ] or conventional bag/mask inflation ( C BMI ) ( n = 55 ) using traditional self-inflating bag ( maximum pressure of 40 cmH2O at a rate of 40–60 per min ) . Failure was defined as the need for DR or first 72 h intubation . Cord and 2-h post-resuscitation blood sample s were collected to measure interleukin (IL)-1β and tumor necrosis factor-α levels before and after intervention . Results : SLI was associated with significantly higher success rate compared to C BMI [ 75.4 versus 54.5 % ; p = 0.017 ] , lower need for DR intubation [ 5.3 % versus 23.6 % ; ( X2 = 7.7 ; p = 0.005 ) ] , higher 5-min-Apgar score ( median 8 versus 7 ; p = 0.018 ) , shorter duration on nasal-CPAP ( p = 0.017 ) , and non-significantly different air leak ( 7 % versus 11 % ; p = 0.3 ) and bronchopulmonary dysplasia rates among survivors ( 2 % versus 11 % ; p = 0.09 ) . Post-resuscitation IL-1β plasma levels increased significantly in C BMI ( p = 0.009 ) and not in SLI group . Conclusion : Delivery room SLI is more effective than intermittent bag and mask inflation for improving short-term respiratory outcome in preterm infants , without significant adverse effects AIM To compare the effects of sustained lung inflation ( SLI ) vs. st and ard resuscitation on physiologic responses of preterm infants during resuscitation . METHODS Preterm infants ( 25 - 32 weeks gestational age ) requiring positive-pressure ventilation or continuous positive airway pressure were r and omly assigned to either the SLI group ( SLI at 25cmH2O for 15s ) or Non-SLI group ( st and ard resuscitation alone ) . The heart rate ( HR ) , oxygen saturation ( SpO2 ) , oxygen requirement , and intubation rate in the delivery room were evaluated . RESULTS Eighty-one infants were enrolled ( SLI group , 43 ; Non-SLI group , 38 ) . The use of SLI effectively reduced the oxygen requirement . The mean fraction of inspired oxygen 10min after birth was 0.28 ( 95 % CI , 0.26 - 0.30 ) in the SLI group and 0.47 ( 95 % CI , 0.43 - 0.52 ) in the Non-SLI group ( p<0.001 ) . During the first 5min , infants in the SLI group trended towards a higher HR and SpO2 than those in the Non-SLI group . The intubation rate in the delivery room was not different between the two groups ; however , among infants ≤28 weeks gestational age , the intubation rate was lower in the SLI than Non-SLI group ( 5 of 17 [ 29 % ] vs. 10 of 16 [ 63 % ] , respectively ; p=0.05 ) . The duration of respiratory support , survival without bronchopulmonary dysplasia , and the occurrence of pneumothorax were not different between the groups . CONCLUSION SLI in infants who require respiratory support appears to be effective in facilitating postnatal transition as determined by HR and SpO2 responses , result ing in less oxygen supplementation . Further studies are needed to confirm the benefits of SLI Background : Sustained lung inflation ( SLI ) applied at birth has been demonstrated to lead to clearance of lung fluid and achievement of a precocious functional residual capacity in animal studies . Objectives : To verify if the application of SLI in preterm infants at birth may reduce the need for mechanical ventilation and improve their respiratory outcome . Methods : We prospect ively studied 89 infants with respiratory distress ( gestational age ( GA ) 28.1 ± 2.2 weeks ) treated at birth with a SLI ( 25 cm H2O , sustained for 15 s ) in addition to AAP recommendations versus a historical control group ( n = 119 ; GA 28.1 ± 2.0 weeks ) treated without SLI with the same device ( controlled positive end-expiratory pressure of 5 cm H2O ) . Results : The SLI group had less need for ( 51 vs. 76 % , p < 0.0001 ) and shorter duration of mechanical ventilation ( 5 ± 11 vs. 11 ± 19 days , p = 0.008 ) , a more frequent occurrence of exclusive nasal continuous airway pressure support ( 49 vs. 24 % , p < 0.0001 ) and INtubation-SURfactant-Extubation ( INSURE ) treatment ( 16 vs. 3 % , p = 0.01 ) , less need for surfactant ( 45 vs. 61 % , p = 0.027 ) and postnatal steroids ( 10 vs. 25 % , p = 0.01 ) , a shorter duration of oxygen therapy ( 21 ± 27 vs. 31 ± 31 days , p = 0.016 ) , and , finally , a lower occurrence of bronchopulmonary dysplasia in survivors ( 7 vs. 25 % , p = 0.004 ) . Multiple regression analysis showed that 23–27 weeks of GA and birth weight < 750 g increased the risk of mechanical ventilation , while a clinical risk index for babies ( CRIB ) score <3 as well as INSURE strategy and SLI treatment in the delivery room decreased it . Conclusions : The application of a SLI at birth in preterm infants with respiratory distress may decrease the need for mechanical ventilation without inducing evident adverse effects The protection of preterm lungs should start immediately after birth , and the current trial is a much awaited research in this direction . This study ( 1 ) evaluates the role of application of prophylactic sustained lung inflation ( SLI ) immediately after birth as a lung protective strategy in decreasing the need of mechanical ventilation ( MV ) in first 72 hours of life and in preventing bronchopulmonary dysplasia ( BPD ) among extreme preterm infants . BPD is a multifactorial disease , and the advantage of SLI over intermittent MV in terms of improving functional residual capacity ( 2,3 ) forms the basis of this trial . The application of SLI immediately after birth is a new strategy which was first evaluated by Lindner et al. in 1999 ( 4 ) . Two additional studies showed beneficial effects of SLI ; however , one was an observational study ( 5 ) and the other did not use positive end expiratory pressure ( 6 ) . The current r and omised trial has used nCPAP immediately after birth in the control group and in the intervention group following SLI , thus overcoming the disadvantage of the previous trial . The investigators eluci date d eligibility and exclusion criteria . The actual time of taking consent ( antenatal or immediately after birth ) is not clear . There was appropriate generation of the r and omisation sequence and allocation concealment . Although the research ers who decided to start MV and those assessing the study end points were blinded to the intervention however , the caregivers were not blinded which could have led to performance bias . Given the paucity of the literature , the amount and duration of pressure chosen for providing SLI seem appropriate . Authors have set the SpO2 targets at 88–95 % against the currently recommended targets of 91–95 % . The sample size was calculated a priori , and the outcomes were clearly defined . All r and omised subjects completed the trial as per protocol , and all predefined outcomes were reported . Authors have used intention-totreat principle . This study has shown that the application of prophylactic SLI followed by nCPAP in the delivery room decreased the need for MV in the first 72 hours of life in extreme preterm infants . However , there is no effect on the robust clinical outcomes such as death and /or BPD . Additionally , there is concern of a trend towards increased incidence of pneumothorax and interstitial emphysema , which may be related to the pressure and duration used in SLI . Moreover , there is no statistically significant difference in need and duration of any respiratory support . Although the trial has not result ed in reduction in BPD or death , the reduction in need of MV in first 72 hours may be beneficial in re source -restricted setting s where the availability of MV is limited . Given these findings , the routine application of SLI at birth can not be recommended in extreme preterm infants . More trials are required across different setting s and gestations to establish its efficacy . Given the risk of air leak syndromes , future trials also need to establish the optimal pressure and duration of SLI . Moreover , the data regarding the neurodevelopmental outcome need to be generated to establish its long-term safety Objective : To assess the need for respiratory support in late preterm infants treated with sustained lung inflation ( SLI ) at birth . Study design : In this controlled trial , we r and omly assigned infants born at 34 + 0 to 36 + 6 weeks of gestation to receive SLI ( 25 cmH2O for 15 s ) at birth , followed by continuous positive airway pressure ( CPAP ) or assistance according to the recommendations of the American Academy of Pediatrics . The primary outcome was the need for any type of respiratory support . The secondary outcomes included neonatal intensive care unit ( NICU ) admission for respiratory distress and length of stay . The risk ratios ( RRs ) and 95 % confidence intervals ( CIs ) of the outcomes were calculated for the SLI group in reference to the control group . Results : A total of 185 infants were enrolled : 93 in the SLI group and 92 in the control group . No difference was found in the need for any type of respiratory support between the infants treated with SLI and the control group ( 10.6 vs 8.7 % , RR 1.24 , 95 % CI 0.51 to 2.99 ) . The NICU admission for respiratory distress and the length of stay did not differ between the groups . Conclusion : Providing SLI at birth in late preterm infants does not affect their need for respiratory support Background : Bronchopulmonary dysplasia ( BPD ) is a common outcome of preterm birth . Experimental animal work has shown that initial ventilation strategies injure the immature lung and may lead to BPD . Studies with asphyxiated babies have shown that , if tidal ventilation at birth is preceded by sustained lung inflation , larger inflation volumes can be achieved , which is thought to lead to clearance of lung fluid and formation of the functional residual capacity ( FRC ) . Objective : To see if sustained lung inflation at initial resuscitation of preterm babies would facilitate the removal of lung fluid , establish the FRC , and allow an even distribution of alveolar opening , permitting less aggressive ventilation , leading to a reduction in pulmonary inflammation and subsequent BPD . Method : The outcomes of 52 babies of less than 31 weeks gestation , resuscitated at birth using either a sustained lung inflation of five seconds or a conventional lung inflation of two seconds for the first assisted breath of resuscitation , were examined . Evidence of pulmonary inflammation was determined by quantification of interleukins 6 , 10 , and 1β and tumour necrosis factor α in bronchoalveolar lavage fluid by enzyme linked immunosorbent assay . Results : There were no significant differences in any of the cytokines . Death occurred in 3/26 babies in the conventional group and 6/26 babies in the sustained lung inflation group . Survival without BPD occurred in 13/26 and 14/26 respectively . Conclusion : The use of sustained lung inflation at resuscitation did not reduce lung injury , as measured by inflammatory markers Background Extremely preterm infants require assistance recruiting the lung to establish a functional residual capacity after birth . Sustained inflation ( SI ) combined with positive end expiratory pressure ( PEEP ) may be a superior method of aerating the lung compared with intermittent positive pressure ventilation ( IPPV ) with PEEP in extremely preterm infants . The Sustained Aeration of Infant Lungs ( SAIL ) trial was design ed to study this question . Methods / Design This multisite prospect i ve r and omized controlled unblinded trial will recruit 600 infants of 23 to 26 weeks gestational age who require respiratory support at birth . Infants in both arms will be treated with PEEP 5 to 7 cm H2O throughout the resuscitation . The study intervention consists of performing an initial SI ( 20 cm H20 for 15 seconds ) followed by a second SI ( 25 cm H2O for 15 seconds ) , and then PEEP with or without IPPV , as needed . The control group will be treated with initial IPPV with PEEP . The primary outcome is the combined endpoint of bronchopulmonary dysplasia or death at 36 weeks post-menstrual age . Trial Registration www . clinical trials.gov , Trial identifier NCT02139800 , Registered 13 May Background Sustained lung inflations ( SLI ) during neonatal resuscitation may promote alveolar recruitment in preterm infants . While most of the studies focus on respiratory outcome , the impact of SLI on the brain has n’t been investigated yet . Objective Do SLI affect cerebral blood volume ( CBV ) in preterm infants ? Methods Preterm infants of gestation 28 weeks 0 days to 33 weeks 6 days with requirement for respiratory support ( RS ) were included in this r and omized controlled pilot trial . Within the first 15 minutes after birth near-infrared spectroscopy ( NIRS ) measurements using ‘ NIRO-200-NX ’ ( Hamamatsu , Japan ) were performed to evaluate changes in CBV and cerebral tissue oxygenation . Two groups were compared based on RS : In SLI group RS was given by applying 1–3 SLI ( 30 cmH2O for 15 s ) continued by respiratory st and ard care . Control group received respiratory st and ard care only . Results 40 infants ( 20 in each group ) with mean gestational age of 32 weeks one day ( ±2 days ) and birth weight of 1707 ( ±470 ) g were included . In the control group ΔCBV was significantly decreasing , whereas in SLI group ΔCBV showed similar values during the whole period of 15 minutes . Comparing both groups within the first 15 minutes ΔCBV showed a tendency toward different overall courses ( p = 0.051 ) . Conclusion This is the first study demonstrating an impact of SLI on CBV . Further studies are warranted including reconfirmation of the present findings in infants with lower gestational age . Future investigations on SLI should not only focus on respiratory outcome but also on the consequences on the developing brain . Trial Registration German Clinical Trials Register DRKS00005161 BACKGROUND High-frequency oscillatory ventilation ( HFOV ) has been advocated for use to improve lung inflation while potentially decreasing lung injury . There were few data on the early use of HFOV in hypoxemic term neonates . AIM To evaluate the effectiveness of HFOV , used as the initial mode of ventilation , in neonates with severe meconium aspiration syndrome ( MAS ) . METHODS In a tertiary care paediatric intensive care unit , 17 term neonates with severe MAS were managed with HFOV , used as the initial mode of ventilation , and prospect ively evaluated . Ventilator setting s , blood gases , oxygenation index ( OI ) and alveolar-arterial oxygen difference ( P(A-a)O2 ) were prospect ively recorded during HFOV treatment and compared at the multiple time intervals . RESULTS Target ventilation was easily achieved with HFOV . Initiation of HFOV caused a significant decrease in FIO2 , achieved as early as 1 hour ( from 0.93 ± 0.11 to 0.78 ± 0.25 ; p=0.031 ) and the improvement was sustained during the 1 - 32 hours period . There were a significant decreases in P ( A-a ) O2 and OI , respectively , at 4 hours ( from 562.5 ± 71.7 to 355.4 ± 206 mm Hg ; p=0.03 ) and 8 hours ( from 23.3±17 to 14.6±16.3 ; p=0.04 ) , that were sustained up to 16 and 40 hours . Three neonates ( 17.6 % ) developed pneumothorax on HFOV . One patient required oxygen support at 28 days . No significant others complications associated with HFOV were detected . Sixteen infants ( 94 % ) were successfully weaned from HFOV and 15 ( 88 % ) survived to hospital discharge . CONCLUSION Use of HFOV as the initial mode of ventilation in neonates with severe MAS is an effective strategy BACKGROUND . Initial ventilation strategy may play an important role in the development of bronchopulmonary dysplasia in very preterm infants . Early nasal continuous positive airway pressure is an accepted approach , but r and omized clinical trials are lacking . Our aim was to determine whether early nasal continuous positive airway pressure , preceded by a sustained inflation , is more effective and less injurious in very preterm infants than conventional intervention . METHODS . Two hundred seven very preterm infants were assigned r and omly in the delivery room to either a sustained inflation through a nasopharyngeal tube followed by early nasal continuous positive airway pressure ( early functional residual capacity intervention ) or repeated manual inflations with a self-inflating bag and mask followed by nasal continuous positive airway pressure , if necessary , after arrival at the NICU . The primary outcome measure was intubation < 72 hours of age and bronchopulmonary dysplasia at 36 weeks was used as secondary outcome . This trial was registered as an early functional residual capacity intervention trial ( IS RCT N 12757724 ) . RESULTS . In the early functional residual capacity intervention group , fewer infants were intubated at < 72 hours of age or received > 1 dose of surfactant , and the average duration of ventilatory support was less . Infants in the early functional residual capacity intervention group developed bronchopulmonary dysplasia less frequently . CONCLUSIONS . A sustained inflation followed by early nasal continuous positive airway pressure , delivered through a nasopharyngeal tube , is a more efficient strategy than repeated manual inflations with a self-inflating bag and mask followed by nasal continuous positive airway pressure on admission to the NICU Importance A sustained inflation ( SI ) provided at birth might reduce bronchopulmonary dysplasia ( BPD ) . Objective This study aims to examine whether an SI-guided exhaled carbon dioxide ( ECO2 ) compared with positive pressure ventilation ( PPV ) alone at birth decreases BPD . Design R and omised controlled trial . Infants were r and omly allocated to either SI ( SI group ) or PPV ( PPV group ) . Participants Participants of this study include infants between 23 + 0 and 32 + 6 weeks gestation with a need for PPV at birth . Intervention Infants r and omised into the SI group received an initial SI with a peak inflation pressure ( PIP ) of 24 cmH2O over 20 s. The second SI was guided by the amount of ECO2 . If ECO2 was ≤20 mm Hg , a further SI of 20 s was delivered . If ECO2 was > 20 mm Hg the second SI was 10 s. Infants r and omised into the PPV group received mask PPV with an initial PIP of 24 cmH2O . Primary outcomes Reduction in BPD defined as the need for respiratory support or supplemental oxygen at corrected gestational age of 36 weeks . Results SI ( n=76 ) and PPV ( n=86 ) group had similar rates of BPD ( 23 % vs 33 % , p=0.090 , not statistically significant ) . The duration of mechanical ventilation was significantly reduced with SI versus PPV ( 63 ( 10–246 ) hours versus 204 ( 17–562 ) hours , respectively ( p=0.045 ) ) . No short-term harmful effects were identified from two SI lasting up to 40 s ( eg , pneumothorax , intraventricular haemorrhage or patent ductus arteriosus ) . Conclusion Preterm infants <33 weeks gestation receiving SI at birth had lower duration of mechanical ventilation and similar incidence of BPD compared with PPV . Using ECO2 to guide length of SI is feasible . Trial registration number NCT01739114 ; Results BACKGROUND Variations exist among the administered pressure and duration of sustained lung inflation ( SLI ) in the delivery room ( DR ) . We aim ed to evaluate the appropriate pressure and duration needed for SLI in preterm infants with respiratory distress syndrome . METHODS We prospect ively r and omized 100 preterm ( < 32 weeks ) infants to receive either conventional therapy of continuous positive airway pressure ( CPAP ) at 5 cm H2O , or four groups of CPAP plus a single maneuver of SLI at four regimens based on administered pressures and duration s ; P20D20 ( Pressure of 20 cm H2O for a duration of 20 seconds ) , P20D10 ( 20 cm H2O for 10 seconds ) , P15D20 ( 15 cm H2O for 20 seconds ) , and P15D10 ( 15 cm H2O for 10 seconds ) using a T-piece ventilator . The primary outcome was the need for endotracheal intubation ( ETT ) in the DR . Broncho-alveolar lavage ( BAL ) was obtained from intubated infants for interleukin-10 ( IL-10 ) assessment . RESULTS SLI decreased the need for ETT in the DR ( 21 % versus 55 % , p < 0.01 ) compared to conventional therapy . ETT requirement was significantly lower in P20D10 ( 20 % ) , P15D20 ( 20 % ) , and P15D10 ( 20 % ) groups , but not P20D20 ( 25 % ) compared to the conventional group ( 55 % , p < 0.05 ) . Group P20D20 had significant higher BAL levels of IL-10 [ 713.8 ( IQR 611 - 874 ) versus 535.4 ( IQR 480 - 563 ) pg/ml , p < 0.05 ] compared to the conventional group , and to other SLI groups . Pneumothorax was not significantly different among studied groups . CONCLUSION SLI for a pressure and duration ≥20 cm H2O for 20 seconds is not superior to lower pressures for shorter duration and may be injurious to lungs Aim : To prove the hypothesis that sustained pressure‐controlled inflation compared to intermittent m and atory ventilation for lung recruitment via nasopharyngeal tube after delivery is more effective in reducing the rate of endotracheal intubation and mechanical ventilation in very preterm infants . Methods : The study was design ed as a r and omized , controlled trial . The setting was the delivery room and neonatal intensive care unit of a university hospital in Germany . Subjects were 61 infants ( 25.0–28.9 wk of gestation ) with signs of respiratory distress immediately after birth . The infants were r and omized in the delivery room to two different respiratory interventions : either to sustained pressure‐controlled inflation ( 15 s ) or to intermittent m and atory ventilation ( rate 60 min−1 ) . This respiratory support was given by a nasopharyngeal tube . The inflation pressure or peak inspiratory pressure was increased stepwise ( 20–25‐30 cm H2O ) according to the response of heart rate and oxygenation . Results : The main outcome measure was treatment failure , i.e. , endotracheal intubation and mechanical ventilation according to given intubation criteria . Treatment failure occurred in 61 % ( 95 % CI , sustained pressure‐controlled inflation : 42–78 ) and 70 % ( 95 % CI , intermittent m and atory ventilation : 51–85 ) ( p= 0.59 ) . The rates of mortality ( 3/61 ) , severe intraventricular haemorrhage ( 5/61 ) and chronic lung disease ( 10/58 ) were not different between groups |
11,884 | 23,934,958 | TwHF may have an add-on effect on remission in patients with primary NS .
There was insufficient evidence to assess if TwHF was as effective as prednisone or CPA . | BACKGROUND Tripterygium wilfordii Hook F ( TwHF ) , a traditional Chinese herbal medicine used as an immunosuppressive agent , has been prescribed in China for patients with primary nephrotic syndrome ( NS ) for more than two decades .
Although patients with primary NS in China have benefited from TwHF treatment , its properties have not yet been fully understood .
OBJECTIVES To assess the benefits and harms of TwHF for patients with primary NS . | Background / Aims : Multi-glycoside from Tripterygium wilfordii Hook f. ( GTW ) is used for treatment of progressive glomerulonephritis ( GN ) in China . We have previously reported the beneficial effects of GTW on acute GN induced by an anti-Thy-1.1 monoclonal antibody ( mAb ) . In the present study , the effect and potential mechanisms of GTW on the chronic irreversible model of GN were investigated . Methods : Progressive GN was induced in rats by two intravenous injections of anti-Thy-1.1 mAb 1 - 22 - 3 . Daily oral administration of GTW was started before the second injection of mAb until the day of sacrifice . Ten rats were r and omly divided into a control ( vehicle-treated ) and a GTW-treated group , and sacrificed on day 45 after the first injection of mAb 1 - 22 - 3 . Proteinuria was determined on days 0 , 1 , 3 , 5 , 7 , 10 , 14 , 20 , 25 , 30 , 35 , 40 , and 45 . Blood biochemical parameters , morphological changes of mesangium , glomerular infiltration of macrophage and T lymphocyte , and glomerular mRNA expression of cytokines ( TGF-β , IL-2 , and IFN-γ ) were examined from the sample s taken at terminal sacrifice . Results : GTW treatment significantly ameliorated proteinuria , renal function , prolonged mesangial lesions and inflammatory cell accumulation in glomerulus . In addition , it significantly reduced the glomerular mRNA expression for TGF-β , IL-2 , and IFN-γ . Conclusion : GTW ameliorates prolonged glomerular lesions presumably through suppression of cytokine production ( TGF-β , IL-2 , and IFN-γ ) . GTW could be an effective therapeutic agent for treatment of chronic renal diseases BACKGROUND In a proportion of adults with steroid-resistant nephrotic syndrome ( SRNS ) , intravenous cyclophosphamide therapy fails . Tacrolimus may be a promising alternative to cyclophosphamide for such patients . STUDY DESIGN Prospect i ve observational study . SETTING & PARTICIPANTS 19 adults with SRNS ( 6 with minimal change nephropathy , 8 with focal segmental glomerulosclerosis [ FSGS ] , and 5 with mesangioproliferative glomerulonephritis ) that did not respond to intravenous cyclophosphamide therapy were studied from January 2003 to September 2006 . Oral tacrolimus was administered ( target trough levels , 5 to 10 ng/mL ) for 24 weeks , then reduced doses were given ( target trough level , 3 to 6 ng/mL ) for another 24 weeks . FACTORS Histopathologic types : minimal change nephropathy ( n = 6 ) , FSGS ( n = 8) , and mesangioproliferative glomerulonephritis ( n = 5 ) . OUTCOMES MEASUREMENTS outcome variables included complete remission ( decrease in daily proteinuria to protein < or = 0.3 g/d ) , partial remission ( decrease in daily proteinuria to protein < 3.5 g/d but > 0.3 g/d ) , relapse ( increase in daily proteinuria to protein > or = 3.5 g/d in patients who had partial or complete remission ) , change in kidney function , and tacrolimus dosing and serum levels . RESULTS 17 patients completed at least 24 weeks of tacrolimus therapy . Complete remission was achieved in 11 patients ( 64.7 % ) , and partial remission was achieved in 3 ( 17.6 % ) . Complete or partial remission was achieved in 5 of 5 patients with minimal change nephropathy , 4 of 7 patients with FSGS , and 5 of 5 patients with mesangioproliferative glomerulonephritis . Primary resistance to tacrolimus was seen in 3 patients ( 17.6 % ) , all with FSGS . Mean times to achieve partial and complete remission were 5.6 + /- 1.4 and 8.0 + /- 5.1 weeks , respectively . In patients who achieved complete or partial remission , 35.7 % experienced relapse during follow-up ( mean , 37.6 + /- 13.4 months ) . Two patients had doubling of serum creatinine levels , both with FSGS . LIMITATIONS Observational study . CONCLUSIONS Tacrolimus rapidly and effectively induced remission of SRNS in Chinese adults with disease refractory to treatment with intravenous cyclophosphamide . Treatment may be less effective in patients with FSGS Context In Chinese medicine , extracts of Tripterygium wilfordii Hook F ( TwHF , known as lei gong teng or thunder god vine ) are used to treat autoimmune and inflammatory conditions . Small clinical trials suggest that TwHF may benefit patients with rheumatoid arthritis . Contribution This trial compared TwHF extract with sulfasalazine in 121 patients with active rheumatoid arthritis who could continue oral prednisone and nonsteroidal anti-inflammatory drugs but not disease-modifying antirheumatic drugs . Among patients who continued treatment for 24 weeks , achievement of 20 % improvement in American College of Rheumatology criteria was greater with TwHF than with sulfasalazine . Adverse event rates were similar . Caution Only 62 % and 41 % of patients continued TwHF and sulfasalazine treatment , respectively , and provided 24 weeks of data . The Editors Rheumatoid arthritis is characterized by chronic inflammation of the joint lining ( synovial membrane ) ( 1 ) , which causes pain and swelling of diarthrodial joints . Over time , uncontrolled disease results in progressive joint damage , disability , and increased mortality ( 2 ) . The evolving underst and ing of the immune mechanisms that perpetuate the inflammatory response has led to effective targeted therapies , including inhibitors of inflammatory cytokines ( tumor necrosis factor , interleukin-1 , and interleukin-6 ) , modulators of activation of CD4 + T cells and dendritic cells , and agents that deplete B cells ( 3 , 4 ) . Despite the clinical efficacy of these therapies , many patients have no clinical ly meaningful response or discontinue treatment because of adverse events . Furthermore , the limited availability of effective biologics in developing countries , the need for parenteral administration of the biologics , and the relatively high cost all restrict access to these therapies in many patients with rheumatoid arthritis around the world ( 5 ) . In traditional Chinese medicine , extracts of the roots of the medicinal vine Tripterygium wilfordii Hook F ( TwHF ) ( known in China as lei gong teng or thunder god vine ) have shown therapeutic promise in treating autoimmune and inflammatory conditions as well as cancer ( 68 ) . More recently , different extracts of TwHF have been used in Chinese allopathic medicine for the treatment of autoimmune and inflammatory diseases , and small controlled trials reported good responses with TwHF extracts in patients with cadaveric kidney transplants ( 9 , 10 ) and Crohn disease ( 11 ) . Of the approximately 380 metabolites isolated from the plant , 95 % are terpenoids ( 12 , 13 ) . Three diterpenoidstriptolide , tripdiolide , and triptonide (13)are the most abundant and account for the immunosuppressive and anti-inflammatory effects observed with the root extracts in both in vitro and in vivo studies ( 6 ) . In 2 previous single-center trials of patients with rheumatoid arthritis , the extract was st and ardized by the content of triptolide and tripdiolide ( 14 ) . This made it possible to use optimal doses identified in an open-label trial ( 15 ) for the design of a subsequent small placebo-controlled study ( 16 ) . Although the number of patients was small , the apparent clinical impact and experimental results indicating potent inhibition of the expression of proinflammatory genes both in vitro and in vivo in animal models ( 1721 ) provided the rationale for our multicenter , double-blind , active comparator trial of a st and ardized TwHF extract in patients with active rheumatoid arthritis . Methods Design Overview This r and omized , controlled , 24-week study was conducted between March 2004 and October 2005 . All participants provided written informed consent to enter the trial , and the institutional review boards at the participating sites approved the protocol . All investigators and outcome assessors were blinded to group assignment of the patients . Our objective was to determine whether therapy with TwHF extract , 180 mg/d , was statistically significantly better than therapy with sulfasalazine , 2 g/d , over 24 weeks in patients with rheumatoid arthritis by using st and ard outcome measures . Setting and Participants Our study was conducted at 11 U.S. centers : 2 academic centers ( National Institutes of Health , Bethesda , Maryl and , and University of Texas , Dallas , Texas ) and 9 rheumatology subspecialty clinics ( 1 each in Dallas and Austin , Texas ; Tampa and Fort Lauderdale , Florida ; Arlington , Virginia ; Duncanville , Pennsylvania ; Wheaton and Greenbelt , Maryl and ; and Lansing , Michigan ) . Eligible patients had to be at least 18 years of age and have established rheumatoid arthritis , defined by the American College of Rheumatology ( ACR ) classification criteria ( 22 ) as rheumatoid arthritis lasting longer than 6 months . Eligible patients had active disease , defined as 6 or more painful and swollen joints , a visual analogue scale score for pain of at least 3 ( on a scale of 1 to 10 , with 1 being mild ) , and a C-reactive protein ( CRP ) level of 57.14 nmol/L or greater ( 0.6 mg/dL ) or an erythrocyte sedimentation rate ( ESR ) greater than 25 mm/h . Patients who were taking any disease-modifying antirheumatic drug at screening underwent a 28-day washout period . The use of oral prednisone , at stable doses up to 7.5 mg/d , and nonsteroidal anti-inflammatory drugs were allowed as long as the dose was not changed for 28 days before r and omization and the patient agreed to continue to take the medication during the study . Table 1 lists baseline patient characteristics . Table 1 . Patient Characteristics at Baseline R and omization and Interventions We used a computer-generated , pseudo-r and om code ( with r and om , permuted blocks ) to assign patients to treatment groups across all centers . We assigned eligible patients at a 1:1 ratio to receive either TwHF extract , 180 mg/d , or sulfasalazine , 2 g/d . In the event of gastrointestinal intolerance , the protocol allowed for temporary dose reduction of 50 % . As described elsewhere ( 15 , 16 ) , the triptolide and tripdiolide content of the ethanol and ethylacetate extract ( measured by high-performance liquid chromatography [ 22 ] ) was used to st and ardize the drug preparation for this study . On the basis of data on in vitro activity and in vivo toxicity , 30 mg of TwHF extract were formulated per capsule . Our study was conducted under the U.S Food and Drug Administrationapproved Investigational New Drug application 39191 . Outcomes and Measurements Patients were evaluated clinical ly and by laboratory measures at baseline , 2 weeks , and every 4 weeks for a total of 24 weeks . A rheumatologist or trained staff member masked to treatment allocation assessed the patients . Serum or plasma specimens were obtained from the patients at baseline , 4 weeks , and 24 weeks and stored at 80C until analysis . Radiographs of h and s and feet were obtained at baseline and 24 weeks or at study discontinuation . The primary end point was a 20 % improvement at 24 weeks , as defined by ACR criteria ( ACR 20 ) ( 23 ) . To meet criteria , a patient must have 20 % or greater improvement in both tender and swollen joints ( 68 tender and 66 swollen joints were assessed ) and 20 % or greater improvement in 3 or more of the following : the physician 's or patient 's assessment of global health status , the patient 's assessment of pain on a visual analogue scale , the patient 's assessment of function ( using a modified version of the Health Assessment Question naire [ HAQ ] ) , and the serum CRP level . Secondary end points included the efficacy of TwHF in achieving ACR 50 and ACR 70 responses at 24 weeks , the improvement in the European League Against Rheumatism Disease Activity Score 28 ( DAS 28 ) measure , and a change in the Sharpvan der Heijde score of the h and and foot radiographs ( 24 ) . Radiographs were obtained at baseline and at the end of the study and were scored by 2 independent readers who were blinded to the r and omization schedule and the radiograph sequence . Drug adherence was assessed by using a daily diary and by pill counts . Body weight , blood pressure , and serum glucose level were measured at each visit . Laboratory assessment s included ESR ( Westergren method ) ; high-sensitivity CRP with normal levels up to 38.1 nmol/L ( 0.4 mg/dL ) , which was analyzed in a central laboratory ; and interleukin-6 levels , which were measured at baseline , 4 weeks , and 24 weeks by using high-sensitivity enzyme-linked immunosorbent assay ( R&D Systems , Minneapolis , Minnesota ) . Rheumatoid factor was measured by immunonephelometry with a BNII analyzer ( Siemens Medical Solutions Diagnostics , Newark , Delaware ) , cortisol and adrenocorticotropic hormone levels by immunochemiluminescence methods with an Immulite 2500 ( Siemens Medical Solutions Diagnostics , Los Angeles , California ) , and plasma lipids by Synchron LX-20 automated analyzers ( Beckman Coulter , Brea , California ) . Safety assessment s consisted of all patients marking adverse events in their drug diaries , which were review ed on each visit . Vital signs and safety laboratory measures , including a complete blood count and a chemistry profile ( electrolyte and liver and kidney function tests ) , were recorded at each visit . Adverse events were grade d by severity according to the National Cancer Institute Common Toxicity Criteria guidelines . An electrocardiogram ( ECG ) was obtained from all patients at baseline , 2 weeks , and the end of study . After 24 weeks , no follow-up was conducted . Statistical Analysis We design ed our study to detect differences in the primary end point with greater than 90 % power at a 2-sided level of significance of 0.05 . To properly account for missing end point data due to dropouts , we used mixed-effects analyses to predict each patient 's ACR response at the end of study visit and to properly account for uncertainty in that prediction . The response was categorized according to the ACR 20 , ACR 50 , and ACR 70 criteria . In a similar manner , we compared changes in DAS 28 from baseline visit between treatment groups . We modeled the treatment group , visit number ( 2 r and om-effect terms for visit number and visit BACKGROUND To examine whether tacrolimus is more effective and safe than cyclosporine ( CsA ) in inducing remission in patients with steroid-resistant nephrotic syndrome ( SRNS ) . STUDY DESIGN R and omized controlled trial , nonblind , parallel group . SETTING S & PARTICIPANTS Tertiary-care hospital ; 41 consecutive patients with idiopathic SRNS , estimated glomerular filtration rate greater than 60 mL/min/1.73 m(2 ) , and histological characteristics showing minimal change disease , focal segmental glomerulosclerosis , or mesangioproliferative glomerulonephritis were r and omly assigned to treatment with tacrolimus ( n = 21 ) or CsA ( n = 20 ) . INTERVENTION Tacrolimus ( 0.1 to 0.2 mg/kg/d ) or CsA ( 5 to 6 mg/kg/d ) for 1 year ; cotreatment with alternate-day prednisolone and enalapril . OUTCOMES Patients achieving complete remission ( urinary protein-creatinine ratio < 0.2 g/g and serum albumin > or = 2.5 g/dL ) or partial remission ( urinary protein-creatinine ratio , 0.2 to 2 g/g , and serum albumin > or = 2.5 g/dL ) at 6 and 12 months ; time to remission ; proportion with relapses ; side effects . RESULTS No patient was lost to follow-up . After 6 months of therapy , remission occurred in 18 ( 85.7 % ) and 16 patients ( 80 % ) treated with tacrolimus and CsA , respectively ( relative risk [ RR ] , 1.07 ; 95 % confidence interval [ CI ] , 0.81 to 1.41 ) . Rates of remission at 12 months were also similar ( RR , 1.14 ; 95 % CI , 0.84 to 1.55 ) . The proportion of patients who experienced relapse was significantly greater in those receiving CsA compared with tacrolimus ( RR , 4.5 ; 95 % CI , 1.1 to 18.2 ; P = 0.01 ) . The decrease in blood cholesterol levels was greater with tacrolimus compared with CsA ( difference in mean values , 45.1 mg/dL ; 95 % CI , 19.1 to 71.2 ) . Persistent nephrotoxicity necessitating stoppage of medicine was seen in 4.7 % and 10 % patients , respectively . Cosmetic side effects ( hypertrichosis and gum hypertrophy ) were significantly more frequent in CsA-treated patients ( P < 0.001 ) . LIMITATIONS Single-center study , small sample size , and short duration of follow-up . CONCLUSIONS Tacrolimus or CsA in combination with low-dose steroids show similar efficacy in inducing remission in patients with SRNS . Therapy with tacrolimus is a promising alternative to CsA in view of the lower risk of relapses and lack of cosmetic side effects We performed a multi-centre r and omized controlled trial to compare the efficacy of mycophenolate mofetil ( MMF ) to that of cyclosporine A ( CsA ) in treating children with frequently relapsing nephrotic syndrome and biopsy-proven minimal change disease . Of the 31 r and omized initially selected patients , seven were excluded . The remaining 24 children received either MMF 1200 mg/m2 per day ( n = 12 ) or CsA 4–5 mg/kg per day ( n = 12 ) during a 12-month period . Of the 12 patients in the MMF group , two discontinued the study medication . Evaluation of the changes from the baseline glomerular filtration rate showed an overall significant difference in favour of MMF over the treatment period ( p = 0.03 ) . Seven of the 12 patients in the MMF group and 11 of the 12 patients in the CsA group remained in complete remission during the entire study period . Relapse rate in the MMF group was 0.83/year compared to 0.08/year in the CsA group ( p = 0.08 ) . None of the patients reported diarrhea . Pharmacokinetic profiles of mycophenolic acid were performed in seven patients . The patient with the lowest area under the curve had three relapses within 6 months . In children with frequently relapsing minimal change nephrotic syndrome , MMF has a favourable side effect profile compared to CsA ; however , there is a tendency towards a higher relapse risk in patients treated with MMF This study was conducted to analyze the trend of histopathologic subtypes in idiopathic nephrotic syndrome ( INS ) in a homogenous racial group in India population . A prospect i ve analysis of 400 consecutive children with INS was performed . Kidney biopsies were performed according to st and ard indications . Steroids were administered following the Arbeitsgeminschaft fur Padiatrische Nephrologie protocol . Cyclophosphamide was administered to children in the frequent-relapser , steroid-dependent , and steroid-nonresponder categories . Of the various histopathologic subtypes , focal segmental glomerulosclerosis ( FSGS ) was the most common ( 87 of 222 subtypes ; 39.1 % ) . Children who underwent biopsy between July 1992 and December 1996 ( group B , n = 157 ) were compared with our initial published data of biopsies performed between January 1990 and June 1992 ( group A , n = 65 ) , with similar indications for biopsy in both groups . The incidence of FSGS was significantly greater in biopsies performed in the recent period ( group B , 47 % versus group A , 20 % ; P = 0.0002 ) . The different clinical and biochemical parameters were also analyzed to differentiate FSGS from the other 2 subtypes . Hypertension ( P = 0 . 005 ) , renal insufficiency at presentation ( P = 0.001 ) , and steroid resistance ( P = 0.0006 ) were significantly greater in children with FSGS . On follow-up ( mean , 5.4 years ) , children with FSGS were at a significantly greater risk for developing renal insufficiency ( P = 0 . 0001 ) . We conclude there is a shift toward an increasing prevalence of FSGS over the years in the Indian population . This trend has immense therapeutic and prognostic significance OBJECTIVE To explore the efficacy and safety of ethyl acetate ( EA ) extracts of the Chinese herbal remedy Tripterygium wilfordii Hook F ( TWHF ) for treatment of patients with a variety of inflammatory and autoimmune diseases including rheumatoid arthritis ( RA ) . METHODS The roots of TWHF were extracted sequentially by ethyl alcohol and ethyl acetate and the content of the extract documented . An open label , dose escalation Phase I study was performed in 1993 in 13 patients with established RA . Clinical manifestations and laboratory findings were examined before and every 4 weeks after starting treatment with the EA extract . RESULTS Three patients withdrew from the trial during the first 16 weeks of the dose escalation . These patients received a maximum dosage of 180 mg/day . There were no adverse effects or disease improvement observed in these patients . Nine of the remaining 10 patients tolerated the EA extract up to a dosage of 570 mg/day . There were no withdrawals related to adverse events in the trial except for one patient who developed diastolic hypertension at a dose of 180 mg/day of EA extract . Six of 10 patients treated with 180 mg/day of EA extract showed disease improvement . Eight of the 9 patients who received EA extract at doses > 360 mg/day experienced improvement in both clinical manifestations and laboratory findings . One patient met American College of Rheumatology criteria for remission . CONCLUSION The EA extract of TWHF at dosages up to 570 mg/day appeared to be safe , and doses > 360 mg/day were associated with clinical benefit in patients with RA OBJECTIVE To examine the safety and efficacy of an extract of Tripterygium wilfordii Hook F ( TWHF ) in the treatment of patients with rheumatoid arthritis ( RA ) . METHODS An ethanol/ethyl acetate extract from the roots of TWHF was prepared and used in a prospect i ve , double-blind , placebo-controlled study in patients with longst and ing RA in whom conventional therapy had failed . Patients were r and omly assigned to receive either placebo or low-dose ( 180 mg/day ) or high-dose ( 360 mg/day ) extract for 20 weeks , followed by an open-label extension period . Clinical responses were defined as 20 % improvement in disease activity according to the American College of Rheumatology criteria . Side effects were actively queried and recorded at each visit . RESULTS A total of 35 patients were enrolled in the trial ; 21 patients completed the 20-week study . One patient from each group withdrew because of side effects . Twelve , 10 , and 10 patients in the placebo , low-dose , and high-dose groups , respectively , completed at least 4 weeks of treatment . Of these patients , 8 and 4 in the high-dose and low-dose groups , but none in the placebo group , met criteria for clinical response . Four , 4 , and 7 patients in the placebo , low-dose , and high-dose groups , respectively , were enrolled in the open-label extension ; of these , 2 , 4 , and 5 patients , respectively , met criteria for clinical response . The most common side effect was diarrhea , which caused 1 patient in the high-dose group to withdraw from the trial . No patients withdrew because of adverse events during the open-label extension . CONCLUSION The ethanol/ethyl acetate extract of TWHF shows therapeutic benefit in patients with treatment-refractory RA . At therapeutic dosages , the TWHF extract was well tolerated by most patients in this study BACKGROUND Treatment of patients with membranous glomerulonephritis ( MGN ) is controversial because of the lack of clear benefit of the immunosuppressive regimens on patient or renal survival . The objective of this study is to evaluate the efficacy and safety of mycophenolate mofetil ( MMF ) for patients with MGN . STUDY DESIGN 1-year prospect i ve , r and omized , and controlled clinical trial . SETTING & PARTICIPANTS 36 patients with biopsy-proven idiopathic MGN and nephrotic syndrome . INTERVENTION 19 patients received MMF ( 2 g/d ) for 12 months and 17 patients were in the control group . All patients had the same conservative treatment based on renin-angiotensin blockers , statins , low-salt and low-protein diet , and diuretics in case of edema . OUTCOMES & MEASUREMENTS End points were the mean proteinuria over creatinuria ratio in mg/g throughout the study and numbers of complete and partial remissions at 1 year ( month 12 ) . Data were analyzed on an intention-to-treat analysis . RESULTS Mean proteinuria over creatinuria ratio was stable in both groups throughout the study ( P = 0.1 ) . Mean proteinuria over creatinuria ratio was 4,690 + /- 2,212 mg/g in the MMF group and 6,548 + /- 4,601 mg/g in the control group ( 95 % confidence interval of the difference , -619 to + 4,247 ; P = 0.1 ) . Remission was complete in 3 patients ( 1 in the MMF group , 2 in the control group ; P = 0.5 ) and partial in 11 patients ( 6 in the MMF group , 5 in the control group ; P = 0.9 ) . The probability of complete or partial remission did not differ between the 2 groups after 12 months ( relative risk , 0.92 ; 95 % confidence interval , 0.48 to 1.75 ; P = 0.7 ) . Kidney function was stable in the 2 groups according to estimated glomerular filtration rate and serum creatinine level . LIMITATIONS The small number of patients and short follow-up prevent generalizations . CONCLUSIONS A 12-month regimen of MMF did not decrease mean proteinuria over creatinuria ratio or increase partial and complete remissions . Serious adverse effects were observed in 4 patients ( 20 % ) receiving MMF Background / Aims : Multi-glycoside from Tripterygium wilfordii Hook f. ( GTW ) is used for various immune and inflammatory diseases including renal diseases represented by mesangial proliferative glomerulonephritis ( MsPGN ) in China . However , there have been no fundamental studies on the operating mechanism of GTW on MsPGN . The aim of this study is to examine as the first step the effects of GTW on acute injurious process such as mesangial injury and proteinuria in an acute and reversible Thy.1.1 glomerulonephritis ( Thy1.1GN ) model and then to clarify the action mechanism of GTW at molecular level by examining its effects on various injurious factors in this model . Methods : Thy1.1 GN was induced in rats by a single intravenous injection with 500 µg of anti-Thy1.1 mAb 1 - 22 - 3 . Daily oral administration of GTW and vehicle as a control was started from 3 days before injection of mAb to the day of sacrifice in each experiment . Fourteen rats were r and omly divided into 2 groups , GTW-treated and vehicle-treated groups , and sacrificed on day 14 in experiment 1 or on day 7 in experiment 2 after induction of Thy1.1 GN . Proteinuria was determined on days 1 , 3 , 5 , 7 , 10 and 14 in experiment 1 or on 1 , 3 , 5 and 7 in experiment 2 . From blood and kidneys taken at sacrifice , blood biochemical parameters , mesangial morphological changes , glomerular macrophage infiltration , and glomerular mRNA expression of cytokines were examined . Results : In experiment 1 , proteinuria and mesangial matrix expansion were significantly attenuated by GTW treatment . In experiment 2 , GTW treatment significantly ameliorated proteinuria , mesangial lesions and macrophage accumulation in glomerulus . In addition , it significantly reduced the glomerular expression of mRNA for PDGF , MCP-1 and IL-2 . Conclusion : GTW ameliorated not only proteinuria but also mesangial alterations in Thy1.1 GN most likely by reducing expression of injurious cytokines , indicating that GTW has suppressive effects on acute inflammatory changes in glomeruli A polyglycosides of Tripterygium wilfodii hook F ( TWH ) preparation with a code name of T2 is used in the present double-blind , controlled , cross-over study on the treatment of 70 cases of rheumatoid arthritis ( RA ) . An impressive curative effect of T2 is confirmed much more convincingly by the present study than that by the previously reported clinical open trials . The adverse reactions and the probable pharmacological mechanism of T2 are also discussed Treatments for idiopathic membranous nephropathy , a common cause of nephrotic syndrome , can be very toxic . In view of the pathogenic potential of B cells in this disease , we studied the effects of four weekly infusions of rituximab ( 375 mg/m(2)-- the monoclonal antibody to B-cell antigen CD20 - -in eight patients who had idiopathic membranous nephropathy with persistent nephrotic syndrome . At weeks 4 and 20 , urinary protein decreased from mean ( SE ) 8.6 g/24 h ( 1.4 ) to 3.8 ( 0.8 ) and 3.7 ( 0.9 ) , respectively ( p<0.0001 ) . At week 20 , albuminuria and albumin fractional clearance decreased by 70 % and 65 % , and serum albumin increased by 31 % . CD20 B lymphocytes fell below normal ranges up to study end . The short-term risk-benefit profile of rituximab seems more favourable to that of any other immunosuppressive drug used to treat idiopathic membranous nephropathy Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials |
11,885 | 26,113,099 | The panel judged the following 4 adjunctive therapies as beneficial with a moderate level of certainty : systemic subantimicrobial-dose doxycycline , systemic antimicrobials , chlorhexidine chips , and photodynamic therapy with a diode laser .
There was a low level of certainty in the benefits of the other included adjunctive therapies . | BACKGROUND Conduct a systematic review and meta- analysis on nonsurgical treatment of patients with chronic periodontitis by means of scaling and root planing ( SRP ) with or without adjuncts . | BACKGROUND The aim of this clinical study was to evaluate the association of locally delivered doxycycline ( 10 % ) with scaling and root planing in the periodontal treatment of smokers . METHODS Forty-three patients with chronic periodontitis and a minimum of four pockets ( > or = 5 mm ) on anterior teeth that bled on probing were selected . Patients were r and omly assigned to scaling and root planing ( SRP ) or scaling and root planing followed by local application of doxycycline ( SRP-D ) . Plaque , bleeding on probing , gingival recession , relative attachment level ( RAL ) , and probing depth ( PD ) were recorded at baseline , 45 days , and 3 and 6 months . Differences between baseline and each period were considered for analysis . RESULTS At 6 months , no difference was found between groups regarding plaque , bleeding reduction , gingival recession or PD ( P > 0.05 ) . However , RAL gain was greater for SRP-D ( 1.63 + /- 0.93 mm ) than for SRP ( 1.04 + /- 0.71 mm ) ( P = 0.025 ) . In addition , deep pockets ( > or = 7 mm ) showed a significant reduction ( 3.78 + /- 1.41 versus 2.60 + /- 1.28 mm , P = 0.039 ) and RAL gain ( 2.54 + /- 1.27 mm versus 1.29 + /- 0.95 mm , P = 0.01 ) when doxycycline was applied . The proportion of sites showing RAL gain of 1 to 2 mm was 36.8 % versus 21.7 % for SRP-D and SRP , respectively ( P = 0.01 ) . CONCLUSION The use of locally delivered doxycycline may constitute an important adjunct for the treatment of severe periodontal disease in smokers AIM To evaluate the potential of antimicrobial photodynamic therapy ( aPDT ) as an adjunct to scaling and root planing ( SRP ) in the treatment of chronic periodontitis . MATERIAL AND METHODS In a single-centred r and omized and controlled clinical trial , 90 patients ( 51 females and 39 males ) with untreated chronic periodontitis were r and omly assigned to receive SRP with aPDT ( test group ) or SRP alone ( control group ) . Clinical parameters and halitosis were recorded for 6 months after treatment by a periodontist who was blinded to the procedure . RESULTS Inter-group and intra-group statistical analyses were performed . Significant difference between the two groups with respect to each variable was assessed using non-parametric Rank Order ancova . Probing pocket depth and clinical attachment levels showed statistically significant reduction in the test group on evaluation at 3 months and 6 months as compared to the control group ( p < 0.05 ) . A statistically significant improvement in gingival index and gingival bleeding index was seen for the test group after 2 weeks and 1 month of aPDT ( p < 0.01 ) , whereas the improvement in gingival index and gingival bleeding index at 3 months and in plaque index at 2 weeks after aPDT was less ( p < 0.05 ) . Also , a significant difference was detected for the test group at 1 month in terms of halitosis ( p < 0.05 ) , which did not persist for long . CONCLUSIONS Antimicrobial photodynamic therapy acts as a beneficial adjunct to SRP in non-surgical treatment and management of chronic periodontitis in short-term . Further studies are required to assess the long-term effectiveness of aPDT Objectives This r and omized split-mouth clinical trial was design ed to evaluate the efficacy of scaling and root planing associated to the high-intensity diode laser on periodontal therapy by means of clinical parameters and microbial reduction . Material s and methods A total of 36 chronic periodontitis subjects , of both genders , were selected . One pair of contralateral single-rooted teeth with pocket depth > 5 mm was chosen from each subject . All patients received non-surgical periodontal treatment , after which the experimental teeth were design ated to either test or control groups . Both teeth received scaling , root planing and coronal polishing ( SRP ) and teeth assigned to the test group ( SRP + DL ) were irradiated with the 808 ± 5 nm diode laser , for 20 s , in two isolated appointments , 1 week apart . The laser was used in the continuous mode , with 1.5 W and power density of 1,193.7 W/cm2 . Clinical and microbiological data were collected at baseline , 6 weeks and 6 months after therapy . Results There was a significant improvement of all the clinical parameters— clinical attachment level ( CAL ) , probing depth ( PD ) , plaque index ( PI ) and Bleeding on Probing (BOP)—for both groups ( P < 0.001 ) , with no statistical difference between them at the 6 weeks and the 6 months examinations . As for microbiological analysis , a significant reduction after 6 weeks ( P > 0.05 ) was observed as far as colony forming units ( CFU ) is concerned , for both groups . As for black-pigmented bacteria , a significant reduction was observed in both groups after 6 months . However , the difference between test and control groups was not significant . There was no association between group and presence of Porphyromonas gingivalis , Prevotella intermedia and Aggregatibacter actinomycetemcomitans at any time of the study . Conclusions After 6 months of evaluation , the high-intensity diode laser has not shown any additional benefits to the conventional periodontal treatment . Clinical relevance The high intensity diode laser did not provide additional benefits to non-surgical periodontal treatment . More studies are necessary to prove the actual need of this type of laser in the periodontal clinical practice BACKGROUND / AIM Tobacco use reduces the effect of non-surgical periodontal therapy . Host-modulation with low-dose doxycycline ( LDD ) might favour repair and promote an improved treatment response . The aim of this study was to investigate the effect of LDD in smokers on non-surgical periodontal therapy . MATERIAL AND METHODS This was a parallel arm , r and omized , identical placebo-controlled trial with masking of examiner , care-giver , participant and statistician and 6 months of follow-up . Patients received non-surgical therapy and 3 months of test or control drug . Statistical analysis used both conventional methods and multilevel modelling . RESULTS Eighteen control and 16 test patients completed the study . The velocity of change was statistically greater for the test group for clinical attachment level -0.19 mm/month ( 95 % CI=-0.34 , 0.04 ; p=0.012 ) and probing depth 0.30 mm/month ( 95 % CI=-0.42 , -0.17 ; p<0.001 ) . However , no differences were observed for absolute change in clinical or biochemical markers at 6 months . CONCLUSIONS This study does not provide evidence of a benefit of using LDD as an adjunct to non-surgical periodontal therapy in smokers BACKGROUND Diabetes and periodontitis are complex chronic diseases with an established bidirectional relationship . There is long-established evidence that hyperglycaemia in diabetes is associated with adverse periodontal outcomes . However , given the ubiquity of periodontal diseases and the emerging global diabetes epidemic , the complications of which contribute to significant morbidity and premature mortality , it is timely to review the role of periodontitis in diabetes . AIMS To report the epidemiological evidence from cross-sectional , prospect i ve and intervention studies for the impact of periodontal disease on diabetes incidence , control and complications and to identify potential underpinning mechanisms . EPIDEMIOLOGY Over the last 20 years , consistent and robust evidence has emerged that severe periodontitis adversely affects glycaemic control in diabetes and glycaemia in non-diabetes subjects . In diabetes patients , there is a direct and dose-dependent relationship between periodontitis severity and diabetes complications . Emerging evidence supports an increased risk for diabetes onset in patients with severe periodontitis . BIOLOGICAL MECHANISMS Type 2 diabetes is preceded by systemic inflammation , leading to reduced pancreatic β-cell function , apoptosis and insulin resistance . Increasing evidence supports elevated systemic inflammation ( acute-phase and oxidative stress biomarkers ) result ing from the entry of periodontal organisms and their virulence factors into the circulation , providing biological plausibility for the effects of periodontitis on diabetes . AGE ( Advanced Glycation Endproducts)-RAGE ( Receptor for AGEs ) interactions and oxidative-stress-mediated pathways provide plausible mechanistic links in the diabetes to periodontitis direction . INTERVENTIONS R and omized controlled trials ( RCTs ) consistently demonstrate that mechanical periodontal therapy associates with approximately a 0.4 % reduction in HbA1C at 3 months , a clinical impact equivalent to adding a second drug to a pharmacological regime for diabetes . RCTs are needed with larger numbers of subjects and longer term follow-up , and if results are substantiated , adjunctive periodontal therapies subsequently need to be evaluated . There is no current evidence to support adjunctive use of antimicrobials for periodontal management of diabetes patients . GUIDELINES Given the current evidence , it is timely to provide guidelines for periodontal care in diabetes patients for medical and dental professionals and recommendations for patients /the public The aim of this r and omized , parallel , controlled clinical trial was to examine the clinical and biochemical efficacy of diode laser as an adjunct to scaling and root planing ( SRP ) . Thirty chronic periodontitis patients were r and omly assigned into two groups to receive SRP alone ( control ) or SRP followed by diode laser ( test ) . Plaque index , gingival index , bleeding on probing , probing depth , and clinical attachment level were measured at baseline and at 1 , 3 , and 6 months after treatment . The gingival crevicular fluid levels of interleukin-1β ( IL-1β ) , interleukin-6 ( IL-6 ) , interleukin-8 ( IL-8 ) , matrix metalloproteinase-1 ( MMP-1 ) , matrix metalloproteinase-8 ( MMP-8 ) and tissue inhibitor matrix metalloproteinase-1 ( TIMP-1 ) were analyzed by enzyme-linked immunosorbent assay . Test group showed significantly a better outcome compared to the control group in full-mouth clinical parameters . MMP-1 , MMP-8 , and TIMP-1 showed significant differences between groups after treatment compared to baseline ( p < 0.05 ) . The total amount of IL-1β , IL-6 , MMP-1 , MMP-8 , and TIMP-1 decreased ( p < 0.05 ) and IL-8 increased after treatment in both test and control groups ( p < 0.05 ) . Diode laser provided significant improvements in clinical parameters and MMP-8 was significantly impacted by the adjunctive laser treatment at first month providing an insight to how lasers can enhance the outcomes of the nonsurgical periodontal therapy The primary goal of periodontal therapy is the removal of supra and subgingival bacterial deposits by mechanical debridement consisting in scaling and root-planing ( SRP ) using manual or power-driven instruments . The complete removal of bacteria and their toxins from periodontal pockets is not always achieved with conventional mechanical treatment . The use of lasers as an adjunctive therapy for periodontal disease may improve tissue healing by bactericidal and detoxification effects . The aim of this study was to compare the effectiveness of Diode laser used as adjunctive therapy of SRP to that of SRP alone for non surgical periodontal treatment in patients with chronic periodontitis . Nineteen pairs of teeth with untreated chronic periodontitis were selected in 13 patients and r and omly treated by SRP alone ( control group ) or by SRP + laser irradiation ( test group ) . Clinical measurements ( PPD , CAL , BOP , GI , PI ) were performed before treatment at baseline ( T0 ) and at T1 ( after 4 weeks ) , T2 ( 8 weeks ) , T3 ( 12 weeks ) , T4 ( 6 months ) . Subgingival plaque sample s were taken at baseline and after treatment and examined for 8 periopathogens bacteria using PCR technique . The present study showed that the additional treatment with diode laser may lead to a slightly improvement of clinical parameters , whereas no significant differences between test and control group in reduction of periodontopathogens were found OBJECTIVE The aim of this clinical trial was to determine the clinical and biochemical efficacy of an 810 nm diode laser as an adjunct to scaling and root planing ( SRP ) . BACKGROUND DATA Lasers can achieve excellent tissue ablation with strong bactericidal and detoxification effects . The use of lasers is one of the most promising new technical modalities for nonsurgical periodontal treatment . However , the most effective wavelength and parameters for their use are still under investigation . METHODS This study was design ed as a single-blinded , r and omized-controlled , split-mouth clinical trial . Twenty-one patients ( 12 females and 9 males between 26 and 55 years of age ) , diagnosed with generalized chronic periodontitis , were included in the study . After initial periodontal therapy , which consisted of oral hygiene instructions and scaling , patients underwent two different treatment modalities . Test and control sites were chosen with coin toss r and omization . At the test site , patients received SRP and laser treatment ; at the contralateral control site , they received SRP treatment alone . RESULTS Both treatment modalities result ed in significant improvements in all clinical and biochemical parameters . Sites irradiated with an 810 nm diode laser using the " hot tip " ( ∼ 760 ° C ) technique showed enhanced healing in all the registered periodontal variables and interleukin (IL)-1β levels , compared with SRP alone . CONCLUSIONS Within the limitations of this study , the use of diode lasers as an adjunct to SRP produced significant improvements in clinical parameters as well as gingival crevicular fluid ( GCF ) IL-1β levels in the 6 month study period Experimental studies in animals and in vitro have shown the usefulness of photodynamic therapy ( PDT ) as an adjunct to periodontal treatment . The aim of this study was to evaluate the long-term clinical and microbiological effects of PDT associated with nonsurgical periodontal treatment . Three sites in each of 33 patients with chronic periodontitis were r and omly allocated in a split-mouth design to a treatment group : ( 1 ) scaling and root planing ( SRP group ) ; ( 2 ) SRP and irrigation with toluidine blue O ( TBO group ) ; and ( 3 ) SRP , irrigation with TBO and low-level laser irradiation ( PDT group ) . Clinical parameters including visible plaque index , bleeding gingival index , bleeding on probing , probing depth , gingival recession and clinical attachment level were measured at baseline , and after 60 , 90 and 180 days . Additionally , subgingival plaque sample s were collected for microbiological analysis by PCR . Intergroup and intragroup statistical analyses were performed . All treatment groups showed an improvement in all clinical parameters , and a significant reduction in the proportion of sites positive for periodontopathogens at 60 , 90 and 180 days compared to baseline ( p < 0.05 ) . None of the periodontal parameters showed a significant difference among the groups ( p > 0.05 ) . At 180 days , PDT treatment led to a significant reduction in the percentage of sites positive for all bacteria compared to SRP alone ( p < 0.05 ) . Within the limits of this study it may be concluded that PDT as an adjunct to periodontal treatment produced statistically significant reductions in some of the key periodontal pathogens but produced no statistically significant benefit in terms of clinical outcome AIM To determine whether adjunctive metronidazole therapy would compensate for the poorer treatment response to scaling and root planing reported in smokers . METHOD A single-blind , r and omised clinical trial of 28 smokers and 56 non-smokers , stratified for periodontitis disease severity and r and omly allocated to 3 treatment groups : ( 1 ) Scaling and root planing using an ultrasonic scaler with local anaesthesia ( SRP ) , ( 2 ) SRP+ metronidazole tabs 200 mg tds for 7 days , ( 3 ) SRP + 2 subgingival applications of 25 % metronidazole gel . Probing depths ( PD ) and attachment levels ( AL ) were recorded with a Florida probe at baseline , 2 months and 6 months post treatment by a single examiner who was unaware of the treatment modality . Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance . RESULTS Reductions in probing depth at 6 months were significantly less ( p < 0.001 ) in the smokers ( mean 1.23 mm , 95 % confidence intervals = 1.05 to 1.40 mm ) than in the non-smokers ( 1.92 , 1.75 to 2.09 mm ) . Attachment level gains were approximately 0.55 mm and there was no statistically significant difference between smokers and non-smokers . There were no differences in any clinical measure in response to the three treatment regimens at 2 or 6 months for either smokers or non-smokers . A reduction in the proportion of spirochaetes was observed at 6 months which was less in smokers than in non-smokers ( p = 0.034 ) . Multiple linear regression analysis on probing depth at 6 months demonstrated that smoking was a significant explanatory factor ( p < 0.001 ) for poor treatment outcome , whilst the presence or absence of adjunctive metronidazole was not ( p = 0.620 ) . CONCLUSION This study confirms that smokers have a poorer treatment response to SRP , regardless of the application of either systemic or locally applied adjunctive metronidazole The present investigation was performed to study the effect of long-term , low dosage tetracycline therapy on advanced periodontal disease in humans . 14 volunteers participated in the trial . Each of the participants had at least 4 pairs of diseased sites around contralateral premolars and incisors with deep pockets and advanced bone loss . The trial extended over a 50-week period and was design ed as a double-blind split-mouth study . A Baseline examination included assessment s of oral hygiene , gingival conditions , probing depth , attachment level and analysis of the composition of the subgingival microbiota in sample s obtained from 8 selected diseased sites . All participants received oral hygiene instruction . In each patient 2 quadrants of the mouth , chosen at r and om , were treated by scaling and root planing . The 2 remaining quadrants were left unscaled . Following the Baseline examination the patients were r and omly distributed into 2 groups of 7 members each . In one of the groups the patients received tetracycline on a daily basis during a 50-week period . The participants of the control group received placebo . Reexaminations were performed 2 , 10 , 20 , 30 and 50 weeks after the Baseline examination . The findings demonstrated that in patients with advanced periodontal disease long-term tetracycline therapy in the absence of scaling result ed in the establishment of a subgingival microbiota almost devoid of motile bacteria and in markedly reduced signs of gingivitis , probing depth and attachment loss . In fact , the alterations observed as a result of tetracycline administration to patients with excellent self-performed plaque control were similar to those obtained by conventional scaling and root planing in the control group Recent results of a limited clinical trial suggest that mechanical root scaling and root planing therapy alone may not be the most effective mode of treatment for patients affected by moderate to severe adult periodontitis . However , scaling and planing combined with laser therapy utilizing a low-powered pulsed Nd : YAG laser have been shown to be successful in the elimination of the bacteria commonly associated with the development of this oral condition . The double-blind , split mouth design study involved 10 human subjects r and omly assigned to one of three treatments : 1 ) scaling and root planing alone , 2 ) dental laser plus scaling and root planing , and 3 ) control only . This article presents the clinical results of the trial , which suggest that laser therapy is a viable adjunct to local , nonsurgical therapy such as scaling and planing AIM This split-mouth , r and omized , clinical trial aim ed to evaluate the efficacy of erbium-doped : yttrium-aluminium-garnet ( Er : YAG ) laser application in non-surgical periodontal treatment . MATERIAL S AND METHODS A total of 27 patients underwent four modalities of non-surgical therapy : supragingival debridement ; scaling and root planing (SRP)+Er : YAG laser ; Er : YAG laser ; and SRP . Each strategy was r and omly assigned and performed in one of the four quadrants . Clinical outcomes were evaluated at 3 and 6 months . Subjective benefits of patients have been evaluated by means of question naires . RESULTS Six months after therapy , Er : YAG laser showed no statistical difference in clinical attachment gain with respect to supragingival scaling [ 0.15 mm ( 95 % CI -0.16 ; 0.46 ) ] , while SRP showed a greater attachment gain than the supragingival scaling [ 0.37 mm ( 95 % CI 0.05 ; 0.68 ) ] . No difference result ed between Er : YAG laser+SRP and SRP alone [ 0.05 mm ( 95 % CI -0.25 ; 0.36 ) ] . CONCLUSIONS The adjunctive use of Er : YAG laser to conventional SRP did not reveal a more effective result than SRP alone . Furthermore , the sites treated with Er : YAG laser showed similar results of the sites treated with supragingival scaling BACKGROUND The present r and omized , double-masked , placebo-controlled , parallel-arm study examines the impact of adjunctive subantimicrobial-dose doxycycline ( SDD ) on the local inflammatory response through cytokine and chemokine levels in gingival crevicular fluid ( GCF ) sample s from patients with chronic periodontitis . METHODS Forty-six patients with chronic periodontitis received scaling and root planing with or without adjunctive SDD . GCF sample s were collected and clinical parameters including probing depth , clinical attachment level , gingival index , and plaque index were recorded every 3 months for 12 months . GCF tumor necrosis factor-α , interleukin (IL)-6 , IL-4 , IL-10 , IL-13 , IL-17 , macrophage inhibitory protein 1α , macrophage inhibitory protein 1β , monocyte chemoattractant protein 1 , and regulated on activated normal T-cell expressed and secreted protein levels were determined by xMAP multiplex immunoassay . RESULTS Significant improvements were observed in all clinical parameters in both groups over 12 months ( P < 0.0125 ) , whereas the SDD group showed significantly better reduction in gingival index , probing depth , and gain in clinical attachment compared to the placebo group ( P < 0.05 ) . Decrease in IL-6 in the SDD group was significantly higher compared to the placebo group at 6 and 9 months in deep pockets ( P < 0.05 ) , whereas tumor necrosis factor-α was significantly reduced in moderately deep pockets ( P < 0.05 ) . SDD result ed in a stable IL-4 and IL-10 response while reducing the monocyte chemoattractant protein 1 levels at 3 months ( P < 0.05 ) . CONCLUSIONS These results show that SDD , as an adjunct to non-surgical periodontal therapy , stabilizes the inflammatory response by promoting the suppression of proinflammatory cytokines and increasing the anti-inflammatory cytokines . The chemokine activity would account for the regulation of the inflammatory response to SDD therapy OBJECTIVE To evaluate the clinical and microbiological effects of systemic azithromycin as an adjunct to scaling and root planing ( SRP ) in the treatment of Porphyromonas gingivalis-associated chronic periodontitis . METHODS Twenty-nine patients harbouring P. gingivalis were r and omized into test and placebo groups . Test patients received SRP plus 500 mg of azithromycin per day ( 3 days ) , and control patients received SRP plus placebo . Clinical [ plaque and bleeding indexes , probing pocket depth ( PPD ) , clinical attachment level ( CAL ) ] and microbiological data ( four-sites pooled sample s , processed by culture ) were collected at baseline , and 1 , 3 and 6 months , post-therapy . Clinical variables were compared by anova , and microbiological variables by chi-square , signed-rank and Wilcoxon tests . RESULTS Fifteen test and 11 placebo patients completed the study . Mean PPD decreased 0.34 mm [ 95 % confidence interval ( CI ) 0.19 - 0.49 ] in the placebo and 0.80 mm ( CI 0.57 - 1.04 ) in the test group after 6 months . For mean CAL gain , the correspondent figures were 0.29 ( CI 0.08 - 0.49 ) and 0.76 ( CI 0.46 - 1.05 ) , respectively . The frequency of detection of P. gingivalis decreased significantly ( p0.01 ) in the test group after 1 , 3 and 6 months . CONCLUSIONS Within the limitations of this study , the adjunctive use of systemic azithromycin in the treatment of P. gingivalis periodontitis demonstrated significant clinical and microbiological benefits when compared with SRP plus placebo AIM To evaluate the clinical , microbiological and immunological effects of systemic doxycycline as an adjunct to scaling and root planing ( SRP ) in chronic periodontitis patients with well-controlled type 2 diabetes . MATERIAL S AND METHODS Sixty-six patients compliant to oral hygiene ( Hygiene Index < 20 % ) allocated to either a test ( systemic doxycycline for 21 days ) or a control ( placebo ) group participated in the present r and omized controlled trial ( RCT ) . Clinical assessment s were recorded at baseline , 3 and 6 months after therapy and included clinical attachment level ( CAL ) , set as the primary outcome of the study , probing pocket depth ( PPD ) , recession ( RE ) and bleeding on probing ( BOP ) . At the same time points , counts of 15 subgingival species were evaluated by " checkerboard " DNA-DNA hybridization , gingival crevicular fluid sample s were analysed for matrix metalloproteinase-8 ( MMP-8 ) by ELISA and HbA1c levels were determined . Comparisons between and within groups were performed by non-parametric tests ( Mann-Whitney , Wilcoxon signed-ranks and z-test for proportions with Bonferroni corrections ) at the 0.05 level . RESULTS No major differences were noticed in clinical and microbiological parameters of periodontal disease or levels of MMP-8 between the two groups . CONCLUSIONS Adjunctive systemic doxycycline does not seem to significantly enhance the effects of SRP in well-controlled diabetes type 2 patients AIM To evaluate the effects of systemic azithromycin ( AZM ) as an adjunct to scaling and root planing ( SRP ) in the treatment of generalized chronic periodontitis ( ChP ) . METHODS Forty subjects were r and omly assigned to receive SRP alone or combined with AZM ( 500 mg/day ) for 5 days ( n=20/group ) . Clinical and microbiological examinations were performed at baseline , 6 months and 1-year post-SRP . Nine plaque sample s per subject were analysed by checkerboard DNA-DNA hybridization for 40 bacterial species . Differences between groups were assessed using the Mann-Whitney test and over time using Friedman and Dunn 's tests . RESULTS No statistically significant differences were observed between groups for any parameters evaluated at 1-year post-treatments . Both therapies equally reduced the mean probing depth ( PD ) ( SRP : 3.83 ± 1.92 , AZM : 3.45 ± 1.74 ) and improved the mean clinical attachment ( SRP : 2.35 ± 1.70 , AZM : 2.68 ± 1.76 ) in sites with initial PD7 mm ( primary outcome variable ) between baseline and 1 year . The mean counts and proportions of several periodontal pathogens were reduced , and those of host-beneficial species were increased after treatments . Nonetheless , an important recolonization with red complex species was observed in both groups over the course of the study . CONCLUSION The data of the present study suggest no adjunctive benefit of AZM in the treatment of generalized Recent pre clinical and clinical data have suggested the potential benefit of photodynamic therapy ( PDT ) in the treatment of periodontitis . However , currently , there are very limited data from controlled clinical trials evaluating the effect of PDT in the treatment of periodontitis . The aim of the present study was to evaluate the clinical and microbiological effects of the adjunctive use of PDT in non-surgical periodontal treatment in patients receiving supportive periodontal therapy . Twenty-four patients receiving regularly supportive periodontal therapy were r and omly treated with either subgingival scaling and root planing followed by a single episode of PDT ( test ) or subgingival scaling and root planing alone ( control ) . The following parameters were evaluated at baseline and at 3 months and 6 months after therapy : full mouth plaque score ( FMPS ) , full mouth bleeding score ( FMBS ) , bleeding on probing ( BOP ) at experimental sites , probing pocket depth ( PPD ) , gingival recession ( REC ) , and clinical attachment level ( CAL ) . Primary outcome variables were changes in PPD and CAL . Microbiological evaluation of Aggregatibacter actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( P.g . ) , Prevotella intermedia ( P.i . ) , Tannerella forsythensis ( T.f . ) , Treponema denticola ( T.d . ) , Peptostreptococcus micros ( P.m . ) , Fusobacterium nucleatum ( F.n . ) , Campylobacter rectus ( C.r . ) , Eubacterium nodatum ( E.n . ) , Eikenella corrodens ( E.c . ) , and Capnocytophaga species ( C.s . ) was also performed at baseline and at 3 months and 6 months after therapy , using a commercially available polymerase chain reaction test . No differences in any of the investigated parameters were observed at baseline between the two groups . At 3 months and 6 months after treatment , there were no statistically significant differences between the groups in terms of PPD , CAL and FMPS . At 3 months and 6 months , a statistically significantly higher improvement of BOP was found in the test group . At 3 months after therapy , the microbiological analysis showed a statistically significant reduction of F.n . and E.n . in the test group . At 6 months , statistically significantly higher numbers of E.c . and C.s . were detected in the test group . The additional application of a single episode of PDT to scaling and root planing failed to result in an additional improvement in terms of PPD reduction and CAL gain , but it result ed in significantly higher reduction of bleeding scores than following scaling and root planing alone AIM Diabetic patients have more severe periodontal destruction , but periodontal therapy can improve metabolic control . Recently , interest has focused on the use of subantimicrobial dose doxycycline ( SDD ) as a treatment paradigm . Therefore , this study was undertaken to evaluate clinical efficacy of SDD with scaling and root planning ( SRP ) in chronic periodontitis patients with diabetes . METHODS AND MATERIAL S Twenty chronic periodontitis patients with diabetes mellitus were r and omly allocated to either a test and a control group . Clinical measurements were recorded at baseline and at six months for probing pocket depth ( PPD ) , clinical attachment level ( CAL ) , and gingival recession ( GR ) . After SRP , patients in the test group were instructed to take SDD 20-mg capsules twice a day while patients in the control group took a placebo twice a day . Both groups were on this regimen for a six-month period . RESULTS A greater reduction in mean PPD was demonstrated in patients in the test group compared to the control group . The mean CAL increase observed in the test group was significantly greater ( 0.67 mm ) than that in the control group . CONCLUSION It can be concluded that SRP , in conjunction with the SDD therapy described , is more effective then SRP alone in terms of CAL gain and PPD reduction in diabetic patients with severe periodontal disease . CLINICAL SIGNIFICANCE Given the widespread prevalence of both chronic periodontitis and diabetes , the proposed treatment approach will prove to be of great value and contribute significantly to the overall health of the patients BACKGROUND Laminin-5 ( Ln-5 ) is involved in the apical migration of epithelial cells during the development of periodontal pockets . Low-dose doxycycline ( LDD ) can therapeutically modulate the host response with its non-antimicrobial properties . In the present r and omized , double-blind , placebo-controlled , parallel arm study , the effectiveness of LDD in combination with non-surgical periodontal therapy on gingival crevicular fluid ( GCF ) Ln-5 gamma2 chain fragment levels and clinical parameters in patients with chronic periodontitis was examined over a 12-month period . METHODS GCF sample s were collected and clinical parameters including probing depth ( PD ) , clinical attachment level , gingival index ( GI ) , and plaque index were recorded . Thirty chronic periodontitis patients were r and omized either to low-dose doxcycline or placebo groups . LDD group received doxycycline ( 20 mg , b.i.d . ) for 3 months plus scaling and root planing ( SRP ) , while placebo group was given placebo capsules b.i.d . for 3 months plus SRP . The patients were evaluated every 3 months during the 12-month study period . All clinical parameters and GCF sampling were repeated at each visit . GCF Ln-5 gamma2 chain fragment levels were determined by Western immunoblotting using specific antibody and quantitated by computerized image analysis . Friedman test was used for intragroup comparisons followed by Wilcoxon signed rank test to analyze significance of changes over time . The Mann-Whitney test was used to determine differences between both LDD and placebo groups . RESULTS Both groups revealed significant improvements in all clinical parameters over the 12-month period ( P < 0.0125 ) . LDD group showed a significantly greater reduction in the mean PD scores at 9 and 12 months and in the mean GI scores at all time points than the placebo group ( P < 0.05 ) . In the LDD group , GCF Ln-5 gamma2 chain fragment levels were significantly reduced at 3 months ( P < 0.0125 ) and then slightly increased during the rest of the study period . In the placebo group , GCF 45 and 70 kDa Ln-5 gamma2 chain fragments tended to decrease at 3 months compared to baseline , but did not reach significance ; these levels continued to increase throughout the remainder of the study period . GCF Ln-5 gamma2 chain fragment levels in LDD group were significantly lower than those of the placebo group during the study period ( P < 0.05 ) . CONCLUSIONS The present data indicate that LDD therapy in combination with SRP therapy can reduce GCF Ln-5 gamma2 chain fragment levels and improve clinical periodontal parameters in patients with chronic periodontitis . Since matrix metalloproteinases (MMP)-mediated fragmentation of laminin-5 can contribute to pocket formation by stimulating epithelial cell migration , the reduction of Ln-5 gamma2 chain fragment levels could provide a new mechanism by which LDD , adjunctive to SRP , inhibits periodontal disease more effectively than SRP alone . Thus , these results provide extended and additional information about the effectiveness of the LDD therapy as an adjunct to non-surgical periodontal therapy in the long-term management of periodontal disease BACKGROUND This research report evaluates clinical changes result ing from local delivery of doxycycline hyclate ( DH ) or traditional scaling and root planing ( SRP ) in a group of patients undergoing supportive periodontal therapy ( SPT ) . METHODS In all , 141 patients received either DH ( 67 ) or SRP ( 74 ) treatment in sites > or = 5 mm on one-half of their dentition at baseline and month 4 . RESULTS Clinical results were determined at month 9 . Baseline mean probing depth recordings were similar between the two groups ( DH = 5.9 mm ; SRP = 5.9 mm ) . Mean month 9 results showed similar clinical results for attachment level gain ( DH 0.7 mm ; SRP 0.8 mm ) and probing depth reduction ( DH 1.3 mm ; SRP 1.1 mm ) . Percentage of sites showing > or = 2 mm attachment level gain at month 9 was 24.7 % in the DH group and 21.2 % in the SRP group . Thirty-nine percent ( 39 % ) of DH sites and 38 % of SRP sites showed > or = 2 mm probing depth reduction . When treated sides of the dentition were compared to untreated sides , DH showed a difference in disease activity ( > or = 2 mm attachment loss ) from 19.3 % ( untreated ) to 7.2 % ( treated ) ; and SRP from 14.3 % ( untreated ) to 8.1 % ( treated ) . CONCLUSIONS Results show that both DH without concomitant mechanical instrumentation and SRP were equally effective as SPT in this patient group over the 9-month study period Studies indicate that a dual pathway between diabetes mellitus and periodontal disease exists . Elimination of periodontal infection by using systemic antibiotics in conjunction with scaling and root planing ( SRP ) improved metabolic control in diabetic patients , as defined by reduction in glycated haemoglobin or reduction in insulin requirements ( Grossi and Genco , 1998 ) . The aim of this r and omised pilot clinical trial was to determine if type 1 diabetes patients with periodontitis will experience a reduction in HbA1c levels when treated with locally delivered minocycline microspheres ( Arestin ) as an adjunct to scaling and root planing . Twenty adult patients with poorly controlled diabetes ( HbA1c 7.5 % ) and adult periodontitis , as determined by the presence of four teeth with 5 mm periodontal pockets , two of which had 6 - 9 mm pockets and bleeding on probing , were included in the study . All patients received full mouth SRP at baseline . Arestin was administered to all pockets > or = > or = 5 mm at baseline and again at 12 weeks in the test group . Probing depth ( PD ) , clinical attachment level ( CAL ) , plaque index ( PI ) , gingival index ( GI ) , and HbA1c were evaluated at baseline and at weeks 6 , 12 , 18 and 24 . The results demonstrated that local administration of Arestin as an adjunct to scaling and root planing is significantly more effective in reducing probing depths and providing a gain in clinical attachment levels than scaling and root planing alone in type 1 diabetic patients . Hb1Ac was reduced in all patients ; however the difference between the test and control groups was not significant BACKGROUND One-stage full-mouth scaling and root planing ( FM-SRP ) in combination with systemically administered azithromycin was shown to be clinical ly and bacteriologically effective in the treatment of chronic periodontitis . However , FM-SRP requires 2 hours for completion . Azithromycin has a long half-life . Therefore , if SRP of the full mouth is performed within 7 days while an effective concentration of azithromycin remains in the gingiva , the effects may be the same as FM-SRP . The aim of this study was to compare the clinical and bacteriologic effects of FM-SRP and partial-mouth scaling and root planing ( PM-SRP ) in patients with chronic periodontitis , which was performed in three sessions within 7 days , during the effective half-life of systemically administrated azithromycin . METHODS Thirty adult subjects with chronic periodontitis were r and omly divided into three groups ( FM-SRP , PM-SRP , and control ) . A clinical examination was conducted to record the probing depth , clinical attachment level gain , bleeding on probing , gingival index , and volume of gingival crevicular fluid ; bacterial sample s were obtained before treatment and 1 , 3 , 6 , 9 , and 12 months thereafter . Quantitative and qualitative analyses were performed using the polymerase chain reaction-Invader method . RESULTS All clinical parameters showed better improvement in FM-SRP and PM-SRP groups compared to the control group , with no significant differences between the two test groups . Periodontal bacteria were well controlled in the two test groups , but they tended to increase gradually 3 months after treatment in the control group . CONCLUSION PM- and FM-SRP demonstrated comparable clinical and bacteriologic results The aim of this study was to evaluate the long-term effects of a combined periodontal treatment of scaling and root planing ( SRP ) and Nd : YAG laser ( NDL ) in chronic periodontitis ( CP ) patients . This was accomplished by determining the periodontal indices and the interleukin-1beta ( IL-1β ) and matrix metalloproteinase-8 ( MMP-8 ) levels of the gingival crevicular fluid ( GCF ) . This study was performed according to a r and om split-mouth- design , controlled clinical trial for sulcular debridement on 40 teeth from 20 patients with generalized moderate chronic periodontitis . The periodontal healing outcomes were compared after periodontal treatment with either SRP + NDL at 1 W ( test side ) or SRP ( control side ) . Plaque index ( PI ) , gingival index ( GI ) , probing pocket depth ( PPD ) , and clinical attachment level ( CAL ) were recorded , and sample s of gingival crevicular fluid ( GCF ) were taken at baseline and post-therapy ( 3 and 9 months after treatment ) . The GCF sample s were analyzed for IL-1β and MMP-8 . There was postoperative improvement of all clinical parameters in both groups , but test side GI , PPD , and CAL recovery was higher than that of the control side ( p < 0.05 ) . Although levels of IL-1β and MMP-8 in GCF after treatment were lower in the test side than the control side , there was not a statistically significant difference ( p > 0.05 ) . In the long term , we found that SRP + NDL treatment of periodontal pockets was more effective than SRP alone in reducing PPD , CAL , GI , and GCF values BACKGROUND The purpose of this study was to evaluate the adjunctive clinical , microbiologic , and immunologic effects of the systemic administration of amoxicillin and metronidazole in the full-mouth ultrasonic debridement of patients with severe chronic periodontitis . METHODS Twenty-five patients presenting at least eight teeth with probing depth ( PD ) > or = 5 mm and bleeding on probing ( BOP ) were selected and r and omly assigned to full-mouth ultrasonic debridement + placebo ( control group ) or full-mouth ultrasonic debridement + amoxicillin and metronidazole ( test group ) . The clinical outcomes evaluated were visible plaque index , BOP , position of the gingival margin , relative attachment level ( RAL ) , and PD . Real-time polymerase chain reaction ( PCR ) was used for quantitative analysis of Aggregatibacter actinomycetemcomitans ( previously Actinobacillus actinomycetemcomitans ) , Porphyromonas gingivalis , and Tannerella forsythia ( previously T. forsythensis ) . The enzyme-linked immunosorbent assay ( ELISA ) technique permitted the detection of prostagl and in E(2 , ) interleukin-1beta , and interferon-gamma levels in gingival crevicular fluid . All parameters were evaluated at baseline and at 3 and 6 months post-treatment . RESULTS At 6 months , the test treatment result ed in lower BOP and an additional reduction ( 0.83 mm ) in PD ( P < 0.05 ) . Data also showed RAL gain > or = 2 mm at 43.52 % of sites in control patients compared to 58.03 % of sites in test patients ( P < 0.05 ) . However , both groups had similar mean RAL gain ( 1.68 and 1.88 mm for the control and test groups , respectively ) . Real-time PCR and ELISA failed to identify significant differences between the groups . CONCLUSIONS Both treatments result ed in significant clinical improvements ; however , there was a slight , but significantly greater , improvement in BOP and the percentage of sites with PD > or = 5 mm exhibiting RAL gain > or = 2 mm in the test group . Nevertheless , no improvement in the microbiologic or immunologic outcome was observed with the adjunctive use of systemic amoxicillin and metronidazole AIM To investigate the effect of photodynamic therapy ( PDT ) as adjunct to mechanical therapy in furcations . MATERIAL S AND METHODS A double-blind , parallel , r and omized controlled clinical trial was conducted in subjects presenting class II furcations . The subjects were r and omly allocated to a test ( PDT ; n = 16 ) or control group ( non-activated laser/only photosensitizer ; n = 21 ) . At baseline , 3 and 6 months , clinical , microbiological and cytokine pattern evaluation was performed . Clinical attachment level was defined as the primary outcome variable . RESULTS Clinical parameters improved after both therapies ( p < 0.05 ) with no differences between groups at any time point ( p > 0.05 ) . At 6 months , real-time PCR evaluation showed a decrease in Porphyromonas gingivalis and Tannerella forsythia only in the PDT group ( p < 0.05 ) with no inter-group differences . Regarding cytokines , IL-4 and IL-10 levels increased in both groups at 6 months . GM-CSF , IL-8 , IL-1β and IL-6 levels decreased only in the PDT group after 3 months ( p < 0.05 ) . At 3 months , inter-group analyses showed that GM-CSF , IFN-γ , IL-6 and IL-8 levels were lower in the PDT group . At 6 months , lower IL-1β levels were also observed in the PDT group ( p < 0.05 ) . CONCLUSION Photodynamic therapy did not promote clinical benefits for class II furcations ; however , advantages in local levels of cytokines and a reduction in periodontopathogens were demonstrated BACKGROUND Antibiotic therapy can be used in very specific periodontal treatment situations such as in refractory cases of periodontal disease found to be more prevalent in smokers . This study was design ed to determine the efficacy of azithromycin ( AZM ) when combined with scaling and root planing ( SRP ) for the treatment of moderate to severe chronic periodontitis in smokers . METHODS Thirty-one subjects were enrolled into a 6-month r and omized , single-masked trial to evaluate clinical , microbial ( using benzoyl- DL-arginine naphthylamine [ BANA ] assay ) , and gingival crevicular fluid ( GCF ) pyridinoline cross-linked carboxyterminal telopeptide of type I collagen ( ICTP ) levels in response to SRP alone or SRP + AZM . At baseline , patients who smoked > or = 1 pack per day of cigarettes who presented with at least five sites with probing depths ( PD ) of > or = 5 mm with bleeding on probing ( BOP ) were r and omized into the test or control groups . At baseline and 3 and 6 months , clinical measurements ( probing depth [ PD ] , clinical attachment loss [ CAL ] , and bleeding on probing [ BOP ] ) were performed . GCF bone marker assessment ( Ctelopeptide [ ICTP ] as well as BANA test analyses ) were performed at baseline , 14 days , and 3 and 6 months . RESULTS The results demonstrated that both groups displayed clinical improvements in PD and CAL that were sustained for 6 months . Using a subject-based analysis , patients treated with SRP + AZM showed enhanced reductions in PD and gains in CAL at moderate ( 4 to 6 mm ) and deep sites ( > 6 mm ) ( P < 0.05 ) . Furthermore , SRP + AZM result ed in greater reductions in BANA levels compared to SRP alone ( P < 0.05 ) while rebounds in BANA levels were noted in control group at the 6-month evaluation . No statistically significant differences between groups on mean BOP and ICTP levels during the course of the study were noted . CONCLUSIONS The utilization of AZM in combination with SRP improves the efficacy of non-surgical periodontal therapy in reducing probing depth and improving attachment levels in smokers with moderate to advanced attachment loss BACKGROUND Previous studies have shown that subantimicrobial dose doxycycline ( SDD ) is of clinical benefit in the treatment of chronic periodontitis ( CP ) . The aim of this study was to further assess the role of SDD as an adjunct to scaling and root planing ( SRP ) in the treatment of CP . METHODS A double-blind , r and omized , placebo-controlled , multicenter clinical study was conducted to test the efficacy of SDD ( 20 mg doxycycline B.I.D. ) in combination with SRP in subjects with moderate to severe CP . Two-hundred ten subjects were treated with a st and ardized episode of SRP and r and omized to receive either adjunctive SDD or placebo for 9 months . Efficacy parameters included per-subject mean changes in clinical attachment level ( CAL ) and probing depth ( PD ) from baseline , and the total number of sites with attachment gains and probing depth reductions > or = 2 mm and > or = 3 mm from baseline . RESULTS In periodontal sites with PD 4 to 6 mm and > or = 7 mm ( N = 209 , intent-to-treat population ) , mean improvements in CAL and PD were greater following SRP with adjunctive SDD than SRP with placebo , achieving statistical significance in all baseline disease categories at month 9 ( P < 0.05 ) . At month 9 , 42.3 % of sites in the SDD group demonstrated CAL gain > or = 2 mm compared to 32.0 % of sites in the placebo group ( P < 0.01 ) . CAL gain > or = 3 mm was seen in 15.4 % of sites in the SDD group compared to 10.6 % of sites in the placebo group ( P < 0.05 ) . When considering the same thresholds of change in PD , 42.9 % of sites in the SDD group compared to 31.1 % of sites in the placebo group demonstrated PD reduction > or = 2 mm ( P < 0.01 ) , and 15.4 % of sites in the SDD group compared to 9.1 % of sites in the placebo group demonstrated PD reduction > or = 3 mm ( P < 0.01 ) . CONCLUSION Adjunctive subantimicrobial dose doxycycline enhances scaling and root planing . It results in statistically significant attachment gains and probing depth reductions over and above those achieved by scaling and root planing with placebo The present clinical trial was performed to study the effect of systemic administration of metronidazole and amoxicillin as an adjunct to mechanical therapy in patients with advanced periodontal disease . 16 individuals , 10 female and 6 male , aged 35 - 58 years , with advanced periodontal disease were recruited . A baseline examination included assessment of clinical , radiographical , microbiological and histopathological characteristics of periodontal disease . The 16 patients were r and omly distributed into 2 different sample s of 8 subjects each . One sample of subjects received during the first 2 weeks of active periodontal therapy , antibiotics administered via the systemic route ( metronidazole and amoxicillin ) . During the corresponding period , the 2nd sample of subjects received a placebo drug ( placebo sample ) . In each of the 16 patients , 2 quadrants ( 1 in the maxilla and 1 in the m and ible ) were exposed to non-surgical subgingival scaling and root planing . The contralateral quadrants were left without subgingival instrumentation . Thus , 4 different treatment groups were formed ; group 1 : antibiotic therapy but no scaling , group 2 : antibiotic therapy plus scaling , group 3 : placebo therapy but no scaling , group 4 : placebo therapy plus scaling . Re-examinations regarding the clinical parameters were performed , sample s of the subgingival microbiota harvested and 1 soft tissue biopsy from 1 scaled and 1 non-scaled quadrant obtained 2 months and 12 months after the completion of active therapy . The teeth included in groups 1 and 3 were following the 12-month examination exposed to non-surgical periodontal therapy , and subsequently exited from the study . Groups 2 and 4 were also re-examined 24 months after baseline . The findings demonstrated that in patients with advanced periodontal disease , systemic administration of metronidazole plus amoxicillin result ed in ( i ) an improvement of the periodontal conditions , ( ii ) elimination/suppression of putative periodontal pathogens such as A. actinomycetemcomitans , P. gingivalis , P. intermedia and ( iii ) reduction of the size of the inflammatory lesion . The antibiotic regimen alone , however , was less effective than mechanical therapy with respect to reduction of BoP - positive sites , probing pocket depth reduction , probing attachment gain . The combined mechanical and systemic antibiotic therapy ( group 2 ) was more effective than mechanical therapy alone in terms of improvement of clinical and microbiological features of periodontal disease Objective To investigate the incidence and time taken to full publication of abstract s presented at dental scientific meetings . Design A retrospective observational study . Setting All abstract s from the 1993 proceedings of the European Orthodontic Society ( EOS ) and European Organisation for Caries Research ( ORCA ) and a 10 % r and om sample of abstract s from the International Association for Dental Research ( IADR ) conferences . Methods A cross-referenced Medline search of abstract title and authors was undertaken to determine whether abstract s had been published as full papers . Search es were censored 1 year prior to and 5 years post publication as an abstract . Publication rate was compared between abstract s presented orally and as posters . Main outcome measures Publication as a full paper and time taken to publication . Results 546 abstract s were investigated . 252 abstract s ( 46.1 % ) were found as full reports . Median time to publication of all abstract s was 18 months ( IQR 9 , 30 months ) . 99 of the oral abstract s ( 57 % ) and 153 ( 41 % ) of the poster abstract s were published . Relative Risk Oral vs Poster=1.37 CI ( 1.19 , 1.55 ) . Conclusion More than half of the research presented at EOS , IADR and ORCA in 1993 remained unpublished 5 years after presentation at the conference . Oral presentations were published more frequently than poster presentations OBJECTIVES The purpose of the present study was to evaluate the clinical effects of non-surgical periodontal treatment , supplemented with enamel matrix derivative ( EMD ) and /or systemic antibiotics , in deep periodontal pockets of patients with chronic periodontitis . METHODS This was a r and omized , placebo-controlled longitudinal clinical trial of 12 months duration . Using a split-mouth design , 16 subjects were r and omly assigned to scaling and root planing ( SRP ) with EMD or placebo in contra-lateral dentition areas . One half of the subjects received 250 mg metronidazole and 375 mg amoxicillin three times a day for 7 days and the other half received a placebo . One inter-proximal periodontal lesion was chosen as study site in each of the contra-lateral quadrants . RESULTS Subjects treated with systemic antibiotics yielded significantly better clinical results than those treated with placebo . In these cases , probing pocket depth was reduced significantly more after 6 months ( 3.0+/-2.1 mm versus 1.6+/-1.4 mm , p=0.05 ) , and the mean clinical attachment gain was significantly greater after 6 months ( 2.3+/-1.9 mm versus 0.7+/-1.6 mm , p=0.02 ) and 12 months ( 2.3+/-3.5 mm versus 0.4+/-3.8 mm , p=0.02 ) . Sites treated with the antibiotics plus EMD gained the largest amount of clinical attachment . There was no significant benefit of EMD adjunctive to SRP in subjects not treated with antibiotics . CONCLUSIONS The present study supports the notion that optimal repair and regeneration of the periodontium requires suppression of the microbiota causing periodontal disease AIM The aim of this r and omised , split-mouth , single-blind study was to determine the efficacy of controlled-release delivery of chlorhexidine gluconate 2.5 mg ( PerioChip ) in patients with residual bleeding pockets ( > 5 mm ) at least 3 months following oral hygiene and root debridement phase therapy . MATERIAL AND METHODS 26 patients ( non-smokers ) were screened and potential study sites identified . Clinical parameters recorded at baseline and all subsequent visits were plaque index ( PI ) , pocket probing depth ( PPD ) , bleeding index ( BI ) and clinical attachment level ( CAL ) . All study sites were debrided using ultrasonic instrumentation . PerioChips ( PC ) were placed in the selected sites of two quadrants ( left or right ) whilst identified sites in the remaining quadrants were left without adjunctive antimicrobial treatment . Clinical measurements were made at follow-up visits after 1 , 3 and 6 months . Mean changes from baseline in PPD , BI and CAL were calculated with the patient as the experimental unit and comparability between the treatments was determined using t-tests . RESULTS At baseline there were no significant differences between PC and control sites for mean PI , PD , BI or CAL . The mean ( SE ) reductions in PPD for PC and control treatments were : 0.47 ( 0.1 ) , 0.46 ( 0.1 ) ; 0.76 ( 0.1 ) , 0.55 ( 0.1 ) ; 0.78 ( 0.1 ) , 0.45 ( 0.1 ) for months 1 , 3 and 6 respectively . Only at month 6 did the difference between treatments approach statistical significance ( p=0.06 ) . Mean ( SE ) reductions in CAL over the same periods were : 0.17 ( 0.1 ) , 0.04 ( 0.08 ) ; 0.38 ( 0.1 ) , 0.21 ( 0.1 ) ; 0.43 ( 0.1 ) , 0.15 ( 0.09 ) p=0.048 . Mean ( SE ) reduction in BI between PC and control treatments only reached statistical significance at 6 months : 1.08 ( 0.1 ) , 0.59 ( 0.1 ) p=0.05 . CONCLUSION These data suggest that PerioChip is beneficial for patients on maintenance therapy although the benefit is not apparent until 6 months after placement BACKGROUND The main objective of periodontal treatment is to control infection and thereby curb disease progression . Recent studies have demonstrated that adjunctive treatment procedures , such as laser irradiation or photodynamic therapy ( PDT ) , may provide some additional benefit in the treatment of chronic periodontitis ( CP ) . The aim of this r and omized controlled trial is to clinical ly evaluate and compare the clinical effects of potassium-titanyl-phosphate ( KTP ) laser and PDT on outcomes of CP treatment . METHODS Twenty-four patients with untreated CP were treated using a split-mouth study design in which the teeth in each quadrant were r and omly treated by scaling and root planing ( SRP ) alone ( group A ) , PDT followed by SRP ( group B ) , or KTP laser followed by SRP ( group C ) . The periodontal pockets were exposed to a KTP laser with the following parameters : 0.8 W output power , 50 milliseconds time on/50 milliseconds time off , 30 seconds per irradiation at 532 nm and 11.7 J/cm(2 ) fluence , with a flexible fiberoptic tip with a diameter of 200 µm . The selected pockets were probed with a pressure-controlled probe , guided by stents . Clinical periodontal parameters assessed included plaque index , gingival index , bleeding on probing ( BOP ) , probing depth ( PD ) , and clinical attachment level ( CAL ) , which were recorded at baseline and at 6 months after therapy . RESULTS Statistical analysis demonstrated no differences between groups at baseline for all parameters ( P > 0.05 ) . All treatments yielded significant improvements in terms of BOP and PD decrease and CAL gain compared to baseline values ( P < 0.05 ) . Group C showed a greater reduction in PD compared to the other groups ( P < 0.05 ) . In addition , group C showed a greater CAL gain compared to the other groups ( P < 0.05 ) . CONCLUSION In patients with CP , clinical outcomes from conventional periodontal treatment of deeper pockets can be improved by using adjunctive KTP laser OBJECTIVE To assess the efficacy of subantimicrobial dose doxycycline ( SDD ; 20 mg doxycycline twice daily ) as an adjunct to scaling and root planing ( SRP ) in the treatment of moderate-severe chronic periodontitis ( CP ) in institutionalised elderly patients aged 65 years or older . BACKGROUND Previous studies have shown that SDD is of clinical benefit in the treatment of CP . However , the benefits of SDD in geriatric population s ( 65 + years ) have not been determined . MATERIAL AND METHODS A 9-month , double-blind , r and omised , placebo-controlled pilot study was conducted . 24 institutionalised geriatric patients ( 65 years or older ) with evidence of CP manifested by baseline clinical attachment levels ( CAL ) 5 - 9 mm , probing depths ( PD ) 4 - 9 mm and bleeding on probing ( BOP ) were recruited . At baseline , patients were treated by a st and ardised episode of SRP , and r and omised to receive either adjunctive SDD or placebo . Full mouth PD and CAL were measured using the manual UNC-15 periodontal probe at 3 , 6 , and 9 months post-baseline to assess the response to treatment . Periodontal sites were stratified by baseline PD value : sites with PD 4 - 5 mm were considered moderately diseased and sites with PD > or = 6 mm severely diseased . RESULTS The SRP + placebo result ed in PD reductions similar to those reported previously in the literature . At all time-points and in both moderate and deep sites , SRP + SDD result ed in significantly greater PD reductions relative to baseline than SRP + placebo . At month 9 , in moderate sites , mean PD reductions of 1.57 + /- 0.11 mm were reported in the adjunctive SDD group , compared with 0.63 + /- 0.11 mm in the adjunctive placebo group ( p < 0.001 ) . In deep sites at month 9 , mean PD reductions of 3.22 + /- 0.29 mm were reported in the adjunctive SDD group , compared with 0.98 + /- 0.31 mm in the adjunctive placebo group ( p < 0.05 ) . Similar improvements were observed for CAL in the SDD group compared with the placebo group . Significantly lower BOP scores were also recorded at month 9 in the SDD group ( 7.5 % ) compared with the placebo group ( 71.2 % ) ( p < 0.01 ) . CONCLUSION SDD used as an adjunct to SRP provides significant benefit for elderly patients with CP compared with SRP alone The present study was undertaken to compare the efficacy of two antibiotics , spiramycin and tetracycline , with a placebo when used adjunctively with scaling and root planing in the treatment of advanced adult chronic periodontitis . This was a double-blind , parallel , r and omized trial with one factor ( drug ) at three levels . Ninety-six patients ( mean age 46 + /- 1 ) were r and omly assigned into one of three groups . All groups were scaled and root planed with each respective group receiving either spiramycin , tetracycline , or a placebo for 2 weeks . Two sites with probing depth of at least 7 mm were evaluated and the following clinical parameters were measured at baseline , 2 , 8 , 12 , and 24 weeks : plaque index , bleeding on probing , crevicular fluid , probing depth , and change in the attachment level . The changes in the subgingival bacteria were monitored also using a differential staining technique . Seventy-nine patients completed the study . At the end of 24 weeks , although all three groups had shown clinical improvement when compared to the baseline data , there were no significant intergroup differences in any of the clinical parameters measured . While the proportion of spirochetes were significantly decreased ( P less than 0.05 ) at 2- and 8-week intervals in both tetracycline and spiramycin groups ( 26 % to 0.04 % and 28 % to 0.04 % , respectively ) , compared to the placebo group ( 30 % to 7 % ) , only in the spiramycin group was the proportion of spirochetes significantly lower than the placebo group at the 24-week interval ( 3 % and 11 % , respectively ) . At week 24 , the proportion of spirochetes in the tetracycline group had rebounded to 7 % , which was not significantly different from the placebo group . ( ABSTRACT TRUNCATED AT 250 WORDS Mechanical removal of microbial biofilm dental plaque from tooth surfaces is important for treatment of periodontal diseases . However , the effectiveness of conventional scaling and root planing ( SRP ) is affected by the local conditions and residual bacteria which may affect the healing process . We performed a r and omized clinical trial to test our hypothesis that adjunctive antimicrobial photodynamic therapy ( aPDT ) plus SRP has significant effect compared with SRP alone , which can last for 1 year . The study included 136 sites in 16 patients with previously untreated chronic periodontitis , at least one premolar and one molar in every quadrant ( minimum , four teeth/quadrant ) and at least one tooth with attachment loss of ≥4 mm in every quadrant . In all patients , two r and omly assigned quadrants were treated with SRP and the other two were treated with SRP + aPDT . The clinical parameters of probing pocket depth ( PPD ) , bleeding on probing ( BOP ) , and clinical attachment level ( CAL ) were evaluated at baseline and after 3 , 6 , and 12 months . There were no significant differences between the two groups at baseline . PPD and BOP showed significant reduction , and CAL showed significant gain from baseline for all three time points in both groups . In addition , there were significantly greater reduction and gain for SRP + aPDT than for SRP at all three time points . No adverse effects of aPDT were observed . These data demonstrate significant improvement in all evaluated clinical parameters for at least 1 year and suggest that aPDT as an adjunctive therapy to SRP represents a promising therapeutic concept for persistent periodontitis The main therapeutic approaches for inflammatory periodontal diseases include the mechanical treatment of root surfaces . Multi-center clinical trials have demonstrated that the adjunctive use of a chlorhexidine ( CHX ) chip is effective in improving clinical results compared to scaling and root planing ( SRP ) alone . However , some recent studies failed to confirm these clinical results , nor have any data been reported regarding the capability of the CHX chip in affecting the activity of alkaline phosphatase ( ALP ) in the gingival crevicular fluid ( GCF ) . This enzyme has been related to a condition of destructive activity of periodontitis . The aim of this study is to provide further data on the clinical and biochemical effects of CHX chips when used as an adjunct to SRP . Eighty-two systemically healthy patients , aged 31 - 63 , with moderate and advanced periodontitis were recruited from the departments of Periodontology of the University of Chieti . In each patient 2 experimental sites , located in two symmetric quadrants , were chosen with a probing depth of > or = 5 mm and bleeding on probing . The 2 sites were selected r and omly at the split-mouth level ; control sites received SRP alone , and test sites SRP plus 1 CHX chip . Clinical indices , including probing depth ( PPD ) , clinical attachment level ( CAL ) , bleeding on probing ( BOP ) , and the ALP activity in GCF were evaluated at baseline and after 6 months . Alkaline phosphatase activity was assayed spectrophotometrically . The PPD and CAL were significantly lower at 6 months as compared to the baseline scores in both treatments ( p less than 0.01 ) . The PPD reduction was 2.7 mm in the CHX+SRP group and 1.9 mm in the SRP alone group . The CHX+SRP group showed a significantly greater gain of clinical attachment ( mean : 1.4 mm ) in comparison with the SRP group ( mean : 0.9 ; p less than 0.05 ) . No differences were observed in the decrease of the percent of BOP-positive sites between the experimental groups . Conversely , the CHX+SRP group underwent a significantly greater decrease ( p less than 0.01 ) of the GCF-ALP activity 6 months after treatment in comparison with the SRP alone group . The adjunctive use of the CHX chip result ed in a significant improvement of pocket reduction and clinical attachment gain as compared with SRP alone . These results were concomitant with a significantly greater reduction of the GCF-ALP activity levels OBJECTIVE This study aim ed to evaluate clinical and microbiological effects of systemic azithromycin ( AZM ) in adjunct to nonsurgical periodontal therapy ( NSPT ; or scaling root planing - SRP ) in treatment of Aggregatibacter actinomycetemcomitans associated periodontitis ( AAAP ) . METHODS AND MATERIAL S Seventy individuals with moderate to severe periodontitis and subgingival detection of A. actinomycetemcomitans were r and omly allocated to two groups . Thirty-five individuals were allocated to full mouth SRP+AZM ( 500 mg oral delivery ( OD ) × 3 days ) while 35 individuals were allocated to SRP+Placebo ( OD × 3 days ) group . The clinical variables evaluated were probing depth ( PD ) , clinical attachment level ( CAL ) , gingival index ( GI ) , plaque index ( PI ) , and percent bleeding on probing sites ( % BOP ) , while microbiologic variables included percentage of subjects positive for A. actinomycetemcomitans at baseline , 3 , 6 , and 12 months . RESULTS The AZM group showed statistically significant reduction in mean PD ( 2.91 ± 0.88 mm ) as compared to placebo ( 1.51 ± 0.98 mm ) ( P < 0.001 ) , while CAL gain was significant in the AZM group ( 2.71 ± 1.15 mm ) as compared to the placebo group ( 1.71 ± 1.29 mm ) ( P < 0.001 ) . There was also a statistically significant reduction in the number of subjects positive for A. actinomycetemcomitans in the AZM group ( P < 0.0001 ) . CONCLUSION Azithromycin was found to significantly improve the clinical and microbiological parameters in AAAP individuals OBJECTIVES The purpose of this study was to evaluate the effect of subgingival administration of doxycycline as an adjunct to periodontal therapy in type 1 diabetes mellitus ( DM ) patients . MATERIAL AND METHODS Twenty-two paired periodontal defects > or = 5.0 mm were treated in 11 patients ( 35 - 55 years old ) . After initial therapy the sites were r and omly assigned into test ( scaling and root planing+subgingival administration of 10 % doxycycline hyclate gel ) or control ( scaling and root planing+subgingival placebo gel ) groups . The clinical parameters of clinical attachment level ( CAL ) , probing depth ( PD ) and gingival margin level ( GML ) for recession determination were assessed at baseline , after 6 weeks , and 6 , 9 and 12 months , using a computerized probe . Data were statistically evaluated using Duncan and F tests . RESULTS Between study group comparisons indicated PD reduction and CAL gain were greater in the test group than in the control group at 6 weeks and 6 , 9 and 12 months but only statistically significant at 12 months ( p<0.05 ) . Within study group comparisons indicated statistically significant differences were found for CAL and PD values favouring the adjunctive doxycycline group from baseline to 6 weeks and 6 , 9 and 12 months ( p<0.05 ) . CONCLUSIONS These findings suggest that subgingivally delivered doxycycline hyclate produces additional favorable clinical results to periodontal therapy in type 1 DM patients OBJECTIVE Along with conventional non-surgical periodontal therapy ( NSPT ) systemic antimicrobials may provide more effective treatment for chronic periodontitis by targeting tissue-invasive bacteria . The aim of this r and omized , placebo-controlled , double-masked clinical trial was to evaluate the adjunctive effects of oral clarithromycin ( CLM ) to non-surgical periodontal therapy for chronic periodontitis . METHODS 40 patients were categorized into two groups : test group - scaling and root planing ( SRP ) plus CLM ( 500 mg b.i.d . for 3 days ) and control group - SRP plus placebo . Clinical parameters were recorded at baseline and at 1 , 3 , 6 , and 9 months . They included gingival index ( GI ) , probing depth ( PD ) , and clinical attachment level ( CAL ) . Also microbial analysis of dental plaque was done at baseline , 3 and 9 months to estimate the levels of periodontopathic organisms using polymerase chain reaction . ANOVA , Chi-square and Bonferroni tests were used for statistical analysis . RESULTS Thirty-seven subjects completed the study and the results demonstrated that both groups displayed clinical improvements . Using a subject-based analysis , patients treated with SRP+CLM showed enhanced reductions in PD and gains in CAL ( p<0.001 ) over time , as compared to control group . Also significant reductions in periodontopathic organisms were noticed in the test group compared to control group . However , no statistically significant differences were noted for Tannerella forsythia levels between the groups during the course of the study . CONCLUSIONS The utilisation of CLM in combination with SRP improves the efficacy of NSPT in reducing PD , improving CAL and in lessening microbial loads . Hence , CLM may be beneficial in the non-surgical treatment regimen of chronic periodontitis 48 adult patients with untreated periodontitis harboring subgingival Actinobacillus actinomycetemcomitans and /or Porphyromonas gingivalis as assessed by PCR were r and omly assigned to receive full-mouth scaling alone ( control ) or scaling with systemic metronidazole plus amoxicillin and supragingival irrigation with chlorhexidine digluconate ( test ) . In patients harboring A. actinomycetemcomitans intraorally at baseline , the adjunctive antimicrobial therapy result ed in a significantly higher incidence of probing attachment level ( PAL ) gain of 2 mm or more compared to scaling alone over 12 months ( p<0.05 ) . In addition , suppression of A. actinomycetemcomitans in subgingival plaque below detectable levels was associated with an increased incidence of PAL gain . In contrast , patients initially harboring P. gingivalis but not A. actinomycetemcomitans in the oral cavity showed a significantly higher incidence of PAL loss following adjunctive antimicrobial therapy compared to scaling alone ( p<0.05 ) . When the presence of pathogens at baseline was disregarded in the analysis , adjunctive antimicrobial therapy did not significantly enhance clinical treatment outcome . The results indicated that adults with untreated periodontitis harboring A. actinomycetemcomitans may benefit from the adjunctive antimicrobial therapy for a minimum of 12 months , whereas , the regimen may adversely affect the clinical treatment outcome of patients harboring P. gingivalis but not A. actinomycetemcomitans BACKGROUND The impact of moxifloxacin ( MOX ) was analyzed in the treatment of severe chronic periodontitis . METHODS In a r and omized , prospect i ve , clinical multicenter trial , 92 subjects with severe chronic periodontitis were treated with scaling and root planing ( SRP ) alone ( control group ; n = 21 ) , SRP plus adjunctive doxycycline ( DOX group ; n = 36 ) , or SRP plus adjunctive MOX ( MOX group ; n = 35 ) . Probing depth ( PD ) , clinical attachment level ( CAL ) , and bleeding on probing ( BOP ) were recorded at baseline and at 3 , 6 , and 12 months after non-surgical periodontal treatment . The load of periodontopathogens , the level of interleukin-8 , and the activities of granulocyte elastase and myeloperoxidase were also measured . RESULTS All three procedures led to significant reductions in PD , CAL , and BOP . PD reduction was significantly greater ( P < 0.05 ) in the MOX group ( 2.46 + /- 1.17 mm at 6 months and 2.84 + /- 1.53 mm at 12 months ) compared to the DOX group ( 1.85 + /- 1.24 mm and 2.19 + /- 1.13 mm at 6 and 12 months , respectively ) and the controls ( 1.77 + /- 0.57 mm and 1.86 + /- 0.56 mm at 6 and 12 months , respectively ) . Only in the MOX group was the load of all investigated bacteria and all inflammatory parameters reduced at each appointment compared to baseline . CONCLUSIONS The adjunctive application of antibiotics improved the treatment outcome in subjects with severe chronic periodontitis . MOX seemed to be more effective than DOX and might be an alternative drug in the treatment of periodontal diseases Locally delivered antibiotics are used to treat periodontitis and these agents are found to be effective in improving the treatment result . Microencapsulated minocycline hydrochloride ( Arestin ) has been tested and reported to provide significantly greater probing depth reduction in conjunction with scaling and root-planing than scaling and root-planing alone . Thus , it was suggested that the use of locally delivered antimicrobial agents should be incorporated as part of an optimal non-surgical therapeutic regimen . This paper evaluates the efficacy of the minocycline microspheres in patients with moderate to severe periodontitis in a model , which is a r and omised , evaluator-blinded study with an open-label ; four arm parallel design . The patients were selected based upon ' active ' disease , as determined by at least two teeth having one site each with pocket depth ( PD ) > or = 6 mm and with prostagl and in E2 ( PGE2 ) levels > 66.2 ng/ml in gingival crevicular fluid . The trial was of 6 months duration and used a formulation of minocycline microspheres containing 1 mg minocycline . Responses of groups receiving SRP followed by one dose per pocket of the minocycline microspheres ( SRP + MPTS ) were compared to SRP alone , MPTS alone or no treatment . There were substantially greater reductions in PD and gains in clinical attachment level ( CAL ) at each post-treatment time point in the SRP + MPTS group compared to the other treatment groups . PD reduction and gain in CAL at month 3 in the SRP + MPTS group vs. SRP alone was statistically significant . These data further support the adjunctive use of minocycline in a slow release vehicle for the treatment of periodontitis with SRP BACKGROUND The main therapeutic approach for periodontal diseases is mechanical treatment of root surfaces via scaling and root planing ( SRP ) . Multicenter clinical trials have demonstrated that the adjunctive use of a chlorhexidine ( CHX ) chip is effective in improving clinical results compared to SRP alone . However , some recent studies failed to confirm these clinical results , and conflicting results were reported regarding the effects of the CHX chip on subgingival microflora . The aim of this study was to provide further data on the clinical and microbiologic effects of CHX chips when used as an adjunct to SRP . METHODS A total of 116 systemically healthy individuals with moderate to advanced periodontitis , aged 33 to 65 years , were recruited from the Departments of Periodontology of four Italian universities . For each subject , two experimental sites were chosen that had probing depths ( PD ) > or = 5 mm and bleeding on probing ( BOP ) and were located in two symmetric quadrants . These two sites were r and omized at the split-mouth level , with one receiving SRP treatment alone and the other receiving treatment with SRP plus one CHX chip ( SRP + CHX ) . PD , relative attachment level ( RAL ) , and BOP were evaluated at baseline , prior to any treatment , and after 3 and 6 months . Supragingival plaque and the modified gingival index were evaluated at baseline and after 15 days and 1 , 3 , and 6 months . Subgingival microbiologic sample s were harvested at baseline and after 15 days and 1 , 3 , and 6 months , cultured for total bacterial counts ( TBCs ) , and investigated by polymerase chain reaction analysis for the identification of eight putative periodontopathogens . RESULTS When all of the pockets were considered , the PD and RAL were significantly less at 3 and 6 months compared to the baseline scores ( P < 0.01 ) for both treatments . Moreover , the PD was reduced in the SRP + CHX treatment group compared to the SRP treatment group at 3 and 6 months , whereas the RAL was similar for both treatments at 3 months and was reduced in the SRP + CHX treatment group at 6 months . The differences in PD reductions between the treatments were 0.30 and 0.55 mm at 3 and 6 months , respectively ( P < 0.01 ) ; for the RAL gain , the differences were 0.28 and 0.64 mm , respectively ( P < 0.001 ) . The TBCs decreased significantly with both treatments . A similar , although less evident , pattern was noted when only the pockets with an initial PD > or = 7 mm were considered . The percentage of sites positive for BOP was similar between the treatments at each time point . At 15 days and 1 month , the TBC for the SRP + CHX treatment group was significantly lower than for the SRP treatment group ( P < 0.01 and P < 0.05 , respectively ) . Over time , both treatments generally reduced the percentages of sites positive for the eight putative periodontopathic bacteria , although greater reductions were seen often for the SRP + CHX treatment group . CONCLUSIONS The adjunctive use of the CHX chip result ed in a significant PD reduction and a clinical attachment gain compared to SRP alone . These results were concomitant with a significant benefit of SRP + CHX treatment on the subgingival microbiota The objective of this study was to compare the efficacy of a systemic antibiotic ( doxycycline ) and a non-steroidal anti-inflammatory drug ( ibuprofen ) , administered either separately or combined , as an adjunctive treatment of scaling/root planing ( SRP ) . Thirty-two subjects diagnosed with generalized moderate adult periodontitis and having at least 2 teeth with > or = 5 mm probing depth were r and omly divided into 4 groups . Each group was treated with oral doxycycline and /or ibuprofen for 6 weeks as follows : group 1 , doxycycline 200 mg the first day followed by 100 mg per day ; group 2 , ibuprofen 800 mg per day ; group 3 , doxycycline plus ibuprofen scheduled as in groups 1 and 2 ; group 4 , one placebo capsule/day ( control ) . A split mouth design was utilized in each subject such that half of the teeth received one session of scaling/root planing ( SRP ) , while the other half received no SRP . Plaque index ( PI ) , gingival index ( GI ) , probing depth ( PD ) , and clinical attachment level ( CAL ) using a customized acrylic stent were recorded at baseline and at 3 , 6 , 12 , and 24 weeks following SRP . Analysis using ANOVA and Student t-test showed statistical significance ( P < or = 0.05 ) from baseline data in : 1 ) gains of 0.4 mm and 0.5 mm of CAL for groups 1 and 3 , respectively ; 2 ) reduction of 0.7 mm PD for group 3 ; 3 ) reduction of 0.4 and 0.1 GI scores for groups 1 and 3 , respectively ; and 4 ) gain of 0.5 mm CAL and reductions of 0.4 mm PD and 0.2 GI score for the SRP group when compared to the no SRP group at 24 weeks . It may be concluded that the adjunctive use of systemic doxycycline alone or in combination with ibuprofen results in a statistically significant , yet modest clinical , improvement beyond that obtained by scaling/root planing OBJECTIVE To compare clinical changes occurring in chronic periodontitis subjects receiving SRP alone or with systemically administered azithromycin , metronidazole or a sub-antimicrobial dose of doxycycline . MATERIAL AND METHODS 92 chronic periodontitis subjects were r and omly assigned to receive SRP alone ( N=23 ) or combined with 500 mg azithromycin per day for 3 days ( N=25 ) , 250 mg metronidazole tid for 14 days ( N=24 ) or 20 mg doxycycline bid for 3 months ( N=20 ) . Gingival redness , bleeding on probing , suppuration , pocket depth and attachment level were measured at baseline and 3 , 6 and 12 months post therapy . The significance of changes in clinical parameters within groups over time was sought using the Friedman test and among groups using ANCOVA or the Kruskal Wallis test . RESULTS All groups showed clinical improvements at 12 months , with subjects receiving adjunctive agents showing a somewhat better response . Sites with initial pocket depth > 6 mm showed significantly greater pocket depth reduction and greater attachment gain in subjects receiving metronidazole or azithromycin than subjects in the other groups . Some subjects showed attachment loss at 12 months in each group ranging from 15 % to 39 % of subjects in the SDD and SRP only groups respectively . CONCLUSION This study , demonstrated that periodontal therapy provides clinical benefits and that antibiotics provide a clinical benefit over SRP alone , particularly at initially deeper periodontal pockets BACKGROUND This study examines the efficacy of azithromycin in combination with non-surgical periodontal therapy on clinical and microbiologic parameters and gingival crevicular fluid ( GCF ) matrix metalloproteinases-8 ( MMP-8 ) levels over 6 months in patients with severe generalized chronic periodontitis ( CP ) . METHODS Twenty-eight of 36 patients with severe generalized CP were included in this r and omized , double-masked , placebo-controlled , parallel-arm study . They were r and omly assigned to azithromycin or placebo groups ( 500 mg , once daily for 3 days ) . Probing depth ( PD ) , clinical attachment level , dichotomous presence or absence of supragingival plaque accumulation , and bleeding on probing were recorded . GCF sample s were obtained from one single-rooted tooth with PD ≥ 6 mm , whereas microbiologic sample s were collected from two single-rooted teeth with PD ≥ 6 mm . Microbiologic parameters were analyzed by quantitative real-time polymerase chain reaction for Aggregatibacter actinomycetemcomitans , Porphyromonas gingivalis , Tannerella forsythia , Fusobacterium nucleatum , Prevotella intermedia , and total bacteria . GCF MMP-8 levels were determined by immunofluorescence assay . RESULTS Azithromycin and placebo groups demonstrated similar but significant improvements in all clinical parameters ( P < 0.05 ) . A. actinomycetemcomitans , P. gingivalis , T. forsythia , P. intermedia , and total bacteria significantly decreased over the 6-month period in both groups , whereas F. nucleatum was significantly reduced in all visits in the azithromycin group , with the levels also being lower compared with those of the placebo group ( P < 0.05 ) . The azithromycin and placebo groups exhibited significant reduction in GCF MMP-8 levels at the post-treatment visit and at 2 weeks ( P < 0.05 ) . CONCLUSION On the basis of the present findings , it can be concluded that adjunctive azithromycin provides no additional benefit over non-surgical periodontal treatment on parameters investigated in patients with severe generalized CP OBJECTIVE The impact of a locally delivered chlorhexidine chip ( Periochip ) on clinical and microbiological parameters of chronic periodontitis requires further documentation . The aim of the present study was to investigate the effects of the chip as an adjunct to mechanical treatment of chronic periodontitis . METHODS Fifty patients with chronic periodontitis were r and omized into two groups . The test group ( n = 25 ) received scaling and root planing and adjunctive Periochip in four pockets . The control group ( n = 25 ) received scaling and root planing only . Clinical indices ( probing depth , probing attachment level , bleeding on probing ) were assessed at baseline , three and six months . Subgingival sample s were analyzed at baseline , three weeks , three and six months after treatment for levels of eight bacterial species using " checkerboard " DNA-DNA hybridization . RESULTS The targeted difference of probing depth of 2 mm between groups was not observed . Both treatments result ed in improvement of clinical indices and non-statistically significant differences were observed between the two groups at any time point , with the exception of bleeding on probing at three months ( ANOVA , p < 0.05 ) . No major differences were observed concerning levels of important periodontal pathogens ( Mann-Whitney test , p < or = 0.05 ) . CONCLUSIONS In this small , six-month , phase 4 trial , no differences in mean probing depth reduction or " red-complex " periodontal pathogens were detected for patients with chronic periodontitis treated with adjunctive chlorhexidine chip ( single administration ) as compared to patients treated with scaling and root planing alone BACKGROUND The benefit of full-mouth disinfection ( FDIS ) over traditional scaling and root planing ( SRP ) remains equivocal , and it is not known whether the use of adjunctive antibiotics may enhance the effect of FDIS . The aim of the present study is to test the hypothesis that there is no difference in the 1-year clinical outcome of therapy among groups of patients treated with conventional SRP performed over 2 to 3 weeks , or same-day FDIS , with or without adjunctive metronidazole . METHODS A total of 184 patients with moderate-to-severe periodontitis were r and omly allocated to one of four treatment groups : 1 ) FDIS+metronidazole ; 2 ) FDIS+placebo ; 3 ) SRP+metronidazole ; or 4 ) SRP+placebo . Recordings of plaque , bleeding on probing , probing depth ( PD ) , and clinical attachment level ( CAL ) were carried out in four sites per tooth at baseline and at 3 and 12 months after treatment . RESULTS No differences were observed in the mean CAL or PD values between the four experimental groups at baseline and 3 or 12 months post-treatment . All four groups displayed significant improvements in all parameters . However , using absence of pockets ≥5 mm as the criterion for treatment success , the two groups receiving adjunctive metronidazole performed significantly better than the two placebo groups . CONCLUSION Metronidazole had a significant , adjunctive effect in patients with a metronidazole-sensitive subgingival microbiota on the clinical parameters of CAL , PD , and absence of pockets ≥5 mm BACKGROUND The clinical efficacy and safety of doxycycline hyclate ( 8.5 % w/w ) delivered subgingivally in a biodegradable polymer ( DH ) was compared to placebo control ( VC ) , oral hygiene ( OH ) , and scaling and root planing ( SRP ) in 2 multi-center studies . METHODS Each study entered 411 patients who demonstrated moderate to severe periodontitis . Patients had 2 or more quadrants each with a minimum of 4 qualifying pockets > or = 5 mm that bled on probing . At least 2 of the pockets were > or = 7 mm . Treatment with DH , VC , OH , or SRP was provided at baseline and again at month 4 . Clinical parameters were recorded monthly . RESULTS DH and SRP result ed in nearly identical clinical changes over time in both studies . Mean 9 month clinical attachment level gain ( ALG ) was 0.8 mm for the DH group and 0.7 mm for the SRP group in Study 1 , and 0.8 mm ( DH ) and 0.9 mm ( SRP ) in Study 2 . Mean probing depth ( PD ) reduction was 1.1 mm for the DH group and 0.9 mm for the SRP group in Study 1 and 1.3 mm for both groups in Study 2 . Frequency distributions showed an ALG > or = 2 mm in 29 % of DH sites versus 27 % of SRP sites in Study 1 and 31 % of DH sites versus 34 % of SRP sites in Study 2 . PD reductions > or = 2 mm were seen in 32 % of DH sites versus 31 % of SRP sites in Study 1 and 41 % of DH sites versus 43 % of SRP sites in Study 2 . Comparisons between DH , VC , and OH treatment groups showed DH treatment to be statistically superior to VC and OH . Safety data demonstrated a benign safety profile with use of the DH product . CONCLUSIONS Results of this trial demonstrate that treatment of periodontitis with subgingivally delivered doxycycline in a biodegradable polymer is equally effective as scaling and root planing and superior in effect to placebo control and oral hygiene in reducing the clinical signs of adult periodontitis over a 9-month period . This represents positive changes result ing from the use of subgingivally applied doxycycline as scaling and root planing was not limited regarding time of the procedure or use of local anesthesia OBJECTIVES The Vector ultrasonic system provides root debridement supported by different abrasive irrigation fluids . The aim of this study was to investigate the clinical outcome of initial therapy with subgingival low-abrasive debridement . MATERIAL AND METHODS Twenty patients , who had at least two teeth with pocket depths > 5 mm in each quadrant , took part in this prospect i ve r and omized clinical study . Patients were treated in a split-mouth design as one test quadrant ( 1 ) subgingivally with Vector fluid polish ( VU-H ) and as three control quadrants , ( 2 ) with only supragingival polishing ( PO-H ) , ( 3 ) with h and instruments ( HI-H ) performed by a hygienist and ( 4 ) with h and instruments ( HI-D ) performed by a dentist . At baseline , 3 and 6 months after treatment , pocket depths and attachment levels ( ALs ) were measured and bleeding on probing ( BOP ) was recorded . RESULTS At 6-month evaluation , all groups showed an improvement in clinical parameters . No statistically significant differences in any of the investigated parameters could be observed between the Vector group and the h and scaling groups , or when comparing the results of the two different operators . CONCLUSION This study demonstrates that Vector treatment with polishing fluid was able to reduce pocket depths and the prevalence of BOP and improve clinical AL in a similar way as scaling with curettes BACKGROUND In a previous study , subantimicrobial dose doxycycline ( SDD ) significantly improved clinical parameters associated with periodontal health in patients with adult periodontitis ( AP ) when used as an adjunct to a maintenance schedule of supragingival scaling and dental prophylaxis . In this double-blind , placebo-controlled , parallel-group , multicenter study , the efficacy and safety of SDD were evaluated in conjunction with scaling and root planing ( SRP ) in patients with AP . METHODS Patients ( n = 190 ) received SRP at the baseline visit and were r and omized to receive either SDD 20 mg bid or placebo bid for 9 months . Efficacy parameters included the per-patient mean changes in clinical attachment level ( CAL ) and probing depth ( PD ) from baseline , the per-patient percentages of tooth sites with attachment loss ( AL ) > or = 2 mm and > or = 3 mm from baseline , and the per-patient percentage of tooth sites with bleeding on probing . Prior to analysis , tooth sites were stratified by the degree of disease severity evident at baseline RESULTS In tooth sites with mild to moderate disease and severe disease ( n = 183 , intent-to-treat population ) , improvements in CAL and PD were significantly greater with adjunctive SDD than with adjunctive placebo at 3 , 6 , and 9 months ( all P < 0.05 ) . In tooth sites with severe disease , the per-patient percentage of sites with AL > or = 2 mm from baseline to month 9 was significantly lower with adjunctive SDD than with adjunctive placebo ( P<0.05 ) . Improvements in clinical outcomes occurred without detrimental shifts in the normal periodontal flora or the acquisition of doxycycline resistance or multiantibiotic resistance . SDD was well tolerated , with a low incidence of discontinuations due to adverse events . CONCLUSIONS The adjunctive use of SDD with SRP is more effective than SRP alone and may represent a new approach in the long-term management of AP The clinical efficacy of minocycline in a subgingival local delivery system was evaluated alone ( M ) or as an adjunct to scaling and root planing ( M + SRP ) , in comparison to scaling and root planing ( SRP ) or to no subgingival treatment ( NoTx ) in adult periodontitis . Fifty-one adult patients with > or = 7 mm periodontal pockets demonstrating the presence by culture of Porphyromonas gingivalis ( Pg ) , Prevotella intermedia ( P(i ) ) , or Actinobacillus actinomycetemcomitans ( Aa ) were r and omized into one of the above 4 treatment groups . All sites > or = 5 mm in the most diseased quadrant in each patient received the therapy . Other quadrants were not treated . All patients received st and ardized oral hygiene instructions at the beginning of the study . At 0 , 1 , 3 and 6 months following therapy the 7 mm experimental sites were evaluated for selected periodontal pathogens by DNA probe analysis . At these same time points , the plaque index , gingival index , and bleeding on probing were evaluated as well as probing depth and relative clinical attachment level which were assessed by means of an automated probe . Probing depth reduction with M + SRP was significantly greater than all other groups at one month and significantly greater than NoTx and SRP at 3 months . There were no differences in probing depth reduction among groups at 6 months . At 6 months the gain in clinical attachment level was significantly greater for SRP than for either the NoTx or M groups . The prevalence of Pg decreased significantly in the M and M + SRP groups at one month . ( ABSTRACT TRUNCATED AT 250 WORDS AIM Comparing the efficacy of photoablative and photodynamic diode laser in adjunct to scaling -root planing ( SRP ) and SRP alone for the treatment of chronic periodontitis . MATERIAL S AND METHODS Twenty-six patients were studied . Maxillary left or right quadrants were r and omly assigned to sham-laser treatment + SRP or laser + SRP . This consisted of photoablative intra/extra-pocket de-epithelization with diode laser ( λ = 810 nm ) , followed by single SRP and multiple photodynamic treatments ( once weekly , 4 - 10 applications , mean ± SD : 3.7 ± 2.4 ) using diode laser ( λ = 635 nm ) and 0.3 % methylene blue as photosensitizer . The patients were monitored at days 0 and 365 by clinical assessment ( probing depth , PD ; clinical attachment level , CAL ; bleeding on probing , BOP ) and at days 0 , 15 , 30 , 45 , 60 , 75 , 90 , 365 by cytofluorescence analysis of gingival exfoliative sample s taken in proximity of the teeth to be treated ( polymorphonuclear leukocytes , PMN ; red blood cells , RBC ; damaged epithelial cells , DEC ; bacteria ) . RESULTS At day 365 , compared with the control quadrants , the laser + SRP therapy yielded a significant ( p < 0.001 ) reduction in PD ( -1.9 mm ) , CAL ( -1.7 mm ) and BOP ( -33.2 % bleeding sites ) , as well as in bacterial contamination - especially spirochetes - and PMN and RBC shedding in the gingival sample s ( p < 0.001 ) . CONCLUSIONS Diode laser treatment ( photoablation followed by multiple photodynamic cycles ) adjunctive to conventional SRP improves healing in chronic periodontitis patients OBJECTIVE To compare the treatment outcome of scaling and root planing ( SRP ) in combination with systemic antibiotics , local antibiotic therapy and /or periodontal surgery . MATERIAL AND METHODS One hundred and eighty-seven patients were assigned to eight groups treated by SRP plus none , one , two or three adjunctive treatments and monitored for 24 months in a r and omized controlled clinical trial using a 2 × 2 × 2 factorial design . Systemic amoxicillin + metronidazole ( SMA ) , local tetracycline delivery ( LTC ) and periodontal surgery ( SURG ) were evaluated as adjuncts . Changes in clinical attachment level ( CAL ) and probing pocket depth ( PPD ) were statistically evaluated by ancova of main effects . RESULTS Effects of adjunctive therapy to SRP were minimal at 3 months . Between 3 and 6 months PPD reduction occurred particularly in patients receiving periodontal surgery . After 6 months , both CAL gain and PPD reduction reached a plateau that was maintained at 24 months in all groups . The 24-month CAL gain was improved by SMA ( 0.50 mm ) while PPD was reduced by SMA ( 0.51 mm ) and SURG ( 0.36 mm ) . Smoking reduced CAL gain and PPD reduction . CONCLUSION Patients receiving adjunctive therapies generally exhibited improved CAL gain and /or PPD reduction when compared with the outcome of SRP alone . Only additive , not synergistic effects of the various adjunctive therapies were observed Tetracyclines are now recognized to have non-antimicrobial properties with therapeutic potential -- for example , these agents can inhibit pathologic collagenolysis by blocking mammalian collagenases and other matrix-degrading metalloproteinases . In the current study , adult human subjects with moderate chronic periodontitis were administered specially formulated capsules of doxycycline , containing lower-than-usual amounts of this semi-synthetic tetracycline , on a daily basis for 2 weeks prior to a full-thickness flap procedure ; control subjects were administered placebo capsules . The gingiva excised during this surgical procedure were extracted , the extracts partially purified and analyzed for collagenase activity using [ 3H-methyl ] collagen as substrate and the techniques of SDS-PAGE/fluorography or liquid scintillation spectrometry . In the absence of any drug pre-treatment , or after a 2-wk regimen of placebo capsules , the gingival extracts exhibited pathologically-excessive mammalian collagenase activity . The 2-wk regimen of low-dose doxycycline capsules reduced this activity by approximately 60 - 80 % ( p less than 0.05 and less than 0.01 , respectively ) ; in vitro exposure of the gingival extract to doxycycline also inhibited its collagenase activity . Collagenase activity in the crevicular fluid of periodontal pockets of an additional group of subjects was also significantly reduced , as was the severity of inflammation at the same gingival sites . The results suggest that a regimen of low-dose doxycycline capsules may provide a safe ( other studies indicate that this regimen may not induce tetracycline resistance in the subgingival plaque ) and effective adjunct to instrumentation therapy in the management of pathologic collagenolysis in the periodontal patient . However , further studies are necessary to confirm this hypothesis AIM To evaluate the direct effects of periodontal therapy in Chronic Obstructive Pulmonary Disease ( COPD ) patients with chronic periodontitis ( CP ) . MATERIAL S AND METHODS In a pilot r and omized controlled trial , 60 COPD patients with CP were r and omly assigned to receive scaling and root planing ( SRP ) treatment , supragingival scaling treatment , or oral hygiene instructions only with no periodontal treatment . We evaluated their periodontal indexes , respiratory function , and COPD exacerbations at baseline , 6 months , 1 , and 2 years . RESULTS Compared with the control group , measurements of periodontal indexes were significantly improved in patients in two treatment groups at 6-month , 1-year , and 2-year follow-up ( all p < 0.05 ) . Overall , the means of forced expiratory volume in the first second/forced vital capacity ( FEV1/FVC ) and FEV1 were significantly higher in the two therapy groups compared with the control group during the follow-up ( p < 0.05 ) . In addition , the frequencies of COPD exacerbation were significantly lower in the two therapy groups than in the control group at 2-year follow-up ( p < 0.05 ) . CONCLUSIONS Our preliminary results from this pilot trial suggest that periodontal therapy in COPD patients with CP may improve lung function and decrease the frequency of COPD exacerbation AIM To evaluate the clinical and microbiological effects of the use of metronidazole ( MTZ ) + amoxicillin ( AMX ) as adjuncts to scaling and root planing ( SRP ) for the treatment of chronic periodontitis ( ChP ) in type 2 diabetic subjects . MATERIAL AND METHODS Fifty-eight type 2 diabetic subjects ( n = 29/group ) with generalized ChP were r and omly assigned to receive SRP alone or with MTZ [ 400 mg/thrice a day (TID)]+AMX ( 500 mg/TID ) for 14 days . Subgingival biofilm sample s were analyzed by qPCR for the presence of seven periodontal pathogens . Subjects were monitored at baseline , 3 , 6 and 12 months post-therapies . RESULTS The group receiving SRP+MTZ+AMX presented greater mean probing depth ( PD ) reduction and clinical attachment gain , a lower number of sites with PD ≥5 mm ( primary outcome variable ) and a reduced number of subjects with ≥9 of these residual pockets than the control group at 1-year post-therapy ( p < 0.05 ) . The antibiotic-treated group also presented reduced levels and greater decreases of the three red complex species , Eubacterium nodatum and Prevotella intermedia , compared to the control group at 1 year ( p < 0.05 ) . CONCLUSIONS The adjunctive use of MTZ+AMX significantly improved the clinical and microbiological outcomes of SRP in the treatment of type 2 diabetic subjects with |
11,886 | 12,221,356 | They showed that massage was inferior to manipulation and transcutaneous electrical nerve stimulation ; massage was equal to corsets and exercises ; and massage was superior to relaxation therapy , acupuncture , and self-care education .
CONCLUSIONS Massage might be beneficial for patients with subacute and chronic nonspecific LBP , especially when combined with exercises and education .
The evidence suggests that acupuncture massage is more effective than classic massage , but this needs confirmation . | BACKGROUND Low back pain ( LBP ) is one of the most common and costly musculoskeletal problems in modern society .
Proponents of massage therapy cl aim it can minimize pain and disability and speed return-to-normal function .
OBJECTIVES To assess the effects of massage therapy for nonspecific LBP . | OBJECTIVE To document the prevalence and patterns of use of alternative medical therapies as well as their perceived effectiveness by patients in a rehabilitation medicine outpatient practice . DESIGN Cross-sectional survey by written question naire . SETTING An urban rehabilitation medicine outpatient referral office . PATIENTS A r and om sample of 103 patients referred for rehabilitation outpatient care , while waiting for their appointment , were given a question naire addressing their use of alternative therapies . MAIN OUTCOME MEASURES Use of alternative therapies and their perceived effectiveness . RESULTS One or more alternative medical therapies had been used by 29.1 % of subjects in the past 12 months for their presenting problem . The most common therapies were massage , chiropractic , vitamin and mineral supplementation , and acupuncture . Musculoskeletal pain syndromes involving the spine and extremities were the most common problems for which patients sought both physiatric and alternative care . Of the patients who used alternative treatments 53 % reported some degree of efficacy . CONCLUSIONS A significant proportion of rehabilitation medicine patients use and frequently perceive a benefit from alternative therapies , particularly massage , chiropractic , vitamin and mineral supplementation , and acupuncture . Incorporating alternative therapies into physiatric practice is a desirable future direction for the specialty Three treatments for non-specific lumbar pain -- balneotherapy , underwater traction bath , and underwater massage -- were assessed in a r and omised prospect i ve controlled trial in 158 out patients . Each group was treated for four weeks and patients were review ed at the end of this period and at 12 months after entry to the trial . The prescription of analgesics and the pain score were significantly reduced in all three treated groups , but there was no difference between the three groups . No significant change occurred in spinal motion and the straight leg raising test . After one year only the analgesic consumption was significantly lower than in the control group OBJECTIVE --To compare the effectiveness of manipulative therapy , physiotherapy , treatment by the general practitioner , and placebo therapy in patients with persistent non-specific back and neck complaints . DESIGN --R and omised clinical trial . SETTING -- Primary health care in the Netherl and s. PATIENTS --256 patients with non-specific back and neck complaints of at least six weeks ' duration who had not received physiotherapy or manipulative therapy in the past two years . INTERVENTIONS --At the discretion of the manipulative therapists , physiotherapists , and general practitioners . Physiotherapy consisted of exercises , massage , and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manipulative therapy consisted of manipulation and mobilisation of the spine . Treatment by general practitioners consisted of drugs ( for example , analgesics ) , advice about posture , home exercises , and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 minutes ) and detuned ultrasound ( 10 minutes ) . MAIN OUTCOME MEASURES --Changes in severity of the main complaint and limitation of physical functioning measured on 10 point scales by a blinded research assistant and global perceived effect measured on a 6 point scale by the patients . RESULTS --Many patients in the general practitioner and placebo groups received other treatment during follow up . Improvement in the main complaint was larger with manipulative therapy ( 4.5 ) than with physiotherapy ( 3.8 ) after 12 months ' follow up ( difference 0.9 ; 95 % confidence interval 0.1 to 1.7 ) . Manipulative therapy also gave larger improvements in physical functioning ( difference 0.6 ; -0.1 to 1.3 ) . The global perceived effect after six and 12 months ' follow up was similar for both treatments . CONCLUSIONS --Manipulative therapy and physiotherapy are better than general practitioner and placebo treatment . Furthermore , manipulative therapy is slightly better than physiotherapy after 12 months BACKGROUND The effectiveness of massage therapy for low-back pain has not been documented . This r and omized controlled trial compared comprehensive massage therapy ( soft-tissue manipulation , remedial exercise and posture education ) , 2 components of massage therapy and placebo in the treatment of subacute ( between 1 week and 8 months ) low-back pain . METHODS Subjects with subacute low-back pain were r and omly assigned to 1 of 4 groups : comprehensive massage therapy ( n = 25 ) , soft-tissue manipulation only ( n = 25 ) , remedial exercise with posture education only ( n = 22 ) or a placebo of sham laser therapy ( n = 26 ) . Each subject received 6 treatments within approximately 1 month . Outcome measures obtained at baseline , after treatment and at 1-month follow-up consisted of the Rol and Disability Question naire ( RDQ ) , the McGill Pain Question naire ( PPI and PRI ) , the State Anxiety Index and the Modified Schober test ( lumbar range of motion ) . RESULTS Of the 107 subjects who passed screening , 98 ( 92 % ) completed post-treatment tests and 91 ( 85 % ) completed follow-up tests . Statistically significant differences were noted after treatment and at follow-up . The comprehensive massage therapy group had improved function ( mean RDQ score 1.54 v. 2.86 - 6.5 , p < 0.001 ) , less intense pain ( mean PPI score 0.42 v. 1.18 - 1.75 , p < 0.001 ) and a decrease in the quality of pain ( mean PRI score 2.29 v. 4.55 - 7.71 , p = 0.006 ) compared with the other 3 groups . Clinical significance was evident for the comprehensive massage therapy group and the soft-tissue manipulation group on the measure of function . At 1-month follow-up 63 % of subjects in the comprehensive massage therapy group reported no pain as compared with 27 % of the soft-tissue manipulation group , 14 % of the remedial exercise group and 0 % of the sham laser therapy group . INTERPRETATION Patients with subacute low-back pain were shown to benefit from massage therapy , as regulated by the College of Massage Therapists of Ontario and delivered by experienced massage therapists Delayed onset muscle soreness is a common problem that can interfere with rehabilitation as well as activities of daily living . The purpose of this study was to test the impact of therapeutic massage , upper body ergometry , or microcurrent electrical stimulation on muscle soreness and force deficits evident following a high-intensity eccentric exercise bout . Forty untrained , volunteer female subjects were r and omly assigned to one of three treatment groups or to a control group . Exercise consisted of high-intensity eccentric contractions of the elbow flexors . Resistance was reduced as subjects fatigued , until they reached exhaustion . Soreness rating was determined using a visual analog scale . Force deficits were determined by measures of maximal voluntary isometric contraction at 90 degrees of elbow flexion and peak torque for elbow flexion at 60 degrees/sec on a Cybex II isokinetic dynamometer . Maximal voluntary isometric contraction and peak torque were determined at the 0 hour ( before exercise ) and again at 24 and 48 hours postexercise . Treatments were applied immediately following exercise and again at 24 hours after exercise . The control group subjects rested following their exercise bout . Statistical analysis showed significant increases in soreness rating and significant decreases in force generated when the 0 hour was compared with 24- and 48-hour measures . Further analysis indicated no statistically significant differences between massage , microcurrent electrical stimulation , upper body ergometry , and control groups We conducted a pilot study to evaluate a practical exercise program for elderly people with chronic musculo-skeletal pain . Thirty-three subjects ( mean age , 73 years ; 69 % back pain ; 24 % knee pain ; 9 % hip pain ) were r and omly assigned to one of three groups . Group 1 received a 6-week supervised program of walking . Group 2 received a pain education program that included instruction and demonstration of use of heat , cold , massage , relaxation and distraction . Group 3 received usual care . Outcomes including pain , self-reported health and functional status , and performance-based measures of functional status were evaluated at baseline , at two weeks and at eight weeks ( end of study ) . Attendance was 100 % for the education sessions and 93 % for walking sessions . No injuries were sustained . Both intervention groups demonstrated significant improvements in pain ( p<0.05 ) and performance-based measures of functional status ( p<0.05 ) , while the control group had no changes . These data suggest that patient education and fitness walking can improve overall pain management and related functional limitations among elderly people with chronic musculo-skeletal pain Evaluating the effectiveness of nursing interventions in decreasing pain is a top priority for clinical research . Unfortunately , most of the research on cancer pain relief has been limited to treatment studies involving the administration of analgesics . Research is needed to determine which nonanalgesic methods of pain control are effective and under what conditions . Consequently , an experimental study was design ed to test the effectiveness of massage as an intervention for cancer pain . Twenty-eight patients were r and omly assigned to a massage or control group . The patients in the massage group were given a 10 minute massage to the back ; the patients in the control group were visited for 10 minutes . For males , there was a significant decrease in pain level immediately after the massage . For females , there was not a significant decrease in pain level immediately after the massage . There were no significant differences between pain 1 hour and 2 hours after the massage in comparison with the initial pain for males or females . Massage was shown to be an effective short-term nursing intervention for pain in males in this sample & NA ; It has recently been shown that ice massage of the web between the thumb and index finger produces significantly greater relief of dental pain than a placebo control procedure . These results indicate that ice massage may be comparable to transcutaneous electrical stimulation ( TES ) and acupuncture , and may be mediated by similar neural mechanisms . The purpose of this study was to examine the relative effectiveness of ice massage and TES for the relief of low‐back pain . Patients suffering chronic low‐back pain were treated with both ice massage and TES . The order of treatments was balanced , and changes in the intensity of pain were measured with the McGill Pain Question naire ( MPQ ) . The results show that both methods are equally effective : based on the Pain Rating Index of the MPQ , 67–69 % of patients obtained pain relief greater than 33 % with each method . The results indicate that ice massage is an effective therapeutic tool , and appears to be more effective than TES for some patients . It may also serve as an additional sensory‐modulation method to alternate with TES to overcome adaptation effects . Evidence that cold signals are transmitted to the spinal cord exclusively by A‐delta fibers and not by C fibers suggests that ice massage provides a potential method for differentiating among the multiple feedback systems that mediate analgesia produced by different forms of intense sensory input One year after head trauma , 23 patients with post-traumatic headache entered a prospect i ve clinical controlled trial to find out if specific manual therapy on the neck could reduce the headache . The study was completed by 19 patients ( 83 % ) . Ten patients were treated twice with manual therapy and nine patients were treated twice with cold packs on the neck . The pain index was calculated blindly . Two weeks after the last treatment the mean pain index was significantly reduced to 43 % in the group treated with manual therapy compared with the pretreatment level . At follow-up five weeks later , the pain index was still lower in this group compared with the group treated with cold packs , but this difference was not statistically significant . The pain index for all 19 patients was significantly correlated to the use of analgesics as well as to the frequency of associated symptoms ( number of days per week with dizziness , visual disturbances and ear symptoms ) . It is concluded that the type of manual therapy used in this study seems to have a specific effect in reducing post-traumatic headache . The result supports the hypothesis of a cervical mechanism causing post-traumatic headache and suggests that post-traumatic dizziness , visual disturbances and ear symptoms could be part of a cervical syndrome Patients with acute or chronic low back pain were treated in a double-blind study that compared transcutaneous electrical nerve stimulation at intense levels and gentle , mechanically administered massage . Transcutaneous electrical nerve stimulation produced significantly greater pain relief , based on two measures of the McGill Pain Question naire , and significant improvement in straight leg raising . There were no significant differences between the two groups in backflexion scores . Pain-relief scores and range-of-motion scores were significantly correlated . The results indicate that pain-relief scores provide valuable information and can easily be obtained from patients for whom pain is a major symptom BACKGROUND Because the value of popular forms of alternative care for chronic back pain remains uncertain , we compared the effectiveness of acupuncture , therapeutic massage , and self-care education for persistent back pain . METHODS We r and omized 262 patients aged 20 to 70 years who had persistent back pain to receive Traditional Chinese Medical acupuncture ( n = 94 ) , therapeutic massage ( n = 78 ) , or self-care educational material s ( n = 90 ) . Up to 10 massage or acupuncture visits were permitted over 10 weeks . Symptoms ( 0 - 10 scale ) and dysfunction ( 0 - 23 scale ) were assessed by telephone interviewers masked to treatment group . Follow-up was available for 95 % of patients after 4 , 10 , and 52 weeks , and none withdrew for adverse effects . RESULTS Treatment groups were compared after adjustment for prer and omization covariates using an intent-to-treat analysis . At 10 weeks , massage was superior to self-care on the symptom scale ( 3.41 vs 4.71 , respectively ; P = .01 ) and the disability scale ( 5.88 vs 8.92 , respectively ; P<.001 ) . Massage was also superior to acupuncture on the disability scale ( 5.89 vs 8.25 , respectively ; P = .01 ) . After 1 year , massage was not better than self-care but was better than acupuncture ( symptom scale : 3.08 vs 4.74 , respectively ; P = .002 ; dysfunction scale : 6.29 vs 8.21 , respectively ; P = .05 ) . The massage group used the least medications ( P<.05 ) and had the lowest costs of subsequent care . CONCLUSIONS Therapeutic massage was effective for persistent low back pain , apparently providing long-lasting benefits . Traditional Chinese Medical acupuncture was relatively ineffective . Massage might be an effective alternative to conventional medical care for persistent back pain STUDY DESIGN A r and omized trial design ed to compare interferential therapy with motorized lumbar traction and massage management for low back pain in a primary care setting . OBJECTIVE To measure and compare the outcome of interferential therapy and management by motorized lumbar traction and massage . SUMMARY OF BACKGROUND DATA Management of low back pain by interferential therapy and motorized lumbar traction and massage is common in Germany . No reports of previous r and omized trials for the outcome from interferential therapy were found . METHODS Consenting patients were r and omly assigned into one of two groups . A pretreatment interview was performed by the patient using a computer-based question naire . It also incorporated the Oswestry Disability Index and a pain visual analog scale . Management consisted of six sessions over a 2- to 3-week period . Oswestry Disability Indexes and pain visual analog scale scores also were obtained immediately after and at 3 months after treatment . RESULTS A total of 152 patients were recruited . The two treatment groups had similar demographic and clinical baseline characteristics . The mean Oswestry Disability Index before treatment was 30 for both groups ( n = 147 ) . After treatment , this had dropped to 25 , and , at 3 months , were 21 ( interferential therapy ) and 22 ( motorized lumbar traction and massage ) . The mean pain visual analog scale score before treatment was 50 ( interferential therapy ) and 51 ( motorized lumbar traction and massage ) . This had dropped , respectively , to 46 and 44 after treatment and to 42 and 39 at 3 months . CONCLUSIONS This study shows a progressive fall in Oswestry Disability Index and pain visual analog scale scores in patients with low back pain treated with either-interferential therapy or motorized lumbar traction and massage . There was no difference in the improvement between the two groups at the end of treatment . Although there is evidence from several trials that traction alone is ineffective in the management of low back pain , this study could not exclude some effect from the concomitant massage A r and omized clinical trial of rotational manipulation was conducted on 95 patients with low back pain selected for ( 1 ) the absence of any contraindications for vertebral manipulation , ( 2 ) the absence of any psychosocial problems that might affect the outcome of treatment , ( 3 ) the absence of any previous experience with manipulative therapy , and ( 4 ) the presence of palpatory cues indicating that manipulation might be successful . Patients were r and omly assigned to one of two groups : an experimental group receiving manipulation therapy and a control group receiving soft-tissue massage . Comparison of the two groups indicated that ( 1 ) patients who received manipulative treatment were much more likely to report immediate relief after the first treatment , and ( 2 ) at discharge , there was no significant difference between the two groups because both showed substantial improvement Forty patients with acute mechanical low-back pain were treated in a double-blind manner with either Rado-Salil ® or placebo for 14 days . Statistically significant improvements in spontaneous pain , muscular contracture and in both the patient 's and physician 's opinions occurred by day 3 . These improvements persisted at day 14 and , in addition , there were statistically significant improvements in the finger – floor distance and the degree of lumbar extension . Treatment with Rado-Salil ® also allowed significant reduction in the use of oral analgesics . Only a few localized transient side-effects , requiring no specific treatment , were observed OBJECTIVE To study the efficacy of manual therapy and physiotherapy in subgroups of patients with persistent back and neck complaints . The second objective was to determine the correlation between three important outcome measures used in this trial . DESIGN R and omized clinical trial ( subgroup analysis ) . SETTING Primary health care in the Netherl and s. PATIENTS Two hundred fifty-six patients with nonspecific back and neck complaints of at least 6 wk duration who had not received physiotherapy or manual therapy in the past 2 yr . INTERVENTIONS At the discretion of the manual therapists , physiotherapists and general practitioners . Physiotherapy consisted of exercises , massage and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manual therapy consisted of manipulation and mobilization of the spine . Treatment by the general practitioner consisted of drugs ( e.g. , analgesics ) , advice about posture , home exercises and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 min ) and detuned ultrasound ( 10 min ) . MAIN OUTCOME MEASURES Changes in severity of the main complaint and limitation of physical functioning measured on 10-point scales by a blinded research assistant and global perceived effect measured on a 6-point scale by the patients . RESULTS Improvement in the main complaint was larger with manual therapy ( 4.3 ) than with physiotherapy ( 2.5 ) for patients with chronic conditions ( duration complaint of 1 yr or longer ) . Also , improvement in the main complaint was larger with manual therapy ( 5.5 ) than with physiotherapy ( 4.0 ) for patients younger than 40 yr ( both were measured after 12-mo follow-up ) . Labeling of patients by the treating manual therapists as " suitable " or " not suitable " for treatment with manual therapy did not predict differences in outcomes . Generally , there was a moderate to strong correlation between the three outcome measures , although a considerable number of patients gave a relatively low score for perceived benefit , while the research assistant gave a high improvement score for the main complaint and physical functioning . CONCLUSIONS The subgroup analysis suggests better results of manual therapy compared to physiotherapy in chronic patients ( duration of present complaints of 1 yr or longer ) and in patients younger than 40 yr old ) . Differences for other subgroups were less clear . The explorative findings of these subgroup analyses have to be investigated in future research In a r and omized trial , the effectiveness of manual therapy , physiotherapy , continued treatment by the general practitioner , and placebo therapy ( detuned ultrasound and detuned short-wave diathermy ) were compared for patients ( n = 256 ) with nonspecific back and neck complaints lasting for at least 6 weeks . The principle outcome measures were severity of the main complaint , global perceived effect , pain , and functional status . These are presented for 3 , 6 , and 12 weeks follow-up . Both physiotherapy and manual therapy decreased the severity of complaints more and had a higher global perceived effect compared to continued treatment by the general practitioner . Differences in effectiveness between physiotherapy and manual therapy could not be shown . A substantial part of the effect of manual therapy and physiotherapy appeared to be due to nonspecific ( placebo ) effects Study Design : A r and omized between-groups design evaluated massage therapy versus relaxation for chronic low back pain . Objectives : Treatment effects were evaluated for reducing pain , depression , anxiety and stress hormones , and sleeplessness and for improving trunk range of motion associated with chronic low back pain . Summary of Background Data : Twenty-four adults ( M age = 39.6 years ) with low back pain of nociceptive origin with a duration of at least 6 months participated in the study . The groups did not differ on age , socioeconomic status , ethnicity or gender . Methods : Twenty-four adults ( 12 women ) with lower back pain were r and omly assigned to a massage therapy or a progressive muscle relaxation group . Sessions were 30 minutes long twice a week for five weeks . on the first and last day of the 5-week study participants completed question naires , provided a urine sample and were assessed for range of motion . Results : By the end of the study , the massage therapy group , as compared to the relaxation group , reported experiencing less pain , depression , anxiety and improved sleep . They also showed improved trunk and pain flexion performance , and their serotonin and dopamine levels were higher . Conclusions : Massage therapy is effective in reducing pain , stress hormones and symptoms associated with chronic low back pain . Precis : Adults ( M age = 39.6 years ) with low back pain with a duration of at least 6 months received two 30-min massage or relaxation therapy sessions per week for 5 weeks . Participants receiving massage therapy reported experiencing less pain , depression , anxiety and their sleep had improved . They also showed improved trunk and pain flexion performance , and their serotonin and dopamine levels were higher & NA ; The effect of intensive dynamic back extensor exercises for patients with chronic low back pain was investigated in a controlled clinical trial in which chronic low back pain patients underwent a 3‐month intensive training program with a total of 30 sessions . The 105 patients were divided into 3 groups : a treatment group , an alternative group which underwent 1/5 of the treatment group 's exercise program per session , and an alternative group in which treatment consisted of thermotherapy , massage and mild exercise . Regardless of whether the treatment outcome is assessed qualitatively or quantitatively , a statistically significant , favorable difference was found between the results for the treatment group and for the alternative groups at conclusion and at the 3‐month follow‐up . It appeared from the quantitative assessment that patients in the treatment group who completed the training program at least once a week for the entire 1‐year follow‐up period were the only patients with a significantly better back status after 1 year compared to the time of inclusion . Irrespective of sex , age , duration and degree of severity of back trouble , or of pre‐existing sciatica or pathological findings upon X‐ray of the spine , patients obtained a favorable result from the training program . The therapy was found to be without risk , but patients with clinical signs of current lumbar nerve root compression or radiological signs of spondylolysis or halisteresis of the spine were excluded from the study The effect of intensive dynamic back extensor exercises for patients with chronic low back was investigated in a controlled clinical trial where the patients underwent a three months intensive training program a total 30 sessions . The 105 patients were divided into three groups : a treatment group , an alternative group which underwent 1/5 of the treatment group 's exercise program per session , and an alternative group in which the treatment consisted of thermotherapy , massage and mild exercise . Regardless of whether the outcome of treatment is assessed qualitatively or quantitatively , a statistically significant , favourable difference was found between the results for the treatment group and those for the alternative groups . The therapy was found to be without risk , but patients with clinical signs of current lumbar nerve root compression or radiological signs of spondylolysis or halisteresis of the column were excluded from the study . The authors recommend the introduction of this form of treatment as a general offer in the primary and secondary health sector . Back exercises can advantageously be conducted in a group ; thus , the re sources required for this treatment do not differ significantly from those required for many of the other forms of treatment generally employed , which often require individual attention STUDY DESIGN A r and omized study comparing the results of active rehabilitation and passive control treatment in patients with chronic low back pain with follow-up at 6 months and 1 year . OBJECTIVES To study the efficacy of active rehabilitation on pain , self-experienced disability , and lumbar fatigability . SUMMARY OF BACKGROUND DATA Exercises in an outpatient setting are widely used for the treatment of chronic low back pain . The efficacy of the active rehabilitation approach has been documented in r and omized control studies , but these studies have seldom been focused on lumbar fatigability , which is now recognized as a frequent problem among patients with chronic low back pain . METHODS Fifty-nine middle-aged patients ( 37 men and 22 women ) with nonspecific chronic low back pain were r and omly assigned to 12 weeks ' active rehabilitation or to a passive control treatment ( massage , thermal therapy ) . Pain and disability index , low back pain intensity ( visual analog scale , 100 mm ) , and the objective ly assessed lumbar muscle fatigability ( spectral electromyogram , mean power frequency slope [ MPFSLOPE ] ) in a new 90-second submaximal isoinertial back endurance test were recorded before and after the interventions and at 6-month and 1-year follow-up visits . RESULTS Results of repeated measures multivariate analysis of variance indicated that back pain intensity ( visual analog scale ) and functional disability ( pain and disability index score ) decreased , and lumbar endurance ( MPFSLOPE ) improved significantly more ( P < 0.05 ) in the active rehabilitation group than in the passive control treatment group , when measured at a 1-year follow-up examination . The group difference in visual analog scale and pain and disability index changes became even more significant at the end of 1 year . The change in lumbar endurance was significantly greater in the active rehabilitation group than in the passive control treatment group at the 6-month follow-up , but not at the 1-year follow-up . CONCLUSIONS The active progressive treatment program was more successful in reducing pain and self-experienced disability and also in improving lumbar endurance than was the passive control treatment . However , the group difference in lumbar endurance tended to diminish at the 1-year follow-up The authors carried out a single-blind , r and omized controlled clinical trial of rotational manipulation for low-back pain of recent onset in 81 adults . Control treatments were minimal massage and low-level electrostimulation . Initial status and outcome were measured on scales quantifying symptoms , activities of dally life , mobility , tenderness to palpation , aggravation of pain by coughing or sneezing , limitation of motion on testing , and forward flexion . Both treated and control patients improved rapidly in the 2 - 3-week observation period . On retest there was no statistically significant difference between the improvement scores of the treated or control groups on any of the scales OBJECTIVE Rehabilitation programs for low back pain ( LBP ) almost always contain massage and exercise therapy in one form or another . AIM This study aim ed to quantify the effectiveness of therapeutic ' Acupuncture ' massage ( APM ; i.e. tonic stimulation of entire meridians ) according to Penzel versus Swedish massage ( SM ) and individual medical exercises ( IE ) versus group exercises ( GE ) in LBP sufferers . PATIENTS AND METHODS 109 patients participating in a complex in-patient rehabilitation program were r and omised to four groups in a 2 x 2 factorial design . Main outcome measures were functional ability/disability ( Functional Question naire Hanover , FFbH ) and pain intensity ( 10 cm visual analogue scale , VAS ) . Pre/post changes were evaluated by means of 2-way analysis of variance ( ANOVA ) . Additionally , lumbar motility was measured by a 2-inclinometer technique . RESULTS Baseline mean FFbH score was 66 ( SD = 18)% , mean pain intensity on VAS was 4.5 ( SD = 2.4 ) cm . Lumbar flexion and extension were 49 ( 13 ) and 13 ( 7 ) . Because of some differences between groups at baseline , group-st and ardized outcomes were used for analysis . APM showed beneficial effects for both disability and pain compared with SM ( group differences : delta FFbH 7.0 % [ 95 % confidence interval ( CI ) 2.5 - 11.6 ] , p = 0.003 ; delta VAS 0.8 cm [ 95 % CI : 2 - 15 ] , p = 0.024 ) . St and ardized response means were SRMFFbH = 0.5 and SRMVAS = 0.8 for APM , as opposed to SRMFFbH = -0.01 and SRMVAS = 0.4 for SM . Neither significant group differences between both exercise groups [ delta FFbH -0.5 % ( 95 % CI -5.2 to 4.2 ) ; delta Vas 0.4 cm ( 95 % CI 0.3 to 1.1 ) ] nor significant interactions between medical exercise and massage were found . CONCLUSIONS Given the fact that even the treatments considered to be the best available achieve at best moderate effects , the observed effect sizes with APM are promising and warrant further investigation in replication studies . In contrast to common view , no superiority of individual versus group exercises could be found in the present study 105 patients who had chronic low back pain without clinical signs of lumbar nerve root compression or radiological evidence of spondylolysis or osteomalacia were r and omised to three treatments : 30 sessions of intensive dynamic back extensor exercises over three months ; a similar programme at one-fifth the exercise intensity ; or one month of thermotherapy , massage , and mild exercises . The results consistently favoured intensive exercise , which had no adverse effects . Since these exercises can be conducted in groups , the intensive programme is no more costly than conventional strategies that require individual attention |
11,887 | 23,289,975 | Conclusion Despite higher complete remission rates , there is no improvement in OS with auto-allo HCT ; but this approach results in higher NRM in patients with newly diagnosed MM . | Background Despite advances in underst and ing of clinical , genetic , and molecular aspects of multiple myeloma ( MM ) and availability of more effective therapies , MM remains incurable .
The autologous-allogeneic ( auto-allo ) hematopoietic cell transplantation ( HCT ) strategy is based on combining cytoreduction from high-dose ( chemo- or chemoradio)-therapy with adoptive immunotherapy .
However , conflicting results have been reported when an auto-allo HCT approach is compared to t and em autologous ( auto-auto ) HCT .
A previously published meta- analysis has been reported ; however , it suffers from serious method ological flaws . | Between August 1990 and August 1995 , 231 patients ( median age 51 , 53 % Durie-Salmon stage III , median serum beta-2-microglobulin 3.1 g/L , median C-reactive protein 4 g/L ) with symptomatic multiple myeloma were enrolled in a program that used a series of induction regimens and two cycles of high-dose therapy ( " Total Therapy " ) . Remission induction utilized non-cross-resistant regimens ( vincristine-doxorubicin-dexamethasone [ VAD ] , high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor with peripheral blood stem cell collection , and etoposide-dexamethasone-cytarabine-cisplatin ) . The first high-dose treatment comprised melphalan 200 mg/m2 and was repeated if complete ( CR ) or partial ( PR ) remission was maintained after the first transplant ; in case of less than PR , total body irradiation or cyclophosphamide was added . Interferon--2b maintenance was used after the second autotransplant . Fourteen patients with HLA-compatible donors underwent an allograft as their second high-dose therapy cycle . Eighty-eight percent completed induction therapy whereas first and second transplants were performed in 84 % and 71 % ( the majority within 8 and 15 months , respectively ) . Eight patients ( 3 % ) died of toxicity during induction , and 2 ( 1 % ) and 6 ( 4 % ) during the two transplants . True CR and at least a PR ( PR plus CR ) were obtained in 5 % ( 34 % ) after VAD , 15 % ( 65 % ) at the end of induction , and 26 % ( 75 % ) after the first and 41 % ( 83 % ) after the second transplants ( intent-to-treat ) . Median overall ( OS ) and event-free ( EFS ) survival duration s were 68 and 43 months , respectively . Actuarial 5-year OS and EFS rates were 58 % and 42 % , respectively . The median time to disease progression or relapse was 52 months . Among the 94 patients achieving CR , the median CR duration was 50 months . On multivariate analysis , superior EFS and OS were observed in the absence of unfavorable karyotypes ( 11q breakpoint abnormalities , -13 or 13-q ) and with low beta-2-microglobulin at diagnosis . CR duration was significantly longer with early onset of CR and favorable karyotypes . Time-dependent covariate analysis suggested that timely application of a second transplant extended both EFS and OS significantly , independent of cytogenetics and beta-2-microglobulin . Total Therapy represents a comprehensive treatment approach for newly diagnosed myeloma patients , using multi-regimen induction and t and em transplantation followed by interferon maintenance . As a result , the proportion of patients attaining CR increased progressively with continuing therapy . This observation is particularly important because CR is a sine qua non for long-term disease control and , eventually , cure Thalidomide ( Thal ) can overcome drug resistance in multiple myeloma ( MM ) but is associated with somnolence , constipation , and neuropathy . In previous in vitro studies , we have shown that the potent immunomodulatory derivative of thalidomide ( IMiD ) CC-5013 induces apoptosis or growth arrest even in resistant MM cell lines and patient cells , decreases binding of MM cells to bone marrow stromal cells ( BMSCs ) , inhibits the production in the BM milieu of cytokines ( interleukin-6 [ IL-6 ] , vascular endothelial growth factor [ VEGF ] , tumor necrosis factor-alpha [ TNF-alpha ] ) mediating growth and survival of MM cells , blocks angiogenesis , and stimulates host anti-MM natural killer ( NK ) cell immunity . Moreover , CC-5013 also inhibits tumor growth , decreases angiogenesis , and prolongs host survival in a human plasmacytoma mouse model . In the present study , we carried out a phase 1 CC-5013 dose-escalation ( 5 mg/d , 10 mg/d , 25 mg/d , and 50 mg/d ) study in 27 patients ( median age 57 years ; range , 40 - 71 years ) with relapsed and refractory relapsed MM . They received a median of 3 prior regimens ( range , 2 - 6 regimens ) , including autologous stem cell transplantation and Thal in 15 and 16 patients , respectively . In 24 evaluable patients , no dose-limiting toxicity ( DLT ) was observed in patients treated at any dose level within the first 28 days ; however , grade 3 myelosuppression developed after day 28 in all 13 patients treated with 50 mg/d CC-5013 . In 12 patients , dose reduction to 25 mg/d was well tolerated and therefore considered the maximal tolerated dose ( MTD ) . Importantly , no significant somnolence , constipation , or neuropathy has been seen in any cohort . Best responses of at least 25 % reduction in paraprotein occurred in 17 ( 71 % ) of 24 patients ( 90 % confidence interval [ CI ] , 52%-85 % ) , including 11 ( 46 % ) patients who had received prior Thal . Stable disease ( less than 25 % reduction in paraprotein ) was observed in an additional 2 ( 8 % ) patients . Therefore , 17 ( 71 % ) of 24 patients ( 90 % CI , 52%-85 % ) demonstrated benefit from treatment . Our study therefore provides the basis for the evaluation of CC-5013 , either alone or in combination , to treat patients with MM at earlier stages of disease BACKGROUND In this trial of the treatment of newly diagnosed multiple myeloma , we compared a protocol that entailed a hematopoietic stem-cell autograft followed by an allograft from an HLA-identical sibling with a protocol of t and em autografts . METHODS We enrolled 162 consecutive patients with newly diagnosed myeloma who were 65 years of age or younger and who had at least one sibling . All patients were initially treated with vincristine , doxorubicin , and dexamethasone , followed by melphalan and autologous stem-cell rescue . Patients with an HLA-identical sibling then received nonmyeloablative total-body irradiation and stem cells from the sibling . Patients without an HLA-identical sibling received two consecutive myeloablative doses of melphalan , each of which was followed by autologous stem-cell rescue . The primary end points were overall survival and event-free survival . RESULTS After a median follow-up of 45 months ( range , 21 to 90 ) , the median overall survival and event-free survival were longer in the 80 patients with HLA-identical siblings than in the 82 patients without HLA-identical siblings ( 80 months vs. 54 months , P=0.01 ; and 35 months vs. 29 months , P=0.02 , respectively ) . Among patients who completed their assigned treatment protocol s , treatment-related mortality did not differ significantly between the double-autologous-transplant group ( 46 patients ) and the autograft-allograft group ( 58 patients , P=0.09 ) , but disease-related mortality was significantly higher in the double-autologous-transplant group ( 43 % vs. 7 % , P<0.001 ) . The cumulative incidence rates of grade s II , III , and IV graft-versus-host disease ( GVHD ) combined and of grade IV GVHD in the autograft-allograft group were 43 % and 4 % , respectively . Overall , 21 of 58 patients ( 36 % ) were in complete remission after a median follow-up of 38 months ( range , 10 to 72 ) after allografting . Of the 46 patients who received two autografts , 25 ( 54 % ) died . CONCLUSIONS Among patients with newly diagnosed myeloma , survival in recipients of a hematopoietic stem-cell autograft followed by a stem-cell allograft from an HLA-identical sibling is superior to that in recipients of t and em stem-cell autografts . ( Clinical Trials.gov number , NCT00415987 [ Clinical Trials.gov ] . ) BACKGROUND AND OBJECTIVES The Dutch-Belgian HOVON group performed a r and omized phase 3 trial to compare single non-myeloablative intensive treatment with double , intensive treatment in previously untreated patients with multiple myeloma ( MM ) . DESIGN AND METHODS Three hundred and three patients with stage II/III MM were r and omized after VAD induction chemotherapy to receive two cycles of non-myeloablative intermediate-dose melphalan ( 70 mg/m2 ) ( single treatment ) or the same regimen followed by cyclophosphamide 120 mg/kg iv plus total body irradiation ( TBI ) 9 Gy and autologous stem cell transplantation ( double , intensive treatment ) . In both treatment arms interferon .IIa was given as maintenance until relapse/progression . RESULTS A significantly higher proportion of patients achieved a complete remission ( CR ) on protocol treatment with double , intensive therapy ( 32 % vs 13 % , p<0.001 ) . Double treatment produced better outcome in terms of event-free survival ( median 22 vs 21 months , 28 % vs 14 % at 4 years and 15 % vs 7 % at 6 years after r and omization ; logrank p=0.013 ; univariate HR 0.74 , 95 % CI , 0.58 - 0.94 ) , progression-free survival ( median 27 vs 24 months , 33 % vs 16 % at 4 years , and 17 % vs 9 % at 6 years after r and omization ; logrank p=0.006 ; HR=0.71 , 95 % CI 0.56 - 0.91 ) , but not overall survival ( median 50 vs 55 months , 52 % vs 56 % at 4 years and 39 % vs 36 % at 6 years after r and omization ; logrank p=0.51 ; HR=1.10 , 95 % CI 0.83 - 1.46 ) . The achievement of a CR had a favorable prognostic impact on event-free survival ( HR=0.60 , 95 % CI=0.44 -0.82 , p=0.001 ) and progression-free survival ( HR=0.62 , 95 % CI=0.45 -0.84 , p=0.002 ) . INTERPRETATION AND CONCLUSIONS Double , intensive treatment result ed in a better CR rate , event-free survival and progression-free survival but not overall survival compared to single non-myeloablative treatment in previously untreated patients with multiple myeloma BACKGROUND Autologous haemopoietic stem-cell transplantation ( HSCT ) improves survival in patients with multiple myeloma , but disease progression remains an issue . Allogeneic HSCT might reduce disease progression , but can be associated with high treatment-related mortality . Thus , we aim ed to assess effectiveness of allogeneic HSCT with non-myeloablative conditioning after autologous HSCT compared with t and em autologous HSCT . METHODS In our phase 3 biological assignment trial , we enrolled patients with multiple myeloma attending 37 transplant centres in the USA . Patients ( < 70 years old ) with adequate organ function who had completed at least three cycles of systemic antimyeloma therapy within the past 10 months were eligible for inclusion . We assigned patients to receive an autologous HSCT followed by an allogeneic HSCT ( auto-allo group ) or t and em autologous HSCTs ( auto-auto group ) on the basis of the availability of an HLA-matched sibling donor . Patients in the auto-auto group subsequently underwent a r and om allocation ( 1:1 ) to maintenance therapy ( thalidomide plus dexamethasone ) or observation . To avoid enrolment bias , we classified patients as st and ard risk or high risk on the basis of cytogenetics and β2-microglobulin concentrations . We used the Kaplan-Meier method to estimate differences in 3-year progression-free survival ( PFS ; primary endpoint ) between patients with st and ard-risk disease in the auto-allo group and the best results from the auto-auto group ( maintenance , observation , or pooled ) . This study is registered with Clinical Trials.gov , number NCT00075829 . FINDINGS Between Dec 17 , 2003 , and March 30 , 2007 , we enrolled 710 patients , of whom 625 had st and ard-risk disease and received an autologous HSCT . 156 ( 83 % ) of 189 patients with st and ard-risk disease in the auto-allo group and 366 ( 84 % ) of 436 in the auto-auto group received a second transplant . 219 patients in the auto-auto group were r and omly assigned to observation and 217 to receive maintenance treatment , of whom 168 ( 77 % ) completed this treatment . PFS and overall survival did not differ between maintenance and observation groups and pooled data were used . Kaplan-Meier estimates of 3-year PFS were 43 % ( 95 % CI 36 - 51 ) in the auto-allo group and 46 % ( 42 - 51 ) in the auto-auto group ( p=0·671 ) ; overall survival also did not differ at 3 years ( 77 % [ 95 % CI 72 - 84 ] vs 80 % [ 77 - 84 ] ; p=0·191 ) . Within 3 years , 87 ( 46 % ) of 189 patients in the auto-allo group had grade 3 - 5 adverse events as did 185 ( 42 % ) of 436 patients in the auto-auto group . The adverse events that differed most between groups were hyperbilirubinaemia ( 21 [ 11 % ] patients in the auto-allo group vs 14 [ 3 % ] in the auto-auto group ) and peripheral neuropathy ( 11 [ 6 % ] in the auto-allo group vs 52 [ 12 % ] in the auto-auto group ) . INTERPRETATION Non-myeloablative allogeneic HSCT after autologous HSCT is not more effective than t and em autologous HSCT for patients with st and ard-risk multiple myeloma . Further enhancement of the graft versus myeloma effect and reduction in transplant-related mortality are needed to improve the allogeneic HSCT approach . FUNDING US National Heart , Lung , and Blood Institute and the National Cancer Institute Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies . We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospect ively enrolled in homogeneous therapeutic trials . All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells . They were systematic ally screened for the following genomic aberrations : del(13 ) , t(11;14 ) , t(4;14 ) , hyperdiploidy , MYC translocations , and del(17p ) . Chromosomal changes were observed in 90 % of the patients . The del(13 ) , t(11;14 ) , t(4;14 ) , hyperdiploidy , MYC translocations , and del(17p ) were present in 48 % , 21 % , 14 % , 39 % , 13 % , and 11 % of the patients , respectively . After a median follow-up of 41 months , univariate statistical analyses revealed that del(13 ) , t(4;14 ) , nonhyperdiploidy , and del(17p ) negatively impacted both the event-free survival and the overall survival , whereas t(11;14 ) and MYC translocations did not influence the prognosis . Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14 ) and del(17p ) retained prognostic value for both the event-free and overall survivals . When compared with the currently used International Staging System , this prognostic model compares favorably . In myeloma , the genomic aberrations t(4;14 ) and del(17p ) , together with beta2-microglobulin level , are important independent predictors of survival . These findings have implication s for the design of risk-adapted treatment strategies The Intergroupe Francophone du Myélome ( IFM ) initiated 2 trials in 1999 to study patients with high-risk ( beta2-microglobulin level greater than 3 mg/L and chromosome 13 deletion at diagnosis ) de novo multiple myeloma . In both protocol s , the induction regimen consisted of vincristine , doxorubicin , and dexamethasone ( VAD ) followed by first autologous stem cell transplantation ( ASCT ) prepared by melphalan 200 mg/m(2 ) . Patients with an HLA-identical sibling donor were subsequently treated with dose-reduced allogeneic stem cell transplantation ( IFM99 - 03 trial ) , and patients without an HLA-identical sibling donor were r and omly assigned to undergo second ASCT prepared by melphalan 220 mg/m(2 ) and 160 mg dexamethasone with or without anti-IL-6 monoclonal antibody ( IFM99 - 04 protocol ) . Two hundred eighty-four patients -65 in the IFM99 - 03 trial and 219 in the IFM99 - 04 trial-were prospect ively treated and received at least one course of VAD . On an intent-to-treat basis , overall survival ( OS ) and event-free survival ( EFS ) did not differ significantly in the studies ( medians 35 and 25 months in the IFM99 - 03 trial vs 41 and 30 months in the IFM99 - 04 trial , respectively ) . With a median follow-up time of 24 months , the EFS of the 166 patients r and omly assigned in the t and em ASCT protocol was similar to the EFS of the 46 patients who underwent the entire IFM99 - 03 program ( median , 35 vs 31.7 months ) , with a trend for a better OS in patients treated with t and em ASCT ( median , 47.2 vs 35 months ; P = .07 ) . In patients with high-risk de novo MM , the combination of ASCT followed by dose-reduced allogeneic transplantation was not superior to t and em dose-intensified , melphalan-based ASCT PURPOSE We performed a prospect i ve , r and omized study of single ( arm A ) versus double ( arm B ) autologous stem-cell transplantation ( ASCT ) for younger patients with newly diagnosed multiple myeloma ( MM ) . PATIENTS AND METHODS A total of 321 patients were enrolled onto the study and were r and omly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 ( arm A ) or melphalan at 200 mg/m2 followed , after 3 to 6 months , by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram ( arm B ) . RESULTS As compared with assignment to the single-transplantation group ( n = 163 patients ) , r and om assignment to receive double ASCT ( n = 158 patients ) significantly increased the probability to attain at least a near complete response ( nCR ; 33 % v 47 % , respectively ; P = .008 ) , prolonged relapse-free survival ( RFS ) duration of 18 months ( median , 24 v 42 months , respectively ; P < .001 ) , and significantly extended event-free survival ( EFS ; median , 23 v 35 months , respectively ; P = .001 ) . Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50 % of patients r and omly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group , whose 7-year rate ( 46 % ) was similar to that of the double-transplantation group ( 43 % ; P = .90 ) . Transplantation-related mortality was 3 % in arm A and 4 % in arm B ( P = .70 ) . CONCLUSION In comparison with a single ASCT as up-front therapy for newly diagnosed MM , double ASCT effected superior CR or nCR rate , RFS , and EFS , but failed to significantly prolong overall survival . Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation BACKGROUND The median survival of patients with myeloma after conventional chemotherapy is three years or less . Promising results have been reported with high-dose therapy supported by autologous bone marrow transplantation . We conducted a r and omized study comparing conventional chemotherapy and high-dose therapy . METHODS Two hundred previously untreated patients under the age of 65 years who had myeloma were r and omly assigned at the time of diagnosis to receive either conventional chemotherapy or high-dose therapy and autologous bone marrow transplantation . RESULTS The response rate among the patients who received high-dose therapy was 81 percent ( including complete responses in 22 percent and very good partial responses in 16 percent ) , whereas it was 57 percent ( complete responses in 5 percent and very good partial responses in 9 percent ) in the group treated with conventional chemotherapy ( P < 0.001 ) . The probability of event-free survival for five years was 28 percent in the high-dose group and 10 percent in the conventional-dose group ( P = 0.01 ) ; the overall estimated rate of survival for five years was 52 percent in the high-dose group and 12 percent in the conventional-dose group ( P = 0.03 ) . Treatment-related mortality was similar in the two groups . CONCLUSIONS High-dose therapy combined with transplantation improves the response rate , eventfree survival , and overall survival in patients with myeloma BACKGROUND We conducted a r and omized trial of the treatment of multiple myeloma with high-dose chemotherapy followed by either one or two successive autologous stem-cell transplantations . METHODS At the time of diagnosis , 399 previously untreated patients under the age of 60 years were r and omly assigned to receive a single or double transplant . RESULTS A complete or a very good partial response was achieved by 42 percent of patients in the single-transplant group and 50 percent of patients in the double-transplant group ( P=0.10 ) . The probability of surviving event-free for seven years after the diagnosis was 10 percent in the single-transplant group and 20 percent in the double-transplant group ( P=0.03 ) . The estimated overall seven-year survival rate was 21 percent in the single-transplant group and 42 percent in the double-transplant group ( P=0.01 ) . Among patients who did not have a very good partial response within three months after one transplantation , the probability of surviving seven years was 11 percent in the single-transplant group and 43 percent in the double-transplant group ( P<0.001 ) . Four factors were significantly related to survival : base-line serum levels of beta2-microglobulin ( P<0.01 ) and lactate dehydrogenase ( P<0.01 ) , age ( P<0.05 ) , and treatment group ( P<0.01 ) . CONCLUSIONS As compared with a single autologous stem-cell transplantation after high-dose chemotherapy , double transplantation improves overall survival among patients with myeloma , especially those who do not have a very good partial response after undergoing one transplantation BACKGROUND Bortezomib , a boronic acid dipeptide , is a novel proteasome inhibitor that has been shown in pre clinical and phase 1 studies to have antimyeloma activity . METHODS In this multicenter , open-label , nonr and omized , phase 2 trial , we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently . Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks , followed by 1 week without treatment , for up to eight cycles ( 24 weeks ) . In patients with a suboptimal response , oral dexamethasone ( 20 mg daily , on the day of and the day after bortezomib administration ) was added to the regimen . The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee . RESULTS Of 193 patients who could be evaluated , 92 percent had been treated with three or more of the major classes of agents for myeloma , and in 91 percent , the myeloma was refractory to the therapy received most recently . The rate of response to bortezomib was 35 percent , and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immunofixation . The median overall survival was 16 months , with a median duration of response of 12 months . Grade 3 adverse events included thrombocytopenia ( in 28 percent of patients ) , fatigue ( in 12 percent ) , peripheral neuropathy ( in 12 percent ) , and neutropenia ( in 11 percent ) . Grade 4 events occurred in 14 percent of patients . CONCLUSIONS Bortezomib , a member of a new class of anticancer drugs , is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy Multiple myeloma is a malignant plasma cell neoplasm that affects more than 20,000 people each year and is the second most common hematologic malignancy . It is part of a spectrum of monoclonal plasma cell disorders , many of which do not require active therapy . During the past decade , considerable progress has been made in our underst and ing of the disease process and factors that influence outcome , along with development of new drugs that are highly effective in controlling the disease and prolonging survival without compromising quality of life . Identification of well-defined and reproducible prognostic factors and introduction of new therapies with unique modes of action and impact on disease outcome have for the first time opened up the opportunity to develop risk-adapted strategies for managing this disease . Although these risk-adapted strategies have not been prospect ively vali date d , enough evidence can be gathered from existing r and omized trials , subgroup analyses , and retrospective studies to develop a working framework . This set of recommendations represents such an effort-the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence BACKGROUND High-dose therapy with supporting autologous stem-cell transplantation remains a controversial treatment for cancer . In multiple myeloma , first-line regimens incorporating high-dose therapy yield higher remission rates than do conventional-dose treatments , but evidence that this translates into improved survival is limited . METHODS In this multicenter study , the Medical Research Council Myeloma VII Trial , we r and omly assigned 407 patients with previously untreated multiple myeloma who were younger than 65 years of age to receive either st and ard conventional-dose combination chemotherapy or high-dose therapy and an autologous stem-cell transplant . RESULTS Among the 401 patients who could be evaluated , the rates of complete response were higher in the intensive-therapy group than in the st and ard-therapy group ( 44 percent vs. 8 percent , P<0.001 ) . The rates of partial response were similar ( 42 percent and 40 percent , respectively ; P=0.72 ) , and the rates of minimal response were lower in the intensive-therapy group than in the st and ard-therapy group ( 3 percent vs. 18 percent , P<0.001 ) . Intention-to-treat analysis showed a higher rate of overall survival ( P=0.04 by the log-rank test ) and progression-free survival ( P<0.001 ) in the intensive-therapy group than in the st and ard-therapy group . As compared with st and ard therapy , intensive treatment increased median survival by almost 1 year ( 54.1 months [ 95 percent confidence interval , 44.9 to 65.2 ] vs. 42.3 months [ 95 percent confidence interval , 33.1 to 51.6 ] ) . There was a trend toward a greater survival benefit in the group of patients with a poor prognosis , as defined by a high beta2-microglobulin level ( more than 8 mg per liter ) . CONCLUSIONS High-dose therapy with autologous stem-cell rescue is an effective first-line treatment for patients with multiple myeloma who are younger than 65 years of age BACKGROUND Patients with myeloma who relapse after high-dose chemotherapy have few therapeutic options . Since increased bone marrow vascularity imparts a poor prognosis in myeloma , we evaluated the efficacy of thalidomide , which has antiangiogenic properties , in patients with refractory disease . METHODS Eighty-four previously treated patients with refractory myeloma ( 76 with a relapse after high-dose chemotherapy ) received oral thalidomide as a single agent for a median of 80 days ( range , 2 to 465 ) . The starting dose was 200 mg daily , and the dose was increased by 200 mg every two weeks until it reached 800 mg per day . Response was assessed on the basis of a reduction of the myeloma protein in serum or Bence Jones protein in urine that lasted for at least six weeks . RESULTS The serum or urine levels of paraprotein were reduced by at least 90 percent in eight patients ( two had a complete remission ) , at least 75 percent in six patients , at least 50 percent in seven patients , and at least 25 percent in six patients , for a total rate of response of 32 percent . Reductions in the paraprotein levels were apparent within two months in 78 percent of the patients with a response and were associated with decreased numbers of plasma cells in bone marrow and increased hemoglobin levels . The microvascular density of bone marrow did not change significantly in patients with a response . At least one third of the patients had mild or moderate constipation , weakness or fatigue , or somnolence . More severe adverse effects were infrequent ( occurring in less than 10 percent of patients ) , and hematologic effects were rare . As of the most recent follow-up , 36 patients had died ( 30 with no response and 6 with a response ) . After 12 months of follow-up , Kaplan-Meier estimates of the mean ( + /-SE ) rates of event-free survival and overall survival for all patients were 22+/-5 percent and 58+/-5 percent , respectively . CONCLUSIONS Thalidomide is active against advanced myeloma . It can induce marked and durable responses in some patients with multiple myeloma , including those who relapse after high-dose chemotherapy One hundred ten patients with multiple myeloma ( MM ) failing to achieve at least near-complete remission ( nCR ) after a first autologous stem cell transplantation ( ASCT ) were scheduled to receive a second ASCT ( 85 patients ) or a reduced-intensity-conditioning allograft ( allo-RIC ; 25 patients ) , depending on the human leukocyte antigen (HLA)-identical sibling donor availability . There was a higher increase in complete remission ( CR ) rate ( 40 % vs 11 % , P = .001 ) and a trend toward a longer progression-free survival ( PFS ; median , 31 months vs not reached , P = .08 ) in favor of allo-RIC . In contrast , it was associated with a trend toward a higher transplantation-related mortality ( 16 % vs 5 % , P = .07 ) , a 66 % chance of chronic graft-versus-host disease and no statistical difference in event-free survival and overall survival . Although the PFS plateau observed with allo-RIC is very encouraging , this procedure is associated with high morbidity and mortality , and therefore it should still be considered investigational and restricted to well- design ed prospect i ve clinical trials . This trial is registered at Clinical Trials.gov ID number NCT00560053 |
11,888 | 29,133,137 | The majority of occupational studies found a negative impact on respiratory health outcomes and increases in inflammatory biomarkers among farm workers exposed to bioaerosols .
Studies investigating the health of communities living near intensive farms had mixed findings .
The review indicated a potential impact of intensive farming on childhood respiratory health , based on a small number of studies using self-reported outcomes , but supported by findings from occupational studies . | BACKGROUND Population growth , increasing food dem and s , and economic efficiency have been major driving forces behind farming intensification over recent decades .
However , biological emissions ( bioaerosols ) from intensified livestock farming may have the potential to impact human health .
Bioaerosols from intensive livestock farming have been reported to cause symptoms and /or illnesses in occupational- setting s and there is concern about the potential health effects on people who live near the intensive farms .
As well as adverse health effects , some potential beneficial effects have been attributed to farm exposures in early life .
The aim of the study was to undertake a systematic review to evaluate potential for adverse health outcomes in population s living near intensive livestock farms . | BACKGROUND Farmers have an increased risk of respiratory morbidity and mortality . The causal agents have not been fully established . METHODS In a cross-sectional study of 4,735 Norwegian farmers , we assessed respiratory symptoms and lung function . Atopy was assessed in a sub sample ( n = 1,213 ) . Personal exposures to dust , fungal spores , actinomycete spores , endotoxins , bacteria , storage mites , (1 - ->3)-ss-D-glucans , fungal antigens , organic dust , inorganic dust , silica , ammonia , and hydrogen sulfide were measured for 127 r and omly selected farms . RESULTS Compared to crop farmers , livestock farmers were more likely to have chronic bronchitis ( odds ratio [ OR ] , 1.9 ; 95 % confidence interval [ CI ] , 1.4 to 2.6 ) and COPD ( OR , 1.4 ; 95 % CI , 1.1 to 1.7 ) . FEV(1 ) ( -41 mL ; 95 % CI , -75 to -7 ) was significantly reduced , but FVC ( -15 mL ; 95 % CI , -54 to 24 ) was not . Exposure to most agents were predictors of respiratory morbidity , except FVC . Ammonia , hydrogen sulfide , and inorganic dust were most strongly associated in multiple regression models adjusted for coexposures , but the effects of specific biological agents could not be assessed in multiple regression models because they were too highly correlated . Farmers with atopy had a significantly lower FEV(1 ) ( OR , -87 mL ; 95 % CI , -170 to -7 ) , but atopy was not directly associated with chronic bronchitis , COPD , and FVC . However , the effects of farming and specific exposures on COPD were substantially greater in farmers with atopy . CONCLUSIONS Livestock farmers have an increased risk of chronic bronchitis , COPD , and reduced FEV(1 ) . Ammonia , hydrogen sulfide , inorganic dust , and organic dust may be causally involved , but a role for specific biological agents can not be excluded . Farmers with atopy appear more susceptible to develop farming-related COPD 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 OBJECTIVES . Little is known about the health effects of living in close proximity to industrial swine operations . We assessed the relationship between estimated exposure to airborne effluent from confined swine feeding operations and asthma symptoms among adolescents who were aged 12 to 14 years . METHODS . During the 1999–2000 school year , 58169 adolescents in North Carolina answered questions about their respiratory symptoms , allergies , medications , socioeconomic status , and household environments . To estimate the extent to which these students may have been exposed during the school day to air pollution from confined swine feeding operations , we used publicly available data about schools ( n = 265 ) and swine operations ( n = 2343 ) to generate estimates of exposure for each public school . Prevalence ratios and 95 % confidence intervals for wheezing within the past year were estimated using r and om-intercepts binary regression models , adjusting for potential confounders , including age , race , socioeconomic status , smoking , school exposures , and household exposures . RESULTS . The prevalence of wheezing during the past year was slightly higher at schools that were estimated to be exposed to airborne effluent from confined swine feeding operations . For students who reported allergies , the prevalence of wheezing within the past year was 5 % higher at schools that were located within 3 miles of an operation relative to those beyond 3 miles and 24 % higher at schools in which livestock odor was noticeable indoors twice per month or more relative to those with no odor . CONCLUSIONS . Estimated exposure to airborne pollution from confined swine feeding operations is associated with adolescents ’ wheezing symptoms OBJECTIVES To describe the relation between spirometric findings and farming characteristics and variables of exposure to organic dust measured during work in animal buildings . Farmers have traditionally been described as having one of the most dangerous occupations , so a large scale study on European farmers was carried out . This is the report of the second part of that study . METHODS 40 pig farmers in Denmark and 36 poultry farmers in Switzerl and were chosen r and omly and were assessed over 1 working day . RESULTS Mean ( SD ) baseline spirometric results in pig farmers were higher than in poultry farmers ( forced expiratory volume in 1 second ( FEV1 ) ( % of reference value ) 108.3 ( 16.7 ) v 100.2 ( 14.2 ) ; p=0.04 ) . Baseline lung function results were significantly associated with ventilation of the animal houses . Furthermore , temperature was related to spirometric findings in pig farmers . CONCLUSIONS Ventilation of the animal house and temperature might influence respiratory morbidity in farmers BACKGROUND Up to now potential health effects of environmental exposure to intensive livestock production facilities have not been thoroughly studied . The aim of the Lower Saxony Lung Study ( NiLS ) was to assess the prevalence of respiratory symptoms and disease in an area with intensive animal production facilities taking into account environmental exposure to emissions from these large-scale farms . METHODS All 10 864 inhabitants ( age 18 to 44 years ) of four towns with a large number of intensive animal production facilities in the area were invited to answer a mail-in question naire . Of these , 6416 subjects were r and omly selected for the clinical part of the study ( specific IgE , lung function measurements , bronchial provocation with methacholine ) . Overall , 6937 subjects answered the question naire ( 68 % ) , 60 % took part in the clinical tests . RESULTS The prevalence of allergic disease in the study population was lower than in urban citizens . Subjects with more than 12 animal houses within 500 m of their home had an increased odds ratio for wheezing without a cold ( odds ratio 2.7 ; 95 % confidence interval 1.4 - 5.4 ) . They also showed a significantly decreased FEV ( 1 ) ( mean 0.26 l ; 0.04 l - 0.48 l ) as well as a trend for a lower Tiffeneau-Index . CONCLUSIONS In result , a large number of intensive animal production facilities might be associated with decreased lung function results in the immediate neighbours . Further studies are necessary to confirm our findings Background : Despite public concern about potential adverse health effects of concentrated animal feeding operations , objective ly assessed data on environmental exposure to concentrated animal feeding operations and respiratory health are sparse . We aim ed to assess respiratory health in neighbors of confined animal feeding operations . Methods : A survey was done in 2002–2004 among all adults ( 18–45 years old ) living in 4 rural German towns with a high density of confined animal feeding operations . Question naire data were available for 6937 ( 68 % ) eligible subjects . In a r and om sample we measured the following outcomes : specific IgE to common and farm-specific allergens , lung function , and bronchial hyperresponsiveness to methacholine . Exposure was measured by collecting data on odor annoyance and geo-coded data on the number of animal houses within 500 m of the home . Locally optimal estimating and smoothing scatter plots were used to model the association between exposure and outcome . Analyses were restricted to subjects without private or professional contact with farming environments . Results : The prevalence of self-reported asthma symptoms and nasal allergies increased with self-reported odor annoyance . The number of animal houses was a predictor of self-reported wheeze and decreased forced expiratory volume in 1 second , but not allergic rhinitis or specific sensitization . Self-reported exposure and results of clinical measurements were poorly correlated . Conclusions : Confined animal feeding operations may contribute to the burden of respiratory disease among their neighbors . Our findings underline the importance of objective assessment of exposure and outcome in environmental epidemiology Numerous articles have been published regarding the adverse respiratory health consequences of working in intensive livestock and poultry housing . Threshold limit exposure guidelines are not currently applied to this environment , but they are essential to implement and monitor effective environmental controls . Previous dose-response research work with swine workers has result ed in exposure limit recommendations of 2.5 mg/m3 total dust , 0.23 mg/m3 respirable dust , 100 EU/m3 endotoxin , and 7 ppm ammonia . No similar recommendations have been reported previously for poultry workers . Therefore , an industry-wide study was conducted to examine dose-response relationships of bioaerosol exposures and worker respiratory health . A total of 257 poultry workers were studied for respiratory symptoms , pulmonary function , and exposure to dust ( total and respirable ) , endotoxin ( respirable and total ) , and ammonia . Details of the sampling plan and environmental assessment are described elsewhere . Relationships between exposures and response were studied by correlation and multiple regressions . Significant dose-response relationships were observed between exposures and pulmonary function decrements over a work shift . Exposure concentrations associated with significant pulmonary function decrements were as follows : 2.4 mg/m3 total dust , 0.16 mg/m3 respirable dust , 614 EU/m3 endotoxin , and 12 ppm ammonia BACKGROUND Exposure to swine dust leads to an intense airway inflammation and increased bronchial responsiveness . The purpose of the present study was to evaluate the effect of a respiratory protection device during exposure in a swine house . METHODS Twenty-two subjects , 11 with a respirator , were exposed . Symptoms , body temperature , nasal lavage , and a bronchial metacholine challenge were performed before and 7 hr after exposure . For exposure assessment a nasal sample r was evaluated . RESULTS The subjects with a respirator showed an attenuated inflammatory nasal response . An increase in bronchial responsiveness was observed in both groups , significantly greater in the unprotected group . The use of respirators reduced endotoxin exposure by more than 90 % ( assessed by nasal sample rs ) . CONCLUSION The use of a respirator attenuated the inflammatory response compared with an unprotected group . The minor effect on bronchial responsiveness suggests that gases and /or ultrafine particles may also be important factors Testing of lung function and bronchial reactivity , bronchoalveolar lavage ( BAL ) , and a skin prick test with a st and ard panel and six " swine " extracts obtained from swine and swine environment were performed in 20 r and omly selected nonsmoking swine confinement workers . In addition , blood sample s for detection of antibodies by the diffusion in gel-enzyme-linked immunosorbent assay ( DIG-ELISA ) technique and precipitating antibodies were drawn . Air sample s for measurement of dust and endotoxin levels were collected . All the farmers regarded themselves as healthy . The results were compared with reference groups consisting of urban nonsmoking subjects who had not been exposed to pig farming environment . The pig farmers had normal lung function and the bronchial reactivity was not different from the reference group . In the BAL fluid of the farmers , the concentration of total cells and granulocytes was increased while the concentrations of lymphocytes and macrophages were normal . The BAL fluid concentrations of albumin , fibronectin , and hyaluronan were elevated in the farmers . Skin prick tests with swine extracts were negative in all farmers . Antibodies ( assessed by DIG-ELISA ) against swine d and er , swine dust , and pig feed were increased and precipitating antibodies against swine d and er were found in 14 , against pig food in five , and against swine confinement dust in three of the 20 pig farmers . The concentration of airborne total dust was 7.4 mg/cu mm and the endotoxin concentration was 37 ( 22 to 60 ) ng/cu mm during tending the pigs and increased , during feeding , to 13.8 mg/cu mm and 315 ( 194 to 716 ) ng/cu mm , respectively . There was no correlation between exposure and lung function or lavage findings . In conclusion , r and omly selected pig farmers had signs of airway inflammatory reaction and activation of the immune system without alteration in lung function and bronchial reactivity A crossover trial was conducted to evaluate the acute human health effects of a dust control technology in a swine confinement facility . Twenty lifetime nonsmoking male subjects , with no evidence of allergy or asthma and no previous swine barn exposure , participated in the study , which included a laboratory session ( baseline ) , 5-h exposure in a swine room sprinkled with canola oil ( treatment ) and 5-h exposure in a traditional swine room ( control ) . Mean values of inhalable dust concentrations and endotoxin levels in the control room were significantly greater than those observed in the treatment room . Mean shift changes in FEV1 from preexposure to end of exposure were 1.1 % ( st and ard error , 0.63 % ) on baseline day , -1.9 % ( 0.63 % ) on treatment day , and -9.9 % ( 1.12 % ) on control day ; the differences in the shift changes were statistically significant . Mean value of methacholine concentration that reduced the FEV1 by 20 % ( PC20 ) in bronchoprovocation tests on baseline day was significantly different from that on treatment day ( p = 0.04 ) and that on control day ( p < 0.001 ) . Significant increases were also observed in white blood cell counts and nasal lavage cell counts on the control day in comparison with the other two days . Blood neutrophil counts after control room exposure were twice those observed on baseline and after exposure to the treatment room . Significant differences were also observed in IL-1 beta , IL-6 , and IL-8 nasal lavage cytokines and in IL-6 serum cytokine . These results suggest that the canola oil dust control method is effective in improving indoor air quality in swine barns and reducing acute health effects in naive healthy subjects |
11,889 | 26,635,788 | Recently , a more focused SR&MA has demonstrated that antibiotics active against BV-related organisms , used in women whose risk of PTB is due to abnormal microflora , and used early in pregnancy before irreversible inflammatory damage has occurred , can reduce the rate of PTB . | Infection-related preterm birth ( PTB ) is more common at early gestational ages and is associated with major neonatal mortality and morbidity .
Abnormal genital tract microflora in early pregnancy predicts late miscarriage and early PTB .
Accordingly , it is logical to consider antibiotics as an intervention .
As a result , many clinicians think that any antibiotic given at any time in pregnancy to any woman at risk of PTB will cause more harm than good . | OBJECTIVES : To determine whether intravaginal clindamycin cream reduces the incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial flora grade d as intermediate or BV and to investigate the effect of the antibiotic on vaginal microbial flora . METHODS : A prospect i ve cohort study of pregnant women in an antenatal clinic of a district general hospital . The subjects were 268 women who had abnormal vaginal microbial flora at first clinic visit by examination of a Gram-stained vaginal smear and 34 women with a normal vaginal flora . Two hundred and thirty-seven women were evaluable . Women with abnormal Gram-stained smears ( grade d as II or III ) on clinic recall were r and omised to receive treatment ( intravaginal clindamycin cream ) or placebo and followed to assess outcome of pregnancy , vaginal flora , and detection of Mycoplasma hominis and Ureaplasma urealyticum after treatment . RESULTS : Abnormal outcomes of pregnancy were not significantly different in treated and placebo groups by Chi square ( P = 0.2 ) . However , women with grade III flora responded better to clindamycin than women with grade II flora by numbers of abnormal outcomes ( P = 0.03 ) and return to normal vaginal flora ( P = 0.01 ) ( logistic regression analysis model ) . This may be due to differences in vaginal bacterial species in these grade s. Women whose abnormal vaginal flora had spontaneously returned to normal on follow-up and were therefore not treated ( revertants ) had as many abnormal outcomes as placebos suggesting that damage by abnormal bacterial species occurred early in pregnancy . CONCLUSIONS : Gram-stain screening distinguishing grade II from grade III flora may be helpful in prescribing treatment other than clindamycin for women with grade II flora . Earlier diagnosis and treatment may be more effective in preventing an abnormal outcome , possibly as soon as pregnancy is diagnosed or even offered as a pre-conception screen Abstract Objective To evaluate whether a screening strategy in pregnancy lowers the rate of preterm delivery in a general population of pregnant women . Design Multicentre , prospect i ve , r and omised controlled trial . Setting Non-hospital based antenatal clinics . Participants 4429 pregnant women presenting for their routine prenatal visits early in the second trimester were screened by Gram stain for asymptomatic vaginal infection . In the intervention group , the women 's obstetricians received the test results and women received st and ard treatment and follow up for any detected infection . In the control group , the results of the vaginal smears were not revealed to the caregivers . Main outcome measures The primary outcome variable was preterm delivery at less than 37 weeks . Secondary outcome variables were preterm delivery at less than 37 weeks combined with different birth weight categories equal to or below 2500 g and the rate of late miscarriage . Results Outcome data were available for 2058 women in the intervention group and 2097 women in the control group . In the intervention group , the number of preterm births was significantly lower than in the control group ( 3.0 % v 5.3 % , 95 % confidence interval 1.2 to 3.6 ; P = 0.0001 ) . Preterm births were also significantly reduced in lower weight categories at less than 37 weeks and ≤ 2500 g. Eight late miscarriages occurred in the intervention group and 15 in the control group . Conclusion Integrating a simple infection screening programme into routine antenatal care leads to a significant reduction in preterm births and reduces the rate of late miscarriage in a general population of pregnant women OBJECTIVE To assess the ability of clindamycin vaginal cream to reduce the incidence of preterm birth in women with abnormal genital tract flora in the second trimester of pregnancy . METHODS This was a r and omized , double-blind , placebo-controlled , tricenter study . A total of 409 women with abnormal genital tract flora on Gram stain of vaginal secretions at 13–20 weeks ' gestation were r and omized to receive a 3-day course of clindamycin vaginal cream or placebo . Those women who still had abnormal vaginal flora 3 weeks later received a 7-day course of the original study drug ( ie , either clindamycin vaginal cream or placebo as per original r and omization ) . The primary outcome measure was the incidence of preterm birth . RESULTS There was a statistically significant reduction in the incidence of preterm birth in the clindamycin vaginal cream group ( 4 % ) compared with placebo ( 10 % ) ( P < .03 ) . Significantly more babies born preterm ( 63 % ) required admission to the neonatal intensive care unit compared with term infants ( 4 % ) ( P < .001 ) . CONCLUSION A 2 % clindamycin vaginal cream , when compared with placebo administered to women with abnormal genital tract flora before 20 weeks ' gestation , can reduce the incidence of preterm birth by 60 % and hence the need for neonatal intensive care OBJECTIVE Our purpose was to analyze ( 1 ) the effects of prevalent lower reproductive tract infections and ( 2 ) the effect of systematic diagnosis and treatment to reduce risks of early pregnancy loss ( < 22 weeks ) , preterm premature rupture of membrances , and overall preterm birth . STUDY DESIGN A prospect i ve , controlled treatment trial was conducted on 1260 women . During the first 7 months of the program ( observation , phase I ) , women were examined at initiation of prenatal care for a panel of lower genital tract microorganisms and bacterial vaginosis . Women were followed up with reexaminations at 22 to 29 weeks and after 32 weeks ' gestation . The recommended treatments of the Centers for Disease Control ( i.e. , 300 mg of clindamycin orally twice daily for 7 days for bacterial vaginosis ) were used for infected women during the second 8 months of the study ( treatment , phase II ) . Data were analyzed according to intent to treat by means of univariate and multivariate methods . RESULTS Overall , presence of bacterial vaginosis ( 32.5 % ) at enrollment was associated with pregnancy loss at < 22 weeks ' gestation ( relative risk 3.1 , 95 % confidence interval 1.4 to 6.9 ) . Among women in the observation phase bacterial vaginosis was associated with increased risk of both preterm birth ( relative risk 1.9 , 95 % confidence interval 1.2 to 3.0 ) and preterm premature rupture of membranes ( relative risk 3.5 , 95 % confidence interval 1.4 to 8.9 ) . Within this population ( phase I ) 21.9 % of preterm birth overall ( 43.8 % premature rupture of membranes ) is estimated as attributable to bacterial vaginosis . Among women with bacterial vaginosis phase II ( treatment ) was associated with reduced preterm birth ( relative risk 0.5 , 95 % confidence interval 0.3 to 0.9 ) ; there was a similar reduction for women with preterm premature rupture of membranes ( relative risk 0.5 , 95 % confidence interval 0.2 to 1.4 ) . Women with both bacterial vaginosis and trichomoniasis were at highest risk of preterm birth ( 28 % ) ; treatment of both conditions ( phase II ) reduced preterm birth ( 17 % ) but did not eliminate this risk . Earlier patient enrollment and oral antibiotic treatment were associated with reduced preterm birth . CONCLUSIONS This prospect i ve , controlled trial confirms that the presence of bacterial vaginosis is associated with increased risks of pregnancy loss at < 22 weeks , preterm premature rupture of membranes , and preterm birth . Orally administered clindamycin treatment is associated with a 50 % reduction of bacterial vaginosis-linked preterm birth and preterm premature rupture of membranes . Women at risk for preterm birth or preterm premature rupture of membranes because of bacterial vaginosis or common genital tract infections should be screened , treated , reevaluated for cure , and re-treated if necessary BACKGROUND Pregnant women with bacterial vaginosis may be at increased risk for preterm delivery . We investigated whether treatment with metronidazole and erythromycin during the second trimester would lower the incidence of delivery before 37 weeks ' gestation . METHODS In 624 pregnant women at risk for delivering prematurely , vaginal and cervical cultures and other laboratory tests for bacterial vaginosis were performed at a mean of 22.9 weeks ' gestation . We then performed a 2:1 double-blind r and omization to treatment with metronidazole and erythromycin ( 433 women ) or placebo ( 191 women ) . After treatment , the vaginal and cervical tests were repeated and a second course of treatment was given to women who had bacterial vaginosis at that time ( a mean of 27.6 weeks ' gestation ) . RESULTS A total of 178 women ( 29 percent ) delivered infants at less than 37 weeks ' gestation . Eight women were lost to follow-up . In the remaining population , 110 of the 426 women assigned to metronidazole and erythromycin ( 26 percent ) delivered prematurely , as compared with 68 of the 190 assigned to placebo ( 36 percent , P = 0.01 ) . However , the association between the study treatment and lower rates of prematurity was observed only among the 258 women who had bacterial vaginosis ( rate of preterm delivery , 31 percent with treatment vs. 49 percent with placebo ; P = 0.006 ) . Of the 358 women who did not have bacterial vaginosis when initially examined , 22 percent of those assigned to metronidazole and erythromycin and 25 percent of those assigned to placebo delivered prematurely ( P = 0.55 ) . The lower rate of preterm delivery among the women with bacterial vaginosis who were assigned to the study treatment was observed both in women at risk because of previous preterm delivery ( preterm delivery in the treatment group , 39 percent ; and in the placebo group , 57 percent ; P = 0.02 ) and in women who weighed less than 50 kg before pregnancy ( preterm delivery in the treatment group , 14 percent ; and in the placebo group , 33 percent ; P = 0.04 ) . CONCLUSIONS Treatment with metronidazole and erythromycin reduced rates of premature delivery in women with bacterial vaginosis and an increased risk for preterm delivery Fourteen of 28 Trichomonas vaginalis isolates collected from patients in Guangzhou , China from 2003 to 2004 were found to be naturally infected with Mycoplasma hominis , as determined by PCR using specific primers . In vitro metronidazole sensitivity assay of the 28 isolates revealed four displaying low susceptibility [ minimum lethal concentration (MLC)=∼13–25 μg/ml ] and another four displaying high resistance ( MLC=50–100 μg/ml ) . The overwhelming majority of these resistant isolates ( 7/8 ) were mycoplasma-infected . The mean of MLCs of mycoplasma-infected isolates is ∼10-fold higher than the mean of noninfected isolates ( p=0.029 ) . Sequence analyses of PCR-amplified small subunit – large subunit rRNA interspacer regions ( ITS1/5.8S/ITS2 ) revealed that 23 of the 28 sample s are identical , the remaining five being separable into two groups , each with a single point mutation . These internal transcribed spacer sequence variants are associated neither with mycoplasma infection nor with drug resistance . In contrast , r and om amplified polymorphic DNA analyses of DNAs using 10 different primers showed that the drug-resistant isolates are clustered together in association with mycoplasma infection , albeit more loosely . Taken together , the results obtained from this study suggest that in vitro metronidazole resistance of T. vaginalis is related to mycoplasma infection of this protozoan BACKGROUND The ORACLE II trial compared the use of erythromycin and /or amoxicillin-clavulanate ( co-amoxiclav ) with that of placebo for women in spontaneous preterm labour and intact membranes , without overt signs of clinical infection , by use of a factorial r and omised design . The aim of the present study --the ORACLE Children Study II -- was to determine the long-term effects on children after exposure to antibiotics in this clinical situation . METHODS We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study and who were eligible for follow-up with a structured parental question naire to assess the child 's health status . Functional impairment was defined as the presence of any level of functional impairment ( severe , moderate , or mild ) derived from the mark III Multi-Attribute Health Status classification system . Educational outcomes were assessed with national curriculum test results for children resident in Engl and . FINDINGS Outcome was determined for 3196 ( 71 % ) eligible children . Overall , a greater proportion of children whose mothers had been prescribed erythromycin , with or without co-amoxiclav , had any functional impairment than did those whose mothers had received no erythromycin ( 658 [ 42.3 % ] of 1554 children vs 574 [ 38.3 % ] of 1498 ; odds ratio 1.18 , 95 % CI 1.02 - 1.37 ) . Co-amoxiclav ( with or without erythromycin ) had no effect on the proportion of children with any functional impairment , compared with receipt of no co-amoxiclav ( 624 [ 40.7 % ] of 1523 vs 608 [ 40.0 % ] of 1520 ; 1.03 , 0.89 - 1.19 ) . No effects were seen with either antibiotic on the number of deaths , other medical conditions , behavioural patterns , or educational attainment . However , more children whose mothers had received erythromycin or co-amoxiclav developed cerebral palsy than did those born to mothers who received no erythromycin or no co-amoxiclav , respectively ( erythromycin : 53 [ 3.3 % ] of 1611 vs 27 [ 1.7 % ] of 1562 , 1.93 , 1.21 - 3.09 ; co-amoxiclav : 50 [ 3.2 % ] of 1587 vs 30 [ 1.9 % ] of 1586 , 1.69 , 1.07 - 2.67 ) . The number needed to harm with erythromycin was 64 ( 95 % CI 37 - 209 ) and with co-amoxiclav 79 ( 42 - 591 ) . INTERPRETATION The prescription of erythromycin for women in spontaneous preterm labour with intact membranes was associated with an increase in functional impairment among their children at 7 years of age . The risk of cerebral palsy was increased by either antibiotic , although the overall risk of this condition was low . FUNDING UK Medical Research Council OBJECTIVE The pathogenesis of preterm birth and other adverse pregnancy outcomes linked with reproductive tract infection remains poorly understood . Mucolytic enzymes , including mucinases and sialidases ( neuraminidase ) , are recognized virulence factors among enteropathogens and bacteria that cause periodontal infection . Perturbation of maternal cervicovaginal mucosa membrane host defenses by such enzyme-producing microorganisms may increase the risk of sub clinical intrauterine infection during pregnancy and thus increase risks of preterm birth . STUDY DESIGN We prospect ively evaluated vaginal fluid mucinase and sialidase and selected cervicovaginal bacteria along with pregnancy outcomes in 271 women . Within this study , women with bacterial vaginosis ( 16 to 27 week ' gestation ) were treated with 2 % clinadmycin vaginal cream or placebo . Enzyme , microbial findings , treatment effects , and pregnancy outcomes were compared among drug- and placebo-treated women and control women without bacterial vaginosis . RESULTS Presence of bacterial vaginosis at intake was associated with increased risk of preterm birth ( relative risk 3.3 , 95 % confidence interval 1.2 to 9.1 , p = 0.02 ) , premature rupture of membranes ( relative risk 3.8 , 95 % confidence interval 1.6 to 9.0 , p = 0.002 ) , and preterm premature rupture of membranes . Mucinase and sialidase activities were more commonly identified , and they occurred in higher concentrations , if present , in women with bacterial vaginosis ( mucinase : 44.3 % with bacterial vaginosis vs 27.4 % without , p = 0.007 ; sialidase : 45 % with bacterial vaginosis vs 12 % without p < 0.001 ) . Sialidase activity was associated with bacterial vaginosis-linked organisms ( Gardnerella vaginalis , Mobiluncus spp , and Mycoplasma hominis ) and Chlamydia trachomatis and yeast species ; mucinase activity was associated only with bacterial vaginosis-linked microorganisms . Clindamycin , 2 % cream , was effective treatment for bacterial vaginosis and temporarily reduced mucinase and sialidase activities . Topical treatment of bacterial vaginosis did not reduce risks of perinatal morbidity . Women with persistent or recurrent sialidase 8 weeks after treatment were at increased risk of preterm birth ( 15.6 % vs 7.4 % ) premature rupture of membranes ( 30 % vs 15 % ) , and low birth weight ( 20 % vs 3 % , relative risk 6.8 , 95 % confidence interval 1.6 to 28.1 ) . CONCLUSIONS Persistence of sialidase-producing vaginal microorganisms in numbers sufficient to increase vaginal fluid sialidase activity may be a risk factor for possibly preventable sub clinical intrauterine infection and preterm birth . This study confirms and further informs our underst and ing of the association of bacterial vaginosis and preterm birth ; studies to evaluate whether systemic treatment for bacterial vaginosis can effectively reduce vaginal mucolytic enzymes and risks of prematurity and other morbid outcomes are continuing Objective : To assess the efficacy of 2 % clindamycin vaginal cream ( CVC ) to treat bacterial vaginosis ( BV ) in pregnancy . Methods : A prospect i ve , r and omized , double-blind , placebo-controlled , tricenter study . Four hundred and four women with BV on Gram stain at their first antenatal clinic visit were r and omized to receive a 3-day course of 2 % CVC or placebo . The outcome was assessed using an intention to treat analysis at 3 weeks and 6 weeks post-treatment according to three different diagnostic methods based on five criteria ( Gram stain and all four elements of clinical composite criteria : vaginal discharge , abnormal vaginal pH , clue cells , amine odor ) , three criteria ( vaginal pH , clue cells , amine odor ) or two criteria ( clue cells and amine odor ) to reflect stringency of diagnosis , historical precedence and government agency recommendations respectively . Results : Using five diagnostic criteria , 18 % of CVC patients were cured and 70.8 % either cured and /or improved compared to 1.6 % and 12 % of placebo patients respectively ( p < 0.0001 ) . Using three diagnostic criteria , 44.8 % of CVC patients were cured and 77.3 % were either cured and /or improved compared to 9.3 % and 28.8 % of placebo patients respectively ( p < 0.0001 ) . Using two diagnostic criteria , 75.0 % of CVC patients were cured compared to 18.0 % of placebo patients ( p < 0.0001 ) . Recurrence rates in those CVC patients successfully treated were approximately 6 % at 6 weeks post baseline and 10 % at 28 to 34 weeks gestation . Conclusions : A 3-day course of CVC appears to be well tolerated by the mother and statistically significantly more efficacious than placebo in the treatment of BV during the second trimester of pregnancy OBJECTIVES To evaluate the efficacy of clindamycin vaginal cream 2 % once daily for 7 days in prolonging pregnancy . STUDY DESIGN R and omised clinical trial of 112 women between 14 and 25 weeks of gestation with diagnosis of asymptomatic bacterial vaginosis were enrolled in a multicenter r and omised trial and assigned to active or no treatment . A total of 55 women were assigned to clindamycin and 57 to no treatment . MAIN OUTCOME MEASURE frequency of pre-term delivery . RESULTS The rates of pre-term delivery was 12.2 % in the clindamycin group and 15.7 % in the no treatment group ( P=0.78 ) . Birth weight was < 2500 g in three and seven babies , respectively , in the two groups ( P=0.32 ) . Mean gestational ages at birth were 38.9 and 39.2 ( P=0.52 ) , respectively , in the clindamycin and no treatment groups . CONCLUSIONS The results of this study suggest that treating asymptomatic bacterial vaginosis does neither markedly prolong pregnancy nor increase birthweight Objective To determine whether treatment of bacterial vaginosis ( BV ) with vaginal clindamycin affects pregnancy outcome OBJECTIVE Our purpose was to determine whether treatment of bacterial vaginosis with metronidazole in patients with preterm delivery in the penultimate pregnancy from preterm labor or premature rupture of membranes reduces the risk of subsequent preterm birth . STUDY DESIGN From January 1989 to June 1992 patients with a singleton gestation between 13 and 20 weeks and a history of preterm birth in the preceding pregnancy from either idiopathic preterm labor or premature rupture of membranes were screened for bacterial vaginosis . Those with a positive screen were r and omized to receive 250 mg of metronidazole three times a day for 7 days or placebo in a double-blind design . Data were analyzed with Student t and chi 2 tests , and differences considered significant at p < 0.05 . RESULTS Of 94 eligible patients , 80 were enrolled and completed the study , of which 44 received metronidazole . Both groups were comparable in number of entry variables . Compared with the placebo group , patients in the metronidazole group had significantly fewer hospital admissions for preterm labor , 12 ( 27 % ) versus 28 ( 78 % ) ; preterm births , eight ( 18 % ) versus 16 ( 39 % ) ; births of infants weighing < 2500 gm , six ( 14 % ) versus 12 ( 33 % ) ; and premature rupture of membranes , two ( 5 % ) versus 12 ( 33 % ) . CONCLUSION Treatment of bacterial vaginosis with metronidazole was effective in reducing preterm births in patients with a history of prematurity in the preceding pregnancy Objective To ascertain whether metronidazole treatment of women with a heavy growth of Gardnerella vaginalis during mid‐pregnancy would reduce the risk of spontaneous preterm birth OBJECTIVE We hypothesized that upper genital tract microbial infection associated with spontaneous preterm birth may precede conception . Our objective was to estimate if antibiotic administration during the interpregnancy interval in nonpregnant women with a previous preterm birth before 34 weeks ' gestational age would reduce the rate of spontaneous preterm birth in the subsequent pregnancy . STUDY DESIGN Women with a spontaneous preterm birth < 34 weeks ' gestational age were r and omized at 4 months ' postpartum to receive oral azithromycin 1 g twice ( 4 days apart ) plus sustained-release metronidazole 750 mg daily for 7 days , or identical-appearing placebos . This regimen was repeated every 4 months until the subsequent pregnancy . RESULTS A total of 241 women were r and omized ; 124 conceived a subsequent pregnancy and were available for study , including 59 in the antibiotic group and 65 in the placebo group . In the antibiotic versus placebo group , neither subsequent spontaneous preterm birth ( < 37 weeks : 52 % vs 46 % , P = .568 ; < 35 weeks : 40 % vs 30 % , P = .276 ; < 32 weeks : 31 % vs 23 % , P = .376 ) nor miscarriage ( < 15 weeks : 12 % vs 14 % , P = .742 ) was significantly different . Although not statistically significant , mean delivery gestational age in the subsequent pregnancy was 2.4 weeks earlier in the antibiotic versus placebo group ( 32.0 + /- 7.9 vs 34.4 + /- 6.3 weeks , P = .082 ) , and mean birth weight was lower in the antibiotic group ( 2046 + /- 1209 vs 2464 + /- 1067 g , P = .060 ) . CONCLUSION Intermittent treatment with metronidazole plus azithromycin of nonpregnant women with a recent early spontaneous preterm birth does not significantly reduce subsequent preterm birth , and may be associated with a lower delivery gestational age and lower birth weight OBJECTIVE To assess the efficacy of treatment of bacterial vaginosis ( BV ) using metronidazole to reduce preterm labour in primigravidae and multigravidae with previous midtrimester abortion or preterm labour . DESIGN R and omised controlled trial . SETTING Tertiary academic hospital . METHOD Two different groups of patients were screened for BV at the first antenatal visit , namely primigravidae and high-risk multigravidae who had had a previous midtrimester abortion or preterm delivery . Patients where BV was diagnosed clinical ly or on Gram 's stain of a smear taken from the posterior vaginal fornix , received either 400 mg metronidazole , or 100 mg vitamin C orally twice daily for 2 days . The Gram 's stain was repeated after 4 weeks . If BV was found again , treatment with the same drug was repeated . OUTCOME MEASURES Preterm delivery , birth weight and perinatal deaths . RESULTS One thous and and five patients entered the study , but 40 were excluded for various reasons and 10 were lost to follow-up . There were 464 primigravidae , of whom 150 ( 32 % ) had BV . Except for the 5-minute Apgar score , no significant differences were found between primigravidae negative for BV and those who received either metronidazole or vitamin C. There were 491 high-risk multigravidae , of whom 127 ( 26 % ) had BV . The mean gestational age in the BV-negative group was 37 weeks , in contrast to 37.4 weeks in the vitamin C group and 35.6 weeks in the metronidazole group . Birth weights in these three groups were 2,752 g , 2,759 g and 2,475 g respectively , significantly less ( P = 0.0109 ) in the metronidazole group in comparison with the BV-negative group . Delivery before 37 weeks occurred in 29 % of high-risk multigravidae with no BV but in 24 % of those who took vitamin C and in 43 % who took metronidazole . Differences were significant between the BV-negative and metronidazole groups ( P = 0.0231 ) and also between the metronidazole and vitamin C groups ( P = 0.0274 ) . Delivery before 28 weeks occurred in 4 % of the high-risk multigravidae with no BV but in 10 % of those with BV who took metronidazole . The difference was significant ( P = 0.0430 ) . Analysis for maximum likelihood estimates for preterm labour identified only previous preterm labour or midtrimester abortion as risk factors . CONCLUSION Metronidazole does not seem to reduce the prevalence of preterm labour when given for BV before 26 weeks ' gestation BACKGROUND Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery . We aim ed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population . METHODS We screened 6120 pregnant women attending hospital for their first antenatal visit -- who were at 12 - 22 weeks ' gestation ( mean 15.6 weeks)--for bacterial vaginosis or abnormal vaginal flora . We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis , in accordance with Nugent 's criteria . We r and omly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days . Primary endpoints were spontaneous preterm delivery ( birth > or = 24 but < 37 weeks ) and late miscarriage ( pregnancy loss > or = 13 but < 24 weeks ) . Analysis was intention to treat . FINDINGS Nine women were lost to follow-up or had elective termination . Thus , we analysed 485 women with complete outcome data . Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries ( 13/244 ) than did those in the placebo group ( 38/241 ; percentage difference 10.4 % , 95 % CI 5.0 - 15.8 , p=0.0003 ) . Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores , with maximum effect in women with the highest Nugent score of 10 . INTERPRETATION Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population The effects of several chemotherapeutic agents on the chemotaxis of human leukocytes were studied in an in vitro system using a Sykes-Moore chamber and a double-filter technique . Chemotactic factor was generated by the interaction of normal human serum and zymosan . At concentrations comparable to and below therapeutic blood levels , tetracycline HCl , erythromycin base and clindamycin HCl were all inhibitory , causing marked suppression of leukocyte chemotaxis and slight reduction of r and om migration . Penicillin G-Na , dapsone , and sulfapyridine did not alter white cell motility at the concentrations of drug tested . It is postulated that the capacity of some of these agents to inhibit leukocyte chemotaxis may account , in part , for their efficacy in inflammatory skin diseases such as acne vulgaris In a 2‐year ( 1990‐92 ) prospect i ve national investigation , comprising all stillborn and live‐born ELBW infants with a birthweight of ≤1000 g born at 23 completed weeks of gestation or more , we examined the incidence , neonatal mortality , major morbidity and infant survival in relation to level of care and place of residence . A total of 633 ELBW infants were live‐born , i.e. 0.26 % of all live‐born infants , and 298 were stillborn . The average neonatal mortality was 37 % and 91 % at 23 weeks , 70 % at 24 weeks , and 40 % at 25 weeks of gestation . Of neonatal survivors , 8 % had intraventricular haemorrhage grade 3,10 % retinopathy of prematurity of stage ≥3 , 2 % necrotizing enterocolitis , and 28 % were oxygen‐dependent at a time corresponding to 36 weeks of gestation . In all , 77 % were treated with mechanical ventilation , whereas 19 % survived without , almost all of them being CPAP treated . Infant mortality among infants born at level III ( tertiary centres ) was 30 % , at level Ha ( with full perinatal service ) 46 % and at level IIb ( with basic neonatal service ) 55 % . Only 1 % was born at hospital level I. Regarding the relation to place of residence , the mortality rates among infants residing in the areas served by levels III , IIa and lib hospitals were 36 % , 45 % and 41 % , respectively . The referral system thus functioned well , but can be improved , and increased perinatal referral , at borderline perinatal viability , might provide a better quality of care and a better chance of survival Abstract Objective : To find out whether women with bacterial vaginosis detected early in pregnancy are at increased risk of preterm delivery . Design : Prospect i ve description cohort study . Setting : Antenatal clinic in a district general hospital . Subjects : 783 women examined during their first antenatal clinic visit and screened for recognised risk factors for preterm delivery and the presence of bacterial vaginosis or intermediate abnormal flora detected by examination of a vaginal smear stained by Gram 's method . Main outcome measures : Gestational age at delivery classified as late miscarriage ( 16 - 24 weeks ' gestation ) , preterm delivery ( 24 - 37 weeks ' gestation ) , term delivery ( > = 37 weeks ' gestation ) . Results : Multiple logistic analysis showed that there was an increased incidence of preterm delivery in women with a previous preterm delivery ( 9/24 ; odds ratio 25 ; 95 % confidence interval 9 to 70 ; P<0.001 ) and bacterial vaginosis ( 9/115 ; 2.8 ; 1.1 to 7.4 ; P=0.04 ) . A further logistic analysis of data from women recruited before 16 weeks ' gestation showed that preterm deliveries or late miscarriages occurred more often in women with bacterial vaginosis ( 12/77 ; 5.5 ; 2.3 to 13.3 ; P<0.001 ) . Conclusions : Late miscarriage and preterm delivery are associated with the presence of bacterial vaginosis in early pregnancy . This is independent of recognised risk factors such as previous preterm delivery BACKGROUND Preterm birth after spontaneous preterm labour is associated with death , neonatal disease , and long-term disability . Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results . We did a r and omised multicentre trial to resolve this issue . METHODS 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were r and omly assigned 250 mg erythromycin ( n=1611 ) , 325 mg co-amoxiclav ( 250 mg amoxicillin and 125 mg clavulanic acid ; n=1550 ) , both ( n=1565 ) , or placebo ( n=1569 ) four times daily for 10 days or until delivery , whichever occurred earlier . The primary outcome measure was a composite of neonatal death , chronic lung disease , or major cerebral abnormality on ultrasonography before discharge from hospital . Analysis was by intention to treat . FINDINGS None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo ( erythromycin 90 [ 5.6 % ] , co-amoxiclav 76 [ 5.0 % ] , both antibiotics 91 [ 5.9 % ] , vs placebo 78 [ 5.0 % ] ) . However , antibiotic prescription was associated with a lower occurrence of maternal infection . INTERPRETATION This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection OBJECTIVE Our goal was to evaluate whether treatment of bacterial vaginosis during pregnancy with 2 % clindamycin vaginal cream reduces the incidence of either preterm delivery or low birth weight or of both . STUDY DESIGN A multicenter , double-blind , r and omized , placebo-controlled trial in Indonesia compared a 2 % clindamycin vaginal cream with a placebo cream . Women seeking prenatal care at 14 to 26 weeks of gestational age who had bacterial vaginosis ( Gram stain score > 6 and pH of vaginal fluid > 4.5 ) were invited to participate . Of the 745 women enrolled , 681 ( 91.4 % ) women were followed up through delivery . RESULTS Clindamycin vaginal cream was an effective treatment for bacterial vaginosis . Two weeks after completion of the treatment , 85.5 % of the women were cured . The rate of preterm delivery ( < 37 weeks ) was 15.0 % for clindamycin patients and 13.5 % for placebo patients ( odds ratio 1.1 , 95 % confidence interval 0.7 to 1.7 ) . The rate of low birth weight was 9.0 % for clindamycin patients and 6.8 % for placebo patients ( odds ratio 1.3 , 95 % confidence interval 0.8 to 2.4 ) . CONCLUSIONS Treatment of bacterial vaginosis with clindamycin vaginal cream did not reduce preterm delivery or low birth weight . Although clindamycin vaginal cream is an effective treatment for bacterial vaginosis , intravaginal treatment would not be effective against bacterial vaginosis-associated microorganisms harbored in the upper genital tract . Systemic treatment may be required to eradicate upper tract infection to reduce preterm delivery Objective To test the hypothesis that prophylactic administration of clindamycin 2 % vaginal cream can reduce the incidence of preterm birth in a high risk population The aim of this study was to analyse how the results of Gram-staining vaginal smears correlated with the clinical criteria for determining the existence of bacterial vaginosis ( BV ) and , in particular , how the category defined as ' intermediate ' or Gram grade II did so and its significance . Women attending an antenatal clinic with an abnormal vaginal flora , that is those who had Gram-stains of grade s II or III , the latter considered to equate with BV , were given clindamycin or a placebo intravaginally and examined again on up to three occasions . Gram-stain readings of grade III correlated with the clinical criteria for BV on 356 ( 91.7 % ) of 388 occasions . Grade II readings covered the spectrum of clinical criteria and correlated with those for BV on 35 ( 37.2 % ) of 94 occasions . Grade I , recorded 231 times and seen usually after clindamycin treatment , was associated with BV only once . The sensitivity , specificity , positive predictive value and negative predictive value of the Gram stain for the diagnosis of BV , based on a combination of grade s II and III , were 99.7 % , 71.6 % , 81 % and 99.6 % , respectively ; based on grade III only , the values were 99.7 % , 87.7 % , 91.6 % and 99.6 % , respectively . Women reported a malodorous vaginal discharge on 49.2 % of the occasions a grade III flora was seen and 13.3 % of the times grade II was recorded . It was not associated with grade I and would seem a useful adjunct to the accepted clinical criteria for diagnosing BV . Each of the clinical criteria was found in about equal proportions ( 87%-91 % ) for women whose Gram grade was III . For grade II , an increased discharge was noted most often ( 76.5 % ) and ' clue ' cells least often ( 24.5 % ) . A positive amine test was the most specific , being associated with < 1 % of grade I smears . Of women with grade III status , 91 % reverted to grade I after treatment with clindamycin for three days . In contrast , of women with grade II status , 53 % reverted to grade I , as did 47 % of those who were given a placebo . The ' intermediate ' ( grade II ) category is a Gram-stain diagnosis and not one that can be made clinical ly . It is important to recognize as a distinct entity not only because amalgamation with grade III diminishes the specificity and positive predictive value of the Gram-stain for diagnosing BV , but also because women of grade II status usually fail to respond to clindamycin treatment , whereas those of grade III do not OBJECTIVE To screen for bacterial vaginosis ( BV ) and to investigate the effect of treatment with vaginal clindamycin in order to observe the effect on late miscarriage and delivery prior to 37 completed weeks ( primary outcome ) . DESIGN R and omised consent design for clinical trials according to Zelen . SETTING Southeast region of Sweden . POPULATION A total of 9025 women were screened in early pregnancy . METHODS A total of 819 women with a Nugent score of 6 and above were considered to have BV and treated according to Zelen allocation . The incidence of late miscarriage and spontaneous ( noniatrogenic ) preterm birth was assessed . MAIN OUTCOME MEASURES Late miscarriage and spontaneous preterm delivery before 37 weeks . RESULTS Therapy with vaginal clindamycin had no significant impact on the incidence of spontaneous preterm delivery prior to 37 completed weeks ; OR 0.90 , 95 % CI 0.40 - 2.02 ( primary outcome variable ) . However , only 1 of 11 women in the treatment group versus 5 of 12 in the control group delivered prior to 33 completed weeks ; OR 0.14 , 95 % CI 0.02 - 0.95 . Treatment was associated with 32 days longer gestation for the 23 participants who had late miscarriage or spontaneous preterm birth ( P= 0.024 , Mann-Whitney U test ) and significantly fewer infants had a birthweight below 2,500 g ( secondary outcome ) . A follow up of infants born preterm 4 years postnatally indicated that extending gestational age did not increase the number of sequelae . CONCLUSIONS Clindamycin vaginal cream therapy was associated with significantly prolonged gestation and reduced cost of neonatal care in women with BV . Early screening for BV and treatment with clindamycin saved approximately 27 euro per woman Objective To determine whether treatment of bacterial vaginosis ( BV ) in early pregnancy decreases the risk of preterm delivery and peripartum infectious morbidity . Methods In this multicenter , r and omized , double-masked , placebo-controlled intervention trial , screening for BV was performed by vaginal Gram stain obtained from 5432 healthy women with singleton pregnancies during the first antenatal clinic visit at 10–17 weeks ' gestation . Bacterial vaginosis-positive women with no past history of preterm delivery were r and omized to a single course of treatment with either 2 % vaginal clindamycin cream or identical placebo cream for 7 days . Repeat Gram stains were taken 1 week after treatment and at 30–36 weeks ' gestation . Preterm delivery was defined as spontaneous delivery before 37 gestational weeks . Peripartum infectious morbidity was defined as postpartum endometritis , postpartum sepsis , postcesarean wound infection , or episiotomy wound infection , necessitating antimicrobial therapy . According to the power analysis , 180 patients were needed for both treatment arms to show a three-fold difference in the rates of preterm births . Results The overall prevalence of BV was 10.4 % . Of all BV-positive women , 375 ( 66 % ) were r and omized to the treatment arms . The primary cure rate was 66 % in the clindamycin group ; in the placebo group , 34 % spontaneously cleared BV ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 , 2.8 ) . The rate of preterm deliveries was 5 % in the clindamycin group and 4 % in the placebo group ( OR 1.3 , 95 % CI 0.5 , 3.5 ) . The rate of peripartum infectious morbidity was 11 % in the clindamycin group and 18 % in the placebo group ( OR 1.6 , 95 % CI 0.9 , 2.8 ) . Bacterial vaginosis recurred in 7 % of women . The rate of preterm deliveries was 15 % in this subgroup compared with 2 % among women who remained BV negative ( OR 9.3 , 95 % CI 1.6 , 53.5 ) . Conclusion Vaginal clindamycin did not decrease the rate of preterm deliveries or peripartum infections , but recurrent or persistent BV increased the risk for these complications BACKGROUND Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery . It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery . METHODS We screened pregnant women for trichomoniasis by culture of vaginal secretions . We r and omly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole ( 320 women ) or placebo ( 297 women ) 48 hours apart . We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation . The primary outcome was delivery before 37 weeks of gestation . RESULTS Between r and omization and follow-up , trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group ( 92.6 percent ) and 92 of 260 women with follow-up cultures in the placebo group ( 35.4 percent ) . Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group . Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group ( 19.0 percent ) and 31 women in the placebo group ( 10.7 percent ) ( relative risk , 1.8 ; 95 percent confidence interval , 1.2 to 2.7 ; P=0.004 ) . The difference was attributable primarily to an increase in preterm delivery result ing from spontaneous preterm labor ( 10.2 percent vs. 3.5 percent ; relative risk , 3.0 ; 95 percent confidence interval , 1.5 to 5.9 ) . CONCLUSIONS Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery . Routine screening and treatment of asymptomatic pregnant women for this condition can not be recommended The purpose of this investigation was to evaluate the efficacy of amoxicillin for treatment of bacterial vaginosis during pregnancy . The diagnosis of bacterial vaginosis was established by clinical examination and microscopic examination of a Gram stain and saline preparation of vaginal secretions . In a double-blind , r and omized manner , 108 patients at 15 - 25 weeks ' gestation were assigned to treatment with oral amoxicillin , 500 mg three times daily for 14 days , or placebo . Patients were evaluated 2 weeks after treatment , at 34 - 36 weeks ' gestation , and at delivery . There were no significant differences between the two groups with respect to any clinical or microbiologic measure of treatment outcome . There were also no significant differences in the frequency of obstetric complications . We conclude that amoxicillin is not effective therapy for bacterial vaginosis in pregnant Preterm delivery , which is associated with infections during pregnancy , is common in sub-Saharan Africa . We enrolled 1,320 pregnant women into a r and omized , controlled trial in Malawi to study whether preterm delivery and low birth weight ( LBW ) incidence can be reduced by intermittent preventive treatment of maternal malaria and reproductive tract infections . The participants received either sulfadoxine-pyrimethamine ( SP ) twice ( controls ) , monthly SP , or monthly SP and two doses of azithromycin ( AZI-SP ) . The incidence of preterm delivery was 17.9 % in controls , 15.4 % in the monthly SP group ( P = 0.32 ) , and 11.8 % in AZI-SP group ( risk ratio = 0.66 , P = 0.01 ) . Compared with controls , those in AZI-SP group had a risk ratio of 0.61 ( P = 0.02 ) for LBW . Incidence of serious adverse events was low in all groups . In conclusion , the incidence of preterm delivery and LBW can in some conditions be reduced by treating pregnant women with monthly SP and two azithromycin doses OBJECTIVE Our purpose was to determine whether endotoxin-induced preterm parturition is preceded by a change in the maternal serum and amniotic fluid concentrations of tumor necrosis factor-alpha , interleukin-6 , and interleukin-1 alpha . STUDY DESIGN C3H/HeN pregnant mice at 15 days of gestation ( 70 % gestation ) were r and omized to receive an intraperitoneal injection of phosphate-buffered saline solution or lipopolysaccharide ( 50 micrograms/mouse ) . Blood ( n = 93 ) and amniotic fluid ( n = 58 ) were collected at 1 , 4 , and 10 hours after lipopolysaccharide injection . Tumor necrosis factor-alpha , interleukin-6 , and interleukin-1 alpha were determined with sensitive and specific enzyme-linked immunoassays . RESULTS The injection-to-delivery interval was shorter in mice injected intraperitoneally with 50 micrograms lipopolysaccharide than in phosphate-buffered saline solution-treated mice ( median 15.5 hours , range : 10 to 105 hours vs median 88.5 hours , range : 53 to 105 hours ; p < 0.001 ) . In comparison with phosphate-buffered saline solution-treated mice , a distinct serum cytokine pattern was observed in lipopolysaccharide-treated mice . Concentrations of tumor necrosis factor-alpha were detectable 1 and 4 hours after lipopolysaccharide injection ( median 874 pg/ml , range : < 100 to 8000 pg/ml , p < 0.001 ; and median 263 pg/ml , range : < 100 to 927 pg/ml , p < 0.001 , respectively ) . Concentrations of interleukin-6 were elevated at 1 , 4 , and 10 hours ( median 11.8 ng/ml , range : 6 to 500 ng/ml , p < 0.001 ; median 27.1 ng/ml , range : 4.5 to 192 ng/ml , p < 0.001 ; median 1.95 ng/ml , range : < 0.05 to 35 ng/ml , p < 0.015 , respectively ) . Concentrations of interleukin-1 alpha were significantly increased 4 hours after lipopolysaccharide injection ( median 102 pg/ml , range : < 15 to 306 pg/ml , p < 0.001 ) . A cytokine pattern distinct from serum was observed in amniotic fluid of lipopolysaccharide-treated mice . In comparison with controls , concentrations of interleukin-6 were significantly elevated 4 and 10 hours after treatment with lipopolysaccharide ( median 0.88 ng/ml , range : 0.40 to 2.7 ng/ml , p < 0.025 ; and median 4 ng/ml , range : 1.9 to 33.6 ng/ml , p < 0.001 , respectively ) . Interleukin-1 alpha was elevated 10 hours after lipopolysaccharide treatment ( median 185.3 pg/ml , range : 38 to 511 pg/ml , p < 0.015 ) . Tumor necrosis factor-alpha was not significantly increased in amniotic fluid . CONCLUSION Preterm delivery after lipopolysaccharide administration is preceded by the appearance of dramatic increases in maternal serum concentrations of tumor necrosis factor-alpha , interleukin-6 , and interleukin-1 alpha and in amniotic fluid concentrations of interleukin-6 and interleukin-1 alpha We prospect ively studied the relationship of pregnancy outcome to bacterial vaginosis , an anaerobic vaginal condition , and to other selected genital pathogens among 534 gravid women . Bacterial vaginosis was presumptively diagnosed by gas-liquid chromatographic identification of microbial organic acid metabolites in 102 women ( 19 % ) , and cervical infection with Chlamydia trachomatis was found in 47 ( 9 % ) of the women . Although women with and without bacterial vaginosis had similar demographic and obstetric factors , neonates born to women with bacterial vaginosis had lower mean birth weight than did neonates born to women without bacterial vaginosis ( 2960 + /- 847 g vs 3184 + /- 758 g ) . Bacterial vaginosis was significantly associated with preterm premature rupture of the membranes ( odds ratio [ OR ] , 2.0 ; 95 % confidence interval [ Cl ] , 1.1 to 3.7 ) , preterm labor ( OR , 2.0 ; Cl , 1.1 to 3.5 ) , and amniotic fluid infection ( OR , 2.7 ; Cl , 1.1 to 6.1 ) , but not with birth weight below 2500 g ( OR , 1.5 ; Cl , 0.8 to 2.0 ) . Cervical infection with C trachomatis was independently associated with preterm premature rupture of the membranes , preterm labor , and low birth weight ( OR , 1.5 ; Cl , 0.8 to 2.0 ) Objective . To evaluate the outcome for all infants born before 26 weeks of gestation in the United Kingdom and the Republic of Irel and . This report is of survival and complications up until discharge from hospital . Methodology . A prospect i ve observational study of all births between March 1 , 1995 and December 31 , 1995 from 20 to 25 weeks of gestation . Results . A total of 4004 births were recorded , and 811 infants were admitted for intensive care . Overall survival was 39 % ( n = 314 ) . Male sex , no reported chorioamnionitis , no antenatal steroids , persistent bradycardia at 5 minutes , hypothermia , and high Clinical Risk Index for Babies ( CRIB ) score were all independently associated with death . Of the survivors , 17 % had parenchymal cysts and /or hydrocephalus , 14 % received treatment for retinopathy of prematurity ( ROP ) , and 51 % needed supplementary oxygen at the expected date of delivery . Failure to administer antenatal steroids and postnatal transfer for intensive care within 24 hours of birth were predictive of major scan abnormality ; lower gestation was predictive of severe ROP , while being born to a black mother was protective . Being of lower gestation , male sex , tocolysis , low maternal age , neonatal hypothermia , a high CRIB score , and surfactant therapy were all predictive of oxygen dependency . Intensive care was provided in 137 units , only 8 of which had > 5 survivors . There was no difference in survival between institutions when divided into quintiles based on their numbers of extremely preterm births or admissions . Conclusions . This study provides outcome data for this geographically defined cohort ; survival and neonatal morbidity are consistent with previous data from the United Kingdom and facilitate comparison with other geographically based data OBJECTIVES To investigate the hypothesis that mother 's use of antibiotics in pregnancy could influence asthma and eczema in early life . STUDY DESIGN Subjects were included from the Copenhagen Prospect i ve Study on Asthma in Childhood cohort of children born of mothers with asthma ( N = 411 ) . Severe asthma exacerbations and eczema were diagnosed by research unit physicians . Replication was sought in children from the Danish National Birth Cohort ( N = 30 675 ) . Asthma outcomes were hospitalization and use of inhaled corticosteroids . Eczema was defined by an algorithm developed from cases of clinical ly verified eczema . All children were followed to age 5 years in a cohort study design . RESULTS The Copenhagen Prospect i ve Study on Asthma in Childhood data showed increased risk of asthma exacerbation ( hazard ratio 1.98 [ 95 % CI 1.08 - 3.63 ] ) if mothers had used antibiotics during third trimester . The Danish National Birth Cohort confirmed increased risk of asthma hospitalization ( hazard ratio 1.17 [ 1.00 - 1.36 ] ) , and inhaled corticosteroids ( 1.18 [ 1.10 - 1.27 ] ) in the children if mothers used antibiotics any time during pregnancy . In the subgroup of mothers using antibiotics for nonrespiratory infection , the children also had increased risk of asthma . CONCLUSION We found increased risk of asthma associated with maternal antibiotic use in a clinical study of a birth cohort with increased risk of asthma and replicated this finding in an unselected national birth cohort , and in a subgroup using antibiotics for nonrespiratory infections . This supports a role for bacterial ecology in pre- or perinatal life for the development of asthma BACKGROUND Bacterial vaginosis has been associated with preterm birth . In clinical trials , the treatment of bacterial vaginosis in pregnant women who previously had a preterm delivery reduced the risk of recurrence . METHODS To determine whether treating women in a general obstetrical population who have asymptomatic bacterial vaginosis ( as diagnosed on the basis of vaginal Gram 's staining and pH ) prevents preterm delivery , we r and omly assigned 1953 women who were 16 to less than 24 weeks pregnant to receive two 2-g doses of metronidazole or placebo . The diagnostic studies were repeated and a second treatment was administered to all the women at 24 to less than 30 weeks ' gestation . The primary outcome was the rate of delivery before 37 weeks ' gestation . RESULTS Bacterial vaginosis resolved in 657 of 845 women who had follow-up Gram 's staining in the metronidazole group ( 77.8 percent ) and 321 of 859 women in the placebo group ( 37.4 percent ) . Data on the time and characteristics of delivery were available for 953 women in the metronidazole group and 966 in the placebo group . Preterm delivery occurred in 116 women in the metronidazole group ( 12.2 percent ) and 121 women in the placebo group ( 12.5 percent ) ( relative risk , 1.0 ; 95 percent confidence interval , 0.8 to 1.2 ) . Treatment did not prevent preterm deliveries that result ed from spontaneous labor ( 5.1 percent in the metronidazole group vs. 5.7 percent in the placebo group ) or spontaneous rupture of the membranes ( 4.2 percent vs. 3.7 percent ) , nor did it prevent delivery before 32 weeks ( 2.3 percent vs. 2.7 percent ) . Treatment with metronidazole did not reduce the occurrence of preterm labor , intraamniotic or postpartum infections , neonatal sepsis , or admission of the infant to the neonatal intensive care unit . CONCLUSIONS The treatment of asymptomatic bacterial vaginosis in pregnant women does not reduce the occurrence of preterm delivery or other adverse perinatal outcomes |
11,890 | 15,769,296 | Conclusion There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI . | Abstract Background Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications .
Methods We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection ( UTI ) in children under five years of age . | OBJECTIVE Experimental evidence suggests that neutrophils and their metabolites play an important role in the pathogenesis of pyelonephritis . The aim of this study was to investigate the diagnostic value of polymorphonuclear elastase-a(1)-antitrypsin complex ( E-a(1)-Pi ) for the detection of acute pyelonephritis in children . METHODS Eighty-three patients , 29 boys and 54 girls , 25 days to 14 years of age , with first-time symptomatic urinary tract infection were prospect ively studied . Fifty-seven healthy children served as controls . Dimercaptosuccinic acid ( DMSA ) scan and voiding cystourethrography were performed in all patients . Plasma and urinary E-a(1)-Pi , C-reactive protein ( CRP ) , erythrocyte sedimentation rate ( ESR ) , neutrophil count , urinary N-acetyl-beta-glucosaminidase ( NAG ) , N-acetyl-beta-glucosaminidase b ( NAG b ) , and creatinine levels were measured in all patients on admission and 3 days after the introduction of antibiotics . The same markers were also measured in the control subjects . RESULTS Planar DMSA scintigraphy demonstrated changes of acute pyelonephritis in 30 of 83 children ( group A ) . It was normal in the remaining 53 children ( group B ) . The sex and age distributions were not significantly different between the 2 groups , as well as between the patients and the control subjects ( group C ) . Nineteen of the 53 children with a normal DMSA had body temperature > /=38 degrees C , whereas all but 4 children with abnormal DMSA had temperature > /=38 degrees C. Therefore , the temperature was significantly different between these 2 groups . The sensitivity and specificity of fever ( > /=38 degrees C ) as an indicator of renal involvement based on isotopic findings were 86 % and 64 % , respectively . Given the significant number of the febrile children with normal DMSA scintiscans , group B was subdivided into B(1 ) with 19 febrile children ( 14 boys and 5 girls ) and B(2 ) with 34 children whose body temperature was below 38 degrees C ( 8 boys and 26 girls ) . The sex and age distribution was significantly different between groups B(1 ) and B(2 ) . The mean age of group B(1 ) was.78 years ( range : 28 days to 9 years ; median:.25 years ; st and ard deviation : 2.1 ) . All but 1 child in this group were younger than 1 year of age . In contrast , in group B(2 ) , there were only 4 infants , the remaining 30 children were older than 2.5 years ( mean age : 6 years ; median : 7 years ; st and ard deviation : 3.5 ; range : 34 days to 12 years ) . The mean duration of fever before hospital admission was 2.8 days for group A and 1.8 days for group B(1 ) . This difference was not statistically significant . Similarly , body temperature was not significantly different between these 2 groups . The distribution of plasma E-a(1)-Pi values was normal in the control subjects . The sensitivity and specificity of plasma E-a(1)-Pi , as an indicator of renal involvement , were 96 % and 50 % , respectively , taking the 95th percentile of the reference range as a cutoff value . However , considering as a cutoff value the level of 72 microg/dL ( 95th percentile of group B(2 ) ) , its sensitivity and specificity were 74 % and 86 % , respectively . Plasma E-a(1)-Pi levels were significantly elevated in group A compared with group B and in both groups , the plasma E-a(1)-Pi values were significantly higher than in the control subjects . A significant difference also was noticed between group A and each of the subgroups B(1 ) and B(2 ) and also between the subgroups themselves . Plasma E-a(1)-Pi concentrations correlated significantly with neutrophil count in groups A ( r = .3 ) , B ( r = .4 ) , and B(2 ) ( r = .46 ) , but the correlation was not significant in group B(1 . ) ESR levels showed , among the different groups , similar differences with those of E-a(1)-Pi values . Unlike E-a(1)-Pi , CRP levels were comparable between groups A and B(1 ) , which both consisted of febrile children . Neutrophil count was not significantly different between subgroups B(1 ) and B(2 ) . ( ABSTRACT TRUNCATED Background . During the course of our routine renal ultrasound examinations , we noticed that some children who developed dilatation of a renal pelvis following voiding had reflux found on voiding cystourethrography ( VCUG ) . Purpose . To determine if increase in renal pelvic size on post-void ultrasound is an accurate predictor of vesicoureteral reflux . Material s and methods . Fifty-seven children ( 113 kidneys ) underwent renal ultrasound and VCUG on the same day . Anteroposterior dimensions of the renal pelves were prospect ively measured on ultrasound prior to and following patient voiding and correlated with the results of the VCUG . Results . The diameter of the renal pelvis increased in 12 and decreased in 38 kidneys on post-void ultrasound . Vesicoureteral reflux occurred in 19 kidneys and among these kidneys , renal pelvic diameter increased in 2 , decreased in 7 , and was unchanged in 10 following voiding . There was no significant correlation between post-void change in renal pelvic diameter and the presence of vesicoureteral reflux . Conclusion . Increase in renal pelvic size on post-void ultrasound is not a reliable indicator of vesicoureteral reflux UNLABELLED The results of serial dimercaptosuccinic acid ( DMSA ) imaging over 5 years are reported in 287 children with severe vesico-ureteral reflux entered into the European Branch of the International Reflux Study in Children . The children were r and omly allocated to medical ( n=147 ) or surgical ( n=140 ) management and DMSA studies were performed during the follow up period at least 6 months after any urinary tract infection . Abnormal images were classified into four types : ( 1 ) large polar hypodensity with normal renal outline ; ( 2 ) peripheral photon deficient defect(s ) in a non-deformed kidney ; ( 3 ) small renal image with normal contour ; and ( 4 ) peripheral defect(s ) with result ant irregularity of the renal outline . The DMSA findings were abnormal at entry in 235 ( 82 % ) with no difference in incidence or severity between the two treatment groups . During follow up , deterioration was observed in 25 medically and 23 surgically treated patients and comprised image deterioration alone in 17 , image deterioration with corresponding reduction in differential function in 16 and reduction in relative function without image change in 15 , with similar distribution between the two treatment groups . Deterioration was more frequent in children entering the study under the age of 2 years and in those with grade IV rather than grade III reflux . These findings , showing no difference in outcome between children managed surgically or medically , are consistent with the radiological results already published . CONCLUSION In the International Reflux Study the DMSA scintigraphic data showed no difference in outcome between children managed surgically or medically A prospect i ve blind study comparing the findings of ultrasonography , intravenous pyelography , and voiding cystourethrography was conducted on 81 patients to examine the place of ultrasonography in the initial radiologic evaluation of children with urinary tract infection . The patients ' mean age was 4.8 years ; 15 were male . Forty-eight were in patients ( mean age , 3.2 years ) and 33 were out patients ( mean age 7.2 years ) . In 29 patients ( 35.8 % ) abnormality of the urinary system was detected by one or more of the three imaging procedures ; 21 were in patients and eight were out patients . The most frequent finding was vesicoureteral reflux , occurring in 62.1 % of the pathologic cases . The findings at ultrasonography correlated well with those of intravenous pyelography in 73 of the 81 studies ( 90.1 % ) , but they failed to demonstrate double collecting systems and several of the minor changes . However , ultrasonography in combination with cystourethrography identified all patients who had abnormal urinary systems , except for two children with negligible findings . Moreover , ultrasonography and cystourethrography together identified all 11 patients , nine of them in patients , in whom surgical treatment was indicated . It is concluded that ultrasonography can successfully replace intravenous pyelography as a screening imaging procedure for the urinary system , but because of the superiority of intravenous pyelography in the detection of some types of lesions , intravenous pyelography will be required whenever ultrasonography or cystourethrography results are abnormal . ( ABSTRACT TRUNCATED AT 250 WORDS UNLABELLED Capabilities of color and power Doppler sonography ( DS ) were prospect ively evaluated for diagnosis of acute pyelonephritis and for prediction of scarring by comparison with 99mTc-dimercaptosuccinic acid scintigraphy ( DMSA ) . METHODS Fifty-seven children ( mean age , 5 + /- 3 y ) with acute pyelonephritis were investigated by biologic testing , DS ( DS 1 ) , and DMSA ( DMSA 1 ) . Patients who were < 6 mo old or had high- grade reflux or obstruction were excluded . Forty-five children had a clinical follow-up examination , biologic testing , DS ( DS 2 ) , and DMSA ( DMSA 2 ) at a mean of 7 + /- 2 mo after acute infection . Sonography ( gray-scale and DS ) was performed by 1 experienced radiologist who was unaware of patient data . DMSA studies were interpreted by 2 physicians who were unaware of patient data . RESULTS Temperature , neutrophil count , and C-reactive protein value were significantly higher in patients with abnormal DMSA 1 findings than in those with abnormal DS 1 findings ( P < 0.05 ) . When compared with DMSA 1 , DS 1 had a sensitivity and specificity of 80 % and 81 % , respectively . At follow-up , all clinical and biologic data had normalized . Scarring after infection occurred in 51 % of children . When compared with DMSA 2 , DS 1 had positive and negative predictive values of 57 % and 75 % , respectively , and DMSA 1 had respective values of 62 % and 100 % . Reflux was not considered a good predictor of scarring . CONCLUSION DS and DMSA results were concordant in 81 % of kidneys with acute pyelonephritis . The predictive value of DS for renal scarring was not considered sufficiently high for DS to be used in routine practice A system for defining renal scarring on ultrasound is proposed and compared with DMSA scintigraphy . Renal scarring was assessed with ultrasound in children following urinary tract infection ( UTI ) using the following criteria : ( 1 ) proximity of sinus echoes to cortical surface ; ( 2 ) loss of pyramids ; ( 3 ) irregularity of outline ; ( 4 ) loss of definition of capsular echo ; and ( 5 ) calyceal dilatation . Three hundred and thirty-nine consecutive ultrasound scans ( US ) and DMSA scintigrams , comprising 648 kidneys , were performed and reported blindly and the results were compared . Using DMSA scintigraphy as the gold st and ard , ultrasound had a positive predictive value of 93 % and a negative predictive value of 95 % . Ultrasound disagreed with DMSA scintigraphy in 5.2 % of kidneys . On review of the cases of disagreement where arbitration was possible by comparison with other imaging , ultrasound was incorrect in 10 kidneys and DMSA was incorrect in 13 . We conclude that the sensitivity in the ultrasound detection of renal scarring can be greatly improved using this method . If no scars were detected at ultrasound an alternative explanation for an abnormal DMSA scintigram should be sought This prospect i ve study was design ed to investigate the most relevant radiological approach for the evaluation of urinary tract infections ( UTI ) in childhood . In the first 48 hours following the diagnosis of UTI , all patients underwent99mTc dimercaptosuccinic acid ( DMSA ) scanning , ultrasonography ( US ) and intravenous urography ( IVU ) . For the imaging of renal parenchymal infection the sensitivity of IVU and US as compared to DMSA scanning were found to be 9.09 % and 25 % , respectively . It was concluded that99mTc DMSA , where available , should be the first step for the accurate diagnosis and follow-up of patients with UTI Abstract . This prospect i ve study , performed in 101 children with a first symptomatic urinary tract infection ( UTI ) , evaluates the diagnostic value of clinical , biological , and ultrasound parameters in detecting children with acute renal infection documented by dimercaptosuccinic acid ( DMSA ) scintigraphy . In children with a positive DMSA scan , mean C-reactive protein ( CRP ) was higher than in children with a normal DMSA scan ( 114±64 vs. 67±38 mg/dl , mean±SD , P=0.0002 ) . The sensitivity and specificity of CRP was 64 % and 68 % , respectively . In children with severe kidney involvement , mean CRP and white blood count ( WBC ) were higher than in children with mild/moderate disease ( 151±83 vs. 92±55 mg/dl for CRP , P=0.0149 ; 20,100±6,854 vs. 15,023±6,145 WBC/ mm3 for WBC , P=0.0131 ) . The sensitivity and specificity was 85 % and 20 % for CRP , and 77 % and 18 % for WBC , respectively . One or more areas of abnormal cortical echogenicity were documented in 3 % of kidneys with positive DMSA scans . Dilatation of the collecting system was observed in 24 % of kidneys . The sensitivity and specificity of ultrasonography was 27 % and 89 % , respectively . In conclusion , clinical , biological , and ultrasound parameters do not accurately distinguish cystitis from pyelonephritis in children with UTI and do not identify children with severe renal damage . Accordingly , we recommend that DMSA scan should be added to the initial work-up of children with UTI Purpose This study assessed the role of renal power Doppler ultrasonography ( PDU ) to identify acute pyelonephritis ( APN ) and to determine whether PDU can replace Tc-99 m DMSA renal scintigraphy in the diagnosis of APN in children . Methods A prospect i ve study was conducted in 40 infants and young children ( 78 kidneys were evaluated ) with a mean age of 25.9 months ( range , 1 to 68 months ) who were hospitalized with a first episode of high fever and bacteruria , possibly APN . All children were examined by PDU and Tc-99 m DMSA within the first 3 days after admission . Patients with congenital abnormalities , hydronephrosis , and urinary reflux were excluded . Results Twenty-seven of the 78 kidneys appeared abnormal on Tc-99 m DMSA , and 20 of them were abnormal on PDU . Fifty-one of 78 kidneys were normal on Tc-99 m DMSA , and 3 of 51 appeared diseased on PDU . The accuracy of PDU was 87 % , sensitivity was 74 % , and specificity was 94 % . The positive predictive and negative predictive values were both 87 % . When considering the numbers of lesions in 27 kidneys with positive Tc-99 m DMSA studies ( 38 lesions ) , PDU did not disclose 16 lesions ( false-negative results ) . Thus , the sensitivity of PDU for diagnosing lesions of APN decreased to 58 % . Conclusions A positive PDU finding should obviate the use of Tc-99 m DMSA in patients thought to have possible APN . However , because of a large number of false-negative results ( 26 % ) and underestimation of the number of pyelonephritic lesions ( low sensitivity of 58 % ) , PDU can not replace Tc-99 m DMSA in the diagnosis of APN in children We design ed a prospect i ve study to evaluate the ability of dimercaptosuccinic acid cortical scintigraphy and ultrasonography to detect renal parenchymal lesions in children with pyelonephritis . One hundred eleven patients 1 week to 16 years of age ( median 5.5 months ) with a urine culture positive for pathogens were included in the study ; cortical scintigraphy and ultrasonography were repeated in 25 children after a mean follow-up of 10.5 months . Cortical scintigraphy showed renal changes in 74 children ( 67 % ) , and ultrasonography showed renal changes in 39 ( 35 % ) ( p < 0.001 ) ; results of the two examinations were discordant in 49 patients ( kappa = 0.19 ) . Children more than 1 year of age had a higher incidence of renal lesions than did younger children ( 85 % vs 66 % ; p = 0.04 ) . The presence of inflammatory signs ( erythrocyte sedimentation rate or C-reactive protein ) had an 89 % sensitivity and a 25 % specificity in identifying renal lesions . Among children with renal changes , vesicoureteric reflux was present in 39 % . At follow-up examination , 16 children ( 64 % ) had scars . Thus we found a high incidence of renal involvement in children with pyelonephritis . We found that cortical scintigraphy is more sensitive than ultrasonography in detecting renal changes , and we believe that it should be added to the initial examination of children with suspected pyelonephritis PURPOSE Attempt to find out an effective and reliable alternative method for the diagnosis of vesicoureteral reflux ( VUR ) , without irradiation , in children , and the comparison of its results with those of voiding cystourethrography ( VCUG ) . METHODS In a prospect i ve comparative study we examined 88 children ( 176 units ) ( average age = 2.8 years ) sonographically and with VCUG , in order to detect VUR . First we examined sonographically the kidney 's morphology on an empty bladder . Then we examined them sonographically after filling the urinary bladder with fluid ( fluid-cystorenography , fluid-CRG ) , and after filling it with air ( air cystorenography , air CRG ) . Within the following 2 - 5 days the st and ard VCUG was performed . We compared the results of these three methods . RESULTS Fluid CRG showed fluid reflux to the pelvicalyceal system in 25/176 Kidneys ( sensitivity = 94.4 % , specificity = 94.9 % , accuracy = 94.9 % ) . Air CRG showed air reflux in 19/176 kidneys ( sensitivity = 83.3 % , specificity = 96.8 % , accuracy = 95.4 % ) . VCUG showed VUR in 18/176 pelvicalyceal systems and /or ureters . CONCLUSION Fluid CRG and /or air CRG can be used as complementary methods to the VCUG , or during the follow up of patients with known VUR : VCUG can not be replaced completely by fluid CRG or air CRG , especially the first and the last one , because of the false negative results of these methods and because none of them can show the renal collecting system , the urinary bladder and the urethra in the st and ard way OBJECTIVE To compare the findings of renal ultrasonography ( RUS ) , 99mTc glucoheptonate renal scan ( GHS ) , and voiding cystourethrography ( VCUG ) in children with urinary tract infection . DESIGN Prospect i ve , masked , clinical study . SETTING Single center , multidisciplinary , in patients . PATIENTS Consecutive cases ( N = 50 ) of children aged 2 months to 15 years ( 8 boys , 42 girls ) with pyelonephritis in whom uroradiologic investigation was indicated . MEASUREMENTS AND MAIN RESULTS All patients underwent GHS , 48 had RUS , and 2 had intravenous pyelography . All but one of the patients had a VCUG . Fifteen children were found to have vesicoureteral reflux ( 6 unilaterally , 9 bilaterally ) . Of 96 kidneys evaluated by both GHS and RUS , 53 were abnormal by GHS versus 28 by RUS ( p < 0.001 ) . Findings of both GHS and US were normal in 36 kidneys and abnormal in 21 kidneys . In 32 kidneys only GHS showed abnormalities . In 7 kidneys only RUS showed abnormalities ; 5 of them had mild to moderate pelvic dilation caused by reflux , which was confirmed in all 5 by VCUG . The VCUG demonstrated reflux in another four units with normal GHS and RUS findings . All combined , GHS and VCUG detected 62 of 64 abnormal renal units ( 96.9 % ) . In the other two cases , RUS showed only focal hyperechogenicity of question able importance . CONCLUSION In the event that one elects to use GHS for the uroradiologic evaluation of children with urinary tract infection , it can be supplemented by VCUG alone , and RUS can be saved for special cases OBJECTIVE The objective of this study was to compare the findings of renal ultrasonography and 99mTc-DMSA renal scintigraphy in children with their first acute febrile urinary tract infection to determine which method is better in detecting patients at risk of renal injury or reflux . PATIENTS AND METHODS Thirty-three children between 0.2 and 12.3 years of age with their first acute febrile urinary tract infection were studied by means of clinical and laboratory assessment , renal ultrasonography and 99mTc-DMSA renal scintigraphy . In 24 patients ( 72.7 % ) a voiding cystourethrography was made . The patients were divided into two groups , those under 2 years of age ( n = 14 ) and those over 2 years old ( n = 19 ) . RESULTS Cortical scintigraphy showed renal changes in 23 patients ( 69.7 % ) and ultrasonography showed renal changes in 2 ( 6.1 % ; p < 0.05 ) . Children over 2 years of age had a higher incidence of renal lesions than did younger children ( 84.2 % vs 50 % ; p < 0.05 ) . There were no differences between girls and boys . Reflux was demonstrated in 13 patients ( 54.2 % ) . Among those kidneys which presented abnormal cortical scintigraphy , vesicoureteral reflux was present in 76.5 % of the studies . Furthermore , of those with abnormal ultrasonography vesicoureteral reflux was present in 17.6 % . CONCLUSIONS We found a high incidence of renal involvement in children with their first acute febrile urinary tract infection . The cortical scintigraphy is more sensitive than ultrasonography in detecting renal changes . The incidence of vesicoureteral reflux in febrile urinary tract infection is high . When there is a renal cortical defect the risk of reflux is higher . This suggests that cortical scintigraphy should be added to the initial examination of children with their first acute febrile urinary tract infection and this could be supplemented by voiding cystourethrography alone , with ultrasonography having a secondary role We describe an alternative technique using color flow Doppler sonography ( CFDS ) for detection of vesicoureteric reflux ( VUR ) . Twenty-one children , ages 2 - 16 years , were investigated for VUR using voiding cystourethrography ( VCU ) and CFDS . Forty-two ureterovesical junctions were studied and a total of 27 were found to be refluxing at VCU . Five of these 21 patients were operated for VUR and they were also reevaluated 3 and 6 months after the operation . With good diuresis ureteric jets could easily be detected with CFDS and if there was a reflux of urine into the ureter this could also be displayed . Afterwards , the patient was asked to urinate and if reflux into the ureter was detected , particular attention was paid to the detection of ureteral and pelvicalyceal dilatation by conventional gray-scale sonography . Taking VCU as the gold st and ard , CFDS revealed reflux in all cases except 1 . There were 3 patients who had only one-sided reflux at VCU and bilateral reflux at CFDS examination ( false-positive : 20 % ) . Correlation of CFDS and VCU was 90 , 100 and 75 % in low grade , grade III and grade IV reflux , respectively . The results of CFDS correlated well with the results of VCU during the follow-up of 5 patients who had antireflux operations . As a conclusion , CFDS could be used as an adjunct to st and ard ultrasonography for detection of VUR A prospect i ve study of detecting vesicoureteric reflux ( VUR ) by ultrasound is to be presented . In case of reflux , gas bubbles can be seen in the renal pelvis during the filling phase of a gas cystogram and during micturition , utilizing ultrasound as the imaging modality . In children under two years 52 sonographic reflux studies were performed and compared with radiographic voiding cystourethrograms ( VCUG ) . All higher grade VUR ( grade s II-IV ) have been detected by our method |
11,891 | 25,644,227 | The risk of overall hypoglycemia and severe adverse effects was comparable between the groups .
CONCLUSIONS IAsp provides better glycemic control when compared with RHI in patients with T1DM and T2DM .
Fewer T1DM patients treated with IAsp experienced nocturnal hypoglycemia , while both interventions showed a comparable risk of severe hypoglycemic events in both types of diabetes | INTRODUCTION Pr and ial insulin is a key component in insulin treatment of type 1 diabetes mellitus ( T1DM ) and in many patients with type 2 diabetes mellitus ( T2DM ) .
The evidence -based data supporting the choice of an insulin preparation are still limited .
OBJECTIVES We performed a systematic review to summarize and up date the evidence on relative efficacy and safety of insulin aspart ( IAsp ) and regular human insulin ( RHI ) in both types of diabetes . | Abbreviations ACCORD Action to Control Cardiovascular Risk in Diabetes ADVANCE Action in Diabetes and Vascular Disease : Preterax and Diamicron Modified-Release Controlled Evaluation AGI α-Glucosidase inhibitor CAD Coronary artery disease CKD Chronic kidney disease CVD Cardiovascular disease DPP-4 Dipeptidyl peptidase IV GIP Glucose-dependent insulinotropic peptide GLP-1 Glucagon-like peptide 1 NPH Neutral protamine Hagedorn TZD Thiazolidinedione UKPDS UK Prospect i ve Diabetes Study VADT Veterans Affairs Diabetes Aim : Type II diabetes mellitus ( DM ) increases the risk of cardiovascular disease . Treatment with insulin substantially reduces C - reactive protein ( CRP ) because of its anti-atherosclerotic action . This study was design ed to explore and compare the cardio protective role of regular human insulin ( RHI ) , aspart and lispro insulin in type II DM . Material s and Methods : A r and omized , open , parallel group , comparative clinical study was conducted on 90 patients of type II DM . After baseline clinical assessment and investigations , RHI was prescribed to 30 patients , aspart insulin to 30 patients and lispro insulin to another 30 patients for 12 weeks . The efficacy variables were change in blood pressure , glycemic control , lipid profile , serum potassium , high-sensitivity CRP ( hsCRP ) and UKPDS 10-year CHD risk scoring over 12 weeks . At the end of the study , the patients were followed up and changes in variables from baseline were analyzed by statistical tools . Results : Systolic blood pressure decreased significantly in aspart group ( P = 0.008 ) whereas diastolic blood pressure was decreased significantly both in aspart ( P < 0.001 ) and lispro group ( P = 0.01 ) . Fasting , postpr and ial blood glucose and HbA1c were decreased in all three groups significantly but change in aspart group was superior ( P = 0.01 ) . Triglyceride was significantly better controlled by lispro ( P < 0.01 ) whereas aspart insulin was superior to decrease total cholesterol and LDL ( P < 0.05 ) . The extent of potassium loss was significantly more with RHI ( P = 0.004 ) than others . CRP-lowering effect ( P = 0.017 ) and decrease in UKPDS risk scoring ( P = 0.019 ) in aspart and lispro group was superior to RHI group . Conclusion : Short acting insulin analogues , especially aspart insulin have been found to have a better cardio protective role than RHI in type II DM OBJECTIVE Because there are limited data on the comparison of insulin aspart and mixed insulin in type 2 diabetes , this trial was performed to compare the efficacy and safety of prepr and ial insulin aspart with human soluble insulin ( HI ) and human premix ( 70 % NPH/30 % regular ) insulin ( MIX ) . RESEARCH DESIGN AND METHODS A total of 231 type 2 diabetic patients were r and omized to insulin aspart ( n = 75 ) , HI ( n = 80 ) , or MIX ( n = 76 ) for 3 months . Insulin aspart and HI were administered with or without bedtime NPH insulin . A total of 204 patients completed the trial according to protocol . HbA1c , 7-point blood glucose , insulin dosage , and hypoglycemic episodes were recorded . The primary end point was " change of HbA1c " from baseline to last visit . Analysis for equivalence was performed by t tests with three subtests . RESULTS HbA1c decreased 0.91 + /- 1.00 for insulin aspart , 0.73 + /- 0.87 for HI , and 0.65 + /- 1.10 for MIX with the following confidence intervals : insulin aspart HI ( -0.21 to 0.57 , P = 0.025 ) , insulin aspart MIX ( -0.17 to 0.69 , P = 0.092 ) , and HI-MIX ( -0.33 to 0.48 , P = 0.006 ) . Postpr and ial blood glucose decreased in the insulin aspart group : 0.44 mmol/l to > 1.67 mmol/l compared with HI and 1.1 mmol/l to > 1.67 mmol/l compared with MIX . Prepr and ial insulin doses were similar in the insulin aspart and HI groups ( 10 - 14.5 U ) . Hypoglycemic events per month were 0.56 HI , 0.40 insulin aspart , and 0.19 MIX . CONCLUSIONS Statistically , insulin aspart was not equivalent to another treatment in terms of HbA1c reduction . Insulin aspart treatment result ed in improved HbA1c and postpr and ial blood glucose . The application of insulin aspart was safe and well tolerated OBJECTIVE To compare the safety and efficacy of insulin aspart ( IAsp ) , buffered regular insulin ( BR ) , and insulin lispro administered by continuous subcutaneous insulin infusion ( CSII ) in patients with type 1 diabetes . RESEARCH DESIGN AND METHODS After completing a 4-week run-in period with BR , 146 adult patients with type 1 diabetes ( with pretrial CSII experience ) were r and omly assigned ( 2:2:1 ) to CSII treatment with IAsp , BR , or lispro for 16 weeks in a multicenter , open-label , r and omized , parallel-group study . Bolus insulin doses were administered 30 min before meals ( BR ) or immediately before meals ( IAsp or lispro ) . RESULTS Treatment groups had similar baseline HbA(1c ) ( 7.3 % + /- 0.7 for IAsp , 7.5 % + /- 0.8 for BR , and 7.3 % + /- 0.7 for lispro ) . After 16 weeks of treatment , HbA1c values were relatively unchanged from baseline , and the mean changes in baseline HbA1c values were not significantly different between the three groups ( 0.00 + /- 0.51 , 0.15 + /- 0.63 , and 0.18 + /- 0.84 for the IAsp , BR , and lispro groups , respectively ) . The rates of hypoglycemic episodes ( blood glucose < 50 mg/dl ) per patient per month were similar ( 3.7 , 4.8 , and 4.4 for the IAsp , BR , and lispro groups , respectively ) . Clogs/blockages in pumps or infusion sets were infrequent ; most subjects ( 76 , 83 , and 75 % in the IAsp , BR , and lispro groups , respectively ) had < or = 1 clog or blockage per 4 weeks during the trial . CONCLUSIONS Insulin aspart in CSII was as efficacious and well tolerated as BR and lispro and is a suitable insulin for continuous subcutaneous insulin infusion using external pumps BACKGROUND Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention . We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes . METHODS We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes , using Cox proportional-hazards models with adjustment for covariates measured at baseline and after r and omization . RESULTS During a median follow-up period of 5 years , 231 patients ( 2.1 % ) had at least one severe hypoglycemic episode ; 150 had been assigned to intensive glucose control ( 2.7 % of the 5571 patients in that group ) , and 81 had been assigned to st and ard glucose control ( 1.5 % of the 5569 patients in that group ) . The median times from the onset of severe hypoglycemia to the first major macrovascular event , the first major microvascular event , and death were 1.56 years ( interquartile range , 0.84 to 2.41 ) , 0.99 years ( interquartile range , 0.40 to 2.17 ) , and 1.05 years ( interquartile range , 0.34 to 2.41 ) , respectively . During follow-up , severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events ( hazard ratio , 2.88 ; 95 % confidence interval [ CI ] , 2.01 to 4.12 ) , major microvascular events ( hazard ratio , 1.81 ; 95 % CI , 1.19 to 2.74 ) , death from a cardiovascular cause ( hazard ratio , 2.68 ; 95 % CI , 1.72 to 4.19 ) , and death from any cause ( hazard ratio , 2.69 ; 95 % CI , 1.97 to 3.67 ) ( P<0.001 for all comparisons ) . Similar associations were apparent for a range of nonvascular outcomes , including respiratory , digestive , and skin conditions ( P<0.01 for all comparisons ) . No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death . CONCLUSIONS Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes . It is possible that severe hypoglycemia contributes to adverse outcomes , but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events . ( Funded by Servier and the National Health and Medical Research Council of Australia ; Clinical Trials.gov number , NCT00145925 . ) This r and omized , open-label , cross-over study compares the efficacy of mealtime rapid-acting analog insulin aspart with human insulin , in combination with metformin . A total of 30 patients with type 2 diabetes , inadequately controlled ( HbA(1c)>7.5 % ) with oral hypoglycemic agents ( OHAs ) , were assigned to human insulin 30 min before meals or aspart immediately before meals , both with metformin 500 mg t.i.d . for 90 days . Patients then switched to the alternate insulin . At 90 and 180 days , blood glucose and lipids were measured at baseline and every 30 min after test meals , for 3h . HbA(1c ) and hypoglycemic events were also assessed . After 3 months , HbA(1c ) was significantly reduced with aspart , but not human insulin ( -0.4+/-0.7 % versus + 0.1+/-0.7 % , p<0.05 ) . During meal tests , blood glucose area under the curve ( AUC ) was significantly lower with aspart than human insulin ( 1240+/-476 min/mmol/l versus 1588+/-766 min/mmol/l , p<0.01 ) . AUCs for lipids were similar for both treatments . Neither group experienced serious hypoglycemic events . These results encourage treatment with mealtime insulin aspart plus metformin , in type 2 diabetes patients with postpr and ial hyperglycemia inadequately controlled by OHAs alone Insulin aspart ( IAsp ) , is a rapid-acting analogue of human insulin ( HI ) , for use in the meal related treatment of diabetes mellitus . The degree of glycaemic control achieved by IAsp in comparison with HI after algorithm-driven dose optimisation was tested over 3 months . The prospect i ve , multicentre , r and omised , open-label study with parallel groups was performed in 48 centres in 11 countries and included 423 basal-bolus treated patients with Type 1 diabetes . Main outcome measures were blood glucose control assessed by HbA1c , nine-point self-monitored blood glucose profiles , insulin dose , quality of life , hypoglycaemia and adverse events . An algorithm-driven increase occurred in the dose and number of daily injections of basal insulin , particularly in the IAsp group . After 12 weeks of treatment , HbA1c was significantly lower in IAsp compared to HI treated subjects by 0.17 ( 95 % CI 0.30 - 0.04 ) ( P<0.05 ) . Comparison of the blood glucose profiles showed lower blood glucose levels with IAsp after breakfast ( mean 8.4 vs 10.1 mmol/l ; P<0.0001 ) and dinner ( 8.2 vs 9.3 mmol/l ; P<0.01 ) . There were no differences between treatments in the incidence of hypoglycaemic episodes or in the adverse event profiles . The WHO Diabetes Treatment Satisfaction Question naire score for perceived hyperglycaemia was lower with Iasp ( P=0.005 ) , and patients found the insulin aspart treatment more flexible ( P=0.022 ) . The current study underlines the need for optimising the basal insulin regimen in order to take full advantage of the pharmacodynamics of IAsp OBJECTIVES Prepr and ial insulin injection in preschool children is complicated by irregular eating habits . Postpr and ial injection of rapid-acting insulin analogs such as insulin aspart ( IAsp ) offers the convenience of adjusting insulin dose to match food consumed . This trial compared safety and efficacy - including parental treatment satisfaction - of two basal-bolus regimens [ IAsp plus Neutral Protein Hagedorn ( NPH ) insulin vs. regular human insulin ( HI ) plus NPH ] in preschool children with type 1 diabetes . METHODS This study is a r and omized , 12-wk , crossover trial comparing IAsp and regular HI in 26 children ( 17 boys and 9 girls ; age : 2.4 - 6.9 yr ) . Regular HI was injected 30 min before and IAsp after or shortly before meals . Treatment satisfaction was assessed by a modified version of the WHO Diabetes Treatment Satisfaction Question naire ( DTSQ-M ) . RESULTS Glycemic control for IAsp treatment was not different from that for regular HI treatment as assessed by mean postpr and ial blood glucose increment ( IAsp vs. regular HI : 2.0 vs. 1.6 mmol/L ) , fructosamine ( 300 vs. 302 micromol/L ) , and hemoglobin A(1c ) ( HbA(1c ) ) ( 7.7 vs. 7.6 % ) . The relative risk of hypoglycemia was not significantly different [ relative risk for IAsp/regular HI ( 95 % CI ) : 1.06 ( 0.96 - 1.17 ) , p = 0.225 ] . Mean total daily insulin dose ( 0.7 U/kg ) remained constant throughout the trial with both treatments . The DTSQ-M score tended to be better for IAsp and reached statistical significance regarding the parental satisfaction with continuing IAsp treatment ( p < 0.05 ) . CONCLUSION In preschool children , a basal-bolus treatment scheme with postpr and ial IAsp as bolus insulin was equally effective and safe compared with prepr and ial regular HI , although the parents showed a preference for the IAsp treatment BACKGROUND We compared the pharmacokinetic and pharmacodynamic profiles of insulin aspart , biphasic insulin aspart 70 ( BIAsp70 ) and 50 ( BIAsp50 ) ( containing 70 % and 50 % rapid-acting insulin aspart , respectively ) , and soluble human insulin under experimental conditions . SUBJECTS AND METHODS In this r and omized , four-period crossover study , 19 type 1 diabetes patients received subcutaneous injections of identical doses ( 0.2 U/kg ) of insulin aspart , BIAsp70 , or BIAsp50 immediately before a st and ardized meal or human insulin 30 min before meal . Plasma glucose and serum insulin were measured for 12 h postpr and ially . RESULTS The pharmacokinetic and pharmacodynamic profiles of human insulin differed from those of insulin aspart , BIAsp70 , and BIAsp50 . The three different aspart preparations had easily distinguishable features with regard to onset and duration of action . Insulin aspart preparations were , on average , absorbed twice as fast as human insulin . In the initial phases ( 0 - 4 h and 0 - 6 h ) , the insulin area under the concentration-time curve ( AUC(ins ) ) was significantly higher during insulin aspart treatment compared with the others , whereas insulin aspart had a significantly lower AUC(ins ) over the last 6 h ( P<0.05 ) . BIAsp70 and BIAsp50 provided insulin coverage comparable to that of human insulin over the last 6 h. Insulin aspart had the most pronounced onset of action and the shortest duration . Comparing with insulin aspart and BIAsp70 , BIAsp50 revealed a closer treatment ratio to human insulin on pharmacodynamic end points . CONCLUSIONS BIAsp70 and BIAsp50 injected immediately before a meal are at least as effective as human insulin injected 30 min earlier in controlling postpr and ial glycemic excursions . BIAsp50 showed the greatest similarity to human insulin with regard to pharmacokinetic and pharmacodynamic profiles OBJECTIVE To compare long-term glycemic control and safety of using insulin aspart ( IAsp ) with that of regular human insulin ( HI ) . RESEARCH DESIGN AND METHODS This was a multicenter r and omized open-label 6-month study ( 882 subjects ) with a 6-month extension period ( 714 subjects ) that enrolled subjects with type 1 diabetes . Subjects administered IAsp immediately before meals or regular HI 30 min before meals ; basal NPH insulin was taken as a single bedtime dose in the majority of subjects . Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals . RESULTS Mean postpr and ial blood glucose levels ( mg/dl + /- SEM ) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast ( 156 + /- 3.4 vs. 185 + /- 4.7 ) , lunch ( 137 + /- 3.1 vs. 162 + /- 4.1 ) , and dinner ( 153 + /- 3.1 vs. 168 + /- 4.1 ) , when assessed after 6 months of treatment . Mean HbA1c values ( % + /- SEM ) were slightly , but significantly , lower for the IAsp group ( 7.78 % + /- 0.03 ) than for the regular HI group ( 7.93 % + /- 0.05 , P = 0.005 ) at 6 months . Similar postpr and ial blood glucose and HbA1c values were observed at 12 months . Adverse events and overall hypoglycemic episodes were similar for both treatment groups . CONCLUSIONS Postpr and ial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment . The improvement was not obtained at an increased risk of hypoglycemia . HbA1c was slightly , but significantly , lower for IAsp compared with HI at 6 and 12 months AIMS Insulin aspart has been shown to improve post-pr and ial and overall glycaemic control in people with Type 1 diabetes . We hypothesized that insulin aspart with intensified basal NPH insulin supplementation would result in better overall glycaemic control than human regular insulin with st and ard basal NPH insulin . METHODS The trial was conducted in 43 centres in seven countries . People with Type 1 diabetes were r and omized to mealtime insulin aspart with up to four daily NPH doses if meals were > 5 h apart and a 25 % increase in bedtime NPH dose ( n = 187 ) , or to mealtime human unmodified insulin with once or twice daily basal NPH insulin ( n = 181 ) . Efficacy and safety were evaluated at 12 weeks ( primary evaluation period ) and 64 weeks . RESULTS At 12 and 64 weeks there was no statistically significant difference in HbA1c between the insulin aspart and regular insulin groups : -0.09 ( 95 % confidence interval ( CI ) -0.23 , + 0.05)% and -0.14 ( -0.32 , + 0.04)% . Post-pr and ial glucose values were lower and the area under the 24-h self-monitored blood glucose curve above 7.0 mmol/l was 28 % smaller with insulin aspart ( 35.2 + /- 3.2 vs. 48.9 + /- 3.1 mmol/l h , P = 0.0015 ) . No significant differences were found in mild or severe hypoglycaemia , or adverse event rate . At 64 weeks treatment satisfaction was higher in the insulin aspart group ( difference 1.57 ( 95 % CI 0.49 , 2.64 ) points , P = 0.004 ) , while quality of life was not different . CONCLUSIONS Improved post-pr and ial glycaemic control and treatment satisfaction with insulin aspart were confirmed . Intensifying basal insulin supplementation result ed in a similar HbA1c decrement as previously found with the use of insulin aspart and st and ard NPH insulin supplementation . This does not support routinely basal NPH insulin intensification when using rapid-acting insulin analogues in daily practice AIMS To compare the effects of the rapid-acting insulin analogue insulin aspart and soluble human insulin on hypoglycaemia and glycaemic control in patients with Type 1 diabetes when injected immediately before meals as part of intensive insulin therapy . METHODS In this multinational , double-blind , r and omised , crossover trial , 155 patients with Type 1 diabetes ( HbA(1c ) < 8.0 % ) were symmetrically r and omised to two 16-week treatment periods on either type of insulin , both injected 0 - 5 min before meals . NPH insulin was given as basal insulin once or twice daily as needed , and insulin dosages were regularly adjusted using pre-defined algorithms to maintain tight glycaemic control . Treatment periods were separated by a 4-week washout . RESULTS The rate of major nocturnal ( 24.00 - 06.00 h ) hypoglycaemic episodes was 72 % lower with insulin aspart than with human insulin ( 0.067 vs. 0.225 events/month ; P = 0.001 ) . Total rate of major hypoglycaemia did not differ significantly between treatments ( insulin aspart/human insulin relative risk 0.72 ; 95 % CI 0.47 - 1.09 , P = 0.12 ) . The rate of minor events was significantly reduced by 7 % with insulin aspart ( P = 0.048 ) . Reductions in rate of hypoglycaemia were achieved with maintained overall glycaemic control : Mean HbA(1c ) remained constant , slightly below 7.7 % on both treatments . CONCLUSIONS The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinical ly significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control . Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid-acting insulin analogues during intensive insulin therapy AIMS To compare the efficacy of insulin aspart , a rapid-acting insulin analogue , with that of unmodified human insulin on long-term blood glucose control in Type 1 diabetes mellitus . METHODS Prospect i ve , multi-centre , r and omized , open-labelled , parallel-group trial lasting 6 months in 88 centres in eight European countries and including 1,070 adult subjects with Type 1 diabetes . Study patients were r and omized 2:1 to insulin aspart or unmodified human insulin before main meals , with NPH-insulin as basal insulin . Main outcome measures were blood glucose control as assessed by HbA1c , eight-point self-monitored blood glucose profiles , insulin dose , quality of life , hypoglycaemia , and adverse events . RESULTS After 6 months , insulin aspart was superior to human insulin with respect to HbA1c with a baseline-adjusted difference in HbA1c of 0.12 ( 95 % confidence interval 0.03 - 0.22 ) % Hb , P < 0.02 . Eight-point blood glucose profiles showed lower post-pr and ial glucose levels ( mean baseline-adjusted -0.6 to -1.2 mmol/l , P < 0.01 ) after all main meals , but higher pre-pr and ial glucose levels before breakfast and dinner ( 0.7 - 0.8 mmol/l , P < 0.01 ) with insulin aspart . Satisfaction with treatment was significantly better in patients treated with insulin aspart ( WHO Diabetes Treatment Satisfaction Question naire ( DTSQ ) baseline-adjusted difference 2.3 ( 1.2 - 3.3 ) points , P < 0.001 ) . The relative risk of experiencing a major hypoglycaemic episode with insulin aspart compared to human insulin was 0.83 ( 0.59 - 1.18 , NS ) . Major night hypoglycaemic events requiring parenteral treatment were less with insulin aspart ( 1.3 vs. 3.4 % of patients , P < 0.05 ) , as were late post-pr and ial ( 4 - 6 h ) events ( 1.8 vs. 5.0 % of patients , P < 0.005 ) . CONCLUSIONS These results show small but useful advantage for the rapid-acting insulin analogue insulin aspart as a tool to improve long-term blood glucose control , hypoglycaemia , and quality of life , in people with Type 1 diabetes mellitus |
11,892 | 20,141,987 | There were no differences in recurrence or complication rate among patients undergoing surgery after the primary dislocation when compared with those undergoing surgery after multiple recurrent episodes .
Clinical outcome measures significantly improved within all independent studies from preoperatively to postoperatively . | PURPOSE The purpose of this study was to systematic ally review the evidence on the outcomes of arthroscopic repair for anterior shoulder instability in first-time dislocators when compared with patients with recurrent instability . | Sixty-two consecutive patients with recurrent traumatic anterior instability of the shoulder were prospect ively observed . Thirty patients were observed after arthroscopic stabilization , and 32 were observed after open Bankart repair during a mean follow-up of 36 and 40 months , respectively ( range , 24 to 60 months for both groups ) . To reattach the labrum , the arthroscopic technique used transglenoid sutures and the open technique used bone anchors . Redislocation occurred in two patients ( 6 % ) in the open repair group and in five patients ( 17 % ) in the arthroscopic repair group . Three of the five patients with redislocations in the arthroscopic repair group underwent reoperation . According to the criteria of Rowe et al. , 29 patients ( 90.6 % ) who had open repair and 24 patients ( 80 % ) who had arthroscopic repair had good-to-excellent results . The patients averaged 90.6 points in the open repair group and 83.1 points in the arthroscopic repair group postoperatively . Little or no limitations in their postoperative sports activities were reported by 30 patients ( 94 % ) who underwent open repair and by 25 patients ( 83 % ) who had arthroscopic repair . Despite similar patient population s and using arthroscopic examination to select the type of repair in both groups , the results of arthroscopic shoulder stabilization are inferior to those of the classic open Bankart procedure BACKGROUND The prevalence and risk factors for recurrent instability and functional impairment following a primary glenohumeral dislocation remain poorly defined in younger patients . We performed a prospect i ve cohort study to evaluate these outcomes . We also aim ed to produce guidelines for the design of future clinical trials , assessing the efficacy of interventions design ed to improve the outcome after a primary dislocation . METHODS We performed a prospect i ve cohort study of 252 patients ranging from fifteen to thirty-five years old who sustained an anterior glenohumeral dislocation and were treated with sling immobilization , followed by a physical therapy program . Patients received regular clinical follow-up to assess whether recurrent instability had developed . Functional assessment s were made and were compared for two subgroups : those who had not had instability develop and those who had received operative stabilization to treat recurrent instability . RESULTS On survival analysis , instability developed in 55.7 % of the shoulders within the first two years after the primary dislocation and increased to 66.8 % by the fifth year . The younger male patients were most at risk of instability , and 86.7 % of all of the patients known to have recurrent instability had this complication develop within the first two years . A small but measurable degree of functional impairment was present at two years after the initial dislocation in most patients . Sample -size calculations revealed that a relatively small number of patients with a primary dislocation would be required in future clinical trials examining the effects of interventions design ed to reduce the prevalence of recurrent instability and improve the functional outcome . CONCLUSIONS Recurrent instability and deficits of shoulder function are common after primary nonoperative treatment of an anterior shoulder dislocation . There is substantial variation in the risk of instability , with younger males having the highest risk and females having a much lower risk . Future clinical trials to evaluate primary interventions should evaluate the prevalence of recurrent instability and functional deficits , with use of an assessment tool specifically for shoulder instability , during the first two years after the initial dislocation BACKGROUND Anterior dislocation of the glenohumeral joint in younger patients is associated with a high risk of recurrence and persistent functional deficits . The aim of this study was to assess the efficacy of a primary arthroscopic Bankart repair , while controlling for the therapeutic effects produced by the arthroscopic intervention and joint lavage . METHODS In a single-center , double-blind clinical trial , eighty-eight adult patients under thirty-five years of age who had sustained a primary anterior glenohumeral dislocation were r and omized to receive either an arthroscopic examination and joint lavage alone or together with an anatomic repair of the Bankart lesion . Assessment of the rate of recurrent instability , functional outcome ( with use of three scores ) , range of movement , patient satisfaction , direct health-service costs , and treatment complications was completed for eighty-four of these patients ( forty-two in each group ) during the subsequent two years . RESULTS In the two years after the primary dislocation , the risk of a further dislocation was reduced by 76 % and the risk of all recurrent instability was reduced by 82 % in the Bankart repair group compared with the group that had arthroscopy and lavage alone . The functional scores were also better ( p < 0.05 ) , the treatment costs were lower ( p = 0.012 ) , and patient satisfaction was higher ( p < 0.001 ) after arthroscopic repair . The improved functional outcome appeared to be mediated through the prevention of instability since the functional outcome in patients with stable shoulders was similar , irrespective of the initial treatment allocation . The patients who had a Bankart repair and played contact sports were also more likely to have returned to their sport at two years ( relative risk = 3.4 , p = 0.007 ) . CONCLUSIONS Following a first-time anterior dislocation of the shoulder , there is a marked treatment benefit from primary arthroscopic repair of a Bankart lesion , which is distinct from the so-called background therapeutic effect of the arthroscopic examination and lavage of the joint . However , primary repair does not appear to confer a functional benefit to patients with a stable shoulder at two years after the dislocation Background Nonoperative treatment of traumatic shoulder dislocations leads to a high rate of recurrent dislocations . Hypothesis Early arthroscopic treatment for shoulder dislocation will result in a lower recurrence rate than nonoperative treatment . Study Design Prospect i ve , r and omized clinical trial . Methods Two groups of patients were studied to compare nonoperative treatment with arthroscopic Bankart repair for acute , traumatic shoulder dislocations in young athletes . Fourteen nonoperatively treated patients underwent 4 weeks of immobilization followed by a supervised rehabilitation program . Ten operatively treated patients underwent arthroscopic Bankart repair with a bioabsorbable tack followed by the same rehabilitation protocol as the nonoperatively treated patients . The average follow-up was 36 months . Results Three patients were lost to follow-up . Twelve nonoperatively treated patients remained for follow-up . Nine of these ( 75 % ) developed recurrent instability . Six of the nine have required subsequent open Bankart repair for recurrent instability . Of the nine operatively treated patients available for follow-up , only one ( 11.1 % ) developed recurrent instability . Conclusions Arthroscopic stabilization of traumatic , first-time anterior shoulder dislocations is an effective and safe treatment that significantly reduces the recurrence rate of shoulder dislocations in young athletes when compared with conventional , nonoperative treatment PURPOSE The aim of this study was to evaluate , prospect ively , outcomes following arthroscopic Bankart repair performed with 2 types of suture anchor -- the G II ( DePuy Mitek , Raynham , MA ) nonabsorbable anchor and the Panalok ( DePuy Mitek ) absorbable anchor . METHODS Patients with a diagnosis of recurrent traumatic anterior instability of the shoulder who were seen in a single unit between April of 2000 and June of 2003 were considered for inclusion in the study . Patients were assessed preoperatively and postoperatively by means of a subjective , patient-related outcome measurement tool ( Oxford Instability Score ) , a visual analogue scale for pain and instability ( VAS Pain and VAS Instability ) , and a quality -of-life question naire ( Short Form-12 [ SF-12 ] ) . Length of follow-up was 1.5 to 5 years ( mean , 2.6 y ) . The incidence of recurrent instability and the level of sporting ability were recorded . Patients were r and omized to undergo surgical repair with nonabsorbable or absorbable anchors . RESULTS A total of 130 patients were included in this study , of whom 6 were lost to follow-up ; therefore 124 patients ( 95 % ) completed the study . Both types of anchor were highly effective . No differences in rate of recurrence or in any of the scores were noted between the 2 groups . In all , 4 patients in the nonabsorbable group and 3 in the absorbable group experienced additional episodes of dislocation after a traumatic event . Rate of redislocation in the whole series was therefore 6 % . In addition , 4 patients , all of them from the absorbable group ( 4 % ) , described ongoing symptoms of instability but no true dislocations . In all , 85 % of the patient group have returned to their previous level of sporting activity . CONCLUSIONS No differences in outcomes of arthroscopic Bankart repair were seen whether absorbable or nonabsorbable anchors were used . Both are highly effective , with a redislocation rate of 6 % . LEVEL OF EVIDENCE Level I , therapeutic r and omized controlled trial The purpose of this study was to compare patients with anterior shoulder instability who were treated with an open Bankart procedure with those treated with an arthroscopic procedure . During a 3-year period , 43 patients ( 44 shoulders ) were surgically treated . Thirty-four patients were available for followup . Eighteen shoulders had open Bankart procedure , and 16 shoulders were treated arthroscopically . Capsular laxity can be better assessed with the open procedure . A Bankart lesion was found in all the patients in both series . Average followup for Group 1 was 34 months , and for Group 2 , it was 23 months . Group 1 had 83 % good to excellent results with no recurrent dislocation or reoperation . Group 2 had 50 % good to excellent results , and 50 % fair to poor results with 3 recurrent dislocations and 4 recurrent subluxations that required second operation . The average loss of external rotation in Group 1 was not significantly greater than that in Group 2 . Sixteen patients in Group 1 and 8 patients in Group 2 were able to return to their primary work or sport . Results of arthroscopic Bankart repair do not equal those of the open Bankart procedure for the rate of recurrence and postoperative range of motion . The followup reported is short , and more dislocations can be anticipated with longer followup Abstract A total of 41 consecutive patients ( 11 women and 30 men , median age 29 ( 18–51 ) years ) with unilateral , isolated , posttraumatic , recurrent anterior shoulder dislocation and a Bankart lesion were operatively repaired , either by an arthroscopic technique including a capsular plication , or by an open procedure with Mitec anchors . All the patients were followed prospect ively and evaluated after a median of 36 ( 30–52 ) months follow-up by a “ blind ” observer . Nineteen patients in each group had excellent or good results , and one in each group was grade d as fair . One patient in the arthroscopic group had a traumatic dislocation 5 months after the operation and was grade d as poor . Three patients experienced subluxations postoperatively , one in the arthroscopic and two in the open group . There was no significant difference in anterior-posterior shoulder laxity measured objective ly with Donjoy . The open Bankart repair group had a statistically significantly longer hospitalization ( P = 0.001 ) , a slight decrease in external range of motion , and more frequent cosmetic complaints . Apart from this , the results revealed no major differences between the two methods after a median of 36 months in this selected group of patients with longst and ing problems We performed a prospect i ve study of 117 patients ( 119 shoulders ) with symptomatic , recurrent anterior post-traumatic shoulder instability to compare open versus arthroscopic reconstruction . Arthroscopic reconstructions ( N = 66 ) were performed using bioabsorbable tacks ( Suretac fixators ) , whereas open reconstructions ( N = 53 ) were performed with suture anchors . All of the patients had a Bankart lesion . Independent observers examined 108 of the 119 shoulders ( 91 % ) at a median follow-up period of 28 months ( range , 24 to 63 ) for the arthroscopic group and 36 months ( range , 24 to 63 ) for the open group . The recurrence rate , including both dislocations and subluxations , was 9 of 60 ( 15 % ) in the arthroscopic group , compared with 5 of 48 ( 10 % ) in the open group . At follow-up , the Rowe score was 93 points ( range , 39 to 100 ) and the Constant score was 91 points ( range , 56 to 100 ) in the arthroscopic group , compared with 89 points ( range , 53 to 100 and 57 to 100 for the Rowe and Constant scores , respectively ) for both scores in the open group . The only significant difference was in external rotation in abduction , which was 90 ° ( range , 50 ° to 135 ° ) in the arthroscopic group and 80 ° ( range , 25 ° to 115 ° ) in the open group . Both methods produced stable and well-functioning shoulders in the majority of patients PURPOSE The purpose of this study was to compare the results of arthroscopic and open repair of isolated Bankart lesions of the shoulder using metallic suture anchors . TYPE OF STUDY Prospect i ve r and omized clinical study . METHODS Sixty patients with traumatic anterior shoulder instability underwent a surgical repair of an isolated Bankart lesion . The patients were divided into 2 groups of 30 patients each . In group 1 , an arthroscopic repair was performed , and in group 2 , an open procedure was performed . The groups were homogeneous for gender , age , dominance , number of dislocations , time elapsed between first dislocation and surgery , and pathologic findings . In all cases of both groups , the lesion was repaired using metallic suture anchors carrying nonabsorbable braided sutures . Postoperative rehabilitation was the same for the 2 groups . Two years ' follow-up evaluation included Constant and Rowe shoulder scores . Statistical analysis of data was performed using an unpaired t test ( significance for P < .05 ) . RESULTS No recurrence of dislocation of the involved shoulder has been reported in either group . Follow-up Constant and Rowe scores of the 2 groups were not significantly different . The only significant difference seen between the 2 groups was for range of motion evaluation with the Constant score . The mean value for group 1 ( 39.6 + /- 0.8 ) was significantly greater ( P = .017 ) than that for group 2 ( 37.8 + /- 2.0 ) . CONCLUSIONS Arthroscopic repair with suture anchors is an effective surgical technique for the treatment of an isolated Bankart lesion . Open repair does not offer a significantly better 2-year result in terms of stability , and furthermore , can negatively affect the recovery of full range of motion of the shoulder . LEVEL OF EVIDENCE Level PURPOSE The aim of the study was to compare the clinical and radiographic results after arthroscopic Bankart reconstruction using 2 different types of absorbable implant . TYPE OF STUDY R and omized controlled trial . METHODS A r and omized series of 40 patients who had recurrent , unidirectional , post-traumatic shoulder instability were included in the study . All patients underwent an arthroscopic Bankart reconstruction involving either polygluconate co-polymer ( PGACP group , n = 20 ) or self-reinforced poly-L-lactic acid polymer ( PLLA group , n = 20 ) tack implants . The patients underwent clinical and radiographic assessment s preoperatively and at 2 years . Additional radiographic assessment s were performed at 6 months . RESULTS Preoperatively , the study groups were comparable in terms of demographics as well as clinical parameters . One patient in each group had a redislocation ( 5 % ) during the follow-up period of 2 years . No subluxations were registered . No statistically significant differences were found between the study groups in terms of strength in abduction , range of motion , and Rowe or Constant scores . There was a significant increase in degenerative changes during the follow-up period in both study groups ( P = .004 ) . However , no significant differences in degenerative changes were registered between the study groups either preoperatively or at the 2-year follow-up . There were no significant differences in the radiographic visibility of the drill holes used for the absorbable implants between the study groups at the 6-month assessment . However , at the 2-year assessment , the radiographic visibility of the drill holes was significantly greater ( P = .004 ) in the patients in the PLLA group than those in the PGACP group . At the 2-year assessment , no correlation was found between the appearance of the drill holes and the degenerative findings ( PGACP group , rho = 0.44 ; PLLA group , rho = 0.42 ) . CONCLUSIONS Two years after arthroscopic Bankart reconstruction using either PGA polymer or PLA polymer implants , the overall clinical results were comparable . Radiographic assessment s revealed that the degenerative changes increased in both study groups during the follow-up period . Furthermore , the visibility of the drill holes on the 2-year radiographs was greater after using PLLA implants than after using PGACP implants . LEVEL OF EVIDENCE Level A prospect i ve study evaluating nonoperative treatment versus arthroscopic Bankart suture repair for acute , ini tial dislocation of the shoulder was undertaken in young athletes . All patients met the following criteria : 1 ) sus tained an acute first-time traumatic anterior dislocation , 2 ) no history of impingement or occult subluxation , 3 ) the dislocation required a manual reduction , and 4 ) no concomitant neurologic injury . Thirty-six athletes ( average age , 20 years ) met the criteria for inclusion . Group I patients were immobilized for 1 month followed by rehabilitation ; they were allowed full activity at 4 months . Group II patients underwent arthroscopic Bankart repair followed by the same protocol as Group I. Group I consisted of 15 athletes . Twelve patients ( 80 % ) developed recurrent instability ; 7 of the 12 have required open Bankart repair for recurrent instability . Group I consisted of 21 patients ; 18 patients ( 86 % ) had no recurrent instability at last followup ( average , 32 months ; range , 15 to 45 ) ( P = 0.001 ) . One patient in Group II has required a subsequent open Bankart repair to treat symptomatic recurrence ( P = 0.005 ) . In this study , arthroscopic Bankart repair significantly reduced the recurrence rate in young athletes who sustained an acute , initial anterior dislocation of the shoulder Two hundred and fifty-six of 257 shoulders in 254 patients who were between the ages of twelve and forty years and who had primary anterior dislocation of the shoulder that was treated by immobilization for at least three weeks or by early movement were followed for five years in a prospect i ve multicenter study . Two or more recurrences had occurred in 55 per cent of the shoulders in patients who were twenty-two years old or younger , in 37 per cent of the shoulders in patients who were twenty-three to twenty-nine years old , and in 12 per cent of the shoulders in patients who were thirty to forty years old . Surgery for the treatment of instability had been performed or was scheduled to be performed in 28 , 18 , and 5 per cent of the shoulders , respectively , in the three age-groups . The dislocation recurred in only one of thirty-two shoulders that had a fracture of the greater tuberosity ( p less than 0.001 ) . The results as regards recurrence after five years were not influenced by immobilization of the shoulder for three to four weeks after the initial dislocation , bilateral dislocation , or the type of initial trauma and athletic activity . A moderate impression fracture of the humeral head ( Hermodsson or Hill-Sachs ) did not change the prognosis in the younger patients ( twenty-two years old or younger ) . However , in the patients who were twenty-three to forty years old the rate of recurrence was significantly higher ( p less than 0.01 ) when this injury was demonstrated . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE The purpose of this study was to compare long-term results after surgical and conservative primary treatment of first-time traumatic anterior shoulder dislocation . METHODS Arthroscopic diagnosis after first-time traumatic anterior shoulder dislocation was performed , and in cases of a Baker type 1 , 2 , or 3 lesion , patients were r and omized either to conservative treatment with a fixed sling for 1 week followed by a rehabilitation program or to open repair with a similar rehabilitation program . RESULTS In this study 76 patients ( 14 female and 62 male patients ) , aged 15 to 39 years , were r and omized to surgical repair ( n = 37 ) or conservative treatment ( n = 39 ) . Of the patients , 6.6 % had Baker type 1 lesions , 13.2 % had type 2 lesions , and 80.3 % had type 3 lesions . After a minimum of 2 years ' follow-up , 56 % had recurrence after conservative treatment and 3 % after open repair ( P < .005 ) . Among nondislocators , 39 % in the conservative group and 7 % in the repair group had a positive apprehension test . When evaluated after 10 years by use of the Oxford self- assessment score , 72 % of patients in the surgical group had good or excellent results . Of the conservatively treated patients , 75 % had unsatisfactory results because of recurrence , instability , and pain or stiffness . CONCLUSIONS Arthroscopic evaluation after first-time anterior shoulder dislocation revealed a Baker type 2 or 3 lesion in 93.5 % of patients . At 2 years ' follow-up , 21 ( 54 % ) of the conservatively treated patients had recurrence , as compared with 1 patient with recurrence ( 3 % ) after open surgical repair . After 8 years , a further 3 patients in the conservatively treated group had redislocations , 1 had subjective instability , and 4 had pain or stiffness , result ing in 74 % having unsatisfactory results according to the Oxford score . Of the patients who had surgical repair , 72 % had good or excellent results after 10 years . Because open repair produces superior results compared with conservative treatment , we recommend that the surgeon consider performing primary repair in active patients to reduce the risk of recurrence . LEVEL OF EVIDENCE Level I , high- quality prospect i ve , r and omized controlled trial From 1993 through 1996 , a multicenter study was conducted on the surgical treatment of patients with posttraumatic recurrent anterior shoulder dislocations . Fifty-six patients ( 40 men , 16 women ; mean age 26 years [ range 18 - 51 years ] ) , were evaluated with shoulder arthroscopy . If a Bankart lesion was present , the patients were r and omly allocated to either an arthroscopic reconstruction with the use of biodegradable tacks or an open reconstruction with suture anchors . The postoperative rehabilitation protocol for the two groups was identical . In all patients , the range of shoulder motion , stability , and the Constant and Rowe scores were evaluated at 3 , 12 , and 24 months postoperatively . Thirty patients were surgically treated with the arthroscopic technique and 26 patients with the open technique . In the arthroscopic group , there were recurrences in 7 ( 23 % ) of 30 patients at a mean of 13 months ( range 5 to 21 months ) after surgery . All patients with stable shoulders had a negative apprehension test result . In the open group , there were recurrences in 3 ( 12 % ) of 26 patients at a mean of 10 months ( range 2 to 23 months ) after surgery ( P = not significant ) . In the arthroscopic group , 2 patients had new traumatic redislocations , whereas 1 patient redislocated during an epileptic seizure . In the open group , 1 traumatic redislocation occurred . The 2-year results in this study demonstrate a large number of redislocations after reconstruction , even in the open surgery group . Patient noncompliance with the rehabilitation protocol and predisposing disease may partially explain these results . A tendency was seen toward more redislocations in the arthroscopic group , which emphasizes the importance of correct patient selection and careful surgical technique in the difficult surgical procedure Background : Sixty-three consecutive patients with recurrent traumatic anterior shoulder instability underwent operative repair . The decision to select either arthroscopic Bankart repair or open capsular shift was based on the findings of an examination under anesthesia and the findings at the time of arthroscopy . Thirty-nine patients with only anterior translation on examination under anesthesia and a discrete Bankart lesion underwent arthroscopic Bankart repair with use of absorbable transfixing implants . Twenty-four patients with inferior translation in addition to anterior translation on examination under anesthesia and capsular laxity or injury on arthroscopy underwent an open capsular shift . Methods : Treatment outcomes for each group were determined according to the scoring systems of Rowe et al. , the American Shoulder and Elbow Surgeons , and the Short Form-36 . Failure was defined as recurrence of dislocation or subluxation or the finding of apprehension . Fifty-nine ( 94 percent ) of the sixty-three patients were examined and filled out a question naire at a mean of fifty-four months ( range , twenty-seven to seventy-two months ) following surgery . Results : There were no significant differences between the two groups with regard to the prevalence of failure or any of the other measured parameters of outcome . An unsatisfactory outcome occurred after nine ( 24 percent ) of thirty-seven arthroscopic repairs and after four ( 18 percent ) of twenty-two open reconstructions . All cases of recurrent instability result ed from a reinjury in a contact sport or a fall less than two years postoperatively . The treatment groups did not differ with regard to patient age , h and dominance , mechanism of initial injury , duration of follow-up , or delay until surgery . Measured losses of motion were minimal and , with the exception of forward elevation , slightly more of which was lost after the open capsular shifts ( p = 0.05 ) , did not differ between the two forms of treatment . Approximately 75 percent of the patients in each group returned to their favorite recreational sports with no or mild limitations . As rated by the patients , the result was good or excellent after thirty-one ( 84 percent ) of the arthroscopic procedures and after twenty ( 91 percent ) of the open procedures . Conclusions : Arthroscopic and open repair techniques for the treatment of recurrent traumatic shoulder instability yield comparable results if the procedure is selected on the basis of the pathological findings at the time of surgery PURPOSE To report the long-term results of a prospect i ve r and omized clinical trial comparing the effectiveness of immediate arthroscopic stabilization versus immobilization and rehabilitation after a first traumatic anterior dislocation of the shoulder . TYPE OF STUDY R and omized clinical trial . METHODS Forty subjects younger than 30 years with a first traumatic anterior shoulder dislocation were r and omized to receive immediate anterior stabilization plus rehabilitation or immobilization followed by rehabilitation . Patients completed the American Shoulder and Elbow Surgeons ( ASES ) , Disabilities of the Arm , Shoulder and H and ( DASH ) , and the Western Ontario Shoulder Instability Index ( WOSI ) question naires . RESULTS At an average follow-up of 75 months , there was a significant difference in the rate of redislocation between the groups but no statistical significant difference in shoulder function with the ASES or the DASH . The mean difference between the 2 groups with the WOSI estimates a small , but clinical ly significant difference . CONCLUSIONS It is recommended that immediate arthroscopic stabilization is the treatment of choice in a subset of patients who are younger than 30 years and are higher level athletes , and the timing for surgery is good or their sport is risky , i.e. , rugby , football , kayaking , rock climbing . LEVEL OF EVIDENCE Level II Our purpose was to compare the effectiveness of traditional treatment with immediate arthroscopic stabilization in young patients who have sustained a first traumatic anterior dislocation of the shoulder . Forty skeletally mature patients younger than 30 years of age were r and omly allocated to immobilization for 3 weeks followed by rehabilitation ( group T ) or arthroscopic stabilization ( within 4 weeks of injury ) followed by an identical immobilization and rehabilitation protocol ( group S ) . A blinded research assistant performed all follow-up evaluations . The dominant arm was involved in 35 % of subjects . The injury occurred in a sporting event in 70 % of subjects . At 24 months , there was a statistically significant difference in the rate of redislocation ( T = 47 % , S = 15.9 % , P = .03 ) . An intention-to-treat analysis comparing disease-specific quality of life using the vali date d Western Ontario Shoulder Instability ( WOSI ) index showed statistically significantly better results in the surgically treated group at the 33 months ( T = 633.93 v S = 287.1 , P = .03 ) and no significant difference in range of motion . At an average 32 months follow-up , a significant reduction in redislocation and improvement in disease-specific quality of life is afforded by early arthroscopic stabilization in patients less than 30 year of age with a first , traumatic , anterior dislocation of the shoulder |
11,893 | 30,464,635 | Conclusion These findings support that vitamin B may have an influence on carcinogenesis of the esophagus .
Vitamin B1 , B3 , B6 , B9 showed a decreased risk of EC , and vitamin B12 showed an increased risk of EC | Background Several epidemiology studies have explored the association between dietary B vitamins ' intake and the risk of esophageal cancer ( EC ) .
However , the results remain inconclusive .
Thus , we conducted a systematic review with meta- analysis to evaluate such association . | Background : Nutrients in the one-carbon metabolism pathway may be involved in carcinogenesis . Few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer . Methods : We prospect ively examined the association between self-reported intakes of folate , methionine , vitamin B6 , and vitamin B12 and gastric and esophageal cancer in 492 293 men and women . Results : We observed an elevated risk of esophageal squamous cell carcinoma with low intake of folate ( relative risk ( 95 % confidence interval ) : Q1 vs Q3 , 1.91 ( 1.17 , 3.10 ) ) , but no association with high intake . Folate intake was not associated with esophageal adenocarcinoma , gastric cardia adenocarcinoma , or non-cardia gastric adenocarcinoma . The intakes of methionine , vitamin B6 , and vitamin B12 were not associated with esophageal and gastric cancer . Conclusion : Low intake of folate was associated with increased risk of esophageal squamous cell carcinoma Evidence shows that there is a rapid increase in the production of markers of oxidative damage immediately following acute stroke and that endogenous antioxidant defences are rapidly depleted , thus permitting further tissue damage . Several studies point to an antioxidant effect of B-group vitamins and a pro-oxidant effect of elevated plasma tHcy ( total homocysteine ) . In the present study , we assessed whether supplementary B-group vitamins during this critical period will enhance antioxidant capacity and mitigate oxidative damage . Forty-eight patients with acute ischaemic stroke within 12 h of symptom onset were assigned to receive daily oral supplements of B-group vitamins comprising 5 mg of folate , 5 mg of vitamin B2 , 50 mg of vitamin B6 and 0.4 mg of vitamin B12 ( n=24 ) or no supplements ( n=24 ) for 14 days . The treatment group and controls were matched for stroke subtype and age . Blood sample s were obtained before intervention and also at 7 and 14 days post-recruitment for measurement of the following biomarkers : red cell folate ( whole blood folate corrected with haematocrit ) , erythrocyte glutathione reductase activity coefficient ( EGRAC ; measure of vitamin B2 status ) , plasma pyridoxal phosphate ( vitamin B6 status ) , plasma vitamin B12 , plasma alpha-tocopherol , plasma ascorbic acid , plasma TAOC ( total antioxidant capacity ) , plasma MDA ( malondialdehyde ) , plasma tHcy and CRP ( C-reactive protein ) . Supplementation for 14 days with B-group vitamins significantly increased the plasma concentrations of pyridoxal phosphate and red blood cell folate and improved a measure of B2 status compared with the control group ( P<0.05 ) . Plasma tHcy decreased in both groups albeit less in the control group , but differences in cumulative changes were not significant . There was , however , a decrease in plasma MDA concentration in the treatment group , in contrast with the increase seen in the control group and these differences were significant ( P=0.05 ) . CRP concentration , a marker of tissue inflammation , was significantly lower in the treatment group compared with controls ( P<0.05 ) . In conclusion , B-group vitamin supplementation immediately post-infa rct may have antioxidant and anti-inflammatory effects in stroke disease independent of a homocysteine-lowering effect BACKGROUND Evidence shows that there is a rapid increase in the production of markers of oxidative damage immediately after acute ischemic stroke and that endogenous antioxidant defenses are rapidly depleted , thus permitting further tissue damage . Several studies point to an antioxidant effect of B-group vitamins and a pro-oxidant effect of elevated total plasma homocysteine ( tHcy ) . METHODS To test whether supplementary antioxidants with or without B-group vitamins during this critical period enhance antioxidant capacity or mitigate oxidative damage , ninety-six acute ischemic stroke patients within 12 hours of symptom onset were r and omly assigned to receive either daily oral 800 IU ( 727 mg ) vitamin E and 500 mg vitamin C ( n = 24 ) , or B-group vitamins ( 5 mg folic acid , 5 mg vitamin B(2 ) , 50 mg vitamin B(6 ) , and 0.4 mg of vitamin B(12 ) ; n = 24 ) , both vitamins together ( n = 24 ) , or no supplementation ( n = 24 ) for 14 days . Treatment groups and controls were matched for stroke subtype and age . Blood was obtained before treatment , at day 7 , and day 14 for measurements of plasma or blood vitamin status , plasma total antioxidant capacity ( TAOC ) , malondialdehyde ( MDA ) , tHcy and C-reactive protein ( CRP ) . RESULTS Supplementation with antioxidant vitamins and B-group vitamins separately or together significantly increased the plasma concentration of vitamin C , E , pyridoxal phosphate ( B(6 ) status ) , red blood cell folate , and improved a measure of B(2 ) status ( red cell glutathione reductase activation coefficient [ EGRAC ] ) , compared with the control group . Plasma TAOC increased significantly in the antioxidant treatment groups compared with the nonsignificant decline seen in the control group . tHcy concentrations decreased in subjects who received B-group vitamins and the control group compared with the rise seen in those who received antioxidants alone . There was a significant reduction in plasma MDA concentration in the 3 treatment groups , in contrast to the increase seen in the control group ; however , the changes were most evident in antioxidant groups . CRP concentrations ( a marker of tissue inflammation ) were significantly lower in the 3 treatment groups compared with the control group . There were no additive or synergistic effects of antioxidants and B-group vitamins together on any outcome measure . CONCLUSIONS Antioxidants supplementation with or without B-group vitamins enhances antioxidant capacity , mitigates oxidative damage , and may have an anti-inflammatory effect immediately postinfa rct in stroke disease CONTEXT Recently , concern has been raised about the safety of folic acid , particularly in relation to cancer risk . OBJECTIVE To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 r and omized controlled trials . DESIGN , SETTING , AND PARTICIPANTS Combined analysis and extended follow-up of participants from 2 r and omized , double-blind , placebo-controlled clinical trials ( Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial ) . A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005 , and were followed up through December 31 , 2007 . INTERVENTIONS Oral treatment with folic acid ( 0.8 mg/d ) plus vitamin B(12 ) ( 0.4 mg/d ) and vitamin B(6 ) ( 40 mg/d ) ( n = 1708 ) ; folic acid ( 0.8 mg/d ) plus vitamin B(12 ) ( 0.4 mg/d ) ( n = 1703 ) ; vitamin B(6 ) alone ( 40 mg/d ) ( n = 1705 ) ; or placebo ( n = 1721 ) . MAIN OUTCOME MEASURES Cancer incidence , cancer mortality , and all-cause mortality . RESULTS During study treatment , median serum folate concentration increased more than 6-fold among participants given folic acid . After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up , 341 participants ( 10.0 % ) who received folic acid plus vitamin B(12 ) vs 288 participants ( 8.4 % ) who did not receive such treatment were diagnosed with cancer ( hazard ratio [ HR ] , 1.21 ; 95 % confidence interval [ CI ] , 1.03 - 1.41 ; P = .02 ) . A total of 136 ( 4.0 % ) who received folic acid plus vitamin B(12 ) vs 100 ( 2.9 % ) who did not receive such treatment died from cancer ( HR , 1.38 ; 95 % CI , 1.07 - 1.79 ; P = .01 ) . A total of 548 patients ( 16.1 % ) who received folic acid plus vitamin B(12 ) vs 473 ( 13.8 % ) who did not receive such treatment died from any cause ( HR , 1.18 ; 95 % CI , 1.04 - 1.33 ; P = .01 ) . Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B(12 ) . Vitamin B(6 ) treatment was not associated with any significant effects . CONCLUSION Treatment with folic acid plus vitamin B(12 ) was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway , where there is no folic acid fortification of foods . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00671346 Abstract Purpose . The incidence of adenocarcinoma of the esophagus is increasing in most Western industrialized nations especially in white males . The impact of vitamins on the development of squamous cell carcinoma ( SCC ) and adenocarcinoma ( AC ) of the esophagus has not been eluci date d. The goal of this pilot- study was to analyze the influence of daily vitamin consumption on the frequency of esophageal carcinoma in Germany . Methods . Ninety-nine patients ( males ) with esophageal carcinoma ( 52 with SCC and 47 with AC ) were compared to a control group of 50 r and omly selected males from the Cologne area . Using a computer program to record the data , patients and controls were question ed in detail about their dietary habits . The interaction between known risk factors and the influence of vitamins on esophageal tumor risk were analyzed using logistic regression analysis . Results . The univariate analysis showed a significant risk reduction with increased intake of β-carotene , vitamin C , vitamin E , and folic acid for both AC and for SCC . The results of logistic regression analysis were compatible with the known risk factors for SCC ( alcohol and tobacco ) and for AC ( obesity , tobacco , and alcohol ) and showed a significant risk reduction with an intake of vitamin E greater than 13 mg/day ( RR=0.13 , 95 % CI=0.1–0.5 , P=0.0004 ) and vitamin C greater than 100 mg/day ( RR=0.33 , 95 % CI=0.11–0.92 , P=0.034 ) for patients with SCC and similar results for patients with AC . Conclusion . Our data showed that low intake of vitamin C and E correlates significantly with the development of squamous cell carcinoma as well as adenocarcinoma of the esophagus in males . The relevance of interaction of vitamins with other dietary factors , alcohol , and tobacco are topics of current research Objective This study aims to investigate the risk of esophageal squamous cell carcinoma in relation to exogenous factors in a rural area of China with a high incidence of esophageal squamous cell carcinoma . Methods A population -based case – control study was conducted in Yangzhong County , Jiangsu Province , China , with 355 histologically confirmed esophageal squamous cell carcinoma cases recruited between 1 January 2004 and 28 February 2006 and 408 controls matched by sex and age , r and omly selected from the local population . Results Stratified logistic regression analysis by sex revealed that hot-temperature food items , pork braised in brown sauce and old stocked rice intake could increase the risk of esophageal squamous cell carcinoma with odds ratio of 2.127 ( 95 % confidence interval : 1.394–3.245 ) , 2.059 ( 95 % confidence interval : 1.417–2.993 ) and 9.059 ( 95 % confidence interval : 5.930–13.840 ) , respectively , in men and 3.048 ( 95 % confidence interval : 1.733–5.364 ) , 1.914 ( 95 % confidence interval : 1.159–3.162 ) and 14.532 ( 95 % confidence interval : 7.816–27.019 ) , respectively , in women , whereas diet high in salt and chili , tobacco smoking and alcohol drinking only showed possible risk effects in men with odds ratio 2.338 ( 95 % confidence interval : 1.568–3.485 ) , 3.378 ( 95 % confidence interval : 2.117–5.389 ) , 1.976 ( 95 % confidence interval : 1.337–2.921 ) and 2.197 ( 95 % confidence interval : 1.510–3.195 ) , respectively . Green tea drinking showed a protective effect in women ( odds ratio=0.257 ; 95 % confidence interval : 0.070–0.941 ) . Conclusions Findings from this study provided evidence that dietary habits , tobacco-smoking and alcohol drinking contribute to the etiology of esophageal squamous cell carcinoma . A healthy dietary habit , with smoking cessation and alcohol controlling is of a great importance in the prevention of esophageal cancer Coenzyme Q10 ( CoQ10 ) and vitamin B6 ( pyridoxine ) have been administered together and separately to three groups of human subjects . The blood levels of CoQ10 increased ( p < 0.001 ) when CoQ10 and pyridoxine were administered together and when CoQ10 was given alone . The blood levels of IgG increased when CoQ10 and pyridoxine were administered together ( p < 0.01 ) and when CoQ10 was administered alone ( p < 0.05 ) . The blood levels of T4-lymphocytes increased when CoQ10 and pyridoxine were administered together ( p < 0.01 ) and separately ( p < 0.001 ) . The ratio of T4/T8 lymphocytes increased when CoQ10 and pyridoxine were administered together ( p < 0.001 ) and separately ( p < 0.05 ) . These increases in IgG and T4-lymphocytes with CoQ10 and vitamin B6 are clinical ly important for trials on AIDS , other infectious diseases , and on cancer |
11,894 | 24,820,100 | IPC may increase healing compared with no compression .
It is unclear whether it can be used instead of compression b and ages .
There is some limited evidence that IPC may improve healing when added to compression b and ages . | BACKGROUND Intermittent pneumatic compression ( IPC ) is a mechanical method of delivering compression to swollen limbs that can be used to treat venous leg ulcers and limb swelling due to lymphoedema .
OBJECTIVES To determine whether IPC increases the healing of venous leg ulcers .
To determine the effects of IPC on health related quality of life of venous leg ulcer patients . | Venous ulcers affect up to 1 % of the population . This review provides the hemodynamic , hematologic and clinical effects of intermittent pneumatic compression ( IPC ) in the treatment of venous ulcers . It presents the different IPCs and their application on venous disease . It points out that a large r and omized study on IPC versus st and ard four-layer compression in the treatment of venous ulcers is needed . The cost-effectiveness of IPC in the treatment of venous ulcers should also be assessed BACKGROUND Intermittent pneumatic compression ( IPC ) has been successfully used in the treatment of venous ulcers , although the optimal setting of pressure , inflation and deflation times has not yet been established . The aim of this study was to compare the effect of two different combinations of IPC pump setting s ( rapid vs slow ) in the healing of venous ulcers . MATERIAL / METHODS 104 patients with pure venous ulcers were r and omized to receive either rapid IPC or slow IPC for one hour daily . The primary and secondary end points were the complete healing of the reference ulcer and the change in the area of the ulcer over the six months observational period , respectively . RESULTS Complete healing of the reference ulcer occurred in 45 of the 52 patients treated with rapid IPC , and in 32 of the 52 patients treated with slow IPC . Life table analysis showed that the proportion of ulcers healed at six months was 86 % in the group treated with the fast IPC regimen , compared with 61 % in the group treated with slow IPC ( p=0.003 , log-rank test ) . The mean rate of healing per day in the rapid IPC group was found to be significantly faster compared to the slow IPC group ( 0.09 cm2 vs 0.04 cm2 , p=0.0002 ) . CONCLUSIONS Treatment with rapid IPC healed venous ulcers more rapidly and in more patients than slow IPC . Both IPC treatments were well tolerated and accepted by the patients . These data suggest that the rapid IPC used in this study is more effective than slow IPC in venous ulcer healing OBJECTIVE It has been previously shown that the SCD Response Compression System , by sensing the postcompression refill time of the lower limbs , delivers more compression cycles over time , result ing in as much as a 76 % increase in the total volume of blood expelled per hour . Extended indications for pneumatic compression have necessitated the introduction of portable devices . The aim of our study was to test the hemodynamic effectiveness of a new portable sequential compression system ( the SCD Express ) , which has the ability to detect the individual refill time of the two lower limbs separately . METHODS This was an open , controlled trial with 30 normal volunteers . The new SCD Express was compared with the SCD Response Compression System in the supine and semirecumbent positions . The refilling time sensed by the device was compared with that determined from velocity recordings of the superficial femoral vein using duplex ultrasonography . Baseline and augmented flow velocity and volume flow , including the total volume of blood expelled per hour during compression with the SCD Express , were compared with those produced by the SCD Response compression system in the same volunteers and positions . RESULTS Both devices significantly increased venous flow velocity as much as 2.26 times baseline in supine position and 2.67 times baseline in semirecumbent position ( all P < .001 ) . There was a linear relationship between duplex ultrasonography-derived refill time and the SCD Express-derived refill time in both the supine ( r = 0.39 , P = .03 ) and semirecumbent ( r = 0.71 , P < .001 ) positions but not with the SCD Response . Refill time measured by the SCD Express device was significantly shorter and the cycle rate higher in comparison with the SCD Response in both positions . The single-cycle flow velocity and volume flow parameters generated by the two devices were similar in both positions . However , median ( interquartile range ) total volume of blood expelled per hour was slightly higher with the SCD Express device in the supine position ( 7206 mL/h [ range , 5042 - 8437 ] vs 6712 mL/h [ 4941 - 10,676 ] ; P = .85 ) and semirecumbent position ( 4588 mL/h [ range , 3721 - 6252 ] vs 4262 mL/h [ 3520 - 5831 ] ; P = .22 ) . Peak volume of blood expelled per hour by the SCD Express device in the semirecumbent position was significantly increased by 10 % in comparison with the SCD Response ( P = .03 ) . CONCLUSIONS Flow velocity and volume flow enhancement by the SCD Response and SCD Express were essentially similar . The latter , a portable device with optional battery power that detects the individual refill time of the lower limbs separately , is anticipated to be associated with improved overall compliance and therefore optimized thromboprophylaxis . Studies testing its potential for improved efficacy in preventing deep vein thrombosis are justified Intermittent pneumatic leg compression ( IPC ) increases arterial calf inflow and foot skin blood flux in normal subjects and claudicants . Our hypothesis was that IPC could enhance foot skin blood flux after infrainguinal grafting and thus promote distal perfusion in limbs with tissue loss . The aim of this study was to compare the effects of three IPC modes [ applied to the foot ( IPCfoot ) , the calf ( IPCcalf ) , or both ( IPCfoot+calf ) ] on foot skin perfusion in healthy individuals , claudicants , and patients after infrainguinal arterial revascularization performed for critical or subcritical limb ischemia . Altogether , 20 healthy limbs , 22 claudicating limbs , and 36 limbs of arteriopaths with prior successful autologous femoropopliteal and femorodistal ( 18 each ) grafts were examined . Five-minute laser Doppler recordings were obtained from the pulp of the big toe in the sitting position , at rest , and during r and om applications of IPCfoot , IPCcalf , and IPCfoot+calf delivered at 120 mmHg for 4 seconds three times per minute . Foot skin blood flux increased using all IPC modes ( p < 0.001 ) , with IPCfoot and IPCfoot+calf generating higher flux levels than IPCcalf ( p < 0.01 ) in all groups . Intergroup differences of flux with each of the three IPC modes were not significant . IPCfoot and IPCfoot+calf similarly ( p > 0.14 ) produced a higher percentage flux increase than IPCcalf in all groups ( p < 0.004 ) . Controls had a higher percentage flux increase with both IPCcalf and IPCfoot than did claudicants ( p ≤ 0.016 ) . No differences were documented between normal and grafted limbs ( p > 0.05 ) . The percentage flux increase with IPCfoot+calf and IPCcalf was significantly higher in femorodistal grafts than in femoropopliteal ones ( p ≤ 0.026 ) . IPC enhances skin blood flux in limbs with infrainguinal bypass , claudication , and normal arteries , with IPCfoot and IPCfoot+calf being more effective than IPCcalf . Our findings suggest that IPC may be beneficial in limbs with impaired distal perfusion and thus may have clinical implication s in the treatment of leg ulcers either prior to or after revascularization BACKGROUND The purpose of the present paper was to compare healing rate and leg swelling with an intermittent compression pump versus compression b and ages in the treatment of venous leg ulcers , and to also compare patient compliance and satisfaction with the two techniques . METHODS A r and omized cross-over study of patients attending an outpatient wound clinic ( n = 16 ) was undertaken . A regular monthly follow-up with measurement of ulcer size and leg volume was carried out , as well as completion of a question naire . RESULTS Assessment was possible in 11 of the 16 patients . There was no significant difference between treatment types with regards to ulcer healing rates or control of leg oedema . The survey revealed that patients found the pump easier and more comfortable to use , with a trend towards increased compliance . CONCLUSIONS Although the present study was too small for generalizable conclusions , compression pumps and b and ages are comparable in efficacy for the healing of venous leg ulcers . The compression pump is reported as being easier and more comfortable to use than b and ages OBJECTIVES To test the hypothesis that the SCD EXPRESS intermittent pneumatic compression applied in combination with a four-layer b and age in patients with venous ulcers increases popliteal vein volume flow and velocity . DESIGN Twenty limbs of 18 patients with venous leg ulcers were studied , median age 76 years . The Total Volume Flow ( TVF ) and the Peak Systolic Velocity ( PSV ) were recorded in the popliteal vein using duplex ultrasonography . Measurements were made ( i ) without b and age , ( ii ) with four layer b and age and ( iii ) following the application of the SCD Compression System on top of a four-layer b and age for at least 15 minutes . RESULTS The median VCSS was 17 ( range , 12 - 22 ) while the median VSDS for reflux was 4.5 ( range , 1 - 7.5 ) . The median TVF was 71 mL/min ( inter-quartile range 57 - 101 ) without b and age , 112 ( IQR 89 - 148 ) with four-layer b and age and 291 ( IQR 241 - 392 ) with the addition of the SCD System ( P<.001 , Wilcoxon signed ranks test ) . The median PSV was 8.4 cm/sec ( IQR 6.8 - 14 ) without b and age , 13 ( 9.0 - 19 ) with four-layer b and age and 27 ( 21 - 31 ) with the addition of the SCD System ( P<.001 , Wilcoxon signed ranks test ) . Both TVF and PSV increased slightly with the addition of the four-layer b and age . However , with the addition of the SCD System these parameters increased three fold . CONCLUSIONS The SCD EXPRESS Compression System accelerates venous flow in the legs of patients with venous ulcers already treated with a four-layer b and age . The combination of four-layer compression with the SCD System on healing venous ulcers needs to be tested by a clinical effectiveness study Compression therapy -- including inelastic , elastic , and intermittent pneumatic compression -- is the st and ard of care for venous ulcers ( VLUs ) and chronic venous insufficiency , but there is no consensus in the literature regarding the most effective type of compression therapy . A prospect i ve , r and omized , clinical pilot study was conducted among 70 patients with unilateral VLUs treated in a hospital dermatology department in Pol and to compare three types of compression therapy ( intermittent pneumatic compression , stockings , and short-stretch b and ages ) in persons with superficial deep venous reflux alone or combined with the segmental variety . Study endpoints were change in ulcer dimensions and proportions healed . Patients with superficial or combined superficial and deep vein insufficiency were r and omly allocated to receive one of the three therapies ( one of each vein type for each treatment option , six groups total ) . All patients received saline-soaked gauze dressings along with micronized purified flavonoid fraction , diosmin , hesperidin , and Daflon 500 once daily . Compression treatments were changed or pneumatic compression provided daily for 15 days . Wound size reduction and percentage of wounds healed were significantly higher in groups receiving intermittent pneumatic compression or stockings than in groups using short-stretch b and ages ( for percentage change of ulcer surface area , P = 0.02 ; for healing rates P = 0.01 ) . These results warrant additional r and omized controlled clinical studies with a larger sample size and longer patient follow-up BACKGROUND A number of different treatment approaches have been recommended for the treatment of venous ulceration , including local ulcer treatment , compression and drug therapy . Recent advances in tissue engineering have result ed in living tissues being developed for cutaneous wound repair and skin replacement . The aim of this pilot study was to compare the rate of healing of venous ulcers in patients treated with Dermagraft ( a human fibroblast-derived dermal replacement ) and compression therapy or compression therapy alone . METHODS A total of 18 patients with venous ulceration of the leg were recruited into the pilot study . Ten patients were treated with Dermagraft and compression therapy , and eight patients were treated with compression therapy alone . Healing was assessed by ulcer tracing and computerised planimetry . Skin perfusion was measured by laser Doppler . RESULTS Five ( 50 % ) of the patients treated with Dermagraft and one ( 12.5 % ) control patient had healed by the end of the 12-week study period ( NS ) . The total ulcer area rate of healing and linear rate of healing was significantly improved in patients treated with Dermagraft ( P=0.001 and P=0.006 , respectively , Mann-Whitney U-test ) . The number of capillaries increased in both the treatment and control group . Peri-ulcer skin perfusion increased by 20 % in patients treated with Dermagraft , compared with 4.9 % in the control group . CONCLUSION The data from this small pilot study suggests that Dermagraft is associated with improved healing of venous ulceration . Following this pilot study , further clinical studies are needed to confirm the validity of these results in ' hard to heal ' venous leg ulcers Despite improvements in healing rates venous ulcer disease still carries significant morbidity and cost . Any therapy that further improves healing rates is worthy of consideration . The recognised effects of intermittent pneumatic compression ( IPC ) on both arterial and venous circulation suggest that its use may confer significant benefits to venous ulcer healing . This study investigates the potential additive effects of adjuvant IPC on the healing and subsequent prevention of venous ulcers . Some improvement in the rate of healing in venous ulcers is noted . These findings are set against a background of very high healing rates in both treatment and control groups . No benefit is seen to accrue if IPC is used as an adjuvant therapy to help prevent recurrence of ulcers although the study period is very short This study investigated the reduction in lower limb oedema achieved when different combinations of intermittent pneumatic compression ( IPC ) pump setting s were used . Twenty-seven individuals aged between 22 and 96 years , with ankle oedema of venous origin , were r and omised to either a treatment or control group . Treatment was delivered via a Flowpac pump ( Huntleigh Healthcare Ltd , Luton , UK ) possessing variable controls . The control group were ' treated ' by elevating both lower limbs . The average difference in limb volumes was compared , for each combination of pump setting , to changes in limb volume in the control group . These comparisons revealed that the highest mean reduction in limb volumes was recorded for a pressure of 40 mmHg ( p = 0.02 ) , 10 second deflation time ( p = 0.0002 ) and 15 second inflation time ( p = 0.0096 ) . Other significant results were obtained by the 30 mmHg pressure ( p = 0.017 ) , 35 second deflation time ( p = 0.018 ) , and 5 and 45 second inflation times ( p = 0.012 , 0.013 respectively ) . For many setting combinations no significant differences were observed between the limb oedema seen in the control and experimental groups . The results should be interpreted with caution because of the large number of tests performed . In addition adverse effects were observed in six out of nine subjects at 70 mmHg pressure and this pressure was discontinued . One subject suffered cramp at 60 mmHg pressure . Lower pressures together with shorter inflation and deflation times appear to be more efficient than higher pressures and long inflation/deflation times . In addition the lack of significant reduction in oedema at pressures above 40 mmHg suggests that the higher pressures cause a tourniquet effect Chronic deep venous insufficiency remains a major health problem in the United States and worldwide . Selected patients benefit from direct deep vein valve repair or valve transplantation ; however , most are not c and i date s for these procedures . Experience with the bovine monocusp venous valve surgically inserted into the common femoral vein ( CFV ) demonstrates potential benefit and good long-term patency . A venous valve placed distal to the CFV via percutaneous access has great appeal and potential for further improving venous hemodynamics , as well as reducing ambulatory venous hypertension and ulceration . Two patients were treated with a percutaneous venous valve bioprosthesis as part of a Phase I trial . The primary objective was to evaluate the safety , patency , and efficacy of the percutaneous venous valve bioprosthesis to restore competency to the deep venous system . OBJECTIVE Intermittent pneumatic compression ( IPC ) devices prevent lower-extremity deep venous thrombosis ( LEDVT ) when used properly , but compliance remains an issue . Devices are frequently discontinued when patients are out of bed , and they are rarely used in emergency departments . Trauma patients are at high risk for LEDVT ; however , IPCs are underused in this population because of compliance limitations . The hypothesis of this study was that a new miniaturized , portable , battery-powered pneumatic compression device improves compliance in trauma patients over that provided by a st and ard device . METHODS This was a prospect i ve trial in which trauma patients ( mean age , 46 years ; revised trauma score , 11.7 ) were r and omized to DVT prophylaxis with a st and ard calf-length sequential IPC device ( SCD group ) or a miniaturized sequential device ( continuous enhanced-circulation therapy [ CECT ] group ) . The CECT device can be battery-operated for up to 6 hours and worn during ambulation . Timers attached to the devices , which recorded the time each device was applied to the legs and functioning , were used to quantify compliance . For each subject in each location during hospitalization , compliance rates were determined by dividing the number of minutes the device was functioning by the total minutes in that location . Compliance rates for all subjects were averaged in each location : emergency department , operating room , intensive care unit , and nursing ward . RESULTS Total compliance rate in the CECT group was significantly higher than in the SCD group ( 77.7 % vs. 58.9 % , P = .004 ) . Compliance in the emergency department and nursing ward were also significantly greater with the CECT device ( P = .002 and P = .008 respectively ) . CONCLUSIONS Previous studies have demonstrated that reduced compliance with IPC devices results in a higher incidence of LEDVT . Given its ability to improve compliance , the CECT may provide superior DVT prevention compared with that provided by st and ard devices Question : In patients who have diabetes mellitus and edema with foot ulcers requiring debridement , how effective is intermittent pneumatic foot compression after debridement in promoting wound-healing ? Design : R and omized , double-blind , placebo-controlled trial with 12-week follow-up . Setting : University hospital and clinics in San Antonio , Texas , USA . Patients : 115 patients who had diabetes mellitus and foot infections requiring incision and debridement . Patients were excluded if they had active congestive heart failure , end-stage The treatment of venous ulcers has remained largely unchanged for centuries . The application of properly applied graduated compression b and ages , the use of graduated compression stockings , and surgery have been shown to achieve healing . However , some ulcers persist despite appropriate management . A r and omized study was undertaken to compare two regimens of treatment for such patients . Both regimens included ulcer debridement , cleaning , nonadherent dressing , and graduated compression stockings . In one regimen , sequential gradient intermittent pneumatic compression was applied for 4 hours each day . Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group . The median rate of ulcer healing in the control group was 2.1 % area per week compared to 19.8 % area per week in the intermittent pneumatic compression group . The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers |
11,895 | 22,336,793 | Based on the results of this systematic review the administration of antibiotic prophylaxis for elective inguinal hernia repair can not be universally recommended .
Neither can the administration be recommended against when high rates of wound infection are observed | BACKGROUND The use of antibiotic prophylaxis for hernia repair is currently a controversial issue given the disparity among study results in this area .
OBJECTIVES The objective of this systematic review was to clarify the effectiveness of antibiotic prophylaxis in reducing postoperative wound infection rates in elective open inguinal hernia repair . | The European Hernia Society ( EHS ) is proud to present the EHS Guidelines for the Treatment of Inguinal Hernia in Adult Patients . The Guidelines contain recommendations for the treatment of inguinal hernia from diagnosis till aftercare . They have been developed by a Working Group consisting of expert surgeons with representatives of 14 country members of the EHS . They are evidence -based and , when necessary , a consensus was reached among all members . The Guidelines have been review ed by a Steering Committee . Before finalisation , feedback from different national hernia societies was obtained . The Appraisal of Guidelines for REsearch and Evaluation ( AGREE ) instrument was used by the Cochrane Association to vali date the Guidelines . The Guidelines can be used to adjust local protocol s , for training purpose s and quality control . They will be revised in 2012 in order to keep them up date d. In between revisions , it is the intention of the Working Group to provide every year , during the EHS annual congress , a short up date of new high-level evidence ( r and omised controlled trials [ RCTs ] and meta-analyses ) . Developing guidelines leads to questions that remain to be answered by specific research . Therefore , we provide recommendations for further research that can be performed to raise the level of evidence concerning certain aspects of inguinal hernia treatment . In addition , a short summary , specifically for the general practitioner , is given . In order to increase the practical use of the Guidelines by consultants and residents , more details on the most important surgical techniques , local infiltration anaesthesia and a patient information sheet is provided . The most important challenge now will be the implementation of the Guidelines in daily surgical practice . This remains an important task for the EHS . The establishment of an EHS school for teaching inguinal hernia repair surgical techniques , including tips and tricks from experts to overcome the learning curve ( especially in endoscopic repair ) , will be the next step . Working together on this project was a great learning experience , and it was worthwhile and fun . Cultural differences between members were easily overcome by educating each other , respecting different views and always coming back to the principles of evidence -based medicine . The members of the Working Group would like to thank the EHS board for their support and especially Ethicon for sponsoring the many meetings that were needed to finalise such an ambitious project A prospect i ve study was carried out to determine the incidence of wound infection following surgery for inguinal hernia repair in a day surgery unit . The study incorporated surveillance for 1 month postoperatively . All patients were contacted by telephone , and reports of possible wound infection investigated via their General Practitioners . Ninety-seven patients were included in the study and the infection rate was 4 % A blinded r and omized clinical trial was undertaken to evaluate the effect of applying ointment to a wound before occlusive dressing , in comparison with no ointment or sterile paraffin Two hundred patients in a major Indian hospital who were undergoing clean operations participated in a prospect i ve , r and omised , controlled clinical trial of the effectiveness of systemic antibiotics in preventing wound infectious . Of the patients on antibiotics 12.6 % developed wound infections and of those not on antibiotics 13.3 % did -- a difference of no significance . Other factors analysed which included age , duration of operation , place on the operating list and length of the incision did not appear to effect the incidence of infection . Wound infection delayed the discharge of the patient from hospital by seven days . Avoiding antibiotic prophylaxis in these operations would have saved our hospital 12,500 pounds a year . We suggest that prophylactic antibiotics are ineffective in preventing wound infection after clean operations in India . Their use is wasteful and should be discouraged In a series of 762 general surgical wounds 376 were selected at r and om to receive three parenteral doses of cephaloridine and 386 remained as untreated controls . In all types of operation , with the exception of wounds in the lower extremities associated with arterial surgery , the rate of wound infection was lowered by the prophylactic use of cephaloridine . The results were statistically significant for total wounds , clean wounds , total contaminated wounds , and contaminated wounds other than in colorectal surgery . We therefore recommend the routine use of three doses of cephaloridine In a r and omised controlled prospect i ve trial , different antibiotic regimens were evaluated as prophylaxis in wound infection following elective surgical procedures . Four hundred and four consecutive cases were divided in four groups . Two groups were allotted two different conventional postoperative antibiotic regimens while the fourth group received short term perioperative antibiotic ; group one served as control . A higher frequency of postoperative wound infection was observed in the controls . Results showed reduction in gross infection in only group III where short term perioperative antibiotic was used . Combination of penicillin and streptomycin were not found effective , and low infection rate was observed with Cephamendole used perioperatively Abstract . Antibiotic prophylaxis is not routinely given for nonimplant , clean operations , although this view has recently been challenged . We have conducted a r and omized multicenter , double-blind prospect i ve trial to compare co-amoxiclav with placebo in 619 patients undergoing open groin hernia repair . Altogether 563 ( 91 % ) patients fulfilled the protocol ; 283 received co-amoxiclav and 280 placebo . There was no difference between the groups in the number of patients receiving local or general anesthetic , the type of repair performed , the use of a subcutaneous fat suture , the type of skin closure used , the use of wound analgesia , or the use of a wound drain . Patients were given a card to return to the hospital in the event of their wound discharging or their needing to see their general practitioner . All patients were review ed at approximately 6 weeks after operation . Fifty ( 8.9 % ) patients sustained a wound infection , 25 in the co-amoxiclav group and 25 in the placebo group . We conclude that antibiotic prophylaxis is of no benefit to patients undergoing open groin hernia repair Objective To assess the value of single-dose , intravenous , prophylactic ampicillin and sulbactam ( AS ) in the prevention of wound infections during open prosthetic inguinal hernia repair by a double-blind , prospect i ve , r and omized trial . Summary Background Data The use of antibiotic prophylaxis during open prosthetic inguinal hernia surgery is controversial , and no prospect i ve trial has been conducted to examine this issue . Methods Patients undergoing unilateral , primary inguinal hernia repair electively with the Lichtenstein technique using polypropylene mesh were r and omized to receive 1.5 g intravenous AS before the incision or an equal volume of placebo according to a predetermined code of which the surgeons were unaware . Patients with recurrent , femoral , bilateral , giant , or incarcerated hernias or any systemic diseases were excluded . Age , sex , body mass index , American Society of Anesthesiologists score , type of hernia , type of anesthesia , duration of surgery , and use of drains were recorded . Infection was defined according to the criteria of Centers for Disease Control . Patients were evaluated 1 week , 1 month , 6 months , and 1 year after surgery by an independent surgeon . All complications were recorded . Results were assessed using chi-square , Fisher ’s exact , and Student t tests as appropriate . Results Between September 1996 and July 1998 , 280 patients ( 140 AS , 140 placebo group ) entered the protocol . Four patients from the AS group and seven from the placebo group were excluded because of inadvertent antibiotic administration or follow-up problems . Groups were well matched for all the variables studied and postoperative complications , excluding wound infections , which occurred at a rate of 0.7 % in the AS group and 9 % in the placebo group ( P = .00153 ) . Twelve patients in the placebo group developed wound infections , requiring five repeat hospital admissions in three patients . These three patients suffered deep infections reaching the graft , which result ed in graft loss in two . The single infected patient in the AS group had his graft removed as well because of deep persistent infection . Conclusions This study documented a significant ( 10-fold ) decrease in overall wound infections when single-dose , intravenous AS was used during Lichtenstein hernia repair . Deep infections and wound infection-related readmissions were also reduced by the use of AS . Proponents of mesh repairs may therefore be advised to use prophylactic single-dose intravenous antibiotic coverage in the light of the results of this trial . AS proved to be an effective antimicrobial agent BACKGROUND Prophylactic antibiotics are recommended for clean-contaminated and selected contaminated surgery . In clean surgery antibiotics are suggested if the operation involves the insertion of prosthetic devices and a potential infection is expected to cause serious morbidity or mortality . Inguinal hernia repair is a clean operation , infections are rare ; they can usually be cured without removing the prosthesis and recurrence is uncommon even after removal of the mesh . Aim of the study is to evaluate whether the lack of antimicrobial prophylaxis increases the risk of postoperative infections in patients treated for groin hernia , compared to those treated with prophylaxis . METHODS One hundred and forty-eight patients underwent inguinal hernia repair with mesh : 64 patients ( 43 % ) received 2 g cefotaxime by intravenous bolus about 30 minutes before the operation , 84 patients ( 57 % ) did not receive any antimicrobic prophylaxis . Mean follow-up was 13 months ( range 1 - 31 months ) for both groups . RESULTS We did not observe any major complication . Among both groups , no patient had developed infection at one week and one month after surgery . CONCLUSIONS In personal experience , any advantage in terms of prevention of infections with antibiotic prophylaxis in patients operated on for groin hernia has been observed . A review of the literature showed no general agreement on this subject with different risk of infections in different trials . A new prospect i ve r and omized trial is necessary to clarify this topic A study was made of the risk factors causing a high incidence of surgical wound infections in clean operations . Identification of these factors in the preoperative stage allows the patients to be divided into two categories : a high risk ( about 10 % of patients for surgery ) and low risk . By giving antibiotic prophylaxis only to patients at high risk , the incidence of postoperative infections can be reduced , decreasing the number of extra days in hospital and consequently lowering costs . This is a new approach to the problem of surgical wound infections since not only is it based on the usual classification of operations into clean , clean-contaminated , contaminated and dirty , but it also takes into account the defensive capacity of the target of the infection : the patient Mesh prosthesis , local anesthesia , and ambulatory care have been widely introduced in recent decades in the treatment of inguinal hernia . The use of antibiotic prophylaxis during open inguinal hernia repair has been controversial . No prospect i ve trial has been conducted to assess the role of antibiotic prophylaxis in patients operated on for inguinal hernia under the above-mentioned conditions . A prospect i ve , r and omized , double-blinded trial was initiated to assess the efficacy of antibiotic prophylaxis in the prevention of wound infection during open mesh inguinal hernia repair under local anesthesia on an ambulatory basis . Ninety-nine consecutive hernia repairs were r and omized to receive 1 g of parenteral Cefazolin preoperatively or a placebo . No wound infections existed in the therapeutic group ( 0/50 ) . Four infections appeared in the control group ( 4/49 ) , and the study was suspended for ethical reasons when differences reached values close to statistical significance ( P=0.059 ) . We conclude that a single dose of intravenous Cefazolin decreases the risk of wound infection during open mesh inguinal hernia repair under local anesthesia on an ambulatory basis Objective : To determine whether the use of prophylactic antibiotics is effective in the prevention of postoperative wound infection after Lichtenstein open mesh inguinal hernia repair . Summary Background Data : A recent Cochrane meta- analysis ( 2003 ) concluded that “ antibiotic prophylaxis for elective inguinal hernia repair can not be firmly recommended or discarded . ” Methods : Patients with a primary inguinal hernia scheduled for Lichtenstein repair were r and omized to a preoperative single dose of 1.5 g intravenous cephalosporin or a placebo . Patients with recurrent hernias , immunosuppressive diseases , or allergies for the given antibiotic were excluded . Infection was defined using the Centers for Disease Control and Prevention criteria . Results : We included 1040 patients in the study between November 1998 and May 2003 . According to the intention-to-treat principle , 1008 patients were analyzed . There were 8 infections ( 1.6 % ) in the antibiotic prophylaxis group and 9 ( 1.8 % ) in the placebo group ( P = 0.82 ) . There was 1 deep infection in the antibiotic prophylaxis group and 2 in the placebo group ( P = 0.57 ) . Statistical analysis showed an absolute risk reduction of 0.19 % ( 95 % confidence interval , −1.78%–1.40 % ) and a number needed to treat of 520 for the total number of infections . For deep infection , the absolute risk reduction is 0.20 % ( 95 % confidence interval , −0.87%–0.48 % ) with a number needed to treat of 508 . Conclusions : A low percentage ( 1.7 % ) of wound infection after Lichtenstein open mesh inguinal ( primary ) hernia repair was found , and there was no difference between the antibiotic prophylaxis or placebo group . The results show that , in Lichtenstein inguinal primary hernia repair , antibiotic prophylaxis is not indicated in low-risk patients Abstract Although antibiotic prophylaxis is not explicitly indicated for hernia repair and breast surgery , its use for these clean procedures is widely adopted , albeit to a different extent in different countries , often on the personal decision of the individual surgeon . The present study was carried out to compare the efficacy of a single pre-operative dose of piperacillin-tazobactam with placebo in preventing surgical wound infections and to determine the main risk factors associated with infections following two main elective surgical clean procedures such as hernia repair and breast surgery . A total of 501 patients undergoing elective inguinal/femoral hernia repair or breast surgery were enrolled in this prospect i ve r and omized clinical study . Patients were r and omly assigned to receive preoperative antibiotic prophylaxis or placebo . One dose of piperacillin-tazobactam 2.250 g or placebo was administered i.v . 30 minutes prior to the surgical procedure . Using statistical univariate analysis , the following variables were correlated with a higher infection risk : age > 40 years , concomitant disease , WBC < 3500 , surgical wound size > 9 cm , use of drainages , non-prophylaxis . Using multivariate analysis , no antibiotic pre-operative prophylaxis , concurrent chronic diseases , especially diabetes ( risk 15 times higher ) , and length of intervention > 45 min ( risk 6 times higher ) were independent predictors of infection . Finally , patients with postoperative infections had a significantly longer hospitalisation . One pre-operative dose of piperacillin-tazobactam 2.250 g is more effective than placebo in preventing postoperative infections in breast surgery and hernia repair Hernia repair is one of the so-called clean operations . Many surgeons , however , use antibiotics , especially in the mesh repair era , without strong evidence to support this policy . We conducted a single-centre prospect i ve r and omised trial with a view to clarify this issue on a scientific basis . From January 2000 all patients undergoing elective inguinal hernia repair using a tension-free polypropylene mesh technique , provided they fulfilled predetermined criteria , were r and omised to have a single dose of amoxicillin and clavoulanic acid or placebo in a double-blind manner . The main end point was to detect any difference in infectious complication rates - with specific interest to wound infection rates - between the two groups . Between January 2000 and June 2004 , 386 patients entered the study ( 364 men and 22 women , median age 63 years , range 15 - 90 years ) and were r and omised to have antibiotic prophylaxis ( group A , n = 193 ) or placebo ( group B , n = 193 ) . The two groups were comparable regarding demographic data . In total , 19 ( 5 % ) cases with infectious complications were detected . Fourteen of these were wound infections ( 3.7 % ) . There were five cases of wound infection in group A and nine in group B ( p = 0.4 , Fisher 's exact test ) . All wound infections were treated with antibiotics . The wound was opened in some cases . Mesh removal was not required in any of the cases . From the results of this study it does not appear that antibiotic prophylaxis offers any benefits in the elective mesh inguinal hernia repair Because wound infection is a major cause of incisional hernia , the question posed is whether or not repairs of incisional hernias are at a higher risk for wound infection also . To answer this , we analyzed the incidence of wound infection after repair of incisional hernias during a 30 month period and compared it with the infection rate in all other clean procedures performed during the same period . All repairs of incisional hernias were performed upon patients with completely healed incisions without clinical signs of infection . Patients undergoing concomitant procedures upon the gastrointestinal tract were excluded . During the 30 month period , 995 clean operations were performed . In the 80 repairs of incisional hernias , there were 13 infections proved by culture , yielding an over-all infection rate of 16 per cent . In the remaining 915 clean procedures , there were 14 wound infections ( 1.5 per cent , p less than 0.0001 ) . Of these 915 clean operations , 241 were repairs of inguinal hernias . Two infections occurred in this subgroup ( 0.8 per cent , p less than 0.0001 , compared with repairs of incisional hernias ) . In patients undergoing repairs of incisional hernias with previously documented wound infections , 41 per cent had infected repairs . By comparison , only 12 per cent of patients without a prior infection had infections develop in the hernial repair ( p less than 0.05 ) . The infection rate for patients not receiving prophylactic antibiotics ( 21 per cent ) was almost twice the rate for those receiving antibiotics ( 11 per cent ) , p = 0.07 . We concluded that repair of incisional hernias has a significantly higher rate of infection than do other clean general surgical procedures . Herniorrhaphy of a wound that was previously infected is at a higher risk for reinfection , despite complete healing of the skin and absence of clinical signs of infection . Perioperative antibiotic prophylaxis may be indicated , but r and omized studies are needed . For reporting and surveillance purpose s , repairs of incisional hernias should not be classified as clean surgical procedures In a district rural hospital in Ug and a , 850 surgical patients were evaluated prospect ively over a 3‐year period to compare the clinical efficacy of conventional postoperative penicillin therapy with single‐dose ampicillin prophylaxis for hernia repair and ectopic pregnancy , and with single‐dose ampicillin‐metronidazole prophylaxis for hysterectomy and caesarean section . The high rate of postoperative infection usually encountered in African hospitals after conventional treatment with penicillin for 7 days was significantly reduced with the new regimen : from 7·5 to 0 per cent in hernia repair and from 10·7 to 2·4 per cent in ectopic pregnancy ; from 20·0 to 3·4 per cent in hysterectomy and from 38·2 to 15·2 per cent in caesarean section . Length of hospital stay and postoperative mortality rates were also significantly reduced . Single‐dose ampicillin prophylaxis with or without metronidazole , although rarely used in developing countries , is more cost effective than st and ard penicillin treatment A question naire survey was sent to a r and om sample of the Spanish network of National Health System public acute-care hospitals . Of responding institutions ( representing 25 % of Spanish hospital beds ) , nearly 75 % had active surveillance programs for the prevention and control of surgical-site infections ( SSIs ) , but only 20 % performed postdischarge surveillance . Overall , perioperative antibiotic prophylaxis ( PAP ) was used in 84 % of all surgical procedures . For 77 % of procedures , there were written guidelines for the choice and use of PAP . Cefazolin was the most commonly used antibiotic ( 38 % ) . Duration of PAP was shorter than 24 hours in 75 % of procedures , and only a single dose was given in 52 % of procedures . PAP was commonly used in breast ( 52 % ) and inguinal hernia repair ( 69 % ) procedures , as well as in laparoscopic abdominal surgery ( 86 % ) . In summary , the use of PAP in Spanish hospitals is adequate , but improvements can be made in the frequency of prolonged PAP and in the use of broad-spectrum antibiotics . Surveillance systems for SSI , including postdischarge follow-up , also should be improved We compared the effects of single dose ( 750 milligrams ) prophylactic cefam and ole delivered directly into the operative wound with local anesthesia ( n = 162 ) with a control group ( no antibiotics ) ( n = 162 ) in a r and omized trial . No adverse effects were observed . There were seven wound abscesses in the untreated group compared with none in the group receiving antibiotic prophylaxis ( p = 0.007 ) . Six of the seven abscesses occurred as late as one month after the patient was discharged from the hospital . The costs of antibiotics used were ten times less than the costs of treatment of wound complications in the control group Purpose In this double-blind prospect i ve r and omized trial , our objective was to investigate the effect of antibiotic prophylaxis in patients undergoing elective inguinal hernia surgery with mesh repair in a large-volume tertiary referral trauma center . Methods Eligible patients were assigned r and omly to either an antibiotic prophylaxis group or a control group . Patients in the prophylaxis group were given 1 g cefazolin by IV bolus injection whereas the placebo control group received an equal volume of sterile saline preoperatively . A Lichtenstein repair was done in all cases . The patients were examined for surgical site infection ( SSI ) and other postoperative local complications before discharge , and reexamined 3 , 5 , 7 , and 30 days after discharge . Results Groups were well matched for age , sex , coexisting diseases , ASA scores , type of hernia , type of anesthesia , duration of surgery . Incidence of infection was 7 % in the control group ( 7/100 ) and 5 % in the prophylaxis group ( 5/100 ) ( P = 0.38 ) . All the infections were superficial and responded well to drainage and proper antibiotic therapy . All other postoperative complications were similar in the two groups . Conclusions In our setting s antibiotic prophylaxis has no significant effect on the incidence of SSI in elective repair of inguinal hernias with mesh . The most effective way to reduce the incidence of infection in prosthetic repair may be a specific center for treatment of abdominal wall hernias The effect of dry powder povidone-iodine ( Disadine D.P. ) on wound healing was assessed experimentally and clinical ly . It did not interfere with wound healing macroscopically , histologically or mechanically in Wistar rats . One hundred and one patients undergoing ' clean ' elective surgery were included in the controlled clinical study and povidone-iodine did not affect wound healing in any way . In the control group 4 % of patients developed infection compared with none of those sprayed with povidone-iodine . No adverse reaction to povidone-iodine was seen in either study . This antiseptic offers a safe alternative to antibiotics for use at operation whenever there is risk of wound infection from operative bacterial contamination In an ongoing prospect i ve study of clean surgical procedures , patients have been examined by specialist research nurses on a minimum of three occasions during the postoperative period to determine the incidence of wound complications . Whereas a previous retrospective audit suggested a wound infection rate of 2 % , this community surveillance programme revealed the true rate as at least fourfold greater ( p less than 0.001 ) . Of these complications , more than 70 % were detected only by the surveillance programme . Immediate benefit was obtained by a reduction in all complications . Despite these improvements , a core of postoperative sepsis remained , particularly in high-risk cases . Thus , a prospect i ve , controlled , prophylactic antibiotic trial has been undertaken , in an attempt to reduce the infection rate still further . An antibiotic regimen of teicoplanin , 400 mg i.v . , given as a single dose , was chosen because of the excellent activity of this agent against staphylococci and streptococci , and also because of the long half-life which renders it suitable for single-dose administration We assessed the efficacy of perioperative antibiotic prophylaxis for surgery in a r and omized , double-blind trial of 1218 patients undergoing herniorrhaphy or surgery involving the breast , including excision of a breast mass , mastectomy , reduction mammoplasty , and axillary-node dissection . The prophylactic regimen was a single dose of cefonicid ( 1 g intravenously ) administered approximately half an hour before surgery . The patients were followed up for four to six weeks after surgery . Blinding was maintained until the last patient completed the follow-up and all diagnoses of infection had been made . The patients who received prophylaxis had 48 percent fewer probable or definite infections than those who did not ( Mantel-Haenszel risk ratio , 0.52 ; 95 percent confidence interval , 0.32 to 0.84 ; P = 0.01 ) . For patients undergoing a procedure involving the breast , infection occurred in 6.6 percent of the cefonicid recipients ( 20 of 303 ) and 12.2 percent of the placebo recipients ( 37 of 303 ) ; for those undergoing herniorrhaphy , infection occurred in 2.3 percent of the cefonicid recipients ( 7 of 301 ) and 4.2 percent of the placebo recipients ( 13 of 311 ) . There were comparable reductions in the numbers of definite wound infections ( Mantel-Haenszel risk ratio , 0.49 ) , wounds that drained pus ( risk ratio , 0.43 ) , Staphylococcus aureus wound isolates ( risk ratio , 0.49 ) , and urinary tract infections ( risk ratio , 0.40 ) . There were also comparable reductions in the need for postoperative antibiotic therapy , non-routine visits to a physician for problems involving wound healing , incision and drainage procedures , and readmission because of problems with wound healing . We conclude that perioperative antibiotic prophylaxis with cefonicid is useful for herniorrhaphy and certain types of breast surgery Objectives Assessment of the usefulness of antibiotic prophylaxis in inguinal hernioplasty . Material s and methods This prospect i ve r and omized double blind study was conducted on 98 patients . Group A ( 50 patients ) received a single dose of intravenous amoxicillin and clavulanic acid , and Group P ( 48 patients ) received an equal volume of normal saline placebo by intravenous bolus 30 min before the induction of anesthesia . Hernioplasty was performed with polypropylene mesh . Skin was closed using skin staples that were removed after complete wound healing . The surgical site infection was diagnosed according to APIC , CDC criteria ( http://www.apic.org ) . Results The mean operative time was 38.8 ± 10.8 min in group A versus 40.9 ± 11.1 min in group P ( P = 0.34 ) . The mean hospitalization time was 1.3 ± 0.463 days in group A versus 1.25 ± 0.438 days in group P ( P = 0.58 ) . Four patients ( 2 % ) in group A and 6 patients ( 2.88 % ) in group P had wound infections ( P = 0.47 ) . Group A had 3 superficial infections and 1 deep infection while group P had 5 superficial infections and 1 deep infection . Antibiotic treatment of the wound infection was successful in all patients . Wound culture showed Staphylococcus aureus infection in 1 patient each group , Streptococcus pyogenes in 1 group A patient and Pseudomonas aeruginosa in 1 group P patient . Cultures in other patients in both groups were reported to be sterile . Conclusion Prophylactic antibiotic usage in patients undergoing tension free inguinal hernioplasty did not show any statistically significant beneficial effects in reduction of surgical site infection BACKGROUND The incidence of surgical site infection ( SSI ) after clean surgical procedure has traditionally been regarded as too low for routine antibiotic prophylaxis . But we now know that host factors may increase the risk of SSI to as high as 20 % . We assessed the value of prophylactic cefotaxime in patients stratified for risk of SSI in a r and omized double-blind trial . METHODS Patients admitted for clean elective operations were enrolled , stratified for risk by National Nosocomial Infection Survey criteria , and r and omized to receive intravenous cefotaxime 2 gm or placebo on call for operation . They were followed for 4 to 6 weeks for SSI diagnosed by Centers for Disease Control and Prevention criteria . RESULTS Analysis of 775 patients showed that the 378 evaluable patients who received cefotaxime had 70 % fewer SSI than those who did not -- Mantel-Haenszel risk ratio ( MH-RR ) 0.31 ; 95 % confidence intervals ( CI ) 0.11 to 0.83 . Benefit was clear in the 616 low risk patients --0.97 % versus 3.9 % SSI ( MH-RR 0.25 , CI 0.07 to 0.87 , p = 0.018 ) , but only a trend was seen in 136 high risk patients --2.8 % versus 6.1 % SSI ( MH-RR 0.48 , CI 0.09 to 2.5 ) . CONCLUSIONS The results indicate clear benefit for routine antibiotic prophylaxis in clean surgical procedures . High risk patients need more study A clinical trial can not be adequately interpreted without information about the methods used in the design of the study and the analysis of the results . To determine the frequency of reporting what we consider 11 important aspects of design and analysis , we surveyed all 67 clinical trials published in the New Engl and Journal of Medicine , the Lancet , and the British Medical Journal from July through December 1979 and in the Journal of the American Medical Association from July 1979 through June 1980 . Of all 11 items in the 67 trials published in all four journals , 56 per cent were clearly reported , 10 per cent were ambiguously mentioned , and 34 per cent were not reported at all . At least 80 per cent of the 67 trials reported information about statistical analyses , statistical methods used , and r and om allocation of subjects , yet only 19 per cent reported the method of r and omization . Loss to follow-up was discussed in 79 per cent of the articles , treatment complications in 64 per cent , and admission of subjects before allocation in 57 per cent , but eligibility criteria for admission to the trial appeared in only 37 per cent . Although information about whether patients were blind to treatment was given in 55 per cent , information about whether there was blind assessment of outcome was reported in only 30 per cent . The statistical power of the trial to detect treatment effects was discussed in only 12 per cent of the articles . The clinical trials published in The New Engl and Journal of Medicine reported 71 per cent of the 11 items , those in the Journal of the American Medical Association 63 per cent , those in the British Medical Journal 52 per cent , and those in the Lancet 46 per cent . These rates are significantly different ( P less than 0.001 ) . We recommend that editors improve the reporting of clinical trials by giving authors a list of the important items to be reported The aim of this study was to compare the efficacy of single-dose intravenous cefazolin prophylaxis with single-dose oral ciprofloxacin prophylaxis in patients undergoing tension-free inguinal hernia repair with polypropylene mesh . In a prospect i ve and r and omized setting , 395 patients received either a single dose of 500 mg of ciprofloxacin orally , 1 - -2h before the operation , or a single dose of 1 g cefazolin intravenously on induction of anaesthesia . The primary outcome was to determine the wound infection rate within one year . The overall infection among the entire study population was 2 % ( eight of 395 ) including 2 % ( four of 199 ) of those receiving intravenous cefazolin and 2 % ( four of 196 ) of those treated with oral ciprofloxacin . There was no statistically significant difference between groups ( P=0.59 ) . All the infections were superficial incisional surgical site infections , and none progressed to a deep infection . Escherichia coli was the most commonly isolated bacterium . None of the infected patients developed recurrence of hernia . The rate of recurrence was 1.3 % ( five of 395 ) at one year including 2 % ( four of 199 ) of those receiving cefazolin and 0.5 % ( one of 196 ) of those receiving ciprofloxacin . Oral ciprofloxacin prophylaxis was found to be an attractive option with its wide antibacterial spectrum , low cost and ease of administration in patients undergoing tension-free inguinal hernia repair with polypropylene mesh Safety and efficacy were evaluated and compared retrospectively in 77 patients who received cefotetan ( CTN ) and 51 patients who received cefoxitin ( CFX ) for surgical prophylaxis . Both groups were similar with respect to age and gender . Surgical procedures were similar between groups ( e.g. , obstetric/gynecologic , renal transplant , colon , exploratory laparotomy , gastroduodenal , hernia repair ) . Postoperative infectious complications were more common in the CTN group ( 11.6 percent [ 9/77 ] ) than in the CFX ( 7.8 percent [ 4/51 ] ) group ; however , this difference was not statistically significant . A higher incidence of wound infections was noted in the CTN group ( 5.2 percent [ 4/77 ] ) than in the CFX group ( 2.0 percent [ 1/51 ] ) ; this difference was also not significant . Patients receiving immunosuppressive therapy were more likely to develop infectious complications when CTN was used for prophylaxis ( p = 0.0001 ) . Clinical ly significant blood loss was not noted during surgery . Elevations in prothrombin times ( > 1 sec ) occurred in 27.3 percent ( 3/11 ) of CTN and 11.1 percent ( 1/9 ) of CFX patients ( not significant ) . Except for the small subset of patients receiving concomitant immunosuppressive therapy , CTN appeared to be as safe and effective as CFX when used for surgical prophylaxis . Although not statistically significant , the increased incidence of wound infections in the CTN-treated patients requires further study in a prospect i ve r and omized comparison BACKGROUND In recent years , use of prosthetic material for inguinal hernia repair has increased dramatically . Tension-free repairs have gained popularity not only for recurrent or complicated hernias , but for primary hernia repairs as well . Although routine use of prophylactic antibiotics is not recommended in the Philippines for open nonimplant herniorrhaphy , there is little direct clinical evidence on which to base recommendations when implantable mesh is used . STUDY DESIGN We conducted a prospect i ve , r and omized , double-blind , placebo-controlled trial comparing wound infection rates in 360 patients ( 180 received prophylactic antibiotics , 180 received a placebo ) undergoing primary inguinal hernia repair electively using polypropylene mesh . Age , gender , American Society of Anesthesiologists class , type of hernia , type of anesthesia , and duration of operation were recorded . Infections were evaluated 1 week , 2 weeks , and 1 month after operation by an independent surgeon . All complications were recorded . Results were assessed using chi-square , Fisher 's exact test , and Student 's t-tests as appropriate . RESULTS Groups were well matched for all preoperative variables studied , including comorbid conditions . Six patients from the antibiotic group and four from the placebo group failed to followup after the second week . Superficial surgical site infection developed in 3 patients ( 1.7 % ) from the antibiotic group and 6 ( 3.3 % ) from the placebo group ( p = 0.50 ) . One from each group developed deep surgical site infection . Both patients were readmitted and underwent repeated debridement , which eventually result ed in graft loss . CONCLUSIONS Preoperative administration of single-dose antibiotic for tension-free inguinal mesh herniorrhaphy did not markedly decrease risk of wound infection in this patient population . Our results do not support use of antibiotic prophylaxis for tension-free mesh herniorrhaphy OBJECTIVE --To assess the effect of a programme of postoperative community surveillance on the rate of detection of wound complications after operation for inguinal hernia . DESIGN -- Prospect i ve audit of wound complications including complications recorded in case notes and those discovered by community surveillance . SETTING --Academic surgical unit of three consultant surgeons . PATIENTS --510 patients undergoing elective inguinal hernia repair between June 1985 and August 1989 . RESULTS --The wound infection rate recorded in the hospital notes was 3 % compared with 9 % when additional information was obtained from community surveillance . Wound complications were detected in 143 ( 28 % ) patients by community surveillance compared with a complication rate of 7 % in the case records for the same patients . CONCLUSIONS --Wound complications are common after clean surgery in patients discharged home early . Complication rates are a reflection not only of the st and ards of surgical practice but also the rigour with which they are sought . Before national comparative audit data are published the method of collection must be st and ardised . For short stay surgery this should include meaningful community surveillance The authors report a controlled series of 40 patients treated for recidivating inguinal hernia and laparocele with the implant of alloplastic material . Short-term prophylaxis with vancomycin was performed in all cases . The antibiotic was found to be well tolerated at the doses used and this was associated with a good clinical success rate . The use of vancomycin in prophylaxis for this type of surgery is considered a rational choice and the use of short-term prophylaxis reduces the risks linked to possible collateral effects The effect of topical ampicillin sodium and polyglycolic acid and silk sutures on the recurrence of an existing hernia or an incisional hernia and on infection rates in clean abdominal wounds ( herniotomies and simple cholecystectomies ) was studied in a triple-blind , r and omized trial with 398 consecutive patients . One infection , three suture sinuses , and two incisional hernias occurred among 113 patients with cholecystectomies , while the corresponding rates in 285 patients with hernia repairs were 11 infections , no suture sinuses , and three recurrent hernias . No effect of ampicillin could be demonstrated , nor was any difference between polyglycolic acid and silk sutures shown . No interaction between the antibiotic and suture material was found , and no side effects were observed . Wound infection was significantly more frequent in patients with postoperative seromas or hematomas The aim of this prospect i ve study was to compare the efficacy of oral versus parenteral prophylactic amoxicillin – clavulanic acid for preventing surgical site infection after open prosthetic mesh repair of inguinal hernia . A total of 480 inguinal-hernia patients were r and omly assigned to two groups . Group I ( n = 240 ) received 1.313 g oral amoxicillin – clavulanic acid 2 hours before operation , and group II ( n = 240 ) received 1.2 g of the same drug combination intravenously approximately 30 minutes before surgery . Patients were examined four times during 1 year of follow-up ( at 7–10 days , 4–6 weeks , 6 months , and 12 months postoperation ) , and data related to surgical site infections were collected . Seventy-two patients were excluded due to confounding factors during and after the operation . There were no statistically significant differences between group I ( final n = 208 ) and group II ( final n = 200 ) with respect to age , sex distribution , body mass index , American Anesthesiology Association grade , frequencies of different hernia types , duration of surgery , and the experience levels of the principal surgeon in the operations . One of the 208 ( 0.5 % ) patients in group I and 3 of the 200 ( 1.5 % ) patients in group II developed superficial surgical site infections ( p > 0.05 ) . None of the infections required mesh removal . There were no deep surgical site infections in either group , and there was one case of hernia recurrence in each group . For patients undergoing open prosthetic repair of inguinal hernia , oral amoxicillin – clavulanic acid is safe , significantly less costly , and equally effective in preventing surgical site infection as the same dose given parenterally OBJECTIVE To find out whether collagen tampons treated with gentamicin would prevent postoperative infections in patients operated on for groin hernias by insertion of prostheses . SETTING University hospital , Italy . DESIGN Prospect i ve r and omised trial . PATIENTS 595 patients who required prosthetic repair of a groin hernia . INTERVENTIONS All repairs were by our st and ard surgical technique including prophylactic ceftriaxone , local anaesthesia , and insertion of a polypropylene mesh . 301 patients also had a gentamicin laced collagen tampon placed in front of the prosthetic mesh before the aponeurosis of external oblique muscle was sutured . RESULTS 1/301 patients in the gentamicin group ( 0.3 % ) developed a postoperative wound infection compared with 6/294 in the control group ( 2.0 % ) , ( p = 0.04 Fisher exact test ) . CONCLUSIONS Gentamicin-laced collagen tampons are effective in reducing the postoperative infection rate in patients operated on for groin hernia by insertion of a prosthesis BACKGROUND Antibiotic prophylaxis for inguinal hernioplasty is still practice d in many hospitals to prevent consequences of infected mesh , mesh removal and hernia recurrence . The common route of administration is intravenous . However this method can be associated with systemic side effects . Alternatively , locally applied antibiotics have been used and proven to significantly reduce the infection rate after inguinal hernioplasty . METHODS This was a single blinded prospect i ve r and omised trial with a primary aim to compare the superficial surgical wound infection ( SSSI ) rate between locally applied gentamicin against systemic gentamicin in elective unilateral inguinal hernioplasty . All patients underwent the Lichtenstein tensionfree repair . The secondary aim was to identify risk factors associated with the development of SSSI . RESULTS A total of 202 patients were recruited . There were fourteen SSSI , seven in each arm . The overall SSSI rate was 6.9 % . There was no significant difference between the locally applied versus intravenous administered antibiotics ( p = 0.97 ) . Factors found to contribute to SSSI were diabetes mellitus ( p = 0.006 ) , age 6070 years ( p = 0.023 ) , adhesions ( p = 0.001 ) , duration of surgery > 90 minutes ( p = 0.048 ) , duration of hernia > 24 months ( p = 0.001 ) and the presence of haematoma ( p = 0.001 ) . CONCLUSION Locally applied gentamicin is equivalent to intravenous gentamicin in preventing SSSI post primary inguinal hernioplasty BACKGROUND Identification of subgroups of patients at high and low risk for global infectious complications ( GIC ) after inguinal hernia repair without mesh . METHODS A data base of 1254 patients who underwent inguinal hernia repair without mesh , issued from 3 prospect i ve multicenter r and omized trials , has been established ( group A ) . After multivariate analysis , a score for GIC was calculated and tested using data from a similar prospect i ve r and omized multicenter study ( group B ) . RESULTS A risk score for GIC was constructed : -4.7 + ( 0.95 x age > or = 75 years ) + ( 1.1 obesity ) + ( 2.1 x urinary catheter ) . In case of score less than -4.2 ( low-risk group ) , the GIC rate was 2.7 % ; therefore , in case of score more than -4.2 ( high-risk score ) , the GIC rate was 14.3 % ( P < .001 ) . In the low-risk group , the administration of antibiotic prophylaxis did not reduce the infectious complication rate , while in high-risk group the administration of antibiotic prophylaxis significantly reduced the rates of surgical site infection , GIC , and urinary infection by 72 % , 67 % , and 76.8 % , respectively . CONCLUSIONS This study demonstrates the efficacy of antibiotic prophylaxis in inguinal hernia surgery in the subgroup of high-risk patients The role of prophylactic antibiotics in mesh repair of inguinal hernia is unclear . A Cochrane meta- analysis in 2005 concluded that " antibiotic prophylaxis for elective inguinal hernia repair can not be firmly recommended or discarded " and " further studies are needed , particularly on the use for mesh repair . " So , we design ed a study to define the role of prophylactic antibiotics in mesh repair of inguinal hernia . We conducted a prospect i ve , r and omized , double-blind , trial comparing wound infection rates in 450 patients ( 225 received intravenous Cefazolin , 225 received a placebo ) undergoing primary inguinal hernia repair electively using polypropylene mesh . 334 patients who completed a followup period of one month were analyzed . Age , American Society of Anesthesiologists class , type of hernia , type of anesthesia , grade of surgeon , pre and postoperative hospital stay and duration of operation were recorded . CDC criteria was used to define wound infection . Groups were well matched for all preoperative variables studied . The overall infection rate was 8.7 % ( 29 out of 334 ) . The incidence of wound infection in antibiotic group was 7 % and 10.5 % in control group . One from each group developed deep surgical site infection . Most of the infections occurred between the 7th and 12th post-operative day after discharge from the hospital . Antibiotic prophylaxis was associated with decreased incidence of wound infection when compared to control group , but the difference was not statistically significant . Based on our results we do not recommend the routine use of antibiotic prophylaxis in elective mesh repair of inguinal hernias |
11,896 | 28,419,406 | The currently available evidence does not support or refute the benefits or harms of routine oro/nasopharyngeal suction over no suction . | BACKGROUND Oro/nasopharyngeal suction is a method used to clear secretions from the oropharynx and nasopharynx through the application of negative pressure via a suction catheter or bulb syringe .
Traditionally , airway oro/nasopharyngeal suction at birth has been used routinely to remove fluid rapidly from the oropharynx and nasopharynx in vigorous and non-vigorous infants at birth .
Concerns relating to the reported adverse effects of oro/nasopharyngeal suctioning led to a practice review and routine oro/nasopharyngeal suctioning is no longer recommended for vigorous infants .
However , it is important to know whether there is any clear benefit or harm for infants whose oro/nasopharyngeal airway is suctioned compared to infants who are not suctioned .
OBJECTIVES To evaluate the effect of routine oropharyngeal/nasopharyngeal suction compared to no suction on mortality and morbidity in newly born infants . | 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 Objectives : Examining the effects of tracheal suctioning on cerebral hemodynamics of normotensive ventilated very low birth weight ( VLBW ) infants with normal cranial ultrasounds ; determining the factor(s ) influencing changes in mean cerebral blood flow velocity ( CBFv ) after suctioning . Methods : Seventy-three VLBW infants had continuous monitoring of mean arterial blood pressure ( MABP ) , PaCO2 , PaO2 and mean CBFv before , during , and after 202 suctioning sessions during the first week of life . Peak ( or nadir ) and relative changes of the four variables for 45 min after suctioning were calculated . Multiple linear regression was used to determine the factor(s ) influencing changes in mean CBFv after suctioning . Result : Birth weight was 928±244 g ; gestational age was 27.0±2.0 weeks . Mean CBFv increased to 31.0±26.4 % after suctioning and remained elevated for 25 min . PaCO2 was highly associated with mean CBFv ( P<0.001 ) , whereas MABP and PaO2 were not . Conclusion : We observed prolonged increases of mean CBFv following suctioning in ventilated VLBW infants that were previously unrecognized . This is concerning since disturbances of CBF may be associated with subsequent brain injury Abstract A numeric scoring system for the assessment of hypoxic ischaemic encephalopathy during the neonatal period was tested . The value of the score in predicting neurodevelopmental outcome at 1 y of age was assessed . Forty‐five infants who developed hypoxic ischaemic encephalopathy after birth were studied prospect ively . In addition to the hypoxic ischaemic encephalopathy score all but two infants had at least one cranial ultrasound examination . Thirty‐five infants were evaluated at 12 months of age by full neurological examination and the Griffiths Scales of Mental Development . Five infants were assessed at an earlier stage , four who died before 6 months of age and one infant who was hospitalized at the time of the 12 month assessment . Twenty‐three ( 58 % ) of the infants were normal and 17 ( 42 % ) were abnormal , 16 with cerebral palsy and one with developmental delay . The hypoxic ischaemic encephalopathy score was highly predictive for outcome . The best correlation with outcome was the peak score ; a peak score of 15 or higher had a positive predictive value of 92 % and a negative predictive value of 82 % for abnormal outcome , with a sensitivity and specificity of 71 % and 96 % , respectively . For the clinician working in areas where sophisticated technology is unavailable this scoring system will be useful for assessment of infants with hypoxic ischaemic encephalopathy and for prognosis of neurodevelopmental outcome The effect of oro-naso-pharyngeal suction at birth on pulmonary mechanics is described in a r and om assigned controlled study of 40 normal term vaginally born infants . Twenty cases had their oro-naso-pharynx suctioned immediately after birth ( S Group ) , whereas 20 were not suctioned in the neonatal period ( NS Group ) . A computerized pneumotachographic system ( MECVENT ) was used for the assessment of respiratory mechanics ( Dynamic Compliance ( C. Dyn . ) and Total Pulmonary Resistance ( R ) in inspiration and expiration at 10 , 30 and 120 minutes after birth . In both groups the C. Dyn increased during the study period whereas the R decreased , mainly in the initial 30 minutes . No significant differences were observed between S and NS groups for any of the parameters of respiratory mechanics . The results obtained in this study provide no physiological basis to recommend routine airway suction at birth in normal , term , vaginally born infants Adverse changes in cerebral hemodynamics during endotracheal suctioning have been reported in conventionally ventilated newborns , whereas observations on the effect of endotracheal suctioning during high-frequency ventilation have not been reported to date . The present study was design ed to investigate the effect of endotracheal suctioning on cerebral hemodynamics in high-frequency and conventionally ventilated infants . Changes in cerebral concentration of oxygenated ( cO(2)Hb ) and deoxygenated hemoglobin ( cHHb ) and oxidized cytochrome aa3 ( cCyt.aa3 ) were measured by noninvasive near-infrared spectroscopy . In an open prospect i ve study , 26 suctioning periods in 9 high-frequency and in 6 conventionally ventilated newborn infants were investigated . Heart rate , arterial oxygen saturation ( SaO(2 ) ) , mean blood pressure ( MABP ) , and transcutaneous carbon dioxide tension ( TcpCO(2 ) ) were monitored continuously . In both groups , a marked decrease in heart rate , SaO(2 ) and in cO(2)Hb , an increase in cHHb , and a variable pattern in the concentration of total hemoglobin were noted during endotracheal suctioning . During suctioning , no statistically significant differences between the two methods of mechanical ventilation could be observed . We conclude that the mode of ventilation had no significant effect on changes in cerebral hemodynamics during endotracheal suctioning BACKGROUND Wiping of the mouth and nose at birth is an alternative method to oronasopharyngeal suction in delivery-room management of neonates , but whether these methods have equivalent effectiveness is unclear . METHODS For this r and omised equivalency trial , neonates delivered at 35 weeks ' gestation or later at the University of Alabama at Birmingham Hospital , Birmingham , AL , USA , between October , 2010 , and November , 2011 , were eligible . Before birth , neonates were r and omly assigned gentle wiping of the face , mouth ( implemented by the paediatric or obstetric resident ) , and nose with a towel ( wipe group ) or suction with a bulb syringe of the mouth and nostrils ( suction group ) . The primary outcome was the respiratory rate in the first 24 h after birth . We hypothesised that respiratory rates would differ by fewer than 4 breaths per min between groups . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT01197807 . FINDINGS 506 neonates born at a median of 39 weeks ' gestation ( IQR 38 - 40 ) were r and omised . Three parents withdrew consent and 15 non-vigorous neonates with meconium-stained amniotic fluid were excluded . Among the 488 treated neonates , the mean respiratory rates in the first 24 h were 51 ( SD 8) breaths per min in the wipe group and 50 ( 6 ) breaths per min in the suction group ( difference of means 1 breath per min , 95 % CI -2 to 0 , p<0·001 ) . INTERPRETATION Wiping the nose and mouth has equivalent efficacy to routine use of oronasopharyngeal suction in neonates born at or beyond 35 weeks ' gestation . FUNDING None OBJECTIVE To assess whether endotracheal suctioning of nonvigorous infants born through meconium stained amniotic fluid ( MSAF ) reduces the risk and complications of meconium aspiration syndrome ( MAS ) . STUDY DESIGN Term , nonvigorous babies born through MSAF were r and omized to endotracheal suction and no-suction groups ( n=61 in each ) . Risk of MAS , complications of MAS and endotracheal suction , mortality , duration of neonatal intensive care unit stay , and neurodevelopmental outcome at 9 months were assessed . RESULTS Maternal age , consistency of meconium , mode of delivery , birth weight , sex , and Apgar scores were similar in the groups . In total , 39 ( 32 % ) neonates developed MAS and 18 ( 14.8 % ) of them died . There were no significant differences in MAS , its severity and complications , mortality , and neurodevelopmental outcome for the 2 groups . One infant had a complication of endotracheal suctioning , which was mild and transient . CONCLUSIONS The current practice of routine endotracheal suctioning for nonvigorous neonates born through MSAF should be further evaluated . TRIAL REGISTRATION Clinical Trial Registry of India : CTRI/2013/03/003469 The purpose of the study was to examine the effects of bulb suctioning on healthy , term newborns and the feasibility of conducting a large-scale study of this practice . In a r and omized , controlled two-group design pilot study , 10 newborns received oronasopharyngeal bulb suctioning at birth and 10 did not . Differences in Apgar scores , heart rates , and oxygen saturation levels were determined . Infants were r and omized to groups before delivery . The participants were 20 term , healthy newborns of uncomplicated pregnancies . Apgar scores , heart rates , and oxygen saturation levels in the first 20 minutes of life were the main outcome variables . There were no statistically significant differences in Apgar scores between groups . Apgar scores at 5 and 10 minutes were 9 or 10 for all newborns . Newborns receiving bulb suctioning showed a statistically significant , lower heart rate ( P=.042 ) during the first 20 minutes and a significantly higher SpO2 level ( P=.005 ) by 15 minutes of age . Although statistically significant , these findings were not considered clinical ly significant because values remained within normal parameters BACKGROUND Meconium aspiration syndrome ( MAS ) is a life-threatening respiratory disorder in infants born through meconium-stained amniotic fluid ( MSAF ) . Although anecdotal data concerning the efficacy of intrapartum oropharyngeal and nasopharyngeal suctioning of MSAF are conflicting , the procedure is widely used . We aim ed to assess the effectiveness of intrapartum suctioning for the prevention of MAS . METHODS We design ed a r and omised controlled trial in 11 hospitals in Argentina and one in the USA . 2514 patients with MSAF of any consistency , gestational age at least 37 weeks , and cephalic presentation were r and omly assigned to suctioning of the oropharynx and nasopharynx ( including the hypopharynx ) before delivery of the shoulders ( n=1263 ) , or no suctioning before delivery ( n=1251 ) . Postnatal delivery-room management followed Neonatal Resuscitation Program guidelines . The primary outcome was incidence of MAS . Clinicians diagnosing the syndrome and design ating other study outcomes were masked to group assignment . An informed consent waiver was used . Analysis was by intention to treat . FINDINGS 18 infants in the suction group and 15 in the no suction group did not meet entry criteria after r and om assignment . 87 in the suction group were not suctioned , and 26 in the no suction group were suctioned . No significant difference between treatment groups was seen in the incidence of MAS ( 52 [ 4 % ] suction vs 47 [ 4 % ] no suction ; relative risk 0.9 , 95 % CI 0.6 - 1.3 ) , need for mechanical ventilation for MAS ( 24 [ 2 % ] vs 18 [ 1 % ] ; 0.8 , 0.4 - 1.4 ) , mortality ( 9 [ 1 % ] vs 4 [ 0.3 % ] ; 0.4 , 0.1 - 1.5 ) , or in the duration of ventilation , oxygen treatment , and hospital care . INTERPRETATION Routine intrapartum oropharyngeal and nasopharyngeal suctioning of term-gestation infants born through MSAF does not prevent MAS . Consideration should be given to revision of present recommendations Abstract Oronasopharyngeal suction ( ONPS ) with a suction bulb at birth is a traditional practice in the initial management of healthy infants in Iran and many other countries . The purpose of this study was to compare the effects of oronasopharyngeal suction ( ONPS ) with those of no suction in normal , term newborns delivered vaginally . A total of 170 healthy term infants of first and single uncomplicated pregnancies , with clear amniotic fluid , vaginal delivery and cephalic presentation , enrolled in the trial during labour . Newborns were r and omised into one of the two groups , according to the use of the ONPS procedure . Arterial oxygen saturation ( SaO2 ) levels , heart rates , blood gases of umbilical cord and Apgar scores were determined . The mean SaO2 values over the first and fifth min of birth were similar in the two groups . The maximum time to reach SaO2 of ≥ 92 % was shorter in the no suction group . There were no statistically significant differences in the mean of heart rates , respiratory rates and Apgar scores between the groups . Apgar scores at 5 and 10 min were between 8 and 10 for all infants , respectively . Newborns receiving suction showed a statistically significant , lower mean partial carbon dioxide pressure ( PCO2 ) and a significantly higher partial oxygen pressure ( PO2 ) of umbilical artery . Although the differences were statistically significant , these were not considered clinical ly significant because values remained within normal ranges . According to this study , ONPS is not recommended as a routine procedure in normal , term infants delivered vaginally Background / Aim : There are controversies about the routine use of oronasopharyngeal suction ( ONPS ) in healthy infants . This study aim ed to compare the effects of oronasopharyngeal suction with those of no suction in normal , term infants delivered by cesarean section . Methods : 140 term , healthy newborns of uncomplicated pregnancies were prospect ively r and omized to one of two groups according to the use of ONPS procedure . Differences in oxygen saturation levels , heart rates , and Apgar scores were determined . Results : The mean SaO2 values through the 2nd and 6th min of life were significantly higher in the no suction group ( p < 0.001 ) . The maximum time to reach SaO2 of ≧92 % ( 6 vs. 11 min ) and ≧86 % ( 5 vs. 8 min ) saturation were shorter in the no suction group than in the ONPS group . The mean heart rates were consistently and significantly lower in the no suction group during the first 6 min except the second one . All neonates without suction had an Apgar score of 10 at the 5th min , while the mean ± SD for ONPS group was 9.34 ± 0.48 ( p < 0.001 ) . Conclusion : Although findings remained on statistical level and did not lead to clinical ly adverse outcomes , there is no statistical or physiological basis for oronasopharyngeal suction as a systematic procedure in healthy , term infants delivered by cesarean section OBJECTIVE Evidence about IP-OP suction and selective tracheal intubation in meconium stained neonates is from developed countries . Little information is available about their role in developing countries with high incidence of meconium staining and MAS . This r and omized trial was planned to evaluate the effectiveness of IP-OP suction in meconium stained term neonates on prevention of MAS and reduction of its severity . PATIENTS AND METHODS Out of 540 meconium stained full term , cephalic presentation , singleton neonates without major congenital malformations born from June'08 to January'09 , 31 were excluded and 509 r and omized . In the intervention group IP-OP suction was done at the time of delivery of head using a 10 Fr suction catheter with a negative pressure of 100 mmHg . No IP-OP suction was performed in control group . All neonates with MSAF were assessed as vigorous or non-vigorous after birth and provided care as per NRP guidelines 2005 . RESULTS Two hundred and fifty three neonates were r and omized to IP-OP suction and 256 to no IP-OP suction . Eighty-two neonates ( 16 % ) developed MAS , the primary outcome parameter , with 40 infants in the intervention group ( 15.8 % ) and 42 ( 16.4 % ) in the non-intervention group ( RR 0.86 , 95 % CI 0.60 - 1.54 ) . Incidence of severe MAS was comparable ( 3.55 % vs. 2.34 % ) ( P value=0.40 ) . Other variables like requirement of oxygen > 48 h ( 9.8 % vs. 10.5 % ) and mortality ( 2.7 % vs. 1.7 % ) were also comparable . CONCLUSIONS IP-OP suctioning did not reduce the incidence or severity of MAS even in a setting of high incidence of MAS in a developing country . The mortality in two groups was comparable The effect of oronasopharyngeal suction ( ONPS ) on arterial oxygen saturation ( SaO2 ) is described in a controlled study of 30 normal term newborn infants . In 15 of them , ONPS was performed immediately after birth . The SaO2 value was recorded through a pulse oximeter . The ONPS group had a significantly lower SaO2 between the first and the sixth minutes of life and took longer to reach 86 % and 92 % saturation . According to this study , ONPS should not be performed as a routine procedure in normal , term , vaginally born infants This prospect i ve r and omised controlled trial aim ed to compare the effects of oronasopharyngeal suction with those of no suction in normal , term and vaginally born infants and was performed at a Turkish tertiary hospital from June 2003 to January 2004 . A total of 140 newborns were enrolled in the trial ( n = 70 per group ) . The no suction group showed lower mean heart rates through the 3rd and 6th minutes and higher SaO2 values through the first 6 mins of life ( P < 0.001 ) . The maximum time to reach SaO2 of ≥ 92 % ( 6 vs. 11 min ) and ≥ 86 % ( 5 vs. 8 min ) were shorter in the no suction group ( P < 0.001 ) |
11,897 | 22,531,897 | There is consensus on the presence of pain , but not on the exact location of pain | Purpose Cervical radiculopathy ( CR ) is a common diagnosis .
It is unclear if intervention studies use uniform definitions and criteria for patient selection .
Our objective was to assess the uniformity of diagnostic criteria and definitions used in intervention studies to select patients with CR . | OBJECTIVE Our objective is to assess the effect of mechanical and manual intermittent cervical traction on pain , use of analgesics and disability during the recent cervical radiculopathy ( CR ) . METHODS We made a prospect i ve r and omized study including patients sent for rehabilitation between April 2005 and October 2006 . Thirty-nine patients were divided into three groups of 13 patients each . A group ( A ) treated by conventional rehabilitation with manual traction , a group ( B ) treated with conventional rehabilitation with intermittent mechanical traction and a third group ( C ) treated with conventional rehabilitation alone . We evaluated cervical pain , radicular pain , disability and the use of analgesics at baseline , at the end and at 1 , 3 and 6 months after treatment . RESULTS At the end of treatment improving of cervical pain , radicular pain and disability is significantly better in groups A and B compared to group C. The decrease in consumption of analgesics is comparable in the three groups . At 6 months improving of cervical and radicular pain and disability is still significant compared to baseline in both groups A and B. The gain in consumption of analgesics is significant in the three groups : A , B and C. CONCLUSION Manual or mechanical cervical traction appears to be a major contribution in the rehabilitation of CR particularly if it is included in a multimodal approach of rehabilitation Background : To date , optimal strategies for the management of patients with cervical radiculopathy remain elusive . Preliminary evidence suggests that a multimodal treatment program consisting of manual therapy , exercise , and cervical traction may result in positive outcomes for patients with cervical radiculopathy . However , limited evidence exists to support the use of mechanical cervical traction in patients with cervical radiculopathy . Objective : The purpose of this study was to examine the effects of manual therapy and exercise , with or without the addition of cervical traction , on pain , function , and disability in patients with cervical radiculopathy . Design : This study was a multicenter r and omized clinical trial . Setting : The study was conducted in orthopedic physical therapy clinics . Patients : Patients diagnosed with cervical radiculopathy ( N=81 ) were r and omly assigned to 1 of 2 groups : a group that received manual therapy , exercise , and intermittent cervical traction ( MT EXTraction group ) and a group that received manual therapy , exercise , and sham intermittent cervical traction ( MTEX group ) . Intervention : Patients were treated , on average , 2 times per week for an average of 4.2 weeks . Measurements : Outcome measurements were collected at baseline and at 2 weeks and 4 weeks using the Numeric Pain Rating Scale ( NPRS ) , the Patient-Specific Functional Scale ( PSFS ) , and the Neck Disability Index ( NDI ) . Results : There were no significant differences between the groups for any of the primary or secondary outcome measures at 2 weeks or 4 weeks . The effect size between groups for each of the primary outcomes was small ( NDI=1.5 , 95 % confidence interval [CI]=−6.8 to 3.8 ; PSFS=0.29 , 95 % CI=−1.8 to 1.2 ; and NPRS=0.52 , 95 % CI=−1.8 to 1.2 ) . Limitations : The use of a nonvali date d clinical prediction rule to diagnose cervical radiculopathy and the lack of a control group without treatment were limitations of this study . Conclusions : The results suggest that the addition of mechanical cervical traction to a multimodal treatment program of manual therapy and exercise yields no significant additional benefit to pain , function , or disability in patients with cervical radiculopathy Ongoing efforts to develop mechanisms-based assessment and treatment of chronic pain have been hindered by the lack of assessment tools differentially sensitive to various phenomena underlying different mechanisms of pain . This study describes the development of an assessment instrument intended to measure neuropathic pain based on qualities of pain as they are inferred from pain descriptors . Subjects were 528 chronic pain patients from several clinics . Of these , 149 had strictly neuropathic pain , while 233 had non-neuropathic pain . Subjects completed a 32 item preliminary question naire , which asked them to rate their usual pain on multiple descriptors , as well as the degree to which their pain differed in response to various internal and external factors . This preliminary question naire was su bmi tted to factor analysis , and this yielded 6 factors . Representatives of each of these factors were combined with additional items that demonstrated significant differences between neuropathic and non-neuropathic pain groups , to yield a 12 item Neuropathic Pain Question naire ( NPQ ) . These items were able to differentiate neuropathic pain patients from non-neuropathic pain patients in a holdout sample with 66.6 % sensitivity and 74.4 % specificity . The newly developed instrument , NPQ , may be used for the initial screening of neuropathic pain patients . It also has the ability to provide a quantitative measure for the descriptors important in the diagnosis and assessment of neuropathic pain . Consequently , it can be used for monitoring of neuropathic pain treatments and as an outcome measure A new design of cervical traction modality with closed loop traction weight control based on electromyographic ( EMG ) biofeedback was developed . It consists of the development of a high signal-to-noise ratio EMG scanner , on-line self-adjusted traction weight controller , computer interface hardware , and closed loop biofeedback control software . Six healthy , young adults received conventional cervical traction to establish basic information of cervical EMG activities . Twenty-four patients with cervical radiculopathy were r and omly divided into two groups for clinical assessment by conventional and new EMG biofeedback traction modality . The average electromyographic activity in healthy subjects ranged from 2.41 to 3.49 microV , whereas EMG activity in patients with neck pain ranged from 4.75 to 6.97 microV. There was a significant decrease of EMG activity during the whole traction phase , especially at pull phase in healthy subjects , but it was not as significant in patients with cervical radiculopathy . There was no significant change of myoelectric activity in the paraspinal muscles at vertebral levels C1 - 2 , C3 - 4 , and C5 - 6 . Comparison of the average EMG activity of the paraspinal C-5 muscle in different phases of cervical traction showed a more significant decrease of EMG activity during the pull phase of traction as well as after traction in the high muscle tension group ( with EMG activity above 5 microV ) , especially with the biofeedback traction modality . The raised traction force from start to optimum was shortened from 4 to 2 wk to achieve the same effective outcome by biofeedback as conventional traction modality OBJECTIVE The objective of this study was to investigate the effect of the cervical traction modality with and without electromyographic ( EMG ) biofeedback for neck muscles in patients with cervical radiculopathy . METHODS This study was carried out at the Department of Rehabilitation Sciences , College of Applied Medical Sciences , King Saud University , Riyadh , Kingdom of Saudi Arabia between February and May 2002 . Twenty patients with cervical radiculopathy were r and omly divided into 2 equal groups . Group A was treated by a conventional traction modality and group B was treated by a conventional traction modality with EMG biofeedback ( to obtain relaxation of paraspinal neck muscles ) . The average EMG activity was recorded pre and post treatment at cervical ( C ) 5 - 6 level for both groups during pull , rest and post traction for a period of 6 weeks . RESULTS Comparison of the average EMG activity of the paraspinal C5 - 6 muscle in different phases of cervical traction showed significant decrease of EMG activity during the pull phases of traction as well as after traction , especially with group B which was treated by the EMG biofeedback modality . CONCLUSION Electromyographic biofeedback with cervical traction showed a significant effect in avoiding muscle spasm and decreasing root compression during traction Objective : To determine if combining intermittent cervical traction with conventional physical therapy methods is more effective than using conventional approaches alone in the improvement of the grip strength and treatment of the patients with unilateral cervical 7 ( C7 ) radiculopathy . Design : R and omized controlled trial ( RCT ) . Setting : An outpatient physical therapy clinic , University of Social Welfare and Rehabilitation Science , Iran . Patients : A sample of convenience of 30 patients with unilateral C7 radiculopathy participated in this study . Patients were assigned r and omly to a control ( N=15 , mean age=46.939 ±5.32 ) and an experimental group ( N=15 , mean age=47.53 ±5.6 ) . Interventions : Electrotherapyu/exercise treatment for control group and combined cervical traction and electrotherapyu/exercise for experimental group . Ten physical therapy sessions , three times a week for each group . Main outcome measures : Grip strength as an appropriate objective parameter was measured before treatment and after 5 and 10 treatment sessions . Results : Statistical analysis ( paired t-test ) revealed significant increase in grip strength after 10 treatment sessions in control ( p<0.01 ) and experimental group ( p<0.01 ) compared with pretreatment score . In the ANCOVA , controlling for pretest scores , no significant difference was found between the two groups in the after 10 treatment sessions grip score ( p=0.65 ) . However , the change in grip strength after five sessions was significantly greater for the experimental group than for the control group ( P=0.04 ) . Conclusions : The application of cervical traction combined with electrotherapy and exercise produced an immediate improvement in the h and grip function in patients with cervical radiculopathy Previous investigations with plain radiography , myelography , and computed tomography have shown that degenerative disease of the cervical spine frequently occurs in the absence of clinical symptoms . We studied the magnetic resonance-imaging scans of sixty-three volunteers who had no history of symptoms indicative of cervical disease . The scans were mixed r and omly with thirty-seven scans of patients who had a symptomatic lesion of the cervical spine , and all of the scans were interpreted independently by three neuroradiologists . The scans were interpreted as demonstrating an abnormality in 19 per cent of the asymptomatic subjects : 14 per cent of those who were less than forty years old and 28 per cent of those who were older than forty . Of the subjects who were less than forty , 10 per cent had a herniated nucleus pulposus and 4 per cent had foraminal stenosis . Of the subjects who were older than forty , 5 per cent had a herniated nucleus pulposus ; 3 per cent , bulging of the disc ; and 20 per cent , foraminal stenosis . Narrowing of a disc space , degeneration of a disc , spurs , or compression of the cord were also recorded . The disc was degenerated or narrowed at one level or more in 25 per cent of the subjects who were less than forty years old and in almost 60 per cent of those who were older than forty . The prevalence of abnormal magnetic-resonance images of the cervical spine as related to age in asymptomatic individuals emphasizes the dangers of predicating operative decisions on diagnostic tests without precisely matching those findings with clinical signs and symptoms PURPOSE To describe and explore the relationships between pain , emotional state and coping strategies in patients with chronic radicular neck pain before and after surgery or conservative treatments . METHODS We r and omize 81 conseutive patients with cervical radicular pain and nerve root compression , verified by MRI , to either surgical decompression with fusion or physiotherapy or neck collar . Emotional state was both measured with Mood Adjective Check List . Hospital Anxiety and Depression Scale and with a Coping Strategies Question naire . Pain was measured with VAS and function with Disability Index Rating . Measurements were made before treatment , and follow ups after 3 and 12 months post treatment . RESULTS We found generally a low emotional state with anxiety , depression and sleep-disturbances not only connected to pain . Pain improved faster in the surgery group but after one year no differences were seen . Surgery and physiotherapy improved function with heavy work compared to collar after 3 months . Many patients used active coping before treatment , but after treatment more passive coping strategies were found . CONCLUSION We recommend a multidisciplinary rehabilitation with cognitive behavioural therapy and psychological interventions This prospect i ve , r and omised study compares the efficacy of surgery , physiotherapy and cervical collar with respect to pain , motor weakness and sensory loss in 81 patients with long-lasting cervical radiculopathy corresponding to a nerve root that was significantly compressed by spondylotic encroachment , with or without an additional bulging disk , as verified by MRI or CT-myelography . Pain intensity was registered on a visual analogue scale ( VAS ) , muscle strength was measured by a h and -held dynamometer , Vigorometer and pinchometer . Sensory loss and paraesthesia were recorded . The measurements were performed before treatment ( control 1 ) , 4 months after the start of treatment ( control 2 ) and after a further 12 months ( control 3 ) . A healthy control group was used for comparison and to test the reliability of the muscle-strength measurements . The study found that before start of treatment the groups were uniform with respect to pain , motor weakness and sensory loss . At control 2 the surgery group reported less pain , less sensory loss and had better muscle strength , measured as the ratio of the affected side to the non-affected side , compared to the two conservative treatment groups . After a further year ( control 3 ) , there were no differences in pain intensity , sensory loss or paraesthesia between the groups . An improvement in muscle strengths , measured as the ratio of the affected to the non-affected side , was seen in the surgery group compared to the physiotherapy group in wrist extension , elbow extension , shoulder abduction and internal rotation , but there were no differences in the ratios between the collar group and the other treatment groups . With respect to absolute muscle strength of the affected sides , there were no differences at control 1 . At control 2 , the surgery group performed somewhat better than the two other groups but at control 3 there were no differences between the groups . We conclude that pain intensity , muscle weakness and sensory loss can be expected to improve within a few months after surgery , while slow improvement with conservative treatments and recurrent symptoms in the surgery group make the 1-year results about equal Study Design . A blinded , prospect i ve diagnostic test study was conducted . Objectives . To assess the reliability and accuracy of individual clinical examination items and self-report instruments for the diagnosis of cervical radiculopathy , and to identify and assess the accuracy of an optimum test-item cluster for the diagnosis of cervical radiculopathy . Summary of Background Data . Although cervical radiculopathy remains largely a clinical diagnosis , the reliability and diagnostic accuracy of clinical examination items , individually or in combination , for cervical radiculopathy is largely unknown . Methods . Patients with suspected cervical radiculopathy or carpal tunnel syndrome received st and ardized electrophysiologic examination of the symptomatic upper quarter followed by a st and ardized clinical examination by physical therapist examiners blinded to diagnosis . Diagnostic properties were assessed using a neural impairment reference criterion st and ard . Results . The study involved 82 patients . More than two thirds of 34 clinical examination items had reliability coefficients rated at least fair or better , and 13 items had likelihood ratio point estimates above 2 or below 0.50 . A single diagnostic test item cluster of four variables was identified and produced a positive likelihood ratio point estimate of 30.3 . The 95 % confidence intervals for all likelihood ratio point estimates in this study were wide . Conclusions . Many items of the clinical examination were found to be reliable and to have acceptable diagnostic properties , but the test item cluster identified was more useful for indicating cervical radiculopathy than any single test item . Upper limb tension Test A was the most useful test for ruling out cervical radiculopathy . Further investigation is required both to vali date the test item cluster and to improve point estimate precision & NA ; Few studies have directly compared the clinical features of neuropathic and non‐neuropathic pains . For this purpose , the French Neuropathic Pain Group developed a clinician‐administered question naire named DN4 consisting of both sensory descriptors and signs related to bedside sensory examination . This question naire was used in a prospect i ve study of 160 patients presenting with pain associated with a definite neurological or somatic lesion . The most common aetiologies of nervous lesions ( n=89 ) were traumatic nerve injury , post herpetic neuralgia and post stroke pain . Non‐neurological lesions ( n=71 ) were represented by osteoarthritis , inflammatory arthropathies and mechanical low back pain . Each patient was seen independently by two experts in order to confirm the diagnosis of neuropathic or non‐neuropathic pain . The prevalence of pain descriptors and sensory dysfunctions were systematic ally compared in the two groups of patients . The analysis of the psychometric properties of the DN4 question naire included : face validity , inter‐rater reliability , factor analysis and logistic regression to identify the discriminant properties of items or combinations of items for the diagnosis of neuropathic pain . We found that a relatively small number of items are sufficient to discriminate neuropathic pain . The 10‐item question naire developed in the present study constitutes a new diagnostic instrument , which might be helpful both in clinical research and daily practice A r and omised clinical trial was conducted in the Department of Physical Medicine , Chittagong Medical College Hospital from July , 2001 to June , 2002 . The objectives of the study were to find out the effects of cervical traction ( CT ) and exercise on the patients with chronic cervical spondylosis . A total of 199 patients with cervical spondylosis were included in the clinical trial . One hundred patients were treated with cervical traction plus exercise and 99 patients were treated with non-steroidal anti-inflammatory drug ( NSAID ) . Posture correction advice was given to all patients . The patients were treated for 6 weeks . There was a marked improvement in both the groups after treatment ( P<0.001 ) . But there was nearly significant difference regarding improvement in treatment with CT plus exercise than with NSAID ( P = 0.06 ) . The results indicate that the improvement of the patients with chronic cervical spondylosis was more in CT plus exercise than analgesics . So , CT & neck muscle strengthening exercise may have some more beneficial effects than NSAIDs on chronic cervical spondylosis & NA ; This study describes the development and validation of a novel tool for identifying patients in whom neuropathic mechanisms dominate their pain experience . The Leeds assessment of neuropathic symptoms and signs ( LANSS ) Pain Scale is based on analysis of sensory description and bedside examination of sensory dysfunction , and provides immediate information in clinical setting s. It was developed in two population s of chronic pain patients . In the first ( n=60 ) , the use of sensory descriptors and questions were compared in patients with nociceptive and neuropathic pain , combined with an assessment of sensory function . This data was used to derive a seven item pain scale , consisting of grouped sensory description and sensory examination with a simple scoring system . The LANSS Pain Scale was vali date d in a second group of patients ( n=40 ) by assessing discriminant ability , internal consistency and agreement by independent raters . Clinical and research applications of the LANSS Pain Scale are discussed Study Design . This prospect i ve , r and omized study compares the efficacy of surgical and conservative treatments in patients with long-lasting cervical radicular pain . Objectives . To compare the effects of surgery , physiotherapy , and a cervical collar . Summary of Background Data . There are no previous controlled outcome studies that have compared surgical treatment with nonsurgical treatment of patients with cervical radicular pain . Methods . The study group comprised 81 patients with cervicobrachial pain of at least 3 months ' duration , in whom the distribution of the arm pain corresponded to a nerve root that was significantly compressed by spondylotic encroachment with or without an additional bulging disc , as verified by magnetic resonance imaging or computed tomographic myelography . The patients were r and omly allocated to surgery ( Cloward technique ) , individually adapted physiotherapy , or a cervical collar . The therapeutic effects were evaluated with respect to pain intensity by the visual analogue scale , function by the Sickness Impact Profile , and mood by the Mood Adjective Check List . The measurements were performed before treatment ( control 1 ) , shortly after treatment ( control 2 ) , and after a further 12 months ( control 3 ) . Results . At control 1 , the groups were uniform . At control 2 , the surgery group reported less pain ( visual analogue scale ) and , like the physiotherapy group , better function ( Sickness Impact Profile ) than the collar group . At control 3 , there was no difference in visual analogue scale , Sickness Impact Profile , and Mood Adjective Check List measurements among the groups . Conclusions . In the treatment of patients with long-lasting cervical radicular pain , it appears that a cervical collar , physiotherapy , or surgery are equally effective in the long term ABSTRACT Objective : Nociceptive and neuropathic components both contribute to pain . Since these components require different pain management strategies , correct pain diagnosis before and during treatment is highly desirable . As low back pain ( LBP ) patients constitute an important subgroup of chronic pain patients , we addressed the following issues : ( i ) to establish a simple , vali date d screening tool to detect neuropathic pain ( NeP ) components in chronic LBP patients , ( ii ) to determine the prevalence of neuropathic pain components in LBP in a large-scale survey , and ( iii ) to determine whether LBP patients with an NeP component suffer from worse , or different , co-morbidities . Methods : In co-operation with the German Research Network on Neuropathic Pain we developed and vali date d the painDETECT question naire ( PD‐Q ) in a prospect i ve , multicentre study and subsequently applied it to approximately 8000 LBP patients . Results : The PD‐Q is a reliable screening tool with high sensitivity , specificity and positive predictive accuracy ; these were 84 % in a palm-top computerised version and 85 % , 80 % and 83 % , respectively , in a corresponding pencil- and -paper question naire . In an unselected cohort of chronic LBP patients , 37 % were found to have predominantly neuropathic pain . Patients with NeP showed higher ratings of pain intensity , with more ( and more severe ) co‐morbidities such as depression , panic/anxiety and sleep disorders . This also affected functionality and use of health-care re sources . On the basis of given prevalence of LBP in the general population , we calculated that 14.5 % of all female and 11.4 % of all male Germans suffer from LBP with a predominant neuropathic pain component . Conclusion : Simple , patient-based , easy-to-use screening question naires can determine the prevalence of neuropathic pain components both in individual LBP patients and in heterogeneous cohorts of such patients . Since NeP correlates with more intense pain , more severe co‐morbidity and poorer quality of life , accurate diagnosis is a milestone in choosing appropriate therapy Abstract Cervical radicular pain affects approximately 1 on 1000 adults per year . Although many treatment modalities are described in the literature , the available evidence for efficacy is not sufficient to allow definitive conclusions on the optimal therapy to be made . The effect of pulsed radiofrequency treatment for this type of patients was evaluated in a prospect i ve audit that showed satisfactory pain relief for a mean period of 9.2 months , justifying a r and omized sham controlled trial . Twenty‐three patients , out of 256 screened , met the inclusion criteria and were r and omly assigned in a double blind fashion to receive either pulsed radiofrequency or sham intervention . The evaluation was done by an independent observer . At 3 months the pulsed radiofrequency group showed a significantly better outcome with regard to the global perceived effect ( > 50 % improvement ) and visual analogue scale ( 20 point pain reduction ) . The quality of life scales also showed a positive trend in favor of the pulsed radiofrequency group , but significance was only reached in the SF‐36 domain vitality at 3 months . The need for pain medication was significantly reduced in the pulsed radiofrequency group after six months . No complications were observed during the study period . These study results are in agreement with the findings of our previous clinical audit that pulsed radiofrequency treatment of the cervical dorsal root ganglion may provide pain relief for a limited number of carefully selected patients with chronic cervical radicular pain as assessed by clinical and neurological examination |
11,898 | 18,425,931 | In patients with clear cell renal cancers who had failed prior cytokine therapy , oral sorafenib gives a better quality of life than placebo as well as improved chance of being free of disease progression ; overall survival may have improved but is hard to evaluate because of crossover of placebo-assigned patients after the study closed to accrual ( Escudier 2007a ) .
Based on less than a decade of experience , some targeted agents with specified molecular targets have demonstrated clinical ly useful benefits over the previous st and ard of care for patients with advanced renal cancer . | BACKGROUND Advanced renal cell carcinoma has been resistant to drug therapy of different types and new types of drug therapy are needed .
Targeted agents inhibit known molecular pathways involved in cellular proliferation and neoangiogenesis , the induction by the tumour of host microvascular networks .
Angiogenesis is of special interest in the clear cell histologic subtype of renal cancer because of its vascularity and constitutively activated hypoxia-inducible path in the majority of tumours .
OBJECTIVES 1 ) To provide a systematic review of studies testing targeted agents.2 ) To identify the type and degree of clinical benefit , if any , of targeted agents over the prior st and ard of care , particularly any impact on overall survival . | PURPOSE To define outcome data and prognostic criteria for patients with metastatic renal cell carcinoma ( RCC ) treated with interferon-alfa as initial systemic therapy . The data can be applied to design and interpretation of clinical trials of new agents and treatment programs against this refractory malignancy . PATIENTS AND METHODS Four hundred sixty-three patients with advanced RCC administered interferon-alpha as first-line systemic therapy on six prospect i ve clinical trials were the subjects of this retrospective analysis . Three risk categories for predicting survival were identified on the basis of five pretreatment clinical features by a stratified Cox proportional hazards model . RESULTS The median overall survival time was 13 months . The median time to progression was 4.7 months . Five variables were used as risk factors for short survival : low Karnofsky performance status , high lactate dehydrogenase , low serum hemoglobin , high corrected serum calcium , and time from initial RCC diagnosis to start of interferon-alpha therapy of less than one year . Each patient was assigned to one of three risk groups : those with zero risk factors ( favorable risk ) , those with one or two ( intermediate risk ) , and those with three or more ( poor risk ) . The median time to death of patients deemed favorable risk was 30 months . Median survival time in the intermediate-risk group was 14 months . In contrast , the poor-risk group had a median survival time of 5 months . CONCLUSION Progression-free and overall survival with interferon-alpha treatment can be compared with new therapies in phase II and III clinical investigations . The prognostic model is suitable for risk stratification of phase III trials using interferon-alpha as the comparative treatment arm Objective : To report side effects seen in a clinical cohort of patients aged > 65 years with rheumatoid arthritis ( RA ) treated with the tumor necrosis factor-α TNF-α blocker etanercept and to compare the side effects rate with patients aged ≤65 years . Methods : All patients with RA that started etanercept and who were referred to our rheumatology unit from November 2005 to March 2009 were included in this study and prospect ively followed to collect side effects related to therapy . Results : One hundred three patients were enrolled : 41 ( 37 females , 4 males ) aged > 65 years and 62 ( 40 females , 22 males ) aged < 65 years . In the patients aged > 65 years , the safety profile ( defined as rate of side effects ) of etanercept was similar to that in patients aged ≤65 years ( P > 0.05 ) and the survival curves between the groups were similar ( P > 0.05 ) . Conclusions : In our three-year experience , the anti-TNFα agent etanercept has been well tolerated and safe in elderly patients . The risk of side effects in these patients was no greater than in subjects aged ≤65 years . However , such inhibitors are associated with various and numerous side effects and elderly patients with RA should be carefully monitored to limit the risk of side effects during anti-TNFα therapy as much as possible Background The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy . It is not known how older patients respond to targeted therapy . Methods This retrospective subgroup analysis of data from the phase 3 , r and omized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older ( age ≥70 years , n = 115 ) and younger patients ( age < 70 years , n = 787 ) who received treatment for advanced renal cell carcinoma . Patient demographics and progression-free survival were recorded . Best tumor response , clinical benefit rate ( defined as complete response plus partial response plus stable disease ) , time to self-reported health status deterioration , and toxic effects were assessed by descriptive statistics . Health-related quality of life was assessed with a Cox proportional hazards model . Kaplan – Meier analyses were used to summarize time-to-event data . Results Median progression-free survival was similar in sorafenib-treated younger patients ( 23.9 weeks ; hazard ratio [ HR ] for progression compared with placebo = 0.55 , 95 % confidence interval [ CI ] = 0.47 to 0.66 ) and older patients ( 26.3 weeks ; HR = 0.43 , 95 % CI = 0.26 to 0.69 ) . Clinical benefit rates among younger and older sorafenib-treated patients were also similar ( 83.5 % and 84.3 % , respectively ) and were superior to those of younger and older placebo-treated patients ( 53.8 % and 62.2 % , respectively ) . Adverse events were predictable and manageable regardless of age . Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients ( 121 days with sorafenib vs 85 days with placebo ; HR = 0.66 , 95 % CI = 0.43 to 1.03 ) and younger patients ( 90 days with sorafenib vs 52 days with placebo ; HR = 0.69 , 95 % CI = 0.59 to 0.81 ) and improved quality of life over that time . Conclusions Among patients with advanced renal cell carcinoma receiving sorafenib treatment , outcomes of older ( ≥70 years ) and younger ( < 70 years ) patients were similar Background The development of novel chemotherapeutic agents in colorectal cancer has improved survival . Following initial response to chemotherapeutic strategies many patients develop refractory disease . This poses a significant challenge common to many cancer subtypes . Newer agents such as Bevacizumab have successfully targeted the tyrosine kinase receptor epidermal growth factor receptor in metastatic colorectal cancer . Human epidermal growth factor receptor-2 is another member of the tyrosine kinase receptor family which has been successfully targeted in breast cancer . This may play a role in colorectal cancer . We conducted a clinicopathological study to determine if overexpression of human epidermal growth factor receptor-2 is a predictor of outcome in a cohort of patients with colorectal cancer . Methods Clinicopathological data and paraffin-embedded specimens were collected on 132 consecutive patients who underwent colorectal resections over a 24-month period at Mayo General Hospital . Twenty-six contained non-malignant disease . Her-2/neu protein overexpression was detected using immunohistochemistry ( IHC ) . The HER-2 4B5 Ventana monoclonal antibody was used . Fluorescent insitu hybridisation ( FISH ) was performed using INFORM HER-2/Neu Plus . Results were correlated with established clinical and pathological predictors of outcome including TNM stage . Statistical analysis was performed using SPSS version 11.5 . Results 114 were HER-2/Neu negative using IHC , 7 showed barely perceptible positivity ( 1 + ) , 9 showed moderate staining ( 2 + ) and 2 were strongly positive ( 3 + ) . There was no correlation with gender , age , grade , Dukes ' stage , TNM stage , time to recurrence and 5-year survival ( p > 0.05 ) . FISH was applied to all 2 + and 3 + cases as well as some negative cases selected at r and om . Three were amplified ( 2 were 3 + and 1 was 2 + ) . Similarly , HER-2 gene overexpression did not correlate with established prognostic indicators . Conclusion HER-2 protein is over expressed in 11 % of colorectal cancer patients . The gene encoding HER-2 is amplified in 3 % of cases . Overexpression of HER-2 is not a predictor of outcome . However , patients who over express HER-2 may respond to Herceptin therapy LBA4 Background : Temsirolimus ( TEMSR , CCI-779 ) is a specific inhibitor of mTOR , a signaling protein that regulates cell growth and angiogenesis . In a single-agent , phase 2 study , TEMSR administration to heavily pretreated patients ( pts , n = 111 ) with adv RCC result ed in a median overall survival ( OS ) of 15.0 mos ( Atkins et al , J Clin Oncol 2004 ) . Retrospectively , 49 pts were categorized in a poor-risk group ( Motzer et al , J Clin Oncol 2002 ) . The TEMSR-treated pts in this group had a 1.7-fold longer median OS than the first-line , IFN-treated , poor-risk group reported by Motzer et al. In a phase 1 study , the maximum tolerated dose of the combination of TEMSR + IFN in adv RCC pts was TEMSR 15 mg intravenously ( IV ) once/wk + IFN 6 million units ( MU ) subcutaneously ( SC ) 3 times weekly ( TIW ) ( Smith et al , Proc ASCO 2004 ) . Thus , this phase 3 study in first-line , poor-risk adv RCC pts was initiated in July 2003 . METHODS Pts with adv RCC and no prior systemic therapy were enrolled in this open-label study if they had ≥3 of 6 risk factors ( the 5 Motzer criteria and > 1 metastatic disease site ) . Pts were r and omized ( 1:1:1 ) to arm 1 , IFN up to 18 MU SC TIW ; arm 2 , TEMSR 25 mg IV once/wk ; or arm 3 , TEMSR 15 mg IV once/wk + IFN 6 MU SC TIW . The primary study endpoint was OS ; the study was powered to compare the TEMSR arms with the IFN arm . RESULTS We report 20 Mar 2006 preliminary data from an interim analysis performed by the IDMC . Of the 626 pts enrolled , 442 deaths occurred . Patients treated with TEMSR had a statistically longer survival than those treated with IFN ( Table ) . OS of patients treated with IFN and TEMSR + IFN were not statistically different . The 3 most frequently occurring adverse events ≥gr 3 were asthenia ( arm 1 : arm 2 : arm 3 , 27 % : 12 % : 30 % pts ) , anemia ( 24 % : 21 % : 39 % pts ) , and dyspnea ( 8 % : 9 % : 11 % pts ) . CONCLUSIONS Single-agent TEMSR significantly increases the OS of first-line , poor-risk adv RCC pts compared with IFN , with an acceptable safety profile . [ Table : see text ] [ Table : see text ] Sir , We thank you for providing us the opportunity to respond to the Letter to the Editor received by your office in response to our article ‘ Sunitinib and bevacizumab for first-line treatment of metastatic renal cell carcinoma : a systematic review and indirect comparison of clinical effectiveness ' ( Thompson Coon et al , 2009 ) . We are pleased that Professor Mickisch recognises the need for and importance of indirect treatment comparisons in the absence of head-to-head comparisons and welcome a debate on the relative merits of indirect treatment comparison methods . It appears that some of the comments outlined by Professor Mickisch stem from a misunderst and ing of the methods used in our analysis . Ideally we would have given a more detailed account in the paper , but owing to restrictions in the length of the article we chose to rely on the cited reference ( Ades , 2003 ) to provide a fuller description of the methods used . Our analysis was mainly conducted within the Bayesian framework and as such issues relating to frequentist hypothesis testing are not applicable . Our analysis compared the reported differences ( hazard ratios ) between the three treatments rather than comparing the absolute effects of sunitinib with those of bevacizumab plus IFN and those of IFN alone . Accordingly , it is important to clarify that we did not use a one-sided t-test to calculate the P-value , as inferred by Professor Mickisch . We acknowledge that the language used in describing the output from the MCMC as a one-sided P-value may give rise to some interpretation issues for an audience who are more familiar with frequentist hypothesis testing than Bayesian analysis . The P-value obtained from the MCMC – although regarded as equivalent to that obtained from a one-sided test – is in reality a direct estimate of the probability that one treatment is better than another . It is one of the advantages of the Bayesian approach that it enables intuitive probability statements to be made about propositions ; in this case , 0.0272 is an estimate of the probability that bevacizumab provides superior PFS gain to sunitinib . As a result , within the context of our analysis , it would have been neither possible nor desirable to adopt the methods suggested by Professor Mickisch , which relate solely to the frequentist paradigm . In terms of the number of simulations used in our analysis , we are unaware of any references suggesting that simulation numbers should be as low as 2000 iterations in an MCMC and we would be interested in the source of Professor Mickisch 's comments . It is important to clarify that we were not simulating individual patient experiences but rather repeatedly sampling the differences between treatments in each of the uncertain distributions ( i.e. , our analysis was at the level of a cohort of patients as reflected in trial results ) . Accordingly , caution s that apply to , for example , bootstrap sampling of individual patient data are not applicable in this instance . Increasing the number of simulations in an MCMC will produce a more accurate estimate ( with less possibility of the outputs being distorted by outlying or extreme simulations ) , but will not result in spurious certainty ( in other words , the posterior distribution will become smoother , but not narrower ) . Notwithst and ing the relevance of guidance from the Canadian Agency for Drugs and Technologies in Health ( CADTH ) to this work , we do not share Professor Mickisch 's conclusion that they have identified the Bucher method as the ‘ gold st and ard ' method for performing indirect treatment comparisons . The CADTH identifies both the Bucher and the Bayesian multiple treatment comparison MTC methods as suitable for conducting indirect treatment comparisons , and concludes that the MTC is elegant and more widely applicable , although it may be perceived to be computationally complex . We feel that the MTC approach is more appropriate in this instance as it uses the data from all three available studies in one analysis , thereby h and ling all the uncertainty at the same time . In contrast , the Bucher method necessitates a two-step analysis in which we would first need to meta-analyse the results from the two trials of bevacizumab plus IFN vs IFN and then perform the indirect comparison of this pooled result with the result of the trial of sunitinib vs IFN . In fact , because the number of trials is small and the evidence network simple , in this instance , performing this analysis on the data set used in our article produces results that are almost identical to those generated in the Bayesian analysis : HR=0.796 ( 95 % CI : 0.629 , 1.007 ) . As our analysis was concerned with differences between treatments estimated in r and omised comparisons , we were unable to utilise the data originating from the single-arm exp and ed access trial ( Gore et al , 2007 ) cited in the letter , in which participants received sunitinib only . We are unclear as to why Professor Mickisch does not regard the trial by Rini and colleagues as providing useful data to incorporate into his ongoing research . Although the trial was open-label in design , a large number of individuals ( n=732 ) were r and omised to receive either bevacizumab plus IFN or IFN alone , and the treatment effects reported to date with respect to progression-free survival are similar to those seen in the trial reported by Escudier and colleagues . We assume that a full peer- review ed presentation of Professor Mikisch 's methods , data , and results will be available in due course , and look forward to reading his findings . We hope that these points serve to clarify both the methods and the outputs of our analysis and once again thank you for giving us the opportunity to engage in the debate Purpose Exploratory subgroup analyses from the phase 3 global advanced renal cell carcinoma ( ARCC ) trial were conducted to assess the influence of tumor histology on outcome of patients treated with temsirolimus ( Torisel ™ ) or interferon-α ( IFN ) . Patients and methods Patients with ARCC including clear cell and other types such as papillary and chromophobe histologies received either IFN ( 3 million units [ MU ] subcutaneously three times weekly , escalating to 18 MU ) or temsirolimus ( 25 mg intravenously weekly ) . Results Approximately 80 % of patients had clear cell and 20 % of patients had other histologies , the majority of which were papillary . Patients with clear cell and other RCC histologies , treated with temsirolimus , demonstrated comparable median overall and progression-free survival . In contrast , patients with other RCC histologies , treated with IFN , demonstrated shorter median overall and progression-free survival than patients with clear cell RCC . Hazard ratios for death for treatment with temsirolimus versus IFN were less than 1 for patients regardless of tumor histology . For patients treated with temsirolimus , 59 % with clear cell and 68 % with other RCC histologies experienced tumor reductions . For patients treated with IFN , 35 % with clear cell and 14 % with other RCC histologies had tumor reductions . However , temsirolimus did not appear to improve the objective response rate compared to IFN . Temsirolimus result ed in a superior clinical benefit rate compared with IFN , regardless of tumor histology . Conclusion Temsirolimus appears to be efficacious in patients with clear cell and non-clear cell histologies and can , therefore , be used for the treatment of all types of RCC PURPOSE Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 ( HER-2 ) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer . In the current phase III open-label trial , lapatinib was compared with hormone therapy ( HT ) in patients with advanced renal cell carcinoma ( RCC ) that express EGFR and /or HER-2 . PATIENTS AND METHODS Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy -- stratified by Karnofsky performance status and number of metastatic sites -- were r and omly assigned to lapatinib 1,250 mg daily or HT . The primary end point was time to progression ( TTP ) ; secondary end points included overall survival ( OS ) , safety , and biomarker analyses . RESULTS Four hundred sixteen patients were enrolled onto the study . Median TTP was 15.3 weeks for lapatinib versus 15.4 weeks for HT ( hazard ratio [ HR ] = 0.94 ; P = .60 ) , and median OS was 46.9 weeks for lapatinib versus 43.1 weeks for HT ( HR = 0.88 ; P = .29 ) . In a biomarker analysis of patients with EGFR-overexpressed tumors ( 3 + by immunohistochemistry [ IHC ] ; n = 241 ) median TTP was 15.1 weeks for lapatinib versus 10.9 weeks for HT ( HR = 0.76 ; P = .06 ) , and median OS was 46.0 weeks for lapatinib versus 37.9 weeks for HT ( HR = 0.69 ; P = .02 ) . These results were confirmed by Cox regression analysis . No unexpected toxicities were observed ; the most commonly reported drug-related adverse events ( all grade s ) for lapatinib were rash ( 44 % ) and diarrhea ( 40 % ) . CONCLUSION Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines , and the study supports that lapatinib prolonged OS relative to HT in patients with 3 + EGFR status determined by IHC Purpose : Angiogenesis is a characteristic of renal cell carcinoma . ABT-510 is an angiogenesis inhibitor that mimics the antiangiogenic properties of thrombospondin-1 . This study was design ed to assess the safety and efficacy of ABT-510 in patients with advanced renal cell carcinoma . Experimental Design : Patients with previously untreated metastatic or unresectable renal cell carcinoma were r and omized to treatment with one of two doses of ABT-510 , self-administered s.c . twice daily in 28-day treatment periods without intervening rest periods . End points were progression-free survival ( PFS ) , objective response rate , overall survival , and toxicity . Results : The objective response rate was 4 % in the 10 mg twice daily group , and there were two unconfirmed PRs in the 100 mg twice daily group . Respective median PFS was 4.2 and 3.3 months , with a 6-month PFS of 39 % and 32 % . Median overall survival was 27.8 months ( 10 mg twice daily ) and 26.1 months ( 100 mg twice daily ) . The most frequent adverse events were injection site reactions ( 84 % ) , fatigue ( 50 % ) , headache ( 20 % ) , and nausea ( 19 % ) . The incidence of treatment-related , grade 3/4 adverse events was low and included three bleeding episodes ( gastrointestinal hemorrhage , intracranial hemorrhage , and hemoptysis ) and one thrombotic event ( deep vein thrombosis ) . No deaths were attributed to ABT-510 . Conclusions : There was little evidence of clinical activity for ABT-510 , and further evaluation as a single agent for treating advanced renal cell carcinoma is not warranted . The evidence of a favorable safety profile may justify further evaluation in combination therapy The majority of sporadic clear cell renal cell carcinoma ( RCC ) is characterized by loss of heterozygosity of the von Hippel-Lindau ( VHL ) tumor suppressor gene and somatic inactivation of the remaining VHL allele . The result ing VHL gene silencing leads to induction of hypoxia-regulated genes including vascular endothelial growth factor ( VEGF ) . Thus , therapeutic inhibition of VEGF holds promise for treatment of this historically refractory malignancy . An antibody to VEGF ( bevacizumab , Avastin ) has demonstrated a significant prolongation of time to disease progression compared with placebo in patients with metastatic RCC . Interferon-α ( IFN-α ) is a st and ard initial cytokine therapy in RCC with a modest response rate and a survival advantage demonstrated in r and omized trials . We hypothesized that the addition of anti-VEGF therapy to IFN-α would prolong survival in untreated metastatic RCC patients . A Phase III trial is now being conducted r and omizing untreated , metastatic clear cell RCC patients to IFN-α alone or IFN-α plus Avastin PURPOSE Mature survival data and evaluation of vascular endothelial growth factor ( VEGF ) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial ( TARGET ) study in patients with renal cell carcinoma ( RCC ) are reported . PATIENTS AND METHODS Nine hundred three previously treated patients were r and omly assigned to receive sorafenib versus placebo . On demonstration of progression-free survival ( PFS ) benefit with sorafenib , patients assigned to placebo were offered sorafenib . Overall survival ( OS ) was determined at two planned interim analyses and one final analysis , with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib . The relationships between baseline VEGF level and prognosis and efficacy were evaluated . RESULTS The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo ( 17.8 v 15.2 months , respectively ; hazard ratio [ HR ] = 0.88 ; P = .146 ) ; however , when post-cross-over placebo survival data were censored , the difference became significant ( 17.8 v 14.3 months , respectively ; HR = 0.78 ; P = .029 ) . Adverse events at 16 months after cross over were similar to those previously reported . Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status ( P < .0001 ) , Memorial Sloan-Kettering Cancer Center score ( P < .0001 ) , and PFS and OS in univariate ( PFS , P = .0013 ; OS , P = .0009 ) and multivariate ( PFS , P = .0231 ; OS , P = .0416 ) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib ( P = .0145 ) . Both high-VEGF ( P < .01 ) and low-VEGF ( P < .01 ) groups benefited from sorafenib . CONCLUSION Although an OS benefit was not seen on a primary intent-to-treat analysis , results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib , suggesting an important cross-over effect . VEGF levels are prognostic for PFS and OS in RCC . The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC BACKGROUND We conducted a phase 3 , r and omized , double-blind , placebo-controlled trial of sorafenib , a multikinase inhibitor of tumor-cell proliferation and angiogenesis , in patients with advanced clear-cell renal-cell carcinoma . METHODS From November 2003 to March 2005 , we r and omly assigned 903 patients with renal-cell carcinoma that was resistant to st and ard therapy to receive either continuous treatment with oral sorafenib ( at a dose of 400 mg twice daily ) or placebo ; 451 patients received sorafenib and 452 received placebo . The primary end point was overall survival . A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo . Consequently , crossover was permitted from placebo to sorafenib , beginning in May 2005 . RESULTS At the January 2005 cutoff , the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( hazard ratio for disease progression in the sorafenib group , 0.44 ; 95 % confidence interval [ CI ] , 0.35 to 0.55 ; P<0.01 ) . The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death , as compared with placebo ( hazard ratio , 0.72 ; 95 % CI , 0.54 to 0.94 ; P=0.02 ) , although this benefit was not statistically significant according to the O'Brien-Fleming threshold . Partial responses were reported as the best response in 10 % of patients receiving sorafenib and in 2 % of those receiving placebo ( P<0.001 ) . Diarrhea , rash , fatigue , and h and -foot skin reactions were the most common adverse events associated with sorafenib . Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo . CONCLUSIONS As compared with placebo , treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed ; however , treatment is associated with increased toxic effects . ( Clinical Trials.gov number , NCT00073307 [ Clinical Trials.gov ] . ) PURPOSE To use pre clinical and clinical pharmacokinetic (PK)/pharmacodynamic ( PD ) modeling to predict optimal clinical regimens of everolimus , a novel oral mammalian target of rapamycin ( mTOR ) inhibitor , to carry forward to exp and ed phase I with tumor biopsy studies in cancer patients . PATIENTS AND METHODS Inhibition of S6 kinase 1 ( S6K1 ) , a molecular marker of mTOR signaling , was selected for PD analysis in peripheral blood mononuclear cells ( P BMC s ) in a phase I clinical trial . PK and PD were measured up to 11 days after the fourth weekly dose . A PK/PD model was used to describe the relationship between everolimus concentrations and S6K1 inhibition in P BMC s of cancer patients and in P BMC s and tumors of everolimus-treated CA20948 pancreatic tumor-bearing rats . RESULTS Time- and dose-dependent S6K1 inhibition was demonstrated in human P BMC s. In the rat model , a relationship was shown between S6K1 inhibition in tumors or P BMC s and antitumor effect . This allowed development of a direct-link PK/PD model that predicted P BMC S6K1 inhibition-time profiles in patients . Comparison of rat and human profiles simulated by the model suggested that a weekly 20- to 30-mg dose of everolimus would be associated with an antitumor effect in an everolimus-sensitive tumor and that daily administration would exert a greater effect than weekly administration at higher doses . CONCLUSION A direct-link PK/PD model predicting the time course of S6K1 inhibition during weekly and daily everolimus administration allowed extrapolation from pre clinical studies and first clinical results to select optimal doses and regimens of everolimus to explore in future clinical trials BACKGROUND Everolimus ( RAD001 ) is an orally administered inhibitor of the mammalian target of rapamycin ( mTOR ) , a therapeutic target for metastatic renal cell carcinoma . We did a phase III , r and omised , double-blind , placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy . METHODS Patients with metastatic renal cell carcinoma which had progressed on sunitinib , sorafenib , or both , were r and omly assigned in a two to one ratio to receive everolimus 10 mg once daily ( n=272 ) or placebo ( n=138 ) , in conjunction with best supportive care . R and omisation was done central ly via an interactive voice response system using a vali date d computer system , and was stratified by Memorial Sloan-Kettering Cancer Center prognostic score and previous anticancer therapy , with a permuted block size of six . The primary endpoint was progression-free survival , assessed via a blinded , independent central review . The study was design ed to be terminated after 290 events of progression . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00410124 . FINDINGS All r and omised patients were included in efficacy analyses . The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed ( 101 [ 37 % ] events in the everolimus group , 90 [ 65 % ] in the placebo group ; hazard ratio 0.30 , 95 % CI 0.22 - 0.40 , p<0.0001 ; median progression-free survival 4.0 [ 95 % CI 3.7 - 5.5 ] vs 1.9 [ 1.8 - 1.9 ] months ) . Stomatitis ( 107 [ 40 % ] patients in the everolimus group vs 11 [ 8 % ] in the placebo group ) , rash ( 66 [ 25 % ] vs six [ 4 % ] ) , and fatigue ( 53 [ 20 % ] vs 22 [ 16 % ] ) were the most commonly reported adverse events , but were mostly mild or moderate in severity . Pneumonitis ( any grade ) was detected in 22 ( 8 % ) patients in the everolimus group , of whom eight had pneumonitis of grade 3 severity . INTERPRETATION Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies 4534 Background : Results from the Phase III TARGETs study showed that sorafenib significantly prolonged progression-free survival compared with placebo in patients with advanced renal cell carcinoma . Overall survival was longer with sorafenib than placebo with a hazard ratio of 0.72 . The impact of sorafenib treatment on health-related quality of life ( HRQL ) and symptoms was also evaluated . METHODS HRQL was measured by the Functional Assessment of Cancer Therapy-General ( FACT-G ) . Symptoms were measured by the FACT-Kidney Cancer Symptom Index ( FKSI ) , in which patients used a Likert scale ( 0 - 4 ) to respond to each of 15 items . FACT-G and FKSI were administered at baseline , at Day 1 of each cycle , and at end-of-treatment visit . Statistical analyses used a r and om coefficient model over five cycles , using MSKCC risk and treatment as factors and baseline score and relative days as covariates , adjusted for multiple comparisons with Bonferroni correction . RESULTS A total of 903 patients were r and omized . The FACT-G completion rates at baseline , and Cycles 2 , 3 , 4 , and 5 were ; 96 % , 91 % , 95 % , 99 % , and 100 % , respectively . The FKSI completion rates were ; 94 % , 89 % , 94 % , 97 % , and 100 % , respectively . The completion rate within each patient reported outcome ( PRO ) measure , across all visits , was 93 % . At baseline , there was no between-treatment difference in score for either FACT-G or FKSI . There was no treatment difference after adjusting for multiple comparisons in mean FACT-G total score ( p = 0.96 ) or its domains ( physical well-being [ p = 0.92 ] ; emotional well-being [ p = 0.46 ] ) ; social well-being [ p = 0.75 ] ; functional well-being [ p = 0.94 ] ) , and no difference in total score of FKSI over time . FKSI single-item analysis showed that sorafenib-treated patients had significantly less symptoms vs placebo ( e.g. cough [ p < 0.0001 ] , fevers [ p = 0.0015 ] , ' worry that condition will worsen ' [ p = 0.0004 ] , shortness of breath [ p ≤ 0.0312 ] , and ' ability to enjoy life ' [ p = 0.0119 ] ) . Only ' concern about treatment side-effects ' favored placebo patients ( p < 0.0001 ) . CONCLUSIONS Sorafenib demonstrates clinical benefit without adversely impacting overall HRQL , and has a positive impact on individual symptoms . [ Table : see text ] BACKGROUND Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability . Temsirolimus , a specific inhibitor of the mammalian target of rapamycin kinase , may benefit patients with this disease . METHODS In this multicenter , phase 3 trial , we r and omly assigned 626 patients with previously untreated , poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly , 3 million U of interferon alfa ( with an increase to 18 million U ) subcutaneously three times weekly , or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly . The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group . RESULTS Patients who received temsirolimus alone had longer overall survival ( hazard ratio for death , 0.73 ; 95 % confidence interval [ CI ] , 0.58 to 0.92 ; P=0.008 ) and progression-free survival ( P<0.001 ) than did patients who received interferon alone . Overall survival in the combination-therapy group did not differ significantly from that in the interferon group ( hazard ratio , 0.96 ; 95 % CI , 0.76 to 1.20 ; P=0.70 ) . Median overall survival times in the interferon group , the temsirolimus group , and the combination-therapy group were 7.3 , 10.9 , and 8.4 months , respectively . Rash , peripheral edema , hyperglycemia , and hyperlipidemia were more common in the temsirolimus group , whereas asthenia was more common in the interferon group . There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group ( P=0.02 ) . CONCLUSIONS As compared with interferon alfa , temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis . The addition of temsirolimus to interferon did not improve survival . ( Clinical Trials.gov number , NCT00065468 [ Clinical Trials.gov ] . ) 5021^ Background : Pazopanib , an oral multikinase angiogenesis inhibitor , has shown clinical efficacy in patients ( pts ) with advanced RCC . In this study ( VEG105192 ) , the efficacy and safety of pazopanib was compared with placebo in advanced RCC . METHODS Pts ( N = 400 planned ) with clear cell advanced RCC and measurable disease with no prior treatment or 1 prior cytokine-based treatment , were stratified and r and omized ( 2:1 ) to pazopanib 800 mg QD or placebo . The primary endpoint was progression-free survival ( PFS ) . Secondary endpoints included overall survival ( OS ) , response rate ( RR ) , and safety . The study had ≥ 90 % power to detect an 80 % improvement in PFS and a 50 % improvement in OS , by stratified log-rank tests with α = 0.025 one-sided . Pts received continuous treatment until disease progression ( PD ) , death or unacceptable toxicity . Upon PD , placebo pts could receive pazopanib via an extension study . Final PFS , RR and safety results are reported here . RESULTS A total of 233 treatment-naïve and 202 cytokine-pretreated pts were enrolled ( 290 pazopanib ; 145 placebo ) . Pt characteristics were balanced between the 2 arms . ECOG 0/1 was 42%/58 % and 41%/59 % for pazopanib and placebo pts , respectively . PFS was significantly prolonged with pazopanib in the overall study population ( 9.2 vs 4.2 mos ; HR : 0.46 ; 95 % CI : 0.34 , 0.62 ; p < 0.0000001 ) , in treatment naïve pts ( 11.1 vs 2.8 mos ; HR : 0.40 ; 95 % CI : 0.27 , 0.60 ; p < 0.0000001 ) , and in cytokine-pretreated pts ( 7.4 vs 4.2 mos ; HR : 0.54 ; 95 % CI : 0.35 , 0.84 ; p < 0.001 ) . RR was 30 % with pazopanib ( vs 3 % with placebo ) and median duration of response was 58.7 wks . Median duration of exposure was 7.4 mos ( pazopanib ) and 3.8 mos ( placebo ) . The majority of adverse events ( AEs ) were grade 1 or 2 . Most common AEs in pazopanib-treated pts were diarrhea ( 52 % ; 4 % Gr 3/4 ) , hypertension ( 40 % ; 4 % Gr 3/4 ) , hair color change ( 38 % ; < 1 % Gr 3/4 ) , nausea ( 26 % ; < 1 % Gr 3/4 ) , anorexia ( 22 % ; 2 % Gr 3/4 ) , and vomiting ( 21 % ; 2 % Gr 3/4 ) . The most common laboratory abnormality was ALT elevation ( 53 % ; 10 % Gr 3 ; 2 % Gr 4 ) . CONCLUSIONS Pazopanib monotherapy was well tolerated and demonstrated a significant improvement in PFS and RR compared to placebo . Final OS results are awaited . [ Table : see text ] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy ( J Clin Oncol . 2006 Jan 20;24[3]:519 - 521 ) and the Accreditation Council for Continuing Medical Education ( ACCME ) , ASCO strives to promote balance , independence , objectivity , and scientific rigor through disclosure of financial and other interests , and identification and management of potential conflicts . According to the ASCO Conflict of Interest Policy , the following financial and other relationships must be disclosed : employment or leadership position , consultant or advisory role , stock ownership , honoraria , research funding , expert testimony , and other remuneration ( J Clin Oncol . 2006 Jan 20;24[3]:520 ) . The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who su bmi t abstract s to the Annual Meeting . For clinical trials that began accrual on or after April 29 , 2004 , ASCO 's Policy places some restrictions on the financial relationships of principal investigators ( J Clin Oncol . 2006 Jan 20;24[3]:521 ) . If a principal investigator holds any restricted relationships , his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception . Among the circumstances that might justify an exception are that the principal investigator ( 1 ) is a widely acknowledged expert in a particular therapeutic area ; ( 2 ) is the inventor of a unique technology or treatment being evaluated in the clinical trial ; or ( 3 ) is involved in international clinical oncology research and has acted consistently with recognized international st and ards of ethics in the conduct of clinical research . NIH-sponsored trials are exempt from the Policy restrictions . Abstract s for which authors requested and have been granted an exception in accordance with ASCO 's Policy are design ated with a caret symbol ( ^ ) in the Annual Meeting Proceedings . For more information about the ASCO Conflict of Interest Policy and the exceptions process , please visit www.asco.org/conflictofinterest PURPOSE To evaluate the efficacy , safety , and pharmacokinetics of multiple doses of CCI-779 , a novel mammalian target of rapamycin kinase inhibitor , in patients with advanced refractory renal cell carcinoma ( RCC ) . PATIENTS AND METHODS Patients ( n = 111 ) were r and omly assigned to receive 25 , 75 , or 250 mg CCI-779 weekly as a 30-minute intravenous infusion . Patients were evaluated for tumor response , time to tumor progression , survival , and adverse events . Blood sample s were collected to determine CCI-779 pharmacokinetics . RESULTS CCI-779 produced an objective response rate of 7 % ( one complete response and seven partial responses ) and minor responses in 26 % of these advanced RCC patients . Median time to tumor progression was 5.8 months and median survival was 15.0 months . The most frequently occurring CCI-779-related adverse events of all grade s were maculopapular rash ( 76 % ) , mucositis ( 70 % ) , asthenia ( 50 % ) , and nausea ( 43 % ) . The most frequently occurring grade 3 or 4 adverse events were hyperglycemia ( 17 % ) , hypophosphatemia ( 13 % ) , anemia ( 9 % ) , and hypertriglyceridemia ( 6 % ) . Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level . Patients were retrospectively classified into good- , intermediate- , or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa . Within each risk group , the median survivals of patients at each dose level were similar . CONCLUSION In patients with advanced RCC , CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested 4502 Background : Lapatinib is an orally-active , reversible inhibitor of EGFR/ErbB2 tyrosine kinases . In Phase I/II trials , lapatinib has demonstrated activity in patients ( pts ) with advanced breast cancer . We report the first results of a r and omized open-label Phase III trial ( EGF20001 ) of lapatinib vs. hormone therapy ( HT ) in pts with advanced RCC that express EGFR and /or ErbB2 by immunohistochemistry ( IHC ) . The main endpoints were time to progression ( TTP ) and overall survival ( OS ) . METHODS Pts with advanced RCC of any histology who had failed first-line cytokine therapy were stratified by Karnofsky performance score ( KPS ) and number of metastatic sites . Pts were r and omized to receive oral lapatinib 1250 mg OD or HT . The primary efficacy endpoint was TTP , with 90 % power to detect a 50 % increase ( i.e. 4 vs. 6 months ) at a two-sided 5 % significance level . All pt scans were interpreted by independent radiologic review . RESULTS At the time of the TTP analysis , 417 pts were r and omized and 298 TTP events were reported . Demographic and baseline characteristics were similar between both arms ; pooled results were : median age : 61 yrs ; Stage IV disease : 97 % , KPS 90 - 100 : 59 % , metastatic sites > 2 : 49 % , prior nephrectomy : 94 % , prior interferon therapy : 64 % . No unexpected toxicities were observed , and drug-related AE ( all grade s ) for lapatinib vs. HT included rash ( 44%:3 % ) , diarrhoea ( 40%:3 % ) . When results from all pts were analysed , median TTP was 15.3 weeks for lapatinib vs. 15.4 weeks for HT ( hazard ratio ( HR ) = 0.94 ; p = 0.60 ) , and median OS was 46.9 weeks for lapatinib vs. 43.1 weeks for HT ( HR=0.88 ; p=0.29 ) . In the major subgroup of 241 pts with EGFR overexpressed disease ( 3 + by IHC ) , median TTP was 15.1 weeks for lapatinib vs. 10.9 weeks for HT ( HR = 0.76 ; p = 0.06 ) , and median OS was 46.0 weeks for lapatinib vs. 37.9 weeks for HT ( HR = 0.69 ; p = 0.02 ) . These results were confirmed by Cox Regression analysis , and additional biomarker evaluation , including FISH , is underway . CONCLUSIONS The EGFR/ErbB2 dual targeted inhibitor , lapatinib , appears to prolong overall survival compared to hormone therapy in advanced RCC pts with overexpressed EGFR who failed prior therapy . [ Table : see text ] PURPOSE To assess the disease-stabilizing activity of carboxyaminoimidazole ( CAI ) in patients with metastatic renal cell cancer ( RCC ) using a r and omized discontinuation trial ( RDT ) design . PATIENTS AND METHODS Recruited patients had a performance status of 0 to 2 , minimal neuropathy or cerebellar dysfunction , measurable disease , and normal organ function . Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response . Protocol treatment was discontinued for unacceptable toxicity or progressive disease ; patients with stable disease at the 16-week evaluation point were r and omly assigned in a double-blind manner to continued CAI or placebo . The primary end point was the stable disease rate in the r and omized groups . RESULTS A total of 368 patients were accrued and received therapy . Ninety percent had a performance status of 0 or 1 , 80 % underwent a prior nephrectomy , and 41 % had received no prior systemic therapy . Serious or life-threatening toxicity was experienced by 34 % , with asthenia ( 15 % ) and neuropsychiatric difficulties ( 7 % ) being most common . At the r and omization point , 51 % of patients had progressed , 30 % withdrew , 1 % experienced a partial response , and 17 % had stable disease and were r and omly assigned . A Bayesian futility analysis utilizing the first 49 r and omly assigned patients suggested that the probability of demonstrating a higher stable disease rate in the experimental group was less than 9 % even under the most optimistic a priori assumptions , and further trial accrual was halted . CONCLUSION CAI is inactive in RCC . The RDT design should be further explored for evaluating activity of putative disease stabilizing agents 4524 Background : Sorafenib was approved for advanced RCC in the USA December 2005 . A Phase III r and omized double-blind , placebo-controlled trial demonstrated an estimated 39 % improvement in survival for patients receiving sorafenib versus placebo ( HR= 0.72 , p = 0.018 ) ( ECCO 2005 ) . These data supported independently review ed doubling of PFS to 24 weeks in RCC patients receiving sorafenib compared with placebo ( 12 weeks ) ( p < 0.000001 ) ( ASCO 2005 ) . Based on the statistical significance and magnitude of PFS benefit , patients were unblinded and placebo patients allowed to crossover to sorafenib in April 2005 . A prospect ively planned interim OS analysis reflecting impact of crossover of placebo patients is presented . METHODS OS data up to November 30 , 2005 , were analyzed in this interim analysis using a stratified log-rank test comparing the two treatment groups . In order to examine the effect of crossover on OS , a secondary analysis was performed censoring data from patients r and omized to placebo at June 30 , 2005 . RESULTS A total of 903 patients were r and omized ( 451 to sorafenib , 452 to placebo ) and > 200 placebo patients crossed over to sorafenib . Baseline characteristics were similar between treatment arms . There were 367 deaths . The median OS was 19.3 months for sorafenib versus 15.9 months for placebo ( HR = 0.77 ; 95 % CI 0.63 , 0.95 ; p = 0.015 ) ; although this did not attain the level of significance specified for the interim analysis ( α = 0.009 ) , a continued favorable trend in survival benefit was observed . With censoring of crossover data , the median OS was 19.3 months for sorafenib versus 14.3 months for placebo ( HR = 0.74 , 95 % CI 0.58 , 0.93 ; p = 0.010 ) . CONCLUSION Sorafenib is the first novel , oral approved treatment for advanced RCC in more than a decade . Previous information on the effect of crossover on OS in r and omized oncology studies is limited . The lower HR observed after censoring placebo patients crossed over to sorafenib suggests a continued beneficial effect of sorafenib . Final results await more mature data . [ Table : see text ] 5032 Background : AV-951 is a potent inhibitor of VEGFR-1 , 2 & 3 kinases ( IC50 0.21 , 0.16 and 0.24 nM respectively ) , and inhibits cKit and PDGFR at 10-times higher concentrations ( IC50 1.63 and 1.72 nM respectively ) . In a phase II RDT of AV-951 ( 1.5 mg/day ; 3 wks on , 1 wk off ) in RCC , preliminary ORR at wk 16 was 28 % ( ASCO GU . 2008 ; abstract # 283 ) . METHODS Pts with locally advanced or metastatic RCC ( any histology ) and no prior VEGF-targeted therapy received AV-951 for 16 wks , after which further treatment was assigned based on response . Pts with ≥ 25 % tumor shrinkage continued treatment with AV-951 , while pts with < 25 % change from baseline were r and omly assigned to receive AV-951 or placebo for 12 wks ( double-blinded ) . The primary end points were ( 1 ) objective response rate ( ORR ) at 16 wks , ( 2 ) percentage of r and omly assigned pts remaining progression free at 12 wks following r and omization , ( 3 ) safety profile . RESULTS 272 pts were enrolled : 70 % male , 93 % white , median age 56 yrs . 53 % pts were treatement naïve , 72 % had undergone nephrectomy and 83 % had RCC with clear cell component . With a median duration of treatment of 5 mo ( range 0 - 12 mo ) , the investigator assessed ORR ( CR+PR ) is 27.2 % ( 30 % in clear cell RCC ) , SD 60.5 % and Disease Control Rate ( CR/PR + SD ) 88 % . 118 ( 43 % ) pts were r and omized to AV-951 or placebo . The most common treatment-related AEs ( all grade s ) were hypertension ( HTN , 42 % ) and dysphonia ( 16 % ) . Guidelines for management of HTN were provided to investigators , and 52 % pts received anti-hypertensives . Minimal ( all grade s ) diarrhea ( 9 % ) , fatigue ( 8 % ) , stomatitis ( 3 % ) and h and -foot syndrome ( 2 % ) were observed . Laboratory abnormalities ( all grade s ) were notable for minimal neutropenia ( 8 % ) and elevations of AST ( 21 % ) and ALT ( 21 % ) . AEs led to dose reduction in 4 % and treatment discontinuation in 5.5 % of pts . CONCLUSIONS Interim results of this phase II study demonstrate that AV-951 is active in RCC . The AE profile of AV-951 is consistent with that of a selective VEGFR inhibitor , with minimal off-target toxicities . Up date d results of ORR ( including independent radiology assessment ) , safety , percentage of r and omly assigned pts remaining progression free at 12 wks , and overall PFS will be presented . [ Table : see text ] Introduction : The aim of the current study was to determine the impact of treatment with sorafenib versus placebo on renal cancer symptoms and quality of life ( QOL ) . Methods : Symptoms were measured by the Functional Assessment of Cancer Therapy (FACT)-Kidney Cancer Symptom Index ( FKSI ) and QOL by the FACT-General ( FACT-G ) . The FACT-G and FKSI were administered at baseline and day 1 of each cycle . Statistical analyses used a r and om coefficient model over 5 cycles for total score and individual items , using Memorial Sloan Kettering Risk Score ( MSK ) and treatment as factors and baseline score and treatment time as covariates . FKSI correlation to survival was based on a Cox proportional hazards model adjusting for treatment , age , and MSK . Results : At baseline and over time , there were no differences in mean scores for either the FACT-G or FKSI between the sorafenib and placebo groups . FKSI single-item analysis showed that sorafenib-treated patients reported significantly fewer symptoms and concerns versus placebo ( eg , cough ( P < 0.0001 ) , fevers ( P = 0.0015 ) , shortness of breath ( P ≤ 0.0312 ) , ability to enjoy life ( P = 0.0119 ) , and worry that condition will get worse ( P = 0.0004 ) . Only concern about treatment side effects favored placebo ( P < 0.0001 ) . Baseline FKSI total score predicted overall survival ( P < 0.0001 ) . Conclusions : Sorafenib shows clinical benefit without adversely impacting overall QOL and has a positive impact on some individual symptoms and concerns . These findings are consistent with other clinical results from this trial of advanced renal cell carcinoma patients treated with sorafenib , which included significantly greater progression-free survival and low risk for treatment limited toxicities The objective of this study was to independently evaluate the objective response rate of sorafenib and sorafenib plus low‐dose interferon‐alfa 2b ( IFN ) as frontline therapy in patients with metastatic renal cell carcinoma ( mRCC ) |
11,899 | 16,469,124 | ConclusionS tudies using a dynamic scale protocol combining a tight glucose target and the last two blood glucose values to determine the insulin infusion rate yielded the best results in terms of glycaemic control and reported low frequencies of hypoglycaemic episodes | Introduction Tight glycaemic control is an important issue in the management of intensive care unit ( ICU ) patients .
The glycaemic goals described by Van Den Berghe and colleagues in their l and mark study of intensive insulin therapy appear difficult to achieve in a real life ICU setting .
Most clinicians and nurses are concerned about a potentially increased frequency of severe hypoglycaemic episodes with more stringent glycaemic control .
One of the steps we took before we implemented a glucose regulation protocol was to review published trials employing insulin/glucose algorithms in critically ill patients . | OBJECTIVE Recent studies suggest that strict perioperative glycemic control improves clinical outcomes after cardiothoracic surgery . However , optimal methods and targets for controlling blood glucose ( BG ) levels in this setting have not been established . Currently published intensive insulin infusion protocol s ( IIPs ) have important practical limitations , which may affect their utility . In this article , the authors present their experience with a safe , effective , nurse-driven IIP , which was implemented simultaneously in 2 cardiothoracic intensive care units ( CTICUs ) . DESIGN Prospect i ve cohort study . SETTING Tertiary referral hospital and community teaching hospital . PARTICIPANTS CTICU patients . INTERVENTIONS A st and ardized , intensive IIP was used for all patients admitted to both CTICUs . Hourly BG levels , relevant baseline variables , and clinical interventions were collected prospect ively from the active hospital chart and CTICU nursing records . MEASUREMENTS AND MAIN RESULTS The IIP was used 137 times in 118 patients . The median time required to reach target BG levels ( 100 - 139 mg/dL ) was 5 hours . Once BG levels decreased below 140 mg/dL , 58 % of 2,242 subsequent hourly BG values fell within the narrow target range , 73 % within a " clinical ly desirable " range of 80 to 139 mg/dL , and 94 % within a " clinical ly acceptable " range of 80 to 199 mg/dL. Only 5 ( 0.2 % ) BG values were less than 60 mg/dL , with no associated adverse clinical events . CONCLUSIONS The IIP safely and effectively improved glycemic control in 2 CTICUs , with minimal hypoglycemia . Based on prior studies showing the benefits of strict glycemic control , the implementation of this IIP should help to reduce morbidity and mortality in CTICU patients Background —This study sought to determine whether tight glycemic control with a modified glucose-insulin-potassium ( GIK ) solution in diabetic coronary artery bypass graft ( CABG ) patients would improve perioperative outcomes . Methods and Results —One hundred forty-one diabetic patients undergoing CABG were prospect ively r and omized to tight glycemic control ( serum glucose , 125 to 200 mg/dL ) with GIK or st and ard therapy ( serum glucose < 250 mg/dL ) using intermittent subcutaneous insulin beginning before anesthesia and continuing for 12 hours after surgery . GIK patients had lower serum glucose levels ( 138±4 versus 260±6 mg/dL ; P < 0.0001 ) , a lower incidence of atrial fibrillation ( 16.6 % versus 42 % ; P = 0.0017 ) , and a shorter postoperative length of stay ( 6.5±0.1 versus 9.2±0.3 days ; P = 0.003 ) . GIK patients also showed a survival advantage over the initial 2 years after surgery ( P = 0.04 ) and decreased episodes of recurrent ischemia ( 5 % versus 19 % ; P = 0.01 ) and developed fewer recurrent wound infections ( 1 % versus 10 % , P = 0.03 ) . Conclusions —Tight glycemic control with GIK in diabetic CABG patients improves perioperative outcomes , enhances survival , and decreases the incidence of ischemic events and wound complications BACKGROUND AND PURPOSE Hyperglycemia following acute stroke is strongly associated with subsequent mortality and impaired neurological recovery , but it is unknown whether maintenance of euglycemia in the acute phase improves prognosis . Furthermore , the safety of such intervention is not established . METHODS In an explanatory , r and omized , controlled trial to test safety , 53 acute ( within 24 hours of ictus ) stroke patients with mild to moderate hyperglycemia ( plasma glucose between 7.0 and 17.0 mmol/L ) were r and omized to receive either a 24-hour infusion of 0.9 % ( 154 mmol/L ) saline or a glucose potassium insulin ( GKI ) infusion at 100 mL/h . The GKI consisted of 16 U human soluble insulin and 20 mmol potassium chloride in 500 mL 10 % glucose . Blood glucose was measured every 2 hours with Boehringer Mannheim Glycaemie test strips , pulse and blood pressure were measured every 4 hours , and plasma glucose sample s were taken every 8 hours . Insulin concentration in the GKI was altered according to BM glucose values . RESULTS There were no statistically significant differences between the 2 groups at baseline . Twenty-five patients received GKI , 1 of whom required intravenous glucose for symptomatic hypoglycemia . Plasma glucose levels were nonsignificantly lower in the GKI group throughout the infusion period . Four-week mortality in the GKI group was 7 ( 28 % ) , compared with 8 ( 32 % ) in the control group . CONCLUSIONS GKI infusions can be safely administered to acute stroke patients with mild to moderate hyperglycemia producing a physiological but attenuated glucose response to acute stroke , the effectiveness of which remains to be eluci date BACKGROUND : Critically ill cardiothoracic patients are prone to hyperglycemia and an increased risk of surgical site infections postoperatively . Aggressive insulin treatment is required to achieve tight glycemic control ( TGC ) and improve outcomes . OBJECTIVE : To examine and report on the performance of an insulin infusion protocol to maintain TGC , defined as a blood glucose level of 80–150 mg/dL , in critically ill cardiothoracic surgical patients . METHODS : A nurse-driven insulin infusion protocol was developed and initiated in postoperative cardiothoracic surgical intensive care patients with or without diabetes . In this before — after cohort study , 2 periods of measurement were performed : a 6–month baseline period prior to the initiation of the insulin infusion protocol ( control group , n = 174 ) followed by a 6–month intervention period in which the protocol was used ( TGC group , n = 168 ) . RESULTS : Findings showed percent and time of blood glucose measurements within the TGC range ( control 47 % vs TGC 61 % ; p = 0.001 ) , AUC of glucose exposure > 150 mg/dL versus time for the first 24 hours of the insulin infusion ( control 28.4 vs TGC 14.8 ; p < 0.001 ) , median time to blood glucose < 150 mg/dL ( control 9.4 h vs TGC 2.1 h ; p < 0.001 ) , and percent blood glucose < 65 mg/dL as a marker for hypoglycemia ( control 9.8 % vs TGC 16.7 % ; NS ) . CONCLUSIONS : An insulin infusion protocol design ed to achieve a goal blood glucose range of 80–150 mg/dL efficiently and significantly improved TGC in critically ill postoperative cardiothoracic surgery patients without significantly increasing the incidence of hypoglycemia Intensive insulin therapy to control blood glucose has been found to reduce mortality among critically ill patients in a surgical intensive care unit , though a simple prescriptive insulin infusion protocol to achieve this has not been published previously . This study documents the development and routine use of a simple prescriptive intravenous insulin infusion protocol for critically ill patients and compares the results with previous practice . During development the protocol was optimized and practical issues of implementation addressed . The optimized protocol was then used for all ICU admissions , and a prospect ively defined retrospective chart audit performed for the first month of use . Results were compared with a similar time period the previous year . In September 2002 , 27 admissions were started on the protocol . Blood glucose for the time on the protocol had a median value of 6.2 ( IQR 5.9 - 7.1 ) mmol/l compared with 9.2 ( IQR 8.1 - 10.2 ) mmol/l for those on insulin in 2001 . Blood glucose for the whole ICU stay for those on the protocol in 2002 had a median value of 6.6 ( IQR 6.0 - 7.4 ) mmol/l compared with 8.6 ( IQR 8.0 - 9.4 ) mmol/l in 2001 . Blood glucose for all ICU patients in 2002 had a median value of 6.5 ( IQR 6.0 - 7.3 ) mmol/l compared with 7.2 ( IQR 6.3 - 8.3 ) mmol/l in 2001 . Three blood glucose recordings were less than 2.2 mmol/l in September 2002 . This study provides initial effectiveness and safety data for the Bath Insulin Protocol . Further audits in a larger patient population are now needed OBJECTIVE To describe the main findings of the Portl and Diabetic Project , which eluci date s the adverse relationship between hyperglycemia and outcomes of cardiac surgical procedures in patients with diabetes and delineates the protective effects of intravenous insulin therapy in reducing those adverse outcomes . RESULTS In this ongoing 17-year prospect i ve , nonr and omized , interventional study of 4,864 patients with diabetes who underwent an open-heart surgical procedure , we investigated the effects of hyperglycemia , and its subsequent reduction by continuous intravenous insulin ( CII ) therapy , on in-hospital outcomes . Increasing blood glucose levels were found to be directly associated with increasing rates of death , deep sternal wound infections ( DSWI ) , length of hospital stay ( LOS ) , and hospital cost . In separate multivariate analyses , increasing hyperglycemia was found to be independently predictive of increasing mortality ( P<0.0001 ) , DSWI ( P = 0.017 ) , and LOS ( P<0.002 ) . Conversely , CII therapy , design ed to achieve predetermined target blood glucose levels , independently reduced the risks of death and DSWI by 57 % and 66 % , respectively ( P<0.0001 for both ) . Target blood glucose levels of less than 150 mg/dL and a 3-day postoperative duration of CII therapy are both important variables that determine the effect of the CII therapy on improved outcomes . Coronary artery bypass grafting-related mortality ( 2.5 % ) and DSWI rates ( 0.8 % ) in patients with diabetes were normalized to those of the nondiabetic population by the use of the Portl and CII Protocol . CONCLUSION Perioperative hyperglycemia in patients undergoing a cardiac surgical procedure affects biochemical and physiologic functions , which , in turn , adversely alter mortality , LOS , and infection rates . The Portl and CII Protocol is a cost-efficient method that effectively eliminates hyperglycemia and reduces postoperative morbidity and mortality in patients with diabetes undergoing an open-heart operation . CII protocol s should be the st and ard care for glycometabolic control in all patients undergoing cardiac surgical procedures OBJECTIVES This study tested the impact of intensive metabolic treatment with insulin on transient myocardial ischaemia detected with continuous 12-lead ST-segment monitoring during non-ST segment elevation acute coronary syndromes in type 2 diabetic patients . METHODS AND RESULTS The study included 57 type 2 diabetic patients with non-ST segment elevation acute coronary syndromes . Twenty-eight patients r and omized to conventional treatment plus intensive insulin therapy ( group A ) and twenty-nine to conventional therapy only ( group B ) . Group A patients received insulin by infusion for 48 hours according to a predefined protocol aim ing to maintain normoglycaemia . Group B patients received st and ard coronary care unit treatment . The ST-segment monitoring was performed for 48 hours in the coronary care unit . The two groups were comparable in terms of medical history , clinical and biochemical data . Three patients from both groups were excluded from the analysis because there was objective evidence for evolution in persistent ST-segment elevation acute myocardial infa rct ion . Six patients ( 24 % ) from group A vs. twelve from group B ( 46.2 % ) had evidence of transient ischaemia ( p = 0.098 ) . Group A patients showed significantly lower values in the mean number [ group A vs. group B : 0.4 + /- 0.8 vs. 2 + /- 3.1 , p < 0.01 ] and total duration of ST-episodes [ group A vs. group B : 2.4 + /- 5.1 vs. 21.2 + /- 31 min , p < 0.01 ] . Multivariate analysis revealed that the mean plasma glucose during the study period was a powerful predictor of the presence ( b:0.377,p < 0.01 ) , the number ( b:0.523,p < 0.001 ) and the total duration ( b : 0.686 , p < 0.001 ) of ST-episodes , respectively . CONCLUSIONS ; Intensive insulin treatment considerably decreases the number and the total duration of ST-episodes in type 2 diabetic patients suffering from non-ST segment elevation acute coronary syndromes Abstract Objective Aggressive glycemic control improves mortality and morbidity in critically ill adults , however implementation of such a strategy can be logistically difficult . This study evaluates the efficiency and safety of a nurse-managed insulin protocol in critically ill adults . Design Combined retrospective- prospect i ve before-after cohort study . Setting Twenty-one bed , medical/surgical ICU in a tertiary care hospital . Patients Two cohorts of 50 consecutive ICU patients requiring insulin infusions . Intervention Patients in the control cohort received insulin infusions titrated according to target blood glucose ranges and sliding scales at the physician ’s discretion . Patients in the interventional cohort received an insulin infusion adjusted using a st and ardized protocol targeting a blood glucose of 4.5–6.1 mmol/l ( 81–110 mg/dl ) . Measurements and main results Efficiency was measured by comparing the time to reach , and the time spent within , the target range between cohorts . Safety was assessed by comparing the incidence of severe hypoglycemia , the frequency of rescue dextrose administration and the cumulative time that the infusion was held for hypoglycemia between cohorts . Patients in the interventional cohort reached their target more rapidly ( 11.3±7.9 vs 16.4±12.6 h ; p=0.028 ) and maintained their blood glucose within the target range longer ( 11.5±3.7 vs 7.1±5.0 h/day ; p<0.001 ) than controls . The st and ardized protocol yielded a four-fold reduction in the incidence of severe hypoglycemia ( 4 vs 16 % ; p=0.046 ) and reduced the median frequency of dextrose rescue therapy ( 0 [ 0–0.91 ] vs 0.17 [ 0–1.2 ] episodes/patient per day ; p=0.01 ) as compared to controls . ConclusionS t and ardization of intensive insulin therapy improves the efficiency and safety of glycemic control in critically ill adults We conducted a r and omized , prospect i ve study to assess the effect of i.v . insulin on blood glucose control , development of ketone bodies and hormonal changes in 60 well-controlled , non-insulin-dependent diabetics ( NIDDM ) undergoing major surgery . In group A , patients were given only 0.9 % saline ; in group B , patients were given insulin as a continuous i.v . infusion ( 1.25 u. h-1 ) ; in group C , patients were given insulin 10 u. i.v . boluses every 2 h. Patients in all three groups were given insulin 5 u. when their intraoperative blood glucose concentration increased to greater than 11.1 mmol litre-1 . Blood glucose concentrations were measured every 15 min , from just before induction of anaesthesia to 2 h after surgery . Plasma lactate , pyruvate , ketone body , C-peptide and counter-regulatory hormone concentrations were also measured . Blood glucose concentrations in the three groups did not differ significantly . There was a mild-to-moderate increase in plasma ketone body concentrations in group A , but without any deleterious consequences . Plasma C-peptide concentrations decreased significantly in groups B and C , especially in patients given bolus injections of insulin . Plasma growth hormone concentrations also increased significantly in group B and C patients . This study indicated that the " no insulin -- no glucose " regimen was a simple , effective way to control blood glucose in well-controlled NIDDM patients , provided blood glucose was measured frequently and insulin used appropriately OBJECTIVE To determine whether attempted glucose control through intraoperative insulin therapy reduces the need for inotropic or antiarrhythmic therapy after cardiopulmonary bypass ( CPB ) . DESIGN Post hoc analysis of a r and omized , masked clinical trial of insulin therapy for prevention of neurobehavioral deficits . SETTING Single university hospital . PARTICIPANTS Nondiabetic patients undergoing elective coronary artery bypass graft surgery ( n = 381 ) . INTERVENTIONS Patients received either insulin infusions in an attempt to maintain blood glucose at 80 to 120 mg/dL ( n = 188 ) or placebo ( saline ; n = 193 ) . Inotropic therapy was defined as the initiation of vasoactive support with epinephrine or amrinone infusions or mechanical support with the initiation of an intra-aortic balloon pump in the operating room or within 12 hours postoperatively . Antiarrhythmic therapy was defined as cardioversion , antiarrhythmic medications , or pacing . MEASUREMENTS AND MAIN RESULTS Of patients , 64 in the placebo group and 71 in the insulin group required inotropic support after CPB ( p = not significant ) . The use of cardioversion ( 55 in placebo group v 61 in insulin group ) , antiarrhythmic medications ( 64 in placebo group v 76 in insulin group ) , and pacing ( 118 in placebo group v 117 in insulin group ) was similar between groups . Inotropic drug support was associated with age > 60 years , female gender , reduced preoperative ejection fraction , history of angina , and increased duration of CPB . CONCLUSION Intraoperative insulin therapy did not reduce the use of inotropic or antiarrhythmic support after cardiac surgery with CPB . The lack of benefit may be due to the inability to prevent hyperglycemia during the physiologic stress of CPB or a tribute to the effectiveness of modern myocardial preservation techniques OBJECTIVES Validation of a novel glucose-insulin-potassium ( GIK ) infusion algorithm to optimize metabolic control in hospitalized diabetic patients . SUBJECTS We r and omized 33 diabetic patients admitted to Sahlgrenska University Hospital with acute internal medicine diseases to either GIK infusion or multiple injection therapy ( MIT ) . The GIK infusion rate and the MIT were controlled according to special algorithms . The treatment efficacy was evaluated through comparisons of capillary blood glucose eight times on day 2 of the study . RESULTS The GIK infusion led to significantly lower mean blood glucose when compared with MIT [ 10.1 ( 9.0 - 11.2 ) vs. 12.3 ( 9.3 - 14.4 ) mmol L(-1 ) , median and interquartile range , P < 0.01 ] . Four episodes of hypoglycaemia without loss of consciousness were recorded in the GIK group whereas no hypoglycaemic event occurred in the MIT group . A mean of 1 ( 1 - 3 ) episodes of blood glucose levels above 12.0 mmol L(-1 ) were recorded in the GIK group compared with 3.5 ( 1.5 - 5.0 ) in the MIT group , P < 0.01 . CONCLUSIONS The algorithm used for the GIK infusion gave an acceptable level of metabolic control and this insulin infusion protocol is safe enough to be used by the nursing staff on a general internal medicine ward OBJECTIVE To assess the effect of an intensive glucose management protocol in a heterogeneous population of critically ill adult patients . PATIENTS AND METHODS This study consisted of 800 consecutive patients admitted after institution of the protocol ( treatment group , between February 1 , 2003 , and January 10 , 2004 ) and 800 patients admitted immediately preceding institution of the protocol ( baseline group , between February 23 , 2002 , and January 31 , 2003 ) . The setting was a 14-bed medical-surgical intensive care unit ( ICU ) in a university-affiliated community teaching hospital . The protocol involved intensive monitoring and treatment to maintain plasma glucose values lower than 140 mg/dL. Continuous intravenous insulin was used if glucose values exceeded 200 mg/dL on 2 successive occasions . RESULTS The 2 groups of patients were well matched , with similar age , sex , race , prevalence of diabetes mellitus , Acute Physiology and Chronic Health Evaluation II scores , and distribution of diagnoses . After institution of the protocol , the mean glucose value decreased from 152.3 to 130.7 mg/dL ( P<.001 ) , marked by a 56.3 % reduction in the percentage of glucose values of 200 mg/dL or higher , without a significant change in hypoglycemia . The development of new renal insufficiency decreased 75 % ( P=-.03 ) , and the number of patients undergoing transfusion of packed red blood cells decreased 18.7 % ( P=.04 ) . Hospital mortality decreased 29.3 % ( P=.002 ) , and length of stay in the ICU decreased 10.8 % ( P=.01 ) . CONCLUSION The protocol result ed in significantly improved glycemic control and was associated with decreased mortality , organ dysfunction , and length of stay in the ICU in a heterogeneous population of critically ill adult patients . These results support the adoption of this low-cost intervention as a st and ard of care for critically ill patients OBJECTIVE In a recent r and omized controlled trial , lowering blood glucose levels to 80 - 110 mg/dl improved clinical outcomes in critically ill patients . In that study , the insulin infusion protocol ( IIP ) used to normalize blood glucose levels provided valuable guidelines for adjusting insulin therapy . In our h and s , however , ongoing expert supervision was required to effectively manage the insulin infusions . This work describes our early experience with a safe , effective , nurse-implemented IIP that provides detailed insulin dosing instructions and requires minimal physician input . RESEARCH DESIGN AND METHODS We collected data from 52 medical intensive care unit ( MICU ) patients who were placed on the IIP . Blood glucose levels were the primary outcome measurement . Relevant clinical variables and insulin requirements were also recorded . MICU nurses were surveyed regarding their experience with the IIP . RESULTS To date , our IIP has been employed 69 times in 52 patients admitted to an MICU . Using the IIP , the median time to reach target blood glucose levels ( 100 - 139 mg/dl ) was 9 h. Once blood glucose levels fell below 140 mg/dl , 52 % of 5,808 subsequent hourly blood glucose values fell within our narrow target range ; 66 % within a " clinical ly desirable " range of 80 - 139 mg/dl ; and 93 % within a " clinical ly acceptable " range of 80 - 199 mg/dl . Only 20 ( 0.3 % ) blood glucose values were < 60 mg/dl , none of which result ed in clinical ly significant adverse events . In general , the IIP was readily accepted by our MICU nursing staff , most of whom rated the protocol as both clinical ly effective and easy to use . CONCLUSIONS Our nurse-implemented IIP is safe and effective in improving glycemic control in critically ill patients BACKGROUND Frequently , the use of insulin is considered for metabolic control in postoperative patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . We sought to determine the best method for control of glucose in NIDDM non-insulin patients during postoperative care . METHODS Two algorithms were developed : subcutaneous administration of insulin ( SC ) , and continuous intravenous infusion ( IV ) . A r and omized , controlled clinical trial was design ed . In addition , both experimental groups were compared with a non-concurrent routinely managed group ( RM ) with insulin administration under no predetermined algorithm . Eligible patients were those subjected to major surgery under general anesthesia or spinal blockade . They were followed for 48 h after surgery . Target variables were capillary and central blood glucose , insulin dose administered , urine glucose and ketone strip determination , and development of hyper- or hypoglycemia . RESULTS A total of 62 patients were studied ( RM = 25 , SC = 19 , IV = 18 ) . Results for both experimental algorithms were similar except for the IV group that required less insulin per hour compared to SC ( 0.64 vs. 0.34 U/h ; p = 0.0003 ) . The RM control group showed poor control in all capillary glucose measurements ( 194.9 + /- 26.8 mg/dL ) compared with the two experimental algorithms ( SC = 129.9 + /- 21 ; IV = 131.6 + /- 20.4 ) ( p < 0.05 ) . More hyperglycemia events appeared in the RM group ( p = 0.016 ) . Only one hypoglycemia event occurred in the IV group . CONCLUSIONS Postoperative control of NIDDM is similar with both tested methods . The use of any of the algorithms studied improves metabolic control substantially because it st and ardizes postoperative management of the diabetic patient with timely determination of capillary blood glucose and insulin administration . However , IV administration has the advantage of accomplishing adequate control with a smaller insulin dose Conventional algorithms for regulating insulin infusion rates in those critical diabetic patients su bmi tted to parenteral glucose and insulin infusions do not allow to approach near normal blood glucose ( BG ) levels since traditional control systems are not fully effective in complex nonlinear systems as BG control is . Thus , we applied fuzzy logic principles and neural network techniques to modify intravenous insulin administration rates during glucose infusion . Forty critically ill , fasted diabetic subjects su bmi tted to glucose and potassium infusion entered the study . They were r and omly assigned to two treatment regimes : in group A , insulin infusion rates were adjusted , every 4 h at any step between -1.5 and + 1.5 U/h , according to a neuro-fuzzy nomogram ; in control group B , insulin infusion rates were modified according to a conventional algorithm . In group A , BG was lowered below 10 mmol/l faster than in group B ( 8.2+/-0.7 vs. 13+/-1.8 h , P<.02 ) . Mean BG was 7.8+/-0.2 in group A and 10.6+/-0.3 mmol/l in group B ( P<.00001 ) . BG values below 4.4 mmol/l were : A=5.8 % and B=10.2 % . BG values lower than 2.5 mmol/l had never been observed . In conclusion , the neuro-fuzzy control system is effective in improving the BG control in critical diabetic patients without increasing either the number of BG determinations or the risk of hypoglycemia OBJECTIVE To investigate the effect of insulin-glucose infusion on metabolic control and hypoglycemie episodes and its feasibility and safety in patients with diabetes and myocardial infa rct ion ( MI ) compared with conventional treatment . RESEARCH DESIGN AND METHODS Of 327 patients with suspected acute MI , 158 were r and omized to insulin-glucose infusion for at least 24 h and 169 received conventional therapy . We determined the 24-h blood glucose profile in the infusion group , the degree of metabolic control , hypoglycemie events , and in-hospital complications within the two study groups . RESULTS Blood glucose fell from 14.6 ± 2.9 to 9.2 ± 2.9 mM during the first 24 h in patients receiving insulin-glucose and from 15.8 ± 4.3 to 12.0 ± 4.4 mM in control patients ( P < 0.01 ) . Serum potassium decreased 0.21 ± 0.56 mM in the infusion group ( P < 0.001 ) and 0.11 ± 0.59 mM in the control group ( P < 0.05 ) . The difference between the groups was not significant . Twenty-eight of the 158 patients developed an episode of hypoglycemia ( blood glucose < 3.0 mM ) during the insulin-glucose infusion . There were no significant differences in the number of episodes of ventricular tachyarrhythmias or in ischemie events between patients with and without hypoglycemia . CONCLUSIONS The protocol outlined in this study gives more rapid and better metabolic control than does conventional treatment . This treatment seems to be a feasible alternative for clinical attempts . Before it can be recommended for general use , the impact on mortality needs to be evaluated |
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