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MS21500	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND There is a pressing need for cost-effective population -based interventions to tackle early-onset antisocial behaviour . As this is determined by many factors , it would seem logical to devise interventions that address several influences while using an efficient means of delivery . The aim of this trial was to change four risk factors that predict poor outcome : ineffective parenting , conduct problems , attention deficit/hyperactivity disorder ( ADHD ) symptoms , and low reading ability . METHODS A r and omised controlled trial was carried out in eight schools in London , Engl and . Nine hundred and thirty-six ( 936 ) 6-year-old children were screened for antisocial behaviour , then parents of 112 high scorers were r and omised to parenting groups held in schools or control ; 109 were followed up a year later . The intervention lasted 28 weeks and was novel as it had components to address both child behaviour ( through the Incredible Years programme ) and child literacy ( through a new ' SPOKES ' programme to help parents read with their children ) . Fidelity of implementation was emphasised by careful training of therapists and weekly supervision . Controls received an information helpline . Assessment of conduct problems was by parent interview , parenting by direct observation and child reading by psychometric testing . RESULTS At follow-up parents allocated to the intervention used play , praise and rewards , and time out more often than controls , and harsh discipline less ; effect sizes ranged from .31 to .59 sd ( p-values .046 to .005 ) . Compared to control children , whose behaviour did n't change , intervention children 's conduct problems reduced by .52sd , ( p < .001 ) , dropping from the 80th to the 61st percentile ; oppositional-defiant disorder ( ODD ) halved from 60 % to 31 % ( p = .003 ) . ADHD symptoms reduced by .44sd ( p = .002 ) , and reading age improved by six months ( .36sd , p = .027 ) . Teacher-rated behaviour did n't change . The programme cost pound2,380 ( $ 3,800 ) per child . CONCLUSIONS Effective population -based early intervention to improve the functioning of with antisocial behaviour is practically feasible by targeting multiple risk factors and emphasising implementation fidelity OBJECTIVE A community-based r and omized controlled trial ( RCT ) was conducted in urban areas characterized by high levels of disadvantage to test the effectiveness of the Incredible Years BASIC parent training program ( IYBP ) for children with behavioral problems . Potential moderators of intervention effects on child behavioral outcomes were also explored . METHOD Families were included if the child ( aged 32 - 88 months ) scored above a clinical cutoff on the Eyberg Child Behavior Inventory ( ECBI ) . Participants ( n = 149 ) were r and omly allocated on a 2:1 ratio to an intervention group ( n = 103 ) or a waiting-list control group ( n = 46 ) . Child behavior , parenting skills , and parent well-being were assessed at baseline and 6 months later using parent-report and independent observations . An intention-to-treat analysis of covariance was used to examine postintervention differences between groups . RESULTS Statistically significant differences in child disordered behavior favored the intervention group on the ECBI Intensity ( effect size = 0.7 , p < .001 ) and Problem subscales ( effect size = 0.75 , p < .001 ) . Intervention effects on child hyperactive-inattentive behaviors and social competence , as well as parent competencies and well-being , were also found . Moderator analyses showed that the effects of the IYBP intervention on the primary child outcomes were not moderated by child or family demographic characteristics or risk factors . CONCLUSION The results demonstrate the effectiveness of the IYBP in alleviating problem behavior among children and in improving well-being among families living in disadvantaged areas . The findings also highlight the importance of parental intervention in early childhood for parents and children most in need of support OBJECTIVE We evaluated the effectiveness of 4 parent-training programs for children with externalizing problems . We tested the effectiveness of 3 behavioral programs ( Comet , Cope , and Incredible Years ) and 1 nonbehavioral program ( Connect ) in reducing child behavior problems and attention-deficit/hyperactivity disorder ( ADHD ) symptoms , in improving positive parenting and parenting competence , and in decreasing negative parenting and parents ' stress and depressive symptoms . METHOD This national study was design ed as a r and omized-controlled effectiveness trial ( RCT ) . The treatments were carried out in 30 clinical and community-based practice s. Parents of 908 children ( ages 3 - 12 years ) were r and omly assigned to 1 of 2 parent training programs available at each practice , or to a wait-list condition , where parents had sought help from regular services . Before and after treatment , parents rated child behavior problems and parenting strategies . RESULTS At posttreatment , children whose parents had received interventions showed a strong decrease in child conduct problems and a moderate to strong decrease in ADHD symptoms . About half of parents whose children scored over the 95th percentile on the behavior measures ( Eyberg Child Behavior Inventory , Swanson , Nolan , and Pelham Rating Scale ) , a clinical ly meaningful cutoff , reported that their children were no longer above the cutoff after the intervention . Parents showed considerably less negative behaviors toward their children at posttest compared with pretest ; they increased in parental competence , and decreased in both stress and depressive symptoms . Overall , the behavioral programs were more effective than the nonbehavioral program . CONCLUSIONS The results support the general efficacy of parent training in a short-term perspective We tested the effectiveness of the preventive behavioral parent training ( BPT ) program , The Incredible Years ( IY ) , and the independent effects of previously suggested sociodemographic and intervention-based moderator variables ( i.e. , initial severity of externalizing problem behavior , child gender , social economic status , family composition , and number of sessions parents attended ) , in a large-scale r and omized controlled trial . Question naire and observation data from 387 parents and children ages 4 - 8 years ( Mage= 6.21 , SD = 1.33 , 55.30 % boys ) across pretest , posttest , and 4-month follow-up were analyzed , using full intention-to-treat analyses and correcting for multiple testing . IY was successful in decreasing parent-reported child externalizing behavior ( Cohen 's d = 0.20 at posttest , d = 0.08 at follow-up ) , increasing parent-reported ( d = 0.49 , d = 0.45 ) and observed ( d = 0.06 , d = 0.02 ) positive parenting behavior , and decreasing parent-reported negative parenting behavior ( d = 0.29 , d = 0.25 ) . No intervention effects were found for reported and observed child prosocial behavior , observed child externalizing behavior , and observed negative parenting behavior . Out of 40 tested moderation effects ( i.e. , 8 Outcomes × 5 Moderators ) , only three significant moderation effects appeared . Thus , no systematic evidence emerged for moderation of IY effects . The present multi-informant trial demonstrated that many previously suggested moderators might not be as potent in differentiating BPT effects as once thought BACKGROUND Children with conduct problems that persist into adulthood are at increased risk for future behavioral , health , and social problems . However , the longer term public service usage among these children has not been fully documented . To aid public health and intervention planning , adult service usage across criminal justice , health care , and social welfare domains is compared among all individuals from a representative cohort who followed different conduct problem trajectories from childhood into adulthood . METHODS Participants are from the Dunedin Multidisciplinary Health and Development Study , a prospect i ve , representative cohort of consecutive births ( N = 1,037 ) from April 1972 to March 1973 in Dunedin , New Zeal and . Regression analyses were used to compare levels of public service usage up to age 38 , gathered via administrative and electronic medical records , between participants who displayed distinct subtypes of childhood conduct problems ( low , childhood-limited , adolescent-onset , and life-course persistent ) . RESULTS Children exhibiting life-course persistent conduct problems used significantly more services as adults than those with low levels of childhood conduct problems . Although this group comprised only 9.0 % of the population , they accounted for 53.3 % of all convictions , 15.7 % of emergency department visits , 20.5 % of prescription fills , 13.1 % of injury cl aims , and 24.7 % of welfare benefit months . Half of this group ( 50.0 % ) also accrued high service use across all three domains of criminal justice , health , and social welfare services , as compared to only 11.3 % of those with low conduct problems ( OR = 7.27 , 95 % CI = 4.42 - 12.0 ) . CONCLUSIONS Conduct problems in childhood signal high future costs in terms of service utilization across multiple sectors . Future evaluations of interventions aim ed at conduct problems should also track potential reductions in health burden and service usage that stretch into midlife BACKGROUND Parenting programs have been shown to work when delivered to motivated ethnic majority parents in demonstration projects , but comparatively little is known about their impact when delivered to high-risk , multi-ethnic population s by routine local services . METHODS The Primary Age Learning Skills ( PALS ) trial was a r and omized controlled trial of an evidence -based parenting-group program that targeted the parent-child relationship and child literacy . Parents of 174 children were selected from a population of 672 5- and 6-year-olds attending four primary schools in a high-risk , ethnically diverse , inner-city area . Eighty-eight children were allocated to the Incredible Years preventive program plus a shortened six-week version of the SPOKES literacy program , delivered by local services ; 86 to usual community services ; 152/174 ( 87 % ) of families were successfully followed up . Parent-child relationship quality and child behavior were measured using direct observation and parent interview ; child reading was assessed psychometrically . RESULTS Two-thirds ( 58/89 ) of those offered the parenting program attended at least one session , with similar enrollment rates across the Black African , African-Caribbean , White-British and Other ethnic groups . Mean attendance was four relationship-building sessions and one literacy-development session . Satisfaction question naires were completed by 43/58 starters ; 93 % said they were well or extremely satisfied , with equally high rates across ethnic groups . At follow-up after one year , those allocated to the intervention showed significant improvements in the parent-child relationship on observation and at interview compared to controls ; effects were similar across all ethnic groups . However , child behavior problems and reading did not improve . The cost was £ 1,343 ( $ 2,100 ) per child . CONCLUSIONS Programs can be organized to be engaging and effective in improving parenting among high-risk , multi-ethnic communities , which is of considerable value . To also be cost-effective in achieving child changes may require a set-up that enables parents to attend more sessions and /or an exclusive focus on children with clinical ly significant behavior problems Aims : To assess the effectiveness of a parenting programme , delivered by health visitors in primary care , in improving the mental health of children and their parents among a representative general practice population . Methods : Parents of children aged 2–8 years who scored in the upper 50 % on a behaviour inventory were r and omised to the Webster-Stratton 10 week parenting programme delivered by trained health visitors , or no intervention . Main outcome measures were the Eyberg Child Behaviour Inventory and the Goodman Strengths and Difficulties Question naire to measure child behaviour , and the General Health Question naire , Abidin ’s Parenting Stress Index , and Rosenberg ’s Self Esteem Scale to measure parents ’ mental health . These outcomes were measured before and immediately after the intervention , and at six months follow up . Results : The intervention was more effective at improving some aspects of the children ’s mental health , notably conduct problems , than the no intervention control condition . The Goodman conduct problem score was reduced at immediate and six month follow up , and the Eyberg Child Behaviour Inventory was reduced at six months . The intervention also had a short term impact on social dysfunction among parents . These benefits were seen among families with children scoring in the clinical range for behaviour problems and also among children scoring in the non- clinical ( normal ) range . Conclusion : This intervention could make a useful contribution to the prevention of child behaviour problems and to mental health promotion in primary care Children of incarcerated mothers are considered at risk for disruptive behavior problems and later delinquency . Parenting may play a key role in this intergenerational transmission of delinquency . The present study aim ed to evaluate the effectiveness of the Incredible Years parent training , enhanced with home visits , for ( formerly ) incarcerated mothers to prevent disruptive behavior problems in their 2- to 10-year-old children , by means of a nationwide r and omized controlled trial . Mothers of 133 children ( M age = 76.91 months ; 48.9 % boys ) were assigned to an intervention , consisting of group sessions and individual home visits , or a no-intervention control group . The intervention yielded significant effects on parenting and child behavior for maternal report . Marginally significant effects on child behavior were found for teacher report . The results show short-term effectiveness of parent training for the high-risk and hard-to-reach population of ( formerly ) incarcerated mothers and their children BACKGROUND To test effectiveness of a parenting intervention , delivered in a community-based voluntary-sector organisation , for reducing conduct problems in clinical ly-referred children . METHODS R and omised controlled trial , follow-up at 6 , 18 months , assessors blind to treatment status . Participants --76 children referred for conduct problems , aged 2 - 9 , primarily low-income families , r and omised Output:	INTERPRETATION We found no evidence for differential effects by social disadvantage , suggesting that Incredible Years is unlikely to widen socioeconomic inequalities in conduct problems . Furthermore , the programme might be an important tool for reducing social disparities and improving poor long-term outcomes in disadvantaged families because follow-up studies indicate that benefits persist .
MS21501	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIM To give a detailed description of the long-term outcome of a cohort of children with glioneuronal tumors regarding pre- and postsurgical factors , including " dual " and " double " pathology , seizure freedom , and psychosocial outcome . METHODS During a fifteen-year period ( 1995 - 2009 ) , all patients ( age 0 - 17.99years ) with a glioneuronal brain tumor diagnosed and treated at Uppsala University Children 's Hospital were identified from the National Brain Tumor Registry and the National Epilepsy Surgery Registry . Hospital medical records were review ed and neuroradiological and neuropathological findings were re-evaluated . A cross-sectional long-term follow-up prospect i ve evaluation , including an interview , neurologic examination , and electroencephalogram , was accomplished in patients accepting participants in the study . RESULTS A total of 25 out of 28 ( 89 % ) eligible patients were included . The M : F ratio was 1.5:1 . Mean follow-up time after surgery was 12.1years ( range 5.0 - 19.3 ) . Twenty patients were adults ( > 18years ) at follow-up . Seizure freedom was achieved in 64 % . Gross total resection ( GTR ) was the only preoperative factor significantly correlating to seizure freedom ( p=0.027 ) . Thirty-eight percent were at some time postoperatively admitted for a psychiatric evaluation . There was a trend towards both higher educational level and employment status in adults who became seizure free . CONCLUSION Long-term outcome is good regarding seizure freedom if GTR can be achieved , but late seizure recurrence can occur . " Dual " and " double " pathology is uncommon and does not influence seizure outcome . Obtaining seizure freedom seems to be important for psychosocial outcome , but there is a risk for psychiatric comorbidities and long-term follow-up by a multi-professional team is advisable OBJECTIVE Self-reported data show differences in social outcomes ( not being married/having a registered partnership ; not living independently ; using social benefits ) for childhood cancer survivors compared with their peers . We aim ed to determine differences in these social outcomes between survivors and the general population using national register data and explored associated risk factors . METHODS We performed medical record linkage between a single-centre cohort of 1768 ≥ 5-year survivors of childhood cancer ( diagnosed 1966 - 2001 ) and two national registers ( 1999 - 2011 ) and obtained a r and om reference sample matched on gender and year of birth per survivor . We used multivariable logistic regression to calculate in adult survivors of childhood cancer ( born before 1990 ) the odds of the specified social outcomes at the end of follow-up in both groups . Within the survivors , we analysed risk factors for the social outcomes . RESULTS We retrieved data from 1283 adult childhood cancer survivors and 25 082 reference persons . Survivors had higher odds ( odds ratio ; 95 % confidence interval ) of not being married ( 1.2 ; 1.07 - 1.42 ) , not living independently ( 1.7 ; 1.41 - 2.00 ) and using social benefits ( 2.3 ; 1.98 - 2.69 ) compared with reference persons . Radiotherapy to head and /or neck , and an original central nervous system tumour diagnosis negatively influenced all social outcomes examined in childhood cancer survivors . CONCLUSIONS National register data show differences between social outcomes in childhood cancer survivors and the general population , especially for survivors treated with radiotherapy to head and /or neck and those originally diagnosed with central nervous system tumours . Development and implementation of effective targeted support strategies to improve social outcomes of childhood cancer survivors needs consideration . Copyright © 2015 John Wiley & Sons , BACKGROUND To determine if a group social skills intervention program improves social competence and quality of life ( QOL ) in pediatric brain tumor survivors ( PBTS ) . METHODS We conducted a r and omized control trial in which PBTS ( 8 - 16 years old , off therapy for over 3 months ) were allocated to receive social skills training ( eg , cooperation , assertion , using social cognitive problem solving strategies , role playing , games , and arts and crafts ) in 8 weekly 2-hour sessions , or an attention placebo control ( games and arts and crafts only ) . Outcomes were self-reported , proxy-reported ( caregiver ) , and teacher-reported using the Social Skills Rating System ( SSRS ) , to measure social competence , and the Pediatric Quality of Life ( PedsQL4.0 , generic ) to measure QOL at baseline , after intervention , and at 6 months follow-up . At baseline , SSRS were stratified into low and high scores and included as a covariate in the analysis . RESULTS Compared to controls ( n = 48 ) , PBTS in the intervention group ( n = 43 ) reported significantly better total and empathy SSRS scores , with improvements persisting at follow-up . The PBTS in the intervention group who had low scores at baseline reported the greatest improvements . Proxy and teacher reports showed no intervention effect . CONCLUSIONS Participating in group social skills intervention can improve self-reported social competence that persisted to follow up . The PBTS should be given the opportunity to participate in social skills groups to improve social competence OBJECTIVE The purpose of this study was to evaluate the feasibility and preliminary outcomes of a social skills group intervention program for child brain tumor survivors . METHODS Participants were 32 survivors ( 14 females ) aged 8 - 18 years . Medulloblastoma ( 28 % ) was the main diagnosis . The intervention consisted of eight 2-hr weekly sessions focused on social skills including friendship making and assertion . Survivors and parents completed measures of social skills , quality of life , behavior and depression , at baseline , pre- and post-intervention , and 6 months later . RESULTS Feasibility analyses revealed promising acceptability , retention , recruitment , and treatment fidelity . Significant improvement was found after intervention based on parents ' reports of self-control [ F(1,27 ) = 5.97 , p < .05 ] , social skills [ F(1,28 ) = 5.70 , p < .05 ] , and quality of life [ F(1,15 ) = 17.98 , p < .01 ] . CONCLUSIONS The intervention is feasible and outcomes based on parental reports provide preliminary support for the efficacy of the program BACKGROUND Adult survivors of childhood cancer ( ASCC ) , especially those of the central nervous system ( CNS ) , have increased risks of educational and social difficulties . It is therefore hypothesized they are more likely to encounter legal difficulties ( LDs ) , such as workplace discrimination and disability insurance denials , which may negatively affect their quality of life ( QoL ) . PROCEDURE We developed a survey to collect information on patients ' legal needs . QoL was assessed using the Functional Assessment of Cancer Therapy ( FACT ) . RESULTS We prospect ively approached 112 ASCC , 111 ( 99.1 % ) of whom completed the survey . The median age of respondents was 7 years at diagnosis and 31 years at survey completion . CNS tumors were the most common malignancy ( 32.4 % ) . LDs were common overall ( 40.7 % ) , though more prevalent in patients with CNS versus non-CNS tumors ( 58.6 % vs. 32.3 % ; P = 0.023 ) . The most prevalent LD was workplace discrimination ( 58.3 % ) . On multivariate analysis , CNS tumor was the only variable significantly associated with LDs ( OR = 4.49 , P = 0.041 ) . Individuals with LDs had lower QoL scores compared to those without LDs ( 79.96 versus 91.83 on the FACT ; P = 0.005 ) . On multivariate analysis , individuals with LDs had lower QoL scores ( 14.95 points lower on the FACT ) , which is both clinical ly and statistically significant ( P = 0.047 ) . CONCLUSIONS Legal difficulties are common in adult survivors of childhood cancer , especially those with brain tumors . Furthermore , individuals with legal difficulties have worse quality of life . Research is needed to develop effective and accessible legal re source programs Quality of life ( QOL ) is important for the survivors of malignancies . We investigated health-related QOL in 51 patients treated with iodine-125 ( ¹²⁵I ) brachytherapy for childhood low- grade gliomas . Instruments included a question naire on life situation , German versions of PEDQOL ( 8 - 18 years ) , EORTC QLQ-30 and head and neck module H&N-35 ( > 18 years ) , strength and difficulties question naire , " Fertigkeitsskala Münster Heidelberg " , and an adapted Rankin score . The time lapsed since ¹²⁵I-brachytherapy was 134 months ( median , range : 29 - 293 months ) . 57 % of the patients were over 18 years of age , 34 % were 11 - 17 years old and 8 % were younger . 14 had undergone other treatments after ¹²⁵I brachytherapy . Over half of the > 18 year olds reported residual problems ; 68 % were disabled , 38 % to a severe degree . Many of the young adults still lived with their parents and 17 % were jobless . 43 % of the children/adolescents needed rehabilitative treatment , 20 % visited special schools and 71 % were disabled , 33 % severely . The patients and their caregivers rated their QOL as not different from that of the normal population . However , many QOL dimensions correlated to the severity of disability . Comparison of QOL outcomes between different treatment measures would require a prospect i ve study controlling for the most important factors of influence BACKGROUND Survivors of pediatric CNS tumors are at risk for persistent tumor/treatment-related morbidity , physical disability and social consequences that may alter self-perception , vital for self-identity , mental health and quality of survival . We studied the long-term impact of childhood CNS tumors and their treatment on the self-perception of adult survivors and compared outcomes with those of the general population . METHODS The cohort included 697 Swedish survivors diagnosed with a primary CNS tumor during 1982 - 2001 . Comparison data were r and omly collected from a stratified general population sample . Survivors and general population individuals were compared as regards self-perception in 5 domains : body image , sports/physical activities , peers , work , and family , and with a global self-esteem index . Within the survivor group , determinants of impact on self-perception were identified . RESULTS The final analyzed sample included 528 survivors , 75.8 % of the entire national cohort . The control sample consisted of 995 , 41 % of 2500 addressed . Survivors had significantly poorer self-perception outcomes in domains of peers , work , body image , and sports/physical activities , and in the global self-perception measure , compared with those of the general population ( all P < .001 ) . Within the survivor group , female gender and persistent visible physical sequelae predicted poorer outcomes in several of the studied domains . Tumor type and a history of cranial radiation therapy were associated with outcomes . CONCLUSION An altered self-perception is a potential late effect in adult survivors of pediatric CNS tumors . Self-perception and self-esteem are significant elements of identity , mental health and quality of survival . Therefore , care and psychosocial follow-up of survivors should include measures for identifying disturbances and for assessing the need for psychosocial intervention Output:	Cranial radiation therapy , neurocognitive deficits , and younger age at diagnosis were associated with poorer outcomes . Hearing loss and bilateral blindness were also related to poorer outcomes . Sex did not impact social attainment outcomes . Survivors of pediatric CNS tumors are at elevated risk for poor attainment of key adult social outcomes .
MS21502	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Context : The role of h and hygiene in preventing health care associated infections ( HCAIs ) has been clearly established . However , compliance rates remain poor among health care personnel . Aims : a ) To investigate the health care workers ’ h and hygiene compliance rates in the intensive care unit ( ICU ) , b ) to assess reasons for non-compliance and c ) to study the efficacy of a multimodal intervention strategy at improving compliance . Setting s : A mixed medical – surgical ICU of a tertiary level hospital . Design : A before – after prospect i ve , observational , intervention study . Material s and Methods : All health care personnel who came in contact with patients in the ICU were observed for their h and hygiene compliance before and after a multimodal intervention strategy ( education , posters , verbal reminders and easy availability of products ) . A self-report question naire was also circulated to assess perceptions regarding compliance . Statistical analysis was done using χ2 test or Fisher exact test ( Epi info software ) . Results : H and hygiene compliance among medical personnel working in the ICU was 26 % and the most common reason cited for non-compliance was lack of time ( 37 % ) . The overall compliance improved significantly following the intervention to 57.36 % ( P<0.000 ) . All health care worker groups showed significant improvements : staff nurses ( 21.48–61.59 % , P<0.0000 ) , nursing students ( 9.86–33.33 % , P<0.0000 ) , resident trainees ( 21.62–60.71 % , P<0.0000 ) , visiting consultants ( 22–57.14 % , P=0.0001 ) , physiotherapists ( 70–75.95 % , P=0.413 ) and paramedical staff ( 10.71–55.45 % , P < 0.0000 ) . Conclusions : H and hygiene compliance among health care workers in the ICU is poor ; however , intervention strategies , such as the one used , can be useful in improving the compliance rates significantly BACKGROUND H and hygiene is a fundamental measure for the control of nosocomial infection . However , sustained compliance with h and hygiene in health care workers is poor . We attempted to enhance compliance with h and hygiene by implementing education , training , and performance feedback . We measured nosocomial infections in parallel . METHODS We monitored the overall compliance with h and hygiene during routine patient care in intensive care units ( ICUs ) ; 1 medical surgical ICU and 1 coronary ICU , of 1 hospital in Buenos Aires , Argentina , before and during implementation of a h and hygiene education , training , and performance feedback program . Observational surveys were done twice a week from September 2000 to May 2002 . Nosocomial infections in the ICUs were identified using the National Nosocomial Infections Surveillance ( NNIS ) criteria , with prospect i ve surveillance . RESULTS We observed 4347 opportunities for h and hygiene in both ICUs . Compliance improved progressively ( h and washing adherence , 23.1 % ( 268/1160 ) to 64.5 % ( 2056/3187 ) ( RR , 2.79 ; 95 % CI : 2.46 - 3.17 ; P < .0001 ) . During the same period , overall nosocomial infection in both ICUs decreased from 47.55 per 1000 patient-days ( 104/2187 ) to 27.93 per 1000 patient days ( 207/7409 ) RR , 0.59 ; 95 % CI : 0.46 - 0.74 , P < .0001 ) . CONCLUSION A program consisting of focused education and frequent performance feedback produced a sustained improvement in compliance with h and hygiene , coinciding with a reduction in nosocomial infection rates in the ICUs OBJECTIVE To evaluate the effectiveness of a positive deviance strategy for the improvement of h and hygiene compliance in 2 adult step-down units . DESIGN A 9-month , controlled trial comparing the effect of positive deviance on compliance with h and hygiene . SETTING Two 20-bed step-down units at a tertiary care private hospital . METHODS The first phase of our study was a 3-month baseline period ( from April to June 2008 ) in which h and hygiene episodes were counted by use of electronic h and washing counters . From July to September 2008 ( ie , the second phase ) , a positive deviance strategy was implemented in the east unit ; the west unit was the control unit . During the period from October to December 2008 ( ie , the third phase ) , positive deviance was applied in both units . RESULTS During the first phase , there was no statistically significant difference between the 2 step-down units in the number of episodes of h and hygiene per 1,000 patient-days or in the incidence density of healthcare-associated infections ( HAIs ) per 1,000 patient-days . During the second phase , there were 62,000 h and hygiene episodes per 1,000 patient-days in the east unit and 33,570 h and hygiene episodes per 1,000 patient-days in the west unit ( P < .01 ) . The incidence density of HAIs per 1,000 patient-days was 6.5 in the east unit and 12.7 in the west unit ( p = .04 ) . During the third phase , there was no statistically significant difference in h and hygiene episodes per 1,000 patient-days ( P = .16 ) or in incidence density of HAIs per 1,000 patient-days . CONCLUSION A positive deviance strategy yielded a significant improvement in h and hygiene , which was associated with a decrease in the overall incidence of HAIs Introduction Achieving a sustained improvement in h and -hygiene compliance is the WHO ’s first global patient safety challenge . There is no RCT evidence showing how to do this . Systematic review s suggest feedback is most effective and call for long term well design ed RCTs , applying behavioural theory to intervention design to optimise effectiveness . Methods Three year stepped wedge cluster RCT of a feedback intervention testing hypothesis that the intervention was more effective than routine practice in 16 English/Welsh Hospitals ( 16 Intensive Therapy Units [ ITU ] ; 44 Acute Care of the Elderly [ ACE ] wards ) routinely implementing a national cleanyourh and s campaign ) . Intervention-based on Goal & Control theories . Repeating 4 week cycle ( 20 mins/week ) of observation , feedback and personalised action planning , recorded on forms . Computer-generated stepwise entry of all hospitals to intervention . Hospitals aware only of own allocation . Primary outcome : direct blinded h and hygiene compliance ( % ) . Results All 16 trusts ( 60 wards ) r and omised , 33 wards implemented intervention ( 11 ITU , 22 ACE ) . Mixed effects regression analysis ( all wards ) accounting for confounders , temporal trends , ward type and fidelity to intervention ( forms/month used ) . Intention to Treat Analysis Estimated odds ratio ( OR ) for h and hygiene compliance rose post r and omisation ( 1.44 ; 95 % CI 1.18 , 1.76;p<0.001 ) in ITUs but not ACE wards , equivalent to 7–9 % absolute increase in compliance . Per- Protocol Analysis for Implementing Wards OR for compliance rose for both ACE ( 1.67 [ 1.28–2.22 ] ; p<0.001 ) & ITUs ( 2.09 [1.55–2.81];p<0.001 ) equating to absolute increases of 10–13 % and 13–18 % respectively . Fidelity to intervention closely related to compliance on ITUs ( OR 1.12 [ 1.04 , 1.20];p = 0.003 per completed form ) but not ACE wards . Conclusion Despite difficulties in implementation , intention-to-treat , per- protocol and fidelity to intervention , analyses showed an intervention coupling feedback to personalised action planning produced moderate but significant sustained improvements in h and -hygiene compliance , in wards implementing a national h and -hygiene campaign . Further implementation studies are needed to maximise the intervention ’s effect in different setting s. Trial Registration Controlled-Trials.com IS RCT Introduction The clinical and economic burden of ventilator-associated pneumonia ( VAP ) is uncontested . We conducted the present study to determine whether low nurse-to-patient ratio increases the risk for VAP and whether this effect is similar for early-onset and late-onset VAP . Methods This prospect i ve , observational , single-centre cohort study was conducted in the medical intensive care unit ( ICU ) of the University of Geneva Hospitals . All patients who were at risk for ICU-acquired infection admitted from January 1999 to December 2002 were followed from admission to discharge . Collected variables included patient characteristics , admission diagnosis , Acute Physiology and Chronic Health Evaluation II score , co-morbidities , exposure to invasive devices , daily number of patients and nurses on duty , nurse training level and all-site ICU-acquired infections . VAP was diagnosed using st and ard definitions . Results Among 2,470 patients followed during their ICU stay , 262 VAP episodes were diagnosed in 209/936 patients ( 22.3 % ) who underwent mechanical ventilation . Median duration of mechanical ventilation was 3 days ( interquartile range 2 to 6 days ) among patients without VAP and 11 days ( 6 to 19 days ) among patients with VAP . Late-onset VAP accounted for 61 % of all episodes . The VAP rate was 37.6 episodes per 1,000 days at risk ( 95 % confidence interval 33.2 to 42.4 ) . The median daily nurse-to-patient ratio over the study period was 1.9 ( interquartile range 1.8 to 2.2 ) . By multivariate Cox regression analysis , we found that a high nurse-to-patient ratio was associated with a decreased risk for late-onset VAP ( hazard ratio 0.42 , 95 % confidence interval 0.18 to 0.99 ) , but there was no association with early-onset VAP . Conclusion Lower nurse-to-patient ratio is associated with increased risk for late-onset VAP OBJECTIVE Our aim was to ascertain the effect of an infection control program , using education and performance feedback on intensive care units , for intravascular device (IVD)-associated bloodstream infection ( BSI ) . METHODS Within 4 level III , adult , intensive care units in Argentina , all admitted , adult patients with a central vascular catheter in place for at least 24 hours were included . This was a prospect i ve before- and -after trial in which rates of IVD-associated BSI determined during a period of active surveillance without education or performance feedback ( phase 1 ) were compared after sequential implementation of an infection control program using education ( phase 2 ) and performance feedback ( phase 3 ) . RESULTS A total of 1219 IVD days were accumulated in phase 1 ; 586 during phase 2 ; and 4140 during phase 3 . Compliance with central vascular catheter -- site care improved significantly from baseline during the study period . Overall rates of IVD-associated BSI were lowered significantly from baseline after sequential implementation of education and performance feedback ( 11.10 vs 46.63 BSI/1000 IVD days ; relative risk=0.25 ; 95 % confidence interval=0.17 - 0.36 ; P<.0001 ) . Rates of IVD-associated BSI decreased significantly after implementation of an educational program ( phase 1 to phase 2 ) ( relative risk 0.37 ; confidence interval 0.19 - 0.73 ; P=.0026 ) and further reductions were seen after implementation of a performance feedback program ( phase 2 to phase 3 ) , although the reduction did not reach statistical significance ( 9.9 vs 17.06 BSI/1000 IVD days ; relative risk 0.58 ; confidence interval 0.29 - 1.18 ; P=.11 ) . Additional analysis of the data using chi2 for trends demonstrated that sequential implementation of an education and performance feedback program result ed in a significant trend toward reduced rates of IVD-associated BSI ( P<.001 ) . CONCLUSION Implementation of an infection control program , using education and performance feedback , result ed in significant reductions in rates of IVD-associated BSI OBJECTIVE To evaluate the effect of education and performance feedback regarding compliance with catheter care and h and washing on rates of catheter-associated urinary tract infection ( UTI ) in intensive care units ( ICUs ) . SETTING Two level III adult ICUs in a private healthcare facility in Argentina . PATIENTS All adult patients admitted to the study units who had a urinary catheter in place for at least 24 hours . METHODS A prospect i ve , open trial in which rates of catheter-associated UTI determined during a baseline period of active surveillance without education and performance feedback were compared with rates of catheter-associated UTI after implementing education and performance feedback . RESULTS There were 1,779 catheter-days during the baseline period and 5,568 catheter-days during the intervention period . Compliance regarding prevention of compression of the tubing by a leg improved ( from 83 % to 96 % ; relative risk [ RR ] , 1.15 ; 95 % confidence interval [ CI Output:	These components comprise manageable and widely applicable ways to reduce health-care-associated infections and improve patients ' safety
MS21503	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective To evaluate the effectiveness of register based , yearly chlamydia screening . Design Controlled trial with r and omised stepped wedge implementation in three blocks . Setting Three regions of the Netherl and s : Amsterdam , Rotterdam , and South Limburg . Participants 317 304 women and men aged 16 - 29 years listed on municipal registers at start of trial . Intervention From March 2008 to February 2011 , the Chlamydia Screening Implementation programme offered yearly chlamydia screening tests . Postal invitations asked people to use an internet site to request a kit for self collection of sample s , which would then be sent to regional laboratories for testing . Treatment and partner notification were done by the general practitioner or at a sexually transmitted infection clinic . Main outcome measures Primary outcomes were the percentage of chlamydia tests positive ( positivity ) , percentage of invitees returning a specimen ( uptake ) , and estimated chlamydia prevalence . Secondary outcomes were positivity according to sex , age , region , and sociodemographic factors ; adherence to screening invitations ; and incidence of self reported pelvic inflammatory disease . Results The participation rate was 16.1 % ( 43 358/269 273 ) after the first invitation , 10.8 % after the second , and 9.5 % after the third , compared with 13.0 % ( 6223/48 031 ) in the control block invited at the end of round two of the intervention . Chlamydia positivity in the intervention blocks at the first invitation was the same as in the control block ( 4.3 % ) and 0.2 % lower at the third invitation ( odds ratio 0.96 ( 95 % confidence interval 0.83 to 1.10 ) ) . No substantial decreases in positivity were seen after three screening rounds in any region or sociodemographic group . Among the people who participated three times ( 2.8 % of all invitees ) , positivity fell from 5.9 % to 2.9 % ( odds ratio 0.49 ( 0.47 to 0.50 ) ) . Conclusions There was no statistical evidence of an impact on chlamydia positivity rates or estimated population prevalence from the Chlamydia Screening Implementation programme after three years at the participation levels obtained . The current evidence does not support a national roll out of this register based chlamydia screening programme . Trial registration NTR 3071 ( Netherl and s Trial Register , www.trialregister.nl ) Objective To determine whether screening and treating women for chlamydial infection reduces the incidence of pelvic inflammatory disease over the subsequent 12 months . Design R and omised controlled trial . Setting Common rooms , lecture theatres , and student bars at universities and further education colleges in London . Participants 2529 sexually active female students , mean age 21 years ( range 16 - 27 ) . Intervention Participants completed a question naire and provided self taken vaginal swabs , with follow-up after one year . Sample s were r and omly allocated to immediate testing and treatment for chlamydial infection , or storage and analysis after a year ( deferred screening controls ) . Main outcome measure Incidence of clinical pelvic inflammatory disease over 12 months . Results Baseline prevalence of chlamydia was 5.4 % ( 68/1254 ) in screened women and 5.9 % ( 75/1265 ) in controls . 94 % ( 2377/2529 ) of women were followed up after 12 months . The incidence of pelvic inflammatory disease was 1.3 % ( 15/1191 ) in screened women compared with 1.9 % ( 23/1186 ) in controls ( relative risk 0.65 , 95 % confidence interval 0.34 to 1.22 ) . Seven of 74 control women ( 9.5 % , 95 % confidence interval 4.7 % to 18.3 % ) who tested positive for chlamydial infection at baseline developed pelvic inflammatory disease over 12 months compared with one of 63 ( 1.6 % ) screened women ( relative risk 0.17 , 0.03 to 1.01 ) . However , most episodes of pelvic inflammatory disease occurred in women who tested negative for chlamydia at baseline ( 79 % , 30/38 ) . 22 % ( 527/2377 ) of women reported being tested independently for chlamydia during the trial . Conclusion Although some evidence suggests that screening for chlamydia reduces rates of pelvic inflammatory disease , especially in women with chlamydial infection at baseline , the effectiveness of a single chlamydia test in preventing pelvic inflammatory disease over 12 months may have been overestimated . Trial registration Clinical Trials.gov NCT00115388 Background The advent of urine testing for Chlamydia trachomatis has raised the possibility of large-scale screening for this sexually transmitted infection , which is now the most common in the United Kingdom . The purpose of this study was to investigate the effect of an invitation to be screened for chlamydia and of receiving a negative result on levels of anxiety , depression and self-esteem . Methods 19,773 men and women aged 16 to 39 years , selected at r and om from 27 general practice s in two large city areas ( Bristol and Birmingham ) were invited by post to send home-collected urine sample s or vulvo-vaginal swabs for chlamydia testing . Question naires enquiring about anxiety , depression and self-esteem were sent to r and om sample s of those offered screening : one month before the dispatch of invitations ; when participants returned sample s ; and after receiving a negative result . Results Home screening was associated with an overall reduction in anxiety scores . An invitation to participate did not increase anxiety levels . Anxiety scores in men were lower after receiving the invitation than at baseline . Amongst women anxiety was reduced after receipt of negative test results . Neither depression nor self-esteem scores were affected by screening . Conclusion Postal screening for chlamydia does not appear to have a negative impact on overall psychological well-being and can lead to a decrease in anxiety levels among respondents . There is , however , a clear difference between men and women in when this reduction occurs Background DNA amplification assays are increasingly being used to facilitate the testing of asymptomatic individuals for urogenital Chlamydia trachomatis . The long-term clinical benefit in terms of avoided infertility and ectopic pregnancy is unknown . Methods In 1997 , 15 459 women and 14 980 men aged 21–23 years were living in Aarhus County , Denmark . A r and om sample of 4000 women and 5000 men was contacted by mail and offered the opportunity to be tested for C trachomatis by means of a sample obtained at home and mailed directly to the laboratory . The remaining 11 459 women and 9980 men received usual care and constituted the control population . All men and women were subsequently followed for 9 years by the use of Danish health registers . Data were collected on pelvic inflammatory disease ( PID ) , ectopic pregnancy ( EP ) , infertility diagnoses , in-vitro fertilisation ( IVF ) treatment and births in women , and on epididymitis in men . The intervention and control groups were compared using Cox regression analyses and the intention-to-screen principle . Results Among women , no differences were found between the intervention group and the control group : HR ( 95 % CI ) for PID 1.12 ( 0.70 to 1.79 ) ; EP 0.97 ( 0.63 to 1.51 ) ; infertility 0.87 ( 0.71 to 1.07 ) ; IVF treatment 0.88 ( 0.62 to 1.26 ) and births 1.02 ( 0.95 to 1.10 ) . In men , the HR for epididymitis was 1.25 ( 0.70 to 2.24 ) . Conclusions A population -based offer to be tested for urogenital C trachomatis infection by the use of non-invasive sample s and DNA amplification did not reduce the long-term risk of reproductive complications in women or of epididymitis in men . Trial registration number in www . clinical trials.gov NCT 00827970 Objective To compare vulvovaginal swabs with endocervical swabs as optimal diagnostic sample for detection of Chlamydia trachomatis infection . Design A diagnostic test study . Setting An urban sexual health centre . Participants 3973 women aged ≥16 years requesting testing for sexually transmitted infections . Interventions Participants took a vulvovaginal swab before routine examination , and clinicians took an endocervical swab during examination . Main outcome measure Diagnosis of chlamydia infection with sample s analysed using the Aptima Combo-2 assay ; positive results confirmed with the Aptima CT assay . Results Of the 3973 participants , 410 ( 10.3 % ) were infected with C trachomatis . Infected women were significantly younger ( 22 v 25 years , P<0.0001 ) and more likely to have symptoms suggestive of a bacterial sexually transmitted infection ( 53 % v 41 % , odds ratio 1.63 ( 95 % CI 1.30 to 2.04 ) ) , be a contact of someone with a sexually transmitted infection ( 25 % v 5 % , odds ratio 6.18 ( 4.61 to 8.30 ) ) , clinical ly diagnosed with cervicitis ( 17 % v 4 % , odds ratio 4.92 ( 3.50 to 6.91 ) ) , and have pelvic inflammatory disease ( 9 % v 3 % , odds ratio 2.85 ( 1.87 to 4.33 ) ) . When women co-infected with gonorrhoea were included in the analysis , there was an association with mixed ethnicity ( 10 % v 7 % , odds ratio 1.53 ( 1.07 to 2.17 ) ) ; but when those with gonorrhoea were removed , women of white ethnicity were significantly more likely to have chlamydia ( 85 % v 80 % , odds ratio 1.40 ( 1.03 to 1.91 ) ) . On analysis of complete paired results , vulvovaginal swabs were significantly more sensitive than endocervical swabs ( 97 % ( 95 % CI 95 % to 98 % ) v 88 % ( 85 % to 91 % ) , P<0.00001 ) ; corresponding specificities were 99.9 % and 100 % . In women with symptoms suggestive of a bacterial sexually transmitted infection , vulvovaginal swabs were significantly more sensitive than endocervical swabs ( 97 % ( 93 % to 98 % ) v 88 % ( 83 % to 92 % ) , P=0.0008 ) , as they were in women without symptoms ( 97 % ( 94 % to 99 % ) v 89 % ( 84 % to 93 % ) , P=0.002 ) . Conclusions Vulvovaginal swabs are significantly better than endocervical swabs at detecting chlamydia in women with and without symptoms suggestive of sexually transmitted infections . In those with symptoms , using endocervical sample s rather than vulvovaginal swabs would have missed 9 % of infections , or 1 in every 11 cases of chlamydia . Trial registration IS RCT N42867448 Objective To compare gonorrhoea detection by self taken vulvovaginal swabs ( tested with nucleic acid amplification tests ) with the culture of urethral and endocervical sample s taken by clinicians . Design Prospect i ve study of diagnostic accuracy . Setting 1 sexual health clinic in an urban setting ( Leeds Centre for Sexual Health , United Kingdom ) , between March 2009 and January 2010 . Participants Women aged 16 years or older , attending the clinic for sexually transmitted infection ( STI ) testing and consenting to perform a vulvovaginal swab themselves before routine examination . During examination , clinicians took urethral and endocervical sample s for culture and an endocervical swab for nucleic acid amplification testing . Interventions Urethra and endocervix sample s were analysed by gonococcal culture . Vulvovaginal swabs and endocervical swabs were analysed by the Aptima Combo 2 ( AC2 ) assay ; positive results from this assay were confirmed with a second nucleic acid amplification test . Main outcome measures Positive confirmation of gonorrhoea . Results Of 3859 women with complete data and test results , 96 ( 2.5 % ) were infected with gonorrhoea ( overall test sensitivities : culture 81 % , endocervical swabs with AC2 96 % , vulvovaginal swabs with AC2 99 % ) . The AC2 assays were more sensitive than culture ( P<0.001 ) , but the endocervical and vulvovaginal assays did not differ significantly ( P=0.375 ) . Specificity of all Aptima Combo 2 tests was 100 % . Of 1625 women who had symptoms suggestive of a bacterial STI , 56 ( 3.4 % ) had gonorrhoea ( culture 84 % , endocervical AC2 100 % , vulvovaginal AC2 100 % ) . The AC2 assays were more sensitive than culture ( P=0.004 ) , and the endocervical Output:	Harms of screening included labeling , anxiety , false-positive and false-negative test results , and other consequences of testing .
MS21504	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A total of 108 heifers were included in a placebo-controlled multicenter study on the use of an experimental Staphylococcus aureus mastitis vaccine containing whole , inactivated bacteria with pseudocapsule , alpha and beta toxoids , and a mineral oil as adjuvant . The heifers were injected in the area of the supramammary lymph nodes twice before calving and were observed and sample d throughout the first lactation . None of the vaccinated cows suffered from clinical Staph . aureus mastitis , and only 8.6 % suffered from sub clinical Staph . aureus mastitis , but a total of 16.0 % of the control cows suffered from clinical or sub clinical Staph . aureus mastitis . Mean SCC in vaccinated and control cows were the same throughout the lactation . Local swellings at the injection site were palpable in a substantial proportion of the vaccinated cows . In the statistical analyses , when cow was used as the unit of concern , no significant differences occurred between groups . However , when all parameters on udder health were considered together , the results indicated a potential protective effect of this vaccine during the entire lactation A vaccine was developed against bovine mastitis based on inactivated , highly encapsulated Staphylococcus aureus cells ; a crude extract of Staph . aureus exopolysaccharides ; and inactivated , unencapsulated Staph , aureus and Streptococcus spp . cells . This vaccine was tested on 30 heifers during a 7-mo period . The 30 heifers were r and omly assigned to three groups of 10 heifers each . The prepartum group received two injections of the vaccine at 8 and 4 wk before calving , and the postpartum group received two injections at 1 and 5 wk after calving . The control group received two injections of a placebo at 8 and 4 wk before calving . The vaccine or the placebo was administered subcutaneously in the brachiocephalicus muscle of the neck . The frequencies of intramammary infections caused by Staph . aureus were reduced from 18.8 % for heifers in the control group to 6.7 and 6.0 % for heifers in the prepartum and postpartum groups , respectively . This protective effect was maintained for at least 6 mo . The relative risk of mastitis caused by Staph . aureus was 0.31 and 0.28 for heifers in the prepartum and postpartum groups , respectively , compared with that for heifers in the control group . The results of the trial indicated the effectiveness of the vaccine in decreasing the incidence of intrammammary infections caused by Staph . aureus . A slight but nonsignificant increase occurred in fat production in the milk of vaccinated cows . The vaccine had no observable effect on somatic cell count or streptococcal infections Sixty-three Staphylococcus aureus isolates recovered from bovine sources in the USA and the Republic of Irel and were characterized by multilocus enzyme electrophoresis ( MLEE ) , ribotyping , and r and om amplified polymorphic DNA polymerase chain reaction ( RAPD-PCR ) typing at two separate laboratories . The S. aureus isolates were assigned by MLEE to 10 electrophoretic types ( ETs ) ( Index of Discrimination , D = 0.779 ) . In contrast , the same isolates were assigned to 13 ribotypes ( D = 0.888 ) , and to 12 RAPD types ( D = 0.898 ) . A common clone , ET3 , of worldwide distribution , was represented by six distinct combinations of ribotypes and RAPD types . S. aureus clones recovered from cows in Irel and were also associated with mastitis in dairy cows in the USA . These findings are consistent with the hypothesis that only a few specialized clones of S. aureus are responsible for the majority of cases of bovine mastitis , and that these clones have a broad geographic distribution The objective of the present study was to analyze an extracellular component from Staphylococcus aureus ( S. aureus ) , which we refer to as slime associated antigenic complex ( SAAC ) , and to investigate the role of SAAC-specific antibody production in protection from S. aureus bovine mastitis . Twelve primiparous gestating cows were r and omly assigned to one of the three groups : Group 1 was vaccinated with a S. aureus bacterin with very limited SAAC content ; Group 2 received a S. aureus bacterin with high SAAC content and Group 3 served as unvaccinated controls . Animals were vaccinated at 45 days before the expected parturition date and revaccinated 35 days later . All groups were challenged by intramammary infusion with a virulent heterologous strain of S. aureus 23 days after calving . Antibody response against SAAC in serum and in milk , general clinical signs , mastitis score , somatic cell count ( SCC ) and count of S. aureus in milk were evaluated before and after challenge . Immunization with a high SAAC content in the S. aureus bacterin ( Group 2 ) significantly enhanced antibody titers against SAAC ( in serum and milk ) and reduced the S. aureus concentration in milk during the post-challenge period compared to Group 1 and Group 3 . Moreover , a significant negative correlation was observed between SAAC antibody production on the day of the challenge and the S. aureus count in milk by 1 day after challenge . However , there was no evidence of a difference between vaccinated and control groups with regard to clinical signs of mastitis following the challenge . Nevertheless , the SAAC antibody concentration on the day of the challenge negatively correlated with the mastitis score in quarters infected with S. aureus at 2 days post-challenge . These results indicate that the vaccines did not prevent S. aureus intramammary infection ( IMI ) after the experimental challenge , but immunization with a S. aureus bacterin with high SAAC content was able to reduce S. aureus multiplication in the mammary gl and after challenge and suggests that the SAAC-specific antibody response could be involved in the protection against S. aureus intramammary infection . Although further studies should be performed to confirm the efficacy ( under experimental conditions and in field trials ) , we propose bacterins from strong biofilm-producing bacteria and with high SAAC content , rather than with limited SAAC content , as a cost-efficient vaccine design against S. aureus bovine mastitis A vaccine composed of three field isolates of Staphylococcus aureus ( S. aureus ) derived from cases of mastitis in cows was developed . The vaccine was administered to nine uninfected cows while 10 other cows were used as controls . All cows were challenged with a highly virulent S. aureus strain administered into two quarters of each cow . Quarters were tested for clinical signs , secretion of S. aureus , and somatic cell count ( SCC ) . No systemic effects were observed in any of the cows , vaccinated or control . Vaccinated cows had 70 % protection from infection compared with fewer than 10 % in the controls . Moreover , all quarters challenged in the vaccinated cows , regardless of whether they were successfully infected or not with S. aureus , exhibited very mild inflammatory reactions , identified by their low SCCs ( < 100,000 ) A recently described new Staphylococcus aureus vaccine " MASTIVAC I " ( Patent no. PTC/IL98/00627 ) against S. aureus udder infection elicited protection against experimentally induced infection in cows . In the present paper we describe a large-scale vaccination field trial . A total of 452 Israeli Holstein heifers were included in the study over two consecutive years . Approximately half of the heifers ( 228 ) were vaccinated while the others ( 224 ) served as a control group . Antibody response was detected in all vaccinated animals 4 - 5 weeks post- primary immunization and it was sustained throughout the experimental period ( 300 - 330 days ) . S. aureus infection could be detected in only 3 out of 228 animals ( 1.3 % ) in the vaccinated group and in 6 out of 224 ( 2.7 % ) in the control group . These numbers were too low to be statistically evaluated . However , when somatic cell counts ( SCC ) and milk yields were considered , a significant difference was found between the two groups , namely , the vaccinated cows in first and second lactation had 42 and 54 % , respectively , lower SCCs and milk yields 0.5 kg per day higher than the non-vaccinated control cows . These results suggest that the new vaccine elicits a non-specific health improvement of the udder in addition to specific protection against S. aureus A placebo-controlled field study was performed to evaluate the effect of a herd-specific vaccine against Staphylococcus aureus on intramammary infection ( IMI ) , somatic cell count ( SCC ) and clinical mastitis . Three hundred and twenty-one heifers were assigned to two groups . Heifers in the vaccination group ( n = 164 ) were vaccinated twice , i.e. 5 and 2 weeks before their expected calving date . Animals of the control group ( n = 157 ) received the same treatment with a placebo containing no bacterial antigen . Quarter milk sample s were collected immediately after parturition prior to the first machine milking , 3 - 4 weeks after calving and before the onset of treatment in animals with signs of clinical mastitis during the first 3 months after calving . For comparison of SCC the data from the monthly milk test records were evaluated . The prevalence of S. aureus in quarter milk sample s taken at calving and 3 - 4 weeks post-partum did not differ significantly between the vaccine and control group . Incidence of clinical mastitis during the first 3 months after calving and the prevalence of S. aureus in quarter milk sample s taken before the onset of treatment did not differ significantly between the groups . The SCC was lower in vaccinated than in control heifers . However , the difference was only significant on the third milk test day . Regarding prevalence of IMI with S. aureus and incidence of clinical mastitis the use of a herd-specific vaccine against S. aureus did not prove to be efficient on this farm A crude ginseng extract ( GS ) and the purified ginsenoside R(b1 ) ( R(b1 ) ) were evaluated for their adjuvant effects in dairy cattle at immunisation with ovalbumin ( OVA ) and /or a Staphylococcus aureus bacterin used for prevention of bovine mastitis . To evaluate a suitable dose of GS as an adjuvant , 36 lactating cows were r and omly divided into six groups . The cows were inoculated twice intramuscularly with a 2-week interval , with saline solution , OVA in saline , or OVA in combination with 4 , 16 or 64 mg GS , or Al(OH)(3 ) . The level of specific antibodies to OVA in serum and milk whey was measured before immunisations and 1 - 5 weeks after the second immunisation . The antibody response in serum was significantly higher in animals immunised with OVA and GS than in animals immunised with OVA alone . A significant increase in milk antibody titres compared with OVA only was only found 2 weeks after the second immunisation in the group immunised with OVA and 4 mg GS . In the second part of the study , 18 heifers were r and omly divided into three groups and were immunised twice intramuscularly with a two week interval , with the S. aureus bacterin ( control ) , or with the bacterin in combination with 4 mg GS or 1 mg R(b1 ) . The specific antibody response to S. aureus and the lymphocyte proliferation after stimulation with PWM , concanavalin A ( Con A ) or a specific S. aureus antigen was evaluated in blood sample s taken before and after immunisations as specified above . Addition of R(b1 ) result ed both in significantly higher antibody production and lymphocyte proliferation in response to PWM , Con A and S. aureus antigens than in the control group . Addition of GS induced a significantly higher lymphocyte proliferation in response to PWM and Con A than the control , but had no additional effect on the antibody production . In conclusion , both GS and R(b1 ) were safe adjuvants , and R(b1 ) had the strongest adjuvant effects , when used for immunisation against S. aureus in dairy cattle . Field trials are warranted to test the ability of GS and R(b1 ) to enhance the efficacy of mastitis vaccines in protection against intramammary infections Vaccination-challenge experiments were carried out with dairy heifers using new , killed cell-toxoid-adjuvant Staphylococcus aureus vaccines . The organisms in the vaccines were cultured under conditions which simulated in vivo growth and induced expression of a pseudocapsule . Dextran sulphate which promotes synthesis of IgG2 antibody was included in the vaccines as the primary adjuvant . Vaccinated heifers developed very high levels of both IgG1 and IgG2 anti-pseudocapsule antibody in serum , however , titres of neutralising antibody against toxoided haemolysins were generally low . Vaccinated and unvaccinated control heifers were challenged by intramammary infusion of three virulent strains of S aureus in four experiments . Vaccinated heifers were more resistant to clinical mastitis following challenge than were controls Output:	This systematic review suggests that vaccines that employ new technologies ( DNA and /or recombinant protein vaccines ) and some long-st and ing bacterins have achieved good results , which supports their use in the prevention and control of bovine mastitis caused by S. aureus .
MS21505	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : To characterize pretreatment behavioral problems and differential effects of initial therapy in children with childhood absence epilepsy ( CAE ) . Methods : The Child Behavior Checklist ( CBCL ) was administered at baseline , week 16–20 , and month 12 visits of a r and omized double-blind trial of ethosuximide , lamotrigine , and valproate . Total problems score was the primary outcome measure . Results : A total of 382 participants at baseline , 310 participants at the week 16–20 visit , and 168 participants at the month 12 visit had CBCL data . At baseline , 8 % ( 95 % confidence interval [ CI ] 6%–11 % ) of children with CAE had elevated total problems scores ( mean 52.9 ± 10.91 ) . At week 16–20 , participants taking valproic acid had significantly higher total problems ( 51.7 [ 98.3 % CI 48.6–54.7 ] ) , externalizing problems ( 51.4 [ 98.3 % CI 48.5–54.3 ] ) , attention problems ( 57.8 [ 98.3 % CI 55.6–60.0 ] ) , and attention-deficit/hyperactivity problems ( 55.8 [ 98.3 % CI 54.1–57.6 ] ) scores compared to participants taking ethosuximide ( 46.5 [ 98.3 % CI 43.4–49.6 ] ; 45.8 [ 98.3 % CI 42.9–48.7 ] ; 54.6 [ 98.3 % CI 52.4–56.9 ] ; 53.0 [ 98.3 % CI 51.3–54.8 ] ) . Lack of seizure freedom and elevated week 16–20 Conner Continuous Performance Test confidence index were associated with worse total problems scores . At month 12 , participants taking valproic acid had significantly higher attention problems scores ( 57.9 [ 98.3 % CI 55.6–60.3 ] ) compared to participants taking ethosuximide ( 54.5 [ 95 % CI 52.1–56.9 ] ) . Conclusions : Pretreatment and ongoing behavioral problems exist in CAE . Valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine , further reinforcing ethosuximide as the preferred initial therapy for CAE . Clinical trials.gov identifier : NCT00088452 . Classification of evidence : This study provides Class II evidence that for children with CAE , valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine Summary : One hundred twenty children aged 10 months to 16 years 9 months were included in three studies with lamotrigine ( LTG ) : a single‐blind study ( n = 60 ) , a pharmacokinetic study ( n = 23 ) , and a compassionate group ( n = 37 ) . At 3 months , 11 patients had become seizure‐free and 34 had > 50 % decrease in seizure frequency . The best results involved absence epilepsy , Lennox‐Gastaut syndrome ( LGS ) , and other symptomatic generalized epilepsy . Forty‐two patients were followed > 1 year , 22 for a mean of 2.2 years , and there was no significant increase in seizure frequency as compared with 3‐month follow‐up . Fourteen patients became seizure‐free for > 6 months ; all except 1 had generalized epilepsy . For 12 patients , treatment could be reduced to monotherapy , but for those with valproate ( VPA ) comedication LTG dosage had to be increased ; 25 % of patients with VPA monotherapy exhibited skin rash , appearing 3–18 days after starting LTG . For 4 patients , LTG could be reintroduced after VPA was withdrawn . Ten patients had ataxia and /or drowsiness and 2 had vomiting . For all other patients , tolerance was excellent The aim of the present study was to verify the clinical efficacy of melatonin ( MLT ) in children , adolescents and young adults with wake-sleep disorder and mental retardation , most of them on chronic anticonvulsant therapy for epileptic seizures , by means of a r and omized , double-blind , placebo-controlled cross-over trial . Twenty-five patients ( 16 males , nine females ) , aged from 3.6 to 26 years ( mean 10.5 years ) , all affected with mental retardation mostly with epileptic seizures , were r and omized to oral synthetic fast-release MLT or placebo . Melatonin was initiated at the daily dose of 3 mg , at nocturnal bedtime . In case of inefficacy , MLT dose could be titrated up to 9 mg the following 2 weeks at increments of 3 mg/week , unless the patient was unable to tolerate it . The analysis of all the sleep logs disclosed a significant treatment effect of melatonin on sleep latency ( P = 0.019 ) . Melatonin was well tolerated in all patients and no side effects were reported . In conclusion , our study supports the efficacy of MLT in young patients with mental disabilities and epileptic seizures in improving the wake-sleep disorders such as time to fall asleep . Overall , MLT appeared to influence the seizure frequency poorly , though there may be occasional seizure worsening or improving . Such a dual effect requires further studies in young epileptic patients OBJECTIVE In this multicenter study , the efficacy and tolerability of lamotrigine were assessed in 285 children less than 13 years of age , recruited from 37 centers in 11 countries . METHODS Pooled data from five open add-on studies have been analyzed . All the children had treatment-resistant epilepsy and most had two or more seizure types . Seizure frequency and global evaluation were assessed at the end of four successive 12-week periods of therapy . RESULTS Seizure frequency was reduced by 50 % or more in one third of the patients . Lamotrigine was effective in all seizure types examined , particularly for typical and atypical absence seizures . Atonic seizures also responded well . Improvement was well maintained during the treatment period . The maintenance dose had to be adjusted according to concomitant medication ; dose ranges were 1 to 5 mg/kg per day for children taking valproate and 5 to 15 mg/kg per day for those not taking valproate . The commonest reported adverse experiences were somnolence , rash , vomiting , and seizure exacerbations . Adverse experiences led to withdrawal of treatment from 36 patients ( 12.6 % ) . CONCLUSIONS These results indicate that lamotrigine is well tolerated and is effective for a broad range of seizure types , especially absence seizures and atonic seizures Summary Purpose To evaluate the efficacy , tolerability , and effects on behavior and psychosocial functioning of lamotrigine monotherapy in children with newly diagnosed typical absence seizures . Patients and methods Children meeting enrollment criteria ( n = 54 ) received a confirmatory 24-h ambulatory electroencephalogram ( EEG ) and then entered a Escalation Phase of up to 20-weeks during which lamotrigine was titrated until seizures were controlled or maximum dose ( 10.2 mg/kg ) was reached . Seizure freedom was assessed by diary review and clinic hyperventilation ( clinic HV ) and then confirmed by EEG with hyperventilation ( HV/EEG ) . Patients who maintained seizure freedom for two consecutive weekly visits were entered into the Maintenance Phase ( n = 30 ) . Diary , clinic HV , and HV/EEG data were supplemented with 24-h ambulatory EEG at baseline and the ends of the Escalation and Maintenance Phases . Health outcome assessment s were completed at screening and at the end of the Maintenance Phase . Results By the end of the Escalation Phase , seizure-free rates ( responders ) were 59 % by seizure diary ( n = 51 ) , 56 % by HV/EEG ( n = 54 ) ( primary endpoint ) , and 49 % by 24-h ambulatory EEG ( n = 49 ) . During the Maintenance Phase , 89 % ( week 24 ) and 86 % ( week 32 ) remained seizure free by diary ( n = 28 ) , 78 % by clinic HV ( n = 27 ) , and 81 % by 24-h ambulatory EEG ( n = 26 ) . Seizure freedom was first observed beginning at the fifth week of the Escalation Phase . The most frequent adverse events were headache and cough . Health outcome scores were either improved or unchanged at the end of the Maintenance Phase . Conclusions Lamotrigine monotherapy results in complete seizure freedom in a substantial number of children with typical absence seizures . Lamotrigine was well tolerated in this study OBJECTIVE To compare the efficacy of valproic acid ( VPA ) and lamotrigine as a monotherapy for absence epilepsy in children . METHODS A r and omized , open-label design was used . Childhood absence epilepsy was diagnosed based on the presence of typical seizures and video-EEG findings . Eligible patients were r and omly treated with VPA or lamotrigine . All patients were followed up for 12 months . RESULTS Forty-five out of 48 eligible children completed the study . There were 23 children in the VPA group and 22 children in the lamotrigine group . Seventeen children were seizure-free in the VPA group 12 months after treatment . Fifteen out of the 17 children showed normal EEG ( no epileptic-formed discharge ) . Twelve children were seizure-free in the lamotrigine group 12 months after treatment . The proportion showing normal EEG in the lamotrigine group ( 6/22 , 27.3 % ) was significantly lower than that in the VPA group ( 15/23 , 65.2 % ) ( P<0.05 ) . Severe adverse effects were not found in both groups . CONCLUSIONS Both VPA and lamotrigine are safe and efficacious for treatment of absence seizures in children . VPA appears to be better than lamotrigine in tapering epileptic-formed discharge OBJECTIVE To explore the efficacy and safety of the combined therapy of valproic acid ( VPA ) and lamotrigine ( LTG ) for various types of epilepsy . METHODS The patients were recruited from the epilepsy center at Affiliated Tongji Hospital , Tongji Medical College , Huazhong Science & Technology University from January 2009 to September 2011 . They were r and omly selected through a number chart and divided into two groups : child group and adult group . The prospect i ve follow-up study lasted for one year to examine the long-term efficacy and safety of combined therapy . Seizure frequency was recorded at Months 3 , 6 and 12 . The changes of seizure frequency were analyzed to calculate the 50 % response rate , 75 % response rate and seizure-free rate . All side effects during therapy were recorded . The correlation of efficacy with seizure type was also examined . Statistical analysis was performed through t test , variance analysis and χ(2 ) test . RESULTS Among a total of 134 patients , 10 of them withdrew . At Months 3 , 6 and 12 , as compared with baseline , the average reduction rate of seizure frequency per month was 56 % , 62 % , 70 % in child group versus 74 % , 82 % , 85 % in adult group ( P < 0.05 ) . Adult group was better than child group . At Month 3 , 50 % response rate , 75 % response rate and seizure-free rate was 70.97 % - 35.48 % in child group versus 83.87 % - 43.01 % in adult group . When compared at Months 3 , 6 and 12 , 50 % response rate , 75 % response rate and seizure-free rate showed no statistical difference ( P > 0.05 ) . The worse outcomes occurred more frequently in the patients with complex partial seizure ( CPS ) and than those with simple partial seizure ( SPS ) and generalized seizure GS ( P < 0.05 ) . Rash was the major side effect for withdrawal . CONCLUSION The co-medication of VPA and LTG is both effective and safe for all epileptic types , especially for SPS and GS . And the efficacy may last for up to one year . Combined therapy shows excellent safety PURPOSE To compare the efficacy of lamotrigine ( LTG ) and valproic acid ( VPA ) in newly diagnosed children and adolescents with typical absence seizures . METHODS A r and omized , open-label parallel-group design was used . After undergoing an awake video-EEG recording , which included one to two trials of 3 min of hyperventilation and intermittent photic stimulation , eligible patients were r and omized to receive LTG or VPA . LTG was initiated at a daily dose of 0.5 mg/kg for 2 weeks in two divided doses , followed by 1.0 mg/kg/day for an additional 2 weeks . Thereafter , doses were increased in 1-mg/kg/day increments every 5 days until seizures were controlled , intolerable adverse effects occurred , or a maximum dose of 12 mg/kg/day had been reached . VPA was equally uptitrated Output:	There are no placebo-controlled trials for ethosuximide or valproate , and hence , no evidence from r and omised controlled trials to support a specific effect on absence seizures for either of these two drugs . Overall , this large study demonstrates the superior effectiveness of ethosuximide and VPA compared to lamotrigine as initial monotherapy aim ed to control seizures without intolerable adverse effects in children with childhood absence epilepsy . With regards to both efficacy and tolerability , ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with absence seizures . However , if absence and generalised tonic-clonic seizures coexist , valproate should be preferred , as ethosuximide is probably inefficacious on tonic-clonic seizures
MS21506	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose : The purpose of this study was to determine the maximum tolerated dose , toxicity , and pharmacokinetics of BMS-247550 administered as a 1-h i.v . infusion every 3 weeks . Experimental Design : Patients with advanced solid malignancies were premedicated and treated with escalating doses of BMS-247550 . Blood sampling was performed to characterize the pharmacodynamics and pharmacokinetics of BMS-247550 . Results : Twenty-five patients were treated at six dose levels ranging from 7.4 to 59.2 mg/m2 . At 50 mg/m2 , 4 of 9 patients ( 44.4 % ) had dose-limiting toxicity ( neutropenia , abdominal pain/nausea ) . At 40 mg/m2 ( the recommended Phase II dose ) , 2 of 12 patients ( 16.7 % ) had dose-limiting neutropenia . Overall , the most common nonhematological toxicity was fatigue/generalized weakness ( grade 3–4 seen in 9.0 % of patients ) , followed by neurosensory deficits manifested as peripheral neuropathy and by gastrointestinal discomfort . At 40 mg/m2 , the incidence of grade 3 fatigue , abdominal pain , diarrhea , and neuropathy was 7.7 % . Grade 1–2 neuropathy was observed in all patients enrolled and treated at 40 mg/m2 . Two patients with paclitaxel-refractory ovarian cancer , one patient with taxane-naïve breast cancer , and another patient with docetaxel-refractory breast cancer had objective partial responses ( lasting 6.0 , 5.3 , 3.0 , and 4.5 months , respectively ) . The mean pharmacokinetic parameter values during course 1 for clearance , volume of distribution , and apparent terminal elimination half-life at the 40 mg/m2 ( recommended Phase II dose ) dose level were 21 liters/h/m2 , 826 liters/m2 , and 35 h ( excluding one outlier of 516 h ) , respectively . Values during course 1 and course 2 were similar . Conclusions : The recommended dose for Phase II evaluation of BMS-247550 is 40 mg/m2 , although more long-term observations are needed . BMS-247550 has advantages over taxanes in relation to drug resistance and warrants further study The epothilones are a novel class of microtubule‐stabilizing agents . Ixabepilone ( BMS‐247550 ; NSC 710428 ) is a semisynthetic analog of the natural product epothilone B. The authors conducted a Phase I study by administering ixabepilone to patients as a 1‐hour intravenous infusion daily for 3 consecutive days every 21 days PURPOSE Ixabepilone ( BMS-247550 ) is a microtubule-stabilizing epothilone B analog with activity in taxane-resistant metastatic breast cancer . The Gynecologic Oncology Group conducted a phase II evaluation of the efficacy and safety of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant primary ovarian or peritoneal carcinoma . PATIENTS AND METHODS Patients with measurable platinum- and taxane-resistant ovarian or peritoneal carcinoma , defined as progression during or within 6 months of one prior course of treatment with each agent , received intravenous ixabepilone 20 mg/m(2 ) administered over 1 hour on days 1 , 8 , and 15 of a 28-day cycle . Results Of 51 patients entered , 49 were eligible . The objective response rate was 14.3 % ( 95 % CI , 5.9 % to 27.2 % ) , with three complete and four partial responses . Twenty patients ( 40.8 % ) had stable disease , whereas sixteen ( 32.7 % ) had increasing disease . The median time to progression was 4.4 months ( 95 % CI , 0.8 to 32.6 + months ) ; median survival was 14.8 months ( 95 % CI , 0.8 to 50.0 ) months . Patients received a median of two treatment cycles ( range , 1 to 29 cycles ) , and 18.4 % of patients received > or = six cycles . Adverse effects included peripheral grade 2 ( 28.5 % ) and grade 3 ( 6.1 % ) neuropathy , grade s 3 to 4 neutropenia ( 20.4 % ) , grade 3 fatigue ( 14.3 % ) , grade 3 nausea/emesis ( 22 % ) , grade 3 diarrhea ( 10 % ) , and grade 3 mucositis ( 4 % ) . CONCLUSION Ixabepilone 20 mg/m(2 ) over 1 hour on days 1 , 8 , and 15 of a 28-day cycle demonstrates antitumor activity and acceptable safety in patients with platinum- and taxane-resistant recurrent or persistent ovarian or primary peritoneal carcinoma Purpose To establish the maximum tolerated dose ( MTD ) , dose-limiting toxicity ( DLT ) , safety and recommended Phase II dose of ixabepilone , administered weekly as an intravenous ( IV ) infusion to patients with solid tumors who have failed st and ard therapy . Method This was an open-label , single-arm , Phase I , dose-escalation study . Results The MTD of ixabepilone [ 30-min , weekly IV infusion on a 21-day schedule ( N = 33 ) ] was established at 25 mg/m2 . Grade 3 fatigue was the DLT in 2/4 patients treated at 30 mg/m2 . Ixabepilone was well tolerated at the MTD . Myelosuppression was rare , with no Grade 3/4 neutropenia . Due to the potential for cumulative neurotoxicity , the protocol was amended to a 1-h infusion , weekly for 3 weeks with a 1-week break . No DLT occurred at starting doses of 15 , 20 and 25 mg/m2 on this modified schedule ( N = 51 ) , although overall toxicity was less at 15 and 20 mg/m2 than 25 mg/m2 . Five patients ( 2 on the 30-min/21-day schedule and 3 on the 60-min/28-day schedule ) achieved durable objective partial responses across a variety of tumor types . Conclusions Ixabepilone had an acceptable safety profile at the MTD of 25 mg/m2 ( as a 30-min weekly infusion on a continuous 21-day schedule ) and at 20 mg/m2 ( as a 1-h weekly infusion on a modified 28-day schedule ) . The clinical activity and acceptable tolerability profile warrant further single- or combination-agent evaluation Purpose : Patupilone is a microtubule-targeting chemotherapeutic agent with clinical activity in a broad range of taxane-sensitive/resistant tumor types . The present phase Ib study examined the safety/tolerability and pharmacokinetics of patupilone in combination with carboplatin in patients with advanced solid tumors . Experimental Design : Patients with advanced cancer received patupilone via a 5- to 10-min i.v . infusion at doses of 3.6 to 6.0 mg/m2 q3w , immediately followed by carboplatin area under the curve ( AUC ) 5 or 6 mg/mL/min . Results : Of the 37 patients enrolled , the majority previously received taxanes ( 81 % ) and /or platinum-containing drugs ( 97.3 % ) . The maximum tolerated dose ( MTD ) of patupilone with carboplatin AUC 6 was 4.8 mg/m2 ; additional patients were enrolled to consoli date experience at this dose . Of the 22 patients who received the MTD , the most common nonhematologic adverse events were fatigue in six ( 27.3 % ) and diarrhea , nausea , vomiting , abdominal pain , and neuropathy in one each ( 4.5 % ; all grade 3 ) ; hematologic toxicities included two patients ( 9.1 % ) with grade 3 neutropenia . The pharmacokinetics of patupilone were similar to those in a previous study of patupilone monotherapy . Of the 26 patients with recurrent platinum-sensitive ovarian cancer , tumor response was assessable by response evaluation criteria in solid tumors in 17 ; 1 patient ( 6 % ) achieved a complete response , and 10 ( 59 % ) achieved a partial response . Conclusions : The combination of patupilone 4.8 mg/m2/carboplatin AUC 6 was well tolerated and showed antitumor activity similar to established regimens in patients with recurrent platinum-sensitive ovarian cancer . The optimal dose for this regimen is currently being further refined in phase II trials Background : Epothilones are a novel class of microtubule-stabilising agents , and sagopilone is a fully synthetic epothilone that has shown marked in vivo and in vitro pre clinical activity . Methods : This phase I , open-label study investigated the maximum tolerated dose ( MTD ) and dose-limiting toxicities ( DLTs ) of weekly sagopilone . Twenty-three patients with malignancy resistant or refractory to st and ard treatment were enrolled into this study evaluating sagopilone doses from 0.6 to 7.0 mg m−2 . Results : The incidence of drug-related haematological adverse events ( AEs ) was low , with two grade 3 events observed . Nonhaematological AEs were generally mild and reversible ; increased γ-GT was the only grade 4 event and grade 3 events comprised peripheral neuropathy ( n=2 ) , diarrhoea ( n=1 ) and fatigue ( n=1 ) . Two grade 3 events were DLTs ( diarrhoea and peripheral neuropathy at 7.0 mg m−2 ) . The MTD of weekly sagopilone was therefore established as 5.3 mg m−2 . Stable disease was the best overall response ( n=3 ) . Microtubule bundle formation in peripheral blood mononuclear cells increased post-treatment , peaking after 1 h. Sagopilone disposition was similar across treatment courses and showed rapidly decreasing serum concentrations after infusion end and a long terminal disposition phase with no obvious accumulation in the serum , probably reflecting a fast uptake into tissues followed by a slow release . Conclusion : Weekly administration of sagopilone could represent an alternative to the 3-weekly administration currently evaluated in phase II trials BACKGROUND Ixabepilone is a semisynthetic epothilone B analogue that is active in taxane-resistant cell lines and has shown activity in patients with refractory breast and ovarian cancer . We carried out a phase I trial of ixabepilone plus pegylated liposomal doxorubicin ( PLD ) in patients with advanced taxane-pretreated ovarian and breast cancer . METHODS Patients with recurrent ovarian or breast carcinoma received PLD every 3 or 4 weeks plus five different dose schemas of ixabepilone in cohorts of three to six patients . RESULTS Thirty patients received a total of 142 treatment cycles of the PLD-ixabepilone combination . The recommended phase II dose and schedule of ixabepilone was 16 mg/m(2 ) on days 1 , 8 , and 15 plus PLD 30 mg/m(2 ) given on day 1 , repeated every 4 weeks . H and -foot syndrome and mucositis were dose limiting when both ixabepilone and PLD were given every 3 or 4 weeks . Objective responses were observed in 3 of 13 patients ( 23 % ) with breast cancer and 5 of 17 patients ( 29 % ) with ovarian cancer . CONCLUSION Ixabepilone may be safely combined with PLD , but tolerability is highly dependent upon the scheduling of both agents . This combination demonstrated efficacy in patients with breast and ovarian cancer and merits further evaluation in these setting PURPOSE The epothilones are a novel class of nontaxane microtubule-stabilizing agents . BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days . PATIENTS AND METHODS Twenty-one patients received BMS-247550 without filgrastim in the first cycle . An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support . Twenty-one of the 27 patients had received prior paclitaxel , docetaxel , or both . RESULTS One hundred seven cycles were administered to 27 patients . The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days . Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support . Nonhematologic grade 3 toxicities included fatigue ( seven cycles ) , stomatitis ( two cycles ) , and anorexia ( one cycle ) . The mean terminal half Output:	Despite the fact that epothilones have proven active in taxane-resistant setting s in pre clinical models , it is not yet clear from Phase II/III studies review ed here that their clinical activity is superior to that of taxanes . Nevertheless , responses to epothilones have been observed in platinum-refractory/resistant ovarian cancer patients . Moreover , despite the shared mechanism of action of epothilones , their clinical profile seems clearly different , with diarrhea being the most common dose-limiting toxicity encountered with patupilone , whereas neutropenia and sensory neuropathy are the most common toxic effects observed with the other epothilones .
MS21507	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background / Objectives : Direct evidence for the effects of vegetable intake on weight loss is qualified . The study aim ed to assess the effect of higher vegetable consumption on weight loss . Subjects/ Methods : A single blind parallel controlled trial was conducted with 120 overweight adults ( mean body mass index=29.98 kg/m2 ) r and omised to two energy deficit healthy diet advice groups differing only by doubling the serving ( portion ) sizes of vegetables in the comparator group . Data were analysed as intention-to-treat using a linear mixed model . Spearmans rho bivariate was used to explore relationships between percentage energy from vegetables and weight loss . Results : After 12 months , the study sample lost 6.5±5.2 kg ( P<0.001 time ) with no difference between groups ( P>0.05 interaction ) . Both groups increased vegetable intake and lost weight in the first 3 months , and the change in weight was significantly correlated with higher proportions of energy consumed as vegetables ( rho=–0.217 , P=0.024 ) . Fasting glucose , insulin and triglyceride levels decreased ( P<0.001 time ) and high-density lipoprotein cholesterol levels increased ( P<0.001 time ) , with no difference between groups . Weight loss was sustained for 12 months by both groups , but the comparator group reported greater hunger satisfaction ( P=0.005 ) . Conclusions : Advice to consume a healthy low-energy diet leads to sustained weight loss , with reductions in cardiovascular disease risk factors regardless of an emphasis on more vegetables . In the short term , consuming a higher proportion of the dietary energy as vegetables may support a greater weight loss and the dietary pattern appears sustainable Noncompliance with therapeutic diets remains a major obstacle to achieving improvements in cardiovascular disease ( CVD ) morbidity and mortality . This study compared dietary compliance and CVD risk factor response to two dietary interventions design ed to treat hypertension , dyslipidemia , and diabetes mellitus . In a multicenter trial , 560 adults were r and omly assigned to either a self-selected , mixed-food plan ( n = 277 ) , or a nutrient-fortified prepared meal plan ( n = 283 ) ; each was design ed to provide 15 - 20 % of energy from fat , 55 - 60 % from carbohydrate , and 15 - 20 % from protein . Nutrient intake was estimated from 3-d food records collected biweekly throughout the 10-wk intervention . Compliance was determined by evaluating the participants ' ability to meet specific criteria for energy intake [ + /-420 kJ ( 100 kcal ) from the midpoint of the prescribed energy range ] , fat intake ( < 20 % , < 25 % , or < 30 % of energy from total fat ) , and the National Cholesterol Education Program/American Heart Association Step 1 and 2 diet recommendations . Compliance with energy , fat , and Step 1 and 2 criteria was better in participants who followed the prepared meal plan than in those who followed the self-selected diet ( P < 0.0001 ) . Compliant participants in both groups achieved greater reductions in body weight , systolic and diastolic blood pressure , and total and low-density-lipoprotein cholesterol than noncompliant participants ( P < 0.05 ) . In general , better endpoint responses were observed with lower fat intakes regardless of group assignment . The prepared meal plan is a simple and effective strategy for meeting the many nutrient recommendations for CVD risk reduction and improving dietary compliance and CVD endpoints Research on the conceptualization of adherence to treatment has not addressed a key question : Is adherence best defined as being a uni-dimensional or multi-dimensional behavioral construct ? The primary aim of this study was to test which of these conceptual models best described adherence to a weight management program . This ancillary study was conducted as a part of the POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for promoting weight loss . A sample of 811 overweight/obese adults was recruited across two clinical sites , and each participant was r and omly assigned to one of four macronutrient prescriptions : ( 1 ) Low fat ( 20 % of energy ) , average protein ( 15 % of energy ) ; ( 2 ) High fat ( 40 % ) , average protein ( 15 % ) ; ( 3 ) Low fat ( 20 % ) , high protein ( 25 % ) ; ( 4 ) High fat ( 40 % ) , high protein ( 25 % ) . Throughout the first 6 months of the study , a computer tracking system collected data on eight indicators of adherence . Computer tracking data from the initial 6 months of the intervention were analyzed using exploratory and confirmatory analyses . Two factors ( accounting for 66 % of the variance ) were identified and confirmed : ( 1 ) behavioral adherence and ( 2 ) dietary adherence . Behavioral adherence did not differ across the four interventions , but prescription of a high fat diet ( vs. a low fat diet ) was found to be associated with higher levels of dietary adherence . The findings of this study indicated that adherence to a weight management program was best conceptualized as being multi-dimensional , with two dimensions : behavioral and dietary adherence BACKGROUND High-fibre and low-carbohydrate diets may enhance satiety and promote weight loss . We compared a diet rich in beans aim ing to increase dietary fibre and promote weight loss with a low-carbohydrate diet in a r and omised controlled trial to assess effect and tolerability of the high-fibre bean-rich diet . METHODS AND RESULTS One hundred and seventy-three women and men , with a mean body mass index of approximately 36 kg m(-2 ) ( one-fifth with diabetes type 2 ) were r and omised to a high-fibre bean-rich diet that achieved mean ( SD ) fibre intakes of 35.5 ( 18.6 ) g day(-1 ) for women and 42.5 ( 30.3 ) g day(-1 ) for men , or a low-carbohydrate diet . Both diets were induced gradually over 4 weeks and included a 3-day feeding phase . Among 123 ( 71.1 % ) completers at 16 weeks , mean ( SD ) weight loss was 4.1 ( 4.0 ) kg in the high-fibre versus 5.2 ( 4.5 ) kg in the low-carbohydrate group [ difference , 1.1 kg , 95 % confidence interval ( CI ) = -2.6 to -0.5 ; P = 0.2 ] , with results similar to the intent-to-treat population . Low-density lipoprotein (LDL)-cholesterol levels decreased with the high-fibre diet ( difference in LDL-cholesterol versus low-carbohydrate diet , 0.2 mmol L(-1 ) , 95 % CI = 0.01 - 0.44 mmol L(-1 ) ; P = 0.045 ) , as did total cholesterol ( P = 0.038 ) , whereas changes in other lipids and glucose did not differ . After 52 weeks , the low-carbohydrate ( n = 24 ) group tended to retain weight loss better than the high-fibre group ( P = 0.06 ) , although total cholesterol remained lower with the bean-rich diet ( P = 0.049 ) . CONCLUSIONS A high-fibre bean-rich diet was as effective as a low-carbohydrate diet for weight loss , although only the bean-rich diet lowered atherogenic lipids Behavioral treatments for obesity seek to modify eating and exercise behaviors by a change in their antecedents and consequences . More direct modification of antecedents and consequences by ( a ) the provision of food to patients and ( b ) the provision of financial rewards for weight loss was hypothesized to improve treatment outcomes . Two hundred two men and women were r and omly assigned to no treatment , st and ard behavioral treatment ( SBT ) , SBT plus food provision , SBT plus incentives , or SBT plus food provision and incentives . The major finding was that food provision significantly enhanced weight loss . Weight losses with SBT averaged 7.7 , 4.5 , and 4.1 kg at 6 , 12 , and 18 months , respectively , compared with 10.1 , 9.1 , and 6.4 kg , respectively , at the same intervals with the addition of food . Food provision also enhanced attendance , completion of food records , quality of diet , and nutrition knowledge . We conclude that the provision of food to weight-loss patients is a promising methodology that deserves further exploration Context Some experts attribute a low incidence of heart disease in Mediterranean countries to dietary habits . Contribution In this multicenter , 3-group trial , investigators r and omly assigned 772 adults at high risk for cardiovascular disease to a low-fat diet or to a Mediterranean diet supplemented with either virgin olive oil ( 1 L per week ) or nuts ( 30 g per day ) . After 3 months , the Mediterranean diet groups had lower mean plasma glucose level , systolic blood pressure , and total cholesterolhigh-density lipoprotein cholesterol ratio than the low-fat diet group . Caution s The Mediterranean diet groups received more nutritional education than the low-fat diet group . Implication s Mediterranean diets supplemented with olive oil or nuts may improve cardiovascular risk factors . The Editors Cardiovascular disease is the main cause of death in industrialized countries , but incidence rates have marked geographic differences . The low incidence of coronary heart disease ( CHD ) in Mediterranean countries has been partly ascribed to dietary habits ( 1 - 3 ) . Recent findings from large European cohort studies ( 4 - 6 ) suggest that a high degree of adherence to the Mediterranean diet is associated with a reduction in mortality . In small clinical studies , the Mediterranean diet or some of its components have reduced blood pressure ( 7 ) and have improved lipid profiles ( 8 , 9 ) and endothelial function ( 10 ) . Moreover , a recent cross-sectional study ( 11 ) and a 2-year feeding trial ( 12 ) have shown that adherence to the Mediterranean diet is associated with reduced markers of vascular inflammation . These beneficial effects on surrogate markers of cardiovascular risk add biological plausibility to the epidemiologic evidence that supports a protective effect of the Mediterranean diet . Olive oil , a rich source of monounsaturated fatty acids , is a main component of the Mediterranean diet . Virgin olive oil retains all the lipophilic components of the fruit , -tocopherol , and phenolic compounds with strong antioxidant and anti-inflammatory properties ( 13 , 14 ) . Tree nuts , which are also typical in the Mediterranean diet , have a favorable fatty acid profile and are a rich source of nutrients and other bioactive compounds that may beneficially influence the risk for CHD , such as fiber , phytosterols , folic acid , and antioxidants ( 15 ) . Frequent nut intake has been associated with decreased CHD rates in prospect i ve studies ( 15 ) . Walnuts differ from all other nuts through their high content of polyunsaturated fatty acids , particularly -linolenic acid , a plant n-3 fatty acid ( 16 ) , which may confer additional antiatherogenic properties ( 17 ) . Therefore , we design ed a large-scale feeding trial in high-risk participants to assess the effects of 2 Mediterranean diets , one supplemented with virgin olive oil and the other supplemented with mixed nuts , compared with a low-fat diet on cardiovascular outcomes . We report the results of a 3-month intervention on intermediate markers of cardiovascular risk in the first 772 participants who were recruited into the trial . Supplement . Original Version ( PDF ) Methods Study Design The Prevencin con Dieta Mediterrnea ( PREDIMED ) Study is a large , parallel-group , multicenter , r and omized , controlled , 4-year clinical trial that aims to assess the effects of the Mediterranean diet on the primary prevention of cardiovascular disease ( www.predimed.org ) . An estimated 9000 high-risk participants ( > 5000 participants are already recruited ) will be assigned to 3 interventions : Mediterranean diet with virgin olive oil , Mediterranean diet with mixed nuts , or low-fat diet . The main outcome is an aggregate of cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke ) . The anticipated completion date of the trial is December 2010 . We design ed our present study to assess the 3-month effects of the dietary interventions on surrogate markers of cardiovascular risk in participants entering the study during the first 6 months of recruitment . The institutional review boards of the 10 participating centers approved the study protocol . Participants and Recruitment From October 2003 to March 2004 , we selected 930 potential participants in primary care centers affiliated with 10 teaching hospitals across Spain . Eligible participants were community-dwelling men , 55 to 80 years of age , and women , 60 to 80 years of age , who fulfilled at least 1 of 2 criteria : type 2 diabetes or 3 or more CHD risk factors ( current smoking , hypertension [ blood pressure > 140/90 mm Hg or treatment with antihypertensive drugs ] , low-density lipoprotein [ LDL ] cholesterol level 4.14 Output:	Food supplementation appeared to result in greater weight loss in dietary trials . Energy restrictions and intensity of interventions were other significant factors influencing weight loss
MS21508	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Asthma self-management programmes have been shown to increase children 's knowledge about asthma and improve their management practice s and health status . However , existing programmes have rarely addressed the unique learning needs of very young children . This study aim ed to develop and assess the effectiveness of a video tape and picture book design ed to teach children about the prevention and management of acute episodes of asthma . The information content of the educational re sources was determined by analysis of relevant medical information and asthma management skills . Social Learning Theory and consideration of the developmental stage of the target population informed the format and style of presentation of the re sources . Eighty children aged between 2 and 5 years who had been diagnosed with asthma by their medical practitioner and who required daily asthma medication participated in a controlled experimental study . The study evaluated the impact of the asthma education re sources on children 's knowledge about asthma , compliance with medication regimens and health status . Children were r and omly allocated to one of three experimental groups . Children in these groups were exposed to either the video tape alone , the book alone or both the video tape and book , or to a control group who viewed material s unrelated to asthma . The results for the three experimental groups were compared with the control group who did not receive exposure to any of the asthma education re sources . The results showed that children in each experimental group had significantly greater gains in asthma-related knowledge than children in the control group and children exposed to both re sources showed the greatest increases in knowledge . Children in each of the three experimental groups also had better compliance and health than children in the control group . These findings indicate that carefully design ed asthma education re sources are useful for providing even the youngest children with information about asthma and its management The parents of asthmatic children treated in the pediatric respiratory service of Wolfson Hospital were r and omly divided into two groups . One group compromised 26 parents who voluntarily attended a teaching session . After completion of the course , a question naire was completed by parents who had attended the course and parents who had not . The first group showed greater knowledge of all aspects of the disease and , after a year 's follow up , it was noted that there was a statistically significant lower hospitalization rate of their asthmatic child This study was conducted to test the efficacy of AIR WISE , an individually administered asthma self-management program . Subjects were paired and r and omly assigned to either an experimental group ( N = 7 ) or a control group ( N = 7 ) . The frequency of experimental group emergency visits , analyzed over a 12-month posttreatment period , was substantially less than those of the control group , supporting the hypothesis that AIR WISE is effective in high-utilizer children through improved self-management An educational training program for children with asthma , aged between 8 and 13 years , was evaluated in an 18-month r and omized , controlled experiment , including three follow-up evaluations . The objective of the program is to improve coping with asthma in daily life . The program , ten 1-hour sessions , is a combination of self-management training and cognitive behaviour therapy in a group , using games and learning material s specifically design ed for this age group . From 195 asthmatic children , 112 with inadequate self-management abilities were selected ; these children were r and omly divided into an experimental group and two control groups . The results indicated highly significant differences in favor of the experimental group on the psychological and medical variables . There were no drop-outs during the program . The conclusion is that this multi-faceted program is an effective method of teaching children how to cope with their asthma and helping them to achieve a less anxious and more realistic attitude towards their illness Twenty children with severe asthma using continual oral beta 2 agonists were r and omized equally into either a behavioral intervention group or a control group . The behavioral intervention consisted of : symptom discrimination of asthma signals , self-management techniques of breathlessness , and contingency management of asthma-related behavior . The purpose of the study was to evaluate the effects of the behavioral treatment when superimposed on a regular medical treatment . The design consisted of a four-week baseline period , a four-week intervention period , and a four-week follow-up period . Results showed that the group receiving the behavioral intervention significantly reduced their use of beta 2 agonist spray doses and days of school absenteeism without increasing the number of asthma symptoms compared with the control group . It was concluded that children with severe asthma may benefit substantially from a behavioral program in addition to their regular medical treatment Care of asthmatic children is often episodic and more therapeutic than preventive . A 2-year r and omized , controlled trial involving 95 children measured the impact of a comprehensive home and ambulatory program for pediatric asthma management using objective outcome measures . Interventions for the study group during the first year included 3-month clinic visits , education , and home visits by a specially trained research nurse . Control subjects continued to receive regular care from a family physician or pediatrician . Eight-nine subjects ( 93 % ) completed the study . Study subjects had less school absenteeism than control subjects ( 10.7 vs. 16.0 days , P = .04 ) and showed significantly better small airway function after 1 year . Asthma severity improved in 13 study subjects and worsened in 5 . The reverse was true for control subjects . Study subjects exhibited better metered aerosol technique than control subjects ( P = .0005 ) . Fewer days were spent in hospital by the study subjects admitted compared with control subjects ( 3.67 vs 11.2 days , P = .02 ) . After 1 year , more study than control families ( 72.1 % vs 33.1 % , P = .006 ) reported that their asthmatic child took responsibility for the asthma management . The intervention failed to reduce exposure to secondh and smoke or to household pets . There were no significant differences in medical visits , theophylline levels , or records of asthma symptoms . One year after discontinuing the intervention , a marked " washout " effect was observed . Comprehensive ambulatory programs of childhood asthma management can improve objective measures of illness severity but must be sustained A r and omised controlled study of an educational programme for children with asthma and their families was carried out by community child health nurses . Three hundred and sixty eight children aged 2 to 14 years were enrolled in the study after admission to hospital for asthma . The intervention group was visited monthly by a nurse for six months . The subjects were assessed six months later by a postal , self administered question naire . European children in the intervention group were taking significantly more drugs for the treatment of asthma six months after the index admission to hospital than those in the control group ( mean ( SD ) intake 2.7 ( 1.1 ) v 2.1 ( 1.0 ) , respectively ) . In particular , they were using more theophylline ( 56.6 % v 37.0 % ) and inhaled steroids ( 34.9 % v 21.0 % ) . There was no difference between the groups for parental reports of improvement , of missed schooling , and in severe attacks of asthma of not responding to the usual treatment at home . European children in the intervention group used the hospital services for severe attacks of asthma more than controls ( 34.2 % v 10.5 % ) . There were more re-admissions in the European intervention group in the subsequent six months after the index admission than in the control group ( mean ( SD ) 0.51 ( 0.97 ) v 0.29 ( 0.65 ) . Re-admission continued to be higher in the 12 months after the nurse had stopped visiting ( 0.81 ( 1.65 ) v 0.25 ( 0.65 ] . There was no difference in the duration of hospital stay between the intervention and control groups . For Polynesian children there was no difference between the groups for any outcome measures A r and omized control trial of a curriculum , A.C.T. ( Asthma Care Training ) for Kids , was conducted . Seventy-six children between the ages of 8 and 12 years , whose asthma required treatment with medications at least 25 % of the days per month , were r and omly assigned to control and experimental groups . The control group received 4 1/2 hours of lecture presentations on asthma and its management . The experimental groups ( consisting of four to seven children and their parents ) received five 1-hour sessions comprising " the treatment . " Children and their parents were interviewed before the sessions and 3 , 6 , and 12 months after the completion of the experimental treatment . Use of emergency rooms and hospitals was determined by review ing the records of these patients ( all members of the Los Angeles Kaiser Permanente health care system ) for the period of 1 year before and 1 year after the treatment . Results include ( 1 ) equivalent increases in knowledge and changes in beliefs in both groups , ( 2 ) significant changes in the self-reported compliance behaviors of the experimental group only , and ( 3 ) significant reductions in emergency room visits and days of hospitalization among those receiving the experimental treatment , compared with the control group . These changes represent an estimated savings of approximately $ 180 per child per year for those in the experimental group Children with asthma are at special risk for problems in psychological functioning , as are children with other chronic illnesses . We conducted a controlled trial of a combined education and stress management program among children ages 6 to 14 years with asthma . Eighty-one children were r and omly assigned to an intervention or a control group ; 56 children completed data collection , 29 intervention and 27 control . Psychological status was assessed by the Child Behavior Checklist ( CBCL ) before and after the intervention , as were children 's knowledge of asthma , stress ( as measured by children 's life events ) , and functional status ( as indicated by such activities as school attendance , time playing with friends , and daily chore performance ) . Children in the intervention group had a significant improvement in the total Behavior Problems score ( p < .04 ) and Internalizing scale ( p < .01 ) on the CBCL and a significant increase in daily chores ( p < .04 ) compared with the control group . Before intervention , the two groups had statistically significant positive relationships between negative life events and behavior problem scores . After intervention , children in the control group still demonstrated a significant relationship between negative life events and total and Internalizing Behavior Problem scores , although participation in the intervention group negated that relationship . Children in the intervention group whose knowledge of asthma increased were more likely to report an increase in daily chores ( p < .02 ) . We conclude that the intervention had a beneficial effect on psychological status and on children 's daily activities . The effect may have occurred in part by decreasing the likelihood that perceived stress from negative life events led to poorer adjustment To evaluate a health education program to improve family management of asthma , 310 children with asthma and their 290 parents were r and omly assigned to a program or control group . Program families participated in health education design ed to resolve specific management problems and build self-confidence in the ability to manage asthma . Following education , program parents scored better on an asthma self-management index than parents in the control group ( + 1.57 versus -0.83 , P less than 0.0001 ) . Program parents also scored better on two subindices of the self-management index : attack management ( + 0.87 vs. + 0.42 , P less than 0.05 ) and preventive measures ( + 0.42 vs. -0.35 , P less than 0.05 ) . Also , program parents reported significantly more use of guidelines to determine appropriate levels of physical activity for children . Following education , program children reported more use of three management steps than control children : productive cough or postural drainage ( 59 % vs. 35 % , P less than 0.004 ) , breathing and relaxation exercises ( 80 % vs. 65 % , P less than 0.05 ) , and attempts to stay calm ( 12 % vs. 2 % , P less than 0.05 ) . Program children reported significantly less worry than control children about the limitations asthma imposes and about making mistakes at school A r and omized trial of an instructional method was conducted in which school nurses taught children asthma self-management principles and skills , including peak flow monitoring , in 20-min , individual sessions over an 8-week period . Thirty-six children participated . An intervention group of 18 children received the teaching sessions . A control group of 18 children received regular care by the nurses , but no teaching sessions . The sample included 64 % boys , 69 % African-Americans , and 69 % Medicaid recipients . The average age of subjects was 10.2 years . The two groups were demographically similar , but despite r and om assignment , the control group had a significantly earlier age of onset of asthma and tended to have had more asthma attacks in the preceding year . These factors were statistically controlled in outcome analyses . Results of group comparisons showed no significant differences in the number of postintervention emergency room visits and days absent from school . However , nurses reported that children who practice d breathing exercises had less anxiety during exacerbations , and the nurses ' knowledge of the children 's baseline peak expiratory flow rates facilitated care of the children . Nurses expressed the opinion that the individual sessions with students might be useful in motivating them to participate effectively in later group sessions . The intervention was well accepted by students , parents , and nurses . We believe that this intervention is promising as a practical , low-cost approach to enhancing children 's asthma self-management skills and warrants further testing in a larger sample , with the intervention conducted over a longer period This study was design ed to answer three main questions : 1 ) Does asthma self-management education reduce asthma morbidity ? 2 ) Are the two programmes " Living With Asthma " and " Open Airways " equally effective in doing so ? 3 ) Is a shortened version of these programmes ( 4 weeks ) as effective as the longer original programme ( 8 weeks ) ? Twelve Italian centres of paediatric bronchopneumology selected 312 children with asthma , who were stratified by disease severity , gender and age , and then r and omly assigned to an Experimental group which received an educational programme or to a Comparison group , which did not . Of the 312 children selected , 209 ( 114 Experimental Output:	Effects of education were greater for most outcomes in moderate-severe , compared with mild-moderate asthma , and among studies employing peak flow versus symptom-based strategies . REVIEW ER 'S CONCLUSIONS Asthma self-management education programs in children improve a wide range of measures of outcome .
MS21509	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To evaluate intravitreal aflibercept injections ( IAI ; also called VEGF Trap-Eye ) for patients with macular edema secondary to central retinal vein occlusion ( CRVO ) . DESIGN R and omized controlled trial . METHODS This multicenter study r and omized 189 patients ( 1 eye/patient ) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept ( IAI 2Q4 ) ( n = 115 ) or sham ( n = 74 ) . From week 24 to week 52 , all patients received 2 mg intravitreal aflibercept as needed ( IAI 2Q4 + PRN and sham + IAI PRN ) according to retreatment criteria . The primary endpoint was the proportion of patients who gained ≥15 ETDRS letters from baseline at week 24 . Additional endpoints included visual , anatomic , and quality -of-life NEI VFQ-25 outcomes at weeks 24 and 52 . RESULTS At week 24 , 56.1 % of IAI 2Q4 patients gained ≥15 letters from baseline compared with 12.3 % of sham patients ( P < .001 ) . At week 52 , 55.3 % of IAI 2Q4 + PRN patients gained ≥15 letters compared with 30.1 % of sham + IAI PRN patients ( P < .001 ) . At week 52 , IAI 2Q4 + PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham + IAI PRN ( P < .001 ) . The most common adverse events for both groups were conjunctival hemorrhage , eye pain , reduced visual acuity , and increased intraocular pressure . CONCLUSIONS Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO result ed in a statistically significant improvement in visual acuity at week 24 , which was largely maintained through week 52 with intravitreal aflibercept PRN dosing . Intravitreal aflibercept injection was generally well tolerated The introduction of anti-vascular endothelial growth factor ( anti-VEGF ) drugs to ophthalmology over the past 7 years has revolutionised the treatment of exudative age-related macular degeneration ( AMD ) and holds great promise for diabetic macular oedema , branch and central retinal vein occlusions , and retinopathy of prematurity . Each of the three available drugs ( pegaptanib , bevacizumab and ranibizumab ) was eagerly embraced by surgeons , but the subsequent clinical results have been mixed , and the regulatory hurdles , particularly those regarding off-label use of bevacizumab , have been challenging . Into this mix enters aflibercept ( VEGF Trap-eye ( VTE ) ; Eylea , Regeneron , Tarrytown , New York , USA ) , for which the US Food and Drug Administration granted approval for the treatment of subfoveal choroidal neovascularisation due to AMD on 18 November 2011 . In contrast to the antibody-based VEGF binding strategy used by ranibizumab and bevacizumab , the VTE incorporates the second binding domain of the VEGFR-1 receptor and the third domain of the VEGFR-2 receptor.1 By fusing these extracellular protein sequences to the Fc segment of a human IgG backbone , in a manner similar to the rheumatoid arthritis drug etanercept , developers have created a chimeric protein with a very high VEGF binding affinity ( Kd≈1 pM).2 Like ranibizumab and bevacizumab , the VTE binds all isomers of the VEGF-A family , and although the clinical significance of this is not yet known , it also binds VEGF-B and placental growth factor . The approval application draws on the strengths of two concurrent AMD trials : the VIEW 1 trial , which enrolled 1217 patients in North American centres , and the VIEW 2 trial , which enrolled 1240 patients in South American , European , Asian and Australian centres . Each trial r and omised patients among four treatment arms : monthly 0.5 mg VTE , monthly or bimonthly 2 mg VTE , and monthly Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To evaluate interobserver agreement between investigator and Reading Center classification of retinal vein occlusion . DESIGN The St and ard Care versus COrticosteroid in REtinal Vein Occlusion ( SCORE ) Study includes 2 multicenter phase 3 r and omized clinical trials evaluating the efficacy and safety of intravitreal triamcinolone : one involves participants with central retinal vein occlusion ( CRVO ) and one for participants with branch retinal vein occlusion ( BRVO ) . Eyes with hemiretinal vein occlusion ( HRVO ) were classified as BRVO . PARTICIPANTS A total of 682 SCORE Study participants , including 271 with CRVO and 411 with BRVO . METHODS Participants were enrolled in each trial on the basis of investigator classification of retinal vein occlusion . Definitions of CRVO , BRVO , and HRVO based on clinical findings were specified in the study protocol . At baseline , 7-field color stereoscopic fundus photographs of the study eye of each participant were forwarded to the University of Wisconsin Fundus Photograph Reading Center ( Reading Center ) for evaluation . MAIN OUTCOME MEASURES Percent agreement and kappa statistics comparing investigator and Reading Center classification of retinal vein occlusion type . RESULTS With HRVO categorized as BRVO ( consistent with the SCORE Study design ) , there was 98.0 % agreement between investigator and Reading Center classification ( 641/654 eyes ; kappa = 0.96 ; 95 % confidence interval , 0.94 - 0.98 ) . Disagreements were fairly evenly divided between classification of an eye as CRVO by the investigator and as BRVO by the Reading Center ( 7/13 disagreements ) and vice versa ( 6 disagreements ) . When all 3 disease categories ( CRVO , BRVO , and HRVO ) were compared , there was 92.2 % agreement ( 603/654 ; unweighted kappa = 0.86 ; 95 % confidence interval , 0.83 - 0.90 ) . Most disagreements ( 38/51 , or 74.5 % ) were between BRVO and HRVO , with 9 between CRVO and BRVO , and 4 between HRVO and CRVO . In univariate analyses , baseline factors significantly associated with disagreement include larger area of capillary loss and black race ; black race was the only significant factor in a multivariate analysis . CONCLUSIONS Investigator and Reading Center agreement was excellent in the SCORE Study ; disease classification would have been altered in only 13 eyes ( 2.0 % ) had Reading Center eligibility been required . Interobserver agreement was least for classification between BRVO and HRVO OBJECTIVE To investigate baseline factors associated with visual acuity and central retinal thickness outcomes in patients with macular edema secondary to retinal vein occlusion in the St and ard Care versus COrticosteroid for REtinal Vein Occlusion ( SCORE ) Study . DESIGN Two multicenter , r and omized clinical trials : one evaluating participants with central retinal vein occlusion ( CRVO ) and one evaluating participants with branch retinal vein occlusion ( BRVO ) . PARTICIPANTS Participants with follow-up data of 1 year or more , including 238 with CRVO and 367 with BRVO . METHODS Visual acuity was measured by the electronic Early Treatment Diabetic Retinopathy Study ( E-ETDRS ) method , and central retinal thickness was measured by optical coherence tomography ( OCT ) . Regression analysis related these outcomes to 20 baseline measures . Multiple P values were adjusted to control the false discovery rate . MAIN OUTCOME MEASURES Outcome measures of visual acuity letter score included absolute change from baseline , a gain of ≥ 15 from baseline , and a loss of ≥ 15 from baseline . Outcome measures of center point thickness included absolute change from baseline , a measurement of ≤ 250 μm , and a measurement of ≥ 500 μm . Outcomes were assessed at 1 and 2 years . RESULTS For CRVO and BRVO , younger age was associated with improved visual acuity and central retinal thickness outcomes . For CRVO , triamcinolone treatment and less severe anatomic abnormalities of the retina ( center point thickness and areas of retinal hemorrhage , thickening , and fluorescein leakage ) were predictive of better visual acuity outcomes . For BRVO , no history of coronary artery disease was predictive of improved visual acuity outcomes . For center point thickness outcomes , shorter duration of macular edema was associated with improvement in both disease entities . For CRVO , higher baseline visual acuity letter score was predictive of favorable OCT outcomes . For BRVO , lower baseline visual acuity letter score , presence of dense macular hemorrhage , and no prior grid photocoagulation were predictive of favorable OCT outcomes . CONCLUSIONS Several factors were predictive of better visual acuity outcomes and more favorable OCT outcomes , including younger age and shorter duration of macular edema , respectively . These factors may assist clinicians in predicting disease course for patients with CRVO and BRVO OBJECTIVE To investigate the relationship between baseline center point retinal thickness measured by optical coherence tomography ( OCT ) and best-corrected visual acuity in eyes with macular edema associated with retinal vein occlusion and to investigate other factors associated with baseline visual acuity letter score . DESIGN The St and ard Care versus COrticosteroid for REtinal Vein Occlusion ( SCORE ) Study includes 2 multicenter , r and omized clinical trials : one evaluating participants with central retinal vein occlusion ( CRVO ) and the other evaluating participants with branch retinal vein occlusion ( BRVO ) . PARTICIPANTS After omitting 17 participants with missing or unreliable OCT measurements , analyses proceeded with 665 enrolled SCORE Study participants ( 665 eyes ) , including 262 with CRVO and 403 with BRVO . METHODS At baseline , center point thickness was measured by OCT ( Stratus OCT 3 [ n=663 ] and OCT2 [ n=2 ] ; Carl Zeiss Meditech , Dublin , CA ) , and visual acuity was measured by the electronic Early Treatment Diabetic Retinopathy Study ( E-ETDRS ) methodology . MAIN OUTCOME MEASURES Center point thickness and best-corrected E-ETDRS visual acuity letter score . RESULTS The correlation coefficient for the association between baseline OCT-measured center point thickness and best-corrected E-ETDRS visual acuity letter score is -0.27 ( 95 % confidence limit : -0.38 to -0.16 ) for participants in the CRVO trial and -0.28 ( 95 % confidence limit : -0.37 to -0.19 ) in the BRVO trial . Regression modeling estimated the following decrease in baseline visual acuity letter score for every 100-microm increase in OCT-measured center point thickness : 1.7 letters ( P=0.0007 ) for CRVO and 1.9 letters ( P<0.0001 ) for BRVO . On the basis of multivariate regression models , baseline factors significantly associated ( P<0.05 , after adjusting for multiple testing ) with baseline visual acuity letter score include age and duration of macular edema for CRVO participants and center point thickness and presence of cystoid spaces for BRVO participants . CONCLUSIONS The correlation between OCT-measured center point thickness and visual acuity letter score is modest . OCT-measured center point thickness represents a useful tool for the detection and monitoring of macular edema in retinal vein occlusion , but it can not reliably substitute for visual acuity measurements PURPOSE Assess the 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion ( CRVO ) . DESIGN Prospect i ve , r and omized , sham injection-controlled , double-masked , multicenter clinical trial . PARTICIPANTS We included 392 patients with macular edema after CRVO . METHODS Eligible patients were r and omized 1:1:1 to receive 6 monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections . After 6 months , all patients with BCVA ≤20/40 or central subfield thickness ≥250 μm could receive ranibizumab . MAIN OUTCOME MEASURES Mean change from baseline best-corrected visual acuity ( BCVA ) letter score at month 12 , additional parameters of visual function , central foveal thickness ( CFT ) , and other anatomic changes were assessed . RESULTS Mean ( 95 % confidence interval ) change from baseline BCVA letter score at month 12 was 13.9 ( 11.2 - 16.5 ) and 13.9 ( 11.5 - 16.4 ) in the 0.3 mg and 0.5 mg groups , respectively , and 7.3 ( 4.5 - 10.0 ) in the sh Output:	Results for pegaptanib and dexamethasone were mixed . Steroids were associated with cataract formation and increased intraocular pressure . No overall increase in adverse events was found with bevacizumab , ranibizumab , aflibercept or pegaptanib compared with control . There was no head-to-head evidence . CONCLUSIONS AND IMPLICATION S OF KEY FINDINGS Bevacizumab , ranibizumab , aflibercept and triamcinolone appear to be effective in treating macular oedema secondary to CRVO .
MS21510	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To examine the long-term effects of an intervention combining teacher training , parent education , and social competence training for children during the elementary grade s on adolescent health-risk behaviors at age 18 years . DESIGN Nonr and omized controlled trial with follow-up 6 years after intervention . SETTING Public elementary schools serving high-crime areas in Seattle , Wash. PARTICIPANTS Of the fifth- grade students enrolled in participating schools , 643 ( 76 % ) were given written parental consent for the longitudinal study and 598 ( 93 % ) were followed up and interviewed at age 18 years . INTERVENTIONS A full intervention provided in grade s 1 through 6 of 5 days of in-service training for teachers each intervention year , developmentally appropriate parenting classes offered to parents when children were in grade s 1 through 3 and 5 through 6 , and developmentally adjusted social competence training for children in grade s 1 and 6 . A late intervention , provided in grade s 5 and 6 only , paralleled the full intervention at these grade s. MAIN OUTCOME MEASURES Self-reported violent and nonviolent crime , substance use , sexual activity , pregnancy , bonding to school , school achievement , grade repetition and school dropout , suspension and /or expulsion , and school misbehavior ; delinquency charges from court records ; grade point average ; California Achievement Test scores : and disciplinary action reports from school records . RESULTS Fewer students receiving full intervention than control students reported violent delinquent acts ( 48.3 % vs 59.7 % ; P=.04 ) , heavy drinking ( 15.4 % vs 25.6 % ; P=.04 ) , sexual intercourse ( 72.1 % vs 83.0 % ; P=.02 ) , having multiple sex partners ( 49.7 % vs 61.5 % ; P=.04 ) , and pregnancy or causing pregnancy ( 17.1 % vs 26.4 % ; P=.06 ) by age 18 years . The full intervention student group reported more commitment ( P=.03 ) and attachment ( P=.006 ) to school , better academic achievement ( P=.01 ) , and less school misbehavior ( P=.02 ) than control students . Late intervention in grade s 5 and 6 only did not significantly affect health-risk behaviors in adolescence . CONCLUSIONS A package of interventions with teachers , parents , and children provided throughout the elementary grade s can have enduring effects in reducing violent behavior , heavy drinking , and sexual intercourse by age 18 years among multiethnic urban children . Results are consistent with the theoretical model guiding the intervention and support efforts to reduce health-risk behaviors through universal interventions in selected communities or schools serving high-crime neighborhoods OBJECTIVE To test the efficacy of 2 programs design ed to reduce high-risk behaviors among inner-city African American youth . DESIGN Cluster r and omized trial . SETTING Twelve metropolitan Chicago , Ill , schools and the communities they serve , 1994 through 1998 . PARTICIPANTS Students in grade s 5 through 8 and their parents and teachers . INTERVENTIONS The social development curriculum ( SDC ) consisted of 16 to 21 lessons per year focusing on social competence skills necessary to manage situations in which high-risk behaviors occur . The school/community intervention ( SCI ) consisted of SDC and school-wide climate and parent and community components . The control group received an attention-placebo health enhancement curriculum ( HEC ) of equal intensity to the SDC focusing on nutrition , physical activity , and general health care . MAIN OUTCOME MEASURES Student self-reports of violence , provocative behavior , school delinquency , substance use , and sexual behaviors ( intercourse and condom use ) . RESULTS For boys , the SDC and SCI significantly reduced the rate of increase in violent behavior ( by 35 % and 47 % compared with HEC , respectively ) , provoking behavior ( 41 % and 59 % ) , school delinquency ( 31 % and 66 % ) , drug use ( 32 % and 34 % ) , and recent sexual intercourse ( 44 % and 65 % ) , and improved the rate of increase in condom use ( 95 % and 165 % ) . The SCI was significantly more effective than the SDC for a combined behavioral measure ( 79 % improvement vs 51 % ) . There were no significant effects for girls . CONCLUSIONS Theoretically derived social-emotional programs that are culturally sensitive , developmentally appropriate , and offered in multiple grade s can reduce multiple risk behaviors for inner-city African American boys in grade s 5 through 8 . The lack of effects for girls deserves further research CONTEXT Despite the recent declines in rates of teenage pregnancy , relatively little is known about the few programs that have been successful in reducing adolescent pregnancy . METHODS Six agencies in New York City each r and omly assigned 100 disadvantaged 13 - 15-year-olds to their usual youth program or to the intervention being tested -- the Children 's Aid Society-Carrera program , a year-round afterschool program with a comprehensive youth development orientation . Both program and control youth were followed for three years . Multivariate regression analyses assessed the effects of program participation on the odds of current sexual activity , use of a condom along with a hormonal contraceptive , pregnancy and access to good health care . RESULTS Seventy-nine percent of participants remained in the program for three full years . Female program participants had significantly lower odds than controls of being sexually active ( odds ratio , 0.5 ) and of having experienced a pregnancy ( 0.3 ) . They had significantly elevated odds of having used a condom and a hormonal method at last coitus ( 2.4 ) . However , participation in the program created no significant impact on males ' sexual and reproductive behavior outcomes . Nonetheless , program participants of both genders had elevated odds of having received good primary health care ( 2.0 - 2.1 ) . CONCLUSIONS This program is one of only four whose evaluation has successfully documented declines in teenage pregnancy using a r and om-assignment design . Better outcomes among males may be achieved if programs reach them even earlier than their teenage years OBJECTIVE To examine the long-term effects of the full Seattle Social Development Project intervention on sexual behavior and associated outcomes assessed at age 21 years . DESIGN Nonr and omized controlled trial with long-term follow-up . SETTING Public elementary schools serving children from high-crime areas in Seattle , Wash. PARTICIPANTS Ninety-three percent of the fifth- grade students enrolled in either the full-intervention or control group were successfully interviewed at age 21 years ( n = 144 [ full intervention ] and n = 205 [ control ] ) . INTERVENTIONS In-service teacher training , parenting classes , and social competence training for children . MAIN OUTCOME MEASURES Self-report measures of all outcomes . RESULTS The full-intervention group reported significantly fewer sexual partners and experienced a marginally reduced risk for initiating intercourse by age 21 years as compared with the control group . Among females , treatment group status was associated with a significantly reduced likelihood of both becoming pregnant and experiencing a birth by age 21 years . Among single individuals , a significantly increased probability of condom use during last intercourse was predicted by full-intervention group membership ; a significant ethnic group x intervention group interaction indicated that after controlling for socioeconomic status , single African Americans were especially responsive to the intervention in terms of this outcome . Finally , a significant treatment x ethnic group interaction indicated that among African Americans , being in the full-intervention group predicted a reduced probability of contracting a sexually transmitted disease by age 21 years . CONCLUSION A theory-based social development program that promotes academic success , social competence , and bonding to school during the elementary grade s can prevent risky sexual practice s and adverse health consequences in early adulthood Sexual risk behavior outcome data from the Healthy for Life ( HFL ) project is presented . Using a social influences model , the intervention was design ed to positively affect the health behaviors of middle school students in five related areas : alcohol use , tobacco use , marijuana use , nutrition , and sexuality . The in-school program was supplemented by parent , community and peer components . The research used self-report data on an initial sample of 2,483 middle school students followed from Grade 6 to Grade 10 . Twenty-one schools were assigned to three conditions -- age appropriate ( program taught in Grade s 6 , 7 , and 8) , intensive ( program taught in Grade 7 ) and control -- using blocked r and omization . Attrition was 20 % ( by Year 4 ) and 33 % ( by Year 5 ) . By ninth grade the lifetime intercourse rate among both groups of HFL subjects was significantly higher than for controls ( controlling for baseline substance use risk and involvement with the opposite sex ) , but reported past month intercourse rates and condom use did not differ . At the tenth grade follow-up , the age appropriate subjects reported higher adjusted rates of lifetime and past month intercourse than did the controls . Intensive subjects perceived significantly lower normative rates of intercourse than controls at ninth grade follow-up , but age appropriate subjects perceived significantly higher norms at tenth grade . Our expectation that this approach would be effective in reducing adolescent sexual risk behavior has not been supported . The influence of social and community norms and context ual factors has a far greater influence on the behavior of students ( even 6 years later ) than this school-based social influences program targeting only one grade cohort PURPOSE This study was undertaken to determine whether the Adult Identity Mentoring ( AIM ) project successfully promotes abstinence , delays initiation of sex , and decreases intention to engage in sex . METHODS Twenty middle school classes of African-American seventh grade rs were r and omly assigned to receive either the AIM intervention or a st and ard health education control curriculum . The AIM is a 10-session curriculum based on the theory of possible selves . Class exercises encourage students to articulate a possible future self-identity and to develop self-promotion skills . Surveys about sexual activity were conducted before the intervention , 19 weeks after baseline , and again at 1 year after the intervention . RESULTS Hierarchical logistic regression analyses showed significant effects for the intervention on sexual intentions , abstinence , and a trend toward fewer virgins initiating intercourse for the first time , 19 weeks after baseline . Specifically , students who received the intervention showed decreased intention to engage in sex and increased abstinence compared with students not receiving the intervention . Effects for 1-year follow-up , with smaller sample size , showed only that AIM male participants maintained the significant abstinence effect . CONCLUSIONS A new intervention , AIM was evaluated among African-American seventh grade rs . This program , by focusing students on positive future selves , effectively modified sexual risk without directly providing instruction on sexually explicit topics PURPOSE To evaluate the sustained effectiveness of a middle school service learning intervention on reducing sexual initiation and recent sex among urban African-American and Latino adolescents from 7th grade through the 10th grade . METHODS During the fall of seventh grade and again in eighth grade , students were r and omly assigned by classroom to participate either in community youth service ( CYS ) or not ( controls ) . Service learning is an educational strategy that couples meaningful service in the community with classroom instruction . Students in both intervention and control conditions received classroom health lessons . Surveys were conducted at seventh grade baseline and at the end of 10th grade , approximately 2 years after intervention . Self-reported sexual behaviors of youths who had participated in CYS were compared with those of controls receiving classroom curriculum alone ( n = 195 ) . RESULTS CYS participants were significantly less likely than controls to report sexual initiation ( 2 years CYS , odds ratio [ OR ] = 0.32 ; 1 year , OR = 0.49 ) as well as recent sex ( 2 years CYS , OR = 0.39 ; 1 year CYS , OR = 0.48 ) . Among those who were virgins at seventh grade , 80 % of males in the curriculum-only condition had initiated sex , compared with 61.5 % who received 1 year of CYS , and 50 % who received 2 years . Among females , the figures were 65.2 % , 48.3 % , and 39.6 % , respectively . CONCLUSION A service learning intervention that combines community involvement with health instruction can have a long-term benefit by reducing sexual risk taking among urban adolescents OBJECTIVES This study evaluated the effectiveness of a community youth service ( CYS ) program in reducing sexual risk behaviors among African American and Latino urban young adolescents . METHODS A total of 1061 students at 2 urban middle schools were surveyed at baseline and 6-month follow-up . Students at one school were r and omly assigned by classroom to receive either the Reach for Health CYS program or the Reach for Health classroom curriculum only . Students at the other school served as controls . RESULTS At follow-up . CYS participants reported significantly less recent sexual activity ( P < .05 ) and scored lower on a sexual activity index than those in the control condition ( P < .03 ) . The greatest effect was among eighth grade rs , who received the most intensive service program ( P < .03 ) . The benefit of the curriculum-only intervention appeared greatest among students in special education classes . CONCLUSIONS Well-organized CYS that couples community involvement with classroom health instruction can have a positive impact on the sexual behaviors of young adolescents at risk for HIV , sexually transmitted diseases , and unintended pregnancy . This study also suggests the importance of including students in special education classes in health education programs OBJECTIVES We sought to test the efficacy of an intervention that was design ed to promote social inclusion and commitment to education , in reducing among students health risk behaviors and improving emotional well-being . METHODS The design was a cluster-r and omized trial in 25 secondary schools in Victoria , Australia . The subjects were 8th- grade students ( aged 13 to 14 y ) in 1997 ( n=2545 ) and subsequent 8th- grade Output:	Effective programs were significantly more likely than those that did not have an impact to strengthen the school context and to deliver activities in a supportive atmosphere . Effective programs were also more likely to build skills , enhance bonding , strengthen the family , engage youth in real roles and activities , empower youth , communicate expectations , and be stable and relatively long-lasting , although these differences between effective and ineffective programs were not statistically significant .
MS21511	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Fifty-four patients with acute cerebral infa rct ion were included in a double-blind study to evaluate Decadron ® as therapy . When comparison of patients with similar levels of consciousness was made , there was no significant difference between those patients receiving Decadron ® and those receiving placebo therapy . Three patients developed gastrointestinal tract bleeding in the placebo group , but there were none in the Decadron ® -treated group . There was no good correlation between the clinical state of the patient and the CSF pressure , either on admission or during the 14-day course of the study Dexamethasone and a placebo were compared as treatment for 40 patients with intracerebral hemorrhage . Of 19 patients receiving dexamethasone , 17 ( 89.5 % ) died during their hospital admission . Of 21 patients receiving a placebo , 16 ( 76.2 % ) died . The mortality rate was 100 % in 15 patients in the dexamethasone-treated group who were in coma or deep stupor on admission , and the mortality rate was 92 % in 12 patients with similar levels of consciousness who received a placebo . Several parameters of the neurological examination showed an improved quality of survival in the Decadron ® -treated group , but this was found only at certain days in the study . No overall statistically significant difference was found between the two therapies In this study with r and omized controls , we administered fludrocortisone acetate to 46 of 91 patients with subarachnoid hemorrhage in an attempt to prevent excessive natriuresis and plasma volume depletion . Fludrocortisone significantly reduced the frequency of a negative sodium balance during the first 6 days ( from 63 % to 38 % , p = 0.041 ) . A negative sodium balance was significantly correlated with decreased plasma volume during both the first 6 days ( p = 0.014 ) and during the entire 12-day study period ( p = 0.004 ) . Although fludrocortisone treatment tended to diminish the decrease in plasma volume , the difference was not significant ( p = 0.188 ) . More patients in the control group developed cerebral ischemia ( 31 % vs. 22 % ) and , consequently , more control patients were treated with plasma volume exp and ers ( 24 % vs. 15 % ) , which may have masked the effects of fludrocortisone on plasma volume . Fludrocortisone therefore reduces natriuresis and remains of possible therapeutic benefit in the prevention of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage A prospect i ve study of 93 acute stroke patients r and omly selected by type of antiedema treatment given ( hypertonic glicerol infusion plus dexamethasone versus dexamethasone alone ) failed to elicit any statistically significant difference between the two treatments on survival rates and quality of survival 7 and 30 days after the stroke Steroid treatment is widely used in acute cerebral infa rct ion yet its value is controversial . High dose dexamethasone ( 480 mg over 12 days ) was given in a double blind , r and omised controlled trial to 113 consecutive eligible patients with acute cerebral infa rct ion admitted to an acute stroke unit . Those with stroke for more than 48 hours , known embolic sources , diabetes , and infection were excluded . Death and quality of survival were recorded over 21 days . The active drug group ( 54 patients ) matched the placebo group ( 59 patients ) for age , initial stroke score , delay in beginning treatment , and other relevant variables . The two groups did not differ significantly in death rate or quality of survivorship . The small difference in mortality between the two groups may have represented a marginal therapeutic effect , which might reach significance in a larger sample . The widespread use of steroids in response to such a marginal therapeutic gain would expose large numbers of patients with stroke to more serious hazards of steroid treatment and convert patients who would otherwise have died into neurovegetative survivors . High dose steroid treatment was ineffective in ischaemic stroke , and the data suggest that further evaluation by a larger multicentre trial is not justified Intramuscular dexamethasone combined with intravenous low-molecular-weight dextran ( dextran 40 ) was compared with placebo in 40 patients with acute ischaemic cerebral infa rct ion . A double-blind procedure was used . Dexamethasone was given for up to 14 days and dextran 40 for up to three days after the infa rct ion . A weighted scoring system was used to evaluate neurological state and mobility . There were no differences in mortality or in improvement of the neurological or mobility scores between the two groups Fifty-three patients with acute cerebral infa rct ion were treated in a double-blind study with either dexamethasone or placebo within 24 hours of the onset of stroke . Forty-one of these survived for longer than 28 days , and the patients treated with the steroid fared slightly worse than those treated with placebo at the end of this time . Two of the five patients who died in the placebo group died of cerebral edema , compared with three out of seven patients who died in the steroid group . Infectious complications , gastrointestinal hemorrhage , and occasional serious exacerbations of diabetes occurred more commonly in the steroid group In the absence of universally accepted criteria for the medical treatment of stroke , we made a rigorously r and omized comparative study of different treatments in 300 patients . One group of patients received only a general supportive treatment design ed to ensure adequate supplies of water , electrolytes and calories , plus whatever was needed to prevent infection and correct extant associated pathology . Three other groups of patients were treated in the same way but were also given , respectively , one of the following medications : Hydergine ( S and oz ) ( a mixture of three ergot alkaloids ) , dexamethasone , and mannitol . No statistically significant difference emerged among any of the treatment groups and the reference group in terms of objective therapeutic results . The authors concluded that , at least with the dosage used in this study , none of the treatments proved more useful than conventional supportive therapy in the first 10 days after a stroke OBJECTIVE Hospital management of acute ischemic stroke varies greatly within and between different countries . This study assesses the current practice s and opinions of doctors in China routinely involved in the treatment of stroke , and compares them with those of British doctors . METHODS Question naires about the usual management of acute ischemic stroke were sent to 247 Chinese hospitals ( mostly urban ) collaborating in an acute stroke trial , seeking responses from five doctors ( one consultant , two registrars , and two house officers ) in each . After one mailing , 1,095 doctors ( 89 % ) responded . RESULTS Sixty-nine percent of the hospitals had computed tomography scanners , and 88 % of the doctors in those hospitals reported that they would routinely scan acute stroke patients ( 78 % usually within 24 hours of admission and 22 % only later ) . Sixty-two percent of doctors reported average hospital stays of 2 to 4 weeks , whereas 36 % reported longer average stays . Treatments reported to be used routinely within the first 48 hours of acute ischemic stroke included glycerol or mannitol ( 69 % of doctors ) , Chinese herb products ( 66 % ) , calcium antagonists ( 54 % ) , and aspirin ( 53 % ) ; for each of these treatments , over 70 % of all doctors believed it produced definite benefit . Reported routine use of dextran ( 44 % ) , snake venom ( 32 % ) , " photo-therapy " ( 22 % ) , and steroids ( 19 % ) was also moderately common , and about half of all doctors believed each was beneficial . In contrast , routine use of thrombolytic agents ( 4 % ) or anticoagulants ( 1 % ) was uncommon . Only one third of the doctors reported active treatment of hypertension immediately after admission . CONCLUSIONS Comparison with a similar survey in Britain showed reported use of most treatments for acute ischemic stroke was more extensive in China , but that within both countries there was wide variation . The substantial variations in clinical practice both within and between China , the United Kingdom and other countries reflect , at least in part , the substantial uncertainty about the effectiveness of many of the possible treatments for acute ischemic stroke . Large-scale r and omized evidence is needed to confirm or refute the efficacy of these and newer treatments for acute stroke The National Institute of Neurological and Communicative Disorders and Stroke initiated the Stroke Data Bank , which is a multicenter project to prospect ively collect data on the clinical course and sequelae of stroke . Additional objectives were to provide information that would enable a st and ard diagnostic clinical evaluation , to identify prognostic factors , and to provide planning data for future studies . A brief description of the structure and methods precede the baseline characterization of 1,805 patients enrolled in the Stroke Data Bank between July 1983 and June 1986 . Two thirds of these patients were admitted within 24 hours after stroke onset . Medical history , neurologic history , and hospitalization summaries are presented separately for the following stroke subtypes : infa rct ion , unknown cause ; embolism from cardiac source ; infa rct ion due to atherosclerosis ; lacune ; parenchymatous or intracerebral hemorrhage ; subarachnoid hemorrhage ; and other . The utility and limitations of these data are discussed 10 percent glycerol was given for 6 days to 30 patients who had had acute ischaemic cerebral infa rct ion , and the results were compared with those obtained after treating 31 similar patients with dexamethasone ( 16 mg . per 24 hours for 6 days ) . 1 patient treated with glycerol died of haemoglobinuria and acute renal failure . 6 patients treated with dexamethasone died--3 from cerebral oedema and 3 from non-neurological complications ( pulmonary embolism , myocardial infa rct ion , and aspiration pneumonia ) . Improvement was significantly greater in the glycerol group after 8 and 15 days . No improvement was noted using either glycerol or dexamethasone in 7 patients with spontaneous intracerebral haemorrhage Over 13 months 118 patients admitted to hospital with acute stroke were allocated at r and om to treatment with either dexamethasone or placebo . At one year there was no significant difference in the numbers of survivors or in the quality of life between the two groups . The results suggest that there is no indication for the routine administration of dexamethasone to a heterogeneous group of patients with stroke To evaluate the efficacy of dexamethasone for treatment of primary supratentorial intracerebral hemorrhage , we studied 93 patients 40 to 80 years old , using a double-blind r and omized block design . After the subjects were stratified according to their level of consciousness ( Glasgow Coma Scale ) , those with objective ly documented primary supratentorial intracerebral hemorrhage were r and omly assigned to either dexamethasone or placebo . For ethical reasons , three interim analyses were planned , to permit early termination of the trial if one study group did better than the other . During the third interim analysis , the death rate at the 21st day was identical in the two groups ( dexamethasone vs. placebo , 21 of 46 vs. 21 of 47 ; chi-square = 0.01 , P = 0.93 ) . In contrast , the rate of complications ( mostly infections and complications of diabetes ) was much higher in the dexamethasone group ( chi-square = 10.89 , P less than 0.001 ) , leading to early termination of the study . In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect , current practice s of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered Output:	Treatment did not appear to improve functional outcome in survivors . The only adverse effects reported were small numbers of gastrointestinal bleeds , infections and deterioration of hyperglycaemia across both groups . REVIEW ER 'S CONCLUSIONS There is not enough evidence to evaluate corticosteroid treatment for people with acute presumed ischaemic stroke
MS21512	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: 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 To evaluate the effectiveness on glycaemic control of a training programme in consultation skills for paediatric diabetes teams . Design Pragmatic cluster r and omised controlled trial . Setting 26 UK secondary and tertiary care paediatric diabetes services . Participants 79 healthcare practitioners ( 13 teams ) trained in the intervention ( 359 young people with type 1 diabetes aged 4 - 15 years and their main carers ) and 13 teams allocated to the control group ( 334 children and their main carers ) . Intervention Talking Diabetes programme , which promotes shared agenda setting and guiding communication style , through flexible menu of consultation strategies to support patient led behaviour change . Main outcome measures The primary outcome was glycated haemoglobin ( HbA1c ) level one year after training . Secondary outcomes were clinical measures ( hypoglycaemic episodes , body mass index , insulin regimen ) , general and diabetes specific quality of life , self reported and proxy reported self care and enablement , perceptions of the diabetes team , self reported and carer reported importance of , and confidence in , undertaking diabetes self management measured over one year . Analysis was by intention to treat . An integrated process evaluation included audio recording a sample of 86 routine consultations to assess skills shortly after training ( intervention group ) and at one year follow-up ( intervention and control group ) . Two key domains of skill assessment were use of the guiding communication style and shared agenda setting . Results 660/693 patients ( 95.2 % ) provided blood sample s at follow-up . Training diabetes care teams had no effect on HbA1c levels ( intervention effect 0.01 , 95 % confidence interval −0.02 to 0.04 , P=0.5 ) , even after adjusting for age and sex of the participants . At follow-up , trained staff ( n=29 ) were more capable than controls ( n=29 ) in guiding ( difference in means 1.14 , P<0.001 ) and agenda setting ( difference in proportions 0.45 , 95 % confidence interval 0.22 to 0.62 ) . Although skills waned over time for the trained practitioners , the reduction was not significant for either guiding ( difference in means −0.33 , P=0.128 ) or use of agenda setting ( difference in proportions −0.20 , −0.42 to 0.05 ) . 390 patients ( 56 % ) and 441 carers ( 64 % ) completed follow-up question naires . Some aspects of diabetes specific quality of life improved in controls : reduced problems with treatment barriers ( mean difference −4.6 , 95 % confidence interval −8.5 to −0.6 , P=0.03 ) and with treatment adherence ( −3.1 , −6.3 to −0.01 , P=0.05 ) . Short term ability to cope with diabetes increased in patients in intervention clinics ( 10.4 , 0.5 to 20.4 , P=0.04 ) . Carers in the intervention arm reported greater excitement about clinic visits ( 1.9 , 1.05 to 3.43 , P=0.03 ) and improved continuity of care ( 0.2 , 0.1 to 0.3 , P=0.01 ) . Conclusions Improving glycaemic control in children attending specialist diabetes clinics may not be possible through brief , team-wide training in consultation skills . Trial registration Current Controlled Trials IS RCT N61568050 OBJECTIVE Sub clinical depression is one of the most frequent mental comorbidities in patients with diabetes and is associated with a poorer long-term prognosis . Since there is a lack of specific intervention concepts for this patient group , a self-management – oriented group program ( DIAMOS [ Diabetes Motivation Strengthening ] ) was newly developed and evaluated in a r and omized trial . RESEARCH DESIGN AND METHODS DIAMOS is composed of cognitive behavioral interventions aim ing at the reduction of diabetes distress . The active control group ( CG ) received diabetes education . The primary outcome was depressive symptoms . Secondary outcomes were diabetes distress , well-being , self-care behavior , diabetes acceptance , diabetes treatment satisfaction , HbA1c , and sub clinical inflammation . RESULTS Two hundred fourteen participants ( mean age 43.3 ± 13.3 years , female sex 56.5 % , type 2 diabetes 34.1 % , mean diabetes duration 14.2 ± 10.5 years , HbA1c 8.9 ± 1.8 % , BMI 28.7 ± 71 kg/m2 ) were r and omized . The 12-month follow-up revealed a significantly stronger reduction of depressive symptoms ( Center for Epidemiologic Studies Depression Scale score ) in the DIAMOS group compared with the CG ( Δ3.9 [ 95 % CI 0.6–7.3 ] , P = 0.021 ) . Of the secondary variables , the Patient Health Question naire-9 ( Δ1.7 [ 95 % CI 0.2–3.2 ] , P = 0.023 ) , Problem Areas in Diabetes scale ( Δ8.2 [ 95 % CI 3.1–13.3 ] , P = 0.002 ) , and Diabetes Distress Scale scores ( Δ0.3 [ 95 % CI 0.1–0.5 ] , P = 0.012 ) displayed significant treatment effects . Moreover , the risk of incident major depression in the DIAMOS group was significantly reduced ( odds ratio 0.63 [ 95 % CI 0.42–0.96 ] , P = 0.028 ) . Inflammatory variables were not substantially affected . CONCLUSIONS DIAMOS is more effective in lowering depressive symptoms and diabetes-related distress in diabetic patients with sub clinical depression . DIAMOS also has a preventive effect with respect to the incidence of major depression OBJECTIVE Given the urgent need to develop effective programs that improve the ability for adolescents to achieve metabolic control equivalent to programs studied in the Diabetes . Control and Complications Trial , we have undertaken a clinical trial to determine if a behavioral intervention ( coping skills training [ CST ] ) combined with intensive diabetes management can improve metabolic control and quality of life in adolescents implementing intensive therapy regimens . RESEARCH DESIGN AND METHODS A total of 65 youths between the ages of 13 and 20 years , who elected to initiate intensive insulin therapy , were r and omly assigned to one of two groups : the intensive management with CST group and the intensive management without CST group . CST consists of a series of small group efforts design ed to teach adolescents the coping skills of social problem-solving , social skills training , cognitive behavior modification , and conflict resolution . Data were collected at pre-intervention and at 3 months following the use of the Self-Efficacy for Diabetes scale , Children 's Depression Inventory , Issues in Coping with IDDM scale , and the Diabetes Quality of Life : Youth scale . Clinical data ( HbA1c , adverse effects ) were collected monthly . RESULTS The experimental and control groups were comparable on all measures at baseline . Results show that adolescents who received CST had lower HbA1c and better diabetes self-efficacy and were less upset about coping with diabetes than adolescents receiving intensive management alone . In addition , adolescents who received the CST found it easier to cope with diabetes and experienced less of a negative impact of diabetes on quality of life than those who did not receive CST . CONCLUSIONS CST is useful in improving not only an adolescent 's metabolic control , but also their quality of life . As more pediatric providers aim for improved control , in adolescents with diabetes , the addition of this behavioral intervention may be helpful in achieving metabolic and life goals PURPOSE this study examined the metabolic and quality -of-life effects of using lispro insulin in teenagers . METHODS Teenagers on multiple daily injections who had not reached metabolic treatment goals were offered the opportunity to use lispro insulin as part of a larger ongoing study of intensive management in youth . Of the 51 who were eligible , 35 used lispro and were followed for 12 months ; the remaining 16 had reached treatment goals , were not offered lispro , and comprised the control group . RESULTS After 12 months , the teens who received lispro insulin achieved equivalent levels of metabolic control to those achieved by teens in the control group , without differences in total daily dose , insulin regimen , or adverse events . Those who received lispro found coping with diabetes less difficult than those who continued on regular insulin , and they reported less negative impact of diabetes on quality of life and fewer worries about diabetes . Both groups were equally satisfied with their diabetes treatment . CONCLUSIONS Lispro insulin is a safe alternative for youth on intensive regimens , may assist youth in coping with diabetes , and may improve their quality of life PURPOSE This study examined the metabolic trend and factors associated with an unexpected rise in HbA1c levels during the summer , with a return to baseline when school resumed , in 40 intensively treated adolescents with type 1 diabetes . METHODS Psychosocial data were collected using a variety of diabetes evaluation instruments . HbA1c was measured monthly . RESULTS HbA1C values increased by a mean of .73 % from May to July and decreased by a mean of .75 % from August to October . Lack of consistency in summer routines compared with school days was associated with a worsening in metabolic control during the summer months . Other factors associated with the summer increase in HbA1c included lower guidance scores on the Diabetes Family Behavior Scale , and higher impact and worry scores on the Diabetes Quality of Life for Youth Scale . CONCLUSIONS Interviews suggested that teenagers need to take a vacation from intensive diabetes care during the summer PURPOSE The purpose of this project was to examine the effectiveness of a stress management training program in helping adolescents with diabetes cope with stress . METHODS Youths who displayed evidence of metabolic control problems received training in the use of both cognitive-restructuring and problem-solving strategies . Treatment impact was assessed on measures of coping , anxiety level , diabetes-specific stress , and metabolic control . RESULTS Analyses of covariance showed no differences between the training group and a control group at posttest and follow-up . However , the small sample size and within-group variability may have precluded finding significant results . Therefore , within-group comparisons were conducted , and improvements were found in the training group on pretest to posttest and pretest to follow-up comparisons for anxiety , stress , and coping measures . No differences were found in the control group . CONCLUSIONS Results suggest that the intervention had some positive impact , although this interpretation must be considered preliminary . Future research should replicate this study and explore the applicability and effectiveness of this intervention in specific population OBJECTIVE To develop and evaluate a health-care communication training programme to help diabetes health-care professionals ( HCPs ) counsel their patients more skilfully , particularly in relation to behaviour change . DESIGN The HCP training was assessed using a pragmatic , cluster r and omised controlled trial . The primary and secondary analyses were intention-to-treat comparisons of outcomes using multilevel modelling to allow for cluster ( service ) and individual effects , and involved two-level linear models . SETTING Twenty-six UK paediatric diabetes services . PARTICIPANTS The training was delivered to HCPs ( doctors , nurses , dietitians and psychologists ) working in paediatric diabetes services and the effectiveness of this training was measured in 693 children aged 4 - 15 years and families after 1 year ( 95.3 % follow-up ) . INTERVENTIONS A blended learning programme was informed by a systematic review of the literature , telephone and question naire surveys of professional practice , focus groups with children and parents , experimental consultations and three developmental workshops involving a stakeholder group . The programme focused on agenda- setting , flexible styles of communication ( particularly guiding ) and a menu of strategies using web-based training and practical workshops . MAIN OUTCOME MEASURES The primary trial outcome was a change in glycosylated haemoglobin ( HbA1c ) levels between the start and finish of a 12-month study period . Secondary trial outcomes included change in quality of life , other clinical [ including body mass index ( BMI ) ] and psychosocial measures ( assessed at participant level as listed above ) and cost ( assessed at service level ) . In addition , patient details ( HbA1c levels , height , weight , BMI , insulin regimen ) , health service contacts and patient-borne costs were recorded at each clinic visit , along with details of who patients consulted with , for how long , and whether or not patients consulted on their own at each visit . Patients and carers were also asked to complete an Output:	Consistent with adult studies , around one third of adolescents experience elevated DD and this is frequently associated with suboptimal glycemic control , low self-efficacy and reduced self-care .
MS21513	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract A clinical trial was conducted in a non-fluori date d water , high-caries community in which school children ( average age = 13.04yr ) were r and omly assigned to one of four groups subjected to two different fluoride procedures . Clinical and radiographic examinations were conducted at baseline , 12 , 24 and 36 months . After 12 months , there was a small but significant rinse effect and a small gel effect which fell short of significance . The effects were additive , and subjects who received both forms of fluoride treatment experienced a 19 per cent reduction in decayed + filled ( DF ) surface increment . The pattern of incremental findings at the end of 24 months was similar to that at 12 months . Both gel and rinse effects were significant and of similar size ; subjects receiving both treatments experienced a 31 per cent reduction in DF surface increment . The incremental findings after 24–36 months 2 yr and 1 yr were similar . The effects were reduced relative to those seen at 24 months ; the gel effect was still statistically significant , but the rinse effect was not . Possible mechanisms underlying the treatment effects include deposition of CaF 2 and fluorapatite , and suppression of microbial flora UNLABELLED The piped water of Kuopio , Finl and , was fluori date d in 1959 . Owing to strong opposition by different civic groups , water fluoridation was stopped at the end of 1992 . OBJECTIVES The aim of this study was to examine the consequences of the discontinuation on dental health . METHODS In 1992 and 1995 , independent r and om sample s of all children aged 6 , 9 , 12 and 15 years were drawn from Kuopio and Jyväskylä , a nearby low fluoride town whose distribution of demographic and socio-economic characteristics was fairly similar to Kuopio 's . The total number of subjects examined was 550 in 1992 and 1198 in 1995 . Caries was registered clinical ly and radiographically by the same two calibrated dentists in both towns . RESULTS In 1992 , the mean DMFS values were lower in the fluori date d town for the two older age groups , the percentage differences for 12- and 15-year-olds being 37 % and 29 % , respectively . For the two younger age groups no meaningful differences could be found . In 1995 , the only difference with possible clinical significance was found in the 15-year-olds in favor of the fluori date d town ( 18 % ) . In 1995 , a decline in caries was seen in the two older age groups in the nonfluori date d town . In spite of discontinued water fluoridation , no indication of an increasing trend of caries could be found in Kuopio . The mean numbers of fluoride varnish and sealant applications decreased sharply in both towns between 1992 and 1995 . In spite of that caries declined . CONCLUSIONS These findings suggest that the decline of caries has little to do with professional preventive measures performed in dental clinics Many dental research ers have been expressing the response to treatment with anticariogenic agents in terms of per cent reduction of caries incidence . Although they have found it desirable from time to time to calculate confidence limits and certain probabilities associated with true per cent reduction in caries incidence , they have not done so because they did not have access to any analytical tool for this purpose . Procedures for calculating confidence intervals associated with a single mean or difference between two means from normal distributions are commonly discussed in statistical texts , but a procedure for calculating a confidence interval associated with the ratio of two means from non-normal distributions with unequal variances is rarely considered . It is the purpose of this paper to make available to the research ers such a procedure . The procedure is based on asymptotic theory , which has application in our problems , since clinical comparisons of control and experimental regimens produce large sets of data The clinical effects of different preventive regimens provided for young people in their early and middle teens were studied during a 2-year period . The regimens studied during the 1st year of the trial were professional tooth-cleaning plus fluoride mouth-rinsing every 3rd week versus fluoride varnish treatment every 6 months . During the 2nd year , the preventive measures were given in accordance with the estimated needs of each individual . The results were related to the individuals ' previous experience with dental prevention to determine whether this had a significant influence . The results showed that fairly good or excellent effects on the individuals ' oral hygiene and gingival status were readily achieved and maintained with a professional tooth-cleaning plus fluoride mouth-rinsing regimen . The study failed to demonstrate any superior caries-preventive effect of the fluoride varnish treatments . Subsequent individualized prevention produced similar average end results in all groups . Differences in the results in accordance with the individuals ' previous experience with dental prevention indicate a superior and prolonged influence on dental health of professional tooth-cleaning plus fluoride mouth-rinsing in comparison with a fluoride-based program alone 251 9 - 12-yr-old children completed a 3-yr , double-blind , clinical trial of two caries preventive fluoride programs . Caries increments and progression patterns were compared in two groups of children who rinsed every fortnight with a 0.2 % NaF solution or received biannual topical applications with a fluoride varnish ( Fluor-Protector ) . Clinical ly recorded mean DFS increments were 3.3 + /- 0.2 ( SE ) in the rinse group and 3.5 + /- 0.2 in the varnish group . In both groups nearly half of these increments were recorded in the occlusal surfaces of second molars . The mean incremental DFS recorded radiographically on approximal surfaces of posterior teeth were 1.1 + /- 0.2 and 1.5 + /- 0.2 in the rinse and varnish group , respectively . None of the inter-group differences were statistically significant ( P greater than 0.05 ) . Detailed analyses of the radiographic scores revealed a similar and extremely slow caries progression in the two study groups and they strengthened the conclusion of equal clinical efficacy of the two treatments . None of the fluoride programs had been able to change preestablished patterns of caries development among the children In a nonfluori date d community of Finl and , where fortnightly fluoride rinsing with 0.2 % sodium fluoride has been used for nearly two decades , a total of 313 children 7 - 8 yr old were recruited and r and omly divided into two groups . 206 children completed the 3-yr trial . The control group ( n = 94 ) participated in the rinsing program which included supervised toothbrushings , while the test group ( n = 112 ) received a new fluoride toothpaste tube ( 0.15 % F ) for home use every second month . Annual dental recordings , treatment plannings and the treatment itself were all carried out by one clinician . At the end of the study the number of caries-free children of the toothpaste group was lower ( P < 0.01 ) and the caries increment higher ( P < 0.05 ) than that of the mouthrinse group . Out of the mean of four dental visits per child and year some 1.5 were prophylactic by nature . No differences were found between the number of treatment visits , time or prophylactic care of the two groups . Unsupervised use of fluoride toothpaste may not be a sufficient substitute for the school-based fortnightly fluoride rinses and supervised toothbrushings in caries prevention of children with erupting permanent teeth 376 three-year old children were divided into four experimental groups and exposed to different combinations of preventive programs for a period of two years . All the groups were given the same basic prophylactic information . Additionally Group I received fluoride tablets ( FLUDENT ) for daily sucking twice a day plus a placebo dentifrice free of fluoride . Group II was given a fluoride dentifrice containing 0.025 % F , ( ACTA ) . Group III was given a placebo dentifrice plus fluoride varnish ( Duraphat ) twice a year . Group IV a fluoride dentifrice containing 0.025 % F ( ACTA ) plus fluoride varnish ( Duraphat ) twice a year . No statistically significant difference in caries increment during the two experimental years was found between the groups . A tendency to lower caries increment was found in Group IV , i.e. in the children using the low fluoride dentifrice and treated twice a year with fluoride varnish 751 14- and 15-year old children completed a 3-year , double-blind , caries preventive program . The effects of daily , supervised toothbrushing with an 0.76 % sodium monofluorophosphate dentifrice , rinsing with a 0.05 % sodium fluoride mouthrinse , and the combined effects of the two treatments were investigated . Both the dentifrice and mouthrinse reduced the incidence of dental caries , but their combined use at the same time had no greater effect than either used alone The study groups using a dentifrice and mouthrinse both containing fluorides , a dentifrice containing stannous fluoride and a mouthrinse containing sodium fluoride , or a mouthrinse containing sodium fluoride with a placebo dentifrice had a 20.7 % to 29.0 % lower DMF increment than the control group after 30 months . These differences were significant . The study groups using a dentifrice containing amine fluorides and a placebo mouthrinse , a mouthrinse containing amine fluorides and a placebo dentifrice , or a dentifrice containing stannous fluoride and a placebo mouthrinse had a 13.6 % to 22.4 % lower DMF increment than the control group . These differences were not statistically significant . There was no significant difference in effectiveness against caries between the use of the organic or inorganic fluoride products The purpose of this study was to evaluate the separate effect of fluoride dentifrice , fluoride mouthrinsing and fluoride varnish on approximal dental caries . All 252 13 - 14-yr-old children at an elementary school were selected at r and om and divided among four groups for a 3-yr longitudinal study . Group 1 received a fluoride dentifrice for home care and a fluoride mouthrinse once a week . Group 2 received a fluoride dentifrice for home care and a placebo mouthrinse once a week . Group 3 received a fluoride dentifrice for home care and a fluoride varnish once every 3 months . Group 4 received a placebo dentifrice for home care and a fluoride rinse once a week . Fluoride rinsing did not give any additional effect compared with placebo-rinsing when a fluoride dentifrice was used for home care . Fluoride varnish gave a significant caries reduction compared with fluoride rinsing A study to test the efficacy of two amine fluoride products in reducing the extent of plaque and the degree of gingivitis was conducted with 6th- grade school children in Pensacola , Florida . The treatment regimens consisted of a daily supervised mouthrinse at school and the ad libitum home use of a dentifrice . Examinations were conducted at 12-week and 20-week intervals after the treatment had begun . There was no recognizable difference between the plaque and gingival reductions achieved with the use of the amine fluoride dentifrice or mouthrinse when compared either with their inorganic counterparts or with placebo treatment The aim of this study was to assess the caries incidence and plaque accumulation in schoolchildren at caries risk , after brushing the teeth fortnightly with gels containing 0 , 0.4 % F , 1.25 % F as amine fluoride ( AmF ) or the common amine fluoride toothpaste containing 0.125 % F. The study was conducted double blind over an 18-month period , and after 6 months discontinuation of brushing . Only the group that brushed with the 1.25 % AmF gel showed a significant decrease in caries development compared to the group that brushed with the 0.125 % AmF toothpaste . During the 6-month discontinuation period , the incidence of caries increased in all groups ; the differences in caries development between all groups were not significant . Plaque indices were significantly lower in the AmF-treated groups . The highest fluoride concentration in the gel reduced the development of caries to zero , probably due to increased fluoride levels in the oral milieu of caries risk children . In order to maintain a positive effect of fluoride over an extended time period , caries-prone subjects should continue an initiated fluoride programme This report describes a clinical study carried out to compare the cariesinhibiting effect of the unsupervised home use of a sodium-monofluorophosphate-calcium-carbonate-based toothpaste formulation The aim of this trial was to compare the caries-preventive effect of sodium fluoride varnish and acidulated phosphate fluoride ( APF ) gel . A total of 254 children aged 12 - 13 years with high past caries experience were r and omly divided into two groups . The participants received semi-annual applications of either fluoride varnish or APF gel for 3 years . During the study , the mean ( + /- SD ) total DMFS increments of the varnish and gel groups were 6.8 + /- 5.6 and 7.7 + /- 6.4 , respectively , when initial caries was included , and 3.1 + /- 3.7 and 3.6 + /- 4.6 when initial caries was excluded . The difference was most evident on the approximal surfaces ( varnish : 1.4 + /- 2.4 ; gel : 1.9 + /- 3.1 ) . However , this difference was not statistically significant . Although larger studies are needed for firm conclusions about the comparative effect of the two fluoride measures , the results suggest that fluoride varnish is as effective as fluoride gel at least in preventing approximal caries . Taking into account the shorter treatment time , using fluoride varnish for professional applications seems justified Output:	REVIEW ER 'S CONCLUSIONS Fluoride toothpastes in comparison to mouthrinses or gels appear to have a similar degree of effectiveness for the prevention of dental caries in children . There is no clear suggestion that fluoride varnish is more effective than mouthrinses and the evidence for the comparative effectiveness of fluoride varnishes and gels , and mouthrinses and gels is inconclusive . Acceptance is likely to be greater for fluoride toothpaste
MS21514	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Concerns about adverse consequences of early childbearing and risk of sexually transmitted diseases ( STD ) have renewed interest in the sexual behaviour of adolescents in developing countries , where they represent a large proportion of the population and are at highest risk . To date , little is known about the sexual knowledge of adolescents in developing countries . This study 's primary objective was to evaluate the effectiveness of a responsible sexuality education programme ( RSP ) in changing knowledge associated with sex and sexuality ; secondary objectives were to evaluate changes in attitudes and behavioural intent . METHODS A cluster r and omized design r and omizing high school classes in Belize City . Subjects were 13 - 19 years old . RESULTS Seven schools in Belize City were selected ; 8 classrooms were r and omized to the intervention arm and 11 classrooms to the control arm ( N = 399 ) . The intervention was associated with two more correct answers on the post-test ( difference score was 2.22 points , 95 % CI = 0.53 , 3.91 ) after adjusting for gender and previous sexual experience . After controlling for gender and previous sexual experience , the intervention was associated with no change in the attitudes ( 0.06 , 95 % CI : -2.89 , 2.82 ) or behavioural intent domains ( 0.84 , 95 % CI : -1.12 , 2.46 ) . CONCLUSIONS Greater changes in knowledge were observed in the intervention group than in the control group following the intervention . Changes were not observed for the attitude or behavioural intent domains . These results and the results of similar studies may be used to further improve sex education programmes as it is imperative that students have access to the information necessary to make informed decisions regarding their sexual health Objective To evaluate the effectiveness of youth development in reducing teenage pregnancy , substance use , and other outcomes . Design Prospect i ve matched comparison study . Setting 54 youth service sites in Engl and . Participants Young people ( n=2724 ) aged 13 - 15 years at baseline deemed by professionals as at risk of teenage pregnancy , substance misuse , or school exclusion or to be vulnerable . Intervention Intensive , multicomponent youth development programme including sex and drugs education ( Young People ’s Development Programme ) versus st and ard youth provision . Main outcome measures Various , including pregnancy , weekly cannabis use , and monthly drunkenness at 18 months . Results Young women in the intervention group more commonly reported pregnancy than did those in the comparison group ( 16 % v 6 % ; adjusted odds ratio 3.55 , 95 % confidence interval 1.32 to 9.50 ) . Young women in the intervention group also more commonly reported early heterosexual experience ( 58 % v 33 % ; adjusted odds ratio 2.53 , 1.09 to 5.92 ) and expectation of teenage parenthood ( 34 % v 24 % ; 1.61 , 1.07 to 2.43 ) . Conclusions No evidence was found that the intervention was effective in delaying heterosexual experience or reducing pregnancies , drunkenness , or cannabis use . Some results suggested an adverse effect . Although method ological limitations may at least partly explain these findings , any further implementation of such interventions in the UK should be only within r and omised trials OBJECTIVE To test the efficacy of a prevention intervention to reduce sexual risk behavior among Latino adolescents . DESIGN R and omized controlled trial from April 2000 through March 2003 , with data collection before and after intervention and at 3 , 6 , and 12 months . SETTING Northeast Philadelphia schools . PARTICIPANTS Latinos aged 13 through 18 years ( 249 males and 304 females ) ; 81.6 % retained at 12-month follow-up . INTERVENTIONS The HIV and health-promotion control interventions consisted of six 50-minute modules delivered by adult facilitators to small , mixed-gender groups in English or Spanish . Main Outcome Measure Self-reported sexual behavior . RESULTS Analyses using generalized estimation equations over the follow-up period revealed that adolescents in the HIV intervention were less likely to report sexual intercourse ( odds ratio , 0.66 ; 95 % confidence interval [ CI ] , 0.46 - 0.96 ) , multiple partners ( odds ratio , 0.53 ; 95 % CI , 0.31 - 0.90 ) , and days of unprotected intercourse ( relative risk , 0.47 ; 95 % CI , 0.26 - 0.84 ) and more likely to report using condoms consistently ( odds ratio , 1.91 ; 95 % CI , 1.24 - 2.93 ) . Baseline sexual experience and language use moderated intervention efficacy . Adolescents assigned to the HIV intervention who were sexually inexperienced at baseline reported fewer days of unprotected sex ( relative risk , 0.22 ; 95 % CI , 0.08 - 0.63 ) ; Spanish speakers were more likely to have used a condom at last intercourse ( odds ratio , 4.73 ; 95 % CI , 1.72 - 12.97 ) and had a greater proportion of protected sex ( mean difference , 0.35 ; P<.01 ) compared with similar adolescents in the health-promotion intervention . CONCLUSION Results provide evidence for the efficacy of HIV intervention in decreasing sexual activity and increasing condom use among Latino adolescents Recent evidence suggests that conditional cash transfer programs for schooling are effective in raising school enrollment and attendance . However , there is also reason to believe that such programs can affect other outcomes , such as the sexual behavior of their young beneficiaries . Zomba Cash Transfer Program is a r and omized , ongoing conditional cash transfer intervention targeting young women in Malawi that provides incentives ( in the form of school fees and cash transfers ) to current schoolgirls and recent dropouts to stay in or return to school . An average offer of US$ 10/month conditional on satisfactory school attendance – plus direct payment of secondary school fees – led to significant declines in early marriage , teenage pregnancy , and self-reported sexual activity among program beneficiaries after just one year of program implementation . For program beneficiaries who were out of school at baseline , the probability of getting married and becoming pregnant declined by more than 40 percent and 30 percent , respectively . In addition , the incidence of the onset of sexual activity was 38 percent lower among all program beneficiaries than the control group . Overall , these results suggest that conditional cash transfer programs not only serve as useful tools for improving school attendance , but may also reduce sexual activity , teen pregnancy , and early marriage Objective To assess the impact of a theoretically based sex education programme ( SHARE ) delivered by teachers compared with conventional education in terms of conceptions and terminations registered by the NHS . Design Follow-up of cluster r and omised trial 4.5 years after intervention . Setting NHS records of women who had attended 25 secondary schools in east Scotl and . Participants 4196 women ( 99.5 % of those eligible ) . Intervention SHARE programme ( intervention group ) v existing sex education ( control group ) . Main outcome measure NHS recorded conceptions and terminations for the achieved sample linked at age 20 . Results In an “ intention to treat ” analysis there were no significant differences between the groups in registered conceptions per 1000 pupils ( 300 SHARE v 274 control ; difference 26 , 95 % confidence interval −33 to 86 ) and terminations per 1000 pupils ( 127 v 112 ; difference 15 , −13 to 42 ) between ages 16 and 20 . Conclusions This specially design ed sex education programme did not reduce conceptions or terminations by age 20 compared with conventional provision . The lack of effect was not due to quality of delivery . Enhancing teacher led school sex education beyond conventional provision in eastern Scotl and is unlikely to reduce terminations in teenagers . Trial registration IS RCT N48719575 CONTEXT Latino and black adolescents are disproportionately affected by STDs , including HIV , and unintended pregnancies . Few parent-based interventions have targeted these youth , focused on early adolescence and had high participation rates . METHODS Between 2003 and 2009 , a r and omized clinical trial was conducted with 2,016 Latino and black mother-adolescent dyads in New York City . Adolescents were eligible if they were in grade 6 or 7 . Dyads were assigned to one of three conditions : a parent-based intervention , Families Talking Together ( FTT ) ; an adolescent-only intervention , Making a Difference ! ( MAD ) ; or a combined FTT+MAD intervention . Respondents completed question naires at baseline and 12 months later . Single-degree-of-freedom contrasts and logistic regression analysis were used to evaluate differences in outcomes by intervention . RESULTS The proportion of youth who reported ever having engaged in vaginal intercourse increased over the study period by eight percentage points among those in the MAD group , five points in the FTT group and three points in the combined group ; the differences among these increases were not statistically significant . Adolescents in the two FTT groups were significantly more likely than those in the MAD group to indicate that their mother had talked to them about not having intercourse ( 79 % vs. 68 % ) . They also scored higher than youth in the MAD group on measures of communication and perceived maternal attributes , and lower on activities that might lead to risky behaviors . CONCLUSIONS The proportions of adolescents who initiated intercourse during the study period were not significantly different across groups , implying that the interventions were comparable . Findings suggest that FTT may have led to improved parenting behaviors IMPORTANCE Preventing early pregnancy among vulnerable adolescents requires innovative and sustained approaches . Prime Time , a youth development intervention , aims to reduce pregnancy risk among adolescent girls seeking clinic services who are at high risk for pregnancy . OBJECTIVE To evaluate sexual risk behaviors and related outcomes with a 24-month postbaseline survey , 6 months after the conclusion of the Prime Time intervention . DESIGN R and omized controlled trial . SETTING Community and school-based primary care clinics . PARTICIPANTS Of 253 sexually active 13- to 17-year-old girls meeting specified risk criteria , 236 ( 93.3 % ) completed the 24-month follow-up survey . INTERVENTION Offered during an 18-month period , Prime Time includes case management and youth leadership programs . MAIN OUTCOME MEASURES Self-reported consistency of condom , hormonal , and dual- method contraceptive use with most recent male sex partner and number of male sex partners in the past 6 months . RESULTS At 24-month follow-up , the intervention group reported significantly more consistent use of condoms , hormonal contraception , and dual- method contraception than the control group . Intervention participants also reported improvements in family connectedness and self-efficacy to refuse unwanted sex , and reductions in the perceived importance of having sex . No between-group differences were found in the number of recent male sex partners . CONCLUSIONS AND RELEVANCE This study contributes to what has been a dearth of evidence regarding youth development interventions offered through clinic setting s , where access to high-risk adolescents is plentiful but few efforts have emphasized a dual approach of strengthening sexual and nonsexual protective factors while addressing risk . Findings suggest that health services grounded in a youth development framework can lead to long-term reductions in sexual risk among vulnerable youth PURPOSE Prime Time , a youth development intervention , aims to reduce pregnancy risk among adolescent girls seeking clinic service who are at high risk for pregnancy . This article examines sexual risk behaviors and hypothesized psychosocial mediators after 12 months of the Prime Time intervention . METHODS This study was a r and omized controlled trial with 253 girls aged 13 - 17 years meeting specified risk criteria . Intervention participants were involved in Prime Time programming plus usual clinic services for 18 months , control participants received usual clinic services . The intervention used a combination of case management and peer leadership programs . Participants in this interim outcomes study completed self-report surveys at baseline and 12 months after enrollment . Surveys assessed sexual risk behaviors and psychosocial factors targeted for change by Prime Time . RESULTS At the 12-month interim , the intervention group reported more consistent use of condoms , hormonal contraception , and dual contraceptive methods with their most recent partner as compared with the control group . The intervention group also reported greater stress management skills with trends toward higher levels of prosocial connectedness at school and with family . No between-group differences were noted in psychosocial measures specific to sex and contraceptive use . CONCLUSION Preventing early pregnancy among high-risk adolescents requires multifaceted , sustained approaches . An important research focus involves testing youth development interventions offered through clinic setting s , where access to high-risk adolescents is plentiful and few efforts have emphasized a dual approach of building protective factors while addressing risk . Findings suggest that youth development interventions through clinic setting s hold promise in reducing pregnancy risk among high-risk youth Abstract Objective : To determine whether a theoretically based sex education programme for adolescents ( SHARE ) delivered by teachers reduced unsafe sexual intercourse compared with current practice . Design : Cluster r and omised trial with follow up two years after baseline ( six months after intervention ) . A process evaluation investigated the delivery of sex education and broader features of each school . Setting : Twenty five secondary schools in east Scotl and . Participants : 8430 pupils aged 13 - 15 years ; 7616 completed the baseline question naire and 5854 completed the two year follow up question naire . Intervention : SHARE programme ( intervention group ) versus existing sex education ( control programme ) . Main outcome measures : Self reported exposure to sexually transmitted disease , use of condoms and contraceptives Output:	However , this reduction was not statistically significant from cluster RCTs . Evidence on the possible effects of interventions on secondary outcomes ( initiation of sexual intercourse , use of birth control methods , abortion , childbirth , sexually transmitted diseases ) was not conclusive . Educational interventions Educational interventions were unlikely to significantly delay the initiation of sexual intercourse among adolescents compared to controls ( RR 0.95 , 95 % CI 0.71 to 1.27 ; 2 studies , 672 participants , low quality evidence ) .Educational interventions significantly increased reported condom use at last sex in adolescents compared to controls who did not receive the intervention ( RR 1.18 , 95 % CI 1.06 to 1.32 ; 2 studies , 1431 participants , moderate quality evidence ) .However , it is not clear if the educational interventions had any effect on unintended pregnancy as this was not reported by any of the included studies . Contraceptive-promoting interventions For adolescents who received contraceptive-promoting interventions , there was little or no difference in the risk of unintended first pregnancy compared to controls ( RR 1.01 , 95 % CI 0.81 to 1.26 ; 2 studies , 3,440 participants , moderate quality evidence ) .The use of hormonal contraceptives was significantly higher in adolescents in the intervention group compared to those in the control group ( RR 2.22 , 95 % CI 1.07 to 4.62 ; 2 studies , 3,091 participants , high quality evidence ) AUTHORS ' CONCLUSIONS A combination of educational and contraceptive-promoting interventions appears to reduce unintended pregnancy among adolescents . Evidence for programme effects on biological measures is limited . The variability in study population s , interventions and outcomes of included trials , and the paucity of studies directly comparing different interventions preclude a definitive conclusion regarding which type of intervention is most effective
MS21515	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The purpose of this study was to determine how often physician-performed high-resolution sonography can detect nonpalpable breast lesions not revealed by mammography . A sonographic classification scheme was tested for its accuracy in predicting malignancy of incidentally detected breast lesions . SUBJECTS AND METHODS Six thous and one hundred thirteen asymptomatic women with breast density grade s 2 - 4 and 687 patients with palpable or mammographically detected breast masses underwent sonography as an adjunct to mammography . All sonographically detected , clinical ly and mammographically occult breast lesions that were not simple cysts were prospect ively classified into benign , indeterminate , or malignant categories . Diagnoses were confirmed by sonographically guided fine-needle aspiration or core needle biopsy . RESULTS In 6113 asymptomatic women , 23 malignancies in 21 patients were detected with sonography only ( prevalence , 0.31 % ) . Five additional malignant lesions were found in patients with a malignant ( n = 3 ) or a benign ( n = 2 ) palpable or mammographically detected index lesion . The mean size of invasive malignancies detected only by sonography was 9.1 mm , which was not significantly different from the mean size of invasive cancers detected by mammography ( p = .07 ) . The sensitivity of the prospect i ve sonographic classification for malignancy was 100 % , and the specificity was 33.5 % . CONCLUSION The use of high-resolution sonography as an adjunct to mammography in women with dense breasts may lead to detection of a significant number of otherwise occult malignancies that are no different in size from nonpalpable mammographically detected lesions . Prospect i ve classification of these lesions based on sonographic characteristics results in a significant reduction in number of unnecessary biopsies performed Abstract Background : Controversies over the frequency and intensity of the follow-up care of breast cancer patients exist . Some physicians have adopted an intensive approach to follow-up care that consists of frequent laboratory tests and routine imaging studies , including chest radiographs , bone scans , and CT scans , whereas others have established a minimalist approach consisting of only history , physical examinations , and mammograms . Objectives : Our objective was to evaluate the role of intensive follow-up on detection of breast cancer recurrence and to examine the impact of follow-up on overall survival . Methods : During a 10-year period ( 1986–1996 ) , 129 patients with recurrent disease were identified from a prospect i ve data base of 1898 breast cancer patients . The patients with recurrent disease were divided into minimalist or intensive groups according to method of detection . Results : Twenty-seven of 126 ( 21 % ) patients were assigned to the intensive method of detection group ( LFT , CEA , CA 15 - 3 , chest radiograph , CT scan , and bone scan ) ; 99 of 126 ( 79 % ) patients were assigned to the minimal detection group ( history , physical examination , and mammography ) . Distant disease to the bone was the most common initial tumor recurrence , at 27 % . History , physical examination , and mammography detected recurrent cancer in approximately the same amount of time as LFTs , tumor markers , CT scans , and chest radiographs ( P=.960 ) . When the recurrent patients were divided into intensive and minimalist groups and analyzed by time to detection of recurrence , there was no significant difference between the time to detection in those recurrences detected by intensive methods and those recurrences detected by minimalist methods (P=.95).The independent variables age , tumor size , type of surgery , number of positive nodes , time to recurrence , method of detection , and site of recurrence ( regional or distant ) were subject to univariate and multivariate analysis by the Cox proportional hazards model . Only two variables had an impact on survival by multivariate analysis : early timing of the recurrence ( P=.0011 ) and the site of the recurrence ( P=.02 ) . Timing was defined as early ( ⩽365 days from the time of diagnosis to recurrence ) or late ( ⩾365 days from the time of diagnosis to recurrence ) . Early recurrence was the first variable found to be significant on stepwise forward regression analysis . The primary site of recurrence was significant at step two . The method of detection — intensive or minimal — did not significantly affect survival ( P=.18 ) . Conclusions : There is no survival benefit to routine intensive follow-up regimens in detecting recurrent breast cancer . Expensive diagnostic tests such as bone scans , CT scans , and serial tumor markers are best used for detection of metastasis in symptomatic patients Results from the completed treatment analysis of the ATAC ( Arimidex , Tamoxifen alone or in combination ) trial indicated that anastrozole was significantly superior to tamoxifen in terms of efficacy and safety in the adjuvant treatment of postmenopausal women with hormone receptor-positive ( HR+ ) early breast cancer . On the basis of these results , this study estimated the cost-effectiveness of anastrozole vs tamoxifen , from the perspective of the UK National Health Service ( NHS ) . A Markov model was developed using the 5-year completed treatment analysis from the ATAC trial ( IS RCT N18233230 ) , as well as data obtained from published literature and expert opinion . Re source utilisation data and associated costs ( 2003–4 UK£ ) were compiled from st and ard sources and expert opinion . Utility scores for a number of health states were obtained from a cross-sectional study of 26 representative patients using the st and ard gamble technique . The utility scores were then inserted into the model to obtain cost per quality adjusted life-year ( QALY ) gained . Costs and benefits were discounted at recommended annual rates of the UK Treasury ( 3.5 % ) . Modelled for 25 years , anastrozole , relative to generic tamoxifen , was estimated to result in 0.244 QALYs gained per patient at an additional cost of £ 4315 per patient ) . The estimated incremental cost-effectiveness of anastrozole compared with tamoxifen was £ 17 656 per QALY gained . There was a greater than 90 % probability that the cost-effectiveness of anastrozole was below £ 30 000 per QALY gained and of the order of 65 % that it was below £ 20 000 per QALY gained . The results were robust to all parameters tested in sensitivity analysis . Compared with commonly accepted thresholds , anastrozole is a cost-effective alternative to generic tamoxifen in adjuvant treatment of postmenopausal women with HR+ early breast cancer from the UK NHS perspective Background Postal surveys are a frequently used method of data collection in health services research . Low response rates increase the potential for bias and threaten study validity . The objectives of this study were to estimate current response rates , to assess whether response rates are falling , to explore factors that might enhance response rates and to examine the potential for non-response bias in surveys mailed to healthcare professionals . Methods A r and om sample of postal or electronic surveys of healthcare workers ( 1996 - 2005 ) was identified from Medline , Embase or Psycinfo data bases or Biomed Central . Outcome measures were survey response rate and non response analysis . Multilevel , multivariable logistic regression examined the relationship between response rate and publication type , healthcare profession , country and number of survey participants , question naire length and use of reminders . Results The analysis included 350 studies . Average response rate in doctors was 57.5 % ( 95%CI : 55.2 % to 59.8 % ) and significantly lower than the estimate for the prior 10 year period . Response rates were higher when reminders were sent ( adjusted OR 1.3 ; 95%CI 1.1 - 1.6 ) but only half the studies did this . Response rates were also higher in studies with fewer than 1000 participants and in countries other than US , Canada , Australia and New Zeal and . They were not significantly affected by publication type or healthcare profession ( p > 0.05 ) . Only 17 % of studies attempted assessment of possible non-response bias . Conclusion Response rates to postal surveys of healthcare professionals are low and probably declining , almost certainly leading to unknown levels of bias . To improve the informativeness of postal survey findings , research ers should routinely consider the use of reminders and assess potential for non-response bias OBJECTIVES To assess whether omission of postoperative radiotherapy in women with ' low-risk ' axillary node negative breast cancer ( T0 - 2 ) treated by breast-conserving surgery and endocrine therapy improves quality of life and is more cost-effective . DESIGN A r and omised controlled clinical trial , using a method of minimisation balanced by centre , grade of cancer , age , lymphatic/vascular invasion and preoperative endocrine therapy , was performed . A non-r and omised cohort was also recruited , in order to complete a comprehensive cohort study . SETTING The setting was breast cancer clinics in cancer centres in the UK . PARTICIPANTS Patients aged 65 years or more were eligible provided that their cancers were considered to be at low risk of local recurrence , were suitable for breast-conservation surgery , were receiving endocrine therapy and were able and willing to give informed consent . INTERVENTIONS The st and ard treatment of postoperative breast irradiation or the omission of radiotherapy . MAIN OUTCOME MEASURES Quality of life was the primary outcome measure , together with anxiety and depression and cost-effectiveness . Secondary outcome measures were recurrence rates , functional status , treatment-related morbidity and cosmesis . The principal method of data collection was by question naire , completed at home with a research nurse at four times over 15 months . RESULTS The hypothesised improvement in overall quality of life with the omission of radiotherapy was not seen in the EuroQol assessment or in the functionality and symptoms summary domains of the European Organisation for Research in the Treatment of Cancer ( EORTC ) scales . Some differences were apparent within subscales of the EORTC question naires , and insights into the impact of treatment were also provided by the qualitative data obtained by open-ended questions . Differences were most apparent shortly after the time of completion of radiotherapy . Radiotherapy was then associated with increased breast symptoms and with greater fatigue but with less insomnia and endocrine side-effects . Patients had significant concerns about the delivery of radiotherapy services , such as transport , accommodation and travel costs associated with receiving radiotherapy . By the end of follow-up , patients receiving radiotherapy were expressing less anxiety about recurrence than those who had not received radiotherapy . Functionality was not greatly affected by treatment . Within the r and omised controlled trial , the Barthel Index demonstrated a small but significant fall in functionality with radiotherapy compared with the no radiotherapy arm of the trial . Results from the non-r and omised patients did not confirm this effect , however . Cosmetic results were better in those not receiving radiotherapy but this did not appear to be an important issue to the patients . The use of home-based assessment s by a research nurse proved to be an effective way of obtaining high- quality data . Costs to the NHS associated with postoperative radiotherapy were calculated to be of the order of 2000 pounds per patient . In the follow-up in this study , there were no recurrences , and the quality of life utilities from EuroQol were almost identical . CONCLUSIONS Although there are no differences in overall quality of life scores between the patients treated with and without radiotherapy , there are several dimensions that exhibit significant advantage to the omission of irradiation . Over the first 15 months , radiotherapy for this population is not a cost-effective treatment . However , the early postoperative outcome does not give a complete answer and the eventual cost-effectiveness will only become clear after long-term follow-up . Extrapolations from these data suggest that radiotherapy may not be a cost-effective treatment unless it results in a recurrence rate that is at least 5 % lower in absolute terms than those treated without radiotherapy . Further research is needed into a number of areas including the long-term aspects of quality of life , clinical outcomes , costs and consequences of omitting radiotherapy Goal To ascertain outcomes of surveillance mammography ( SM ) following treatment of early stage unilateral primary breast cancer ( PBC ) in a population based case series . Methods R and om sample s from all 12,279 women having breast surgery within 4 months after diagnosis of PBC , between July 1991 and December 1993 in Ontario , were drawn from a data base created by deterministic linkage of PBC files from the Ontario Cancer Registry ( OCR ) with episodes of breast surgery extracted from the hospital Discharge Abstract Data base ( DAD ) , and mammography from the Ontario physician billings data base ( OHIP ) . Among women having ≥1 episode(s ) of breast surgery subsequent ( SBS ) to the date of diagnosis up to December 2000 , a sample of 1,200/5,064 ( 23.7 % ) was drawn , and among women with no SBS , a sample of 400/7,215 ( 5.5 % ) . Among these two sample s , operative , pathology , and mammography reports were abstract ed from original charts . Treatments were abstract ed and categorized . Women with complete data for Stages 1 and 2 unilateral PBC were included . From the subsequent surgery sample , 609/1,200 ( 50.8 % ) were excluded because of simultaneous or sequential bilateral breast cancers or mastectomies within 6 months , missing stage information , Stage 3 or 4 PBC , or missing primary charts . From the no subsequent surgery sample , 90/400 ( 22.5 % ) were excluded by the same criteria . Episodes of bilateral 2-view X-ray mammography , beginning ≥6 months after the diagnosis of unilateral PBC , and if multiple , at least 11 months apart , and not prompted by a clinical concern or symptom , were classified as SM . We confirmed episodes of cancer recurrence within the ipsilateral conserved breast ( CRICB ) and metachronous contralateral primary breast cancer ( CPBC ) ≥6 months after the diagn Output:	Data set analysis showed that IBTR has an adverse effect on survival . Furthermore , women experiencing a second tumour measuring > 20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was < 10 mm in diameter . There was no useable evidence contained in the Breast Cancer Registry data base to assess the effectiveness of surveillance mammography directly . Surveillance is likely to improve survival and patients should gain maximum benefit through optimal use of re sources , with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance .
MS21516	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND & AIMS Rectal indomethacin , a nonsteroidal anti-inflammatory drug , is given to prevent pancreatitis in high-risk patients undergoing endoscopic retro grade cholangiopancreatography ( ERCP ) , based on findings from clinical trials . The European Society for Gastrointestinal Endoscopy guidelines recently recommended prophylactic rectal indomethacin for all patients undergoing ERCP , including those at average risk for pancreatitis . We performed a r and omized controlled trail to investigate the efficacy of this approach . METHODS We performed a prospect i ve , double-blind , placebo-controlled trial of 449 consecutive patients undergoing ERCP at Dartmouth Hitchcock Medical Center , from March 2013 through December 2014 . Approximately 70 % of the cohort were at average risk for PEP . Subjects were assigned r and omly to groups given either a single 100-mg dose of rectal indomethacin ( n = 223 ) or a placebo suppository ( n = 226 ) during the procedure . The primary outcome was the development of post-ERCP pancreatitis ( PEP ) , defined by new upper-abdominal pain , a lipase level more than 3-fold the upper limit of normal , and hospitalization after ERCP for 2 consecutive nights . RESULTS There were no differences between the groups in baseline clinical or procedural characteristics . Sixteen patients in the indomethacin group ( 7.2 % ) and 11 in the placebo group ( 4.9 % ) developed PEP ( P = .33 ) . Complications and the severity of PEP were similar between groups . Per a priori protocol guidelines , the study was stopped owing to futility . CONCLUSIONS In a r and omized controlled study of consecutive patients undergoing ERCP , rectal indomethacin did not prevent post-ERCP pancreatitis . ClincialTrials.gov no : NCT01774604 BACKGROUND AND AIMS Acute pancreatitis following endoscopic retro grade cholangiography presents a unique opportunity for prophylaxis and early modification of the disease process because the initial triggering event is temporally well defined and takes place in the hospital . We report a prospect i ve , single-center , r and omized , double-blind controlled trial to determine if rectal diclofenac reduces the incidence of pancreatitis following cholangiopancreatography . METHODS Entry to the trial was restricted to patients who underwent endoscopic retro grade pancreatography . Immediately after endoscopy , patients were given a suppository containing either 100 mg diclofenac or placebo . Estimation of serum amylase level and clinical evaluation were performed in all patients . RESULTS One hundred patients entered the trial , and 50 received rectal diclofenac . Fifteen patients developed pancreatitis ( 15 % ) , of whom two received rectal diclofenac and 13 received placebo ( P < 0.01 ) . CONCLUSIONS This trial shows that rectal diclofenac given immediately after endoscopic retro grade cholangiopancreatography can reduce the incidence of acute pancreatitis BACKGROUND Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retro grade cholangiopancreatography ( ERCP ) . METHODS In this multicenter , r and omized , placebo-controlled , double-blind clinical trial , we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP . Patients were determined to be at high risk on the basis of vali date d patient- and procedure-related risk factors . The primary outcome was post-ERCP pancreatitis , which was defined as new upper abdominal pain , an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure , and hospitalization for at least 2 nights . RESULTS A total of 602 patients were enrolled and completed follow-up . The majority of patients ( 82 % ) had a clinical suspicion of sphincter of Oddi dysfunction . Post-ERCP pancreatitis developed in 27 of 295 patients ( 9.2 % ) in the indomethacin group and in 52 of 307 patients ( 16.9 % ) in the placebo group ( P=0.005 ) . Moderate-to-severe pancreatitis developed in 13 patients ( 4.4 % ) in the indomethacin group and in 27 patients ( 8.8 % ) in the placebo group ( P=0.03 ) . CONCLUSIONS Among patients at high risk for post-ERCP pancreatitis , rectal indomethacin significantly reduced the incidence of the condition . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT00820612 . ) 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 Acute pancreatitis is the most common major complication after endoscopic retro grade cholangiopancreatography ( ERCP ) . Many drugs have been evaluated for prophylaxis , including nonsteroidal anti-inflammatory drugs ( NSAIDs ) , which are potent inhibitors of phospholipase A2 and play a role in the pathogenesis of acute pancreatitis . Rectal NSAIDs have been shown in prospect i ve studies to decrease the incidence of this complication , but the indication is not generalized in clinical practice . The aim of this study was to evaluate the efficacy of rectal administration of indomethacin in reducing the incidence of post-ERCP pancreatitis in high-risk patients . Methods This was a controlled clinical trial where patients with an elevated risk of developing post-ERCP pancreatitis were assigned to receive 100 mg of rectal indomethacin or a 2.6 g suppository of glycerin immediately after ERCP , without placement of a pancreatic stent . The patients were determined to be at high risk based on vali date d patient- and procedure-related risk factors . Post-ERCP pancreatitis was defined as the presence of new upper abdominal pain , hyperamylasemia/hyperlipasemia ( at least three times the upper limit ) 2 hours after the procedure and hospitalization at least 48 hours because of the complication . Pancreatitis severity was defined according to Cotton ’s criteria . Results One hundred sixty-six patients were included ; 82 in the study group and 84 in the placebo group . Patients had at least one major and /or two minor risk factors for developing post-ERCP pancreatitis . The incidence of the complication was 4.87 % ( 4/82 ) in the study group and 20.23 % ( 17/84 ) in the placebo group ; this difference was significant ( P = 0.01 ) . According to Cotton ’s criteria , 17 patients ( 80.9 % ) developed mild pancreatitis and 4 ( 19.1 % ) had moderate pancreatitis ; 3 of these 4 patients belonged to the placebo group ( P = 0.60 ) . Based on these results , an absolute risk reduction of 0.15 ( 15 % ) , a relative risk reduction of 0.75 ( 75 % ) and a number needed to treat of 6.5 patients were calculated to prevent an episode of post-ERCP pancreatitis . There was no mortality . Conclusions Rectal indomethacin reduced the incidence of post-ERCP pancreatitis among patients at high risk of developing this complication . Trial registration National Clinical Trials NCT02110810 . Date April 7 , 2014 Background and study aims : Several meta-analyses and r and omized control trials have demonstrated the efficacy of rectal nonsteroidal anti-inflammatory drugs for preventing post-endoscopic retro grade cholangiopancreatography ( ERCP ) pancreatitis ( PEP ) . Diclofenac or indomethacin was administered at a dose of 100 mg in those studies , which may be too high for Asian population . In addition , rectal administration can be considered complicated . Patients and methods : This study was a prospect i ve , r and omized , placebo-controlled trial . Patients with a PEP risk score ≥ 1 were r and omly assigned to receive intravenous injection of 50 mg flurbiprofen axetil ( flurbiprofen group ) or saline only ( placebo group ) . The primary outcome was reduced PEP . The secondary outcome was amylase level after 2 hours of ERCP as a predictor of PEP . ( Clinical Trials.gov , ID UMIN000011322 ) Results : In total , 144 patients were enrolled from August 2013 to March 2015 . We performed an interim analysis of the first 100 patients : 47 received flurbiprofen axetil and 53 received placebo . PEP occurred in 11 patients ( 11 % ): 2 of 47 ( 4.3 % ) in the flurbiprofen group and 9 of 53 ( 17 % ) in the placebo group ( P = 0.042 ) . Relative risk reduction was 62.4 % . Hyperamylasemia did not differ significantly ( 17.0 % vs. 26.4 % , P = 0.109 ) . This analysis result ed in early termination of the study for ethical reasons . Conclusions : Intravenous injection of low-dose flurbiprofen axetil after ERCP can reduce the incidence of PEP in high-risk BACKGROUND Post-ERCP pancreatitis is poorly understood . The goal of this study was to comprehensively evaluate potential procedure- and patient-related risk factors for post-ERCP pancreatitis over a wide spectrum of centers . METHODS Consecutive ERCP procedures were prospect ively studied at 11 centers ( 6 private , 5 university ) . Complications were assessed at 30 days by using established consensus criteria . RESULTS Pancreatitis occurred after 131 ( 6.7 % ) of 1963 consecutive ERCP procedures ( mild 70 , moderate 55 , severe 6 ) . By univariate analysis , 23 of 32 investigated variables were significant . Multivariate risk factors with adjusted odds ratios ( OR ) were prior ERCP-induced pancreatitis ( OR 5.4 ) , suspected sphincter of Oddi dysfunction ( OR 2.6 ) , female gender ( OR 2.5 ) , normal serum bilirubin ( OR 1.9 ) , absence of chronic pancreatitis ( OR 1.9 ) , biliary sphincter balloon dilation ( OR 4.5 ) , difficult cannulation ( OR 3.4 ) , pancreatic sphincterotomy ( OR 3.1 ) , and 1 or more injections of contrast into the pancreatic duct ( OR 2.7 ) . Small bile duct diameter , sphincter of Oddi manometry , biliary sphincterotomy , and lower ERCP case volume were not multivariate risk factors for pancreatitis , although endoscopists performing on average more than 2 ERCPs per week had significantly greater success at bile duct cannulation ( 96.5 % versus 91.5 % , p = 0.0001 ) . Combinations of patient characteristics including female gender , normal serum bilirubin , recurrent abdominal pain , and previous post-ERCP pancreatitis placed patients at increasingly higher risk of pancreatitis , regardless of whether ERCP was diagnostic , manometric , or therapeutic . CONCLUSIONS Patient-related factors are as important as procedure-related factors in determining risk for post-ERCP pancreatitis . These data emphasize the importance of careful patient selection as well as choice of technique in the avoidance of post-ERCP pancreatitis AIM To determine the efficacy of rectally administered naproxen for the prevention of post-endoscopic retro grade cholangiopancreatography ( ERCP ) pancreatitis ( PEP ) . METHODS This double-blind r and omized control trial conducted from January 2013 to April 2014 at the Gastrointestinal and Liver Diseases Research Center in Rasht , Iran . A total of 324 patients were selected from c and i date s for diagnostic or therapeutic ERCP by using the simple sampling method . Patients received a single dose of Naproxen ( 500 mg ; n = 162 ) or a placebo ( n = 162 ) per rectum immediately before ERCP . The overall incidence of PEP , incidence of mild to severe PEP , serum amylase levels and adverse effects were measured . The primary outcome measure was the development of pancreatitis onset of pain in the upper abdomen and elevation of the serum amylase level to > 3 × the upper normal limit ( 60 - 100 IU/L ) within 24 h after ERCP . The severity of PEP was classified according to the duration of therapeutic intervention for PEP : mild , 2 - 3 d ; moderate 4 - 10 d ; and severe , > 10 d and /or necessitated surgical or intensive treatment , or contributed to death . RESULTS PEP occurred in 12 % ( 40/324 ) of participants , and was significantly more frequent in the placebo group compared to the naproxen group ( P < 0.01 ) . Of the participants , 25.9 % ( 84/324 ) developed hyperamylasemia within 2 h of procedure completion , among whom only 35 cases belonged to the naproxen group ( P < 0. Output:	Subgroup analyses showed difference in clinical efficacy of NSAID prophylaxis regardless of route , timing , or specific type of NSAID . Conclusion NSAIDs were associated with a significant reduction in risk of PEP and moderate to severe PEP compared to the control group
MS21517	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Self-management improves oral anticoagulation control . Here we provide data of a preplanned interim analysis of very low-dose early self-controlled anticoagulation . METHODS In a prospect i ve , r and omized , multicenter trial , 1,137 patients performed low-dose international normalized ratio ( INR ) self-management with a target INR range of 1.8 . to 2.8 for aortic valve replacement recipients and 2.5 to 3.5 for mitral or double valve replacement recipients for the first six postoperative months . Thereafter , 379 patients continued to achieve the aforementioned INR target range ( LOW group ) , whereas the INR target value was set at 2.0 ( range , 1.6 to 2.1 ) for the remaining patients with aortic valve replacement and 2.3 ( range , 2.0 to 2.5 ) for the remaining patients with mitral valve or double valve replacement . One half of this latter group had to check their INR values once a week ( VL1 group ) the other half twice a week ( VL2 group ) . Patients were followed up for 24 months . RESULTS Beyond study month six , the incidence of thromboembolic events that required hospital admission was 0.58 % , 0.0 % , and 0.58 % in the LOW , VL1 , and VL2 groups , respectively ( p = 0.368 ) . The incidence of bleeding events per patient-year was 1.16 % , 1.07 % , and 0.58 % in the LOW , VL1 , and VL2 groups , respectively ( p = 0.665 ) . Mortality rate did not differ among study groups . CONCLUSIONS Data demonstrate the efficacy and safety of very low-dose INR self-management Background Computer-assistance and self-monitoring lower the cost and may improve the quality of anticoagulation therapy . The main purpose of this clinical investigation was to use computer-assisted oral anticoagulant therapy to improve the time to reach and the time spent within the therapeutic target range compared to traditional oral anticoagulant therapy by physicians . Methods 54 patients were r and omized equally into 3 groups . Patients in two groups used CoaguChek ® systems to measure international normalized ratio ( INR ) values and had dosages of anticoagulation treatment calculated in a computer system by an algorithm specific to each group . The third group received traditional anticoagulation treatment by physicians . The obtained INR values were compared regarding the time to reach , and the time spent within , the therapeutic target range , corresponding to INR values from 2 to 3 . Results Patients r and omized to computer-assisted anticoagulation and the CoaguChek ® system reached the therapeutic target range after 8 days compared to 14 days by prescriptions from physicians ( p = 0.04 ) . Time spent in the therapeutic target range did not differ between groups . The median INR value measured throughout the study from all patients by CoaguChek ® at 2.5 ( 2.42–2.62 ) was lower than measured by a hospital-based Clinical and Biochemical Laboratory at 2.6 ( 2.45–2.76 ) , ( p = 0.02 ) . Conclusions The therapeutic target range was reached faster by the use of computer-assisted anticoagulation treatment than prescribed by physicians , and the total time spent within the therapeutic target range was similar . Thus computer-assisted oral anticoagulant therapy may reduce the cost of anticoagulation therapy without lowering the quality . INR values measured by CoaguChek ® were reliable compared to measurements by a clinical and biochemical laboratory Self-management is safe and reliable in patients with long-term oral anticoagulation ( OAC ) . However , no study has yet assessed the safety and efficacy of OAC self-management in elderly patients with major thromboembolic and haemorrhagic complications as primary outcomes . In this multi-centre , open , r and omised controlled trial , patients aged 60 years or more were r and omised into the self-management group ( SMG ) ( N = 99 ) or routine care group ( RCG ) ( N = 96 ) . We describe the rationale , design , baseline characteristics and interim analyses of oral anticoagulation control quality within the first year of follow-up . The medians of the squared international normalised ratio ( INR ) value deviations after six and 12 months were significantly lower in the SMG with medians of 0.16 and 0.16 compared to the RCG with medians of 0.25 and 0.25 . The percentage of time within target range and the percentage of INR measurements within target range were significantly higher in the SMG versus the RCG within the first six months ( medians 71 % vs. 58 % and 69 % vs. 57 % ) , and during the second six months of the study ( 75 % vs. 67 % and 72 % vs. 57 % ) . The numbers of all thromboembolic events requiring hospitalisation , major bleeding events , and deaths were similar in both groups . These preliminary results suggest that self-management of oral anticoagulation is safe and feasible for elderly patients willing to participate in a structured training programme CONTEXT Control of oral anticoagulation therapy has been reported to often be inadequate . Previous retrospective investigations suggest that patients ' self-adjustment of oral anticoagulants may lead to improved control . OBJECTIVE To investigate the effects of patients ' self-management of oral anticoagulation therapy on accuracy of control and measures of treatment-related quality of life . DESIGN R and omized , single-blind , multicenter trial . SETTING AND PARTICIPANTS A total of 179 patients receiving long-term oral anticoagulation treatment were enrolled at 5 referral centers in Germany . INTERVENTION Patients were r and omized to an oral anticoagulation self-management group based on a structured treatment and teaching program and international normalized ratio ( INR ) self-monitoring . The control group received conventional care as provided by family physicians , including referral to specialists if necessary . MAIN OUTCOME MEASURES Deviation of INR values from the individual INR target range ( squared ) and the 5 categories of treatment-related quality of life . RESULTS Deviation of INR value from the mean of the INR target range was significantly lower in the intervention group at 3-month ( squared INR deviation , 0.59 vs 0.95 ; P<.001 ) and 6-month follow-up ( 0.65 vs 0.83 ; P=.03 ) compared with the control group . Also , the intervention group had INR values within the target range more often ( repeated measurement analysis for categorical data , P=.006 ) . The results were mainly due to less frequent suboptimal INR values in the intervention group ( 32.8 % vs 50.0 % [ P=.03 ] at 3-month , and 33.7 % vs 48.2 % [ P=.08 ] at 6-month follow-up ) . Treatment-related quality -of-life measures , especially treatment satisfaction scores , were significantly higher in the intervention group compared with controls . CONCLUSIONS An anticoagulation education program that includes self-management of anticoagulation therapy results in improved accuracy of anticoagulation control and in treatment-related quality -of-life measures . Further studies are needed to describe whether the program will reduce risk of bleeding or thromboembolism OBJECTIVE Self-management of oral anticoagulant therapy ( OAT ) has shown good results on a short-term basis . We hypothesize that self-management of OAT provides a better quality of treatment than conventional management also on a long-term basis . The aim of this study was to assess the quality of self-management of OAT in patients with mechanical heart valve prostheses on a 4-year perspective in a prospect i ve , non-r and omized study . DESIGN Twenty-four patients with mechanical heart valves and on self-managed OAT were followed for up to 4 years . A matched , retrospectively selected group of conventionally managed heart valve patients ( control group ) was used as reference . RESULTS The median observation time was 1175 days ( range : 174 - 1428 days ) . The self-managed patients were within therapeutic INR target range for a mean of 78.0 % ( range : 36.1%-93.9 % ) of the time compared with 61.0 % ( range 37.4%-2.9 % ) for the control group . CONCLUSION Self-management of OAT is a feasible and safe concept for selected patients with mechanical heart valve prostheses also on a long-term basis . It provides at least as good and most likely better quality of anticoagulant therapy than conventional management assessed by time within the therapeutic International Normalized Ratio ( INR ) target range Background Point of care testing ( PoCT ) may be a useful adjunct in the management of chronic conditions in general practice ( GP ) . The provision of pathology test results at the time of the consultation could lead to enhanced clinical management , better health outcomes , greater convenience and satisfaction for patients and general practitioners ( GPs ) , and savings in costs and time . It could also result in inappropriate testing , increased consultations and poor health outcomes result ing from inaccurate results . Currently there are very few r and omised controlled trials ( RCTs ) in GP that have investigated these aspects of PoCT . Design / Methods The Point of Care Testing in General Practice Trial ( PoCT Trial ) was an Australian Government funded multi-centre , cluster r and omised controlled trial to determine the safety , clinical effectiveness , cost effectiveness and satisfaction of PoCT in a GP setting .The PoCT Trial covered an 18 month period with the intervention consisting of the use of PoCT for seven tests used in the management of patients with diabetes , hyperlipidaemia and patients on anticoagulant therapy . The primary outcome measure was the proportion of patients within target range , a measure of therapeutic control . In addition , the PoCT Trial investigated the safety of PoCT , impact of PoCT on patient compliance to medication , stakeholder satisfaction , cost effectiveness of PoCT versus laboratory testing , and influence of geographic location . Discussion The paper provides an overview of the Trial Design , the rationale for the research methodology chosen and how the Trial was implemented in a GP environment . The evaluation protocol and data collection processes took into account the large number of patients , the broad range of practice types distributed over a large geographic area , and the inclusion of pathology test results from multiple pathology laboratories . The evaluation protocol developed reflects the complexity of the Trial setting , the Trial Design and the approach taken within the funding provided . The PoCT Trial is regarded as a pragmatic RCT , evaluating the effectiveness of implementing PoCT in GP and every effort was made to ensure that , in these circumstances , internal and external validity was maintained . Trial Registration Background Stroke prevention in atrial fibrillation ( AF ) , most commonly with warfarin , requires maintenance of a narrow therapeutic target ( INR 2.0 to 3.0 ) and is often poorly controlled in practice . Poor patient-underst and ing surrounding AF and its treatment may contribute to the patient ’s willingness to adhere to recommendations . Method A theory-driven intervention , developed using patient interviews and focus groups , consisting of a one-off group session ( 1–6 patients ) utilising an “ expert-patient ” focussed DVD , educational booklet , self-monitoring diary and worksheet , was compared in a r and omised controlled trial ( IS RCT N93952605 ) against usual care , with patient postal follow-ups at 1 , 2 , 6 , and 12-months . Ninety-seven warfarin-naïve AF patients were r and omised to intervention ( n=46 , mean age ( SD ) 72.0 ( 8.2 ) , 67.4 % men ) , or usual care ( n=51 , mean age ( SD ) 73.7 ( 8.1 ) , 62.7 % men ) , stratified by age , sex , and recruitment centre . Primary endpoint was time within therapeutic range ( TTR ) ; secondary endpoints included knowledge , quality of life , anxiety/depression , beliefs about medication , and illness perceptions . Main Findings Intervention patients had significantly higher TTR than usual care at 6-months ( 76.2 % vs. 71.3 % ; p=0.035 ) ; at 12-months these differences were not significant ( 76.0 % vs. 70.0 % ; p=0.44 ) . Knowledge increased significantly across time ( F ( 3 , 47 ) = 6.4 ; p<0.01 ) , but there were no differences between groups ( F ( 1 , 47 ) = 3.3 ; p = 0.07 ) . At 6-months , knowledge scores predicted TTR ( r=0.245 ; p=0.04 ) . Patients ’ scores on subscales representing their perception of the general harm and overuse of medication , as well as the perceived necessity of their AF specific medications predicted TTR at 6- and 12-months . Conclusions A theory-driven educational intervention significantly improves TTR in AF patients initiating warfarin during the first 6-months . Adverse clinical outcomes may potentially be reduced by improving patients ’ underst and ing of the necessity of warfarin and reducing their perception of treatment harm . Improving education provision for AF patients is essential to ensure efficacious and safe treatment . The trial is registered with Current Controlled Trials , IS RCT N93952605 , and details are available at www.controlled-trials.com/IS RCT N93952605 Background : The increase in numbers of patients receiving warfarin treatment has led to the development of alternative models of service delivery for oral anticoagulant monitoring . Patient self management for oral anticoagulation is a model new to the UK . This r and omised trial was the first to compare routine primary care management of oral anticoagulation with patient self management . Aim : To test Output:	Participants who self-monitor or self-manage can improve the quality of their oral anticoagulation therapy . Thromboembolic events were reduced , for both those self-monitoring or self-managing oral anticoagulation therapy . A reduction in all-cause mortality was observed in trials of self-management but not in self-monitoring , with no effects on major haemorrhage
MS21518	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Differents protocol es therapeutiques et differents dosages de neuroleptiques chez des Abstract Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant treatment for tardive dyskinesia ( TD ) conducted by the Department of Veteran Affairs Cooperative Studies Program . One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia . Dyskinetic h and movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient . In the present report , we describe the training procedures and results of a multi-center reliability assessment of this procedure . Data from nine study centers comprising 45 individual patients with six trials each ( three from left h and and three from right h and ) were reanalyzed by an independent investigator and the results were subjected to reliability assessment . For the statistic of interest ( average coefficient of variation over trials 2 and 3 for each h and , then take the larger of these two values ) , we found very high intraclass correlation coefficients for reliability over all patients across sites ( ICC = 0.995 ) . We also calculated the reliability of the measures across trials within patient for each combination of h and ( right , left , dominant ) , rater group ( site , control ) , and trials set ( all three , trials 2 and 3 ) . For a given h and and trial set , the reliability of the site raters was similar to that of the control . This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training BACKGROUND Several open trials and case studies have reported beneficial effects following the addition of risperidone for partial responders to clozapine . The purpose of this study was to carry out a placebo-controlled , r and omized , double-blind trial of the efficacy , safety , and tolerability of adjunctive treatment with risperidone in patients with schizophrenia partially responsive to clozapine . METHOD In this 6-week double-blind study , 30 patients with DSM-IV schizophrenia who had partial response to clozapine despite being treated for a mean of 32 months were r and omly assigned to risperidone ( N = 16 ) up to 6 mg/day or placebo ( N = 14 ) . Efficacy assessment s included the Positive and Negative Syndrome Scale ( PANSS ) , the Calgary Depression Scale , the Clinical Global Impressions-Severity of Illness scale , the Global Assessment of Functioning scale , and the Quality of Life Scale . A variety of safety and tolerability measures were also obtained . Data were collected between November 2001 and July 2003 . RESULTS Significant improvement was noted in both groups on a variety of measures of psychopathology , but there was significantly greater improvement in the placebo-treated patients on the primary outcome measure , the PANSS positive symptom subscale . There were no significant differences between the treatment groups regarding extrapyramidal symptoms , weight gain , vital signs , serum clozapine levels , and QTc interval . The only side effect significantly more severe in risperidone-treated compared to placebo-treated patients was sedation . The patients treated with risperidone developed significant increases in plasma prolactin levels . CONCLUSION Adjunctive risperidone treatment in schizophrenia patients partially responsive to clozapine does not significantly improve psychopathology or quality of life compared to placebo in a 6-week period BACKGROUND Amisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors . The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia . METHOD This was a multi-centre , r and omised , parallel-group , double-blind study . Patients received either amisulpride ( 100 mg/day ) or placebo over a six-month treatment period . RESULTS A total of 141 patients were included , 69 received amisulpride , 72 placebo . Fifty-eight patients ( 41 % ) had received neuroleptic treatment prior to inclusion . The percentage of amisulpride patients completing the study ( 55 % ) was significantly higher than that with placebo ( 32 % ) , and drop-out rates due to lack of efficacy were 27 % with amisulpride and 47 % with placebo . All efficacy assessment s were statistically in favour of amisulpride compared with placebo . The overall incidence of extrapyramidal symptoms was comparable in both groups ; only five patients started anti-Parkinsonian treatment during the study ( one in the placebo and four in the amisulpride group ) . CONCLUSION Amisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms 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 BACKGROUND A relative lack of extrapyramidal symptoms ( EPS , i.e. , the syndromes of dystonia , parkinsonism , akathisia , dyskinesia ) is one criterion used to determine whether an antipsychotic is " atypical . " The extrapyramidal symptom profiles of the novel antipsychotic olanzapine and the conventional antipsychotic haloperidol were compared in a population of 2606 patients from three well-controlled prospect i ve clinical trials . METHOD Extrapyramidal symptom data were analyzed for 1796 patients treated with olanzapine ( 5 to 20 mg/day ) and 810 patients treated with haloperidol ( 5 to 20 mg/day ) for up to 6 weeks of therapy . Patients were monitored weekly by three methods of extrapyramidal symptom assessment : ( 1 ) detection of extrapyramidal adverse events ( signs and symptoms ) by casual observation , nonprobing inquiry , and spontaneous report ; ( 2 ) objective rating scale scores : and ( 3 ) use of concomitant anticholinergic medications . Emergence of EPS was assessed by ( 1 ) analysis of the incidence of extrapyramidal syndrome categories based on adverse events , ( 2 ) the incidence of extrapyramidal syndromes based on categorical analysis of rating scale scores , ( 3 ) analysis of mean maximum change in rating scale scores , and ( 4 ) categorical analysis of anticholinergic medication use . Outcome of EPS was assessed by ( 1 ) analysis of mean change in rating scale scores at endpoint and ( 2 ) mean anticholinergic use at endpoint . RESULTS Olanzapine was statistically significantly ( p = .014 , p < .001 ) superior to haloperidol in all four analyses related to emergence of EPS and in the two analyses related to outcome . Furthermore , during acute treatment , statistically significantly fewer patients treated with olanzapine ( 0.3 % ) discontinued the study because of any extrapyramidal adverse event than patients treated with haloperidol ( 2.7 % , p < .001 ) . CONCLUSION Olanzapine exhibited a statistically significantly lower extrapyramidal symptom profile than the conventional antipsychotic haloperidol at comparably effective antipsychotic doses . The lower extrapyramidal symptom profile with olanzapine was evident despite statistically significantly more frequent use of anticholinergic drugs among haloperidol-treated patients . Fewer olanzapine-treated than haloperidol-treated patients discontinued because of EPS , suggesting that olanzapine should contribute to better compliance with longer term maintenance treatment , with minimal anticholinergic-associated events Olanzapine and risperidone , both second-generation antipsychotic agents , represent two different pharmacologic strategies . Although they share some in vitro properties , they differ by virtue of their chemical structure , spectrum of receptor binding affinities , animal neuropharmacology , pharmacokinetics , and in vivo neuroimaging profile . Based on such differences , it was hypothesized that the two compounds would show distinct safety and /or efficacy characteristics . To test this hypothesis , an international , multicenter , double-blind , parallel-group , 28-week prospect i ve study was conducted with 339 patients who met DSM-IV criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms . However , olanzapine demonstrated significantly greater efficacy in negative symptoms ( Scale for Assessment of Negative Symptoms summary score ) , as well as overall response rate ( > or = 40 % decrease in the Positive and Negative Syndrome Scale total score ) . Furthermore , a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves . The incidence of extrapyramidal side effects , hyperprolactinemia , and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients . In addition , statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts . Thus , the differential pre clinical profiles of these two drugs were also evident in a controlled , clinical investigation . Olanzapine seemed to have a risk-versus-benefit advantage OBJECTIVE This study was design ed to compare the efficacy and safety of five different doses of risperidone with a fixed dose of haloperidol in patients with chronic schizophrenia . METHOD After a 1-week single-blind , placebo washout phase , 99 chronic schizophrenic patients were r and omly assigned to double-blind treatment with 1 , 4 , 8 , 12 or 16 mg risperidone or 10 mg haloperidol daily for 8 weeks . Efficacy was assessed throughout the study by the Positive and Negative Syndrome Scale ( PANSS ) for schizophrenia , and Clinical Global Impression ( CGI ) . Safety assessment s included the Extrapyramidal Symptom Ratinf Scale ( ESRS ) UKU Side Effect Rating Scale , vital signs , body weight , ECG and laboratory screening . RESULTS Risperidone had a bell-shaped dose-response curve , with optimal therapeutic responses occurring at a daily dose of 8 mg . The therapeutic response to haloperidol was similar to that seen with risperidone 16 mg . Risperidone was associated with significantly less extrapyramidal symptoms than haloperidol , as assessed by the ESRS . The effect was mirrored by the requirement for antiparkinson rescue medication . Furthermore , the overall incidence of adverse events was markedly lower with the optimum dose of risperidone than with haloperidol . CONCLUSIONS Risperidone is at least as effective as haloperidol for the treatment of chronic schizophrenia . Moreover , risperidone is associated with an improved adverse event profile and significantly less extrapyramidal symptoms which will have beneficial implication s on patient quality of life and compliance . These results are in agreement with the results from the international multicenter trial OBJECTIVE The authors assessed the efficacy and safety of the first long-acting atypical antipsychotic ( long-acting injectable risperidone ) in patients with schizophrenia . METHOD In a 12-week , multicenter , double-blind , r and omized study , patients received intramuscular injections every 2 weeks of placebo or long-acting risperidone ( 25 mg , 50 mg , or 75 mg ) . The primary measure of efficacy was the change in total score on the Positive and Negative Syndrome Scale . RESULTS Of the 554 patients who were enrolled , 400 entered the double-blind study , and 370 received at least one postbaseline assessment . Mean changes in score of -6.2 , -8.5 , and -7.4 on the Positive and Negative Syndrome Scale were seen at endpoint for the 25- , 50- , and 75-mg risperidone groups Output:	AUTHORS ' CONCLUSIONS Based on low quality evidence , risperidone appears to be benefitial in improving mental state compared with placebo , but it also causes more adverse events .
MS21519	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Therapeutic interventions that incorporate training in mindfulness meditation have become increasingly popular , but to date little is known about neural mechanisms associated with these interventions . Mindfulness-Based Stress Reduction ( MBSR ) , one of the most widely used mindfulness training programs , has been reported to produce positive effects on psychological well-being and to ameliorate symptoms of a number of disorders . Here , we report a controlled longitudinal study to investigate pre-post changes in brain gray matter concentration attributable to participation in an MBSR program . Anatomical magnetic resonance ( MR ) images from 16 healthy , meditation-naïve participants were obtained before and after they underwent the 8-week program . Changes in gray matter concentration were investigated using voxel-based morphometry , and compared with a waiting list control group of 17 individuals . Analyses in a priori regions of interest confirmed increases in gray matter concentration within the left hippocampus . Whole brain analyses identified increases in the posterior cingulate cortex , the temporo-parietal junction , and the cerebellum in the MBSR group compared with the controls . The results suggest that participation in MBSR is associated with changes in gray matter concentration in brain regions involved in learning and memory processes , emotion regulation , self-referential processing , and perspective taking Previous work suggests that explicit and implicit evaluations ( goodbad ) involve somewhat different neural circuits that process different dimensions such as valence , emotional intensity , and complexity . To better underst and these differences , we used functional magnetic resonance imaging to identify brain regions that respond differentially to such dimensions depending on whether or not an explicit evaluation is required . Participants made either goodbad judgments ( evaluative ) or abstract concrete judgments ( not explicitly evaluative ) about socially relevant concepts ( e.g. , murder , happiness , abortion , welfare ) . After scanning , participants rated the concepts for goodness , badness , emotional intensity , and how much they tried to control their evaluation of the concept . Amygdala activation correlated with emotional intensity and right insula activation correlated with valence in both tasks , indicating that these aspects of stimuli were processed by these areas regardless of intention . In contrast , for the explicitly evaluative goodbad task only , activity in the anterior cingulate , frontal pole , and lateral areas of the orbital frontal cortex correlated with ratings of control , which in turn were correlated with a measure of ambivalence . These results highlight that evaluations are the consequence of complex circuits that vary depending on task dem and Mindfulness meditation reduces pain in experimental and clinical setting s. However , it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect ( e.g. , conditioning , psychosocial context , beliefs ) . To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo , we r and omly assigned 75 healthy , human volunteers to 4 d of the following : ( 1 ) mindfulness meditation , ( 2 ) placebo conditioning , ( 3 ) sham mindfulness meditation , or ( 4 ) book-listening control intervention . We assessed intervention efficacy using psychophysical evaluation of experimental pain and functional neuroimaging . Importantly , all cognitive manipulations ( i.e. , mindfulness meditation , placebo conditioning , sham mindfulness meditation ) significantly attenuated pain intensity and unpleasantness ratings when compared to rest and the control condition ( p < 0.05 ) . Mindfulness meditation reduced pain intensity ( p = 0.032 ) and pain unpleasantness ( p < 0.001 ) ratings more than placebo analgesia . Mindfulness meditation also reduced pain intensity ( p = 0.030 ) and pain unpleasantness ( p = 0.043 ) ratings more than sham mindfulness meditation . Mindfulness-meditation-related pain relief was associated with greater activation in brain regions associated with the cognitive modulation of pain , including the orbitofrontal , subgenual anterior cingulate , and anterior insular cortex . In contrast , placebo analgesia was associated with activation of the dorsolateral prefrontal cortex and deactivation of sensory processing regions ( secondary somatosensory cortex ) . Sham mindfulness meditation-induced analgesia was not correlated with significant neural activity , but rather by greater reductions in respiration rate . This study is the first to demonstrate that mindfulness-related pain relief is mechanistically distinct from placebo analgesia . The elucidation of this distinction confirms the existence of multiple , cognitively driven , supraspinal mechanisms for pain modulation . SIGNIFICANCE STATEMENT Recent findings have demonstrated that mindfulness meditation significantly reduces pain . Given that the “ gold st and ard ” for evaluating the efficacy of behavioral interventions is based on appropriate placebo comparisons , it is imperative that we establish whether there is an effect supporting meditation-related pain relief above and beyond the effects of placebo . Here , we provide novel evidence demonstrating that mindfulness meditation produces greater pain relief and employs distinct neural mechanisms than placebo cream and sham mindfulness meditation . Specifically , mindfulness meditation-induced pain relief activated higher-order brain regions , including the orbitofrontal and cingulate cortices . In contrast , placebo analgesia was associated with decreased pain-related brain activation . These findings demonstrate that mindfulness meditation reduces pain through unique mechanisms and may foster greater acceptance of meditation as an adjunct pain therapy OBJECTIVE The aim of the current study is to investigate structural changes on brain MRI using voxel based morphometry ( VBM ) related to an eight-week mindfulness based intervention ( MBI ) in Parkinson 's Disease ( PD ) . METHODS A total of 27 out of 30 PD patients completed a r and omized controlled longitudinal trial . Fourteen patients participated in a structured eight-week program of MBI . Thirteen patients received usual care ( UC ) alone . MRI data sets of the brain were obtained at baseline and after eight weeks follow-up . VBM analysis was performed using DARTEL from the SPM8 software . The result ing difference maps were statistically compared to examine gray matter density ( GMD ) differences . Results were reported at p<0.001 , uncorrected for multiple comparisons . RESULTS Increased GMD was found in the MBI compared to the UC group in the region of interest ( ROI ) analysis in the right amygdala , and bilaterally in the hippocampus . Whole brain analysis showed increased GMD in the left and right cau date nucleus , the left occipital lobe at the lingual gyrus and cuneus , the left thalamus , and bilaterally in the temporo-parietal junction . In contrast , GMD differences were found in the UC group in the left anterior lobe and dentate nucleus of the cerebellum . CONCLUSIONS To the best of our knowledge this is the first quantitative analysis of neurobiological effects of MBI in PD . Increased GMD was found in the MBI group in the neural networks that have been postulated to play an important role in PD . These areas have also been implicated in the functional networks mediating the benefits of meditation 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 Emotions have been shown to exert influences on decision making during economic exchanges . Here we investigate the underlying neural mechanisms of a training regimen which is hypothesized to promote emotional awareness , specifically mindfulness training ( MT ) . We test the hypothesis that MT increases cooperative economic decision making using fMRI in a r and omized longitudinal design involving 8 weeks of either MT or active control training ( CT ) . We find that MT results in an increased willingness to cooperate indexed by higher acceptance rates to unfair monetary offers in the Ultimatum Game . While controlling for acceptance rates of monetary offers between intervention groups , subjects in the MT and CT groups show differential brain activation patterns . Specifically , a subset of more cooperative MT subjects displays increased activation in the septal region , an area linked to social attachment , which may drive the increased willingness to express cooperative behavior in the MT cohort . Furthermore , MT result ed in attenuated activity in anterior insula compared with the CT group in response to unfair monetary offers post-training , which may suggest that MT enables greater ability to effectively regulate the anterior insula and thereby promotes social cooperation . Finally , functional connectivity analyses show a coupling between the septal region and posterior insula in the MT group , suggesting an integration of interoceptive inputs . Together , these results highlight that MT may be employed in context s where emotional regulation is required to promote social cooperation The beneficial effects of mindful awareness and mindfulness meditation training on physical and psychological health are thought to be mediated in part through changes in underlying brain processes . Functional connectivity MRI ( fcMRI ) allows identification of functional networks in the brain . It has been used to examine state-dependent activity and is well suited for study ing states such as meditation . We applied fcMRI to determine if Mindfulness-Based Stress Reduction ( MBSR ) training is effective in altering intrinsic connectivity networks ( ICNs ) . Healthy women were r and omly assigned to participate in an 8-week Mindfulness-Based Stress Reduction ( MBSR ) training course or an 8-week waiting period . After 8 weeks , fMRI data ( 1.5 T ) was acquired while subjects rested with eyes closed , with the instruction to pay attention to the sounds of the scanner environment . Group independent component analysis was performed to investigate training-related changes in functional connectivity . Significant MBSR-related differences in functional connectivity were found mainly in auditory/salience and medial visual networks . Relative to findings in the control group , MBSR subjects showed ( 1 ) increased functional connectivity within auditory and visual networks , ( 2 ) increased functional connectivity between auditory cortex and areas associated with attentional and self-referential processes , ( 3 ) stronger anticorrelation between auditory and visual cortex , and ( 4 ) stronger anticorrelation between visual cortex and areas associated with attentional and self-referential processes . These findings suggest that 8 weeks of mindfulness meditation training alters intrinsic functional connectivity in ways that may reflect a more consistent attentional focus , enhanced sensory processing , and reflective awareness of sensory experience Mindfulness meditation is a set of attention-based , regulatory , and self-inquiry training regimes . Although the impact of mindfulness training ( MT ) on self-regulation is well established , the neural mechanisms supporting such plasticity are poorly understood . MT is thought to act through interoceptive salience and attentional control mechanisms , but until now conflicting evidence from behavioral and neural measures renders difficult distinguishing their respective roles . To resolve this question we conducted a fully r and omized 6 week longitudinal trial of MT , explicitly controlling for cognitive and treatment effects with an active-control group . We measured behavioral metacognition and whole-brain blood oxygenation level-dependent ( BOLD ) signals using functional MRI during an affective Stroop task before and after intervention in healthy human subjects . Although both groups improved significantly on a response-inhibition task , only the MT group showed reduced affective Stroop conflict . Moreover , the MT group displayed greater dorsolateral prefrontal cortex responses during executive processing , consistent with increased recruitment of top-down mechanisms to resolve conflict . In contrast , we did not observe overall group-by-time interactions on negative affect-related reaction times or BOLD responses . However , only participants with the greatest amount of MT practice showed improvements in response inhibition and increased recruitment of dorsal anterior cingulate cortex , medial prefrontal cortex , and right anterior insula during negative valence processing . Our findings highlight the importance of active control in MT research , indicate unique neural mechanisms for progressive stages of mindfulness training , and suggest that optimal application of MT may differ depending on context , contrary to a one-size-fits-all approach Mindfulness-based stress reduction ( MBSR ) is thought to reduce emotional reactivity and enhance emotion regulation in patients with social anxiety disorder ( SAD ) . The goal of this study was to examine the neural correlates of deploying attention to regulate responses to negative self-beliefs using functional magnetic resonance imaging . Participants were 56 patients with generalized SAD in a r and omized controlled trial who were assigned to MBSR or a comparison aerobic exercise ( AE ) stress reduction program . Compared to AE , MBSR yielded greater ( i ) reductions in negative emotion when implementing regulation and ( ii ) increases in attention-related parietal cortical regions . Meditation practice was associated with decreases in negative emotion and social anxiety symptom severity , and increases in attention-related parietal cortex neural responses when implementing attention regulation of negative self-beliefs . Changes in attention regulation during MBSR may be an important psychological factor that helps to explain how mindfulness meditation training benefits patients with anxiety disorders Mindfulness training aims to impact emotion regulation . Generalized anxiety disorder ( GAD ) symptoms can be successfully addressed through mindfulness-based interventions . This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training . Furthermore , we compared brain activation between GAD patients and healthy participants at baseline . 26 patients with a current DSM-IV GAD diagnosis were r and omized to an 8-week Mindfulness Based Stress Reduction ( MBSR , N = 15 ) or a stress management education ( SME , N = 11 ) active control program . 26 healthy participants were included for baseline comparisons . BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions . At baseline , GAD patients showed higher amygdala activation than healthy participants in response to neutral , but not angry faces , suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients . In patients , amygdala activation in response to neutral faces decreased following both interventions . BOLD response in ventrolateral prefrontal regions ( VLPFC ) showed greater increase in MBSR than SME participants . Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR , but not SME group . Both , change in VLPFC activation and amygd Output:	RESULTS The prefrontal cortex , the cingulate cortex , the insula and the hippocampus showed increased activity , connectivity and volume in stressed , anxious and healthy participants . Additionally , the amygdala showed decreased functional activity , improved functional connectivity with the prefrontal cortex , and earlier deactivation after exposure to emotional stimuli . Demonstrable functional and structural changes in the prefrontal cortex , cingulate cortex , insula and hippocampus are similar to changes described in studies on traditional meditation practice . In addition , MBSR led to changes in the amygdala consistent with improved emotion regulation . These findings indicate that MBSR-induced emotional and behavioral changes are related to functional and structural changes in the brain
MS21520	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The rapid and reliable diagnosis of acute myocardial infa rct ion is a major unmet clinical need . METHODS We conducted a multicenter study to examine the diagnostic accuracy of new , sensitive cardiac troponin assays performed on blood sample s obtained in the emergency department from 718 consecutive patients who presented with symptoms suggestive of acute myocardial infa rct ion . Cardiac troponin levels were determined in a blinded fashion with the use of four sensitive assays ( Abbott-Architect Troponin I , Roche High-Sensitive Troponin T , Roche Troponin I , and Siemens Troponin I Ultra ) and a st and ard assay ( Roche Troponin T ) . The final diagnosis was adjudicated by two independent cardiologists . RESULTS Acute myocardial infa rct ion was the adjudicated final diagnosis in 123 patients ( 17 % ) . The diagnostic accuracy of measurements obtained at presentation , as quantified by the area under the receiver-operating-characteristic curve ( AUC ) , was significantly higher with the four sensitive cardiac troponin assays than with the st and ard assay ( AUC for Abbott-Architect Troponin I , 0.96 ; 95 % confidence interval [ CI ] , 0.94 to 0.98 ; for Roche High-Sensitive Troponin T , 0.96 ; 95 % CI , 0.94 to 0.98 ; for Roche Troponin I , 0.95 ; 95 % CI , 0.92 to 0.97 ; and for Siemens Troponin I Ultra , 0.96 ; 95 % CI , 0.94 to 0.98 ; vs. AUC for the st and ard assay , 0.90 ; 95 % CI , 0.86 to 0.94 ) . Among patients who presented within 3 hours after the onset of chest pain , the AUCs were 0.93 ( 95 % CI , 0.88 to 0.99 ) , 0.92 ( 95 % CI , 0.87 to 0.97 ) , 0.92 ( 95 % CI , 0.86 to 0.99 ) , and 0.94 ( 95 % CI , 0.90 to 0.98 ) for the sensitive assays , respectively , and 0.76 ( 95 % CI , 0.64 to 0.88 ) for the st and ard assay . We did not assess the effect of the sensitive troponin assays on clinical management . CONCLUSIONS The diagnostic performance of sensitive cardiac troponin assays is excellent , and these assays can substantially improve the early diagnosis of acute myocardial infa rct ion , particularly in patients with a recent onset of chest pain . ( Clinical Trials.gov number , NCT00470587 . Objective To analyse whether levels of high-sensitivity cardiac troponin ( hs-cTn ) below their respective 99th percentile can be used as a single parameter to rule out acute myocardial infa rct ion ( AMI ) at presentation . Design Prospect i ve , multicentre study . Main outcome measures We measured hs-cTn using four different methods ( hs-cTnT Roche , hs-cTnI Siemens , hs-cTnI Beckman Coulter and hs-cTnI Abbott ) in consecutive patients presenting to the emergency department with acute chest pain . Two independent cardiologists adjudicated the final diagnosis . Patients were followed for death or AMI during a mean period of 24 months . Results Among 2072 consecutive patients with hs-cTnT measurements available , 21.4 % had an adjudicated diagnosis of AMI ( sensitivity 89.6 % , 95 % CI 86.4 % to 92.3 % , negative predictive value ( NPV ) : 96.5 % , 95 % CI 95.4 % to 97.4 % ) . Among 1180 consecutive patients with hs-cTnI Siemens measurements available , 20.0 % had AMI ( sensitivity 94.1 % , 95 % CI 90.3 % to 96.7 % , NPV : 98.0 % , 95 % CI : 96.6 % to 98.9 % ) . Among 1151 consecutive patients with hs-cTnI Beckman Coulter measurements available , 19.7 % had AMI ( sensitivity 92.1 % , 95 % CI 87.8 % to 95.2 % , NPV : 97.5 % , 95 % CI 96.0 % to 98.5 % ) . Among 1567 consecutive patients with hs-cTnI Abbott measurements available , 20.0 % had AMI ( sensitivity 77.2 % , 95 % CI 72.1 % to 81.7 % , NPV : 94.3 % , 95 % CI 92.8 % to 95.5 % ) . Conclusions Normal hs-cTn levels at presentation should not be used as a single parameter to rule out AMI as 6%–23 % of adjudicated AMI cases had normal levels of hs-cTn levels at presentation . Our data highlight the lack of st and ardisation among hs-cTnI assays result ing in substantial differences in sensitivity and NPV at the 99th percentile BACKGROUND Two recent clinical trials showed that adding copeptin to a conventional cardiac troponin assay improved diagnostic performance for patients with chest pain early after symptom onset . We prospect ively tested whether copeptin adds information to that provided by a high-sensitivity cardiac troponin T ( hscTnT ) assay in the early evaluation of patients with suspected acute myocardial infa rct ion , particularly non-ST-segment elevation myocardial infa rct ion ( non-STEMI ) . METHODS We enrolled 503 patients with suspected acute coronary syndrome and onset of chest pain occurring within the previous 12 h. Copeptin was measured on presentation , and hscTnT was measured serially at baseline and after 3 and 6 h. We used ROC curve analysis and likelihood ratio χ² statistics for nested models . Diagnostic sensitivities , specificities , positive predictive values ( PPVs ) , and negative predictive values ( NPVs ) were calculated for admission values of copeptin alone , hscTnT alone , and the combination of both markers . RESULTS For ruling out non-STEMI ( after excluding STEMI ) , an hscTnT concentration < 14 ng/L ( 99th percentile ) plus a copeptin concentration < 14 pmol/L yielded a diagnostic sensitivity of 97.7 % ( 95 % CI , 91.9%-99.7 % ) , an NPV of 99.03 % ( 95 % CI , 96.6%-99.9 % ) , a diagnostic specificity of 55.9 % ( 95 % CI , 50.6%-61.0 % ) , and a PPV of 34.4 % ( 95 % CI , 28.5%-40.7 % ) . ROC curve analysis of the continuous biomarker values on admission demonstrated no added value of using this marker combination for ruling out non-STEMI when hscTnT was used as the st and ard for diagnosing non-STEMI . CONCLUSIONS A strategy using copeptin with hscTnT at prespecified cutoffs improves the ruling out of non-STEMI , compared with using hscTnT alone ; thus , this strategy could help to obviate a prolonged stay in the emergency department BACKGROUND The role of the arginine-vasopressin ( AVP ) system in the response to myocardial ischemia is unclear . Copeptin , the C-terminal part of the AVP prohormone is secreted stoichiometrically with AVP . METHODS A total of 253 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography ( SPECT ) were enrolled . We evaluated the response of copeptin during exercise and determined whether measurement of copeptin may be helpful in the detection of myocardial ischemia . RESULTS Myocardial ischemia on perfusion images was detected in 127 patients ( 50 % ) . Median copeptin levels increased significantly with exercise in patients with ischemia as well as in patients without ischemia ( from 3.8 [ IQR 2.8 - 6.6 ] to 12.3 [ IQR 5.2 - 39.6 ] pmol/l , P<0.001 ; and from 3.6 [ IQR 2.6 - 5.7 ] to 10.8 [ IQR 5.0 - 24.5 ] pmol/l , P<0.001 ) . Median exercise-induced changes in copeptin ( Deltacopeptin ) were similar in both groups ( 7.7 versus 5.1 pmol/l , P=0.150 ) . The area under the ROC curve for the ability of Deltacopeptin to detect myocardial ischemia was 0.552 . CONCLUSIONS Copeptin levels increased threefold with exercise , irrespective of the presence or absence of myocardial ischemia . Therefore , myocardial ischemia does not seem to be a major trigger of the AVP system . Measurement of copeptin does not seem helpful in the detection of exercise-induced myocardial ischemia BACKGROUND High-sensitivity cardiac troponin ( hs-cTn ) assays seem to improve the early diagnosis of acute myocardial infa rct ion ( AMI ) , but it is unknown how to best use them in clinical practice . Our objective was to develop and vali date an algorithm for rapid rule-out and rule-in of AMI . METHODS A prospect i ve multicenter study enrolling 872 unselected patients with acute chest pain presenting to the emergency department . High-sensitivity cardiac troponin T ( hs-cTnT ) was measured in a blinded fashion at presentation and after 1 hour . The final diagnosis was adjudicated by 2 independent cardiologists . An hs-cTnT algorithm incorporating baseline values as well as absolute changes within the first hour was derived from 436 r and omly selected patients and vali date d in the remaining 436 patients . The primary prognostic end point was death during 30 days of follow-up . RESULTS Acute myocardial infa rct ion was the final diagnosis in 17 % of patients . After applying the hs-cTnT algorithm developed in the derivation cohort to the validation cohort , 259 patients ( 60 % ) could be classified as " rule-out , " 76 patients ( 17 % ) as " rule-in , " and 101 patients ( 23 % ) as in the " observational zone " within 1 hour . Overall , this result ed in a sensitivity and negative predictive value of 100 % for rule-out , a specificity and positive predictive value of 97 % and 84 % , respectively , for rule-in , and a prevalence of AMI of 8 % in the observational zone group . Cumulative 30-day survival was 99.8 % , 98.6 % , and 95.3 % ( P < .001 ) in patients classified as rule-out , observational zone , and rule-in , respectively . CONCLUSIONS Using a simple algorithm incorporating hs-cTnT baseline values and absolute changes within the first hour allowed a safe rule-out as well as an accurate rule-in of AMI within 1 hour in 77 % of unselected patients with acute chest pain . This novel strategy may obviate the need for prolonged monitoring and serial blood sampling in 3 of 4 patients Objective To investigate the diagnostic and prognostic role of heart-type fatty acid-binding protein ( hFABP ) compared with copeptin and in addition to high-sensitivity cardiac troponin T ( hs-cTnT ) in patients with chest pain suspected of acute myocardial infa rct ion ( AMI ) . Design Diagnostic and prognostic performances of hFABP , copeptin and hs-cTnT were evaluated and compared . The final diagnosis was adjudicated by two independent cardiologists . Setting This prospect i ve observational multicentre study took place in four primary and one secondary hospital from April 2006 to September 2009 . Patients We enrolled 1247 consecutive patients with suspected AMI to the emergency department . For analysis , patients were included , if baseline levels for hs-cTnT and hFABP were available ( n=1074 ) , patients with ST-segment elevation myocardial infa rct ion ( STEMI ) were excluded for the diagnostic analysis ( n=43 ) . Interventions Treatment was left to the discretion of the emergency physician . Main outcome measures AMI and mortality . Results 4 % of the patients had STEMI and 16 % of the patients had non-STEMI . Patients with AMI had significantly higher levels of hFABP at presentation ( p<0.001 ) . Neither the combination with hFABP nor with copeptin increased the diagnostic accuracy of hs-cTnT at admission , quantified by the area under the receiver operating characteristic curve ( AUC ) ( p>0.05 ) . The negative predictive value regarding 90-day , 1-year and 2-year mortality was 100 % ( 99–100 ) , 99 % ( 98–100 ) and Output:	Conclusion : Despite substantial between- study heterogeneity , this meta- analysis demonstrates that copeptin significantly improves baseline cTn sensitivity .
MS21521	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Incidence of end-stage renal disease due to hypertension has increased in recent decades , but the optimal strategy for treatment of hypertension to prevent renal failure is unknown , especially among African Americans . OBJECTIVE To compare the effects of an angiotensin-converting enzyme ( ACE ) inhibitor ( ramipril ) , a dihydropyridine calcium channel blocker ( amlodipine ) , and a beta-blocker ( metoprolol ) on hypertensive renal disease progression . DESIGN , SETTING , AND PARTICIPANTS Interim analysis of a r and omized , double-blind , 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease ( glomerular filtration rate [ GFR ] of 20 - 65 mL/min per 1.73 m(2 ) ) enrolled between February 1995 and September 1998 . This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000 . INTERVENTIONS Participants were r and omly assigned to receive amlodipine , 5 to 10 mg/d ( n = 217 ) , ramipril , 2.5 to 10 mg/d ( n = 436 ) , or metoprolol , 50 to 200 mg/d ( n = 441 ) , with other agents added to achieve 1 of 2 blood pressure goals . MAIN OUTCOME MEASURES The primary outcome measure was the rate of change in GFR ; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50 % or 25 mL/min per 1.73 m(2 ) , end-stage renal disease , or death . RESULTS Among participants with a urinary protein to creatinine ratio of > 0.22 ( corresponding approximately to proteinuria of more than 300 mg/d ) , the ramipril group had a 36 % ( 2.02 [ SE , 0.74 ] mL/min per 1.73 m(2)/y ) slower mean decline in GFR over 3 years ( P = .006 ) and a 48 % reduced risk of the clinical end points vs the amlodipine group ( 95 % confidence interval [ CI ] , 20%-66 % ) . In the entire cohort , there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups ( P = .38 ) . However , compared with the amlodipine group , after adjustment for baseline covariates the ramipril group had a 38 % reduced risk of clinical end points ( 95 % CI , 13%-56 % ) , a 36 % slower mean decline in GFR after 3 months ( P = .002 ) , and less proteinuria ( P<.001 ) . CONCLUSION Ramipril , compared with amlodipine , retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria BACKGROUND Patients with hypertension may require a combination of > or = 2 antihypertensive agents to achieve blood pressure ( BP ) control . OBJECTIVE The aim of this study was to determine whether a triple combination of olmesartan medoxomil ( OM ) , amlodipine besylate ( AML ) , and hydrochlorothiazide ( HCTZ ) had a clinical ly significant benefit compared with dual combinations of the individual components in patients with moderate to severe hypertension . METHODS This was a multicenter , r and omized , doubleblind , parallel-group study in which triple combination treatment with OM 40 mg + AML 10 mg + HCTZ 25 mg was compared with dual combinations of the individual components-OM 40 mg/AML 10 mg in fixed-dose combination , OM 40 mg/HCTZ 25 mg in fixed-dose combination , and AML 10 mg + HCTZ 25 mg-in patients aged > or = 18 years who had a mean seated BP > or = 140/100 mm Hg or > or = 160/90 mm Hg . The study consisted of a 3-week washout period with no study medication and a 12-week double-blind treatment period . In the first 2 weeks of the double-blind treatment period , all patients were r and omized to receive dual combination treatment or placebo . All patients assigned to a dual combination treatment group continued the assigned treatment until week 4 , and all patients assigned to placebo were switched at week 2 to receive 1 of the dual combination treatments until week 4 . At week 4 , patients either continued dual combination treatment or switched to triple combination treatment until week 12 . The primary end point was the change in seated diastolic BP ( SeDBP ) from baseline to week 12 ; SeDBP reduction of > or = 2 mm Hg was considered a clinical ly significant benefit . Secondary efficacy end points included the change in seated systolic BP ( SeSBP ) at week 12 and the percentages of patients achieving BP targets of < 140/90 mm Hg , < 120/80 mm Hg , SeSBP < 140 mm Hg , and SeDBP < 90 mm Hg at week 12 . The tolerability of the treatments was also evaluated based on adverse events ( AEs ) , clinical laboratory evaluations ( chemistry , hematology , and urinalysis ) , physical examinations , and 12-lead ECGs . RESULTS The 2492 r and omized patients ( 52.9 % male , 66.8 % white , 30.4 % black ) had a mean ( SD ) age of 55.1 ( 10.9 ) years and a mean weight of 96.0 ( 22.9 ) kg . Diabetes was present in 15.5 % of the population , chronic cardiovascular disease in 9.1 % , and chronic kidney disease in 4.1 % . At baseline , the mean SeBP was 168.5/100.9 mm Hg . At week 12 , triple combination treatment was associated with significantly greater least squares mean reductions in SeBP compared with the dual combinations ( SeDBP : -21.8 vs -15.1 to -18.0 mm Hg , respectively [ P < 0.001 ] ; SeSBP : -37.1 vs -27.5 to -30.0 mm Hg [ P < 0.001 ] ) . A significantly higher proportion of patients receiving triple combination treatment reached BP targets compared with the dual combinations at week 12 ( P < 0.001 ) . The proportions of patients reaching the BP target of < 140/90 mm Hg at week 12 was 69.9 % in the triple combination treatment group and 52.9 % , 53.4 % , and 41.1 % in the treatment groups receiving OM 40 mg/AML 10 mg , OM 40 mg/HCTZ 25 mg , and AML 10 mg + HCTZ 25 mg , respectively ( P < 0.001 , triple combination vs each dual combination ) . The incidence of treatment-emergent AEs ( TEAEs ) was 58.4 % for triple combination treatment and 51.7 % to 58.9 % for the dual combinations ; most TEAEs were mild or moderate in severity . The most common TEAEs in the triple combination treatment group were dizziness ( 9.9 % ) , peripheral edema ( 7.7 % ) , and headache ( 6.4 % ) . In total , 52 patients ( 2.3 % ) discontinued the study due to TEAEs-6 ( 1.0 % ) in the OM 40 mg/AML 10 mg group , 12 ( 2.1 % ) in the OM 40 mg/HCTZ 25 mg group , 11 ( 2.0 % ) in the AML 10 mg + HCTZ 25 mg group , and 23 ( 4.0 % ) in the OM 40 mg + AML 10 mg + HCTZ 25 mg group . Thirty-two patients (1.4%)-4 ( 0.7 % ) , 5 ( 0.9 % ) , 5 ( 0.9 % ) , and 18 ( 3.1 % ) in the respective treatment groups-discontinued the study due to drug-related TEAEs . CONCLUSIONS In these adult patients with moderate to severe hypertension , triple combination treatment with OM 40 mg + AML 10 mg + HCTZ 25 mg was associated with significant BP reductions compared with dual combinations of the individual components . All treatments were generally well tolerated . Clinical Trials . gov identifier : NCT00649389 The Losartan Intervention For Endpoint ( LIFE ) reduction in hypertension study is a double-blind , prospect i ve , parallel group study design ed to compare the effects of losartan with those of atenolol on the reduction of cardiovascular morbidity and mortality . A total of 9194 patients with hypertension and ECG left ventricular hypertrophy ( LVH ) by Cornell voltage- duration product and /or Sokolow-Lyon voltage criteria were enrolled in the study , with baseline clinical and ECG data available in 8785 patients ( 54 % women ; mean age , 67±7 years ) . ECG LVH by Cornell voltage- duration product criteria was present in 5791 patients ( 65.9 % ) and by Sokolow-Lyon voltage in 2025 patients ( 23.1 % ) . Compared with patients without ECG LVH by Cornell voltage- duration product criteria , patients with ECG LVH by this method were older ; more obese ; more likely to be female , white , and to have never smoked ; more likely to be diabetic and have angina ; and had slightly higher systolic , diastolic , and pulse blood pressures . In contrast , patients with ECG LVH by Sokolow-Lyon criteria were slightly younger ; less obese ; more likely to be male , black , and current smokers ; less likely to have diabetes ; more likely to have angina and a history of cerebrovascular disease ; and had higher systolic and pulse blood pressure but slightly lower diastolic blood pressure than patients without ECG LVH by this method . By use of multivariate logistic regression analyses , presence of ECG LVH by Cornell voltage- duration product criteria was predominantly associated with higher body mass index , increased age , and female gender , whereas presence of ECG LVH by Sokolow-Lyon voltage criteria was predominantly related to lower body mass index , male gender , and black race . Thus , hypertensive patients who meet Cornell product and Sokolow-Lyon voltage criteria are associated with different , but potentially equally adverse , risk factor profiles CONTEXT Few cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme ( ACE ) inhibitors or calcium channel blockers ( CCBs ) . OBJECTIVE To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease ( CVD ) incidence in racial subgroups . DESIGN , SETTING , AND PARTICIPANTS Prespecified subgroup analysis of ALLHAT , a r and omized , double-blind , active-controlled , clinical outcome trial conducted between February 1994 and March 2002 in 33,357 hypertensive US and Canadian patients aged 55 years or older ( 35 % black ) with at least 1 other cardiovascular risk factor . INTERVENTIONS Antihypertensive regimens initiated with a CCB ( amlodipine ) or an ACE inhibitor ( lisinopril ) vs a thiazide-type diuretic ( chlorthalidone ) . Other medications were added to achieve goal blood pressures ( BPs ) less than 140/90 mm Hg . MAIN OUTCOME MEASURES The primary outcome was combined fatal coronary heart disease ( CHD ) or nonfatal myocardial infa rct ion ( MI ) , analyzed by intention-to-treat . Secondary outcomes included all-cause mortality , stroke , combined CVD ( CHD death , nonfatal MI , stroke , angina , coronary revascularization , heart failure [ HF ] , or peripheral vascular disease ) , and end-stage renal disease . RESULTS No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup . For amlodipine vs chlorthalidone only , HF was the only prespecified clinical outcome that differed significantly ( overall : relative risk [ RR ] , 1.37 ; 95 % confidence interval [ CI ] , 1.24 - 1.51 ; blacks : RR , 1.46 ; 95 % CI , 1.24 - 1.73 ; nonblacks : RR , 1.32 ; 95 % CI , 1.17 - 1.49 ; P<.001 for each comparison ) with no difference in treatment effects by race ( P = .38 for interaction ) . For lisinopril vs chlorthalidone , results differed by race for systolic BP ( greater decrease in blacks with chlorthalidone ) , stroke , and combined CVD outcomes ( P<.001 , P = .01 , and P = .04 , respectively , for interactions ) . In blacks and nonblacks , respectively , the RRs for stroke were 1.40 ( 95 % CI , 1.17 - 1.68 ) and 1.00 ( 95 % CI , 0.85 - 1.17 ) and for combined CVD were 1. Output:	Aside from the well-known blood pressure efficacy of calcium channel blockers and diuretics , with lesser effect of ACE inhibitors and beta-blockers , nebivolol was not more effective than placebo in reducing systolic blood pressure levels . In conclusion , in patients of African ethnicity , treatment initiated with ACE inhibitor or angiotensin II receptor blocker monotherapy was associated with adverse cardiovascular outcomes . We found no evidence of different efficacy of antihypertensive drugs in South Asians , but there is a need for trials with morbidity and mortality outcomes . Screening for cardiovascular risk at a younger age , treating hypertension at lower thresholds , and new delivery models to find , treat and follow hypertensives in the community may help reduce the excess cardiovascular mortality in these high-risk groups
MS21522	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : The Women 's Health Initiative r and omized trial found greater coronary heart disease ( CHD ) risk in women assigned to estrogen/progestin therapy than in those assigned to placebo . Observational studies had previously suggested reduced CHD risk in hormone users . Methods : Using data from the observational Nurses ’ Health Study , we emulated the design and intention-to-treat ( ITT ) analysis of the r and omized trial . The observational study was conceptualized as a sequence of “ trials , ” in which eligible women were classified as initiators or noninitiators of estrogen/progestin therapy . Results : The ITT hazard ratios ( HRs ) ( 95 % confidence intervals ) of CHD for initiators versus noninitiators were 1.42 ( 0.92–2.20 ) for the first 2 years , and 0.96 ( 0.78–1.18 ) for the entire follow-up . The ITT HRs were 0.84 ( 0.61–1.14 ) in women within 10 years of menopause , and 1.12 ( 0.84–1.48 ) in the others ( P value for interaction = 0.08 ) . These ITT estimates are similar to those from the Women 's Health Initiative . Because the ITT approach causes severe treatment misclassification , we also estimated adherence-adjusted effects by inverse probability weighting . The HRs were 1.61 ( 0.97–2.66 ) for the first 2 years , and 0.98 ( 0.66–1.49 ) for the entire follow-up . The HRs were 0.54 ( 0.19–1.51 ) in women within 10 years after menopause , and 1.20 ( 0.78–1.84 ) in others ( P value for interaction = 0.01 ) . We also present comparisons between these estimates and previously reported Nurses ’ Health Study estimates . Conclusions : Our findings suggest that the discrepancies between the Women 's Health Initiative and Nurses ’ Health Study ITT estimates could be largely explained by differences in the distribution of time since menopause and length of follow-up Background A large prospect i ve study in patients with type 2 diabetes ( T2D ) , the German D2C cohort , is presently being enumerated to investigate risk factors of incident cancer in diabetic patients . Study setting A disease management program was offered , on a voluntary basis , to all T2D patients who were members of a statutory health insurance fund in Germany . This first feasibility report uses data from 26.742 T2D patients , who were 40 to 79 years old , resided in the Muenster District , and who were enrolled between June 2003 and July 2008 . Cancer cases were identified through the regional Cancer Registry . Methods Invasive cancer cases were identified using probabilistic record linkage procedures and pseudonymised personal identifiers . Censoring date was December 31 , 2008 . We included only first cancers , leaving 12.650 male and 14.092 female T2D with a total of 88.778 person-years ( py ) . We computed st and ardised incidence ratios ( SIR ) for external comparisons and we employed Cox regression models and hazard ratios ( HR ) within the cohort . Results We identified 759 first cancers among male T2D patients ( 18.7 per 1,000 py ) and 605 among females ( 12.7 per 1,000 py ) . The risk of any incident cancer in T2D was raised ( SIR = 1.14 ; 95 % confidence interval [ 1.10 - 1.21 ] ) , in particular for cancer of the liver ( SIR = 1.94 [ 1.15 - 2.94 ] ) and pancreas ( SIR = 1.45 [ 1.07 - 1.92 ] ) . SIRs decreased markedly with time after T2D diagnosis . In Cox models , adjusting for diabetes duration , body mass index and sex , insulin therapy was related to higher cancer risk ( HR = 1.25 [ 1.17 - 1.33 ] ) . No effect was seen for metformin . Discussion Our study demonstrates feasibility of record linkage between DMP and cancer registries . These first cohort results confirm previous reports . It is envisaged to enhance this cohort by inclusion of further regions of the state , expansion of the follow-up times , and collection of a more detailed medication history Aims /hypothesisObservational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes . We extracted data for malignancies from the ADOPT ( A Diabetes Outcome Progression Trial ) and RECORD ( Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes ) r and omised controlled clinical trials , in which the efficacy and /or safety of metformin was assessed in comparison with sulfonylureas and rosiglitazone . Methods Neoplasm occurrences were collected as adverse events in these studies . We review ed and re-analysed the individual participant data in both studies for serious adverse events , malignancies reported as adverse events and related neoplasms of special interest . Results In ADOPT , 50 participants ( 3.4 % ) on metformin and 55 ( 3.8 % ) on each of rosiglitazone and glibenclamide ( known as glyburide in the USA and Canada ) developed serious adverse event malignancies ( excluding non-melanoma skin cancers ) . This corresponds to 1.03 , 1.12 and 1.31 per 100 person-years , giving hazard ratios for metformin of 0.92 ( 95 % CI 0.63–1.35 ) vs rosiglitazone and 0.78 ( 0.53–1.14 ) vs glibenclamide . In RECORD , on a background of sulfonylurea , 69 ( 6.1 % ) participants developed malignant neoplasms in the metformin group , compared with 56 ( 5.1 % ) in the rosiglitazone group ( HR 1.22 [ 0.86–1.74 ] ) . On a background of metformin , 74 ( 6.7 % ) participants in the sulfonylurea group developed malignant neoplasms , compared with 57 ( 5.1 % ) in the rosiglitazone group ( HR 1.33 [ 0.94–1.88 ] ) . Conclusions /interpretationThe malignancy rates in these two r and omised controlled clinical trials do not support a view that metformin offers any particular protection against malignancy compared with rosiglitazone . However , they do not refute the possibility of a difference compared with sulfonylureas OBJECTIVE The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase ( AMPK ) . Activation of AMPK can suppress tumor formation and inhibit cell growth in addition to lowering blood glucose levels . We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes . RESEARCH DESIGN AND METHODS In an observational cohort study using record-linkage data bases and based in Tayside , Scotl and , U.K. , we identified people with type 2 diabetes who were new users of metformin in 1994–2003 . We also identified a set of diabetic comparators , individually matched to the metformin users by year of diabetes diagnosis , who had never used metformin . In a survival analysis we calculated hazard ratios for diagnosis of cancer , adjusted for baseline characteristics of the two groups using Cox regression . RESULTS Cancer was diagnosed among 7.3 % of 4,085 metformin users compared with 11.6 % of 4,085 comparators , with median times to cancer of 3.5 and 2.6 years , respectively ( P < 0.001 ) . The unadjusted hazard ratio ( 95 % CI ) for cancer was 0.46 ( 0.40–0.53 ) . After adjusting for sex , age , BMI , A1C , deprivation , smoking , and other drug use , there was still a significantly reduced risk of cancer associated with metformin : 0.63 ( 0.53–0.75 ) . CONCLUSIONS These results suggest that metformin use may be associated with a reduced risk of cancer . A r and omized trial is needed to assess whether metformin is protective in a population at high risk for cancer There is growing evidence that patients with type 2 diabetes mellitus have increased cancer risk . We examined the association between diabetes , cancer , and cancer-related mortality and hypothesized that insulin sensitizers lower cancer-related mortality . Participants in the Diabetes Cardiovascular Risk and Evaluation : Targets and Essential Data for Commitment of Treatment study , a nationwide cross-sectional and prospect i ve epidemiological study , were recruited from German primary care practice s. In the cross-sectional study , subjects with type 2 diabetes mellitus had a higher prevalence of malignancies ( 66/1308 , 5.1 % ) compared to nondiabetic subjects ( 185/6211 , 3.0 % ) ( odds ratio , 1.64 ; 95 % confidence interval , 1.12 - 2.41 ) before and after adjustment for age , sex , hemoglobin A(1c ) , smoking status , and body mass index . Patients on metformin had a lower prevalence of malignancies , comparable with that among nondiabetic patients , whereas those on any other oral combination treatment had a 2-fold higher risk for malignancies even after adjusting for possible confounders ; inclusion of metformin in these regimens decreased the prevalence of malignancies . In the prospect i ve analyses , diabetic patients in general and diabetic patients treated with insulin ( either as monotherapy or in combination with other treatments ) had a 2- and 4-fold , respectively , higher mortality rate than nondiabetic patients , even after adjustment for potential confounders ( incidence of cancer deaths in patients with type 2 diabetes mellitus [ 2.6 % ] vs the incidence of cancer deaths in patients without type 2 diabetes mellitus [ 1.2 % ] ) . Our results suggest that diabetes and medications for diabetes , with the exception of the insulin sensitizer metformin , increase cancer risk and mortality OBJECTIVE Meta-analyses of epidemiologic studies have suggested that metformin may reduce cancer incidence , but r and omized controlled trials did not support this hypothesis . RESEARCH DESIGN AND METHODS A retrospective cohort study , Clinical Practice Research Data link , was design ed to investigate the association between use of metformin compared with other antidiabetes medications and cancer risk by emulating an intention-to-treat analysis as in a trial . A total of 95,820 participants with type 2 diabetes who started taking metformin and other oral antidiabetes medications within 12 months of their diagnosis ( initiators ) were followed up for first incident cancer diagnosis without regard to any subsequent changes in pharmacotherapy . Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios ( HR ) and 95 % CI . RESULTS A total of 51,484 individuals ( 54 % ) were metformin initiators and 18,264 ( 19 % ) were sulfonylurea initiators , and 3,805 first incident cancers were diagnosed during a median follow-up time of 5.1 years . Compared with initiators of sulfonylurea , initiators of metformin had a similar incidence of total cancer ( HR 0.96 ; 95 % CI 0.89–1.04 ) and colorectal ( HR 0.92 ; 95 % CI 0.76–1.13 ) , prostate ( HR 1.02 ; 95 % CI 0.83–1.25 ) , lung ( HR 0.85 ; 95 % CI 0.68–1.07 ) , or postmenopausal breast ( HR 1.03 ; 95 % CI 0.82–1.31 ) cancer or any other cancer . CONCLUSIONS In this large study , individuals with diabetes who used metformin had a similar risk of developing cancer compared with those who used sulfonylureas Summary Background Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa ; whether benefits occur alongside combination antiretroviral therapy ( ART ) is unclear . We estimated the effect of prophylaxis after ART initiation in adults . Methods Participants in our observational analysis were from the DART r and omised trial of management strategies in HIV-infected , symptomatic , previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per μL. Co-trimoxazole prophylaxis was not routinely used or r and omly allocated , but was variably prescribed by clinicians . We estimated effects on clinical outcomes , CD4 cell count , and body-mass index ( BMI ) using marginal structural models to adjust for time-dependent confounding by indication . DART was registered , number IS RCT N13968779 . Findings 3179 participants contributed 14 214 years of follow-up ( 8128 [ 57 % ] person-years on co-trimoxazole ) . Time-dependent predictors of co-trimoxazole use were current CD4 cell count , haemog Output:	The studies least likely to be affected by bias did not support a causal effect of metformin on cancer risk
MS21523	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The partogram is a pictorial representation of the progress of labour , used in an effort to enhance early recognition of dystocia and help avoid Caesarean section ( CS ) . The objective of this study was to evaluate the effect of partogram use on the CS and obstetric intervention rates . METHODS We conducted a r and omized controlled trial of use of the partogram in 1932 primiparous women with uncomplicated pregnancies at term . Patients were r and omly assigned to one of two groups : the st and ard group , who had the progress of labour charted in written notes , or the partogram group , whose progress in labour was recorded using a bedside graphical partogram as well as in written notes . Outcomes were stratified according to whether labour was spontaneous or induced and whether membranes were initially intact or ruptured . The primary outcome was the rate of CS ; secondary outcome measures were rates of obstetric intervention for dystocia . RESULTS There was no significant difference between the groups in rates of CS ( partogram 24 % , st and ard notes 25 % ) , rates of other interventions , amniotomy , oxytocin use , or the mean cervical dilatation in labour . CONCLUSION In this study , the use of a partogram without a m and atory management of labour protocol had no effect on rates of CS or other intrapartum interventions in healthy primiparous women at term Background The partograph is currently the main tool available to support decision-making of health professionals during labour . However , the rate of appropriate use of the partograph is disappointingly low . Apart from limitations that are associated with partograph use , evidence of positive impact on labour-related health outcomes is lacking . The main goal of this study is to develop a Simplified , Effective , Labour Monitoring-to-Action ( SELMA ) tool . The primary objectives are : to identify the essential elements of intrapartum monitoring that trigger the decision to use interventions aim ed at preventing poor labour outcomes ; to develop a simplified , monitoring-to-action algorithm for labour management ; and to compare the diagnostic performance of SELMA and partograph algorithms as tools to identify women who are likely to develop poor labour-related outcomes . Methods / Design A prospect i ve cohort study will be conducted in eight health facilities in Nigeria and Ug and a ( four facilities from each country ) . All women admitted for vaginal birth will comprise the study population ( estimated sample size : 7,812 women ) . Data will be collected on maternal characteristics on admission , labour events and pregnancy outcomes by trained research assistants at the participating health facilities . Prediction models will be developed to identify women at risk of intrapartum-related perinatal death or morbidity ( primary outcomes ) throughout the course of labour . These predictions models will be used to assemble a decision-support tool that will be able to suggest the best course of action to avert adverse outcomes during the course of labour . To develop this set of prediction models , we will use up-to- date techniques of prognostic research , including identification of important predictors , assigning of relative weights to each predictor , estimation of the predictive performance of the model through calibration and discrimination , and determination of its potential for application using internal validation techniques . Discussion This research offers an opportunity to revisit the theoretical basis of the partograph . It is envisioned that the final product would help providers overcome the challenging tasks of promptly interpreting complex labour information and deriving appropriate clinical actions , and thus increase efficiency of the care process , enhance providers ’ competence and ultimately improve labour outcomes .Please see related articles ‘ http://dx.doi.org/10.1186/s12978-015-0027-6 ’ and ‘ http://dx.doi.org/10.1186/s12978-015-0028-5 ’ Background The Normalization Process Model is a theoretical model that assists in explaining the processes by which complex interventions become routinely embedded in health care practice . It offers a framework for process evaluation and also for comparative studies of complex interventions . It focuses on the factors that promote or inhibit the routine embedding of complex interventions in health care practice . Methods A formal theory structure is used to define the model , and its internal causal relations and mechanisms . The model is broken down to show that it is consistent and adequate in generating accurate description , systematic explanation , and the production of rational knowledge cl aims about the workability and integration of complex interventions . Results The model explains the normalization of complex interventions by reference to four factors demonstrated to promote or inhibit the operationalization and embedding of complex interventions ( interactional workability , relational integration , skill-set workability , and context ual integration ) . Conclusion The model is consistent and adequate . Repeated calls for theoretically sound process evaluations in r and omized controlled trials of complex interventions , and policy-makers who call for a proper underst and ing of implementation processes , emphasize the value of conceptual tools like the Normalization Process Model As part of the Safe Motherhood Initiative , launched in 1987 , the World Health Organization have produced and promoted a partograph with a view to improving labour management and reducing maternal and fetal morbidity and mortality . This partograph has been tested in a multicentre trial in south east Asia involving 35,484 women . Introduction of the partograph with an agreed labour-management protocol reduced both prolonged labour ( from 6.4 % to 3.4 % of labours ) and the proportion of labours requiring augmentation ( from 20.7 % to 9.1 % ) . Emergency caesarean sections fell from 9.9 % to 8.3 % , and intrapartum stillbirths from 0.5 % to 0.3 % . Among singleton pregnancies with no complicating factors , the improved outcome was even more marked , with caesarean sections falling from 6.2 % to 4.5 % . The improvements took place among both nulliparous and multiparous women . The World Health Organisation partograph clearly differentiates normal from abnormal progress in labour and identifies those women likely to require intervention . Its use in all labour wards is recommended Summary In an attempt to evaluate the contributory factors to the high frequency of referred cases in obstructed labour at the State 's referral hospital , a question naire-based survey of 396 maternity care-providers from 66 r and omly selected peripheral delivery units in Ogun State , Nigeria was conducted over a 2-month period , to evaluate their knowledge and use of the partograph . The majority of the personnel were nurses/midwives ( 45.5 % ) and community health extension workers ( CHEW ) ( 42.7 % ) . Of the 216 personnel ( 54.5 % ) who were aware of the partograph , 36 ( 16.7 % ) , 119 ( 55.5 % ) and 61 ( 28.2 % ) demonstrated poor , fair and good levels of knowledge , respectively . No junior CHEW had a satisfactory knowledge of the partograph . Only 39 ( 9.8 % ) of all the personnel routinely employed the partograph for labour management and almost half of these individuals had a poor level of knowledge . Efforts to limit the frequency of referred cases of established obstructed labour to the State 's referral hospital should include training of care-providers at the peripheral delivery units , especially junior personnel in the effective use of the partograph , in addition to employing quality assurance measures to check inappropriate use OBJECTIVE : To assess the ability of midwives to interpret antenatal cards and partograms correctly following completion of the Maternal Care Manual of the Perinatal Education Programme . STUDY DESIGN : We conducted a prospect i ve , controlled trial in a study town and two control towns in the Eastern Cape Province of South Africa . All 93 midwives caring for pregnant women in the three towns were included in the study . Sample s were compared using the two-tailed Student ’s t-test . RESULTS : The marks achieved by the study group for questions from the antenatal card and the partogram improved by 33.0 % ( p < 0.001 ) and 17.5 % ( p = 0.001 ) , respectively . No changes were observed in the control group . CONCLUSION : Midwives that studied the Maternal Care Manual significantly improved their ability to interpret clinical information and apply knowledge . If this ability is applied in clinical practice , a reduction in maternal and perinatal deaths is possible OBJECTIVE to assess the effectiveness of promoting the use of the World Health Organization ( WHO ) partograph by midwives for labour in a maternity home by comparing outcomes after birth . SETTING Medan city , North Sumatera Province , Indonesia . PARTICIPANTS 20 midwives who regularly conducted births in maternity homes , r and omly allocated into two equal groups . DESIGN cluster r and omised-control trial . INTERVENTION under supervision from a team of obstetricians , midwives in the intervention group were introduced to the WHO partograph , trained in its use and instructed to use it in subsequent labours . MEASUREMENTS AND FINDINGS there were 304 eligible women with vertex presentations among 358 labouring women in the intervention group and 322 among 363 in the control group . Among the intervention group , 304 ( 92.4 % ) partographs were correctly completed . From 71 women with the graph beyond the alert line , 42 ( 65 % ) were referred to hospital . Introducing the partograph significantly increased referral rate , and reduced the number of vaginal examinations , oxytocin use and obstructed labour . The proportions of caesarean sections and prolonged labour were not significantly reduced . Apgar scores of less than 7 at 1min was reduced significantly , whereas Apgar scores at 5mins and requirement for neonatal resuscitation were not significantly different . Fetal death and early neonatal death rates were too low to compare . IMPLICATION S FOR PRACTICE a training programme with follow-up supervision and monitoring may be of use when introducing the WHO partograph in other similar setting s , and the findings of this study suggest that the appropriate time of referral needs more emphasis in continuing education . CONCLUSION the WHO partograph should be promoted for use by midwives who care for labouring women in a maternity home OBJECTIVE To determine the effect of partogram on the frequency of prolonged labour , augmented labour , operative deliveries and whether appropriate interventions based on the partogram will reduce maternal and perinatal complications . METHOD A case controlled , prospect i ve and interventional study on 1000 women in labour was carried out in the obstetric unit of Jinnah Post graduate medical center , Karachi , from 1st July to 30th December , 2002 . Five hundred women were studied before and after the introduction of partogram . Duration of labour , mode of delivery , number of cases augmented and neonatal outcome were noted RESULTS Labour was shorter than 12 hours in 80.8 % primigravida , 18.4 % had labour shorter than 24 hours and only 0.8 % had labour longer than 24 hours . After introduction of partogram 91.6 % delivered within 12 hours and rest ( 8.4 % ) delivered within 24 hours . Normal vaginal delivery was had in 88 % , 5.6 % had operative vaginal delivery and 6.4 % had caesarean section . Introduction of partogram showed significant impact on duration of labour ( p < 0.001 ) as well as on mode of delivery ( p < 0.01 ) . In multigravidae 94.4 % delivered within 12 hours and rest 5.6 % delivered within 24 hours when partogram was used while 88.4 % delivered within 12 hours and the rest 11.6 % ) within 24 hours before the use of partogram . Partogram showed significant reduction in duration of labour ( p < 0.01 ) . Results also showed significant reduction in number of augmented labour ( p < 0.001 ) and vaginal examinations ( p < 0.001 ) . CONCLUSION By using partogram , frequency of prolonged and augmented labour , postpartum haemorrhage , ruptured uterus , puerperal sepsis and perinatal morbidity and mortality was reduced OBJECTIVE To study the impact of an educational intervention of midwives ' use of the Angolan model of the World Health Organization 's ( WHO ) partograph . SETTING A peripheral delivery unit with approximately 1500 deliveries per year , run by eleven midwives in Lu and a , Angola . DESIGN The quasi-experimental , One-Group Pre-test-Post-test design was used in this study . Fifty partographs plotted with an initial dilatation < 8 cm were r and omly selected from the first period of six month to form sample I , and another fifty from the second six-months period to form sample II . INTERVENTION In-service education ( theory and practice ) performed by a team of midwives and an obstetrician . MEASUREMENTS AND FINDINGS When comparing sample II with sample I , statistically significant improvements were found in seven of 10 measured variables . This indicates a positive effect of the educational intervention on a proper use of the partograph . Due to the small sample size , however , this study can not evaluate action taken in relation to prolonged labour . IMPLICATION S FOR PRACTICE The in-service educational programme may be of use when introducing the WHO partograph in similar setting s , and the findings of this study may indicate which parts of the programme need more emphasis . CONCLUSIONS The midwives improved in general their documentation of the partograph . However , they tended to exceed established criteria for responsibilities at the peripheral delivery unit , a fact supported by an increased number of missed transfers . The study did not , however , answer the question why the midwives acted as they did in the referred cases A 6-week prospect i ve study of women referred to Korle Bu Teaching Hospital during labour and delivery was conducted to determine the sources of and indications for referral , and to assess the adequacy of various aspects of the referral mechanisms . Of 396 women referred , 86 % were referred from polyclinics ( which are state-owned ) and private midwives . The commonest indications were failure to progress ( 21.5 % ) and hypertensive disease ( 15.7 % ) . A total of 35 ( 8.8 % ) women were referred with third-stage or immediate Output:	Results The evidence synthesis relates the evidence to identified theories of health worker acceptability , health system support , effective referral systems , human re sources and health worker competence , highlighting barriers and facilitators .
MS21524	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND / OBJECTIVE Repetitive transcranial magnetic stimulation ( rTMS ) has been mainly studied as adjunctive treatment for drug-resistant patients . We assessed the effectiveness of rTMS started concomitantly with antidepressant medications in non-drug-resistant major depressive disorder patients . We also evaluated if , among the 3 antidepressants administered , one had a better synergy with rTMS . METHOD In this 5-week , double-blind , r and omized , sham-controlled study , we recruited 99 in patients suffering from a major depressive episode ( DSM-IV criteria ) . They were r and omly assigned to receive venlafaxine , sertraline , or escitalopram in combination with a 2-week period of sham or active 15-Hz rTMS on the left dorso-lateral prefrontal cortex . Data were gathered from February 2004 to June 2005 . RESULTS The active rTMS group showed a significantly faster reduction in Hamilton Rating Scale for Depression ( HAM-D ) scores compared with the sham group ( p = .0029 ) . The response and remission rates were significantly greater in the active rTMS group after the stimulation period ( p = .002 and p = .003 , respectively ) , but not at the endpoint . We found no significant difference in HAM-D score reduction among the 3 drugs administered , either in the active or in the sham group . CONCLUSION These findings support the efficacy of rTMS in hastening the response to antidepressant drugs in patients with major depressive disorder . The effect of rTMS seems to be unaffected by the specific concomitantly administered drug BACKGROUND Carefully design ed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation ( TMS ) in psychiatric disorders . A major method ological concern is the design of the " sham " control for TMS . An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment . Strategies employed so far include alterations in the position of the stimulating coil , but there has been little systematic study of their validity . In this study , we investigated the effects of different coil positions on cortical activation and scalp sensation . METHODS In nine normal subjects , single TMS pulses were administered at a range of intensities with a " figure eight " coil held in various positions over the left primary motor cortex . Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle . Scalp sensation to TMS with the coil in various positions over the prefrontal area was also assessed . RESULTS None of the coil positions studied met the criteria for an ideal sham . Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex . CONCLUSIONS The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive " stimulation . " Further research is needed to develop the best sham condition for a range of applications This 5-week , r and omized , double-blind , placebo-controlled trial investigated the efficacy and tolerability of high frequency repetitive transcranial magnetic stimulation ( rTMS ) directed to the left prefrontal cortex in drug-resistant depressed patients . Fifty-four patients were r and omly assigned to receive 10 daily applications of either real or sham rTMS . Subjects assigned to receive active stimulation were divided into two further subgroups according to the intensity of stimulation : 80 % vs. 100 % of motor threshold ( MT ) . At study completion , the response rates were 61.1 % ( n=11 ) , 27.8 % ( n=5 ) and 6.2 % ( n=1 ) for the 100 % MT group , 80 % MT group and sham group , respectively . A significant difference ( Pearson chi(2 ) test ) was found between the 100 % MT and sham groups , while the 80 % MT group did not differ significantly from the sham group . Between the two active groups , a marginally significant difference was observed . Analysis of variance with repeated measures on Hamilton Depression Rating Scale scores revealed a significantly different decrease over time of depressive symptomatology among the three treatment groups . Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded , and on the whole the technique was well tolerated . The results of this double-blind trial showed that rTMS may be a useful and safe adjunctive treatment for drug-resistant depressed patients BACKGROUND The role of high-frequency rTMS over the left cortex as an add-on strategy in the treatment of major depression is still uncertain even in patients resistant to pharmacotherapy . We had planned a large sham TMS controlled study in the acute phase with a placebo-controlled relapse-prevention phase with escitalopram . However , because a recent meta- analysis showed only a small effect size of rTMS over sham TMS in the acute treatment phase of depressed patients , we decided to make an interim analysis . METHOD In patients with medication-resistant major depression we administered in a r and omised trial 15 sessions of sham-controlled rTMS over three weeks in combination with 20 mg escitalopram daily . After the last rTMS , the patients were followed for another 9 weeks on 20 mg escitalopram daily . The antidepressant effect was measured by the HAM-D(6 ) as primary outcome scale . RESULTS A total of 45 patients with complete data were r and omised so that 23 patients received sham TMS and 22 patients received active , high-frequency rTMS over the left cortex . Over the 3 weeks , the active rTMS treatment was superior to sham TMS with effect sizes on the HAM-D(6 ) above 0.70 , which indicates not only a statistically but also a clinical ly significant effect . The patients had typically been through two failed antidepressant treatment attempts with non-tricyclics before inclusion in the study . Both the rTMS and escitalopram were well-tolerated . CONCLUSION High-frequency rTMS over the left cortex is an add-on strategy of clinical significance in combination with escitalopram in patients with major depression resistant to non-tricyclic antidepressants 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 BACKGROUND Transcranial magnetic stimulation ( TMS ) is a noninvasive method to stimulate the cortex , and the treatment of depression is one of its potential therapeutic applications . Three recent meta analyses strongly suggest its benefits in the treatment of depression . The present study investigates whether repetitive TMS ( rTMS ) accelerates the onset of action and increases the therapeutic effects of amitriptyline . METHODS Forty-six out patients meeting DSM-IV criteria for nonpsychotic depressive episode were r and omly assigned to receive rTMS ( n = 22 ) or sham repetitive TMS ( sham ) ( n = 24 ) during 4 weeks over dorsolateral prefrontal cortex ( DLPFC ) in this double-blind controlled trial . All patients were concomitantly taking amitriptyline ( mean dose 110 mg/d ) . The rTMS group received 20 sessions ( 5 sections per week ) of 5 Hz rTMS ( 120 % of motor threshold and 1250 pulses per session ) . Sham stimulation followed the same schedule , however , using a sham coil . The efficacy variables were the Hamilton Depression Rating Scale-17 items ( HAM-D/17 ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , a Visual Analogue Scale ( VAS ) , and the Clinical Global Impression ( CGI ) . Tolerability was assessed by clinical examination and a safety screening of TMS side effects . RESULTS Repetitive TMS had a significantly faster response to amitriptyline . There was a significant decrease in HAM-D/17 scores , already after the first week of treatment ( p < .001 compared with baseline and p < .001 compared with sham ) . The decrease in HAM-D/17 scores in the rTMS group was significantly superior compared with the sham group throughout the study ( p < .001 at fourth week ) . CONCLUSIONS Repetitive TMS at 5 Hz accelerated the onset of action and augmented the response to amitriptyline Objective : This study investigated the impact of latency ( the time between illness onset and initiation of prophylactic treatment ) on the outcome of prophylaxis in bipolar disorders Escitalopram , a selective serotonin reuptake inhibitor ( SSRI ) , was compared to placebo in a study of patients with major depressive disorder ( DSM-IV ) who had baseline Montgomery – Åsberg Depression Rating Scale ( MADRS ) total scores ≥22 and ≤40 . After a 1-week , single-blind placebo period , patients were r and omized to receive escitalopram 10 mg/day ( n = 191 ) or placebo ( n = 189 ) in an 8-week , double-blind period . The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 ( last observation carried forward , LOCF ) of 2.7 points ( SE 0.85;P = 0.002 ) . In further by-week efficacy analyses , the effect of escitalopram was consistently larger than that of placebo ( P < 0.05 ) beginning at week 1 ( Clinical Global Impression – Improvement score ) , week 2 ( MADRS score ) or week 3 ( Clinical Global Impression – Severity score ) . Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo . Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients , although it was infrequent and transient . Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1 , and was safe and very well tolerated BACKGROUND / OBJECTIVE There is evidence for an antidepressant effect of repetitive transcranial magnetic stimulation ( rTMS ) , but little is known about posttreatment course . Therefore , we conducted a placebo-controlled , double-blind study in depressed patients in order to investigate the effect of rTMS on depression over 12 weeks after completion of the 2-week stimulation period . METHOD 55 patients with a moderate or severe DSM-IV major depressive episode were r and omly assigned to rTMS or sham treatment . rTMS was given daily for 10 days over the left dorsolateral prefrontal cortex with the following treatment parameters : 20 Hz , 20 trains of 2 seconds , 30 seconds between trains , and 80 % motor threshold . The effect of rTMS on depression was rated repeatedly with the 17-item Hamilton Rating Scale for Depression ( HAM-D ) during the 2-week period of stimulation and the 12-week follow-up period conducted from 1997 to 2001 . RESULTS We found a modest , clinical ly nonrelevant decrease in HAM-D scores in both rTMS and sham patients over 2 weeks of treatment . However , over the subsequent 12-week follow-up , the rTMS group continued to improve significantly compared with the placebo group . CONCLUSION Decrease of depressive symptoms may continue after the cessation of rTMS stimulation BACKGROUND Studies of repetitive transcranial magnetic stimulation ( rTMS ) in depression have mostly involved once-daily treatment , with positive but modest clinical results . This study tested the efficacy and safety of twice-daily rTMS over 2 weeks . METHOD Thirty-eight depressed subjects enrolled in a double-blind , sham-controlled trial of twice-daily rTMS ( left prefrontal cortex , 10 Hz , 110 % intensity , 1500 stimuli per session ) over 2 weeks . Mood and neuropsychological functioning were assessed weekly by blind raters , using the Montgomery-Asberg Depression Rating Output:	Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy , but not with age , gender and sham method utilized . / SIGNIFICANCE We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination ( add-on rTMS studies ) . The magnitude of the placebo response seems to be related with study population and study design rather than the intervention itself
MS21525	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction : More than half the patients with gastroesophageal reflux disease ( GERD ) show no endoscopic abnormality or minimal change esophagitis ( non-erosive reflux disease , NERD ) . We investigated the value of endoscopic and histological markers for the prediction of NERD before and after treatment with 20 mg esomeprazole . Methods : Between July and October 2002 , consecutive patients presenting for upper endoscopy were stratified into GERD and non-reflux patients ( control group ) with the help of a question naire . The endoscopist was blind to the presence of reflux symptoms . Using magnifying endoscopes minimal change esophagitis was defined by the presence of vascular injection or vascular spots above the Z-line , villous mucosal surface and isl and s of squamous cell epithelium below the Z-line . Targeted and r and om biopsies were taken below and above the Z-line . Patients with endoscopically visible classical signs of esophagitis ( Los Angeles A – D ) or histologically proven Barrett ’s esophagus were not further investigated in the study ( drop out ) . The esophageal specimens were histologically evaluated for erosions , infiltration with leukocytes , hyperplasia of basal cells and length of papillae . Patients with NERD were treated with 20 mg esomeprazole/day for 4 weeks and reevaluated by endoscopy as described before . Results : 39 patients with heartburn and 39 patients without reflux symptoms ( controls ) were finally included in the analysis ( per protocol ) . Patients with NERD significantly ( p = 0.005 ) more often showed endoscopic signs of minimal change esophagitis ( 27/39 ) than the control group ( 8/39 ) . An increased length of papillae ( 14/39 versus 2/39 ; p = 0.005 ) and basal cell hyperplasia ( 17/39 versus 4/39 ; p = 0.009 ) were significantly more common in the heartburn group . After treatment with esomeprazole , no significant endoscopic or histological differences between the NERD and control group could be observed . Conclusions : Minimal change esophagitis can be seen with high resolution magnifying endoscopy . By combining endoscopic and histological markers NERD can be predicted with a sensitivity of 62 % and a specificity of 74 % . Treatment with esomeprazole for 4 weeks reverses the slight alterations to normal Introduction : Irritable bowel syndrome ( IBS ) and functional dyspepsia ( FD ) are highly prevalent in the general population as does gastroesophageal reflux disease ( GERD ) . Therefore , it is expected that these conditions may frequently overlap . Objective : We aim ed at evaluating the presence ofFD and IBS symptoms in patients with erosive ( ERD ) , non-erosive reflux disease ( NERD ) and Barrett ’s esophagus ( BE ) . Patients and Methods : 71 patients presenting at the reflux disease outpatient clinic were prospect ively included in this study . 33 patients had NERD , 25 ERD and 13 BE according to the Montreal classification . All patients with ERD and NERD had typical reflux symptoms , as assessed by a vali date d GERD question naire ( RDQ ) . The diagnosis of functional dyspepsia and IBS symptoms was assessed according to the Rome III criteria . Results : IBS symptoms ( bloating , abdominal pain , constipation and diarrhea ) were slightly more prevalent in NERD ( 54.6 , 63.6 , 21.20 , 24.2 % , respectively ) than in ERD ( 48.0 , 44.0 , 12.0 , 20.0 % , respectively ) and in BE ( 53.9 , 23.10 , 15,4 , 23.1 % , respectively ) , but none of these differences reached statistical significance . NERD patients had more FD symptoms than patients with ERD or BE , but again this difference did not reach statistical significance . Conclusion : Our data show that IBS and FD are common in the entire spectrum of GERD . The presence of these disorders might explain why many patients with GERD are deemed as treatment failures if they have no complete symptom relief with proton pump inhibitors OBJECTIVES /HYPOTHESIS Laryngitis secondary to gastric acid reflux is a prevalent , yet incompletely understood , otolaryngological disorder . Further characterization of the relationship between symptoms and signs and reflux severity is needed . STUDY DESIGN Prospect i ve clinical trial . METHODS Forty-two consecutive , nonsmoking patients with one or more reflux laryngitis symptoms were recruited to complete a symptom question naire , videostrobolaryngoscopy , and 24-hour , dual-sensor pH probe testing . Twenty-nine patients had more than four episodes of laryngopharyngeal reflux , and the remaining 13 served as control subjects . Symptom scores were produced by multiplying the severity by the frequency for the following : hoarseness , throat pain , " lump-in-throat " sensation , throat clearing , cough , excessive phlegm , dysphagia , odynophagia , and heartburn . Endoscopic laryngeal signs included erythema and edema of the vocal folds and arytenoids , and interarytenoid irregularity . RESULTS Symptom scores varied significantly , with throat clearing being greater than the rest . None of the symptoms , except heartburn , correlated with reflux ( laryngopharyngeal and esophageal ) severity . Patients with worse laryngopharyngeal reflux were found to have worse esophageal reflux . Endoscopic laryngeal signs were rated as mild , on average , and did not correlate with laryngopharyngeal reflux severity . The number of laryngopharyngeal reflux episodes ( per 24 h ) ranged from 0 to 40 ( mean number , 10.6 episodes ) . CONCLUSIONS Throat clearing was the most intense symptom in the present group of patients with proven reflux laryngitis . Dual-sensor pH probe testing could not predict the severity of patient 's reflux laryngitis symptoms or signs . Only the heartburn symptom correlated with laryngopharyngeal and esophageal reflux OBJECTIVE : Previous uncontrolled studies suggested a therapeutic benefit for treating gastroesophageal reflux disease ( GERD ) among patients with laryngitis . The present study is the first r and omized , placebo-controlled , double-blind study of gastric acid suppression among patients with laryngitis in the United States . METHODS : Patients diagnosed with idiopathic chronic laryngitis were r and omized to receive either lansoprazole 30 mg p.o . b.i.d . or a matching placebo for 3 months . Before r and omization , all patients underwent upper endoscopy , dual probe ambulatory 24-h esophageal pH-metry , and laryngoscopy , as well as completing a symptom question naire for GERD and laryngitis . The primary outcome of treatment was the complete resolution of laryngeal symptoms . RESULTS : A total of 22 patients with symptoms and signs of chronic laryngitis were enrolled , 20 of whom completed the study . At baseline , there were no significant differences between the two groups with regards to GERD symptoms , erosive esophagitis , proximal and distal esophageal pH-metry , or laryngeal signs and symptoms . In an intention-to-treat analysis , six patients in the lansoprazole group ( 50 % ) and only one patient ( 10 % ) in the placebo group achieved a complete symptomatic response , p = 0.04 . Apart from receiving lansoprazole , there were no significant differences between responders and nonresponders in any of baseline esophageal or laryngeal signs and symptoms . CONCLUSIONS : Empirical treatment with lansoprazole is efficacious in relieving symptoms of laryngitis compared to placebo . Such treatment can be considered as a first-line option in managing patients with idiopathic chronic laryngitis Objective : Recent studies suggest an association between chronic cough and gastroesophageal reflux . Our study aims were 1 ) to define the prevalence of acid reflux induced cough in the general community , 2 ) to examine the ability of esophageal testing to identify gastroesophageal reflux related cough , and 3 ) to assess the utility of omeprazole in a chronic cough algorithm . Methods : Patients with chronic cough of unknown etiology , who were mostly from the community , were evaluated . Subjects underwent a chest x-ray , methacholine challenge test , and empiric trial of postnasal drip therapy , and completed daily cough symptom diaries subjectively evaluating cough frequency and severity on a grade d scale of 0–4 ( combined maximum 8) . After excluding other causes of cough , the remaining patients underwent esophageal and pH testing . Those testing positive were r and omized to omeprazole 40 mg b.i.d . or placebo for 12 weeks . Follow-up was 1 yr . Results : A total of 71 patients were screened ; 48 were excluded . Twenty-three patients were evaluated for gastroesophageal reflux disease ; six ( 26 % ) were eventually determined to have an acid-related cough . Of these patients , 17 had a positive pH test , six ( 35 % ) of whom showed a striking improvement or resolution of their cough during omeprazole treatment which was sustained for up to 1 yr . Six had a negative pH test , none of whom responded to omeprazole therapy . No significant differences were seen between responders ( n = 6 ) and nonresponders ( n = 11 ) for demographic factors , baseline symptom frequency and duration , or physiological parameters ( motility/pH ) . Conclusions : Acid-related chronic cough was present in 26 % ( six of 23 ) of patients evaluated for gastroesophageal reflux disease . Esophageal testing does not reliably identify patients with acid induced chronic cough responsive to proton pump inhibitor therapy . We suggest that the best diagnostic and therapeutic approach , after excluding asthma and postnasal drip syndrome , is empiric treatment for 2 wk with a high dose proton pump inhibitor The hypothesis that non-erosive reflux disease ( NERD ) patients comprise various subgroups is gaining popularity . This study was conducted to investigate the possibility of categorizing NERD patients according to symptom types and response to acid-suppressive drug rabeprazole ( RPZ ) 10 mg/day . NERD patients were classified as grade N ( endoscopically normal ) , M ( minimal change ) , or erosive GERD , and answered a 51-item , yes-or-no question naire pre and post-treatment . Compared to erosive GERD , clear differences existed in pretreatment prevalence of symptoms and responsiveness to RPZ in grade s N and M ; the results suggested stomachaches ( especially at night ) were significant symptoms in grade N and dysmotility-like symptoms like bloated stomach were significant in grade M while gastroesophageal reflux symptoms were significant in erosive GERD . Clinical significance of classifying NERD was indicated from different symptoms and responsiveness to PPI Aim : To determine whether symptomatic response to lansoprazole predicts abnormal acid reflux in endoscopy‐negative patients with non‐cardiac chest pain Background Persistent gastro‐oesophageal reflux disease ( GERD ) , despite proton pump inhibitor ( PPI ) therapy , is a common problem . Combined pH/impedance monitoring ( pH/MII ) enables detection of reflux episodes Abstract Objectives . Data supporting the use of the proton pump inhibitor ( PPI ) test as a diagnostic test of gastroesophageal reflux disease ( GERD ) in Asia are lacking . The aims of this study were to evaluate the diagnostic characteristics of the PPI test and factors associated with responsiveness to PPIs . Methods . The PPI test was evaluated using lansoprazole ( 30 mg bid ) for two weeks . All patients underwent endoscopy after symptom assessment . Patients without erosive esophagitis ( ERD ) underwent 48 h esophageal Bravo pH monitoring . Subjects were considered to be responsive to PPIs if they reported a > 50 % reduction in reflux symptom score . Results . Seventy-three patients ( M : F = 40:37 , 47 ± 13 years ) were enrolled . We identified 46 patients with ERD , 18 patients with nonerosive reflux disease ( NERD ) and 9 patients without GERD . The PPI response rate was higher in patients with GERD than in patients without GERD ( 49/64 , 77 % vs. 4/9 , 44 % ; p < 0.05 ) . The sensitivity , specificity , and positive and negative predictive values were 77 % , 56 % , 92 % and 25 % , respectively . The PPI responsiveness was 80 % ( 37/46 ) in the ERD group and 67 % ( 12/18 ) in the NERD group . PPI response was not affected by age , sex , Helicobacter pylori , the psychological characteristics or cytochrome P2C genotypes . ERD and symptom-reflux association were the factors affecting PPI responsiveness . Conclusions . The PPI test was mod Output:	That is , the PPI test has been proven to be a sensitive tool for diagnosing GERD in patients with non-cardiac chest pain and in some preliminary trials regarding extraesophageal manifestations of GERD . Ambulatory pH monitoring of the esophagus helps to confirm gastroesophageal reflux in patients with persistent symptoms ( both typical and atypical ) in the absence of esophageal mucosal damage , especially when a trial of acid suppression has failed . Impedance pH test is useful in refractory reflux patients with primary complaints of typical GERD symptoms , but this value has not been proved in patients with non-cardiac chest pain or extraesophageal symptoms .
MS21526	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Evidence -based practice is important to . clinical health care professionals . Clinical nurses can make informed decisions by applying the best evidence to their care . However , st and ardized curricula on evidence -based medicine are lacking in nursing education programs . This study evaluated a critical appraisal education program and assessed its value in increasing nurses ' knowledge of critical appraisal and confidence in their critical appraisal skills . METHODS A controlled before- and -after study design was used . The education program integrated lectures , practice , and group discussion . A question naire was used to evaluate participants ' knowledge and confidence in critical appraisal pre- and postintervention . RESULTS Participants ' knowledge and confidence in critical appraisal improved significantly postintervention(both p < .001 ) . CONCLUSION A 1-day , small group discussion education program can effectively improve nurses ' knowledge and confidence in critical appraisal . Educators and administrators may replicate this education program to improve the quality of nursing Although evidence -based practice ( EBP ) improves health care quality , decreases costs , and empowers nurses , there is a paucity of intervention studies design ed to test models of how to enhance nurses ' use of EBP . Therefore , the specific aim of this study was to determine the preliminary effects of implementing the Advancing Research and Clinical practice through close Collaboration ( ARCC ) model on nurses ' EBP beliefs , EBP implementation behaviors , group cohesion , productivity , job satisfaction , and attrition/turnover rates . A 2-group r and omized controlled pilot trial was used with 46 nurses from the Visiting Nurse Service of New York . The ARCC group versus an attention control group had stronger EBP beliefs , higher EBP implementation behaviors , more group cohesion , and less attrition/turnover . Implementation of the ARCC model in health care systems may be a promising strategy for enhancing EBP and improving nurse and cost outcomes Background This study evaluated the effectiveness of the context ualized EBP training program for Filipino physical therapists in terms of knowledge , skills , attitudes and behavior . Methods A r and omized controlled trial was design ed to assess the effectiveness of the EBP training program . Fifty four physical therapists were r and omly allocated to the EBP group ( intervention ) and waitlist ( control ) group . The EBP group had a one day face-to-face training with an online support , whilst the control was waitlisted . There were three measurement points which were pre , post , and three months post intervention for knowledge , skills and attitudes . Activity diaries were used to measure behavior . The diaries were collected after three months . Data analysis was by intention to treat in EBP domains of knowledge , skills and attitudes . Results Fifty-four physical therapists were included in the study . Fifty two ( 52 ) completed the post training assessment and 26 completed the 3 months post training assessment for EBP knowledge , skills and attitudes . There were significant improvements in these domains in the EBP group from pre to post training and over a period of three months ( p < 0.05 ) compared with the waitlist control group . Thirty seven ( 37 ) physical therapists completed their activity diaries over three months . Behavior significantly improved in the EBP group in terms of EBP behaviors ( formulating PICO , search ing , appraising and applying the evidence ) when faced with both new/unique and usual case scenarios ( p < 0.05 ) . More physical therapists in the waitlist control group significantly performed non-EBP behaviors ( asking doctors and reading textbooks ) when faced with new/unique cases compared with the EBP group ( p < 0.05 ) . No differences were noted between groups regarding non-EBP behaviors ( asking colleagues and doctors and reading textbooks ) particularly when faced with usual cases . Conclusion The context ually design ed EBP training program for Filipino physical therapists was effective in improving knowledge , skills and attitudes to EBP from pre to post training . Improvements were also observed at three months post training in knowledge , skills , attitudes and behavior to EBP . This model of training can be modified as needed based on the needs of the local context . Findings need to be interpreted with caution due to study limitations .Current controlled trialsIS RCT N74485061 ( Registration date : February 9 , 2011 ) Background Presentation of results of diabetes prevention studies as relative risk reductions and the use of diagnostic categories instead of metabolic parameters leads to overestimation of effects on diabetes risk . This survey examines to what extent overestimation of diabetes prevention is related to overestimation of prevention of late complications . Methods Participants of two postgraduate courses in clinical diabetology in Austria ( n = 69 ) and Germany ( n = 31 ) were presented a question naire with 8 items at the beginning of the meetings . All 100 question naires were returned with 92 filled in completely . Participants were asked 1 ) to rate the importance of differently framed results of prevention studies and , for comparison , of the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) , 2 ) to estimate to what extent late complications could be prevented by the achieved reductions in diabetes risk or HbA1c values , respectively . Results Prevention of diabetes by 60 % was considered important by 84 % of participants and 35 % thought that complications could be prevented by ≥ 55 % . However , if corresponding HbA1c values were presented ( 6.0 % versus 6.1 % ) only 19 % rated this effect important , and 12 % thought that late complications could be prevented by ≥ 55 % . The difference in HbA1c of 0.9 % over 10 years in the UKPDS was considered important by 75 % of participants and 16 % thought that complications ( ' any diabetes related endpoint ' ) were reduced by ≥ 55 % ( correct answer < 15 % by 20 % participants ) . Conclusion The novel key message of this study is that the misleading reporting of diabetes prevention studies results in overestimation of effects on late complications RATIONALE , AIMS AND OBJECTIVES Continuing health education is essential but challenged . In 2006 , the Brazilian Cochrane Center , in collaboration with the Ministry of Health , launched a mass teaching initiative in evidence -based health care ( EBH ) for public-sector professionals via teleconferencing . This 152-hour , interactive EBH course has enrolled over 4500 professionals . This study aim ed to assess the acquisition EBH knowledge and skills , as well as the attitudes and perceptions of a sample of students enrolled in the 2009 course via teleconferencing . METHODS This prospect i ve cohort study analyzed three aspects of this 152-hour EBH course that recruited 1040 volunteer participants , all public health sector employees working in 131 different hospitals or health agencies . Pre- and post-course tests using a modified version of the Berlin question naire with 20 multiple-choice questions were used to examine knowledge acquisition in a sample of 297 students . Tests were completed upon registration and at course completion . The research projects su bmi tted by 872 participants were evaluated to assess skill acquisition . Answers to an anonymous survey assessed the attitudes and perceptions of 914 participants . RESULTS There was a significant increase in knowledge from baseline to course completion ( mean scores 8.2 ± 3.3 versus 13.7 ± 3.0 , P < 0.001 ) . Over 90 % of the research projects were judged to be of adequate quality ( appropriate rationale for the study , well-formulated research question and feasible execution ) ; over 95 % of the participants were satisfied with the course . CONCLUSION The Brazilian EBH course via teleconference improved the knowledge and skills of public-sector health professionals and was approved by the vast majority of students BACKGROUND Evidence -based public health decision-making depends on high quality and transparent accounts of what interventions are effective , for whom , how and at what cost . Improving the quality of reporting of r and omized and non-r and omized study design s through the CONSORT and TREND statements has had a marked impact on the quality of study design s. However , public health users of systematic review s have been concerned with the paucity of synthesized information on context , development and rationale , implementation processes and sustainability factors . METHODS This paper examines the existing reporting frameworks for research against information sought by users of systematic review s of public health interventions and suggests additional items that should be considered in future recommendations on the reporting of public health interventions . RESULTS Intervention model , theoretical and ethical considerations , study design choice , integrity of intervention/process evaluation , context , differential effects and inequalities and sustainability are often overlooked in reports of public health interventions . CONCLUSION Population health policy makers need synthesized , detailed and high quality a priori accounts of effective interventions in order to make better progress in tackling population morbidities and inequalities . Adding simple criteria to reporting st and ards will significantly improve the quality and usefulness of published evidence and increase its impact on public health program planning Critical thinking is essential for professional nursing practice . Promoting critical thinking with teaching strategies has been a focus of nursing education and nursing research . Reading and writing assignments are teaching strategies for fostering critical thinking ability . We developed a course with the emphasis on critical reading and writing . The purpose s of this study were to explore the effect of the course and teaching strategies on promoting critical thinking and to underst and the learning experience and perception of nursing students as part of the course assessment plan . Quasi-experimental design and purposive sampling were used . 170 students of a two-year nursing program were grouped into an experimental and a control group depending on whether or not they took the course . The change in critical thinking ability was evaluated and determined based on performance in an article critique test before and after the course . Data was collected with an assessment tool developed for the purpose s of the research and was analyzed with descriptive statistics , paired t-test , and two-factor analysis of variance with repeated measures and content analysis . The findings were : ( 1 ) The scores on the critique test at the end of the course in both groups were significantly higher than before the course ( p<.001 ) . The improvement in score of the experimental group , however , was significantly higher than that of the control group ( p<.001 ) . ( 2 ) Changes in thinking pattern and learning attitude , as well as a feeling of growth and achievement , were found in content analysis of students ' self-evaluation of their learning experience and perception . Critical thinking skills were applied while learning the course . The results not only provide evidence to support the positive effect of reading and writing assignments on critical thinking ability but also confirm the teaching and learning activity design for the course Background and objectives Evidence -based health care requires clinicians to engage with use of evidence in decision-making at the workplace . A learner-centred , problem-based course that integrates e-learning in the clinical setting has been developed for application in obstetrics and gynaecology units . The course content uses the WHO reproductive health library ( RHL ) as the re source for systematic review s. This project aims to evaluate a clinical ly integrated teaching programme for incorporation of evidence provided through the WHO RHL . The hypothesis is that the RHL-EBM ( clinical ly integrated e-learning ) course will improve participants ' knowledge , skills and attitudes , as well as institutional practice and educational environment , as compared to the use of st and ard postgraduate educational re sources for EBM teaching that are not clinical ly integrated . Methods The study will be a multicentre , cluster r and omized controlled trial , carried out in seven countries ( Argentina , Brazil , Democratic Republic of Congo , India , Philippines , South Africa , Thail and ) , involving 50 - 60 obstetrics and gynaecology teaching units . The trial will be carried out on postgraduate trainees in the first two years of their training . In the intervention group , trainees will receive the RHL-EBM course . The course consists of five modules , each comprising self-directed e-learning components and clinical ly related activities , assignments and assessment s , coordinated between the facilitator and the postgraduate trainee . The course will take about 12 weeks , with assessment s taking place pre-course and 4 weeks post-course . In the control group , trainees will receive electronic , self-directed EBM-teaching material s. All data collection will be online . The primary outcome measures are gain in EBM knowledge , change in attitudes towards EBM and competencies in EBM measured by multiple choice questions ( MCQs ) and a skills-assessing question niare administered eletronically . These questions have been developed by using questions from vali date d question naires and adapting them to the current course . Secondary outcome measure will be educational environment towards EBM which will be assessed by a specifically developed question naire . Expected outcomes The trial will determine whether the RHL EBM ( clinical ly integrated e-leraning ) course will increase knowledge , skills and attitudes towards EBM and improve the educational environment as compared to st and ard teaching that is not clinical ly integrated . If effective , the RHL-EBM course can be implemented in teaching institutions worldwide in both , low- and middle income countries as well as industrialized setting s. The results will have a broader impact than just EBM training because if the approach is successful then the same educational strategy can be used to target other priority clinical and method ological areas .Trial Registration BACKGROUND As course directors , we wished to incorporate small group learning into our Evidence -based Medicine course for students to get feedback on the development of a well constructed , research able clinical question . Scheduling of these groups was problematic . We sought to evaluate computer-mediated communication as an alternative to face-to-face small groups . METHODS Students were r and omly assigned to either face-to-face small groups or asynchronous , electronic , small groups . Final examination scores were analyzed with an analysis of variance to determine if there were differences in student performance based on group type . Student survey items were analyzed using Fisher 's Exact test to determine if there were differences in student attitudes based on group type . RESULTS There were no significant differences found in overall student performance . Significant differences in student attitudes were found to exist with respect to : ( 1 ) participation in discussion s , with face-to-face groups reporting greater participation ; ( 2 ) putting more thought into comments , with electronic groups reporting more thought put into Output:	EbM training shows some impact on knowledge and skills , whereas the impact on practical EbM application remains unclear . Conclusions EbM training has some positive effects on knowledge and skills of healthcare professionals .
MS21527	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIM The aim of the present prospect i ve study was to evaluate the long-term outcome of implants placed simultaneously with guided bone regeneration ( GBR ) using resorbable and non-resorbable membranes . MATERIAL S AND METHODS The original study population consisted of 72 patients receiving a total of 265 implants . In all GBR-treated sites , demineralized bovine bone mineral ( DBBM ) was used in combination either with a collagen ( CM ) or an Exp and ed polytetrafluoroethylene ( e-PTFE ) membrane . A total of 112 implants was treated with CM , 41 implants were treated with e-PTFE membranes , and 112 served as a control group because implants were entirely surrounded by bone and did not need any GBR procedures . Clinical and radiographic analyses were performed after a period of 12 - 14 years . RESULTS The median follow-up time was 12.5 years ( range 12 - 14 years ) . A total of 58 patients participated in the present investigation , corresponding to 80.5 % of the original study population . The cumulative implant survival rate at the follow-up examination was 93.2 % . For the control group the cumulative survival rate was 94.6 % , for the CM 91.9 % , and for the e-PTFE 92.6 % . Differences among the groups were not statistically significant . The radiographically determined marginal bone level ( MBL ) amounted to : control 2.36 mm ( SD ) , CM 2.4 mm ( SD ) , e-PTFE 2.53 mm ( SD ) . There is no evidence ( P < 0.2 ) that the slope of bone level over time is different for the three treatment groups . CONCLUSION It is concluded that implants placed simultaneously with GBR procedures using resorbable or non-resorbable membranes reveal a high survival rate ranging from 91.9 % to 92.6 % , therefore it is considered to be a safe and predictable therapy . [ Correction added after online publication 30 November 2012 : the marginal bone level of CM , e-PTFE , and control was corrected to ' control 2.36 mm ( SD ) , CM 2.4 mm ( SD ) , e-PTFE 2.53 mm ( SD ) ' in the Results section ] PURPOSE This r and omized clinical trial was conducted to assess the safety and effectiveness of the ErhBMP-2 in alveolar bone regeneration as well as preservation of the β-TCP bone graft material that contains ErhBMP-2 . MATERIAL S AND METHODS This study involved 72 patients at the 3 study centers . The patients , who were divided into 2 groups : the experiment group who had ErhBMP-2 coated TCP/HA and the control group who had TCP/HA graft material alone transplanted immediately after tooth extraction . CT was taken before and 3 months after the transplantation and healing status was compared between the two groups . The efficacy endpoints that were used to measure the degree of bone induction included alveolar bone height and 3 measurements of bone width . The paired t test was used to determine the significance of the changes ( P<.05 ) . RESULTS Changes in alveolar bone height were -1.087 ± 1.413 mm in the control group and -.059 ± 0.960 mm in the experimental group ( P<.01 ) . At 25 % extraction socket length [ ESL ] , the changes were 0.006 ± 1.149 mm in the control group and 1.279 ± 1.387 mm in the experimental group . At 50 % ESL , the changes were 0.542 ± 1.157 mm and 1.239 ± 1.249 mm , respectively ( P<.01 for 25 % ESL , and P<.05 for 50 % ESL ) . During the experiment , no adverse reactions to the graft material were observed . CONCLUSION ErhBMP-2 coated β-TCP/HA were found to be more effective in preserving alveolar bone than conventional β-TCP/HA alloplastic bone graft material BACKGROUND Reduction of alveolar height and width after tooth extraction may present problems for implant placement , especially in the anterior maxilla where bone volume is important for biologic and esthetic reasons . Different graft material s have been proposed to minimize the reduction in ridge volume . The aim of this study was to compare radiographic and histomorphometric results of magnesium-enriched hydroxyapatite ( MHA ) and calcium sulfate ( CS ) grafts in fresh sockets after tooth extraction s. METHODS Forty-five fresh extraction sockets with three bone walls were selected in 15 patients . A split-mouth design was used : 15 sockets on the right side of the jaw received MHA , 15 sockets on the left side received CS , and 15 r and om unfilled sockets were considered the control ( C ) group . Intraoral digital radiographs were taken at baseline and at 3 months after graft material placement . At 3 months , cylinder bone sample s were obtained for histology and histomorphometry analysis . RESULTS The difference in mean radiographic vertical bone level from baseline to 3 months was -2.48 + /- 0.65 mm in the CS group , -0.48 + /- 0.21 mm in the MHA group , and -3.75 + /- 0.63 mm in the unfilled C group . Statistically significant differences ( P < 0.05 ) were found between CS and MHA groups and between MHA and C groups . Histologic examination revealed bone formation in all treated sites ; trabecular bone assessment did not differ among apical , mesial , and coronal portions of the specimens . Mean vital bone measurements for CS , MHA , and C groups were 45.0 % + /- 6.5 % , 40.0 % + /- 2.7 % , and 32.8 % + /- 5.8 % , respectively . Statistically significant differences ( P < 0.05 ) were found among all groups . Connective tissue percentages averaged 41.5 % + /- 6.7 % for the CS group , 41.3 % + /- 1.3 % for the MHA group , and 64.6 % + /- 6.8 % for the C group . Statistically significant differences ( P < 0.05 ) were found between CS and C groups and between MHA and C groups . The CS-grafted sockets showed 13.9 % + /- 3.4 % residual implant material , whereas the MHA-treated sockets showed 20.2 % + /- 3.2 % residual material . The difference between the groups was statistically significant ( P < 0.05 ) . CONCLUSIONS Radiographs revealed a greater reduction of alveolar ridge in the CS group than in the MHA group . Histologic examination showed more bone formation and faster resorption in the CS group and more residual implant material in the MHA group Background and Purpose : The resorption of alveolar bone following tooth extraction results in a narrowing and shortening of the residual ridge , which leads to esthetic and restorative problems , and reduces the bone volume available for implant therapy . The aim of this study was to evaluate the prevention of alveolar collapse after tooth extraction , using titanium membrane ( Frios Boneshield ; DENTSPLY Friadent , Mannheim , Germany ) , associated ( or not ) with autologous bone graft . Material s and Methods : A total of 10 nonsmoking healthy subjects , ranging from 35 to 60 years old , were selected for this study . Each patient had a minimum of 2 uni-radicular periodontally hopeless teeth , which were scheduled for extraction . After the procedure , 2 titanium pins were fixed on the vestibular bone surfaces that were used as references for the initial measures ( depth , width , and height ) of the socket . Of the sockets,1 was r and omly chosen to be filled with autologous bone graft ( test ) removed from superior maxillary tuber , and the other one did not receive the graft ( control ) . A titanium membrane was adapted and fixed , covering the sockets , which remained for at least 10 weeks . After a 6-month healing , the final measures were performed . Results : There was exposure of the membrane in 5 of the 10 treated subjects . Average bone filling ( ±st and ard deviation ) among the 10 subjects was 8.80 ± 2.93 mm ( range 4 - 13 ) in the control group and 8.40 ± 3.35 mm ( range 4 - 13 ) in the test group . Average bone loss in width in both group was 1.40 ± 1.97 mm ( range −4 - 1 ) in the control group and 1.40 ± 0.98 mm ( range −4 - 0 ) in the test group . There was no significant statistical difference between groups considering the evaluated st and ards . Conclusion : The use of titanium membrane , alone or in association with autogenous bone , favored the prevention of alveolar ridge after tooth extraction . This membrane seems to be a possible and safe alternative to other nonresorbable membranes when the prevention of alveolar ridge resorption is the objective BACKGROUND The placement of different graft material s and /or the use of occlusive membranes to cover the extraction socket entrance are techniques aim ed at preserving/reducing alveolar ridge resorption . The use of grafting material s in fresh extraction sockets has , however , been question ed because particles of the grafted material have been found in alveolar sockets 6 - 9 months following their insertion . AIM The aims of the study were to ( i ) . evaluate whether alveolar ridge resorption following tooth extraction could be prevented or reduced by the application of a bioabsorbable polylactide-polyglycolide sponge used as a space filler , compared to natural healing by clot formation , and ( ii ) . evaluate histologically the amount and quality of bone tissue formed in the sockets , 6 months after the use of the bioabsorbable material . MATERIAL AND METHODS Thirty-six patients , undergoing periodontal therapy , participated in this study . All patients were scheduled for extraction of one or more compromised teeth . Following elevation of full-thickness flaps and extraction of teeth , measurements were taken to evaluate the distance between three l and marks ( mesio-buccal , mid-buccal , disto-buccal ) on individually prefabricated stents , and the alveolar crest . Twenty-six alveolar sockets ( test ) were filled with a bioabsorbable polylactide-polyglycolide acid sponge ( Fisiograft ) , while 13 sockets ( controls ) were allowed to heal without any filling material . The flaps were sutured with no attempt to achieve primary closure of the surgical wound . Re-entry for implant surgery was performed 6 months following the extraction s. Thirteen biopsies ( 10 test and three control sites ) were harvested from the sites scheduled for implant placement . RESULTS The clinical measurements at 6 months revealed , in the mesial-buccal site , a loss of bone height of 0.2 mm ( 1.4 SD ) in the test and 0.6 mm ( 1.1 SD ) in the controls ; in the mid-buccal portion a gain of 1.3 mm ( 1.9 SD ) in the test and a loss of 0.8 mm ( 1.6 SD ) in the controls ; and in the distal portion a loss of 0.1 mm ( 1.1 SD ) in the test and of 0.8 ( 1.5 SD ) mm in the controls . The biopsies harvested from the test sites revealed that the new bone formed at 6 months was mineralized , mature and well structured . Particles of the grafted material could not be identified in any of the 10 test biopsies . The bone formed in the control sites was also mature and well structured . CONCLUSION The results of this study indicate that alveolar bone resorption following tooth extraction may be prevented or reduced by the use of a bioabsorbable synthetic sponge of polylactide-polyglycolide acid . The quality of bone formed seemed to be optimal for dental implant insertion OBJECTIVES The aim of this study was to compare a nanocrystalline hydroxyapatite ( NCHA ) , NanoBone ( ® ) and a deproteinized bovine bone mineral ( DBBM ) , Bio-Oss ( ® ) with a collagen membrane on the horizontal ridge width alterations following tooth extraction , in addition to histologic aspects of the grafted extraction sockets . MATERIAL AND METHODS In this r and omized clinical trial , 28 symmetrical , non-molar , extraction sockets using a split-mouth design in 12 patients ( eight women and four men ; aged 21 - 60 ; mean 44.6 ± 11.4 years ) , were r and omly selected in the first group to be grafted with DBBM granules covered with a collagen membrane and in the other group grafted with NCHA covered with a collagen membrane . Following extraction horizontal ridge width was measured using caliper and was blindly compared to the dimensions measured prior to implant placement , at the 6- to 8-month follow-up . Subsequently , a 2 × 6 mm trephine core was obtained with aid of acrylic stent and routine histologic preparation was performed on the specimens . RESULTS The width of the DBBM group decreased from 7.75 ± 1.55 to 6.68 ± 1.85 mm ( P < 0.05 ) , whereas the width of the NCHA group decreased from 7.36 ± 1.94 to 6.43 ± Output:	Examination of ARP sites revealed significant variation in vital and trabecular bone percentages and keratinised tissue width and thickness . ARP results in a significant reduction in the vertical bone dimensional change following tooth extraction when compared to unassisted socket healing . No evidence was identified to clearly indicate the superior impact of a type of ARP intervention ( GBR , socket filler and socket seal ) on bone dimensional preservation , bone formation , keratinised tissue dimensions and patient complications
MS21528	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To pilot , among women with gestational diabetes mellitus ( GDM ) , the feasibility of a prenatal/postpartum intervention to modify diet and physical activity similar to the Diabetes Prevention Program . The intervention was delivered by telephone , and support for breastfeeding was addressed . RESEARCH DESIGN AND METHODS The goal was to help women return to their prepregnancy weight , if it was normal , or achieve a 5 % reduction from prepregnancy weight if overweight . Eligible participants were identified shortly after a GDM diagnosis ; 83.8 % consented to be r and omly assigned to intervention or usual medical care ( 96 and 101 women , respectively ) . The retention was 85.2 % at 12 months postpartum . RESULTS The proportion of women who reached the postpartum weight goal was higher , although not statistically significant , in the intervention condition than among usual care ( 37.5 vs. 21.4 % , absolute difference 16.1 % , P = 0.07 ) . The intervention was more effective among women who did not exceed the recommended gestational weight gain ( difference in the proportion of women meeting the weight goals : 22.5 % , P = 0.04 ) . The intervention condition decreased dietary fat intake more than the usual care ( condition difference in the mean change in percent of calories from fat : −3.6 % , P = 0.002 ) and increased breastfeeding , although not significantly ( condition difference in proportion : 15.0 % , P = 0.09 ) . No differences in postpartum physical activity were observed between conditions . CONCLUSIONS This study suggests that a lifestyle intervention that starts during pregnancy and continues postpartum is feasible and may prevent pregnancy weight retention and help overweight women lose weight . Strategies to help postpartum women overcome barriers to increasing physical activity are needed Objective To assess the feasibility of implementing a dedicated feeding support team on a postnatal ward and pilot the potential effectiveness and cost-effectiveness of team ( proactive ) and woman-initiated ( reactive ) telephone support after discharge . Design R and omised controlled trial embedded within a before- and -after study . Participatory approach and mixed- method process evaluation . Setting A postnatal ward in Scotl and . Sample Women living in disadvantaged areas initiating breast feeding . Methods Eligible women were recruited to a before- and -after intervention study , a proportion of whom were independently r and omised after hospital discharge to intervention : daily proactive and reactive telephone calls for ≤14 days or control : reactive telephone calls ≤ day 14 . Intention-to-treat analysis compared the r and omised groups on cases with complete outcomes at follow-up . Main outcome measures Primary outcome : any breast feeding at 6–8 weeks assessed by a telephone call from a research er blind to group allocation . Secondary outcomes : exclusive breast feeding , satisfaction with care , NHS costs and cost per additional woman breast feeding . Results There was no difference in feeding outcomes for women initiating breast feeding before the intervention ( n=413 ) and after ( n=388 ) . 69 women were r and omised to telephone support : 35 intervention ( 32 complete cases ) and 34 control ( 26 complete cases ) . 22 intervention women compared with 12 control women were giving their baby some breast milk ( RR 1.49 , 95 % CI 0.92 to 2.40 ) and 17 intervention women compared with eight control women were exclusively breast feeding ( RR 1.73 , 95 % CI 0.88 to 3.37 ) at 6–8 weeks after birth . The incremental cost of providing proactive calls was £ 87 per additional woman breast feeding and £ 91 per additional woman exclusively breast feeding at 6–8 weeks ; costs were sensitive to service organisation . Conclusions Proactive telephone care delivered by a dedicated feeding team shows promise as a cost-effective intervention for improving breastfeeding outcomes . Integrating the FEeding Support Team ( FEST ) intervention into routine postnatal care was feasible . Trial registration number IS RCT N27207603 . The study protocol and final report are available on request Background Postnatal women ( < 12 months postpartum ) are at increased risk of physical inactivity . Purpose To evaluate the efficacy and feasibility of a theory-based physical activity ( PA ) intervention delivered to postnatal women primarily via mobile telephone short message service ( SMS ) . Methods Eighty-eight women were r and omized to the intervention ( n = 45 ) or minimal contact control ( n = 43 ) condition . The 12-week intervention consisted of a face-to-face PA goal - setting consultation , a goal - setting magnet , three to five personally tailored SMS/week and a nominated support person who received two SMS per week . SMS content targeted constructs of social cognitive theory . Frequency ( days/week ) and duration ( min/week ) of PA participation and walking for exercise were assessed via self-report at baseline , 6 and 13 weeks . Results Intervention participants increased PA frequency by 1.82 days/week ( SE ± 0.18 ) by 13 weeks ( F(2,85 ) = 4.46 , p = 0.038 ) and walking for exercise frequency by 1.08 days/week ( SE ± 0.24 ) by 13 weeks ( F(2,85 ) = 5.38 , p = 0.02 ) . Positive trends were observed for duration ( min/week ) of PA and walking for exercise . Conclusions Intervention exposure result ed in increased frequency of PA and walking for exercise in postnatal women The purpose of this prospect i ve , r and omized controlled study was to determine the efficacy of an intensified , late pregnancy , smoking cessation intervention for resistant pregnant smokers ( n = 269 ) . Participants received 3 - 5 min of counseling plus a self-help booklet at their first prenatal visit and seven booklets mailed weekly thereafter ; at 28 weeks , all had been smoking in the past 28 days . The experimental group received a stage of change-based , personalized feedback letter and two telephone counseling calls using Motivational Interviewing ( MI ) strategies . The control group received care as usual . The 34th week cotinine data demonstrated no overall difference between groups . However , an implementation analysis suggested that 43 % of women who received the full intervention ( E2 ) were classified as not smoking compared to 34 % of the control group . At 6 weeks postpartum , 27.1 % of the E2 group reported being abstinent or light smokers vs. 14.6 % of the controls . No differences were detected at 3 and 6 months postpartum . Results lend preliminary but very modest support for this intervention with resistant pregnant smokers . Improvements in the intervention and implementation issues are discussed Lactation counsellors were trained to advise mothers of partially breast-fed infants who were admitted to hospital because of diarrhoea , so that they could start exclusive breast-feeding during their hospital stay . Infants ( n = 250 ) up to 12 weeks of age were r and omized to intervention and control groups . Mothers in the intervention group were individually advised by the counsellors while mothers in the control group received only routine group health education . During follow-up at home by the counsellors a week later , only the mothers in the intervention group were counselled . All the mothers were evaluated for infant feeding practice s at home two weeks after discharge . Among the 125 mother-infant pairs in each group , 60 % of mothers in the intervention group were breast-feeding exclusively at discharge compared with only 6 % in the control group ( P < 0.001 ) ; two weeks later , these rates rose to 75 % and 8 % in the intervention and control groups , respectively ( P < 0.001 ) . However , 49 % of mothers in the control group reverted back to bottle-feeding compared with 12 % in the intervention group ( P < 0.001 ) . Thus , individual counselling had a positive impact on mothers to start exclusive breast-feeding during hospitalization and to continue the practice at home . Maternal and child health facilities should include lactation counselling as an integral part of their programme to improve infant feeding practice This study reports on the evaluation of the feasibility , cost , and cost-effectiveness of a proactively provided telephone-based motivational smoking cessation intervention to an underserved population of pregnant smokers who may or may not receive ongoing prenatal care . As part of the New Engl and SCRIPT r and omized clinical trial comparing the efficacy of three types of smoking cessation interventions for pregnant smokers , one-third of the women ( n = 358 ) received a motivational telephone counseling intervention ( MI ) delivered by trained counselors using a semistructured protocol . Although this population was very mobile , the MI counselors were able to reach 86 % of the women with at least one call and 46 % received all three calls . The group receiving three MI calls had a cotinine-confirmed quit rate of 23 % . Cost-effectiveness analyses for those women receiving telephone counseling supported the net benefit in favor of the three phone calls compared with the women who did not receive any telephone calls , with an effectiveness to cost ratio of 1:US dollars 84 . Our results suggest that telephone-based motivational smoking cessation counseling may be a feasible and cost-effective method for low-income pregnant smokers enrolled in prenatal care This study examined the effect of a mother-baby intervention on the quality of mother-child interaction , infant-mother attachment security , and infant socioemotional functioning in a group of depressed mothers with infants aged 1 - 12 months . A r and omized controlled trial compared an experimental group ( n = 35 ) receiving the intervention ( 8 - 10 home visits ) with a control group ( n = 36 ) receiving parenting support by telephone . There were assessment s pre , post , and follow-up after 6 months . The intervention had positive effects on the quality of mother-infant interaction . Infants in the experimental group had higher scores for attachment security and for one aspect of socioemotional functioning , namely , competence . The intervention proved successful in preventing deterioration of the quality of mother-child interaction A r and omized controlled trial including 2235 women at high risk of low birthweight was conducted in four Latin American institutions . The objective of this trial was to evaluate a psychosocial support intervention during pregnancy aim ed at improving perinatal health and mothers ' psychosocial conditions . The core of the intervention was four to six home visits where emotional support , counseling and strengthening of the woman 's social network was provided . Outcomes were measured at 36 weeks of pregnancy , post-partum and 40 days after delivery . The intervention was not successful in either altering women 's perception of social support and satisfaction with the reproductive experience , as well as maternal and newborn 's health care . It is concluded that although high levels of psychosocial distress during pregnancy may play an independent role in determining adverse pregnancy outcomes , this adverse effect does not appear to be ameliorated by psychosocial interventions conducted only during pregnancy , particularly those of a magnitude that can be realistically implemented ( in content and frequency ) at public care services in most developing countries OBJECTIVE Maternal obesity is associated with poor breastfeeding outcomes , yet no intervention has been developed to improve them . To ascertain whether increased breastfeeding support or provision of a breast pump is a feasible , effective intervention to improve breastfeeding , we enrolled obese women who intended to breastfeed in two r and omized trials . METHODS In Bassett Improving Breastfeeding Study ( BIBS ) 1 , 40 women received targeted breastfeeding support in the hospital and via telephone or usual care . Information regarding breastfeeding was collected via telephone for 7 days after delivery and at 30 and 90 days postpartum . In BIBS 2 , 34 obese mothers received a manual or electric breast pump to use for 10 - 14 days or no pump ; data collection was similar . RESULTS In both experiments , r and omization failed to distribute women of differing postpartum body mass index adequately among the treatment groups . When analyses were adjusted for this , there was no difference in BIBS 1 between targeted and usual care groups and in BIBS 2 among the treatment groups in the proportion of women still breastfeeding at the times studied . CONCLUSIONS In future studies of obese women , stratified r and omization may be necessary . Further development of interventions to help obese women achieve optimal breastfeeding outcomes is required Background Telephone hotlines design ed to address common concerns in the early postpartum could be a useful re source for parents . Our aim was to test the feasibility of using a telephone as an intervention in a r and omized controlled trial . We also aim ed to test to use of algorithms to address parental concerns through a telephone hotline . Methods Healthy first-time mothers were recruited from postpartum wards of hospitals throughout Lebanon . Participants were given the number of a 24-hour telephone hotline that they could access for the first four months after delivery . Calls were answered by a midwife using algorithms developed by the study team whenever possible . Callers with medical complaints were referred to their physicians . Call patterns and content were recorded and analyzed . Results Eighty-four of the 353 women enrolled ( 24 % ) used the hotline . Sixty percent of the women who used the service called more than once , and all callers reported they were satisfied with the service . The midwife received an average of three calls per day and most calls occurred during the first four weeks postpartum . Our algorithms were used to answer questions in 62.8 % of calls and 18.6 % of calls required referral to a physician . Of the questions related to mothers , 66 % were about breastfeeding . Sixty percent of questions related to the infant were about routine care and 23 % were about excessive crying . Conclusions Utilization of a telephone hotline service for postpartum support is highest in the first four weeks Output:	Overall , results were inconsistent and inconclusive although there was some evidence that telephone support may be a promising intervention . Results from trials offering breastfeeding telephone support were also inconsistent , although the evidence suggests that telephone support may increase the duration of breastfeeding . There was no strong evidence that women receiving telephone support were less likely to be smoking at the end of pregnancy or during the postnatal period .
MS21529	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock . There is a continuing controversy about whether one agent is superior to the other . METHODS In this multicenter , r and omized trial , we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure . When blood pressure could not be maintained with a dose of 20 microg per kilogram of body weight per minute for dopamine or a dose of 0.19 microg per kilogram per minute for norepinephrine , open-label norepinephrine , epinephrine , or vasopressin could be added . The primary outcome was the rate of death at 28 days after r and omization ; secondary end points included the number of days without need for organ support and the occurrence of adverse events . RESULTS The trial included 1679 patients , of whom 858 were assigned to dopamine and 821 to norepinephrine . The baseline characteristics of the groups were similar . There was no significant between-group difference in the rate of death at 28 days ( 52.5 % in the dopamine group and 48.5 % in the norepinephrine group ; odds ratio with dopamine , 1.17 ; 95 % confidence interval , 0.97 to 1.42 ; P=0.10 ) . However , there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine ( 207 events [ 24.1 % ] vs. 102 events [ 12.4 % ] , P<0.001 ) . A subgroup analysis showed that dopamine , as compared with norepinephrine , was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock ( P=0.03 for cardiogenic shock , P=0.19 for septic shock , and P=0.84 for hypovolemic shock , in Kaplan-Meier analyses ) . CONCLUSIONS Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine , the use of dopamine was associated with a greater number of adverse events . ( Clinical Trials.gov number , NCT00314704 . AIMS The aim of this study was to assess long-term safety of intravenous cardiovascular agents-vasodilators , inotropes and /or vasopressors-in acute heart failure ( AHF ) . METHODS AND RESULTS The European Society of Cardiology Heart Failure Long-Term ( ESC-HF-LT ) registry was a prospect i ve , observational registry conducted in 21 countries . Patients with unscheduled hospitalizations for AHF ( n = 6926 ) were included : 1304 ( 18.8 % ) patients received a combination of intravenous ( i.v . ) vasodilators and diuretics , 833 ( 12 % ) patients received i.v . inotropes and /or vasopressors . Primary endpoint was long-term all-cause mortality . Main secondary endpoints were in-hospital and post-discharge mortality . Adjusted hazard ratio ( HR ) showed no association between the use of i.v . vasodilator and diuretic and long-term mortality [ HR 0.784 , 95 % confidence interval ( CI ) 0.596 - 1.032 ] nor in-hospital mortality ( HR 1.049 , 95 % CI 0.592 - 1.857 ) in the matched cohort ( n = 976 paired patients ) . By contrast , adjusted HR demonstrated a detrimental association between the use of i.v . inotrope and /or vasopressor and long-term all-cause mortality ( HR 1.434 , 95 % CI 1.128 - 1.823 ) , as well as in-hospital mortality ( HR 1.873 , 95 % CI 1.151 - 3.048 ) in the matched cohort ( n = 606 paired patients ) . No association was found between the use of i.v . inotropes and /or vasopressors and long-term mortality in patients discharged alive ( HR 1.078 , 95 % CI 0.769 - 1.512 ) . A detrimental association with inotropes and /or vasopressors was seen in all geographic regions and , among catecholamines , dopamine was associated with the highest risk of death ( HR 1.628 , 95 % CI 1.031 - 2.572 vs. no inotropes ) . CONCLUSIONS Vasodilators did not demonstrate any association with long-term clinical outcomes , while inotropes and /or vasopressors were associated with increased risk of all-cause death , mostly related to excess of in-hospital mortality in AHF Background Clinical evidence continues to exp and and is increasingly difficult to overview . We aim ed at conceptualizing a visual assessment tool , i.e. , a matrix for overviewing studies and their data in order to assess the clinical evidence at a glance . Methods A four-step matrix was constructed using the three dimensions of systematic error , r and om error , and design error . Matrix step I ranks the identified studies according to the dimensions of systematic errors and r and om errors . Matrix step II orders the studies according to the design errors . Matrix step III assesses the three dimensions of errors in studies . Matrix step IV assesses the size and direction of the intervention effect . Results The application of this four-step matrix is illustrated with two examples : peri-operative beta-blockade initialized in relation to surgery versus placebo for major non-cardiac surgery , and antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation . When clinical evidence is deemed both internally and externally valid , the size of the intervention effect is to be assessed . Conclusion The error matrix provides an overview of the validity of the available evidence at a glance , and may assist in deciding which interventions to use in clinical practice BACKGROUND Worsening renal function ( WRF ) and hypokalemia related to diuretic use for acute decompensated heart failure ( ADHF ) are common and associated with poor prognosis . Low-dose dopamine infusion improves renal perfusion ; its effect on diuresis or renal function specifically in ADHF is not known . METHODS AND RESULTS Sixty consecutive ADHF patients ( age 75.7 ± 11.2 years ; 51.7 % female ; left ventricular ejection fraction 35.3 ± 12.1 % ) were r and omized , after receiving a 40 mg intravenous furosemide bolus , to either high-dose furosemide ( HDF , 20 mg/h continuous infusion for 8 hours ) or low-dose furosemide combined with low-dose dopamine ( LDFD , furosemide 5 mg/h plus dopamine 5 μg kg(-1 ) min(-1 ) continuous infusion for 8 hours ) . Both strategies were compared for total diuresis , WRF ( defined as a rise in serum creatinine of > 0.3 mg/dL from baseline to 24 hours ) , electrolyte balance , and 60-day postdischarge outcomes . Mean hourly excreted urine volume ( 272 ± 149 mL in HDF vs 278 ± 186 mL in LDFD group ; P = .965 ) and changes in dyspnea score ( Borg index : -4.4 ± 2.1 in HDF group vs -4.7 ± 2.0 in LDFD group ; P = .575 ) during the 8 hours of protocol treatment were similar in the two groups . WRF was more frequent in the HDF ( n = 9 ; 30 % ) than in the LDFD group ( n = 2 ; 6.7 % ; P = .042 ) . Serum potassium changed from 4.3 ± 0.5 to 3.9 ± 0.4 mEq/L at 24 hours ( P = .003 ) in the HDF group and from 4.4 ± 0.5 to 4.2 ± 0.5 mEq/L at 24 hours ( P = .07 ) in the LDFD group . Length of stay and 60-day mortality or rehospitalization rates ( all-cause , cardiovascular , and worsening HF ) were similar in the two groups . CONCLUSIONS In ADHF patients , the combination of low-dose furosemide and low-dose dopamine is equally effective as high-dose furosemide but associated with improved renal function profile and potassium homeostasis Thirty-six patients with preoperative renal dysfunction were studied to evaluate the effects of dopamine ( D ) and dopamine-nitroprusside ( DN ) on renal function during cardiopulmonary bypass ( CPB ) . No differences from the control group ( C ) were found in creatinine clearance , fractional sodium excretion , osmolarity and free-water clearance . Sodium output/intake ratio during CPB was higher in group D than in groups C and DN ( P less than 0.05 ) ; water output/intake ratio was higher in group D than in group C ( P less than 0.05 ) . Urine lysozime levels and alpha-glycosidase/creatinine ratios increased similarly in the three groups , suggesting ischemic tubular cell damage . No patients showed acute postoperative renal failure or a worsening of their renal dysfunction . The data suggest an increased water and sodium excretion during CPB with a dopamine infusion , possibly result ing from a renal vasodilator effect that was abolished by simultaneous nitroprusside administration Objective : To compare the efficacy and safety of dopexamine with dopamine in the treatment of low cardiac output syndrome after cardiac surgery . Design : This was a multicentre , double-blind , r and omised , parallel-group study conducted in intensive care units at centres in Holl and and Belgium . Patients were r and omised to receive dopexamine ( up to 2.0 μg/kg per min ) or dopamine ( up to 6.0 μg/kg per min ) for 6 h after low cardiac output syndrome was confirmed . Results : 70 patients were enrolled ( 35/group ) and there was no significant difference in the operative procedures or haemodynamics at entry into the study . Clinical efficacy , defined as a cardiac index > 2.5 l/min per m2 with urine production > 0.5 ml/kg per h and stable haemodynamics for two consecutive readings 1 h apart , was achieved by 90 and 87 % of patients in the dopexamine and dopamine groups , respectively . However , more patients maintained clinical efficacy over the 6-h period in the dopexamine group , which was statistically significant at 1–2 h and approached significance at all other time points . Safety was assessed by comparing the adverse events and concomitant medication . Fewer patients on dopexamine had cardiac events compared with dopamine-treated patients ( 25 vs 38 events ) , although there was no difference in the pattern of rhythm disturbance . Fewer patients in the dopexamine group required concomitant vasodilating drugs ( 18 vs 30 ) . Conclusion : Taking the proportion of patients achieving clinical efficacy , the time to achieve it and the maintenance of it along with the adverse event profile , dopexamine was shown to be an effective and safe drug to use in the management of low cardiac output syndrome after coronary artery bypass graft surgery and may be superior to dopamine Background —Acute renal failure is a serious complication of cardiac surgery causing high morbidity and mortality . The aim of this study was to evaluate the usefulness of fenoldopam , a specific agonist of the dopamine-1 receptor , in patients at high risk of perioperative renal dysfunction . Methods and Results —A prospect i ve single-center , r and omized , double-blind trial was performed after local ethical committee approval and after written consent was obtained from 80 patients undergoing cardiac surgery . Patients received either fenoldopam at 0.05 & mgr;g/kg per minute or dopamine at 2.5 & mgr;g/kg per minute after the induction of anesthesia for a 24-hour period . All these patients were at high risk of perioperative renal dysfunction as indicated by Continuous Improvement in Cardiac Surgery Program score > 10 . Primary end point was defined as 25 % creatinine increase from baseline levels after cardiac surgery . The 2 groups ( fenoldopam versus dopamine ) were homogeneous cohorts , and no difference in outcome was observed . Acute renal failure was similar : 17 of 40 ( 42.5 % ) in the fenoldopam group and 16 of 40 ( 40 % ) in the dopamine group ( P=0.9 ) . Peak postoperative serum creatinine level , intensive care unit and hospital stay , and mortality were also similar in the 2 groups . Conclusions —Despite an increasing number of reports of renal protective properties from fenoldopam , we observed no difference in the clinical outcome compared with dopamine in a high-risk population undergoing cardiac surgery Mitral valve surgery may be complicated by a post-operative low output state requiring inotropic support , and a wide variety of factors may influence the choice of agents used to treat this condition . The authors have examined and compared the haemodynamic effects of the highly specific phosphodiesterase inhibitor en Output:	There were also no statistically significant associations for any of the outcomes in subgroup analyses by type of comparator ( inactive compared to potentially active ) , dopamine dose ( low compared to moderate dose ) , or setting ( cardiac surgery compared to heart failure ) .
MS21530	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A major hurdle in the long-term treatment of chronic hepatitis B ( CHB ) patients is to maintain viral suppression in the absence of drug resistance . To date , no evidence of resistance to tenofovir disoproxil fumarate ( TDF ) has been observed . A cumulative evaluation of CHB patients who qualified for resistance surveillance over 8 years of TDF treatment was conducted . Patients in studies GS-US-174 - 0102 ( HBeAg- ) and GS-US-174 - 0103 ( HBeAg+ ) were r and omized 2:1 to receive TDF or adefovir dipivoxil ( ADV ) for 48 weeks followed by open-label TDF through year 8 . Population sequencing of HBV pol/RT was attempted for all TDF-treated patients at baseline and , annually if viremic , at discontinuation , or with addition of emtricitabine . Overall , 88/641 ( 13.7 % ) patients qualified for sequence analysis at one or more time points . The percentage of patients qualifying for sequence analysis declined over time , from 9 to 11 % in years 1 - 2 to < 4 % over years 3 - 8 . Forty-one episodes of virologic breakthrough ( VB ) occurred throughout the study , with most ( n=29 , 70 % ) associated with nonadherence to study medication . Fifty-nine per cent of VB patients with an opportunity to resuppress HBV achieved HBV DNA resuppression . A minority of patients who qualified for sequencing had polymorphic ( 41/165 , 24.8 % ) or conserved ( 17/165 , 10.3 % ) site changes in pol/RT , with six patients developing lamivudine and /or ADV resistance-associated mutations . No accumulation of conserved site changes was detected . The long-term treatment of CHB with TDF monotherapy maintains effective suppression of HBV DNA through 8 years , with no evidence of TDF resistance or accumulation of conserved site changes BACKGROUND Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus ( HBV ) . METHODS In this phase 3 , double-blind trial , we r and omly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) at week 48 . Secondary end points included a reduction in the serum HBV DNA level , HBeAg loss and seroconversion , and normalization of the alanine aminotransferase level . RESULTS Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group ( 72 percent ) and 195 of 314 patients in the lamivudine group ( 62 percent , P=0.009 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay ( 67 percent vs. 36 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 68 percent vs. 60 percent , P=0.02 ) . The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine ( 6.9 vs. 5.4 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine ( P=0.33 ) . No viral resistance to entecavir was detected . Safety was similar in the two groups . CONCLUSIONS Among patients with HBeAg-positive chronic hepatitis B , the rates of histologic , virologic , and biochemical improvement are significantly higher with entecavir than with lamivudine . The safety profile of the two agents is similar , and there is no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035633 . ) BACKGROUND The proposed definition of a partial virological response ( PVR ) to nucleos(t)ide analogue therapy in the 2009 European Association for the Study of the Liver ( EASL ) guidelines is based on limited evidence , especially in terms of the cutoff HBV DNA level and the time point at which to judge it . This study assessed optimal PVR criteria for predicting virological response ( VR ) at week 96 in treatment-naive patients with chronic hepatitis B ( CHB ) receiving entecavir ( ETV ) . METHODS A total of 175 patients ( 126 men , 49 women ) who completed 96 weeks of first-line ETV therapy were prospect ively recruited . For predicting VR at week 96 , the area under the receiver operating characteristic curve ( AUC ) was used to find the optimal time point and the Youden index was used to calculate the optimal cutoff HBV DNA level . RESULTS After 96 weeks of ETV therapy , 139 ( 79.4 % ) patients achieved VR . The AUC at week 48 was significantly better than that at week 24 for predicting VR at week 96 ( P=0.023 ) . The optimal cutoff HBV DNA level at week 48 was 35 IU/ml . Forty-one ( 23.4 % ) patients met this PVR criteria of ETV ( HBV DNA level > 35 IU/ml at week 48 ) . CONCLUSIONS An HBV DNA level > 35 IU/ml at week 48 is the optimal PVR criteria for predicting non-VR at week 96 in treatment-naive patients with CHB who are receiving ETV . This study supports the proposed EASL PVR for ETV based on scientific evidence Background and aims In patients with chronic hepatitis B ( CHB ) who have failed on other nucleos(t)ide analogs ( NUCs ) , the combination of entecavir ( ETV ) plus tenofovir disoproxil fumarate ( TDF ) , two potent agents with non-overlapping resistance profiles , may provide a single rescue regimen . Methods In this single-arm , open-label study , 92 CHB patients with a primary non-response , partial response , or virologic breakthrough on their current NUC were switched to ETV ( 1 mg ) plus TDF ( 300 mg ) and treated for 96 weeks . Results At baseline , 62 % of patients were HBeAg(+ ) and mean HBV DNA was 4.4 log10IU/mL. Patients had received ≥1 line of prior NUC therapy , with the latest regimen consisting of monotherapy with ETV ( 53 % ) , lamivudine ( LVD 22 % ) , TDF ( 12 % ) , adefovir ( ADV 4 % ) , or telbivudine ( 2 % ) , or combinations of these agents ( 7 % ) ; 58 % had evidence of single- or multidrug resistance mutations ( LVD 52 % , ETV 26 % ; ADV 7 % ) . Response rates for HBV DNA < 50 IU/mL were 76 % ( 70/92 ) at week 48 ( primary endpoint ) , and 85 % ( 78/92 ) at week 96 , including 80 % ( 16/20 ) in prior LVD failures , 100 % ( 4/4 ) in ADV failures , 82 % ( 9/11 ) in TDF failures , and 88 % ( 42/48 ) in ETV failures . No treatment-emergent resistance to ETV or ADV was observed . ETV/TDF was well tolerated , with no significant renal or additive toxicities observed . Conclusions In NUC-experienced patients who have failed prior NUC therapy , ETV/TDF was well tolerated and effective , achieving virologic suppression through 96 weeks in the majority ( 85 % ) , irrespective of prior NUC exposure , without occurrence of treatment-emergent resistance to either agent Background / Aims Entecavir is a potent nucleoside analogue with high efficacy and barrier for resistance . We aim ed to investigate the long-term efficacy and viral resistance rate of entecavir and explore the factors associated with virologic response , including quantitative hepatitis B surface antigen ( qHBsAg ) levels . Methods One thous and and nine treatment-naïve chronic hepatitis B ( CHB ) patients were evaluated for cumulative rates of virologic response , biochemical response , and entecavir mutations . The role of baseline qHBsAg for virologic response was assessed in 271 patients with qHBsAg prior to entecavir treatment . Results The median duration of entecavir treatment was 26.5 months . The cumulative rate of virologic response at years 1 , 3 , and 5 were 79.0 % , 95.6 % , and 99.4 % , respectively . The cumulative rate of entecavir resistance was 1.0 % and 2.1 % in years 3 and 5 . Multivariate analysis identified baseline hepatitis B e antigen ( HBeAg ) negative status ( p < 0.001 ) and lower hepatitis B virus ( HBV ) DNA ( p < 0.001 ) as predictors of virologic response . Lower qHBsAg was an independent predictor of virologic response in patients with baseline qHBsAg . There were no serious adverse events during treatment . Conclusions Long-term entecavir treatment of nucleos(t)ide-naïve CHB patients was associated with an excellent virologic response and a low rate of entecavir-resistant mutations at 5 years . Baseline HBV DNA load , qHBsAg levels , and HBeAg status were predictors of virologic response during entecavir treatment We previously demonstrated superior efficacy and safety advantages in HIV-infected , virologically suppressed adults switched to a regimen containing tenofovir alafenamide ( TAF ) as compared with those remaining on a tenofovir disoproxil fumarate ( TDF ) regimen through week 48 . We now report long-term data through week 96 . In this r and omized , active-controlled , multicenter , open-label , noninferiority trial ( Clinical Trials.gov No. NCT01815736 ) , we r and omized virologically suppressed ( HIV-1 RNA < 50 copies/ml ) adults ( 2:1 ) to receive a once-daily , single-tablet regimen containing elvitegravir ( EVG ) , cobicistat ( COBI ) , emtricitabine ( FTC ) , and TAF group or to continue one of four TDF-containing regimens ( TDF group ) for 96 weeks . We evaluated efficacy ( HIV-1 RNA < 50 copies/ml using the FDA snapshot algorithm ) and prespecified bone and renal endpoints at week 96 . We r and omized and treated 1,436 participants in this study ( TAF n = 959 , TDF n = 477 ) . At week 96 , TAF was superior to TDF in virologic efficacy , with 93 % on TAF and 89 % on TDF having HIV-1 RNA < 50 copies/ml ( difference 3.7 % , 95 % confidence interval : 0.4%-7.0 % ) . Improvements in hip and spine bone mineral density for those assigned to TAF versus TDF continued through week 96 ( p < .001 ) . Significant improvements in urine protein or albumin to creatinine ratios were also seen among those in the TAF group versus TDF through week 96 ( p < .001 ) . There were no cases of investigator-reported proximal renal tubulopathy in the TAF group as compared with one case in the TDF group . Switching to EVG/COBI/FTC/TAF ( E/C/F/TAF ) was associated with statistically significant efficacy and safety advantages over remaining on a st and ard-of-care TDF-based regimen BACKGROUND Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS In this phase 3 , double-blind trial , we r and omly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) . RESULTS Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated ( 70 percent ) , as compared with 174 of 287 such patients in the lamivudine group ( 61 percent , P=0.01 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus ( HBV ) DNA levels according to a polymerase-chain-reaction assay ( 90 percent vs. 72 Output:	Telbivudine and TAF were the best for ALT norm . Certain nucleos(t)ide combinations also had high probability of achieving positive outcomes . Conclusions Our results are consonant with current clinical guidelines and other evidence review s. For both HBeAg-positive and HBeAg-negative population s , TDF and TAF are the most effective agents for virologic suppression , and TAF is effective across all outcomes
MS21531	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To conduct the first rigorous evaluation of the long-term effect of the Comprehensive Rural Health Project on childhood mortality in rural Maharashtra . METHODS Background information and full birth histories were collected by conducting household surveys and interviewing women . Control villages resembling project villages in terms of population size were r and omly selected from an area enclosed by two ellipses centred around , but not including , the project area . An equal number of villages and approximately equal numbers of households and women were r and omly sample d from both areas . Cox models with robust st and ard errors were used to compare the hazard of death among children under 5 years of age in project and control villages . FINDINGS The hazard of death was reduced by 30 % ( 95 % confidence interval , CI : 6 % to 48 % ) after the neonatal period in the project villages compared with control villages after adjustment for caste and religion of subjects and for availability of irrigation in the villages . During the neonatal period there was an increase of 3 % in the hazard of death , but it was not statistically significant ( 95 % CI : -18 % to 29 % ) . CONCLUSION Our methods provide useful tools for evaluating long-running community-based primary health care programmes . Our findings add to the growing debate on the long-term sustainability of community-based interventions design ed to reduce child mortality Although evidence suggests that lifestyle interventions can reduce blood pressure ( BP ) and glucose levels , there is little information about the feasibility of such interventions when implemented in community setting s. This study evaluated the effectiveness of a community-based lifestyle intervention on BP and glucose in the middle-aged and older Chinese population . By using a cluster r and omisation approach , 474 participants from two communities were assigned to the intervention group which received intensive health education and behavioural intervention , or the control group which received conventional education . Linear mixed models were used to compare between-group differences on change in BP and fasting glucose after 6 , 12 and 24 months . At the 12-month follow-up , the intervention group experienced significantly reductions in systolic BP ( −4.9 vs. 2.4 mmHg ; mean difference [ MD ] −7.3 mmHg ; p < 0.001 ) , diastolic BP ( −1.9 vs. 1.9 mmHg ; MD −3.8 mmHg ; p < 0.001 ) and fasting glucose ( −0.59 vs. 0.08 mmol/L ; MD −0.67 mmol/L ; p < 0.001 ) . These differences were sustained at the 24-month follow-up . With only two communities , it was not possible to adjust for potential clustering by site . This approach of lifestyle interventions conducted through primary care services may be a potential solution for combating hypertension and diabetes in a re source -limited country context in China Background After the launch of Janani Suraksha Yojana , a conditional cash transfer scheme in India , the proportion of women giving birth in institutions has rapidly increased . However , there are important gaps in quality of childbirth services during institutional deliveries . The aim of this intervention was to improve the quality of childbirth services in selected high caseload public health facilities of 10 districts of Rajasthan . This intervention titled “ Parijaat ” was design ed by Action Research & Training for Health , in partnership with the state government and United Nations Population Fund . Methods The intervention was carried out in 44 public health facilities in 10 districts of Rajasthan , India . These included district hospitals ( 9 ) , community health centres ( 32 ) and primary health centres ( 3 ) . The main intervention was orientation training of doctors and program managers and regular visits to facilities involving assessment , feedback , training and action . The adherence to evidence based practice s before , during and after this intervention were measured using structured checklists and scoring sheets . Main outcome measures included changes in practice s during labour , delivery or immediate postpartum period . Results Use of several unnecessary or harmful practice s reduced significantly . Most importantly , proportion of facilities using routine augmentation of labour reduced ( p = 0 ) , episiotomy for primigravidas ( p = 0.0003 ) , fundal pressure ( p = 0.0003 ) , and routine suction of newborns ( 0 = 0.0005 ) . Among the beneficial practice s , use of oxytocin after delivery increased ( p = 0.0001 ) and the practice of listening foetal heart sounds during labour ( p = 0.0001 ) . Some practice s did not show any improvements , such as dorsal position for delivery , use of partograph , and h and -washing . Conclusions An intervention based on repeated facility visits combined with actions at the level of decision makers can lead to substantial improvements in quality of childbirth practice s at health facilities Background The high burden of undetected and undertreated hypertension and diabetes mellitus is a major health challenge worldwide . The mPower Heart Project aim ed to develop and test a feasible and scalable intervention for hypertension and diabetes mellitus by task‐sharing with the use of a mobile phone – based clinical decision support system at Community Health Centers in Himachal Pradesh , India . Methods and Results The development of the intervention and mobile phone – based clinical decision support system was carried out using mixed methods in five Community Health Centers . The intervention was subsequently evaluated using pre – post evaluation design . During intervention , a nurse care coordinator screened , examined , and entered patient parameters into mobile phone – based clinical decision support system to generate a prescription , which was vetted by a physician . The change in systolic blood pressure , diastolic blood pressure , and fasting plasma glucose ( FPG ) over 18 months of intervention was quantified using generalized estimating equations models . During intervention , 6797 participants were enrolled . Six thous and sixteen participants had hypertension ( mean systolic blood pressure : 146.1 mm Hg , 95 % CI : 145.7 , 146.5 ; diastolic blood pressure : 89.52 mm Hg , 95 % CI : 89.33 , 89.72 ) , of which 3152 ( 52 % ) subjects were newly detected . Similarly , 1516 participants had diabetes mellitus ( mean FPG : 177.9 mg/dL , 95 % CI : 175.8 , 180.0 ) , of which 450 ( 30 % ) subjects were newly detected . The changes in systolic blood pressure , diastolic blood pressure , and FPG observed at 18 months of follow‐up were −14.6 mm Hg ( 95 % CI : −15.3 , −13.8 ) , −7.6 mm Hg ( CI : −8.0 , −7.2 ) , and −50.0 mg/dL ( 95 % CI : −54.6 , −45.5 ) , respectively , and were statistically significant even after adjusting for age , sex , and Community Health Center . Conclusions A nurse‐facilitated , mobile phone – based clinical decision support system‐enabled intervention in primary care was associated with improvements in blood pressure and blood glucose control and has the potential to scale‐up in re source poor setting s. Clinical Trial Registration URL : https://www . clinical trials.gov . Unique identifiers : NCT01794052 . Clinical Trial Registry — India : CTRI/2013/02/003412 Background Very few studies having decision support systems as an intervention report on patient outcomes for cardiovascular disease in the Western world . The potential role of decision support system for the management of blood pressure among Indian hypertensives remains unclear . We propose a cluster r and omised trial that aims to test the effectiveness and cost effectiveness of DSS among Indian hypertensive patients . Methods The trial design is a cluster r and omised community intervention trial , in which the participants would be adult male and female hypertensive patients , in the age group of 35 to 64 years , reporting to the Primary Health Care centres of Mahabubnagar district , And hra Pradesh , India . The objective of the study is to test the effectiveness and compare the cost effectiveness and cost utility among hypertensive subjects r and omized to receive either decision support system or a chart based algorithmic support system in urban and rural areas of a district in the state of And hra Pradesh , India ( baseline versus 12 months follow up ) . The primary outcome would be a comparison of the systolic blood pressure at 0 and 12 months among hypertensive patients r and omized to receive the decision support system or the chart based algorithmic support system . Computer generated r and omisation and an investigator and analyser blinded method would be followed . 1600 participants ; 800 to each arm ; each arm having eight clusters of hundred participants each have been recruited between 01 August 2011 - 01 March 2012 . A twelve month follow up will be completed by March 2013 and results are expected by April 2013 . Discussion This cluster r and omized community intervention trial on DSS will enable policy makers to find out the effectiveness , cost effectiveness and cost utility of decision support system for management of blood pressure among hypertensive patients in India . Most of the previous studies on decision support system have focused on physician performance , adherence and on preventive care reminders . The uniqueness of the proposed study lies in finding out the effectiveness of a decision support system on patient related outcomes .Trial registration CTRI/2012/03/002476 , Clinical Trial Registry - India Delivering health care to mystery patients Many families in developing countries do not have access to medical doctors and instead receive health care from informal providers . Das et al. used “ mystery ” patients ( trained actors ) to test whether a 9-month training program improved the quality of care delivered by informal providers in West Bengal ( see the Perspective by Powell-Jackson ) . The patients did not identify themselves to the providers and were not told which providers had participated in the training program . The results of this blinded assessment showed that medical doctors delivered better care than informal providers but that the training program closed much of the gap . Science , this issue p. 80 ; see also p. 34 Training helped informal providers deliver better care for angina , diarrhea , and asthma . [ Also see Perspective by Powell-Jackson ] INTRODUCTION In rural India , health care providers without formal medical training and self-declared “ doctors ” are sought for up to 75 % of primary care visits . The frequent use of such informal providers , despite legal prohibitions on their practice s , in part reflects the absence of trained medical professionals in rural locations . For example , in the majority of villages in the Indian states of Rajasthan , Madhya Pradesh , and West Bengal , informal providers are the only proximate source of health care . RATIONALE The status of informal providers in the complex Indian health system is the subject of a highly charged debate among policy-makers and the medical establishment . The official view of the establishment is that fully trained providers are the only legitimate source of health care , and training informal providers legitimizes an illegal activity and worsens population health outcomes . In contrast , given the lack of availability of trained providers and the fact that informal providers are tightly linked with the communities that they serve , others believe that training can serve as a stopgap measure to improve health care in t and em with better regulation and reform of the public health care system . However , despite the policy interest and important ramifications for the country , there is little evidence regarding the benefits ( or lack thereof ) of training informal providers . We report on the impact of a multitopic training program for informal providers in the Indian state of West Bengal that provided 72 sessions of training over 9 months . We used a r and omized controlled trial design , together with visits by unannounced st and ardized patients ( “ mystery clients ” ) , to measure the extent to which training could improve the clinical practice of informal providers over the range of conditions that they face . The conditions presented by st and ardized patients were blinded from program implementers . Therefore , we view the evaluation of this multitopic training program as a measure of impact on primary care in general . St and ardized patient data are accompanied by data from day-long clinical observations , providing a comprehensive picture of provider practice . Our study also benchmarks the impact of training against the performance of doctors in public primary health centers serving the same region . Lastly , it explores whether the training affected patient dem and for informal providers . RESULTS Mean attendance at each training session was 56 % [ 95 % confidence interval ( CI ) : 51 , 62 % ] , with no contamination from the control group . Using st and ardized patient data , we find that providers allocated to the training group were 4.1 ( 1.7 , 6.5 ) percentage points , or 15.2 % , more likely to adhere to condition-specific checklists than those in the control group . The training increased rates of correct case management by 7.9 ( 0.4 , 15.5 ) percentage points , or 14.2 % , and patient caseload by 0.8 to 1.8 ( 0.13 , 3.57 ) patients per day , or 7.6 to 17.0 % . Data from clinical observations show similar patterns . Although correct case management among doctors in public clinics was 14.7 ( –0.1 , 30.4 ) percentage points , or 28.3 % , higher than among untrained informal providers , the training program reduced this gap by half for providers with mean attendance and reduced the gap almost entirely for providers who completed the full course . However , the training had no effect on the use of unnecessary medicines and antibiotics , although both training- and control-group informal providers prescribed 18.8 ( 7.7 , 28.9 ) percentage points , or 28.2 % , fewer unnecessary antibiotics than public-sector providers . CONCLUSION Training informal providers increased correct case management rates but did not reduce the use of unnecessary medicines or antibiotics . At the same time , training did not lead informal providers to violate rules with greater frequency or worsen their clinical practice , both of which are concerns that have been raised by representatives of the Indian Medical Association . Our findings thus suggest that mult Output:	We found evidence on the impact of non-physician health workers ( NPHWs ) on coverage and quality of care , though better integration with other PHC services is needed . Community-based services are most effective when well integrated through functional referral systems and supportive supervision arrangements , and have a reliable supply of medicines . Many studies point to the importance of community engagement in improving service dem and .
MS21532	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The objective of this study was to examine different clinical scenarios of in-vitro conception , viz . fertilization with conventional IVF , IVF with high insemination concentration ( HIC ) and intracytoplasmic sperm injection ( ICSI ) , and assess on a sibling oocyte comparison the hypothesis that ICSI should be performed in all cases requiring in-vitro conception . ICSI with husb and 's spermatozoa had a higher incidence of fertilization as compared with IVF or IVF with HIC with donor spermatozoa ( if previous failure of fertilization had occurred ) for unexplained infertility . Similarly , ICSI with husb and 's spermatozoa had as high an incidence of fertilization as IVF with donor spermatozoa for patients with severe oligozoospermia , asthenozoospermia and /or teratozoospermia , even when the spermatozoa were not selected for their morphology . Two studies were performed to assess ICSI in potential oocyte-related failure of IVF , viz . when fertilization occurred in > 50 % of oocytes for one group of patients , and in < 50 % of oocytes in a second group . In both of these studies a significant proportion of the oocytes that failed to fertilize with conventional IVF eventually fertilized after ICSI . The overall conclusion was that ICSI as a first option offers a higher incidence of fertilization , maximizes the number of embryos and minimizes the risk of complete failure of fertilization for all cases requiring in-vitro conception . However , among other concerns , current knowledge of ICSI as an outcome procedure does not provide the confidence to use this process in all cases of IVF for the time being BACKGROUND The evidence underpinning the timing of an oocyte collection in IVF or ICSI is limited . The aim of this study was to assess the effect of the follicle diameter size of the dominant follicle on ongoing pregnancy rates . METHODS We conducted a r and omized controlled trial , including women aged between 18 and 43 years who were scheduled for GnRH agonist down-regulated IVF/ICSI treatment in four assisted conception units . Women were r and omized between timing oocyte collection when the leading follicle had a diameter of 22 mm or when the leading follicle had a diameter of 18 mm . The primary end-point was ongoing pregnancy , defined as a viable pregnancy at 12 weeks of gestation . RESULTS The trial had major problems with recruiting patients and after the planned 2 years of recruiting only half of the aim ed 400 inclusion s were obtained . We allocated 97 women to the 22-mm group and 93 women to the 18-mm group . In the 22-mm group more women reached an ongoing pregnancy ( 37 of 97 women , 38 % ) compared with the 18-mm group ( 22 of 93 women , 24 % ) result ing in a relative risk of 1.6 [ 95 % confidence interval ( CI ) : 1.03 - 2.5 ] . In a logistic regression analysis , the timing of oocyte collection , adjusted for female age , IVF/ICSI and centre , was still associated with ongoing pregnancy , although the association was no longer statistically significant ( OR : 2.0 ; 95 % CI : 0.96 - 4.2 ) CONCLUSIONS : This study suggests that delaying the timing of oocyte collection in IVF or ICSI results in better ongoing pregnancy rates , however , larger studies have to be performed to prove or refute these findings . TRIAL REGISTRATION IS RCT N24724622 OBJECTIVE To determine whether a crossover design results in a different estimate of treatment effect compared with a parallel design . DESIGN With the aid of a computer program , data sets of subfertile patients were simulated under different assumptions . These patients were subjected to 2 treatments that were compared in either a parallel- design or a crossover- design trial . Results were analyzed using logistic regression . SETTING University hospital . PATIENT(S ) Simulated patients of a heterogeneous subfertile population . INTERVENTION(S ) Two treatment modalities with a pregnancy rate of 10 % and of 20 % in the first cycle were offered for 6 cycles to simulated heterogeneous population s. MAIN OUTCOME MEASURE(S ) After 1,000 simulations for each assumption , median pregnancy rates and odds ratios were compared between the crossover- and parallel- design trials . RESULT ( S ) No relevant difference in estimated treatment effect was found between the design s. The crossover design result ed in more pregnancies overall than the parallel design . CONCLUSION ( S ) In infertility research , parallel and crossover design s will lead to about the same results . Although the crossover design showed a slight tendency to overestimate the treatment effect of the most effective treatment , this overestimation is clinical ly not relevant and is small in relation to the r and om error . Because of its practical advantages and because more pregnancies are achieved , a crossover design should be the first choice in infertility research Objectives To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child . Design Multicentre , open label , three arm , parallel group , r and omised controlled non-inferiority trial . Setting 17 centres in the Netherl and s. Participants Couples seeking fertility treatment after at least 12 months of unprotected intercourse , with the female partner aged between 18 and 38 years , an unfavourable prognosis for natural conception , and a diagnosis of unexplained or mild male subfertility . Interventions Three cycles of in vitro fertilisation with single embryo transfer ( plus subsequent cryocycles ) , six cycles of in vitro fertilisation in a modified natural cycle , or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after r and omisation . Main outcome measures The primary outcome was birth of a healthy child result ing from a singleton pregnancy conceived within 12 months after r and omisation . Secondary outcomes were live birth , clinical pregnancy , ongoing pregnancy , multiple pregnancy , time to pregnancy , complications of pregnancy , and neonatal morbidity and mortality Results 602 couples were r and omly assigned between January 2009 and February 2012 ; 201 were allocated to in vitro fertilisation with single embryo transfer , 194 to in vitro fertilisation in a modified natural cycle , and 207 to intrauterine insemination with controlled ovarian hyperstimulation . Birth of a healthy child occurred in 104 ( 52 % ) couples in the in vitro fertilisation with single embryo transfer group , 83 ( 43 % ) in the in vitro fertilisation in a modified natural cycle group , and 97 ( 47 % ) in the intrauterine insemination with controlled ovarian hyperstimulation group . This corresponds to a risk , relative to intrauterine insemination with ovarian hyperstimulation , of 1.10 ( 95 % confidence interval 0.91 to 1.34 ) for in vitro fertilisation with single embryo transfer and 0.91 ( 0.73 to 1.14 ) for in vitro fertilisation in a modified natural cycle . These 95 % confidence intervals do not extend below the predefined threshold of 0.69 for inferiority . Multiple pregnancy rates per ongoing pregnancy were 6 % ( 7/121 ) after in vitro fertilisation with single embryo transfer , 5 % ( 5/102 ) after in vitro fertilisation in a modified natural cycle , and 7 % ( 8/119 ) after intrauterine insemination with ovarian hyperstimulation ( one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation ; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation ) . Conclusions In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable , low multiple pregnancy rates . Trial registration Current Controlled Trials IS RCT N52843371 ; Nederl and s Trial Register NTR939 OBJECTIVE To determine whether crossover trials with simple pooling of data over different study periods leads to a different estimate of treatment effect compared with parallel group trials in infertility research using pregnancy as the outcome measure . DESIGN An observational study using nine overviews that included trials with both crossover and parallel group design s. These overviews comprised 17 crossover and 17 parallel group trials . In total , there were 5,291 outcomes including 775 pregnancies . The association between study design and treatment effect estimate was analyzed using multiple logistic regression , controlling for differences in the therapeutic interventions and variations in the method ological quality of the trials . SETTING Infertile patients in an academic research environment . PATIENTS Infertile patients undergoing treatment efficacy evaluation in controlled trials . INTERVENTIONS R and om allocation to a variety of treatments including clomiphene citrate , hCG , IUI , tamoxifen , and bromocriptine . MAIN OUTCOME MEASURE Estimate of bias between study design s , based on the interaction of study design and treatment in the logistic regression model . RESULTS Crossover trials produced a larger average estimate of treatment effect compared with trials with a parallel group design , overestimating the odds ratio by 74 % ( 95 % confidence interval , 2 % to 197 % ) . CONCLUSION The use of a crossover design for evaluating infertility treatments with outcomes that prevent patients from completing later phases of the trial should be avoided because it leads to exaggerated estimates of treatment effect and may result in erroneous inferences and clinical decisions . Furthermore , the type of study design should be taken into account when assessing the method ological quality of therapy trials in infertility Purpose To reevaluate the effect of isolated teratozoospermia on IVF and determine if there was any therapeutic benefit to isolated teratozoospermia by ICSI , since there are no widely accepted criteria for the treatment technique about isolated teratozoospermia . Methods A total of 441 couples with > 20 million and progressive motility > 30 % sperm undergoing their first IVF/ICSI cycle were included in the study between 2008 and 2010 , for whom at least 8 oocytes were retrived . Isolated teratozoospermia was diagnosed in 183 of the included couples , and the rest couples ( normal sperm morphology ) were studied as control . Sibling oocytes were r and omized to be inseminated either by ICSI or IVF . Fertilization rate , embryo quality , pregnancy rate , implantation rate and spontaneous abortion rate were assessed . Results There was no difference in the percentage of eggs fertilized , implantation rate , pregnancy rate and spontaneous abortion rate between conventional IVF and ICSI regardless of the percentage of normal morphology . The day 3 embryonic morphology and rate of development were not different despite the insemination method and percentage of normal morphology . Conclusion Because isolated teratozoospermia did not influence the major indices of IVF and the unnecessary use of ICSI is time-consuming , costly and potential risks , couples with isolated teratozoospermia need not be subjected to ICSI Background Multiple pregnancies are high risk pregnancies with higher chances of maternal and neonatal mortality and morbidity . In the past decades the number of multiple pregnancies has increased . This trend is partly due to the fact that women start family planning at an increased age , but also due to the increased use of ART.Couples with unexplained or mild male subfertility generally receive intrauterine insemination IUI with controlled hormonal stimulation ( IUI COH ) . The cumulative pregnancy rate is 40 % , with a 10 % multiple pregnancy rate . This study aims to reveal whether alternative treatments such as IVF elective Single Embryo Transfer ( IVF e SET ) or Modified Natural Cycle IVF ( MNC IVF ) can reduce the number of multiple pregnancy rates , but uphold similar pregnancy rates as IUI COH in couples with mild male or unexplained subfertility . Secondly , the aim is to perform a cost effective analyses and assess treatment preference of these couples . Methods / Design We plan a multicentre r and omised controlled clinical trial in the Netherl and s comparing six cycles of intra-uterine insemination with controlled ovarian hyperstimulation or six cycles of Modified Natural Cycle ( MNC ) IVF or three cycles with IVF-elective Single Embryo Transfer ( eSET ) plus cryo-cycles within a time frame of 12 months . Couples with unexplained subfertility or mild male subfertility and a poor prognosis for treatment independent pregnancy will be included . Women with anovulatory cycles , severe endometriosis , double sided tubal pathology or serious endocrine illness will be excluded . Our primary outcome is the birth of a healthy singleton . Secondary outcomes are multiple pregnancy , treatment costs , and patient experiences in each treatment arm . The analysis will be performed according tot the intention to treat principle . We will test for non-inferiority of the three arms with respect to live birth . As we accept a 12.5 % loss in pregnancy rate in one of the two IVF arms to prevent multiple pregnancies , we need 200 couples per arm ( 600 couples in total ) . Discussion Determining the safest and most cost-effective treatment will ensure optimal chances of pregnancy for subfertile couples with substantially Output:	None of the women had OHSS.Overall , we found no evidence of a difference between any of the groups in rates of live birth , pregnancy or adverse events ( multiple pregnancy , miscarriage ) . We found insufficient evidence to determine whether there was any difference in safety and effectiveness between different treatments for male subfertility .
MS21533	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Heavy exercise causes gut symptoms and , in extreme cases , " heat stroke " partially due to increased intestinal permeability of luminal toxins . We examined bovine colostrum , a natural source of growth factors , as a potential moderator of such effects . Twelve volunteers completed a double-blind , placebo-controlled , crossover protocol ( 14 days colostrum/placebo ) prior to st and ardized exercise . Gut permeability utilized 5 h urinary lactulose-to-rhamnose ratios . In vitro studies ( T84 , HT29 , NCM460 human colon cell lines ) examined colostrum effects on temperature-induced apoptosis ( active caspase-3 and 9 , Baxα , Bcl-2 ) , heat shock protein 70 ( HSP70 ) expression and epithelial electrical resistance . In both study arms , exercise increased blood lactate , heart rate , core temperature ( mean 1.4 ° C rise ) by similar amounts . Gut hormone profiles were similar in both arms although GLP-1 levels rose following exercise in the placebo but not the colostrum arm ( P = 0.026 ) . Intestinal permeability in the placebo arm increased 2.5-fold following exercise ( 0.38 ± 0.012 baseline , to 0.92 ± 0.014 , P < 0.01 ) , whereas colostrum truncated rise by 80 % ( 0.38 ± 0.012 baseline to 0.49 ± 0.017 ) following exercise . In vitro apoptosis increased by 47 - 65 % in response to increasing temperature by 2 ° C . This effect was truncated by 60 % if colostrum was present ( all P < 0.01 ) . Similar results were obtained examining epithelial resistance ( colostrum truncated temperature-induced fall in resistance by 64 % , P < 0.01 ) . Colostrum increased HSP70 expression at both 37 and 39 ° C ( P < 0.001 ) and was truncated by addition of an EGF receptor-neutralizing antibody . Temperature-induced increase in Baxα and reduction in Bcl-2 was partially reversed by presence of colostrum . Colostrum may have value in enhancing athletic performance and preventing heat stroke This study investigated plasma lipopolysaccharides ( LPS ) concentration and intestinal permeability after 60-min run at 70 % maximum oxygen uptake ( VO2max ) in hot [ 33 ° C , 50 % relative humidity ( rH ) ] and cool ( 22 ° C , 62 % rH ) conditions . Fifteen volunteers gave their informed consent to participate in this study . Their venous blood sample s were taken before , after , 2 and 5 h after exercise in each of the conditions . The order of the two environmental conditions in which they exercised in was r and omised and counterbalanced . Plasma LPS concentration increased by an average of 54.0 % ( 95 % confidence interval : 30.7 , 75.1 % ) after exercising in the hot trial but no significant changes were observed in cool trial , where mean plasma LPS concentration was 12.0 ± 6.4 pg mL−1 ( before ) , 10.9 ± 5.4 pg mL−1 ( after ) , 10.7 ± 6.0 pg mL−1 ( 2 h after ) and 10.6 ± 5.7 pg mL−1 ( 5 h after ) . Median ( range ) plasma claudin-3 ( CLDN3 ) concentration was significantly higher after exercise ( hot : 8.2 [ 1.0–13.0 ] ng mL−1 and cool : 7.6 [ 0.6–13.4 ] ng mL−1 ) as compared to before exercise ( hot : 6.6 [ 0.7–11.8 ] ng mL−1 and cool : 6.7 [ 0.8–12.6 ] ng mL−1 ) ( p < 0.05 ) , but there is no significant difference observed between trials ( p > 0.05 ) . Changes in intestinal permeability are only affected by exercise while exercise-induced endotoxemia is affected by environmental conditions . This study , thus , highlights that an increase in intestinal permeability is not sufficient to trigger exercise-induced endotoxemia , suggesting that post-LPS translocation events may have a greater impact in its occurrence The purpose of this study was to determine whether aspirin ( A ) ingestion combined with prolonged exercise increases gastrointestinal permeability and whether consumption of a carbohydrate-containing ( CHO ) or a CHO + glutamine-containing ( CHO+G ) beverage would reduce this effect . Seventeen subjects completed six experiments . They ingested A ( 1,300 mg ) or placebo ( P ) pills the evening before and before running 60 min at 70 % maximal oxygen uptake . Also , before running they ingested a solution containing 5 g lactulose ( L ) , 5 g sucrose ( S ) , and 2 g rhamnose ( R ) . During each trial , either a 6 % CHO beverage , a 6 % CHO+G ( 0.6 % ; 41 mM ) beverage , or a water placebo ( WP ) was consumed . For 4 h after a run , all urine was collected to measure urinary excretion of L , R , and S. S excretion ( percentage of dose ingested ; measure of gastroduodenal permeability ) was significantly greater ( P < 0.05 ) during the A trial while the subjects drank the WP compared with all other trials . Administration of A also significantly increased L/R ( measure of intestinal permeability ) for the CHO and WP trials compared with all P trials . Ingestion the CHO or CHO+G beverages significantly reduced S excretion and L excretion when A was administered , but it did not reduce L/R. These results indicate that gastroduodenal and intestinal permeability increase after A ingestion during prolonged running and that ingestion of a CHO beverage attenuates the gastroduodenal effect but not the intestinal effect . Furthermore , addition of G to the CHO beverage provided no additional benefit in reducing gastroduodenal or intestinal permeability Thermotolerance and heat acclimation are key adaptation processes that have been hitherto viewed as separate phenomena . Here , we provide evidence that these processes may share a common basis , as both may potentially be governed by the heat shock response . We evaluated the effects of a heat shock response-inhibitor ( quercetin ; 2,000 mg/day ) on established markers of thermotolerance [ gastrointestinal barrier permeability , plasma TNF-α , IL-6 , and IL-10 concentrations , and leukocyte heat shock protein 70 ( HSP70 ) content ] . Heat acclimation reduced body temperatures , heart rate , and physiological strain during exercise/heat stress ) in male subjects ( n = 8) completing a 7-day heat acclimation protocol . These same subjects completed an identical protocol under placebo supplementation ( placebo ) . Gastrointestinal barrier permeability and TNF-α were increased on the 1st day of exercise/heat stress in quercetin ; no differences in these variables were reported in placebo . Exercise HSP70 responses were increased , and plasma cytokines ( IL-6 , IL-10 ) were decreased on the 7th day of heat acclimation in placebo ; with concomitant reductions in exercise body temperatures , heart rate , and physiological strain . In contrast , gastrointestinal barrier permeability remained elevated , HSP70 was not increased , and IL-6 , IL-10 , and exercise body temperatures were not reduced on the 7th day of heat acclimation in quercetin . While exercise heart rate and physiological strain were reduced in quercetin , this occurred later in exercise than with placebo . Consistent with the concept that thermotolerance and heat acclimation are related through the heat shock response , repeated exercise/heat stress increases cytoprotective HSP70 and reduces circulating cytokines , contributing to reductions in cellular and systemic markers of heat strain . Exercising under a heat shock response-inhibitor prevents both cellular and systemic heat adaptations BACKGROUND Glutamine ( GLN ) is the preferred fuel for enterocytes , and GLN supplementation is critical during stressful conditions . The aim of this study was to evaluate the effect of GLN on intestinal barrier permeability and bacterial translocation in a murine experimental model . METHODS Swiss male mice ( 25 - 30 g ) were r and omized into 3 groups : ( 1 ) sham group ; ( 2 ) intestinal obstruction ( IO ) group ; ( 3 ) IO and GLN ( 500 mg/kg/d ) group . Two different experiments were carried out to assess intestinal permeability and bacterial translocation . In the first experiment , the animals were divided into the 3 groups described above and received diethylenetriamine pentaacetate radiolabeled with technetium ( (99m)Tc ) on the eighth day . At different time points after intestinal obstruction , blood was collected to determine radioactivity . The animals were killed , and the small intestine was removed for histological analyses . In the bacterial translocation study , on the eighth day all groups received Escherichia coli labeled with (99m)Tc . After 90 minutes , the animals underwent intestinal obstruction and were killed 18 hours later . Blood , mesenteric lymph nodes , liver , spleen , and lungs were removed to determine radioactivity . Statistical significance was considered when P < or = .05 . RESULTS The levels of intestinal permeability and bacterial translocation were higher in the IO group than in the sham and GLN groups ( P < .05 ) . GLN decreased intestinal permeability and bacterial translocation to physiologic levels in the treated animals and preserved intestinal barrier integrity . CONCLUSIONS GLN had a positive impact on the intestinal barrier by reducing permeability and bacterial translocation to physiologic levels and preserving mucosal integrity Purpose This study aim ed to investigate the effects of multi-strain probiotics supplementation on gastrointestinal permeability , systemic markers of inflammation and running performance when exercising in the heat . Methods Ten male runners were r and omized to 4 weeks of daily supplementation with a probiotics capsule ( 45 billion CFU of Lactobacillus , Bifidobacterium and Streptococcus strains ) or placebo , separated by a washout period ( double-blind , cross-over trial ) . After each treatment , the runners exercised to fatigue at 80 % of their ventilatory threshold at 35 ° C and 40 % humidity . To assess gastrointestinal permeability , runners ingested lactulose and rhamnose before exercise and post-exercise urine was collected to measure sugar concentrations . Venous blood sample s were collected before , immediately after and 1 h after exercise , and core temperature was monitored during exercise . Results Probiotics supplementation significantly increased run time to fatigue ( min : s 37:44 ± 2:42 versus 33:00 ± 2:27 ; P = 0.03 , d = 0.54 ) . Average core temperature during exercise was similar between trials ( probiotic 38.1 ± 0.2 ° C , placebo 38.1 ± 0.1 ° C ; P = 0.77 , d = 0.13 ) . Serum lipopolysaccharide concentration increased post-exercise ( P < 0.001 ) , while there was a moderate to large reduction in pre-exercise ( d = 0.70 ) and post-exercise ( d = 1.24 ) concentration following probiotics supplementation . Plasma concentrations of IL-6 , IL-10 and IL-1ra increased after exercise ( P < 0.01 ) , but there was no significant difference between trials ( P > 0.05 ) . There was a small to moderate reduction ( d = 0.35 ) in urine lactulose : rhamnose and a small reduction ( d = 0.25 ) in symptoms of gastrointestinal discomfort following probiotics supplementation ( both P = 0.25 ) . Conclusion Four weeks of supplementation with a multi-strain probiotic increased running time to fatigue in the heat . Further studies are required to eluci date the exact mechanisms for this performance benefit Non-steroidal anti-inflammatory drugs ( NSAIDs ) are effective analgesics but cause gastrointestinal injury . Present prophylactic measures are suboptimal and novel therapies are required . Bovine colostrum is a cheap , readily available source of growth factors , which reduces gastrointestinal injury in rats and mice . We therefore examined whether spray-dried , defatted colostrum could reduce the rise in gut permeability ( a non-invasive marker of intestinal injury ) caused by NSAIDs in volunteers and patients taking NSAIDs for clinical reasons . Healthy male volunteers ( n=7 ) participated in a r and omized crossover trial comparing changes in gut permeability ( lactulose/rhamnose ratios ) before and after 5 days of 50 mg of indomethacin three times daily ( tds ) per oral with colostrum ( 125 ml , tds ) or whey protein ( control ) co-administration . A second study examined the effect of colostral and control solutions ( 125 ml , tds for 7 days ) on gut permeability in patients ( n=15 ) taking a substantial , regular dose of an NSAID for clinical reasons . For both studies , there was a 2 week washout period between treatment arms . In volunteers , indomethacin caused a 3-fold increase in gut permeability in the control arm ( Output:	Conclusion The magnitude of exercise-induced hyperthermia is directly associated with the increase in intestinal permeability
MS21534	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND In the treatment of severe malaria , intravenous artesunate is more rapidly acting than intravenous quinine in terms of parasite clearance , is safer , and is simpler to administer , but whether it can reduce mortality is uncertain . METHODS We did an open-label r and omised controlled trial in patients admitted to hospital with severe falciparum malaria in Bangladesh , India , Indonesia , and Myanmar . We assigned individuals intravenous artesunate 2.4 mg/kg bodyweight given as a bolus ( n=730 ) at 0 , 12 , and 24 h , and then daily , or intravenous quinine ( 20 mg salt per kg loading dose infused over 4 h then 10 mg/kg infused over 2 - 8 h three times a day ; n=731 ) . Oral medication was substituted when possible to complete treatment . Our primary endpoint was death from severe malaria , and analysis was by intention to treat . FINDINGS We assessed all patients r and omised for the primary endpoint . Mortality in artesunate recipients was 15 % ( 107 of 730 ) compared with 22 % ( 164 of 731 ) in quinine recipients ; an absolute reduction of 34.7 % ( 95 % CI 18.5 - 47.6 % ; p=0.0002 ) . Treatment with artesunate was well tolerated , whereas quinine was associated with hypoglycaemia ( relative risk 3.2 , 1.3 - 7.8 ; p=0.009 ) . INTERPRETATION Artesunate should become the treatment of choice for severe falciparum malaria in adults Cerebral malaria remains a major cause of childhood morbidity . Quinine is the drug of choice for which resistance is now emerging . A total of 77 children admitted to Khartoum Children Emergency Hospital who conform to WHO criteria of cerebral malaria were r and omly allocated to receive either artemether ( 1.6 mg/kg body wt . , repeated after 12 hrs and then daily for four days ) or quinine ( 10 mg/kg body wt in 10 ml/kg body wt of 5 % dextrose in 0.9 % saline intravenously . Repeated every 8 hrs and changed to oral administration when the child was able to drink to finish seven days ) . Response to therapy was evaluated using fever clearance time ( FCT ) , time of regaining consciousness ( TRC ) and parasite clearance time ( PCT ) . The FCT ( mean+SD ) , TRC and PCT for the artemether-treated group were 32 ( + 13 ) hrs , 21 ( + 11 ) hrs and 36 ( + 18 ) hrs , respectively , while for the quinine-treated group the respective figures were 36 ( + 18 ) , 26 ( + 15 ) hrs and 41 ( + 12 ) hrs . The response to artemether was slightly better than that of quinine , but the differences between the two groups were not statistically significant . The outcome in terms of cure rate , neurological sequalae and case fatality was also comparable We have compared the efficacy of artemether versus quinine as treatment for cerebral malaria in children in an open r and omized clinical trial in Kenya . Children admitted to hospital with coma and Plasmodium falciparum parasitaemia were treated with either intramuscular artemether ( 3.2 mg/kg loading dose followed by 1.6 mg/kg daily ) or intravenous quinine ( 20 mg/kg loading dose followed by 10 mg/kg every 8 h ) . Both drugs were well tolerated and no significant adverse effect was observed . Parasite clearance times ( 50 % and 90 % ) were shorter in patients treated with artemether ( median times [ h ] , with interquartile ranges in brackets , were : 50 % , 7.3 [ 4.2 - 12.4 ] vs. 15.5 [ 9 - 22 ] ; 90 % , 16.9 [ 13.2 - 25 ] vs. 28.5 [ 22 - 35 ] ; P < 0.0001 ) . The total mortality in 160 children with cerebral malaria was 16.25 % , with no overall significant difference between the 2 treatment groups . In a subgroup of children with respiratory distress , mortality was higher in those treated with artemether ( 43.7 % vs. 11.1 % , P < 0.05 ) . The frequency of neurological sequelae and clinical recovery times were similar in both treatment groups . We conclude that there would currently be no advantage in replacing quinine with artemether for the treatment of cerebral malaria in African children ABSTRACT We present the first population pharmacokinetic analysis of quinine in patients with Plasmodium falciparum malaria . Ghanaian children ( n = 120 ; aged 12 months to 10 years ) with severe malaria received an intramuscular loading dose of quinine dihydrochloride ( 20 mg/kg of body weight ) . A two-compartment model with first-order absorption and elimination gave post hoc estimates for pharmacokinetic parameters that were consistent with those derived from non- population pharmacokinetic studies ( clearance [ CL ] = 0.05 liter/h/kg of body weight ; volume of distribution in the central compartment [ V1 ] = 0.65 liter/kg ; volume of distribution at steady state = 1.41 liter/kg ; half-life at β phase = 19.9 h ) . There were no covariates ( including age , gender , acidemia , anemia , coma , parasitemia , or anticonvulsant use ) that explained interpatient variability in weight-normalized CL and V1 . Intramuscular quinine was associated with minor , local toxicity in some patients ( 13 of 108 ; 12 % ) , and 11 patients ( 10 % ) experienced one or more episodes of postadmission hypoglycemia . A loading dose of intramuscular quinine results in predictable population pharmacokinetic profiles in children with severe malaria and may be preferred to the intravenous route of administration in some circumstances OBJECTIVES To compare the efficacy of intramuscular artemether and intravenous quinine in the treatment of severe falciparum malaria . DESIGN An open r and omized controlled clinical trial . SETTING New Halfa Teaching Hospital , Eastern Sudan , in the period November 2001-January 2002 . SUBJECTS Forty one male and female children ; 21 on artemether and 20 on quinine . MAIN OUTCOME MEASURES Fever clearance time , parasite clearance time , coma resolution time and side effects of the two drugs . RESULTS The two groups ( artemether and quinine ) were well matched in the admission variable . The mean + /- ( SD ) fever clearance time was 30.5 + /- ( 20.9 ) hours in the artemether group , while it was 18.0 + /- ( 8.1 ) hours in the quinine group ; the difference was highly significant ( P=0.02 ) . The mean parasite clearance time was shorter in the artemether group than in the quinine group , but it was not statistically significant , ( 16.0 vs. 22.4 hours ; p>0.05 ) . In comatose patients ( three in the artemether group , three in the quinine group ) the time of recovery from coma was significantly shorter in artemether group than in quinine group ( 12.5 vs. 20.16 hours ; P<0.05 ) . Recrudescence of P. falciparum ( confirmed by polymerase chain reaction ) occurred in one out of fifteen patients ( 6.6 % ) in the quinine group seen on day 28 , which was successfully treated by sulphadoxine-pyrimethamine . In the quinine group , one patient died and one patient developed hypoglycaemia . CONCLUSION Artemether caused faster parasite clearance than quinine , but quinine lowered the temperature in shorter time than artemether . The results obtained show that artemether can be used as safe and effective alternative drug for the treatment of severe falciparum malaria in the wake of the growing resistance to quinine in Sudan Severe malaria remains a major cause of mortality and morbidity for children living in many tropical regions . With the emergence of strains of Plasmodium falciparum resistant to both chloroquine and quinine , alternative antimalarial agents are required . The artemisinin group of compounds are rapidly effective in severe disease when given by intramuscular or intravenous injection . However , these routes of administration are not always available in rural areas . In an open , r and omized comparison 109 Vietnamese children , aged between 3 months and 14 years , with severe P.falciparum malaria , were allocated at r and om to receive artemisinin suppositories followed by mefloquine ( n = 37 ) , intramuscular artesunate followed by mefloquine ( n = 37 ) , or intravenous quinine followed by pyrimethamine/sulfadoxine ( n = 35 ) . There were 9 deaths : 2 artemisinin , 4 artesunate and 5 quinine-treated children . There was no difference in fever clearance time , coma recovery , or length of hospital stay among the 3 groups . However , parasite clearance times were significantly faster in artemisinin and artesunate-treated patients than in those who received quinine ( P < 0.0001 ) . Both artemisinin and artesunate were very well tolerated , but children receiving these drugs had lower peripheral reticulocyte counts by day 5 of treatment than those in the quinine group ( P = 0.011 ) . No other adverse effect or toxicity was found . There was no treatment failure in these 2 groups , but 4 patients in the quinine group failed to clear their parasites within 7 d of starting treatment and required alternative antimalarial therapy . Artemisinin suppositories are easy to administer , cheap , and very effective for treating children with severe malaria . In rural areas where medical facilities are lacking these drugs will allow antimalarial therapy to be instituted earlier in the course of the disease and may therefore save lives The efficacy of a 5-day treatment with intramuscular artemether ( 3.2-mg/kg loading dose followed by 1.6 mg/kg daily ) was compared to that of the st and ard 7-day treatment with quinine ( 20-mg/kg loading dose followed by 10 mg/kg every 8 h ) in a r and omised clinical trial including 103 children aged 12 - 60 months with cerebral malaria between 1994 and 1996 . No statistical difference of immediate efficacy was found between the two treatments . There were 11 ( 20 % ) deaths in the artemether group and 14 ( 28 % ) in the children who received quinine . The respective artemether versus quinine median fever clearance times ( h ) were 39 ( interquartile ranges [ IQ ] 30 - 54 ) vs. 48 ( IQ 30 - 60 ) , and parasite clearance 42 ( IQ 24 - 60 ) vs. 36 ( IQ 30 - 48 ) . However , one patient who received artemether had a recrudescence on day 14 , which was successfully treated with sulphadoxine-pyrimethamine . Times to recovery from coma were 24 h ( IQ 18 - 45 ) and 33 h ( IQ 19 - 57 ) , respectively . The occurrence of transient neurological sequelae including motor disabilities , cortical blindness , and afebrile seizures was also similar in the two groups . No adverse reactions to the two drugs were recorded during the study period . Artemether represents an important option in the management of cerebral malaria in Nigeria especially in rural areas where facilities for intravenous administration may not yet be optimal OBJECTIVE To compare the efficacy of artemether and quinine in the treatment of severe malaria in hospitalized children . STUDY DESIGN Open r and omized trial . SETTING Pediatric ward of a tertiary care center . METHODS All children admitted with clinical manifestations of severe malaria ( as per WHO criteria ) and asexual forms of Plasmodium falciparum demonstrated on peripheral smear were r and omized to receive either artemether or quinine . Their clinical status and smears for parasite count were assessed every 12 hours until two successive blood films were negative . The primary end point of the study was death in the hospital and residual damage to the organ involved . The secondary end points were clearance of parasites and fever , length of time of recovery from coma and normal functions of the involved system . RESULTS Forty-six cases completed the study protocol , 23 assigned to each drug group . Cerebral malaria was the commonest manifestation ( 76.1 % ) . Mean age in artemether versus quinine group ( 6.6 + /- 3.5 and 5.8 + /- 2.4 years ) as well as degree of parasitemia at admission ( 55,800 and 60,300 per microlitre ) were comparable . The overall mortality rate was 23.9 % with no significant difference between the two groups . Twenty six cases ( 56.5 % ) presented with more than one manifestations of severe malaria . The mortality rate was 100 % with four coexisting manifestations of severe malaria . Fever clearance time in artemether and quinine group was 44.5 and 45. Output:	There was no statistically significant difference between the two groups in parasite clearance time , fever clearance time , incidence of neurological sequelae and 28th day cure rate . Conclusion There was no evidence that treatment of children with severe malaria with parenteral artemisinin derivatives was associated with lower mortality or long-term morbidity compared to parenteral quinine .
MS21535	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Patients with chronic hepatitis B virus ( HBV ) infection are at risk for death from complications of liver disease and development of hepatocellular carcinoma ( HCC ) . To identify the time course and risk factors associated with these events , we conducted a prospect i ve study in chronic hepatitis B patients referred to our clinic . Methods From January 1989 to March 1998 , 400 hepatitis B surface antigen (HBsAg)-positive patients were classified into three categories : inactive carriers ( N=110 ) , chronic hepatitis ( N=151 ) , and cirrhosis ( N=139 ) . These patients were observed at 3- to 6-month intervals with liver tests , alpha-fetoprotein ( AFP ) levels , and ultrasound examinations . The study endpoints were death from liver disease complications and development of HCC . Results The patients were followed for a mean time ( ± SD ) of 83.6 ± 39.6 months . During this period , no liver-related deaths or HCC were noted in inactive carriers . However , 38 of 139 ( 27.3 % ) patients with cirrhosis died from non-HCC-related liver complications . Multivariate analysis demonstrated that male sex ( odds ratio [ OR ] 5.9 ; 95 % confidence interval [ CI ] , 2.0 - 22.6 ; P=.003 ) , decreased initial serum albumin ( OR 69.1 ; 95 % CI , 11.5 - 486.4 ; P=.0009 ) , low platelet count ( OR 8.8 ; 95 % CI , 0.96 - 92.9 ; P=.05 ) , and presence of cirrhosis ( OR 14.2 ; 95 % CI , 3.4 - 111.8 ; P=.0009 ) were independently associated with increased mortality from chronic hepatitis B. During the same time period , nine of 151 ( 6.0 % ) chronic hepatitis patients and 22 of 139 ( 15.8 % ) patients with cirrhosis developed HCC . By multivariate analysis , progression to HCC was associated with advanced age ( OR 19.7 ; 95 % CI , 1.9 - 231.9 ; P=.01 ) and presence of cirrhosis ( OR 3.6 ; 95 % CI , 1.6 - 8.9 ; P=.003 ) . Patients positive for hepatitis B early antigen ( HBeAg ) and HBeAg antibodies experienced liver-related deaths and developed HCC at similar rates . Conclusions This prospect i ve study from the United States confirms previous observations of the high risk of mortality and development of HCC in patients infected with HBV . To decrease the risk of these complications , antiviral therapy should be initiated early in the course of the disease . In addition , surveillance for HCC must be performed at least every 6 months in patients with chronic hepatitis and cirrhosis Thirty male patients ( 27 homosexual ) with biopsy proven chronic active hepatitis B were r and omised to receive lymphoblastoid interferon ( Wellferon ) or no treatment . All patients were HBeAg positive and had continuing viral replication . Patients receiving treatment were given a single daily intramuscular injection of interferon for 28 days at a starting dose of 2.5 MU/m2 increasing to a maximum of 7.5 MU/m2/day . Transient side effects of malaise and influenza like symptoms occurred in all patients and resolved rapidly after treatment . Hepatitis B viral replication was suppressed during interferon treatment in all patients but the effect was limited to the period of therapy . After one year there was no appreciable difference in viral markers between the two groups of patients and this treatment schedule appears less effective than the thrice weekly , three month regimes recently reported from other centres BACKGROUND Long-term effects of lamivudine treatment on chronic hepatitis B patients without advanced disease remain unknown . Our aim was to investigate the effects of long-term lamivudine treatment and lamivudine-resistant virus ( YMDD ) on the development of cirrhosis and hepatocellular carcinoma ( HCC ) in asymptomatic patients without advanced disease . METHODS One hundred and forty-two hepatitis B e antigen (HBeAg)-positive patients ( median age : 33.9 years ) on long-term lamivudine ( median treatment duration : 89.9 months ) and 124 HBeAg-positive controls ( median age : 33.4 years ) were prospect ively followed up . Patients were monitored for the development of cirrhosis and HCC , liver biochemistry , hepatitis B virus ( HBV ) DNA levels , HBeAg seroconversion and hepatitis flares . YMDD mutations ( YMDD-MT ) were determined annually . RESULTS Lamivudine-treated patients had a significantly lower cumulative rate of development of cirrhosis and /or HCC compared with controls ( P = 0.005 ) . YMDD-MT occurred in 76.3 % of patients after 8 years of lamivudine treatment . When compared with controls and patients with YMDD-MT , patients without YMDD-MT had the greatest reduction of HBV DNA and bilirubin levels , slowest decline of albumin level , highest rate of HBeAg seroconversion and lowest risk of hepatitis flare . Patients with YMDD-MT still had a lower risk for developing cirrhosis and /or HCC ( P = 0.024 ) and a greater HBV DNA reduction ( P = 0.001 ) in comparison with controls . Patients with YMDD-MT and controls had a similar chance of hepatitis flares and hepatic decompensation . CONCLUSIONS Long-term lamivudine treatment was associated with a reduced chance of developing cirrhosis and HCC in patients without advanced disease . Although YMDD-MT reduced the benefits from lamivudine therapy , the outcome of these patients was still better than untreated patients BACKGROUND The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown . METHODS Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were r and omly assigned in a 2:1 ratio to receive lamivudine ( 100 mg per day ) or placebo for a maximum of five years . Of 651 patients , 436 were assigned to receive lamivudine and 215 to receive placebo . The primary end point was time to disease progression , defined by hepatic decompensation , hepatocellular carcinoma , spontaneous bacterial peritonitis , bleeding gastroesophageal varices , or death related to liver disease . An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data . RESULTS We r and omly assigned 651 patients ( 98 percent Asian and 85 percent male ) to receive lamivudine or placebo . The study was terminated after a median duration of treatment of 32.4 months ( range , 0 to 42 ) owing to a significant difference between treatment groups in the number of end points reached . End points were reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of those receiving placebo ( hazard ratio for disease progression , 0.45 ; P=0.001 ) . The Child-Pugh score increased in 3.4 percent of the patients receiving lamivudine and 8.8 percent of those receiving placebo ( hazard ratio , 0.45 ; P=0.02 ) , whereas hepatocellular carcinoma occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of those in the placebo group ( hazard ratio , 0.49 ; P=0.047 ) . Genotypic resistance YMDD mutations developed in 49 percent of the patients treated with lamivudine , and the Child-Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine ( 7 percent vs. < 1 percent ) . Overall , 12 percent of the patients in the lamivudine group and 18 percent of the patients in the placebo group reported serious adverse events . CONCLUSIONS Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma BACKGROUND Antiviral therapy for hepatitis B virus ( HBV ) infection is frequently prescribed for patients with chronic HBV infection during surveillance for hepatocellular carcinoma ( HCC ) . In patients who subsequently develop HCC , the impact of antiviral therapy on the outcome of HCC remains unclear . AIMS We aim ed to study the impact of antiviral therapy on the survival of patients who developed HCC . METHODS From two prospect i ve surveillance cohorts , the use of antiviral therapy for patients with HCC was retrospectively review ed . We compared the overall survival , liver function and tumour characteristics between patients with and without antiviral therapy during surveillance . Multivariate analysis was conducted to determine the independent prognostication of antiviral therapy . RESULTS During a median follow-up of 10.1 years of 1429 patients , 148 cases of HCC were diagnosed and followed up for a median of 5.7 years . Twenty-nine patients were given antiviral therapy during surveillance and continued treatment after diagnosis of HCC . The median survival of this group of patients was better than the rest of cohorts ( hazard ratio : 0.472 ; 95 % CI : 0.25 - 0.89 ; P = 0.0191 ) . Use of antiviral therapy remained an independent prognostic factor after adjustment for demographic factors and tumour staging on multivariate analysis . Exploratory analysis revealed that patients who commenced antiviral therapy during surveillance had lower HBV DNA , lower serum alanine transaminase , better hepatic reserves and higher rate of local treatment at diagnosis of HCC . CONCLUSION This study provides evidence that commencement of antiviral therapy during the surveillance period is associated with improvement in overall survival in HBV-related HCC The long-term usefulness of interferon-alpha ( IFN-alpha ) in chronic hepatitis B remains controversial . To investigate the long-term efficacy of IFN-alpha therapy in chronic hepatitis B , 62 Japanese patients , including 27 patients treated with IFN-alpha ( IFN group ) and 35 patients without antiviral therapy matched by age and sex as controls ( control group ) , were followed up for 2 - 14 years . At entry , the serum alanine aminotransferase ( ALT ) level in the IFN group was significantly higher than that in the control group ( 238.6+/-250.1 vs. 142.3+/-152.1 IU/l , P < 0.05 ) . The prevalence of genotype C was 89 % , with no difference between the two groups ( 93 vs. 86 % ) . There was no significant difference in the presence of the precore mutation or the dual core promoter mutations between the IFN and control groups ( 37 vs. 46 % , 74 vs. 66 % ) . After long-term follow-up , the rate of sustained HBeAg seroconversion was comparable in the two groups ( 33 vs. 31 % ) . Normalization of serum ALT level was seen in 44 % of the IFN group and 51 % of the control group , with no difference . There was also no difference in the percentage of cases with loss of serum HBV-DNA by PCR assay between the two groups ( 33 vs. 29 % ) . During follow-up , two patients of the control group and three patients of the IFN group developed cirrhosis , and one of the IFN- treated patients progressed to hepatocellular carcinoma . The results of this long-term follow-up study showed that no benefit of IFN-alpha treatment was detectable during long-term follow-up in Japanese patients with chronic hepatitis BACKGROUND Data regarding the outcome of hepatitis B virus (HBV)-related cirrhosis after the onset of decompensation is scanty . METHOD From January 1998 to December 2008 , a retrospective- prospect i ve inception cohort study involving HBV-related decompensated cirrhotics was performed . Predictors of death and clinical events after the onset of decompensation were evaluated . Patients with co-infection with hepatitis C virus and /or human immunodeficiency virus , alcohol consumption to any degree and diabetes diagnosed before the detection of liver disease were excluded . RESULT AND ANALYSIS Two hundred and fifty-three patients ( 231 males , 139 e-negative ) , including 102 untreated patients , were analysed . The mean ( + /-SD ) age was 43.0 ( + /-12.0 ) years . The mean ( + /-SD ) follow-up period was 47 ( + /-47 ) months . Decompensation was the first presentation of liver disease in 210 ( 83 % ) patients . Ascites ( 70 % ) and variceal bleed ( 28 % ) were predominant modes of decompensation . Forty-three ( 17 % ) patients died ( 22 vs 14 % in untreated and treated cohort , respectively ; P=0.002 ) . Type 2 hepato-renal syndrome was the commonest cause of death ( 32 % ) . Survival was independent of e-antigen status . In the total cohorts , predictors of death were occurrence of sepsis Output:	Conclusions The effect of antiviral therapy on clinical outcomes in HBV remains to be established .
MS21536	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: INTRODUCTION The purpose of this study was to clinical ly evaluate the effect of low-level laser therapy ( LLLT ) as a method of reducing pain reported by patients after placement of their first orthodontic archwires . METHODS The sample comprised 60 orthodontic patients ( ages , 12 - 18 years ; mean , 15.9 years ) . All patients had fixed orthodontic appliances placed in 1 dental arch ( maxillary or m and ibular ) , received the first archwire , and were then r and omly assigned to the experimental ( laser ) , placebo , or control group . This was a double-blind study . LLLT was started in the experimental group immediately after placement of the first archwire . Each tooth received a dose of 2.5 J per square centimeter on each side ( buccal and lingual ) . The placebo group had the laser probe positioned into the mouth at the same areas overlying the dental root and could hear a sound every 10 seconds . The control group had no laser intervention . All patients received a survey to be filled out at home describing their pain during the next 7 days . RESULTS The patients in the LLLT group had lower mean scores for oral pain and intensity of pain on the most painful day . Also , their pain ended sooner . LLLT did not affect the start of pain perception or alter the most painful day . There was no significant difference in pain symptomatology in the maxillary or m and ibular arches in an evaluated parameter . CONCLUSIONS Based on these findings , we concluded that LLLT efficiently controls pain caused by the first archwire The control of pain during orthodontic treatment is of great interest to both clinicians and patients . However , there has been limited research into the control of this pain , and there is no st and ard of care for controlling this discomfort . This prospect i ve study determines the pain sequelae in fixed orthodontic treatment and evaluates comparatively the analgesic effects of nonsteroidal anti-inflammatory drugs for the control of this pain . One hundred and fifty orthodontic patients who were to have teeth bonded in at least one arch were r and omly assigned to one of six groups : ( 1 ) placebo/placebo , ( 2 ) ibuprofen/ibuprofen , ( 3 ) flurbiprofen/flurbiprofen , ( 4 ) acetaminophen/acetaminophen , ( 5 ) naproxen sodium/naproxen sodium , and ( 6 ) aspirin/aspirin . The pain evaluations were made during chewing , biting , fitting the front teeth , and fitting the back teeth using a 100-mm visual analogue scale ( VAS ) for seven days . All the analgesics succeeded in decreasing the pain levels compared with the placebo group . However , naproxen sodium and aspirin groups showed the lowest pain values , and the acetaminophen group showed VAS results similar to those of the two analgesics OBJECTIVE To test the hypothesis that there is no difference in the pain associated with orthodontic force application after the application of local CO(2 ) laser irradiation to the teeth involved . MATERIAL S AND METHODS Separation modules were placed at the distal contacts of the maxillary first molars in 90 patients in this single-blinded study . In 60 of these patients ( 42 females and 18 males ; mean age = 19.22 years ) this was immediately followed by laser therapy . The other 30 patients ( 18 females and 12 males ; mean age = 18.8 years ) did not receive active laser irradiation . Patients were then instructed to rate their levels of pain on a visual analog scale over time , and the amount of tooth movement was analyzed . RESULTS Significant pain reductions were observed with laser treatment from immediately after insertion of separators through day 4 , but no differences from the nonirradiated control side were noted thereafter . No significant difference was noted in the amount of tooth movement between the irradiated and nonirradiated group . CONCLUSIONS The hypothesis was rejected . The results suggest that local CO(2 ) laser irradiation will reduce pain associated with orthodontic force application without interfering with the tooth movement The present study compared the effect of acetaminophen , ibuprofen and misoprostol on PGE2 synthesis and orthodontic tooth movement . Guinea pigs were r and omly assigned into one of three test groups or a control group . Each group received study treatments every 12 hours as an orthodontic force was applied to the maxillary incisors . Direct linear measurements of tooth separation were recorded at days 2 , 4 , 6 , 10 , and 11 , and inflammatory exu date from the periodontal ligament ( PDL ) space was extracted and quantitatively analyzed radioimmunologically for the presence of PGE2 at days 4 and 9 . Comparing the concentration of PGE2 in sample extracts , a significant difference ( P = 0.001 ) was found among drug groups . A highly significant difference was found between the mean tooth separation among the various drug groups ( P < 0.001 ) . At day 11 the misoprostol group exhibited 4.49 + /- 0.49 mm of separation ; ibuprofen 2.56 + /- 0.11 mm , and the control and acetaminophen groups exhibited similar degrees of tooth separation : 3.31 + /- 0.07 mm and 3.31 + /- 0.08 mm , respectively . A highly significant difference occurred between the mean rates of tooth separation among the various drug groups after day 8 ( P < 0.001 ) . Results of this study suggest that acetaminophen is the analgesic of choice for the relief of minor discomfort associated with orthodontic treatment The aim of this study is to compare the effectiveness of low-level laser irradiation to traditional topical fluoride treatment for treatment choices of dentinal hypersensitivity following scaling and root planing . The experimental group ( 15 patients ) was treated with low-energy-level diode laser at each site of dentinal hypersensitivity following scaling and root planning . The control group ( 15 patients ) received topical fluoride treatment ( protective varnish for desensitization ) . All the patients were treated at baseline visit , and then at day 2 and 4 after the initial treatment ; the pain was subjectively assessed by the patients as strong , medium , medium low , low , or no pain . Total absence of the dental hypersensitivity was reported in 26.66 % of the examined group even after the second visit , compared to the control group where complete resolution of the hypersensitivity was not present after the second visit in any of the treated cases . Complete absence of pain was achieved in 86.6 % of patients treated with laser and only in 26.6 % in the fluoride treated group , after the third visit . Based on our findings , we conclude that low-energy biostimulative laser treatment can be successfully used for treatment of dental hypersensitivity following scaling and root planing Low-level laser therapy ( LLLT ) has been found to produce anti-inflammatory effects in a variety of disorders . Tendinopathies are directly related to unbalance in expression of pro- and anti-inflammatory cytokines which are responsible by degeneration process of tendinocytes . In the current study , we decided to investigate if LLLT could reduce mRNA expression for TNF-α , IL-1β , IL-6 , TGF-β cytokines , and COX-2 enzyme . Forty-two male Wistar rats were divided r and omly in seven groups , and tendinitis was induced with a collagenase intratendinea injection . The mRNA expression was evaluated by real-time PCR in 7th and 14th days after tendinitis . LLLT irradiation with wavelength of 780 nm required for 75 s with a dose of 7.7 J/cm2 was administered in distinct moments : 12 h and 7 days post tendinitis . At the 12 h after tendinitis , the animals were irradiated once in intercalate days until the 7th or 14th day in and them the animals were killed , respectively . In other series , 7 days after tendinitis , the animals were irradiated once in intercalated days until the 14th day and then the animals were killed . LLLT in both acute and chronic phases decreased IL-6 , COX-2 , and TGF-β expression after tendinitis , respectively , when compared to tendinitis groups : IL-6 , COX-2 , and TGF-β . The LLLT not altered IL-1β expression in any time , but reduced the TNF-α expression ; however , only at chronic phase . We conclude that LLLT administered with this protocol reduces one of features of tendinopathies that is mRNA expression for pro-inflammatory mediators The control of pain during orthodontic treatment is of vital interest to both clinicians and patients . Surprisingly , there has been limited research into the control of orthodontic pain , and there is no st and ard of care for controlling this discomfort . The purpose of this study was to compare the effectiveness of preemptive ibuprofen therapy , postoperative ibuprofen therapy , and a combination of the 2 therapies . Forty-one orthodontic patients aged 9 years 3 months to 16 years 11 months who were to undergo separator placement were enrolled in this prospect i ve study . Patients were r and omly assigned to 1 of 3 experimental conditions : ( 1 ) 400 mg ibuprofen taken orally 1 hour before separator placement and 400 mg ibuprofen taken orally 6 hours after the initial dose , ( 2 ) 400 mg ibuprofen taken orally 1 hour before separator placement and a lactose capsule taken orally 6 hours after the initial dose , or ( 3 ) a lactose capsule taken orally 1 hour before separator placement and 400 mg ibuprofen taken 6 hours after the initial placebo . The results revealed that preemptive ibuprofen therapy significantly decreased pain that was experienced 2 hours after separator placement and at bedtime . Beginning on day 2 , there was a trend for patients who had taken both preemptive and postoperative ibuprofen doses to have lower pain scores compared with the other 2 groups . In conclusion , these data indicate that ibuprofen taken 60 minutes before separator placement alleviates pain at 2 hours and at bedtime after treatment . Further study with the use of additional postoperative doses is warranted Gallium-arsenide ( GaAs ) and helium-neon ( HeNe ) lasers are the most commonly used low-energy lasers in physiotherapy for promoting wound healing and pain modulation . The aim of this study was investigate the effect of low-power laser irradiation ( LPLI ) at different wavelengths and doses on oxidative stress and fibrogenesis parameters in an animal model of wound healing . The animals were r and omly divided into five groups ( n = 6 ) : Controls ( skin injured animals without local or systemic treatment ) , skin injury treated with HeNe 1 J/cm2 ( two seg ) ; skin injury treated with HeNe 3 J/cm2 ( six seg ) ; skin injury treated with GaAs 1 J/cm2 ( three seg ) ; skin injury treated with GaAs 3 J/cm2 ( nine seg ) . A single circular wound measuring 8 mm in diameter was surgically created on the back of the animal . The rats were irradiated at 2 , 12 , 24 , 48 , 72 , 96 , and 120 h after skin injury . The parameters , namely hydroxyproline content , activities of the antioxidant enzymes superoxide dismutase ( SOD ) and catalase ( CAT ) , and lipid ( TBARS ) and protein oxidation ( carbonyl groups ) measurements were assessed . In addition , wound size regression was also analyzed . The results showed an improvement in the wound healing reflected by the reduction in wound size and increased collagen synthesis . Moreover , a significant reduction in TBARS levels , carbonyl content , and SOD and CAT activities were observed after laser irradiation , particularly with the treatments HeNe laser 1 and 3 J/cm2 dose and GaAs 3 J/cm2 dose . The data strongly indicate that LPLI therapy is efficient in accelerating the skin wound healing process after wounding , probably by reducing the inflammatory phase and inducing collagen synthesis The aims of this study were to investigate the initial time at which pain occurs after insertion of two initial wires of different sizes , the duration of the pain , the areas affected within the mouth , the level of self-medication , the effect of this pain on daily life , and whether gender is important in the perception of pain . The study group consisted of 109 patients ( 52 boys , 57 girls ) with a mean chronological age of 13.6 years for boys and 14.7 years for girls . Insertion of either a 0.014 or 0.016 inch wire was by r and om selection . Following insertion of the archwires , a question naire comprising a total of 49 questions was given to the patients . They described the time of initial pain in the first question , answered the next 24 questions as ' yes ' or ' no ' , and used a visual analogue scale for the final 24 questions . No significant differences were found in terms of gender , in the perception period of initial pain as regards the areas affected within the mouth or the effect of pain on daily living when the 0.014 and 0.016 inch wire groups were compared at 6 hours , 1 , 2 , 3 , 4 , 5 , 6 and 7 days . At 24 hours , which was found to be statistically significant , more pain relief was used in the 0.014 inch archwire group . The results show that in both groups , initial pain was perceived at 2 hours , peaked at 24 hours and had decreased by day 3 The effects of soft laser ( low reactive level laser ) on reduction of pain while undergoing orthodontic treatment was examined in this study . These patients were r and omly separated into 3 groups : non-treated control group ( CG ) , blind irradiation group ( BG ) , Output:	However , because of the method ological shortcomings and risk of bias of included trials , LLLT was proved with limited evidence in delaying pain onset and reducing pain intensity .
MS21537	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We investigated whether serum cardiac troponin T levels are altered in septic patients undergoing hemodialysis and whether polymyxin B-immobilized fiber ( PMX-F ) treatment affects these levels . Fourteen hemodialysis patients with sepsis , 14 hemodialysis patients without sepsis , and 12 age matched healthy controls were included in this study . Cardiac troponin T levels in hemodialysis patients with sepsis ( 0.56 ± 0.28 & mgr;g/L ) were higher than levels in hemodialysis patients without sepsis ( 0.16 ± 0.06 & mgr;g/L , p < 0.01 ) and healthy control subjects ( 0.03 ± 0.01 & mgr;g/L , p < 0.001 ) . The 14 hemodialysis patients with sepsis were r and omly assigned to one of two treatment approaches : PMX-F treatment ( n = 7 ) or conventional treatment ( n = 7 ) . Plasma endotoxin levels were significantly reduced from 46.6 ± 17.8 pg/ml to 8.2 ± 2.4 pg/ml , p < 0.01 , in patients treated with PMX-F , and serum cardiac troponin T levels were also reduced from 0.62 ± 0.30 & mgr;g/L to 0.26 ± 0.12 & mgr;g/L , p < 0.05 . Cardiac troponin T levels were unchanged in patients under conventional treatment . These data suggest that cardiac troponin T is indeed elevated in septic patients undergoing hemodialysis and may reflect sub clinical myocardial cell damage . PMX-F is effective in reducing myocardial damage , in part , due to reducing plasma endotoxin levels Introduction The objective of this study was to clarify the efficacy and mechanism of action of direct hemoperfusion with an immobilized polymyxin B fiber column ( DHP-PMX ) in patients with acute lung injury or acute respiratory distress syndrome caused by sepsis . Method Thirty-six patients with sepsis were included . In each patient a thermodilution catheter was inserted , and the oxygen delivery index and oxygen consumption index were measured . DHP-PMX was performed in patients with a normal oxygen delivery index and oxygen consumption index ( > 500 ml/minute per m2 and > 120 ml/minute per m2 , respectively ) . The Acute Physiology and Chronic Health Evaluation II score was used as an index of the severity of sepsis , and survival was assessed after 1 month . The humoral mediators measured were the chemokine IL-8 , plasminogen activator inhibitor-1 , and neutrophil elastase ( NE ) . These mediators were measured before DHP-PMX treatment , and at 24 , 48 , and 78 hours after the start of treatment . The arterial oxygen tension (PaO2)/fractional inspired oxygen ( FiO2 ) ratio was measured before DHP-PMX treatment and at 24 , 48 , 72 , 92 , and 120 hours after the start of treatment . Results All patients remained alive after 1 month . Before DHP-PMX treatment , the Acute Physiology and Chronic Health Evaluation II score was 24 ± 2.0 , the IL-8 level was 54 ± 15.8 pg/ml , plasminogen activator inhibitor-1 was 133 ± 28.1 ng/ml , and NE was 418 ± 72.1 μg/l . These three humoral mediators began to decrease from 24 hours after DHP-PMX treatment , and the decline became significant from 48 hours onward . The PaO2/FiO2 ratio was 244 ± 26.3 before DHP-PMX treatment but improved significantly from 96 hours onward . There were significant negative correlations between the PaO2/FiO2 ratio and blood levels of NE and IL-8 . Conclusion The mechanism of action of DHP-PMX is still not fully understood , but we report the following findings . The mean blood levels of plasminogen activator inhibitor-1 , NE , and IL-8 were significantly decreased from 48 hours after DHP-PMX treatment . The mean PaO2/FiO2 ratio was significantly improved from 96 hours after DHP-PMX treatment . Improvement in the PaO2/FiO2 ratio appeared to be related to the decreases in blood NE and IL-8 levels Endotoxin plays an important role in the pathogenesis of septic shock . Exposure of endothelial cells to endotoxin activates endothelial cells and increases the surface expression of adhesion molecules , markers of endothelial damage in organ dysfunction . Endotoxin adsorption therapy by polymyxin B-immobilized fiber column ( PMX ) hemoperfusion has been used for the treatment of septic shock patients . In this study , we measured plasma concentrations of endotoxin and soluble adhesion molecules in septic shock patients before and after the PMX treatment then observed on the relationships between actual duration of use and various outcomes . Sixteen patients with septic shock were studied . The 28-day mortality rate was 50 % . The elevated plasma concentrations of endotoxin decreased after the PMX treatment in the survivors but not in the nonsurvivors . The norepinephrine dose and plasma concentrations of soluble endothelial leukocyte adhesion molecule 1 and soluble intercellular adhesion molecule 1 significantly ( P < 0.05 ) decreased in the PMX greater-than-2-h ( prolonged ) group than in the PMX 2-h ( conventional ) group ( −17.8 ± 14.6 vs. −1.8 ± 2.7 & mgr;g/min , −143.0 ± 111.0 vs. 0 ± 2.8 ng/mL , and −126.2 ± 144.9 vs. 16.5 ± 108.1 ng/mL , respectively ) . Changes in the PaO2-FiO2 ratio and the Sequential Organ Failure Assessment score were significantly ( P < 0.05 ) more improved in the PMX greater-than-2-h group than in the PMX 2-h group ( 75.4 ± 80.7 vs. 1.2 ± 49.2 and −0.8 ± 1.8 vs. 2.2 ± 1.9 torr , respectively ) . We thus suggest that a longer duration of PMX treatment may improve the pulmonary oxygenation associated with decreased adhesion molecules in septic shock Objective To analyze the effects of polymyxin B-immobilized fiber ( PMX-F ) on bone resorption in septic patients . Design and setting Observational prospect i ve study in intensive care units of a general hospital . Patients and participants 25 patients with severe sepsis and 20 healthy controls . Measurements and results Septic patients were r and omly assigned to two groups : PMX-F treatment group ( n=15 ) and conventional treatment group ( n=10 ) . Total pyridinium crosslink pyridinoline ( PYD ) and deoxypyridinoline ( DPD ) in urine were determined by modified high-performance liquid chromatography . Nitric oxide production was assessed by measuring the ratio of the nitric oxide breakdown products to urinary creatinine ( NOx/Cr ) . Plasma endotoxin levels were determined by endospecy test . The blood albumin , ionized calcium , and parathyroid hormone were also measured . PMX-F treatment was performed twice separated by 24 h. Urinary NOx/Cr , PYD/Cr , and DPD/Cr were significantly increased in septic patients compared with those in healthy controls . Blood ionized calcium in septic patients was lower than in healthy controls , while parathyroid hormone levels in septic patients were higher than in healthy controls ( P<0.01 ) . PMX-F treatment reduced plasma endotoxin , urinary NOx/Cr , PYD/Cr , DPD/Cr , and serum parathyroid hormone levels and increased blood ionized calcium significantly ; however , conventional treatment did not affect these levels . Conclusions Septic patients increased nitric oxide production and bone resorption , and PMX-F treatment is effective in reducing nitric oxide levels and bone resorption markers Endotoxin is an important pathogenic trigger for sepsis . The polymyxin B-immobilized endotoxin removal hemoperfusion cartridge , Toraymyxin ( hereafter PMX ) , has been shown to remove endotoxin in pre clinical and open-label clinical studies . In a multicenter , open-label , pilot , r and omized , controlled study conducted in the intensive care unit in six academic medical centers in Europe , 36 postsurgical patients with severe sepsis or septic shock secondary to intra-abdominal infection were r and omized to PMX treatment of 2 h ( n = 17 ) or st and ard therapy ( n = 19 ) . PMX was well tolerated and showed no significant side effects . There were no statistically significant differences in the change in endotoxin levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups . There was also no significant difference in the change in interleukin (IL)-6 levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups . Patients treated with PMX demonstrated significant increases in cardiac index ( CI ; P = 0.012 and 0.032 at days 1 and 2 , respectively ) , left ventricular stroke work index ( LVSWI , P = 0.015 at day 2 ) , and oxygen delivery index ( DO2I , P = 0.007 at day 2 ) compared with the controls . The need for continuous renal replacement therapy ( CRRT ) after study entry was reduced in the PMX group ( P = 0.043 ) . There was no significant difference between the groups in organ dysfunction as assessed by the Sequential Organ Failure Assessment ( SOFA ) scores from day 0 ( baseline ) to day 6 . Treatment using the PMX cartridge is safe and may improve cardiac and renal dysfunction due to sepsis or septic shock . Further studies are needed to prove this effectiveness Objective To test the hypothesis that extracorporeal therapy with polymyxin B ( PMX-B ) may prevent Gram-negative sepsis-induced acute renal failure ( ARF ) by reducing the activity of proapoptotic circulating factors . Setting Medical-Surgical Intensive Care Units . Patients and interventions Sixteen patients with Gram-negative sepsis were r and omized to receive st and ard care ( Surviving Sepsis Campaign guidelines ) or st and ard care plus extracorporeal therapy with PMX-B. Measurements and results Cell viability , apoptosis , polarity , morphogenesis , and epithelial integrity were evaluated in cultured tubular cells and glomerular podocytes incubated with plasma from patients of both groups . Renal function was evaluated as SOFA and RIFLE scores , proteinuria , and tubular enzymes . A significant decrease of plasma-induced proapoptotic activity was observed after PMX-B treatment on cultured renal cells . SOFA and RIFLE scores , proteinuria , and urine tubular enzymes were all significantly reduced after PMX-B treatment . Loss of plasma-induced polarity and permeability of cell cultures was abrogated with the plasma of patients treated with PMX-B. These results were associated to a preserved expression of molecules crucial for tubular and glomerular functional integrity . Conclusions Extracorporeal therapy with PMX-B reduces the proapoptotic activity of the plasma of septic patients on cultured renal cells . These data confirm the role of apoptosis in the development of sepsis-related ARF Objective : To find out whether polymyxin B-immobilized fiber ( PMX-F ) treatment affects the clinical parameters and plasma concentrations of erythropoietin ( EPO ) and interleukin (IL)-6 . Design : A prospect i ve case series study . Setting : Intensive care unit of the Department of Internal Medicine , Misato Junshin Hospital , Saitama , and Koto Hospital , Tokyo , Japan . Patients : 17 consecutive patients ( 10 men , 7 women ; mean age 54.6 years ) with clinical ly defined septic shock and 20 healthy volunteers ( 12 men , 8 women ; mean age 52.2 years ) . Main results : Of the 17 patients with septic shock , 9 ( 53 % ) survived . The systolic blood pressure increased significantly from 78 ± 6 to 106 ± 8 mm Hg 2 h after PMX-F treatment in patients with septic shock . Plasma endotoxin levels decreased significantly after treatment , from 40 ± 6 to 12 ± 4 pg/ml . The pretreatment plasma concentrations of EPO and IL-6 were significantly higher in the 8 nonsurviving patients with septic shock ( EPO : 400 ± 36 mlU/ml ; IL-6 : 6260 ± 1180 pg/ml ) than in the 9 surviving patients ( EPO : 120 ± 22 mlU/ml ; IL-6 : 680 ± 138 pg/ml ) and the 20 control subjects ( EPO , 12 ± 6 mlU/ml ; IL-6 , 8 ± 2 pg/ml ) . Plasma concentrations of EPO and IL-6 in patients with septic shock decreased significantly after PMX-F treatment ( EPO , nonsurviving : 320 ± 28 mlU/ml , p < 0.05 ; survivors : 26 ± 8 mlU/ml , p < 0.001 ; IL-6 , nonsurviving : 3860 ± 840 Output:	Polymyxin B-immobilized fiber column hemoperfusion adsorbed monocytes , activated neutrophils , and an and amide , as well as endotoxin through direct covalent bond , hydrophobic and ionic interactions , and hydrodynamics , and reduced the blood concentrations of inflammatory cytokines , plasminogen activator inhibitor 1 and adhesion molecules . Polymyxin B-immobilized fiber column hemoperfusion increased blood pressure and reduced the dosage requirements for vasopressive/inotropic agents . The meta- analysis showed that PMX treatment had beneficial effects on the hemodynamics , pulmonary oxygenation , and mortality . These beneficial effects may be attributable to the direct adsorption of endotoxin , monocytes , activated neutrophils , and an and amide , as well as indirect decrease in inflammatory cytokines and other mediators . Polymyxin B-immobilized fiber column hemoperfusion treatment has additional effects on reducing endothelial damage , proapoptotic activity , and immunosuppression .
MS21538	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We assessed the effectiveness of the home-visiting system in reducing the care provided in maternity units , especially hospitalization , and attempted to establish whether this system increases women 's satisfaction with medical care . The trial involved 158 women and was conducted in four maternity units in Paris . A policy of one or two weekly visits by domiciliary midwives was compared with the usual policy of the hospitals . The study was restricted to women with moderate threatened preterm labor between 26 and 36 weeks of gestation . No decrease in the number of women hospitalized or the number of days spent in hospital was observed in the intervention group , but the number of prenatal visits to outpatient clinics was significantly smaller in the intervention than control group . Satisfaction with medical care during the episode of threatened preterm labor was much greater in the intervention group . Home visits by a midwife were considered by the women to be a better care system than numerous outpatient visits or hospitalization . Our results for medical care suggest that the introduction of the home-visiting system did not greatly alter medical practice in the maternity units , although this system had been design ed to avoid or reduce hospitalization The relative contribution of uterine activity obtained by home monitoring with a guard ring tocodynamometer compared with seven specific signs and symptoms reported during patient/nurse contact as an aid in detecting preterm labor has not been studied . In this prospect i ve , multicenter study , patients at risk for developing early labor who were r and omized to receive home uterine activity monitoring and perinatal nursing support were assessed . The initiator of provider contact ( uterine activity detected on routine transmission , patient-perceived signs and symptoms of preterm labor during perinatal nurse contact , or both ) result ing in a diagnosis of preterm labor was recorded . Contraction data were then analyzed for an association with preterm labor . There was a strong association of increased uterine activity ( four or more contractions per hour ) on a repeat monitoring strip with preterm labor ( P<.001 ) . Among patients diagnosed with preterm labor , 31 % had increased uterine activity detected on a routine transmission without patient reported signs and symptoms , compared with 24 % who were diagnosed as the result of patient-reported symptoms without increased uterine activity . Daily objective uterine activity data alone have greater incremental value over and above other signs and symptoms as an aid to the physician in diagnosing preterm We conducted a health technology assessment of the care of women with high-risk pregnancies in the South Wales valleys . Women in the control arm were intended to receive conventional care with st and ard midwifery visits . Women in the intervention arm received additional or longer visits and domiciliary fetal heart rate telemonitoring . Eighty-one mothers were r and omized . There were significant differences in midwifery intervention re sources between domiciliary and control groups , with the former receiving a mean of 3.7 visits lasting 33.5 min , compared with 1.4 visits lasting 12.8 min for the latter . There were slightly more spontaneous labours and fewer Caesarean sections in the domiciliary group . Maternal satisfaction and anxiety were high in both groups . Domiciliary care increased the service costs by 21.02 per woman in terms of extra midwife travel and visiting time , and by a further £ 18.38 per woman in home monitoring equipment costs . This , however , was more than offset by health service savings from fewer clinic visits ( £ 35.60 ) and fewer clinic ultrasound scans ( £ 9.01 ) . Adding the reductions in lost productivity to women and their partners ( £ 34.51 ) suggests that domiciliary care was cheaper than conventional care , even if it did not greatly reduce inpatient days ( a reduction nonetheless saving £ 184.24 ) . While clinical processes were similar in both groups , there were useful practical advantages and savings for patients and the health service from the domiciliary intervention BACKGROUND The measurement of the frequency of uterine contractions has not been useful for reducing the rate of preterm delivery in r and omized trials . Nonetheless , ambulatory monitoring of contractions continues to be used in clinical practice . METHODS We assessed the frequency of uterine contractions as a predictor of the risk of spontaneous preterm delivery before 35 weeks of gestation . We enrolled women with singleton pregnancies between 22 and 24 weeks of gestation . The women used a contraction monitor at home to record contraction frequency twice daily on 2 or more days per week from enrollment to delivery or 37 weeks of gestation . RESULTS We obtained 34,908 hours of successful monitoring recordings from 306 women . Although more contractions were recorded from women who delivered before 35 weeks than from women who delivered at 35 weeks or later , we could identify no threshold frequency that effectively identified women who delivered preterm infants . The sensitivity and positive predictive value of a maximal hourly frequency of contractions of four or more between 4 p.m. and 3:59 a.m. were 9 percent and 25 percent , respectively , at 22 to 24 weeks and 28 percent and 23 percent at 27 to 28 weeks . Other proposed screening tests , such as digital and ultrasound evaluations of the cervix and assays for fetal fibronectin in cervicovaginal secretions , also had low sensitivity and positive predictive value for preterm labor . CONCLUSIONS Although the likelihood of preterm delivery increases with an increased frequency of uterine contractions , measurement of this frequency is not clinical ly useful for predicting preterm delivery In this investigation , 45 women with twin gestations in four centers were r and omly assigned to either daily home uterine activity monitoring and perinatal nursing support ( 19 ) or an education group ( 26 ) . Patients in the home uterine activity monitoring and perinatal nursing support group monitored uterine activity twice daily , transmitted the data each day , and had 24 hour-a-day access to nursing support . Education patients were counseled regarding the common signs and symptoms of preterm labor . Both groups had scheduled prenatal visits at least every 2 weeks . Sixteen ( 62 % ) of the education group and 14 ( 74 % ) of the home uterine activity monitoring and perinatal nursing support group developed preterm labor , values that were not significantly different . Of the monitored group who experienced preterm labor , all 14 were dilated 3 cm or less at diagnosis of the first preterm labor , compared with ten of 16 in the education group ( P= .01 ; one-tailed Fisher test ) . The mean cervical dilatation at the first preterm labor episode in the group receiving daily monitoring and contact ( 1.6 cm ) was significantly less ( P= .01 ) than that in the education group ( 2.9 cm ) . Thus , fewer preterm births were recorded in the home uterine activity monitoring and perinatal nursing support group and significantly fewer patients delivered because of tocolysisfailed(P= .03 BACKGROUND Preterm labour occurs in about 10 % of all pregnancies and is the most important cause of premature birth . Women with preterm labour are admitted to hospital to have the contractions stopped . Thereafter , many women remain in hospital until delivery . We conducted a r and omized clinical trial to compare hospital care with home care of women who had been admitted to hospital for preterm labour . METHODS After they had received treatment for an acute episode of premature labour , women at 2 regional perinatal centres associated with teaching hospitals were r and omly assigned to home care or hospital care . Eligible women ( n = 250 ) were aged 18 years or older , lived within 50 km of the hospital , had a gestational age between 20 and 35 weeks , had no prior preterm delivery and were experiencing their first episode of preterm labour and first admission to hospital for preterm labour . Analysis was by intention to treat . RESULTS There were no significant differences between the 2 groups in mean gestational age at delivery ( home : 37.52 weeks , hospital : 37.50 weeks ) or in mean birth weight ( home : 2974 g , hospital : 3020 g ) . There were no significant differences between the 2 groups with respect to the proportions of babies born before term or the mean duration of neonatal hospital stay , neonatal intensive care unit stay and intermediate care nursery stay . The mean duration of the first stay in hospital for the women in the home group ( 3.8 days ) was significantly shorter than the mean duration for women in the hospital group ( 6.1 days ) . In addition , the mean duration of all maternal stays in hospital was significantly shorter for the women in the home group ( 3.7 days ) than in the hospital group ( 5.0 days ) . INTERPRETATION Home care management is an efficient and acceptable alternative to hospital care for women experiencing preterm labour In a prospect i ve trial we enrolled 157 women at increased risk of preterm birth , r and omly assigning women in a ratio of 1:2 to receive either frequent ( greater than or equal to 5 days/wk ) nursing contact , education in preterm labor symptoms , and self-palpation of uterine activity ( group E , n = 50 ) , or daily nursing contact , preterm labor education , and the Term Guard home uterine activity monitor ( group EM , n = 107 ) . Comparison of the rate of preterm birth , the incidence of preterm labor and successful tocolysis , and the mean birth weight and gestational age revealed no significant differences and suggested that beneficial effects previously attributed to monitored contraction data may in fact be the result of frequent ( five or more times per week ) nursing contact and careful attention to preterm labor symptoms and perceived contractions Home uterine activity monitoring has been described as an effective means of detecting uterine contractions , but controversy exists whether it is home uterine activity monitoring or increased nursing support in conjunction with it that contributes to earlier detection of preterm labor . In this study 377 women at risk for preterm labor from three centers were prospect ively , r and omly assigned to high-risk prenatal care alone ( not monitored ) or to the same care with twice-daily home uterine activity monitoring without increased nursing support ( monitored ) . The two groups were medically and demographically similar at entry into the study . Routine visits , nonroutine visits , and gestational age at diagnosis of preterm labor were similar in both groups . Preterm labor occurred in 41 of 198 monitored and 39 of 179 not monitored patients . Mean cervical dilatation was 1.4 cm in 41 monitored compared with 2.5 cm for 37 not monitored ( p = 0.0006 ) ; 73.1 % of monitored and 27.5 % of not monitored had preterm labor detected before 2 cm dilatation ( p = 0.00009 ) . Neonatal outcome of singleton pregnancies showed greater birth weight , fewer days in the neonatal intensive care unit , and fewer babies requiring oxygen therapy and mechanical ventilation in the monitored group . The better outcomes are probably due to the increased likelihood of diagnosis of preterm labor before advanced cervical dilatation with home uterine activity monitoring , thus providing the clinician with a better chance to initiate tocolytic therapy directed at improving pregnancy outcome OBJECTIVE To compare safety and cost-effectiveness of domiciliary antenatal fetal monitoring ( cardiotocography and obstetric surveillance ) with in-hospital monitoring in high-risk pregnancies . METHODS From September 1992 to June 1994 , 150 consecutive women with high-risk pregnancies , who would otherwise be monitored in the hospital , entered a r and omized controlled trial of in-hospital ( n = 74 ) or domiciliary ( n = 76 ) monitoring . The main outcome measures were neonatal safety ( Prechtl neurologic optimality score , the proportion of non-optimals ) and cost-effectiveness . To test a two-point difference in mean Prechtl scores ( two-tailed o = .05 . 1-beta = .80 ) , 150 women were needed . Safety and cost-effectiveness were analyzed according to intention to treat . Conditional on the safety outcomes , a cost-minimization analysis based on actual re source use was performed . Uncertainty of results was explored by sensitivity analyses . RESULTS Neonatal outcomes were equal . No cost-shifting between the antenatal and postpartum period occurred . Substituting domiciliary for in-hospital monitoring reduced mean ( st and ard deviation ) antenatal costs from $ 3558 ( $ 2841 ) to $ 1521 ( $ 1459 ) per woman ( P < .001 ) . If costs were varied by the addition of 50 % , costs were still reduced . The magnitude of the reduction was sensitive to the costs of hospital care and less sensitive to the costs of domiciliary monitoring . CONCLUSION Domiciliary monitoring is safe and reduces costs by one-half . The technique seems transferable to other setting s but local circumstances may sometimes hamper its dissemination OBJECTIVE Is domiciliary antenatal fetal surveillance for selected high risk pregnancies , a feasible alternative for hospital admission ? DESIGN A r and omized controlled trial conducted at the Academical Medical Centre , Amsterdam , The Netherl and s. SUBJECTS Between September 1992 and June 1994 , 76 women were at r and om allocated to domiciliary care and 74 women to hospital care . Criteria for inclusion were hypertension ( 26 % ) , fetal growth retardation ( 24 % ) , post term pregnancy ( 23 % ) , diabetes ( 24 % ) , preterm rupture of membranes ( 2 % ) and previous recurrent antenatal death ( 1 % ) . MAIN OUTCOME MEASURES Primary outcome measure was perinatal morbidity , measured by Prechtl 's neonatal neurological optimality score . Secondary outcome variables were the occurrence of complications , obstetric interventions at labour , birthweight , gestational age at delivery and maternal and neonatal admission rates . RESULTS In both groups there was one case of perinatal mortality . In both treatment groups the median of the neurological optimality score was found at 59 . Also secondary outcome variables did not show significant differences . CONCLUS Output:	Important group differences were not evident when we undertook sensitivity analysis using only trials at low risk of bias . There is no impact on maternal and perinatal outcomes such as perinatal mortality or incidence of preterm birth
MS21539	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Antral biopsy specimens from 89 consecutive patients with nonulcer dyspepsia and erosive prepyloric changes included in a prospect i ve , r and omized , double-blind 4-wk study of the effect of an aluminum-magnesium antacid ( 120 mmol/day ) or pirenzepine ( 50 mg b.i.d . ) vs. placebo were examined histologically . Campylobacter pylori ( CP ) was found by light microscopy of silver-stained sections in 25 patients ( 28 % ) . Campylobacter pylori-positive patients were on average older than CP-negative patients ( p = 0.02 ) . There was a strong association between CP colonization and acute inflammation ( p less than 0.001 ) , both being rare in the absence of chronic inflammation . During treatment with antacids , the density of CP decreased ( p less than 0.001 ) without any improvement of the inflammatory reaction . On the contrary , the number of patients with gastritis tended to increase after antacids as compared with placebo ( p less than 0.10 ) . A separate analysis showed no symptomatic effect of the drugs . Thus , neither nonulcer dyspepsia nor erosive prepyloric changes are strongly associated with antral CP colonization or acute inflammation . Aluminum-magnesium antacids may suppress antral CP infection without healing the gastritis or relieving symptoms The aim of this study was to determine the effect of colloidal bismuth subcitrate ( De Nol ) on symptoms and gastric histology in patients with non-ulcer dyspepsia . In a single centre trial , patients with food related upper abdominal pain not caused by ulcer disease were r and omised to receive one tablet of colloidal bismuth subcitrate or matching placebo four times daily for eight weeks . Seventy three patients were entered and 51 completed the trial : 28 patients in the colloidal bismuth subcitrate group and 23 in the placebo group . Overall there was no difference between the two groups in terms of symptom relief . Among patients with histological gastritis ( n = 23 ) , however , those who took colloidal bismuth subcitrate used fewer antacid tablets ( for three of four fortnightly periods ) and were more likely to become asymptomatic ( eight of 11 v three of 12 , p less than 0.05 ) ; their gastritis was more likely to resolve ( five of 10 v 0 of 12 , p less than 0.025 ) and their gastric biopsies more likely to become negative for Helicobacter like organisms ( eight of nine v 0 of 12 , p less than 0.001 ) when compared with patients taking placebo . In contrast , patients who did not have gastritis in their index biopsies ( n = 28 ) fared similarly whether they received colloidal bismuth subcitrate or placebo . Our results indicate that the administration of colloidal bismuth subcitrate benefited non-ulcer dyspepsia patients with gastritis but had no effect on those without Duodenal biopsy specimens from 471 adults and 47 children were examined to determine the prevalence and distribution of gastric epithelium in the duodenal bulb in relation to age , gender , gastroduodenal inflammation , smoking , alcohol and consumption of nonsteroidal anti-inflammatory drugs ( NSAID ) . Gastric metaplasia was present in the anterior wall duodenal biopsy specimen in 31 % , was significantly less common in patients under 17 than in adults , and was more common in males than females . In sixty two adults who underwent multiple radial duodenal biopsy gastric metaplasia was r and omly distributed around the duodenal circumference ; sixty three per cent of the patients with gastric metaplasia found on multiple biopsy were detected by just the anterior biopsy . Gastric metaplasia was not obviously associated with alcohol , cigarette , or NSAID consumption . While the presence of gastric metaplasia was associated with adulthood , male sex , and low fasting gastric juice pH , its extent was associated with active duodenitis and Helicobacter-associated gastritis . On logistic regression , gastric metaplasia in the duodenum and gastric Helicobacter pylori were independent predictors of active duodenitis , but were not significantly associated with inactive duodenal inflammation . H pylori was observed in duodenal biopsy specimens from 32 patients , all with active duodenitis ; bacteria were present only on foci of gastric metaplasia , and were more likely to be seen when the metaplasia was extensive . It is proposed that inflammatory injury to the duodenal mucosa by H pylori may stimulate the development of further gastric metaplasia , and that the area of duodenum susceptible to colonisation with H pylori may therefore increase progressively until mucosal integrity is compromised and ulceration supervenes BACKGROUND The efficacy of anti-Helicobacter pylori treatment and cytoprotective drugs in H. pylori-positive and -negative non-ulcer dyspepsia ( NUD ) , respectively , is debatable . METHODS In a r and omized study , the efficacy of anti-H. pylori treatment versus sucralphate was tested in patients with NUD . One hundred and twelve patients with NUD , 62 positive and 50 negative for H. pylori were studied . Of 62 patients positive for H. pylori , 32 were treated with triple therapy ( colloidal bismuth subcitrate , tetracycline and metronidazole ) for 2 weeks and the remaining 30 were treated with sucralphate ( 1 g , q.i.d . ) for 4 weeks . Of 50 patients negative for H. pylori , 25 each were treated with either sucralphate ( 1 g , q.i.d . ) or ranitidine ( 150 mg , b.d . ) for 4 weeks . RESULTS In patients with NUD and H. pylori infection , triple therapy eradicated H. pylori in 88 % and was superior to sucralphate in producing symptom relief ( 81 vs 33 % , P = 0.0003 ) and histological improvement in gastritis ( 73 vs 30 % , P = 0.003 ) . In the H. pylori-negative group , sucralphate was superior to ranitidine with regard to symptom relief ( 68 vs 36 % , P = 0.04 ) and improvement in gastritis ( 44 vs 12 % , P = 0.09 ) . The symptomatic improvement persisted until 12 weeks after the start of treatment in triple therapy group only . CONCLUSIONS In patients with NUD associated with H. pylori , triple therapy was better than sucralphate in terms of symptomatic and histological improvement . However , sucralphate was superior to ranitidine in providing symptom relief in patients with H. pylori-negative NUD This study investigated the effect of colloidal bismuth subcitrate and cimetidine on Campylobacter pylori in peptic disease . In 74 % of 135 patients with peptic disease diagnosed at endoscopy C pylori was detected before treatment . Compared with cimetidine , colloidal bismuth subcitrate significantly decreased the incidence of C pylori after six weeks of treatment ( p less than 0.001 ) . In the colloidal bismuth subcitrate group , subsequent healing of the lesion was correlated with the clearance of C pylori , unlike in the cimetidine group . C pylori was strongly associated with the presence of histological gastritis , which was decreased by colloidal bismuth subcitrate ( p less than 0.001 ) Gastritis caused byHelicobacter pylori ( HP ) is common in patients with nonulcer dyspepsia ( NUD ) , but an etiologic relationship between the histologic lesion and clinical symptoms is unproven . HP is inhibited by bismuth subsalicylate ( BSS ) , a traditional remedy for dyspeptic complaints . The aim of this study was to assess the short- and long-term effects of BSS on HP , gastritis , and symptoms in patients with NUD . One hundred twenty-six patients with NUD who were shown to be infected withH. pylori ( HP+ ) were enrolled . There was a two-week placebo run-in period to eliminate placebo responders . Fifty patients remained symptomatic and were r and omly assigned to therapy with either BSS liquid or a matching placebo . EGD , biopsy , and clinical evaluations were performed at entry , at week 5 ( end of therapy ) , at week 9 ( four weeks after therapy ) , or at time of symptomatic relapse . Twenty-seven patients received placebo and 23 patients received BSS . BSS suppressedH. pylori in 15/23 patients ( 65 % ) and eradicated it in one patient , whereas the placebo had no effect onH. pylori . Gastritis improved during therapy with BSS but relapsed by week 9 . There was no significant change in level of dyspeptic symptoms during or after treatment , although one month after the end of treatment , the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured . The study confirms that BSS given for three weeks suppresses but does not usually eradicateH. pylori . Such short-term suppression ofH. pylori heals gastritis but does not result in clinical improvement We conducted a 12-week , double-blind , r and omized , placebo-controlled trial to determine whether cimetidine ( 300 mg with meals and at bedtime ) or a convenient , liquid aluminum-magnesium antacid regimen ( 15 ml one hour after meals and at bedtime ) would expedite healing or relief of symptoms in patients with benign gastric ulcer . Of the 101 patients who completed the trial according to protocol , 32 received the antacid , 36 cimetidine , and 33 placebo . At 4 , 8 , and 12 weeks after entry , ulcers had healed in a larger percentage of patients treated with cimetidine than of those treated with placebo : 53 , 86 , and 89 per cent of the cimetidine group versus 26 , 58 , and 70 per cent of the placebo group ( P = 0.02 , 0.01 , 0.05 ) , respectively . Healing at the three intervals had occurred in 38 , 70 , and 84 per cent , respectively , of the antacid-treated patients . Neither cimetidine nor antacid was more effective than placebo in relieving symptoms . The presence or absence of symptoms during the fourth and eighth treatment weeks was a poor predictor of the presence of absence of an ulcer crater . We conclude that cimetidine significantly hastens the healing of benign gastric ulcer Non-ulcer dyspepsia ( NUD ) is a common complaint in which no systematic illness or organic proximal alimentary tract disease can be identified . The pathophysiology of NUD is probably heterogeneous . Eighty-two subjects with NUD were studied in a prospect i ve r and omized placebo-controlled study to assess the efficacy of colloidal bismuth subcitrate ( CBS ) chewable tablets at a dose of four tablets daily for 1 month . The role of Campylobacter pylori and associated histological gastritis was evaluated . Sixty-one percent of NUD patients had C. pylori in the gastric antrum compared with 25 % of age-matched controls . C. pylori was associated with acute and chronic inflammation ( P less than 0.001 ) in the antrum . C. pylori was cleared in 59 % of CBS-treated subjects compared with only 4 % placebo ( P less than 0.05 ) . Both acute and chronic inflammation improved in subjects cleared of bacteria . Clearance of C. pylori and histological improvement was associated with a significant decrease in symptoms . In C. pylori negative subjects improvement in symptoms occurred in both the placebo and active treatment groups . This study would suggest that C. pylori and associated histological gastritis may play a role in non-ulcer dyspepsia The association of Helicobacter pylori and functional dyspepsia is not well defined . The role of H.pylori on dyspeptic symptoms is still controversial . The aim of this study is to confirm the efficacy of H. pylori eradication by two differentcommonly used treatment regimens , as well as to examinethe improvement of the dyspeptic symptoms by eradicatingH. pylori . H. pylori functional dyspepsia is prevalent in people over 60 years old . In this age groupwe treated 126 patients with bismuth plus metronidazole and amoxicillin ( group A , 67 patients ) versus omeprazoleplus amoxicillin ( group B , 59 patients ) . Results were statistically analyzed utilizing theWilcoxon signed-rank test , McNemer test and chi-squaretest ; P < 0.05 was considered significant . Two monthsafter the end of therapy we observed an eradication rate of 66.1 % in group A vs 64.3 % in group B.All treated patients showed improvement insymptomatology . Although there was no significantdifference between patients in whom H. pylori was or wasnot eradicated within the respective groups , when examiningall H. pylori-positive patients versus H.pylori-negative posttreatment patients , there was asignificant reduction ( P < 0.05 ) in all four symptomsof functional dyspepsia measured . In conclusion , we suggestthat patients treated with H. pylori-eradicatingtherapeutic regimens have an improvement in functionaldyspepsia sympt Output:	These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia . REVIEW ER 'S CONCLUSIONS H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia .
MS21540	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS Routine catheterization following vaginal prolapse surgery has advantages like prevention of postoperative retention of urine and prevention of any adverse effect on surgical outcome . However , it increases the risk of urinary tract infection ( UTI ) , prevent early ambulation and prolong hospital stay . This r and omized controlled trial was done on how best to minimize catheter related complication after prolapse surgery . METHODS 200 patients planned for vaginal prolapse surgery were recruited and r and omized into two groups . In group I and group II catheter was removed on 1(st ) and 4(th ) post operative day , respectively . After removal , if patient could not void or when residual urine volume exceeds 150 mL , recatheterisation was done for another three days . Sample of urine was sent for culture during catheter removal . RESULTS Age , parity , type of surgery and mean operation time did not differ significantly between the two groups . Mean duration of catheterization was significantly shorter ( 1.64 vs 4.09 ) and mean duration of hospital stay was shorter by 1.2 days , in first group . However a significantly higher number of retention of urine or residual urine more than 150 mL was found in the early removal group ( OR 3.10 ) but lesser chance of development of urinary tract infection ( OR 0.10 ) . CONCLUSIONS The early removal of catheter seems more advantageous , with lower incidence of urinary tract infection and a shorter hospital stay although associated with an increased risk of recatheterisation OBJECTIVE It is unclear if any catheterisation is necessary after vaginal surgery for pelvic organ prolapse . The aim of this study was to determine if indwelling catheterisation is necessary after these procedures . STUDY DESIGN A r and omised controlled trial of immediate post-operative removal of catheter compared to a suprapubic catheter ( SPC ) after vaginal prolapse surgery . In the Suprapubic group the catheter was left on free drainage until a voiding trial was commenced at 48h . Women in the immediate removal group underwent in/out catheterisation only if they had not voided by 8h after surgery to ensure the bladder did not over-distend . RESULTS 55 % ( n=17 ) of patients in the immediate removal group did not require catheterisation postoperatively . A further 13 ( 42 % ) patients only required one in/out catheterisation 8h post operatively . In the immediate removal group duration of catheterisation was significantly shorter ( median 0h , IQR 0 - 8h , range 0 - 16h ) vs ( 6days ( IQR 2 - 8days , range 2 - 19h ) p=0.001 ) . The duration of hospital stay ( 7days ( range 3 - 16 ) vs. 9 ( range 3 - 27 ) p=0.014 ) , day of first mobilisation ( Day 1 , range 0 - 2 , vs. Day 2 , range 1 - 4 , p=0.001 ) , and rate of Symptomatic bacturia ( 16 % vs. 52 % , p<0.01 ) were all significantly better with immediate catheter removal . CONCLUSIONS After vaginal surgery for pelvic organ prolapse , the majority of patients do not require extended catheterisation . Early removal of a catheter reduces urinary tract infection and significantly decreases hospital stay . Such a policy should result in improved patient satisfaction and reduced hospital costs Introduction and hypothesisThe purpose was to determine if pre-operative guided imagery ( GIM ) would help women to feel more prepared , less anxious , and have higher satisfaction scores 6 weeks after surgery compared with routine care . Methods Eligible women planning to undergo pelvic floor surgery were enrolled and r and omized . The GIM group received an institution-specific CD that uses GIM to detail day of surgery ( DOS ) events and expectations . Participants were asked to listen to the CD once daily during the week before surgery . At three time points ( surgical consent visit , DOS , and 6-weeks post-operatively ) , we measured anxiety using the State and Trait Anxiety Inventory for Adults ( STADI ) , in addition to preparedness for surgery and overall satisfaction ( ten-point Likert scales ) . Data were analyzed in SPSS 23 using two-tailed t tests . Results A total of 38 out of 44 ( 86 % ) enrolled participants completed the study ( GIM : 18 , control : 20 ) . The GIM self-reported compliance rate was 72 % , with an average use of 4.8 times ( range = 3–8 times ) . Women in the GIM group reported a significant increase from baseline in preparedness for surgery on both DOS and 6 weeks post-operatively ( 7.32 ± 1.81 vs 9.11 ± 1.13 , p = 0.001 ) and ( 7.32 ± 1.81 vs 9.22 ± 0.81 , p = 0.001 ) respectively ; a change that was not seen in the control group . Satisfaction was high in both the GIM and the control group ( 9.55 ± 0.85 and 9.05 ± 1.70 , p = 0.263 ) . In all patients , anxiety increased from baseline to DOS and dropped at 6 weeks post-operatively , and was not significantly different in the two groups . Conclusions Guided imagery improved patient preparedness for pelvic floor surgery with an overnight stay on their DOS and 6 weeks post-operatively Introduction and hypothesisThe aim of this study was to compare the number of temporary catheter replacements and urinary tract infections after indwelling catheterization for 2 versus 5 days following an anterior colporrhaphy . Methods Two hundred forty-six patients were r and omly assigned to 2 or 5 days of indwelling catheterization . Outcome measures were temporary catheter replacements because of post-voiding residual > 200 mL after removal of the indwelling catheter , urinary tract infections , and hospital stay . All patients were analyzed according to the intention to treat principle . Results Compared to the 5-day protocol group , in the 2-day protocol group more patients needed temporary catheter replacement ( 9 % versus 28 % , odds ratio ( OR ) 4.0 , confidence interval ( CI ) 1.9–8.3 , p < 0.01 ) , whereas less patients had a urinary tract infection ( 37 % versus 22 % , OR 0.5 , CI 0.3–0.9 , p = 0.02 ) and median hospital stay was lower . Conclusions Removal of an indwelling catheter after 2 versus 5 days following anterior colporrhaphy is associated with more temporary catheter replacements , but less urinary tract infections and a shorter hospital stay Introduction and hypothesisThere is evidence that in nonsurgical population s , pelvic floor muscle training ( PFMT ) and lifestyle advice improves symptoms and stage of pelvic organ prolapse ( POP ) . Some women , however , require surgery , after which de novo symptoms can develop or additional surgery is required due to recurrence . Robust evidence is required as to the benefit of perioperative PFMT in the postsurgery reduction of symptoms and POP recurrence . The aim of this study was to assess the feasibility of and collect pilot data to inform sample size ( SS ) calculation for a multicentre r and omised controlled trial ( RCT ) of perioperative PFMT following surgical intervention for POP . Methods Fifty-seven participants were recruited and r and omised to a treatment group ( one pre and six postoperative PFMT sessions ) or a control group ( usual care ) . The primary outcome measure was the Pelvic Organ Prolapse Symptom Score ( POP-SS ) at 12 months ; secondary outcome measures included measurement of prolapse , the pelvic floor and question naires relating to urinary and bowel incontinence . All outcomes were measured at 0 , 6 and 12 months . Results Information on recruitment , retention and appropriateness of outcome measures for a definitive trial was gathered , and data enabled us to undertake an SS calculation . When compared with the control group ( n = 29 ) , benefits to the intervention group ( n = 28 ) were observed in terms of fewer prolapse symptoms at 12 months [ mean difference 3.94 ; 95 % confidence interval ( CI ) 1.35–6.75 ; t = 3.24 , p = 0.006 ] ; however , these results must be viewed with caution due to possible selection bias . Conclusion With modifications to design identified in this pilot study , a multicentre RCT is feasible Objective To evaluate the use and effect of early administration of vaginal estrogen via a continuous low-dose estradiol vaginal ring placed immediately after pelvic reconstructive surgery . Methods This was a r and omized controlled trial of 65 postmenopausal women undergoing vaginal reconstructive surgery . The subjects were r and omly assigned to receive an estradiol-releasing vaginal ring , placebo vaginal ring , or control without vaginal ring for 12 weeks immediately after vaginal reconstructive surgery . The primary outcome was tissue quality based on vaginal maturation 3 months postoperatively . Secondary outcome measures were subjective and objective signs of atrophy ; vaginal pH ; the presence of granulation tissue , microscopic inflammation , and major healing abnormalities ; and the ability to tolerate an intravaginal ring . Results At 12 weeks , the estradiol ring group had a significantly improved maturation value ( P<0.01 ) and objective atrophy assessment ( P<0.01 ) compared with the placebo ring and control arms . Granulation tissue was increased in the placebo ring arm ( P<0.01 ) . Subjective atrophy scores did not differ among the groups ( P=0.39 ) . Conclusions Early administration of vaginal estrogen after vaginal surgery via an estradiol-releasing ring is feasible and results in improved markers of tissue quality postoperatively compared to placebo and controls OBJECTIVE : To compare surgeons ' intraoperative surgeon acceptability or assessment of the operative field regarding bowel contents and patients ' satisfaction with or without a mechanical bowel preparation before reconstructive vaginal prolapse surgery . METHODS : In this single-blind , r and omized trial , women scheduled to undergo vaginal prolapse surgery with a planned apical suspension and posterior colporrhaphy were allocated using block r and omization to an intervention or control group . Surgeons were blinded to patient allocation . One day before surgery , mechanical bowel preparation instructions consisted of a clear liquid diet and two self-administered saline enemas ; the participants in the control group sustained a regular diet and nothing by mouth after midnight . The primary outcome was surgeons ' intraoperative assessment of the surgical field regarding bowel content as measured on a 4-point Likert scale ( 1 , excellent ; 4 , poor ) . Secondary outcomes included participant satisfaction and bowel symptoms . The primary outcome was determined by intention-to-treat analysis and other analyses were per protocol . RESULTS : Of the 150 women r and omized ( 75 women to intervention and control group ) , 145 completed the study . No differences existed in the demographic , clinical , and intraoperative characteristics between groups ( P>.05 ) . Surgeons ' intraoperative assessment rating was 85 % “ excellent or good ” with bowel preparation compared with 90 % for participants in the control group ( odds ratio [ OR ] 0.59 , 95 % confidence interval [ CI ] 0.21–1.61 ; P=.30 ) . The bowel preparation group was less likely to report “ complete ” satisfaction compared with the participants in the control group ( OR 0.11 , 95 % CI 0.04–0.35 ; P<.001 ) . Abdominal fullness and cramping , fatigue , anal irritation , and hunger pains were greater in the bowel preparation group ( all P<.01 ) . CONCLUSION : Before reconstructive vaginal surgery , mechanical bowel preparation conferred no benefit regarding surgeons ' intraoperative assessment of the operative field , reflected decreased patient satisfaction , and had increased abdominal symptoms . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT01431040 . LEVEL OF EVIDENCE : Introduction and hypothesisHydrodissection incorporating different types of vasoconstrictors is commonly used in vaginal prolapse surgery . There is little evidence as to whether it adds clinical value or whether it exposes the patient to unnecessary risk . The aim of this study was to compare the effect of a vasoconstrictor compared with saline alone on operative blood loss and cardiovascular parameters in a r and omised clinical trial setting . Methods Patients undergoing vaginal prolapse surgery were r and omised to an ornipressin ( Por-8 , Ferring ) solution or saline alone for hydrodissection . The surgeon and patient were blinded to the solution used . Operative blood loss was accurately quantified and blood pressure and pulse readings recorded Pre , intra- and postoperatively . Results Eighty women were r and omised . There was a statistically significant difference in the median blood loss : 35 ml ( 1 - 209 ml ) in the ornipressin group compared with 81 ml ( 2 - 328 ml ) in the saline group , p = 0.03 . There was no statistically significant difference in the median pre and postoperative blood pressure or pulse rate between groups . Conclusions The use of a vasoconstrictor ( ornipressin ) result ed in a statistically significant decrease in operative blood loss during vaginal prolapse surgery . This occurred without any significant changes in measured cardiovascular parameters INTRODUCTION This assessor-blinded r and omized controlled trial investigated the effect of a pre- and post-operative physiotherapy-supervised pelvic floor muscle ( PFM ) training program in women Output:	With regard to other interventions ( preoperative bowel preparation and injection of vasoconstrictor agent , ureteral stent placement during uterosacral ligament suspension , postoperative vaginal pack insertion , use of vaginal dilators , prophylactic antibiotics for postoperative catheter care ) , we found no evidence regarding rates of recurrent prolapse and no clear evidence that these interventions were associated with clinical ly meaningful reductions in adverse effects , such as intraoperative or postoperative blood transfusion , intraoperative ureteral injury , or postoperative urinary tract infection
MS21541	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aims To assess whether associations between maternal smoking during pregnancy and offspring smoking initiation are due to intrauterine mechanisms . Design Comparison of associations of maternal and partner smoking behaviour during pregnancy with offspring smoking initiation using partner smoking as a negative control ( n = 6484 ) and a Mendelian r and omization analysis ( n = 1020 ) , using a genetic variant in the mothers as a proxy for smoking cessation during pregnancy . Setting A longitudinal birth cohort in South West Engl and . Participants Participants of the Avon Longitudinal Study of Parents and Children ( ALSPAC ) . Measurements Smoking status during pregnancy was self-reported by mother and partner in question naires administered at pregnancy . Latent classes of offspring smoking initiation ( non-smokers , experimenters , late-onset regular smokers and early-onset regular smokers ) were previously developed from question naires administered at 14–16 years . A genetic variant , rs1051730 , was genotyped in the mothers . Findings Both mother and partner smoking were similarly positively associated with offspring smoking initiation classes , even after adjustment for confounders . Odds ratios ( OR ) [ 95 % confidence interval ( CI ) ] for class membership compared with non-smokers were : experimenters : mother OR = 1.33 ( 95 % CI = 1.06 , 1.67 ) , partner OR = 1.28 ( 95 % CI = 1.06 , 1.55 ) , late-onset regular smokers : mother OR = 1.80 ( 95 % CI = 1.43 , 2.26 ) , partner OR = 1.86 ( 95 % CI = 1.52 , 2.28 ) and early-onset regular smokers : mother OR = 2.89 ( 95 % CI = 2.12 , 3.94 ) , partner OR = 2.50 ( 95 % CI = 1.85 , 3.37 ) . There was no clear evidence for a dose – response effect of either mother or partner smoking heaviness on class membership . Maternal rs1051730 genotype was not clearly associated with offspring smoking initiation class in pre-pregnancy smokers ( P = 0.35 ) . Conclusion The association between smoking during pregnancy and offspring smoking initiation does not appear to operate through intrauterine mechanisms Background : Nicotine replacement therapy ( NRT ) helps smokers quit smoking , but trials indicate that there is no evidence that it is effective during pregnancy . As metabolism increases during pregnancy , NRT may deliver insufficient nicotine to alleviate withdrawal symptoms . There is mixed evidence as to what levels of cotinine are reached from nicotine exposure during pregnancy while using NRT compared with smoking . Methods : We analyzed data on 33 pregnant participants from the NRT arm of a r and omized control trial who had stopped smoking and were still using 15mg/16hr nicotine patches 1 month after quitting . Salivary cotinine levels when smoking at baseline were compared with levels on NRT at 1 month using the Wilcoxon test . Results : Cotinine levels were a median of 98.5ng/ml while smoking and 62.8ng/ml while using NRT and remaining abstinent ( p = .045 ) . Participants with the highest cotinine measurements when smoking also tended to have the steepest reduction in cotinine levels while using NRT . This was most noticeable among participants with baseline cotinine levels more than 150ng/ml ( n = 9 ) who had a greater reduction in median cotinine levels ( median difference −134.8ng /ml [ 95 % CI = −144.5 to −125.9 ] ) than those with a baseline cotinine level under 150ng/ml ( n = 24 ; median difference −27.9ng/ml [ 95 % CI = −49.35 to −1.75 ] ) . Conclusions : In a pragmatic trial that replicated clinical practice , cotinine levels generated using NRT during pregnancy were lower than levels achieved from smoking . Although the sample size of this study was small , our findings are significant and are consistent with the hypothesis that NRT patches deliver an inadequate dose of nicotine to aid smoking cessation during pregnancy INTRODUCTION Nicotine replacement therapy ( NRT ) medications have been shown to be effective in increasing smoking cessation rates . There is , however , a lack of good evidence describing how individuals in primary care use these medications and which factors are likely to affect this . The study objectives are to describe adherence and consumption , examine key factors that may determine use , and examine the relationship between consumption of NRT and abstinence from smoking . METHODS Secondary analysis of data from a r and omized controlled trial conducted in smoking cessation services in primary care . Adult smokers ( n = 633 ) starting a quit attempt within smoking cessation clinics were followed for 6 months , with NRT use closely monitored for an initial treatment period of 4 weeks . The main outcomes were 4-week adherence to prescribed NRT , mean daily consumption of NRT over the 4-week period , and abstinence from smoking at 4 weeks . RESULTS Levels of adherence to prescribed NRT were high : more than 94 % in participants who completed the treatment period . After controlling for possible confounders , prescribing higher doses of patch and oral NRT was associated with higher mean daily consumption of NRT . Using an inhalator to deliver oral NRT was associated with both higher adherence and higher consumption . The amount of NRT consumed predicted future abstinence when reverse causation was accounted for . CONCLUSIONS Most individuals within a clinical trial in primary care who persisted with a quit attempt adhered closely to their prescription . Prescribing higher doses of NRT led to higher consumption and higher consumption to higher abstinence BACKGROUND Nicotine-replacement therapy is effective for smoking cessation outside pregnancy and its use is widely recommended during pregnancy . We investigated the efficacy and safety of nicotine patches during pregnancy . METHODS We recruited participants from seven hospitals in Engl and who were 16 to 50 years of age with pregnancies of 12 to 24 weeks ' gestation and who smoked five or more cigarettes per day . Participants received behavioral cessation support and were r and omly assigned to 8 weeks of treatment with active nicotine patches ( 15 mg per 16 hours ) or matched placebo patches . The primary outcome was abstinence from the date of smoking cessation until delivery , as vali date d by measurement of exhaled carbon monoxide or salivary cotinine . Safety was assessed by monitoring for adverse pregnancy and birth outcomes . RESULTS Of 1050 participants , 521 were r and omly assigned to nicotine-replacement therapy and 529 to placebo . There was no significant difference in the rate of abstinence from the quit date until delivery between the nicotine-replacement and placebo groups ( 9.4 % and 7.6 % , respectively ; unadjusted odds ratio with nicotine-replacement therapy , 1.26 ; 95 % confidence interval , 0.82 to 1.96 ) , although the rate was higher at 1 month in the nicotine-replacement group than in the placebo group ( 21.3 % vs. 11.7 % ) . Compliance was low ; only 7.2 % of women assigned to nicotine-replacement therapy and 2.8 % assigned to placebo used patches for more than 1 month . Rates of adverse pregnancy and birth outcomes were similar in the two groups . CONCLUSIONS Adding a nicotine patch ( 15 mg per 16 hours ) to behavioral cessation support for women who smoked during pregnancy did not significantly increase the rate of abstinence from smoking until delivery or the risk of adverse pregnancy or birth outcomes . However , low compliance rates substantially limited the assessment of safety . ( Funded by the National Institute for Health Research Health Technology Assessment Programme ; Current Controlled Trials number , IS RCT N07249128 . ) OBJECTIVE : To estimate the safety and efficacy of treatment with 2-mg nicotine gum for smoking cessation during pregnancy . METHODS : Pregnant women who smoked daily received individualized behavioral counseling and r and om assignment to a 6-week treatment with 2-mg nicotine gum or placebo followed by a 6-week taper period . Women who did not quit smoking were instructed to reduce the number of cigarettes smoked by substituting with gum . Measures of tobacco exposure were obtained throughout the study . RESULTS : Participants in the nicotine ( nequals;100 ) and placebo ( nequals;94 ) groups were comparable in age , race/ethnicity , and smoking history . Biochemically vali date d smoking-cessation rates were not significantly higher with nicotine gum compared with placebo ( after 6 weeks of treatment : 13 % compared with 9.6 % , P=.45 ; at 32–34 weeks of gestation : 18 % compared with 14.9 % , P=.56 ) . Using a completer analysis , nicotine gum significantly reduced the number of cigarettes smoked per day ( nicotine gum : −5.7 [ st and ard deviation (SD)=6.0 ] ; placebo : −3.5 [ SD=5.7 ] , P=.035 ) , and cotinine concentration ( nicotine gum : −249 ng/mL [ SD=397 ] ; placebo : −112 ng/mL [ SD=333 ] ; P=.04 ) . Birth weights were significantly greater with nicotine gum compared with placebo ( 3,287 g [ SD=566 ] and 2,950 g [ SD=653 ] , respectively , P<.001 ) . Gestational age was also greater with nicotine-replacement therapy than with placebo ( 38.9 weeks [ SD=1.7 ] and 38.0 weeks [ SD=3.3 ] , respectively ; P=.014 ) . CONCLUSION : Although nicotine gum did not increase quit rates , use of nicotine gum increased birth weight and gestational age , two key parameters in predicting neonatal wellbeing . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00115687 LEVEL OF EVIDENCE : In a prospect i ve , population -based cohort study , the authors investigated the effect of in-utero exposure to maternal smoking and consumption of alcohol , coffee , and tea on the risk of strabismus . They review ed medical records for children in the Danish National Birth Cohort identified through national registers as possibly having strabismus . Relative risk estimates were adjusted for year of birth , social class , maternal smoking , maternal age at birth , and maternal coffee and tea consumption . The authors identified 1,321 cases of strabismus in a cohort of 96,842 Danish children born between 1996 and 2003 . Maternal smoking was associated with a significantly elevated risk of strabismus in the child , increasing with number of cigarettes smoked per day ( < 5 cigarettes/day : relative risk ( RR ) = 0.95 , 95 % confidence interval ( CI ) : 0.80 , 1.14 ; 5-<10 cigarettes/day : RR = 1.38 , 95 % CI : 1.12 , 1.70 ; > or = 10 cigarettes/day : RR = 1.90 , 95 % CI : 1.57 , 2.30 ) . Nicotine replacement therapy was not associated with strabismus risk ( RR = 1.22 , 95 % CI : 0.92 , 1.61 ) . Light maternal alcohol consumption was inversely associated with strabismus risk , whereas maternal coffee and tea drinking were not associated with strabismus risk . In conclusion , smoking during pregnancy is associated with an increased risk of strabismus in the offspring . Conversely , light alcohol consumption is associated with decreased risk Objective To determine the efficacy of 16 hour nicotine patches among pregnant smokers , with the dose individually adjusted according to saliva cotinine levels ( potential range 10 - 30 mg/day ) . Design R and omised , double blind , placebo controlled , parallel group , multicentre trial ( Study of Nicotine Patch in Pregnancy , SNIPP ) between October 2007 and January 2013 . Setting 23 maternity wards in France . Participants 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks ’ gestation , who smoked at least five cigarettes a day . After exclusions , 402 women were r and omised : 203 to nicotine patches and 199 to placebo patches . Data were available on 192 live births in each group . Interventions Nicotine and identical placebo patches were administered from quit day up to the time of delivery . Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100 % . Participants were assessed monthly and received behavioural smoking cessation support . Main outcome measures The primary outcomes were complete abstinence ( self report confirmed by carbon monoxide level in expired air ≤8 ppm ) from quit date to delivery , and birth weight . The secondary outcomes were point prevalence of abstinence , time to lapse ( a few puffs ) or relapse , and delivery and birth characteristics . All data were analysed on an intention to treat basis . Output:	Pregnant women who use nicotine replacement therapy instead of smoking reduce their nicotine exposure
MS21542	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To evaluate the best method of palliation for obstructing nonresectable squamous cell carcinoma of the mid or distal esophagus , 27 patients were prospect ively r and omized to one of three treatment arms : ( 1 ) esophageal intubation with an Atkinson tube ( AT , 10 patients ) , ( 2 ) esophageal intubation followed by radiation therapy ( AT/RT , 8 patients ) , and ( 3 ) endoscopic laser therapy followed by irradiation ( L/RT , 9 patients ) . Pretreatment characteristics were similar in the three groups . There was no procedure-related mortality . There were eight total complications related to the tube and none related to laser treatment ( p = 0.02 ) . Mean survival was 119 days in the AT group , 72 days in the AT/RT group , and 169 days in the L/RT arm ( p = not significant ) . Quality of survival was most dependent on swallowing ability , and the swallowing score increased by 2.3 units in the AT group , 1.8 units in the AT/RT group , and 1.4 units in the L/RT group ( p = not significant ) . Adding RT to laser therapy significantly increased time in treatment ( mean , 38.7 days ) when compared with the AT group ( mean , 12.5 days ) ( p less than 0.001 ) . However , only 1 patient required repeat laser ablation . It is concluded that AT and L/RT result in good palliation as measured by relief of dysphagia and survival time . However , morbidity of AT is significantly greater than that of L/RT . Laser and radiation therapy with a reduced total dosage of RT or with a change in fractionation schedule to limit treatment time is the preferred method of palliation In all , 144 patients with advanced cardiac cancers have been treated by photodynamic therapy ( PDT ) , combined chemotherapy and chemotherapy alone from September 1982 to July 1990 . A total of 5 mg kg-1 haematoporphyrin derivative ( HpD ) was intravenously given 48 - 72 h prior to PDT . The light source was an argon dye laser with an output beam of 630 nm . The irradiation time varied between 12 and 25 min with a fluence of 100 - 350 mW cm-2 . The entire tumour was irradiated with a light dose of 100 - 250 J cm-2 . The combination of UFT and mitomycin C was used as st and ard chemotherapy . There were 26 responders out of 55 patients ( 47.3 % ) in the group treated with PDT alone , 24 out of 41 ( 58.5 % ) in the PDT+chemotherapy group , and 24 out of 48 ( 50.0 % ) in the chemotherapy alone group . In the PDT+chemotherapy group 19.5 % patients had complete remission , which was better than the other two groups ( 5.5 % , 8.3 % , p less than 0.05 ) . The following survey of all patients lasted from six months to seven years . The results suggest that a combination of PDT and chemotherapy may prove effective BACKGROUND & AIMS Light dosimetry analysis to achieve predictable tumor necrosis has not been performed for photodynamic therapy ( PDT ) in the gastrointestinal tract . We evaluated dihematoporphyrin ethers for sensitizing esophageal carcinomas to 630 nm light and compared PDT with neodymium : yttrium-aluminum-garnet ( Nd : YAG ) laser therapy in a r and omized trial . METHODS Of 52 patients with dysphagia , 32 received palliative PDT . Ten patients treated with PDT participated in a preliminary trial using various doses of 630-nm light , and 22 patients treated with PDT participated in a r and omized trial using a derived st and ardized light dose for comparison with 20 patients treated with the Nd : YAG laser . RESULTS Light dosimetry correlated with depth of tumor necrosis ( r = 0.664 ; P < 0.001 ) . PDT activity was similar for squamous cell and adenocarcinoma . Among r and omized patients , both PDT and Nd : YAG therapy relieved dysphagia , but PDT result ed in improved Karnofsky performance status at 1 month ( + 7 vs. -7 ; P < 0.001 ) and longer duration of response ( 84 vs. 57 days ; P = 0.008 ) . Skin photoreactions were unique to PDT . CONCLUSIONS The extent of PDT tumor ablation correlates with light dosimetry , enabling selection of a st and ardized light dose . PDT can relieve esophageal obstruction from squamous cell and adenocarcinoma and is an alternative to Nd : YAG thermal necrosis with a longer duration of response . However , PDT requires patient pre caution s to minimize skin photoreactions BACKGROUND Photodynamic therapy ( PDT ) is a different type of laser treatment from Nd : YAG thermal ablation for palliation of dysphagia from esophageal cancer . METHODS In this prospect i ve , multicenter study , patients with advanced esophageal cancer were r and omized to receive PDT with porfimer sodium and argon-pumped dye laser or Nd : YAG laser therapy . RESULTS Two hundred thirty-six patients were r and omized and 218 treated ( PDT 110 , Nd : YAG 108 ) at 24 centers . Improvement in dysphagia was equivalent between the two treatment groups . Objective tumor response was also equivalent at week 1 , but at month 1 was 32 % after PDT and 20 % after Nd : YAG ( p < 0.05 ) . Nine complete tumor responses occurred after PDT and two after Nd : YAG . Trends for improved responses for PDT were seen in tumors located in the upper and lower third of the esophagus , in long tumors , and in patients who had prior therapy . More mild to moderate complications followed PDT , including sunburn in 19 % of patients . Perforations from laser treatments or associated dilations occurred after PDT in 1 % , Nd : YAG 7 % ( p < 0.05 ) . Termination of laser sessions due to adverse events occurred in 3 % with PDT and in 19 % with Nd : YAG ( p < 0.05 ) . CONCLUSIONS Photodynamic therapy with porfimer sodium has overall equal efficacy to Nd : YAG laser thermal ablation for palliation of dysphagia in esophageal cancer , and equal or better objective tumor response rate . Temporary photosensitivity is a limitation , but PDT is carried out with greater ease and is associated with fewer acute perforations than Nd : YAG laser therapy BACKGROUND The aim of therapy for advanced esophageal cancer is relief of dysphagia with minimal treatment-related morbidity . This study assessed the efficacy of endoscopic intratumoral injection of cisplatin/epinephrine gel to relieve obstruction and improve swallowing . The gel is design ed to minimize diffusion of active drug away from the tumor injection site . METHODS Patients with inoperable esophageal cancer and dysphagia caused by exophytic esophageal tumor underwent up to 6 weekly endoscopic injections of the gel . Response was documented objective ly ( exophytic tumor volume , lumen size , dysphagia grade ) and subjectively ( achievement of treatment goal ) . RESULTS Twenty-four patients were treated . Primary evaluation criteria for 18 evaluable patients were as follows : dysphagia grade improved in 4 ( duration 30 to 45 days ) and stabilized in 11 ; lumen patency improved in 6 ( duration 29 to 56 days ) and stabilized in 10 ; exophytic tumor volume decreased in 8 ( duration 29 to 114 days ) . Eight patients felt that their ability to swallow improved . One patient with intramural and exophytic tumor developed a tracheoesophageal fistula , possibly related to treatment . Other complications were tolerable and self-limited . No nephrotoxicty or severe nausea/vomiting typical of systemic administration of cisplatin occurred . CONCLUSIONS Endoscopic injection of cisplatin/epinephrine gel is a straightforward procedure with st and ard equipment and techniques , which can provide palliation for patients with exophytic malignant tumors of the esophagus . Assessment of this method in conjunction with other therapeutic options such as brachytherapy is warranted Abstract Background . The DBCG-IMN is a nationwide population -based cohort study on the effect of internal mammary node radiotherapy ( IMN-RT ) in patients with node positive early breast cancer . Due to the risk of RT-induced heart disease , only patients with right-sided breast cancer received IMN-RT , whereas patients with left-sided breast cancer did not . At seven-year median follow-up , a 3 % gain in overall survival with IMN-RT has been reported . This study estimates IMN doses and doses to organs at risk ( OAR ) in patients from the DBCG-IMN . Numbers needed to harm ( NNH ) if patients with left-sided breast cancer had received IMN-RT are compared to the number needed to treat ( NNT ) . Material and methods . Ten percent of CT-guided treatment plans from the DBCG-IMN patients were selected r and omly . IMNs and OAR were contoured in 68 planning CT scans . Dose distributions were re-calculated . IMNs and OAR dose estimates were compared in right-sided versus left-sided breast cancer patients . In six left-sided patients , IMN-RT was simulated , and OAR doses were compared to those in the original plan . The NNH result ing from the change in mean heart dose ( MHD ) was calculated using a published model for risk of RT-related ischemic heart death . Results . In original plans , the absolute difference between right- and left-sided V90 % to the IMNs was 38.0 % [ 95 % confidence interval ( 5.5 % ; 70.5 % ) , p < 0.05 ] . Heart doses were higher in left-sided plans . With IMN-RT simulation without regard to OAR constraints , MHD increased 4.8 Gy ( 0.9 Gy ; 8.7 Gy ) , p < 0.05 . Result ing NNHs from ischemic heart death were consistently larger than the NNT with IMN-RT . Conclusion . Refraining from IMN-RT on the left side may have spared some ischemic heart deaths . Assuming left-sided patients benefit as much from IMN-RT as right-sided patients , the benefits from IMN-RT outweigh the costs in terms of ischemic heart death The aim of this paper is to present the up date d experience of the Yorkshire Laser Centre in PDT for esophageal cancer and to identify its role in specific subsets of patients . Also , in the light of this experience , to compare and contrast the results of PDT with appropriate subsets of patients treated in my esophageal surgery practice . 102 consecutive patients ; 84 with advanced ( Group A ) and 18 with early ( Group E ) stage esophageal cancer undergoing endoscopic PDT were entered into a prospect i ve study . Every patient had st and ard work up including clinical staging . PDT protocol was intravenous administration of Photofrin 2mg/kg body weight followed 24–72 hours later by endoscopic illumination using 630 nm laser light . Assessment of results was made on the basis of mortality , morbidity , patient satisfaction to treatment , symptom relief and survival . For comparison of PDT role with non PDT treated patients , reference is made to 3 previous publications comprising over 1100 patients [ Moghissi , K. , Br . J. Surg . 79 , 935–937 ( 1992 ) ( ref . 1 ) ; Sawant , D. , Moghissi , K. Eur . J. Cardio-Thorac . Surg . 8 , 113–117 ( 1994 ) ( ref . 2 ) ; Sharpe , D. A. C. , Moghissi , K. Eur . J. Cardiothorac . Surg . 10 , 359–364 ( 1996 ) ( ref . 3 ) ] . There was no mortality associated with PDT . All patients expressed satisfaction to treatment . Post PDT complications consisted of photosensitivity skin reaction ( sunburn ) in 5 patients ( 5 % ) and esophageal stricture in 8 ( 8 % ) patients . Group A : There was significant symptom and dysphegia grade improvement . Mean survival was 9.5 months . Group E : There were no significant symptoms pre or post PDT and mean survival was 60.5 months . Comparison of PDT results in Group A with results of other palliative treatment methods , indicates that palliation can be achieved in all intraluminal cancer using PDT which is at least as good as other treatments . There is , in addition , advantage over other methods in patients with cervical esophageal cancer and in cases with re-growth of tumor obstructing previously placed stents . In early cases PDT appears capable of replicating surgical results in selected cases . PDT is an effective and safe treatment method in esophageal cancer . In advance disease it improves swallowing . In early stage disease it offers long survival and the prospect of cure in some patients . At present the role of PDT in early stage cancer should be limited to patients who are unsuitable for surgical resection . Therefore , PDT should be considered as a valid oncological option to be applied in selected cases Output:	CONCLUSION PDT is a useful method for the treatment of middle-advanced stage upper gastrointestinal carcinomas . PDT combined with chemotherapy or radiotherapy can enhance its efficacy and prolong survival time
MS21543	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Similar to most chronic diseases , Alzheimer 's disease ( AD ) develops slowly from a pre clinical phase into a fully expressed clinical syndrome . We aim ed to use longitudinal data to calculate the rates of amyloid β ( Aβ ) deposition , cerebral atrophy , and cognitive decline . METHODS In this prospect i ve cohort study , healthy controls , patients with mild cognitive impairment ( MCI ) , and patients with AD were assessed at enrolment and every 18 months . At every visit , participants underwent neuropsychological examination , MRI , and a carbon-11-labelled Pittsburgh compound B ( (11)C-PiB ) PET scan . We included participants with three or more (11)C-PiB PET follow-up assessment s. Aβ burden was expressed as (11)C-PiB st and ardised uptake value ratio ( SUVR ) with the cerebellar cortex as reference region . An SUVR of 1·5 was used to discriminate high from low Aβ burdens . The slope of the regression plots over 3 - 5 years was used to estimate rates of change for Aβ deposition , MRI volumetrics , and cognition . We included those participants with a positive rate of Aβ deposition to calculate the trajectory of each variable over time . FINDINGS 200 participants ( 145 healthy controls , 36 participants with MCI , and 19 participants with AD ) were assessed at enrolment and every 18 months for a mean follow-up of 3·8 ( 95 % CI CI 3·6 - 3·9 ) years . At baseline , significantly higher Aβ burdens were noted in patients with AD ( 2·27 , SD 0·43 ) and those with MCI ( 1·94 , 0·64 ) than in healthy controls ( 1·38 , 0·39 ) . At follow-up , 163 ( 82 % ) of the 200 participants showed positive rates of Aβ accumulation . Aβ deposition was estimated to take 19·2 ( 95 % CI 16·8 - 22·5 ) years in an almost linear fashion-with a mean increase of 0·043 ( 95 % CI 0·037 - 0·049 ) SUVR per year-to go from the threshold of (11)C-PiB positivity ( 1·5 SUVR ) to the levels observed in AD . It was estimated to take 12·0 ( 95 % CI 10·1 - 14·9 ) years from the levels observed in healthy controls with low Aβ deposition ( 1·2 [ SD 0·1 ] SUVR ) to the threshold of (11)C-PiB positivity . As AD progressed , the rate of Aβ deposition slowed towards a plateau . Our projections suggest a prolonged pre clinical phase of AD in which Aβ deposition reaches our threshold of positivity at 17·0 ( 95 % CI 14·9 - 19·9 ) years , hippocampal atrophy at 4·2 ( 3·6 - 5·1 ) years , and memory impairment at 3·3 ( 2·5 - 4·5 ) years before the onset of dementia ( clinical dementia rating score 1 ) . INTERPRETATION Aβ deposition is slow and protracted , likely to extend for more than two decades . Such predictions of the rate of pre clinical changes and the onset of the clinical phase of AD will facilitate the design and timing of therapeutic interventions aim ed at modifying the course of this illness . FUNDING Science and Industry Endowment Fund ( Australia ) , The Commonwealth Scientific and Industrial Research Organisation ( Australia ) , The National Health and Medical Research Council of Australia Program and Project Grants , the Austin Hospital Medical Research Foundation , Victorian State Government , The Alzheimer 's Drug Discovery Foundation , and the Alzheimer 's Association Output:	Conclusion Patients with aMCI showed a similar distribution of amyloid deposition determined by both visual reading and SUVR to that observed in patients with and without dementia coming to autopsy . Most of the aMCI patients , who are already within the AD continuum , had widespread amyloid deposition in terms of amount and topographical progression .
MS21544	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Physician empathy is an essential attribute of the patient – physician relationship and is associated with better outcomes , greater patient safety and fewer mal practice cl aims . Objective We tested whether an innovative empathy training protocol grounded in neuroscience could improve physician empathy as rated by patients . Design R and omized controlled trial . InterventionWe r and omly assigned residents and fellows from surgery , medicine , anesthesiology , psychiatry , ophthalmology , and orthopedics ( N = 99 , 52 % female , mean age 30.6 ± 3.6 ) to receive st and ard post-graduate medical education or education augmented with three 60-minute empathy training modules . Main MeasurePatient ratings of physician empathy were assessed within one-month pre-training and between 1–2 months post-training with the use of the Consultation and Relational Empathy ( CARE ) measure . Each physician was rated by multiple patients ( pre-mean = 4.6 ± 3.1 ; post-mean 4.9 ± 2.5 ) , who were blinded to physician r and omization . The primary outcome was change score on the patient-rated CARE.Key Results The empathy training group showed greater changes in patient-rated CARE scores than the control ( difference 2.2 ; P = 0.04 ) . Trained physicians also showed greater changes in knowledge of the neurobiology of empathy ( difference 1.8 ; P < 0.001 ) and in ability to decode facial expressions of emotion ( difference 1.9 ; P < 0.001 ) . Conclusions A brief intervention grounded in the neurobiology of empathy significantly improved physician empathy as rated by patients , suggesting that the quality of care in medicine could be improved by integrating the neuroscience of empathy into medical education Background To provide patient-centred holistic care , doctors must possess good interpersonal and empathic skills . Medical schools traditionally adopt a skills-based approach to such training but creative engagement with the arts has also been effective . A novel arts-based approach may help medical students develop empathic underst and ing of patients and thus contribute to medical students ’ transformative process into compassionate doctors . This study aim ed to evaluate the impact of an arts-making workshop on medical student empathy . Methods This was a mixed- method quantitative-qualitative study . In the 2011–12 academic year , all 161 third year medical students at the University of Hong Kong were r and omly allocated into either an arts-making workshop or a problem-solving workshop during the Family Medicine clerkship according to a central ly-set timetable . Students in the arts-making workshop wrote a poem , created artwork and completed a reflective essay while students in the conventional workshop problem-solved clinical cases and wrote a case commentary . All students who agreed to participate in the study completed a measure of empathy for medical students , the Jefferson Scale of Empathy ( JSE ) ( student version ) , at the start and end of the clerkship . Quantitative data analysis : Paired t-test and repeated measures ANOVA was used to compare the change within and between groups respectively . Qualitative data analysis : Two research ers independently chose representational narratives based on criteria adapted from art therapy . The final 20 works were agreed upon by consensus and thematically analysed using a grounded theory approach . Results The level of empathy declined in both groups over time , but with no statistically significant differences between groups . For JSE items relating to emotional influence on medical decision making , participants in the arts-making workshop changed more than those in the problem-solving workshop . From the qualitative data , students perceived benefits in arts-making , and gained underst and ing in relation to self , patients , pain and suffering , and the role of the doctor . Conclusions Though quantitative findings showed little difference in empathy between groups , arts-making workshop participants gained empathic underst and ing in four different thematic areas . This workshop also seemed to promote greater self-awareness which may help medical students recognize the potential for emotions to sway judgment . Future art workshops should focus on emotional awareness and regulation BACKGROUND AND PURPOSE Optimizing communication between radiotherapy team members and patients and between colleagues requires training . This study applies a r and omized controlled design to assess the efficacy of a 38-h communication skills training program . MATERIAL AND METHODS Four radiotherapy teams were r and omly assigned either to a training program or to a waiting list . Team members ' communication skills and their self-efficacy to communicate in the context of an encounter with a simulated patient were the primary endpoints . These encounters were scheduled at the baseline and after training for the training group , and at the baseline and four months later for the waiting list group . Encounters were audiotaped and transcribed . Transcripts were analyzed with content analysis software ( LaComm ) and by an independent rater . RESULTS Eighty team members were included in the study . Compared to untrained team members , trained team members used more turns of speech with content oriented toward available re sources in the team ( relative rate [RR]=1.38 ; p=0.023 ) , more assessment utterances ( RR=1.69 ; p<0.001 ) , more empathy ( RR=4.05 ; p=0.037 ) , more negotiation ( RR=2.34 ; p=0.021 ) and more emotional words ( RR=1.32 ; p=0.030 ) , and their self-efficacy to communicate increased ( p=0.024 and p=0.008 , respectively ) . CONCLUSIONS The training program was effective in improving team members ' communication skills and their self-efficacy to communicate in the context of an encounter with a simulated patient . Future study should assess the effect of this training program on communication with actual patients and their satisfaction . Moreover a cost-benefit analysis is needed , before implementing such an intensive training program on a broader scale Introduction Physician empathy is a complex phenomenon known to improve illness outcomes ; however , few tools are available for deliberate practice of empathy . We used a virtual patient ( VP ) to teach empathic communication to first-year medical students . We then evaluated students ’ verbal empathy in a st and ardized patient ( SP ) interaction . Methods Seventy medical students , r and omly assigned to 3 separate study groups , interacted with ( 1 ) a control VP portraying depression , ( 2 ) a VP with a backstory simulating patient shadowing , or ( 3 ) a VP able to give immediate feedback about empathic communication ( empathy-feedback VP ) . Subsequently , the students interviewed an SP portraying a scenario that included opportunities to express empathy . All SP interviews were recorded and transcribed . The study outcomes were ( 1 ) the students ’ verbal response to the empathic opportunities presented by the SP , as coded by reliable assessors using the Empathic Communication Coding System , and ( 2 ) the students ’ responses as coded by the SPs , using a communication checklist . Results There were no significant differences in student demographics between groups . The students who interacted with the empathy-feedback VP showed higher empathy in the SP interview than did the students in the backstory VP and the control VP groups [ mean ( SD ) empathy scores coded on a 0–6 scale were 2.91 ( 0.16 ) vs. 2.20 ( 0.22 ) and 2.27 ( 0.21 ) , respectively ) . The difference in scores was significant only for the empathy-feedback VP versus the backstory VP group ( P = 0.027 ) . The SPs rated the empathy-feedback and the backstory VP groups significantly higher than the control VP group on offering empathic statements ( P < 0.0001 ) , appearing warm and caring ( P = 0.015 ) , and forming rapport ( P = 0.004 ) . Conclusions Feedback on empathy in a VP interaction increased students ’ empathy in encounters with SPs , as rated by trained assessors , whereas a simulation of patient shadowing did not . Both VP interventions increased students ’ empathy as rated by SPs , compared with the control VP group PURPOSE To use a st and ardized videotape stimulus to assess the effect of physician compassion on viewers ' anxiety , information recall , treatment decisions , and assessment of physician characteristics . PARTICIPANTS AND METHODS One hundred twenty-three healthy female breast cancer survivors and 87 women without cancer were recruited for this study . A r and omized pretest/posttest control group design with a st and ardized videotape intervention was used . Participants completed the State-Trait Anxiety Inventory ( STAI ) , an information recall test , a compassion rating , and physician attribute rating scales . RESULTS Women who saw an " enhanced compassion " videotape rated the physician as warmer and more caring , sensitive , and compassionate than did women who watched the " st and ard " videotape . Women who saw the enhanced compassion videotape were significantly less anxious after watching it than the women in the other group . Nevertheless , information recall was relatively low for both groups , and enhanced compassion did not influence patient decisions . Those who saw the enhanced compassion videotape rated the doctor significantly higher on other positive attributes , such as wanting what was best for the patient and encouraging the patient 's questions and involvement in decisions . CONCLUSION The enhanced compassion segment was short , simple , and effective in decreasing viewers ' anxiety . Further research is needed to translate these findings to the clinical setting , where reducing patient anxiety is a therapeutic goal CONTEXT Medical errors are associated with feelings of distress in physicians , but little is known about the magnitude and direction of these associations . OBJECTIVE To assess the frequency of self-perceived medical errors among resident physicians and to determine the association of self-perceived medical errors with resident quality of life , burnout , depression , and empathy using vali date d metrics . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve longitudinal cohort study of categorical and preliminary internal medicine residents at Mayo Clinic Rochester . Data were provided by 184 ( 84 % ) of 219 eligible residents . Participants began training in the 2003 - 2004 , 2004 - 2005 , and 2005 - 2006 academic years and completed surveys quarterly through May 2006 . Surveys included self- assessment of medical errors and linear analog scale assessment of quality of life every 3 months , and the Maslach Burnout Inventory ( depersonalization , emotional exhaustion , and personal accomplishment ) , Interpersonal Reactivity Index , and a vali date d depression screening tool every 6 months . MAIN OUTCOME MEASURES Frequency of self-perceived medical errors was recorded . Associations of an error with quality of life , burnout , empathy , and symptoms of depression were determined using generalized estimating equations for repeated measures . RESULTS Thirty-four percent of participants reported making at least 1 major medical error during the study period . Making a medical error in the previous 3 months was reported by a mean of 14.7 % of participants at each quarter . Self-perceived medical errors were associated with a subsequent decrease in quality of life ( P = .02 ) and worsened measures in all domains of burnout ( P = .002 for each ) . Self-perceived errors were associated with an odds ratio of screening positive for depression at the subsequent time point of 3.29 ( 95 % confidence interval , 1.90 - 5.64 ) . In addition , increased burnout in all domains and reduced empathy were associated with increased odds of self-perceived error in the following 3 months ( P=.001 , P<.001 , and P=.02 for depersonalization , emotional exhaustion , and lower personal accomplishment , respectively ; P=.02 and P=.01 for emotive and cognitive empathy , respectively ) . CONCLUSIONS Self-perceived medical errors are common among internal medicine residents and are associated with substantial subsequent personal distress . Personal distress and decreased empathy are also associated with increased odds of future self-perceived errors , suggesting that perceived errors and distress may be related in a reciprocal cycle OBJECTIVE To assess the effects of Balint groups on empathy measured by the Consultation And Relational Empathy Measure ( CARE ) scale rated by st and ardized patients during objective structured clinical examination and self-rated Jefferson 's School Empathy Scale - Medical Student ( JSPE-MS © ) among fourth-year medical students . METHODS A two-site r and omized controlled trial were planned , from October 2015 to December 2015 at Paris Diderot and Paris Descartes University , France . Eligible students were fourth-year students who gave their consent to participate . Participants were allocated in equal proportion to the intervention group or to the control group . Participants in the intervention group received a training of 7 sessions of 1.5-hour Balint groups , over 3months . The main outcomes were CARE and the JSPE-MS © scores at follow-up . RESULTS Data from 299 out of 352 r and omized participants were analyzed : 155 in the intervention group and 144 in the control group , with no differences in baseline measures . There was no significant difference in CARE score at follow-up between the two groups ( P=0.49 ) . The intervention group displayed significantly higher JSPE-MS © score at follow-up than the control group [ Mean ( SD ) : 111.9 ( 10.6 ) versus 107.7 ( 12.7 ) , P=0.002 ] . The JSPE-MS © score increased from baseline to follow-up in the intervention group , whereas it decreased in the control group [ 1.5 ( 9.1 ) versus -1.8 ( 10.8 ) , P=0.006 ] . CONCLUSIONS Balint groups may contribute to promote clinical empathy among medical students . TRIAL REGISTRATION NCT02681380 Empathy is an essential attribute for medical professionals . Yet , evidence Output:	We identified the following key behaviors to be effective : ( 1 ) sitting ( versus st and ing ) during the interview ; ( 2 ) detecting patients ' non-verbal cues of emotion ; ( 3 ) recognizing and responding to opportunities for compassion ; ( 4 ) non-verbal communication of caring ( e.g. eye contact ) ; and ( 5 ) verbal statements of acknowledgement , validation , and support . These behaviors were found to improve patient perception of physician empathy and /or compassion . CONCLUSION Evidence suggests that training can enhance physician empathy and compassion .
MS21545	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Coronary heart disease ( CHD ) risk factors and the risk of CHD increase with increased adiposity . Fat loss induced by negative energy balance improves all metabolic CHD risk factors . To determine whether fat loss induced by long-term calorie restriction ( CR ) or increased energy expenditure induced by exercise ( EX ) has different effects on CHD risk factors in nonobese subjects , we conducted a 1-yr controlled trial involving 48 nonobese subjects who were r and omly assigned to one of three groups : CR , 20 % CR diet ( n = 18 ) ; EX , 20 % increase in energy expenditure through daily exercise with no increase in energy intake ( n = 18 ) ; or HL , healthy lifestyle guidelines ( n = 10 ) . Subjects were 29 women and 17 men aged 57 + /- 3 yr , with BMI 27.3 + /- 2.0 kg/m(2 ) . Assessment s included total body fat by DEXA , lipoproteins , blood pressure , HOMA-IR , C-reactive protein ( CRP ) , and estimated 10-yr CHD risk score . Body fat decreased by 6.3 + /- 3.8 kg in CR , 5.6 + /- 4.4 kg in EX , and 0.4 + /- 1.7 kg in HL , which corresponded to reductions of 24.9 , 22.3 , and 1.2 % of baseline body fat mass , respectively . These CR- and EX-induced energy deficits were accompanied by reductions in most of the major CHD risk factors , including plasma LDL-cholesterol , total cholesterol/HDL ratio , HOMA-IR index , and CRP concentrations that were similar in the two intervention groups . Data from the present study provide evidence that CR- and EX-induced negative energy balance result in substantial and similar improvements in the major risk factors for CHD in normal-weight and overweight middle-aged adults We studied the effect of exercise on circulating adipokine , high sensitivity C-reactive protein ( hs-CRP ) , and metabolic parameters in obese young women . Ninety-six healthy Japanese young female students aged 18 - 23 years were studied . The longitudinal intervention study of a 7-month exercise training program ( 30 - 60 min/day , 60 - 70 % HR-reserve , 200 - 400 kcal , 4 - 5 days/week ) was performed in eight obese female students ( BMI > or = 25 kg/m(2 ) ) . Eight control female students ( mean BMI = 22 kg/m(2 ) ) were included in the follow-up study . Body weight , body mass index ( BMI ) , percentage of body fat ( % Fat ) , body fat mass , lean body mass , health-promoting lifestyle profile-scale ( L-scale ) , VO(2)max ( maximal oxygen uptake ) , hs-CRP , lipids , insulin homeostasis model assessment ( HOMA-R ) , fasting levels for circulating adiponectin , leptin , and TNF-alpha , were measured before and after the exercise program . In obese subjects , body weight , BMI , % Fat , body fat mass , lean body mass , hs-CRP , leptin , and TNF-alpha were significantly higher , and L-scale and adiponectin were lower than those in control subjects . In obese subjects , exercise decreased body weight , BMI , % Fat , body fat mass , lean body mass , hs-CRP , leptin , and TNF-alpha , and increased L-scale , VO(2)max , HDL-cho , and adiponectin . It was concluded that changes in circulating adipokine levels are involved in the improvement of the metabolic state by exercise and may be useful markers for evaluation and prescription of exercise Background — Inflammatory processes are putative mechanisms underlying the cardioprotective effects of physical activity . An inverse association between physical activity and inflammation has been demonstrated , but no long-term prospect i ve data are available . We therefore examined the association between physical activity and inflammatory markers over a 10-year follow-up period . Methods and Results — Participants were 4289 men and women ( mean age , 49.2 years ) from the Whitehall II cohort study . Self-reported physical activity and inflammatory markers ( serum high-sensitivity C-reactive protein and interleukin-6 ) were measured at baseline ( 1991 ) and follow-up ( 2002 ) . Forty-nine percent of the participants adhered to st and ard physical activity recommendations for cardiovascular health ( 2.5 h/wk moderate to vigorous physical activity ) across all assessment s. Physically active participants at baseline had lower C-reactive protein and interleukin-6 levels , and this difference remained stable over time . Compared with participants who rarely adhered to physical activity guidelines over the 10-year follow-up , the high-adherence group displayed lower loge C-reactive protein ( & bgr;=−0.07 ; 95 % confidence interval , −0.12 to −0.02 ) and loge interleukin-6 ( & bgr;=−0.07 ; 95 % confidence interval , −0.10 to −0.03 ) at follow-up after adjustment for a range of covariates . Compared with participants who remained stable , those who reported an increase in physical activity of at least 2.5 h/wk displayed lower loge C-reactive protein ( & bgr ; coefficient=−0.05 ; 95 % confidence interval , −0.10 to −0.001 ) and loge interleukin-6 ( & bgr ; coefficient=−0.06 ; 95 % confidence interval , −0.09 to −0.03 ) at follow-up . Conclusions — Regular physical activity is associated with lower markers of inflammation over 10 years of follow-up and thus may be important in preventing the proinflammatory state seen with aging Background Coronary heart disease as well as major cardiovascular risk factors are associated with elevated levels of proinflammatory markers . There is , however , limited information about how changes in lifestyle improving the cardiovascular risk profile influence these levels . The aim of the study was to evaluate whether changes in lifestyle measures with special attention to physical activity , were associated with the levels of such markers . Design Coronary heart disease patients ( n = 197 ) were r and omized to either a comprehensive lifestyle intervention programme comprising regular physical activity , low fat diet and smoking cessation , or usual care with routine follow-up in the outpatient clinic for 6 months . An exercise test and fasting blood sample s analysed for soluble cell adhesion molecules , C reactive protein and pro-inflammatory cytokines were evaluated before and at the end of the study . Results Improved diet , physical performance and reduction in smoking were obtained in the intervention programme when compared with usual care patients , but no significant group differences in levels of inflammatory markers were observed . In the total population , however , physical performance significantly and inversely predicted levels of soluble cell adhesion molecule 1 , ( P>0.001 ) , C-reactive protein ( P>0.001 ) and interleukin-6 ( P=0.01 ) at 6 months . Smokers had elevated levels of soluble cell adhesion molecule 1 when compared with non-smokers ( P=0.011 ) . Conclusions We demonstrated that physical performance is inversely correlated with levels of pro-inflammatory markers in coronary heart disease patients , possibly retarding the process of atherosclerosis . No effect on inflammatory markers was obtained with a 6-month lifestyle intervention programme when compared with patients who received usual care follow-up . Eur J Cardiovasc Prev Rehabil 13:356 - 362 © 2006 The European Society of The primary purpose of this study was to investigate the effects of high-intensity exercise training under relatively equal energy expenditure on whole body fat and abdominal fat loss , and cardiorespiratory fitness . Twenty-two untrained middle-aged Korean females were r and omized into one of the following groups : control , low-intensity training group ( LI ) , and high-intensity training group ( HI ) . Subjects completed 14 weeks of training at 50 % maximal oxygen consumption ( LI ) or 70 % maximal oxygen consumption ( HI ) with the volume of exercise equated relative to kilograms of body weight . Weekly exercise volumes were 13.5 METs⋅h/week for the first 4 weeks , 18 METs⋅h/week for next 5 weeks , and 22.5 METs⋅h/week for the final 5 weeks . Data were analyzed using 2-way repeated measures ANOVA with post hoc test , using Bonferroni 's correction . HI showed significant reductions in fat mass ( p < 0.05 ) , total abdominal fat ( p < 0.01 ) , and subcutaneous abdominal fat ( p < 0.01 ) . LI reduced total abdominal fat ( p < 0.05 ) , but there were no other significant changes found in the control or LI groups . Maximal oxygen consumption was enhanced in both HI and LI with no significant group difference . High-density lipoprotein cholesterol increased significantly in HI ( p < 0.05 ) . IL-6 , C-reactive protein , TNF-α , and other blood lipids were unaltered following training . Results indicate that high-intensity exercise training is more beneficial in whole body and abdominal fat loss ; however , cardiorespiratory enhancement shows a dose-response relationship with weekly exercise volume . It is suggested that 14 weeks of aerobic exercise training at either high- or low-intensity is not sufficient enough to induce changes in levels of inflammatory proteins PURPOSE To investigate the effect of a yearlong moderate-intensity aerobic exercise intervention on C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , and interleukin 6 ( IL-6 ) among overweight or obese postmenopausal women . METHODS In a r and omized controlled trial , 115 postmenopausal , overweight or obese , sedentary women , aged 50 - 75 yr were r and omized to an aerobic exercise intervention of moderate-intensity ( 60%-75 % observed maximal HR ) , for > or = 45 min x d(-1 ) , 5 d x wk ( n = 53 ) , or to a 1-d x wk(-1 ) stretching control ( n = 62 ) , on an intent-to-treat basis . CRP , SAA , and IL-6 were measured at baseline , at 3 months , and at 12 months . RESULTS From baseline to 12 months , CRP decreased 10 % in exercisers and increased 12 % in controls ( P = 0.01 ) ; no effects were observed for SAA and IL-6 . Among participants at baseline who were obese ( body mass index ( BMI ) > or = 30 kg x m(-2 ) ) or had abdominal obesity ( waist circumference ( WC ) > or = 88 cm ) , exercise result ed in a more pronounced reduction in CRP ( BMI > or = 30 kg x m(-2 ) , P = 0.002 ; WC > or = 88 cm , P < 0.0001 ) , borderline for SAA ( BMI > or = 30 kg x m(-2 ) , P = 0.08 ; WC > or = 88 cm , P = 0.04 ) ; no intervention effects were observed among women who did not have these characteristics . Overall , weight loss was minimal in the exercise intervention ( approximately 1.8 kg ) . Linear trends were observed between CRP and 12-month changes in aerobic fitness ( Ptrend = 0.006 ) , exercise adherence ( Ptrend = 0.004 ) , percentage body fat ( Ptrend = 0.002 ) , body weight ( Ptrend = 0.002 ) , WC ( Ptrend = 0.02 ) , and intra-abdominal fat ( Ptrend = 0.03 ) . CONCLUSIONS A moderate-intensity exercise intervention reduced CRP for 12 months among women who were obese at baseline . These findings support the role of exercise in modulating inflammatory processes that are related to increased risk of chronic disease among obese women Background —C-reactive protein ( CRP ) has been proposed as an independent risk factor for cardiovascular disease and has been positively associated with body weight and body fatness . We examined the hypothesis that weight loss would reduce plasma CRP levels in obese postmenopausal women . Methods and Results —In a sample of 61 obese ( body mass index , 35.6±5.0 kg/m2 ) , postmenopausal women ( age , 56.4±5.2 years ) , we found that plasma CRP levels were positively associated with dual x-ray absorptiometry – measured total body fatness ( r = 0.36 , P < 0.005 ) and CT-measured intra-abdominal body fat area ( r = 0.30 , P < 0.02 ) . Significant correlations were also found between plasma CRP and triglyceride levels ( r = 0.33 , P < 0.009 ) and glucose disposal measured by the hyperinsulinemic-euglycemic clamp technique ( r = −0.29 , P < 0.03 ) . Twenty-five of the 61 women tested at baseline completed a weight loss protocol . The average weight loss was 14.5±6.2 kg ( −15.6 % , P < 0.0001 ) , with losses of 10.4±5.4 kg fat mass ( −25.0 % , P < 0.0001 ) and 2.8±1.4 kg fat-free mass ( −6.0 % , P < 0.0 Output:	Heterogeneity between studies could not be attributed to age , gender , intervention length , intervention type , or inclusion of diet modification . Exercise interventions reduced hsCRP levels in adults irrespective of the presence of heart
MS21546	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Cognitive impairment and depression often co-occur in older adults , but it is not clear whether depression is a risk factor for cognitive decline , a psychological reaction to cognitive decline , or whether changes in depressive symptoms correlate with changes in cognitive performance over time . The co-morbid manifestation of depression and cognitive impairment may reflect either a causal effect or a common cause , depending on the specific symptoms experienced and the cognitive functions affected . Method The study sample comprised 1506 community-dwelling older adults aged ⩾65 years from the Longitudinal Aging Study Amsterdam ( LASA ) . We conducted cross-domain latent growth curve analyses to examine longitudinal associations between late-life depression dimensions ( i.e. depressed affect , positive affect , and somatic symptoms ) and specific domains of cognitive functioning ( i.e. processing speed , inductive reasoning , immediate recall , and delayed recall ) . Results Poorer delayed recall performance at baseline predicted a steeper increase in depressed affect over time . Steeper decline in processing speed correlated with a steeper increase in somatic symptoms of depression over time . Conclusions Our findings suggest a prospect i ve association between memory function and depressed affect , whereby older adults may experience an increase in depressed affect in reaction to poor memory function . Somatic symptoms of depression increased concurrently with declining processing speed , which may reflect common neurodegenerative processes . Our findings do not support the hypothesis that depression symptoms may be a risk factor for cognitive decline in the general population . These findings have potential implication s for the treatment of late-life depression and for the prognosis of cognitive outcomes Indices of functional connectivity in the default mode network ( DMN ) are promising neural markers of treatment response in late-life depression . We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults . Forty-seven depressed older adults underwent MRI scanning pre- and post-pharmacotherapy . Forty-six never depressed older adults underwent MR scanning as comparison subjects . Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment . We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest . The result ing correlation maps were employed to investigate between-group differences . Additionally we examined the association between white matter hyperintensity burden and functional connectivity results . Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal pre central gyrus . Relative to treatment-responsive participants , treatment-resistant participants had increased functional connectivity in the left striatum . When adjusting for white matter hyperintensity burden , the observed differences lost significance for the PCC-prefrontal functional connectivity , but not for the PCC-striatum functional connectivity . The post-treatment " frontalization " of the DMN connectivity suggests a normalizing effect of antidepressant treatment . Moreover , our study confirms the central role of white matter lesions in disrupting brain functional connectivity Kendall 's coefficient concordance ( KCC ) can measure the similarity of a number of time series . It has been used for purifying a given cluster in functional MRI ( fMRI ) . In the present study , a new method was developed based on the regional homogeneity ( ReHo ) , in which KCC was used to measure the similarity of the time series of a given voxel to those of its nearest neighbors in a voxel-wise way . Six healthy subjects performed left and right finger movement tasks in event-related design ; five of them were additionally scanned in a rest condition . KCC was compared among the three conditions ( left finger movement , right finger movement , and the rest ) . Results show that bilateral primary motor cortex ( M1 ) had higher KCC in either left or right finger movement condition than in rest condition . Contrary to prediction and to activation pattern , KCC of ipsilateral M1 is significantly higher than contralateral M1 in unilateral finger movement conditions . These results support the previous electrophysiologic findings of increasing ipsilateral M1 excitation during unilateral movement . ReHo can consider as a complementary method to model-driven method , and it could help reveal the complexity of the human brain function . More work is needed to underst and the neural mechanism underlying ReHo BACKGROUND Mild cognitive impairment is increasingly recognized as an important public health problem associated with increased risk of developing dementia . Annual conversion rates , however , vary across different studies with clinic sample s showing higher rates of conversion than community-based sample s. OBJECTIVES To establish whether the rates of conversion from mild cognitive impairment to dementia differed according to recruitment source and , if so , to investigate factors that might explain this discrepancy . DESIGN Rates and predictors of conversion were examined in a prospect i ve longitudinal study at a single center . SETTING Among the participants , 46 % were recruited from a clinical setting and 54 % were recruited directly through community outreach . PARTICIPANTS One hundred eleven individuals with mild cognitive impairment were followed up longitudinally for an average of 2.4 years ( range , 0.5 - 4.0 years ) . MAIN OUTCOME MEASURES Conversion from mild cognitive impairment to dementia . RESULTS During the follow-up period , 28 individuals progressed to dementia with a mean ( SD ) time to conversion of 2.19 ( 0.72 ) years . The clinic sample had an annual conversion rate of 13 % , whereas the community sample had an annual conversion rate of 3 % . In a Cox proportional hazards model , clinic recruitment source alone was associated with an increased hazard of incident dementia ( hazard ratio = 3.50 ; 95 % confidence interval , 1.31 - 9.18 ; P = .01 ) . When other variables were added to the model , only baseline functional impairment as measured by the Clinical Dementia Rating Scale ( and no demographic , cognitive , or neuroimaging variables or mild cognitive impairment subtype ) accounted for the differences in conversion rates across the 2 cohorts . CONCLUSIONS These findings add to the growing literature to suggest that the degree of functional impairment at baseline is an important predictor of conversion to dementia and may help explain differences in findings between epidemiological and clinic-based studies Objectives : To provide up date d estimates of Alzheimer disease ( AD ) dementia prevalence in the United States from 2010 through 2050 . Methods : Probabilities of AD dementia incidence were calculated from a longitudinal , population -based study including substantial numbers of both black and white participants . Incidence probabilities for single year of age , race , and level of education were calculated using weighted logistic regression and AD dementia diagnosis from 2,577 detailed clinical evaluations of 1,913 people obtained from stratified r and om sample s of previously disease-free individuals in a population of 10,800 . These were combined with US mortality , education , and new US Census Bureau estimates of current and future population to estimate current and future numbers of people with AD dementia in the United States . Results : We estimated that in 2010 , there were 4.7 million individuals aged 65 years or older with AD dementia ( 95 % confidence interval [ CI ] = 4.0–5.5 ) . Of these , 0.7 million ( 95 % CI = 0.4–0.9 ) were between 65 and 74 years , 2.3 million were between 75 and 84 years ( 95 % CI = 1.7–2.9 ) , and 1.8 million were 85 years or older ( 95 % CI = 1.4–2.2 ) . The total number of people with AD dementia in 2050 is projected to be 13.8 million , with 7.0 million aged 85 years or older . Conclusion : The number of people in the United States with AD dementia will increase dramatically in the next 40 years unless preventive measures are developed There is scarce information about the pathophysiological processes underlying Late-Life Depression ( LLD ) . We aim ed to determine the neurobiological abnormalities related to LLD through a multi-modal biomarker approach combining a large , unbiased peripheral proteomic panel and structural brain imaging . We examined data from 44 LLD and 31 control participants . Plasma proteomic analysis was performed using a multiplex immunoassay . We evaluated the differential protein expression between groups with r and om intercept models . We carried out enrichment pathway analyses ( EPA ) to uncover biological pathways and processes related to LLD . Machine learning analysis was applied to the combined data set to determine the accuracy with which specific proteins could correctly discriminate LLD versus control participants . Sixty-one proteins were differentially expressed in LLD ( p < 0.05 and FDR < 0.01 ) . EPA showed that these proteins were related to abnormal immune-inflammatory control , cell survival and proliferation , proteostasis control , lipid metabolism , intracellular signaling . Machine learning analysis showed that a panel of three proteins ( C-peptide , FABP-liver , ApoA-IV ) discriminated LLD and control participants with 100 % accuracy . The plasma proteomic profile in LLD revealed dysregulation in biological processes essential to the maintenance of homeostasis at cellular and systemic levels . These abnormalities increase brain and systemic allostatic load leading to the downstream negative outcomes of LLD , including increased risk of medical comorbidities and dementia . The peripheral biosignature of LLD has predictive power and may suggest novel putative therapeutic targets for prevention , treatment , and neuroprotection in LLD Output:	Further , posterior midline regions ( posterior cingulate cortex and precuneus ) appeared to have the most structural and functional alterations in all patient groups .
MS21547	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Contingency management ( CM ) rapidly reduces cocaine use , but its effects subside after treatment . Cognitive-behavioral therapy ( CBT ) produces reductions months after treatment . Combined , the 2 might be complementary . One hundred ninety-three cocaine-using methadone-maintained out patients were r and omly assigned to 12 weeks of group therapy ( CBT or a control condition ) and voucher availability ( CM contingent on cocaine-negative urine or noncontingent ) . Follow-ups occurred 3 , 6 , and 12 months posttreatment . Primary outcome was cocaine-negative urine ( urinalysis 3 times/week during treatment and once at each follow-up ) . During treatment , initial effects of CM were dampened by CBT . Posttreatment , there were signs of additive benefits , significant in 3- versus 12-month contrasts . Former CBT participants were also more likely to acknowledge cocaine use and its effects and to report employment A r and omized trial was conducted to test the effectiveness of couple-based HIV counseling and testing ( CB-HIV-CT ) and women-only relationship-focused HIV counseling and testing ( WRF-HIV-CT ) in reducing HIV risk compared to the National Institute on Drug Abuse HIV-CT st and ard intervention . Substance using HIV-negative women and their primary heterosexual partner ( N = 330 couples ) were r and omized to 1 of the 3 interventions . Follow-up assessment s measuring HIV risk behaviors and other relevant variables were conducted at 3- and 9-months postintervention . Repeated measures generalized linear mixed model analysis was used to assess treatment effects . A significant reduction in HIV risk was observed over the 9-month assessment in the CB-HIV-CT group compared to that of the control group ( b = −0.51 , t[527 ] = −3.20 , P = 0.002 ) and compared to that of the WRF-HIV-CT group ( b = −0.34 , t[527 ] = −2.07 , P = 0.04 ) , but no significant difference was observed between WRF-HIV-CT and controls ( b = −0.17 , t[527 ] = −1.09 , P = 0.28 ) . A brief couple-based HIV counseling and testing intervention design ed to address both drug-related and sexual risk behaviors among substance using women and their primary male partners was shown to be more effective at reducing overall HIV risk compared to a st and ard HIV-CT intervention in an urban setting Background : There is a lack of effective behavioral interventions for HIV-positive injection drug users ( IDUs ) . We sought to evaluate the efficacy of an intervention to reduce sexual and injection transmission risk behaviors and to increase utilization of medical care and adherence to HIV medications among this population . Methods : HIV-positive IDUs ( n = 966 ) recruited in 4 US cities were r and omly assigned to a 10-session peer mentoring intervention or to an 8-session video discussion intervention ( control condition ) . Participants completed audio computer-assisted self-interviews and had their blood drawn to measure CD4 cell count and viral load at baseline and at 3-month ( no blood ) , 6-month , and 12-month follow-ups . Results : Overall retention rates for r and omized participants were 87 % , 83 % , and 85 % at 3 , 6 , and 12 months , respectively . Participants in both conditions reported significant reductions from baseline in injection and sexual transmission risk behaviors , but there were no significant differences between conditions . Participants in both conditions reported no change in medical care and adherence , and there were no significant differences between conditions . Conclusions : Both interventions led to decreases in risk behaviors but no changes in medical outcomes . The characteristics of the trial that may have contributed to these results are examined , and directions for future research are identified OBJECTIVES We evaluated the efficacy of a peer-mentoring behavioral intervention design ed to reduce risky distributive injection practice s ( e.g. , syringe lending , unsafe drug preparation ) among injection drug users with hepatitis C virus ( HCV ) infection . METHODS A r and omized trial with a time-equivalent attention-control group was conducted among 418 HCV-positive injection drug users aged 18 to 35 years in 3 US cities . Participants reported their injection-related behaviors at baseline and at 3- and 6-month follow-ups . RESULTS Compared with the control group , intervention-group participants were less likely to report distributive risk behaviors at 3 months ( odds ratio [OR]=0.46 ; 95 % confidence interval [CI]=0.27 , 0.79 ) and 6 months ( OR=0.51 ; 95 % CI=0.31 , 0.83 ) , a 26 % relative risk reduction , but were no more likely to cite their HCV-positive status as a reason for refraining from syringe lending . Effects were strongest among intervention-group participants who had known their HCV-positive status for at least 6 months . Peer mentoring and self-efficacy were significantly increased among intervention-group participants , and intervention effects were mediated through improved self-efficacy . CONCLUSIONS This behavioral intervention reduced unsafe injection practice s that may propagate HCV among injection drug users Background We evaluated brief combination interventions to simultaneously reduce sexual and injection risks among female sex workers who inject drugs ( FSW-IDUs ) in Tijuana and Ciudad Juarez , Mexico during 2008–2010 , when harm reduction coverage was exp and ing rapidly in Tijuana , but less so in Juarez . Methods FSW-IDUs ≥18 years reporting sharing injection equipment and unprotected sex with clients within the last month participated in a r and omized factorial trial comparing four brief , single-session conditions combining either an interactive or didactic version of a sexual risk intervention to promote safer sex in the context of drug use , and an injection risk intervention to reduce sharing of needles/injection paraphernalia . Women underwent quarterly interviews and testing for HIV , syphilis , gonorrhea , Chlamydia and Trichomonas , blinding interviewers and assessors to assignment . Poisson regression with robust variance estimation and repeated measures ordinal logistic regression examined effects on combined HIV/STI incidence and receptive needle sharing frequency . Findings Of 584 initially HIV-negative FSW-IDUs , retention was ≥90 % . After 12 months , HIV/STI incidence decreased > 50 % in the interactive vs. didactic sex intervention ( Tijuana : AdjRR:0.38,95 % CI:0.16–0.89 ; Juarez : AdjRR:0.44,95 % CI:0.19–0.99 ) . In Juarez , women receiving interactive vs. didactic injection risk interventions decreased receptive needle-sharing by 85 % vs. 71 % , respectively ( p = 0.04 ) ; in Tijuana , receptive needle sharing declined by 95 % , but was similar in active versus didactic groups . Tijuana women reported significant increases in access to syringes and condoms , but Juarez women did not . Interpretation After 12 months in both cities , the interactive sexual risk intervention significantly reduced HIV/STI incidence . Exp and ing free access to sterile syringes coupled with brief , didactic education on safer injection was necessary and sufficient for achieving robust , sustained injection risk reductions in Tijuana . In the absence of exp and ing syringe access in Juarez , the injection risk intervention achieved significant , albeit more modest reductions , suggesting that community-level interventions incorporating harm reduction are more powerful than individual-level interventions . Trial Registration clinical trials.gov Active injection drug users ( IDUs ) who are also hazardous alcohol users are at particularly high risk for HIV transmission due to sharing of injection equipment . We recruited AUDIT-positive injectors from the Providence , RI needle exchange program for a r and omized clinical trial testing the effect of a brief motivational intervention ( MI ) on frequency of injection-related HIV risk behavior ( IRRB ) . HIV drug risk behavior was measured as the number of days on which subjects reported sharing works using the 30-day Timeline Followback Method . Overall , 109 subjects reported a mean reduction of IRRB days of 9.1 days from baseline to 6-month follow-up ( p < .001 ) . When compared to controls , there was a trend in reduction of IRRB days to zero at follow-up for MI subject ( OR = 2.1 ; 95 % CI = 0.9 - 4.5 ) , and strongly significant reductions in IRRB days across a range of alternative improvement thresholds . Results from this study demonstrate that MI reduces drug-related HIV risk behaviors among active IDUs . As a brief intervention , MI may be a useful adjunct to existing services intended to reduce harm BACKGROUND This study estimates the past year prevalence of and factors associated with sex trading ( offering sex for money , drugs or something else ) among 1796 men and women presenting to 342 drug misuse treatment agencies in Engl and , and identifies service development and delivery implication s. METHODS Secondary analysis of baseline data from a prospect i ve cohort was conducted . Short Form-12 measured mental and physical wellbeing , psychiatric diagnoses were self-reported and the circumstances , motivation and readiness tool assessed readiness for/pressure to enter treatment . Logistic regression models determined associations with sex trading separately by sex . Inverse probability population weights were calculated , utilising demographics from the National Drug Treatment Monitoring System and agency specific data collection windows . RESULTS The estimated prevalence rate of sex trading in the past 12 months was 5.1 % ( 15.0 % for women and 2.1 % for men ) . For women , adjusted models identified crack use ( aOR 1.83 , 95 % CI 1.22 - 2.74 , p=0.004 ) , previous treatment ( aOR 3.00 , 95 % CI 1.31 - 6.86 , p=0.010 ) and greater readiness for treatment ( aOR 1.12 , 95 % CI 1.01 - 1.24 , p=0.027 ) as independently associated with sex trading . For men , lower mental wellbeing ( aOR 0.97 , 95 % CI 0.94 - 0.99 , p=0.030 ) was independently associated and marginal effects were identified for syringe sharing ( aOR 2.89 , 95 % CI 0.94 - 8.86 , p=0.064 ) and unprotected sex ( aOR 2.23 , 95 % CI 0.95 - 5.26 , p=0.065 ) . CONCLUSIONS Sex trading among drug misusers is associated with additional health risks and specific treatment needs . Given the scale of the problem it is important that treatment providers have the competencies to adequately address the issue and provide accessible and appropriate services Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES We compared the effects of 2 interventions on alcohol use , use of a new syringe at last injection , and condom use at last sexual encounter in a community sample of injection drug users . METHODS Between 2003 and 2006 , 851 out-of-treatment injection drug users were recruited in Raleigh , NC , and Durham , NC , through street outreach and were r and omly assigned to either a 6-session educational intervention or a 6-session motivational intervention . Intervention effects were examined at 6 and 12 months after enrollment . RESULTS In multiple logistic regression analyses adjusted for baseline alcohol use and HCV status , participants assigned to the motivational intervention were significantly less likely than were participants in the educational intervention to be drinking at the 6-month follow-up ( odds ratio = 0.67 ; 95 % confidence interval = 0.46 , 0.97 ) . There were no significant between-group differences in use of a new syringe at last injection or condom use at last sexual encounter at either follow-up . CONCLUSIONS Reducing alcohol use among persons with HCV may slow disease progression and provide important health benefits . Additional strategies are needed for slowing HCV disease progression until more effective HCV treatments are available This study r and omized 90 HIV-seropositive , methadone-maintained injection drug users ( IDUs ) to an HIV Harm Reduction Program ( HHRP+ ) or to an active control that included harm reduction components recommended by the National AIDS Demonstration Research Project . The treatment phase lasted 6 months , with follow-ups at 6 and 9 months after treatment entry . Patients in both treatments showed reductions in risk behaviors . However , patients assigned to HHRP+ were less likely to use illicit opiates and were more likely to adhere to antiretroviral medications during treatment ; at follow-up , they had lower addiction severity scores and were less likely to have engaged in high risk behavior . Findings suggest that enhancing methadone maintenance with an intervention targeting HIV-seropositive IDUs increases both harm reduction and health promotion behaviors AIMS Social norms are a key source of influence on health behaviors . This study examined changes in social norms and relationships between HIV injection risk behaviors and social norms among injection drug users ( IDUs ) involved in an experimental intervention . DESIGN R and omized clinical trial . SETTING An HIV Prevention Trials Network study , Philadelphia , USA . PARTICIPANTS IDUs , called indexes , and their social network members , who were drug or sex partners , were recruited for an HIV prevention intervention and followed for up to 30 months ( n = 6 Output:	Such interventions could be included with other harm reduction approaches to prevent BBV transmission among PWID.ResumenEl tratamiento de sustitución de opiáceos y los programas de intercambio de jeringuillas han disminuido la transmisión de virus transmitidos por sangre ( VTS ) entre los usuarios de drogas inyectadas ( UDI ) .
MS21548	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: More effective therapeutic strategies are required for patients with poor-prognosis systemic sclerosis ( SSc ) . A phase 2 single-arm study of high-dose immunosuppressive therapy ( HDIT ) and autologous CD34-selected hematopoietic cell transplantation ( HCT ) was conducted in 34 patients with diffuse cutaneous SSc . HDIT included total body irradiation ( 800 cGy ) with lung shielding , cyclophosphamide ( 120 mg/kg ) , and equine antithymocyte globulin ( 90 mg/kg ) . Neutrophil and platelet counts were recovered by 9 ( range , 7 to 13 ) and 11 ( range , 7 to 25 ) days after HCT , respectively . Seventeen of 27 ( 63 % ) evaluable patients who survived at least 1 year after HDIT had sustained responses at a median follow-up of 4 ( range , 1 to 8) years . There was a major improvement in skin ( modified Rodnan skin score , -22.08 ; P < .001 ) and overall function ( modified Health Assessment Question naire Disability Index , -1.03 ; P < .001 ) at final evaluation . Importantly , for the first time , biopsies confirmed a statistically significant decrease of dermal fibrosis compared with baseline ( P < .001 ) . Lung , heart , and kidney function , in general , remained clinical ly stable . There were 12 deaths during the study ( transplantation-related , 8 ; SSc-related , 4 ) . The estimated progression-free survival was 64 % at 5 years . Sustained responses including a decrease in dermal fibrosis were observed exceeding those previously reported with other therapies . HDIT and autologous HCT for SSc should be evaluated in a r and omized clinical trial Autologous hematopoietic stem cell transplantation ( HSCT ) utilizing a myeloablative regimen containing total body irradiation has been performed in patients with systemic sclerosis ( SSc ) , but with substantial toxicity . We , therefore , conducted a phase I non-myeloablative autologous HSCT study in 10 patients with SSc and poor prognostic features . PBSC were mobilized with CY and G-CSF . The PBSC graft was cryopreserved without manipulation and re-infused after the patient was treated with a non-myeloablative conditioning regimen of 200 mg/kg CY and 7.5 mg/kg rabbit antithymocyte globulin . There was a statistically significant improvement of modified Rodnan skin score whereas cardiac ( ejection fraction , pulmonary arterial pressure ) , pulmonary function ( DLCO ) and renal function ( creatinine ) remained stable without significant change . One patient with advanced disease died 2 years after the transplant from progressive disease . After median follow-up of 25.5 months , the overall and progression-free survival rates are 90 and 70 % respectively . Autologous HSCT utilizing a non-myeloablative conditioning regimen appears to result in improved skin flexibility similar to a myeloablative TBI containing regimen , but without the toxicity and risks associated with TBI BACKGROUND Non-r and omised studies of haemopoietic stem-cell transplantation ( HSCT ) in systemic sclerosis have shown improvements in lung function and skin flexibility but high treatment-related mortality . We aim ed to assess safety and efficacy of autologous non-myeloablative HSCT in a phase 2 trial compared with the st and ard of care , cyclophosphamide . METHODS In our open-label , r and omised , controlled phase 2 trial , we consecutively enrolled patients at Northwestern Memorial Hospital ( Chicago , IL , USA ) who were aged younger than 60 years with diffuse systemic sclerosis , modified Rodnan skin scores ( mRSS ) of more than 14 , and internal organ involvement or restricted skin involvement ( mRSS < 14 ) but coexistent pulmonary involvement . We r and omly allocated patients 1:1 by use of a computer-generated sequence with a mixed block design ( blocks of ten and four ) to receive HSCT , 200 mg/kg intravenous cyclophosphamide , and 6·5 mg/kg intravenous rabbit antithymocyte globulin or to receive 1·0 g/m(2 ) intravenous cyclophosphamide once per month for 6 months . The primary outcome for all enrolled patients was improvement at 12 months ' follow-up , defined as a decrease in mRSS ( > 25 % for those with initial mRSS > 14 ) or an increase in forced vital capacity by more than 10 % . Patients in the control group with disease progression ( > 25 % increase in mRSS or decrease of > 10 % in forced vital capacity ) despite treatment with cyclophosphamide could switch to HSCT 12 months after enrolment . This study is registered with Clinical Trials.gov , number NCT00278525 . FINDINGS Between Jan 18 , 2006 , and Nov 10 , 2009 we enrolled 19 patients . All ten patients r and omly allocated to receive HSCT improved at or before 12 months ' follow-up , compared with none of nine allocated to cyclophosphamide ( odds ratio 110 , 95 % CI 14·04-∞ ; p=0·00001 ) . Eight of nine controls had disease progression ( without interval improvement ) compared with no patients treated by HSCT ( p=0·0001 ) , and seven patients switched to HSCT . Compared with baseline , data for 11 patients with follow-up to 2 years after HSCT suggested that improvements in mRSS ( p<0·0001 ) and forced vital capacity ( p<0·03 ) persisted . INTERPRETATION Non-myeloablative autologous HSCT improves skin and pulmonary function in patients with systemic sclerosis for up to 2 years and is preferable to the current st and ard of care , but longer follow-up is needed . FUNDING None OBJECTIVE The aim of this study was to find a new and less cardiotoxic conditioning regimen for high-dose chemotherapy and autologous stem cell transplantation ( aSCT ) in patients with severe SSc and pre-existing cardiac involvement . METHODS Six patients with cardiac involvement were treated for SSc with a conditioning regimen including reduced-dose CYC plus the non-cardiotoxic alkylant thiotepa . All patients received an implantable cardioverter defibrillator ( ICD ) before aSCT . The response at months 6 and 12 was measured according to reduction of the modified Rodnan skin score ( mRSS ) . CT histography was used to monitor pulmonary manifestations , as were echocardiography , N-terminal pro-brain natriuretic peptide ( NT-proBNP ) and troponin for the cardiac involvement . Cardiac events were defined as death or hospitalisation due to heart failure or appropriate discharge of the ICD . RESULTS Between December 2008 and May 2012 , four male and two female patients with a median age of 41 years received aSCT . The median mRSS significantly decreased from 26.5 to 18 and 17.5 at month 6 and 12 , respectively . The total lung volume also significantly improved . Within the median follow-up of 1.6 years ( range 1 - 3.8 ) two patients experienced a relapse of SSc , which results in a progression-free survival rate of 66.6 % . Three patients experienced ICD discharge . CONCLUSION For patients with SSc and cardiac involvement , the use of thiotepa and reduced-dose CYC is feasible and effective . The rate of ICD discharge underlines the need for protection in these endangered patients . This preliminary experience allowed us to use this regimen for our currently recruiting prospect i ve trial ( NCT01895244 ) Objective : Systemic sclerosis ( SSc ) is a generalised autoimmune disease , causing morbidity and a reduced life expectancy , especially in patients with rapidly progressive diffuse cutaneous SSc . As no proven treatment exists , autologous haematopoietic stem cell transplantation ( HSCT ) is employed as a new therapeutic strategy in patients with a poor prognosis . This study reports the effects on survival , skin and major organ function of HSCT in patients with severe diffuse cutaneous SSc . Patients and methods : A total of 26 patients were evaluated . Peripheral blood stem cells were collected using cyclophosphamide ( 4 g/m2 ) and rHu G-CSF ( 5 to 10 μg/kg/day ) and were reinfused after positive CD34 + selection . For conditioning , cyclophosphamide 200 mg/kg was used . Results : After a median follow-up of 5.3 ( 1–7.5 ) years , 81 % ( n = 21/26 ) of the patients demonstrated a clinical ly beneficial response . The Kaplan – Meier estimated survival at 5 years was 96.2 % ( 95 % CI 89–100 % ) and at 7 years 84.8 % ( 95 % CI 70.2–100 % ) and event-free survival , defined as survival without mortality , relapse or progression of SSc , result ing in major organ dysfunction was 64.3 % ( 95 % CI 47.9–86 % ) at 5 years and 57.1 % ( 95 % CI 39.3–83 % ) at 7 years . Conclusion : This study confirms that autologous HSCT in selected patients with severe diffuse cutaneous SSc results in sustained improvement of skin thickening and stabilisation of organ function up to 7 years after transplantation Output:	All the studies showed an improvement in mRSS . We conclude that ASCT is beneficial in some patients with SSc and that patient selection and conditioning regimens are critical determinants of prognosis and mortality post-ASCT
MS21549	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : This study was performed to identify tumor- and patient-related risk factors for distal rectal cancer in patients treated with an abdominoperineal resection ( APR ) associated with positive circumferential resection margin ( CRM ) , local recurrence ( LR ) , and overall survival ( OS ) . Background : The introduction of total mesorectal excision ( TME ) has improved the outcome of patients with rectal cancer . However , survival of patients treated with an APR improved less than of those treated with low anterior resections ( LAR ) . Besides , an APR is associated with a higher LR rate . Methods : Patients were selected from the TME trial , which is a r and omized , multicenter trial , study ing the effects of preoperative radiotherapy ( RT ) in 1861 patients . Of the Dutch patients , 455 underwent an APR . Location of the bulk of the tumor was scored with surgery , pathology , or other reports . CRM was available from pathology reports . Result : A positive CRM was found in 29.6 % of all patients , 44 % for anterior , 21 % for lateral , 23 % for posterior , and 17 % for (semi)circular tumor location ( P < 0.0001 ) . In a multivariate analysis , T-stage , N-stage , and tumor location were independent risk factors for CRM . If a ( partial ) resection of the vaginal wall was performed in women , 47.8 % of patients still had a positive CRM . T-stage , N-stage , and CRM were risk factors for LR and age , T-stage , N-stage , CRM , and distance of the inferior tumor margin to the anal verge for OS . Conclusion : Age , T-stage , N-stage , CRM , distance of the tumor to the anal verge , and tumor location were independent risk factors for adverse outcome in patients treated with an APR for low rectal cancer . Anterior location , specifically in women , more often requires downstaging and /or more extended resection to obtain free margins PURPOSE : This study was design ed to examine the outcome of cancer of the lower rectum , particularly the rates of local recurrence and survival for tumors located in this area that have been treated by anterior or abdominoperineal resections . METHODS : A prospect i ve , observational , national , cohort study which is part of the Norwegian Rectal Cancer Project . The present cohort includes all patients undergoing total mesorectal excision in 47 hospitals during the period November 1993 to December 1999 . A total of 2,136 patients with rectal cancer within 12 cm of the anal verge were analyzed ; there were 1,315 ( 62 percent ) anterior resections and 821 ( 38 percent ) abdominoperineal resections . The lower edge of the tumor was located 0 to 5 cm from the anal verge in 791 patients , 6 to 8 cm in 558 patients , and 9 to 12 cm in 787 patients . According to the TNM classification , there were 33 percent Stage I , 35 percent Stage II , and 32 percent Stage III . RESULTS : Univariate analyses : The five-year local recurrence rate was 15 percent in the lower level , 13 percent in the intermediate level , and 9 percent in the upper level ( P = 0.014 ) . It was 10 percent local recurrence after anterior resection and 15 percent after abdominoperineal resection ( P = 0.008 ) . The five-year survival rate was 59 percent in the lower level , 62 percent in the intermediate level , and 69 percent in the upper level ( P < 0.001 ) , respectively , and it was 68 percent in the anterior-resection group and 55 percent in the abdominoperineal-resection group ( P < 0.001 ) . Multivariate analyses : The level of the tumor influenced the risk of local recurrence ( hazard ratio , 1.8 ; 95 percent confidence interval , 1.1–2.3 ) , but the operative procedure , anterior resection vs. abdominoperineal resection , did not ( hazard ratio , 1.2 ; 95 percent confidence interval , 0.7–1.8 ) . On the contrary , operative procedure influenced survival ( hazard ratio , 1.3 ; 95 percent confidence interval , 1–1.6 ) , but tumor level did not ( hazard ratio , 1.1 ; 95 percent confidence interval , 0.9–1.5 ) . In addition to patient and tumor characteristics ( T4 tumors ) , intraoperative bowel perforation and tumor involvement of the circumferential margin were identified as significant prognostic factors , which were more common in the lower rectum , explaining the inferior prognosis for tumors in this region . CONCLUSIONS : T4 tumors , R1 resections , and /or intraoperative perforation of the tumor or bowel wall are main features of low rectal cancers , causing inferior oncologic outcomes for tumors in this area . If surgery is optimized , preventing intraoperative perforation and involvement of the circumferential resection margin , the prognosis for cancers of the lower rectum seems not to be inherently different from that for tumors at higher levels . In that case , the level of the tumor or the type of resection will not be indicators for selecting patients for radiotherapy Aim Conventional outcomes such as survival , tumour recurrence and complication rates after surgery for rectal cancer have been rigorously assessed , but the importance of maintaining quality of life ( QOL ) after surgery for rectal cancer has received less attention . The aim of the current study was to analyse QOL and the occurrence of pelvic dysfunction after the surgical treatment of rectal cancer BACKGROUND Minimum numbers of cases required for certification by the American Board of Colon and Rectal Surgery ( ABCRS ) have been determined from a prospect i ve data base of all applicants applying for examination since 1989 . These data represent the longitudinal evolution of practice patterns in tertiary colorectal training programs . STUDY DESIGN After obtaining permission from the ABCRS , access to the data base was obtained and data from the 12-year period 1994 to 2005 were analyzed . RESULTS The data base contains the operative and endoscopic case numbers of 673 residents . The number of training programs increased from 28 to 39 ( 28 % ) and the number of residency positions from 50 to 66 ( 24 % ) . Median numbers of anorectal patients per resident remained remarkably constant over the period of study . Both rigid sigmoidoscopy ( 67 to 44 per resident ) and flexible sigmoidoscopy ( 135.5 to 39 per resident ) decreased substantially ; colonoscopy volume increased ( 209 to 264 per resident ) . Perineal procedures for rectal prolapse consistently comprise 50 % to 60 % of the total procedures for prolapse . Low anterior resection for rectal cancer outnumber abdominoperineal resections by a 3/1 ratio . Coloanal anastomoses have steadily increased . Laparoscopic approaches for all abdominal operations have increased substantially , with the greatest increase being in diverticular resections ( 6.5 % to 44.7 % ) . CONCLUSIONS Prospect i ve data collection by ABCRS has permitted calculation of minimum numbers of operative cases for training colorectal surgeons , with the advantage of a rolling average that reflects evolving practice patterns in teaching programs . Analysis of these data allows planning of needs-based educational programs and may ultimately be involved in design ing the maintenance of certification process Purpose Local recurrence and cure rates following abdominoperineal resections have been reported to be much worse than sphincter-preserving anterior resections . We compared the oncologic outcomes of patients treated by abdominoperineal resections with those following sphincter-preserving anterior resections . Methods The medical records of patients who underwent radical rectal resection for rectal carcinoma at the Colorectal Surgery Department , Singapore General Hospital , during the period from April 1989 to April 2002 were review ed . A total of 791 cases were studied . Operative procedures were classified as either abdominoperineal resections or anterior resections with either straight or pouch anastomosis . Total mesorectal excision was routinely performed for carcinomas of the lower middle and lower third of the rectum . Sentinel events , including local and systemic recurrences or morbidity and mortality , were tracked prospect ively . Results There were a total of 93 abdominoperineal resections ( 12.1 percent ) , 547 anterior resections with straight anastomoses ( 71 percent ) , and 130 anterior resections with pouch anastomoses ( 16.9 percent ) . Postoperative mortality was 2.6 percent and postoperative morbidity was 13.6 percent with an overall anastomotic leakage rate of 2.5 percent . The cumulative five-year local recurrence rate was 5.4 percent for abdominoperineal resections , 3.6 percent for anterior resections with straight anastomoses , and 3.8 percent for anterior resections with pouch anastomoses ( P = 0.73 by log-rank test ) . The median time to local recurrence also did not differ significantly between the different procedures ( abdominoperineal resections , 17 months , anterior resections with straight anastomoses , 18 months , anterior resections with pouch anastomoses , 13 months ) . Independent predictors for local recurrence included advanced tumor stage , tumor depth , and poorly differentiated tumors . The five-year cancer-specific survival was 70 percent . The type of anastomosis did not influence disease-free survival with median disease-free survival for patients who underwent abdominoperineal resections being 100 months , survival of anterior resections with straight anastomoses being 135 months , and survival of anterior resections with pouch anastomoses being 121 months ( P = 0.33 by log-rank test ) . The independent factors for poor survival were age greater than 65 years , advanced tumor stage , tumor depth , and poorly differentiated tumors . Conclusion Both abdominoperineal resections and sphincter-preserving anterior resections can be performed safely with low morbidity and mortality in a specialized high-volume hospital unit without compromising oncologic outcomes . With appreciation of the anatomic relations in total mesorectal excision and st and ardized consistent surgical technique , the oncologic outcomes of patients treated by abdominoperineal resections are not worse than those treated by sphincter-preserving anterior resections PURPOSE Despite the major improvements that have been made due to total mesorectal excision ( TME ) , low rectal cancer still remains a challenge . METHODS By investigating a prospect i ve r and omized rectal cancer trial in which surgeons had undergone training in TME the factors responsible for the poor outcome were determined and a new method for assessing the quality of surgery was tested . RESULTS Survival differed greatly between abdominoperineal resection ( APR ) and anterior resection ( AR ; 38.5 % v 57.6 % , P = .008 ) . Low rectal carcinomas have a higher frequency of circumferential margin involvement ( 26.5 % v 12.6 % , P < .001 ) . More positive margins were present in the patients operated with APR ( 30.4 % ) compared to AR ( 10.7 % , P = .002 ) . Furthermore , more perforations were present in these specimens ( 13.7 % v 2.5 % , P < .001 ) . The plane of resection lies within the sphincteric muscle , the submucosa or lumen in more than 1/3 of the APR cases , and in the remainder lay on the sphincteric muscles . CONCLUSION We systematic ally described and investigated the pathologic properties of low rectal cancer in general , and APR in particular , in a prospect i ve r and omized trial including surgeons who had been trained in TME . The poor prognosis of the patients with an APR is ascribed to the resection plane of the operation leading to a high frequency of margin involvement by tumor and perforation with this current surgical technique . The clinical results of this operation could be greatly improved by adopting different surgical techniques and possibly greater use of radiochemotherapy PURPOSE : Issues related to body image and a permanent stoma after abdominoperineal resection may decrease quality of life in rectal cancer patients . However , specific problems associated with a low anastomosis may similarly affect quality of life for patients undergoing low anterior resection . The aim of this study was to compare quality of life of low rectal cancer patients after undergoing abdominoperineal resection versus low anterior resection . METHODS : Demographics , tumor and treatment characteristics , and prospect ively collected preoperative quality -of-life data for patients undergoing low anterior resection or abdominoperineal resection for low rectal cancer between 1995 and 2009 were compared . Quality of life collected at specific time intervals was compared for the two groups , adjusting for age , body mass index , use of chemoradiation , and 30 days postoperative complications . The short-form-36 question naire was used to determine quality of life . RESULTS : The query returned 153 patients ( abdominoperineal resection = 68 , low anterior resection = 85 ) with a median follow-up of 24 ( 3 - 64 ) mo . The after abdominoperineal resection group had a higher mean age ( 63 ± 12 vs. 54 ± 12 , p < 0.001 ) and more American Society of Anesthesiologists classification 3/4 patients ( 65 percent vs. 43 percent , p = 0.03 ) than low anterior resection . Other demographics , tumor stage , use of chemoradiation , overall postoperative complication rates , and quality -of-life follow-up time were Output:	Patients treated by APR have a higher rate of CRM involvement , a higher local recurrence , and poorer prognosis than LAR . And there is evidence that in selected low rectal cancer patients , LAR can be used safely with a better oncological outcome than APR .
MS21550	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The outcome of different treatment modalities after 7 years was investigated in a selected group of 50 patients with craniom and ibular disorders of muscular origin . To minimize the possible effects of selection on the clinical material , the selected treatment group was compared to a consecutive group of patients in terms of age , gender , intensity/ duration of pain , and socioeconomic profile . Both groups were comparable in most respects , but the selected group had a longer duration and a higher intensity of pain at baseline . There were more men in the consecutive group than in the selected group . A combined treatment approach result ed in a better outcome than single treatments . Sixty-five percent of all patients in the selected group reported improvement at the 7-year follow-up . All of the 19 patients who received counseling combined with different occlusal treatments improved . Forty-three percent of the patients treated otherwise showed improvement . Patients who were aware of stress responded better to treatment A double-blind pilot study was undertaken to test the administration of low doses of the long-acting benzodiazepine drug clonazepam in the management of chronic intractable temporom and ibular disorder/myofascial pain patients who were not responsive to occlusal splint , behavioral , and physical therapy . Clonazepam was selected for its long duration and its cholinergic/GABA-ergic/serotonergic , anxiolytic , muscle relaxant , and sedative properties . Clonazepam appears to be effective when compared to a placebo . However , caution must be observed with long-term administration of clonazepam because of potential side effects such as depression and liver dysfunction . Indiscriminate administration of clonazepam may be harmful to the patient The hypothesis that the response to conventional physical therapy of patients suffering from chronic cervicobrachial pain and /or headache can be improved by adjusting dental occlusion , was tested . Forty patients seeking treatment were interviewed and examined prior to treatment , and 6 weeks , 12 months and 60 months after treatment . All patients underwent routine physical therapies . They were pairwise matched for age , gender and type of dental occlusion , and r and omly allocated to a true occlusal adjustment group or to a mock adjustment group . The patients and the examiners were unaware of the type of dental treatment given . The outcome variables included subjective pain and discomfort , cervical spine mobility and pain on movement , and comparison of relative EMG activities . The short-term response to therapy was good in both groups . In the long-term , however , the response was significantly better in the patients who had undergone occlusal adjustment than in the mock-adjusted controls The aim of this study was to evaluate the therapeutic effect of occlusal adjustment on symptoms and signs of craniom and ibular disorders ( CMD ) , including headaches , after 3 and 6 months . Fifty patients were selected and r and omly assigned to a treatment ( T ) or a control ( C ) group . All patients in the treatment group were subjected to occlusal adjustment , whereas the controls were comforted only . Pre- and post-treatment assessment of subjective symptoms and clinical signs was made by a dentist not performing the occlusal adjustment . There was significant improvement in overall subjective symptoms within the T group at the 3- and 6-month follow-up visits , but a statistically significant difference between groups was found at the 3-month follow-up only . With regard to changes in frequency of facial pain a significant deterioration was reported within the C group , which result ed in a significant difference between groups at the 6-month follow-up . No other significant differences were found within or between groups at the follow-ups with regard to the variables investigated . In conclusion , the results from this study that occlusal adjustment is a treatment modality with a statistically significant short-term effect on symptoms of CMD of muscular origin and superior to counseling Sixty-two dental students judged not to be in need of treatment for craniom and ibular disorder ( CMD ) were r and omly divided into two groups , one receiving occlusal adjustment and the other mock adjustment . A double-blind study design was applied . After 2 years of education in dentistry , including courses in stomatognathic physiology , the increase in the subjective symptoms of CMD was significantly greater in the placebo control group than in the treatment group . The difference between the groups in the increase of sites tender to palpation was less clear , showing only a trend . However , the increase was statistically significant within the placebo group but not within the treatment group . Prophylactic occlusal adjustment thus appears to be effective in reducing the occurrence of symptoms of CMD , and possibly also the occurrence of clinical signs The aim of this study was to evaluate the effect of occlusal adjustment in a prospect i ve longitudinal study . Fifty selected patients with craniom and ibular disorders ( CMD ) including headaches were r and omly assigned to a treatment ( T ) or a control ( C ) group . Both groups received counselling and occlusal adjustment was performed in T group . Subjective symptoms and clinical findings were registered before and 2 years after treatment . At a follow-up 48 % in the T group and 84 % in the C group had dem and ed rescue treatment . Eleven patients in the T group ( 48 % ) and 3 patients in the C group ( 13 % ) without rescue treatment , reported overall subjective improvement . No difference was found between the groups regarding overall intensity of pain expressed by the visual analogue scale . When all kinds of treatment were taken into account , 70 % and 79 % of the patients in the T and C group reported overall subjective improvement at follow-up . The conclusions from this study were that in a two-year perspective only single patients improved from counselling alone . A few more patients improved if one more kind of treatment , for example occlusal adjustment , was added to the initial counselling , but the majority of the patients required a comprehensive treatment program The aim of this study was to assess the short-term effect of occlusal adjustment on craniom and ibular disorders . Fifty patients were r and omly selected and divided into a treatment ( T ) and a control ( C ) group . The initial clinical examination and the follow-up were made by one observer and the occlusal adjustment by another . There were no significant differences between groups with regard to frequency of headaches , facial pain , pain on m and ibular function , or duration of headaches and facial pain . Fifty-two percent of the patients in the treatment group and 20 % of the patients in the control group reported reduced subjective symptoms overall at follow-up examination . The improvement was statistically significant within the T group and significantly greater than in the C group . There was no significant change within or between groups with regard to frequency of headaches , facial pain , or pain on m and ibular movements . There was an almost significant difference between groups after treatment with regard to changes in the number of tender muscles . The results of this study indicate that occlusal adjustment provides a general subjective improvement of craniom and ibular disorders In a double-blind study , 22 patients with typical globus symptoms were investigated by both otolaryngological and odontological methods . All the patients underwent thorough hematological , endoscopic and radiological examinations . They were r and omly divided into a treatment group and a placebo group and underwent either simple occlusal adjust or mock adjustment , respectively . The result of occlusal adjustment was assessed immediately after completion of treatment . The effect of treatment on globus symptoms was assessed 2 to 3 months later in a double-blind study . Binomial tests showed that there was a significant association between the success of occlusal adjustment and disappearance of the globus symptom . A new name for this disease is proposed : the globus syndrome STATEMENT OF PROBLEM Contrary to clinical opinion , the structural risk from dental occlusion in temporom and ibular disorders has been question ed or considered to be insignificant in clinical practice . PURPOSE This study tested the effect of elimination of occlusal interference through occlusal adjustment , on the incidence of temporom and ibular disorders . MATERIAL AND METHODS In a controlled clinical trial of 146 healthy children and adolescents , half of the subjects underwent occlusal adjustment aim ed at elimination of the presumed structural risk , and the other half underwent mock adjustment . Adjustments were repeated every 6 months over a period of 4 years . The outcome variable was the incidence of temporom and ibular disorders , operatively defined as request for treatment of symptoms characteristic of the disorders with presence of clinical signs demonstrated in the muscles of mastication and /or jaw joint . RESULTS The cumulative incidence rate was 9/67 in the mock adjustment group and 1/60 in the real adjustment group , for a relative risk of 8.06 . The difference between groups was statistically significant ( p = 0.019 ) . CONCLUSIONS Elimination of the presumed structural risk from the dental occlusion appeared to significantly reduce the incidence of temporom and ibular disorders in a select group of young subjects Twenty-two patients seeking treatment for the globus symptom were examined for the presence of symptoms and signs of TMJ dysfunction . They were r and omly divided into a treatment group ( N = 13 ) and a placebo group ( N = 9 ) and underwent either simple occlusal adjustment or mock adjustment , respectively . The result of occlusal adjustment was assessed immediately after completion of treatment . The effect of treatment on the globus symptom was assessed 2 to 3 months later in a double-blind study design . Binomial tests showed that there was a significant association between the success of occlusal adjustment and disappearance of the globus symptom . Three patients in the placebo group subsequently received occlusal adjustment and splint therapy . When all patients were interviewed 20 to 44 months later , only two of them reported no improvement . Both had unstable occlusion when the treatment was terminated Recommendations about the need for occlusal adjustment after malocclusion therapy are inconclusive . A total of 123 orthodontically treated healthy adolescents ( 88 girls , 35 boys ; 14.8 + /- 1.7 years old ) agreed to participate in the present study . The subjects were interviewed and examined for signs and symptoms related to temporom and ibular disorder ( TMD ) and were r and omly allocated to intervention ( n = 63 ) and control ( n = 60 ) groups . At base line , occlusal adjustment was carried out for the intervention group and repeated every 6 months thereafter as needed . Mock adjustments were performed for the control group . At the end of the 3rd year 118 subjects ( 96 % ) turned up for re-examination . The number of subjects with palpatory pain of the masticatory muscles , and with occlusal centric slides decreased significantly in the intervention group but not in the control group ( P < 0.001 ) . In conclusion , occlusal adjustment therapy may prevent the occurrence of TMD signs in orthodontically treated healthy adolescents Fifty-one patients with craniom and ibular disorders were divided in two groups . One group underwent mock occlusal adjustment , the other was treated with adjustments to remove significant slides and non-working side interferences . Both groups received identical counseling . The results show that there was no significant difference in the improvements on the signs and symptoms obtained by real or mock adjustments after the first treatment session A group of headache patients who also had many signs and symptoms of m and ibular dysfunction were r and omly assigned to treatment and placebo groups . All 48 patients in the treatment group received occlusal adjustment and 19 of them also splint therapy . In the placebo group all 43 patients received mock adjustment . The changes in symptoms and signs of m and ibular dysfunction were evaluated after 8 months in the treatment group and after 4 months in the placebo group , in a double-blind design . Placebo treatment and real treatment were equally effective in relieving symptoms of m and ibular dysfunction , but there was significantly more reduction in signs of dysfunction in the treatment group than in the placebo group . When tested statistically , this reduction appeared to be independent of the use of splints as an aid to treatment . It can be concluded that the elimination of occlusal disturbances was an effective treatment for m and ibular dysfunction The purpose of this study is to assess what impact shortening disclusion time to less than .5 seconds during right and left m and ibular excursions has on myofascial pain(s ) symptoms present in a dental student population . Twenty-five dental students , who exhibited symptomatology consistent with myofascial pains patient , were divided into a treatment , control , and an untreated group . They participated in an occlusal adjustment study which measured changes in disclusion time , as well as , myofascial pains muscular symptom remissions result ant from treatment . The treated group of ten subjects received ICAGD occlusal adjustments to shorten their disclusion time to less than .5 seconds per m and ibular excursion . The goal of this therapy was to totally disclude the posterior teeth in a measurable time frame of .5 seconds or less . The control group of eight subjects received mock ICAGD with tooth polishing . The goal of this therapy was to simulate ICAGD adjustments for possible placebo effect on symptom remissions . The untreated group had their disclusion times measured but received no treatment to adjust , or to simulate adjustment to their occlusion . The goal of analyzing an untreated group was to attempt to show that mock treatment ( performed on the control subjects ) , or no treatment ( performed on the untreated subjects ) , result ed in no measurable change in the disclusion time in either of these two subject groups . Each subject was recalled for disclusion time measurement four to five times in a one-year period of observation , at which time , they were required to report their myofascial pains symptom status by answering an ordinal scale question naire . The results suggest that shortening disclusion time to less than .5 seconds per m and ibular excursion can induce remissions of many muscular myofascial pains symptoms . Additionally , mock ICAGD occlusal adjustments did not appear to be a factor in the control subjects treatment response , as this group showed no statistically significant symptom remissions Thirty patients with craniom and ibular disorders and headache were r and omly divided into two groups . One received occlusal equilibration ( O group ) and the Output:	REVIEW ER 'S CONCLUSIONS There is an absence of evidence , from RCTs , that occlusal adjustment treats or prevents TMD . Occlusal adjustment can not be recommended for the management or prevention of TMD .
MS21551	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This 18-week , r and omized , flexible-dose , double-blind , double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients . Patients had a DSM-IV diagnosis of schizophrenia , a history of resistance and /or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses , PANSS score > or=80 , and CGI-S score > or=4 . Patients were r and omized to ziprasidone ( 80 - 160 mg/day , n=73 ) or clozapine ( 250 - 600 mg/day , n=74 ) . On the primary ITT-LOCF analysis , baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone ( -25.0+/-22.0 , 95 % CI -30.2 to -19.8 ) and clozapine ( -24.5+/-22.5 , 95 % CI -29.7 to -19.2 ) groups . A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms . There were also significant improvements on PANSS subscales , CGI-S , CG-I , CDSS , and GAF , without between-drug differences . The two treatment groups had similar rates of early discontinuations due to AEs . AEs were mostly of similar mild-moderate severity in the two groups . There were also no detrimental effects on prolactin , renal and liver function , hematology , and cardiovascular parameters . However , ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores . Moreover , when compared with clozapine , ziprasidone also had a more favorable metabolic profile , with significant endpoint differences in weight , fasting glucose , total cholesterol , LDL cholesterol , and triglycerides . In conclusion , this trial indicates that both ziprasidone and clozapine , having comparable efficacy coupled with satisfactory general safety and tolerability , may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and /or intolerance to antipsychotics . The more favorable metabolic profile of ziprasidone may represent an added value that could guide clinicians , at least in the presence of patients at high risk for metabolic disorders OBJECTIVE This prospect i ve , double-blind , multicenter , parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response . METHOD Male or female patients aged 18 - 65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response ( N=273 ) were r and omly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments . The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale ( BPRS ) and Clinical Global Impression ( CGI ) scores . Adverse events were recorded throughout the study . RESULTS The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group . Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures ( Positive and Negative Syndrome Scale , Calgary Depression Scale , Psychotic Depression Scale , and Psychotic Anxiety Scale ) . The adverse event profile was similar for both treatment groups , with a lower risk of extrapyramidal symptoms in the clozapine group . CONCLUSIONS Clozapine showed superior efficacy over risperidone in this patient population . Both treatments were equally well tolerated as demonstrated through their adverse event profiles , although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone OBJECTIVE When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug , it is unclear what other antipsychotic to switch to and when to use clozapine . In this study , the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness ( CATIE ) investigation . METHOD Ninety-nine patients who discontinued treatment with olanzapine , quetiapine , risperidone , or ziprasidone in phase 1 or 1B of the trials , primarily because of inadequate efficacy , were r and omly assigned to open-label treatment with clozapine ( N=49 ) or blinded treatment with another newer atypical antipsychotic not previously received in the trial ( olanzapine [ N=19 ] , quetiapine [ N=15 ] , or risperidone [ N=16 ] ) . RESULTS Time until treatment discontinuation for any reason was significantly longer for clozapine ( median=10.5 months ) than for quetiapine ( median=3.3 ) , or risperidone ( median=2.8 ) , but not for olanzapine ( median=2.7 ) . Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine , quetiapine , or risperidone . At 3-month assessment s , Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine . One patient treated with clozapine developed agranulocytosis , and another developed eosinophilia ; both required treatment discontinuation . CONCLUSIONS For these patients with schizophrenia who prospect ively failed to improve with an atypical antipsychotic , clozapine was more effective than switching to another newer atypical antipsychotic . Safety monitoring is necessary to detect and manage clozapine 's serious side effects BACKGROUND 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 OBJECTIVE The authors compared the efficacy and safety of three atypical antipsychotics ( clozapine , olanzapine , and risperidone ) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder . METHOD In a double-blind trial , 157 in patients with a history of suboptimal treatment response were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol for 14 weeks ( an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period ) . RESULTS Clozapine , risperidone , and olanzapine ( but not haloperidol ) result ed in statistically significant improvements in total score on the Positive and Negative Syndrome Scale . Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol . The atypical drugs , particularly olanzapine and clozapine , were associated with weight gain . CONCLUSIONS The effects of atypical antipsychotics in this population were statistically significant but clinical ly modest . The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective . Clozapine was the most effective treatment for negative symptoms . However , the differences among treatments were small BACKGROUND Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia , questions remain regarding its efficacy for primary negative symptoms , comparison with a moderate dose of a first-generation antipsychotic , and adverse effects during a longer-term trial . This study examined its efficacy in partially responsive , community-based patients , compared clozapine with moderate-dose haloperidol , and extended treatment to 6 months . METHODS R and omized , double-blind , 29-week trial comparing clozapine ( n = 37 ) with haloperidol ( n = 34 ) . Subjects with schizophrenia who were being treated in community setting s at 3 collaborating clinical facilities were enrolled . RESULTS Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy ( 51 % ) than were those treated with clozapine ( 12 % ) . A higher proportion of clozapine-treated subjects met an a priori criterion of improvement ( 57 % ) compared with haloperidol-treated subjects ( 25 % ) . Significantly greater improvement was seen in symptoms of psychosis , hostile-suspiciousness , anxiety-depression , thought disturbance , and total score measured on the Brief Psychiatric Rating Scale . No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms . Subjects treated with clozapine experienced more excess salivation , dizziness , and sweating and less dry mouth and decreased appetite than those treated with haloperidol . CONCLUSIONS Compared with a first-generation antipsychotic given in a moderate dose , clozapine offers substantial clinical benefits to treatment-refractory subjects who can be treated in the community . Advantages are seen in a broad range of symptoms but do not extend to negative symptoms BACKGROUND The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge . Clozapine has been one treatment option ; however , it is not universally effective and is limited in its use by safety concerns . With the introduction of newer agents , their performance relative to clozapine is of great clinical interest . METHODS The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients . The study was primarily design ed to demonstrate the " noninferiority " of olanzapine compared to clozapine after 18 weeks of double-blind treatment . Conclusions were based on the one-sided lower 95 % confidence limit about the treatment effect observed from the primary efficacy variable ( Positive and Negative Syndrome Scale [ PANSS ] Total ) . RESULTS Mean changes from baseline to end point in PANSS Total score , using a last observation carried forward technique , showed that both agents were comparably effective in neuroleptic resistant patients , i.e. , demonstrated the " noninferiority " of olanzapine when compared to clozapine . Overall , significantly fewer olanzapine-treated patients ( 4 % ) discontinued for an adverse event than their clozapine-treated ( 14 % ) counterparts ( p = .022 ) . Among spontaneously reported adverse events , increased salivation , constipation , dizziness , and nausea were reported significantly more often among clozapine-treated patients , whereas only dry mouth was reported more often among olanzapine-treated patients . CONCLUSIONS Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinical ly eligible for treatment with clozapine The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge . Clozapine , an atypical antipsychotic drug , has long been of scientific interest , but its clinical development has been delayed because of an associated risk of agranulocytosis . This report describes a multicenter clinical trial to assess clozapine 's efficacy in the treatment of patients who are refractory to neuroleptics Output:	These reductions are clinical ly meaningful .
MS21552	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To investigate whether electrical stimulation is effective in improving quadriceps strength in healthy subjects and to compare interferential and low-frequency current in terms of the effects on quadriceps strength and perceived discomfort . DESIGN R and omized , controlled study . SETTING Physical Medicine and Rehabilitation Department in a university hospital . SUBJECTS Thirty medical faculty students , divided into three groups , participated in the study . INTERVENTIONS Group A received electrical stimulation with bipolar interferential current while group B received electrical stimulation with low-frequency current ( symmetrical biphasic ) . Group C served as the control group . Electrical stimulation was given for 15 minutes , five days a week for three weeks , at a maximally tolerated intensity with the knee fully extended in the sitting position . MAIN OUTCOME MEASURES Before and after the study , quadriceps strength was measured with a Cybex dynamometer isokinetically at the angular velocities of 60 degrees/s and 120 degrees/s . The perceived discomfort experienced with each type of electrical stimulation was quantified by the use of a visual analogue scale ( VAS ) . RESULTS Statistically significant increase in isokinetic strength was observed after training in group A and group B. Increase in strength did not differ between the stimulation groups . No significant change in strength occurred in group C. Perceived discomfort by the stimulation groups was not significantly different . CONCLUSION Both interferential and low-frequency currents can be used in strength training with the parameters used in this study Cross-education enhances the performance of muscles not directly involved in the chronic conditioning of the muscles in a remote limb . Substantial cross-education occurs after training with eccentric contractions or with contractions evoked by electromyostimulation ( EMS ) . Since during EMS and eccentric contractions , skin and muscle afferents are activated that have excitatory effects on contralateral homologous muscles , it was hypothesized that exercise training with stimulated vs. voluntary eccentric contractions would lead to greater cross-education . Thirty-two women were r and omly assigned to a voluntary ( Vol ) , an EMS , or remote EMS ( rEMS ) exercise group and performed 840 voluntary or stimulated eccentric contractions over 6 weeks . All subjects , including nonexercising controls ( Con ) , were tested pre- and posttraining for maximal voluntary and stimulated isometric and eccentric quadriceps strength . Ipsilateral voluntary and stimulated forces increased in all groups . Changes in EMG activity paralleled those in voluntary force in each limb . No changes occurred in grip strength . The great contra- and ipsilateral strength gains after EMS training were most likely related to an additive effect of EMS and muscle lengthening INTRODUCTION A variety of techniques have been used with variable success in an attempt to reverse the loss of muscle strength , bulk , and endurance that occurs during spaceflight . This study was design ed to evaluate a new " hybrid " approach that uses the resistance provided by an electrically stimulated antagonist muscle to resist the volitional contraction of its agonist . METHODS There were 20 subjects who were r and omized into 3 groups that received either the new hybrid program ( HYB ) , isotonic weight training ( WT ) , or isometric electrical stimulation ( ES ) . Subjects trained 3 times per week for 8 wk with each session consisting of their non-dominant upper extremity performing 10 sets of 10 reciprocal 2-s elbow flexion and extension contractions separated by 1-min rest intervals . Elbow flexion\extension torques and biceps\triceps cross-sectional areas ( CSA ) were measured at the beginning , midpoint , and end of training as well as at follow-up 4 wk later . RESULTS The HYB group demonstrated statistically significant increases in elbow flexion and extension torques ( 56 % and 31 % , respectively ) at the end of training that were similar to or larger than the gains in the other groups with benefits that persisted at follow-up 4 wk later . Muscle CSA increases in the HYB group ( 10 % ) were comparable or larger than those in WT and ES subjects . CONCLUSIONS These results suggest that HYB training may be an effective way to maintain and increase muscle bulk and strength for patients during bed rest , as well as astronauts in space This study aim ed to compare voluntary and stimulated exercise for changes in muscle strength , growth hormone ( GH ) , blood lactate , and markers of muscle damage . Nine healthy men had two leg press exercise bouts separated by 2 wk . In the first bout , the quadriceps muscles were stimulated by biphasic rectangular pulses ( 75 Hz , duration 400 mus , on-off ratio 6.25 - 20 s ) with current amplitude being consistently increased throughout 40 contractions at maximal tolerable level . In the second bout , 40 voluntary isometric contractions were performed at the same leg press force output as the first bout . Maximal voluntary isometric strength was measured before and after the bouts , and serum GH and blood lactate concentrations were measured before , during , and after exercise . Serum creatine kinase ( CK ) activity and muscle soreness were assessed before , immediately after , and 24 , 48 , and 72 h after exercise . Maximal voluntary strength decreased significantly ( P < 0.05 ) after both bouts , but the magnitude of the decrease was significantly ( P < 0.05 ) greater for the stimulated contractions ( -22 % ) compared with the voluntary contractions ( -9 % ) . Increases in serum GH and lactate concentrations were significantly ( P < 0.05 ) larger after the stimulation compared with the voluntary exercise . Increases in serum CK activity and muscle soreness were also significantly ( P < 0.05 ) greater for the stimulation than voluntary exercise . It was concluded that a single bout of electrical stimulation exercise result ed in greater GH response and muscle damage than voluntary exercise The effect of different training intensities of electro-motor stimulation ( EMS ) on strength gains produced in the quadriceps femoris muscle group was investigated . Twenty-four subjects were r and omly assigned to one of three groups : Control ( C ) , Low Intensity ( LI ) trained at 25 % of their maximum voluntary isometric contraction ( MVIC ) , and High Intensity ( HI ) trained at 50 % of MVIC . Results indicated a significant strength improvement in both training groups ( p<0.01 ) following a three-week EMS training program . The HI group showed significantly greater strength gains ( 48.5 % ) than the LI group ( 24.2 % ) ( p<0.01 ) . A significant carry-over effect was also demonstrated in a three-week follow-up period , specifically in the HI group . Positive isokinetic strength changes in the concentric mode were observed in both training groups . In addition , a significant cross transfer effect was demonstrated in the contralateral homologous muscle group ( p<0.01 ) for both HI and LI groups The effects of two methods of electrical stimulation on maximum isometric force , calf girth , and skinfold thickness of stimulated and nonstimulated ( contralateral ) legs were studied . Thirty-six male volunteers , divided into three groups , participated in the experiment . Groups I and II were subjected to the procedure of electrical stimulation of m. triceps surae daily for a period of 21 days . Group I was stimulated by an alternating current of low frequency ( 50 Hz ) ; group II was also stimulated by an alternating current but of higher frequency ( 2000 Hz ) . Group III served as control group . In groups I and II significant increases of the maximum isometric force ( as measured on an electronic dynamometer ) of the stimulated ( 50.3 % and 58.8 % ) and also of the nonstimulated ( contralateral ) muscles ( 39.7 % and 32.2 % ) were found . In group III no significant increase of the maximum isometric force was registered . After the period of stimulation , the skinfold thickness was notably reduced by 21.6 % in group II , and calf girth was enlarged in both experimental groups . Relatively large changes were realized in the calf girth and the skin-fold thickness of the nonstimulated legs . The changes in group III were insignificant . It is concluded that electrical stimulation with low as well as high frequencies exerts great effects on muscle force The present study assessed the effects of training using electrostimulation of muscle ( EMS ) on the torque-angular velocity and torque-angle relationships , and the cross-sectional area ( CSA ) of the triceps surae . Twelve physical education students , divided into two groups ( 6 controls , 6 experimental ) , participated in the experiment . The EMS sessions were undertaken using a ' Complex-type ' stimulator . Flexible elastomer electrodes were used . The current used discharged pulses lasting for 200 microseconds at a frequency of 70 Hz . The duration s of contraction and rest were 5 and 15 s , respectively . The session lasted for 10 min for each muscle . The training regimen was three sessions per week for 4 weeks . Biomechanical tests were performed with the Biodex ( Biodex Corporation , Shirley , NY , USA ) isokinetic ergometer . Plantar flexions of the ankle over a concentric range of voluntary contractions were performed at different angular velocities ( 1.05 , 2.10 , 3.14 , 4.20 , 5.23 and 6.28 rad s-1 ) and maximum voluntary isometric contractions were held for 5 s at several ankle flexion angles ( -30 degrees , -15 degrees , 0 degree and 15 degrees ; 0 degree corresponds to foot flexion of 90 degrees relative to the leg axis ) . The peak value of the torque was recorded . Morphological tests consisted of measuring the CSA of the triceps surae on the right leg , 15 cm below the tibial protuberance , by a computerized tomography technique . The torque-velocity relationship was seen to shift significantly upwards after EMS training . The increase in the isometric torque observed after EMS training was greater in dorsiflexion than in plantarflexion . ( ABSTRACT TRUNCATED AT 250 WORDS Neuromuscular electrical stimulation ( NMES ) may be used to prevent strength loss associated with post-surgical immobilization . Most studies testing the effectiveness of NMES have trained the knee extensors . The purpose of this investigation was to test the effectiveness of NMES when training the elbow flexors . Twenty-four students were r and omly assigned to one of three groups : NMES training , isometric training or control . Testing and training were completed using a Biodex ™ dynamometer . After a st and ard warm-up , subjects were positioned on the Biodex ™ with left shoulder in anatomical neutral , elbow flexed to 90(o ) and forearm supinated . Subjects performed three maximum isometric contractions of 5 seconds duration , with 1 min rest between repetitions . Average peak torque during three repetitions was calculated . Subjects trained on three days per week for four weeks . Training included 15 maximum contractions of 15 seconds duration with 45 seconds recovery between repetitions . Russian current was delivered by a Forte ™ 400 Combo via electrodes placed over ends of biceps brachii . A maximum tolerable ramped intensity was delivered with frequency of 90 bps and duty cycle of 15:45 . After training , subjects were post-tested in a manner identical to pretest . Mean normalized strength data were analyzed using a 3 ( Group ) x 2 ( Test ) ANOVA . The Group x Test interaction was significant . Post-hoc analyses revealed that the voluntary training group ( normalized means of 0.49 to 0.71 for the pretest and post-test , respectively ) had a significantly greater increase than the other two groups , which were not significantly different from each other . The lack of significant strength gains with NMES was likely due to low average training intensity , which was only 20.4 % of MVIC . Based on these results , NMES training may not be an effective alternative to voluntary training in healthy subjects . Key PointsTraining the elbow flexors with voluntary isometric contractions produced significantly greater strength gains than did training with NMES.Strength gains when training with NMES were no greater than with no training . The lack of strength gains with NMES was likely due to a low average training torque of 20.4 % of MVIC PURPOSE The aim of this study was to examine the influence of a short-term electromyostimulation ( EMS ) training program on the strength of knee extensors , skating , and vertical jump performance of a group of ice hockey players . METHODS Seventeen ice hockey players participated in this study , with nine in the electrostimulated group ( ES ) and the remaining height as controls ( C ) . EMS sessions consisted of 30 contractions ( 4-s duration , 85 Hz ) and were carried out 3x wk for 3 wk . Isokinetic strength of the knee extensor muscles was determined with a Biodex dynamometer at different eccentric and concentric angular velocities ( angular velocities ranging from -120 to 300 degrees .s ) . Jumping ability was evaluated during squat jump ( SJ ) , countermovement jump ( CMJ ) , drop jump ( DJ ) , and 15 consecutive CMJ ( 15J ) . Sprint times for 10- and 30-m skates in specific conditions were measured using an infrared photoelectric system . RESULTS After 3 wk of EMS training , isokinetic torque increased significantly ( P<0.05 ) for ES group in eccentric ( -120 and -60 degrees .s ) and concentric conditions ( 60 and 300 degrees .s ) , whereas vertical jump height decreased significantly ( P<0.05 ) for SJ ( -2.9+/-2.4 cm ) , CMJ ( -2.1+/-2.0 cm ) , and DJ ( -1.3+/-1.1 cm ) . The 10-m skating performance was significantly improved ( from 2.18+/-0.20 to 2 Output:	To generate this level of MVC , it was possible to identify guidelines for effectively combining training regimens ( 4.4 ± 1.5 weeks , 3.2 ± 0.9 sessions per week , 17.7 ± 10.9 minutes per session , 6.0 ± 2.4 seconds per contraction with 20.3 ± 9.0 % duty cycle ) with relevant stimulation parameters ( impulse width 306.9 ± 105.1 microseconds , impulse frequency 76.4 ± 20.9 Hz , impulse intensity 63.7 ± 15.9 mA ) to optimize training for systematic ally developing strength abilities ( maximal strength , speed strength , jumping and sprinting ability , power )
MS21553	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This paper describes the 5-year results of a comparative study between Astra Tech and Brånemark system implants . The aim was to compare the systems primarily with regard to bone level changes , and also with regard to other variables of interest . Sixty-six patients with edentulous jaws were included in the study . R and omisation schedules were used to allocate the patients to the two implant systems . 184 Astra Tech implants with a titanium-blasted surface and 187 Brånemark implants with a turned surface were used . The implants were inserted with a two-stage technique and the insertion followed the routines for the respective implant system . All patients were provided with full-arch fixed bridges . All patients were followed up with clinical and radiographic examinations from fixture insertion to the 5-year follow-up . The total mean bone level change in the upper jaw between fixture insertion and the 5-year examination was -1.74+/-0.45 mm at the Astra implants and -1.98+/-0.21 at the Brånemark implants . The corresponding values for the lower jaw were -1.06+/-0.19 for Astra and -1.38+/-0.17 for Brånemark . The major postoperative changes of the marginal bone level took place between fixture insertion and baseline . During this period , there was also a different pattern of bone remodelling between the implant systems . Between baseline ( prosthesis connection ) and the 5-year examination , the marginal bone level changes were small , with no difference between the implant systems . The implant stability was examined with the supraconstructions removed . At the 5-year examination , the survival rate for Astra Tech implants was 98.4 % and for the Brånemark implants it was 94.6 % . The difference was not statistically significant PURPOSE Bone resorption following tooth loss often limits the quantity of bone available for implant placement . The purpose of the present study was to evaluate the clinical outcome of 10-mm or shorter machined-surface implants when used exclusively in the treatment of various forms of edentulism . MATERIAL S AND METHODS Two hundred sixty-nine screw-type Brånemark System implants ( Nobel Biocare ) , 10 mm or shorter , were placed in 111 consecutively treated patients . Of the total , 88.8 % were placed in the m and ible and 11.2 % were placed in the maxilla ; 95.2 % were used to treat partially edentulous situations , including single-tooth losses , of which 96.6 % were in the premolar and molar regions . The patients were followed for periods of 12 to 92 months . RESULTS Of the 269 placed implants , 12 were lost . The overall survival rate was 95.5 % . Bone quality 2 and 3 ( Lekholm-Zarb classification of 1985 ) was found in 88.8 % of the treated sites . There was no statistical difference in the survival rate of the 10-mm implants when compared to the shorter series ( P > .05 ) or between the various implant diameters . The mean marginal bone loss was 0.71 + /- 0.65 mm . DISCUSSION The failure rate of 4.5 % compares favorably with that of implants of different shape , surface characteristics , and length . Bone quality appeared to be the critical factor in implant survival , rather than bone quantity , in this patient series . CONCLUSIONS This study supports the survival of short , machined-surface implants when used for the treatment of partial edentulism in bone of good quality PURPOSE A prospect i ve study on m and ibular implant-supported overdentures using more than 2 Brånemark implants splinted with multiple round bars evaluated a hypothesis that unnecessary prosthodontic maintenance would result from the contravention of accepted biomechanical principles . MATERIAL S AND METHODS A r and omized prospect i ve trial on 59 edentulous patients details prosthodontic maintenance and complications of 52 m and ibular overdentures ( 11 unsplinted , 41 splinted ) over a 3-year period . RESULTS Prosthodontic maintenance was greater in the first year than in subsequent years , regardless of design . Comparison between the splinted design s with round bars revealed no statistically significant difference with either retentive clip activation or fractures . More than 70 % of the retention clips in the 2-implant ( single round bar ) design needed activation , as compared to 44 % of those with the 3-implant ( double round bar ) or 4-implant ( triple round bar ) design . Retention clip fracture occurred in 30 % of patients with 3 or 4 implants and 16 % of those with 2 implants . Relining the overdentures , regardless of design , revealed an excessive maintenance burden in 40 % of overdentures . Remaking of overdentures was necessary in 21 % of patients . CONCLUSION Multiple round bars splinting 3 or 4 implants can still be a treatment concept in m and ibular overdenture treatment . Results from prospect i ve evaluation of this design indicate less prosthodontic maintenance of clip activation but more clip fractures than with 2 implants splinted with single round bars , although not at statistically significant levels This report is an up date on a group of 46 clinical trial patients who each received 3 free-st and ing Endopore dental implants placed using a 2-stage surgical approach in the anterior m and ible . After an initial healing interval of 10 weeks , the implants were used in each case to retain an over-denture , and at the time of the report , all patients had passed 5 years of continuous function . The 5-year cumulative " survival " rate based on a life table analysis was 93.4 % and this remained unchanged after 6 years . The 5-year " success rate " was 83.3 % when assessed qualitatively with the published criteria of others using a four-field table analysis categorizing every implant in the study as one of " Grade 1 Success " , " survival " , " unaccounted for " or " failure " . Modified periodontal parameters verified continued peri-implant soft tissue health . No implant still in function had more than 1.8 mm cumulative bone loss during the first 5 years of function . These results provide clear evidence that Endopore implants despite their short lengths function at least as well as other dental implant design s used in much longer lengths PURPOSE This r and omized controlled clinical trial aim ed to evaluate the efficacy of splinted implants versus unsplinted implants in overdenture therapy over a 10-year period . MATERIAL S AND METHODS The study sample comprised 36 completely edentulous patients , 17 men and 19 women ( mean age 63.7 years ) . In each patient , 2 implants ( Brånemark System , Nobel Biocare , Göteborg , Sweden ) were placed in the interforaminal area . Three to 5 months after placement , they were connected to st and ard abutments . The patients were then rehabilitated with ball-retained overdentures , magnet-retained overdentures , or bar-retained overdentures ( the control group ) . Patients were followed for 4 , 12 , 60 , and 120 months post-abutment connection . Group means as well as linear regression models were fitted with attachment type and time as classification variables and corrected for simultaneous testing ( Tukey ) . RESULTS After 10 years , 9 patients had died and 1 was severely ill . Over 10 years , no implants failed . Mean Plaque Index , Bleeding Index , change in attachment level , Periotest values , and marginal bone level at the end of the follow-up period were not significantly different among the groups . DISCUSSION The annual marginal bone loss , excluding the first months of remodeling , was comparable with that found around healthy natural teeth . CONCLUSION The fact that no implants failed and that overall marginal bone loss after the first year of bone remodeling was limited suggested that implants in a 2-implant m and ibular overdenture concept have an excellent prognosis in this patient population , irrespective of the attachment system used Osseointegrated implants as anchors for various prosthetic reconstructions have become a predictable treatment alternative . It was expected that implants required submucosal placement during the healing period for successful tissue integration . However , it has been demonstrated that healing and long-term health of implants could be achieved with equal predictability in a 1-stage , non-submerged approach . This prospect i ve 5-year study not only calculates implant success by life table analysis , but also evaluates the correlation between observed bone level changes with clinical parameters as measured by suppuration , plaque indices , bleeding indices , probing depth , attachment level and mobility . A total of 112 ITI dental implants were inserted in different areas of the jaws . Clinical and radiographic parameters were evaluated annually for 5 years , whereas a portion of the study group for which 6-year evaluations were available were included in the life-table analysis . The overall success rate after 5 years in service was 99.1 % , while after 6 years it was reduced to 95.5 % due to the fracture of 3 implants in 1 patient . The mean crestal bone loss experienced during the first year was 0.6 mm followed by an annual yearly loss of approximately 0.05 mm . No significant differences could be found between the amount of bone loss measured at each of the yearly follow-up visits . This suggests that statistically the followed implants did not show any radiographically measurable bone loss following the initial period of bone loss associated with implant placement and osseointegration . Low levels of correlation between the individual and cumulative clinical parameters with radiographically measured bone loss suggests that these parameters are of limited clinical value in assessing and predicting future peri-implant bone loss BACKGROUND Maintenance of the health and integrity of the bone-implant complex ( osseointegration ) has been shown to be essential for long term success of root-form , endosseous dental implants . If reliable clinical indicators of adequacy of the bone-implant complex existed , they could stimulate new and innovative early intervention research to arrest of reverse early deterioration of the bone-implant complex . In the absence of such indicators , this has been problematic . The Periotest may have the potential to provide this information by indirectly assessing the status of the bone-implant complex . However , little information is available that documents either the capability of the Periotest to reliably assess changes of the bone-implant complex or the " normal variations " in Periotest values ( PTVs ) for both HA-coated and non-coated implants . METHODS The purpose of this paper was to document changes in PTVs as influenced by various implant surfaces , implant design s , and bone densities . The mean PTVs recorded for each visit , for all implant types and bone densities , were combined to provide an overall average PTV ( A-PTV ) . The changes in stability ( PTVs ) were analyzed using a generalized linear model ( GLM ) with repeated measures ( Hotelling 's Trace ) . RESULTS The A-PTV for all implants over all visits was -3.5 . The mean PTVs ranged from -4.2 ( SD = 2.4 ) at uncovering to -3.9 ( SD = 2.9 ) at 60 months . All implants in bone qualities 1 and 2 ( BQ-1 and BQ-2 ) became more stable over time , while those in bone quality 3 or 4 ( BQ-3 and BQ-4 ) showed a slight decrease in stability . In BQ-1 , the mean PTVs increased from -4.7 at uncovering to -4.9 at 60 months . A similar increase in stability occurred in BQ-2 ( -4.1 at uncovering to -4.4 at 60 months ) . In BQ-3 , the stability of the implants decreased over time ( -3.6 at uncovering to -2.9 at 60 months ) , with similar changes recorded for BQ-4 ( -2.5 at uncovering to -1.0 at 60 months ) . When comparing the stability of all HA-coated with all non-coated implants , the HA implants became less stable ( -4.4 to -3.4 ) over time , while non-coated implants showed an improvement in stability ( -3.5 to -4.5 ) . The changes in stability found in BQ-1 , BQ-2 , and BQ-3 were similar , with HA implants becoming less stable and non-coated more stable . HA- and non-coated comparisons were not possible in BQ-4 since there were too few non-coated implants placed in this type of bone . The HA-coated screw showed a decrease in stability when compared to the non-coated screw . CONCLUSIONS Conclusions of the study are as follows : 1 ) PTVs are influenced by bone quality and surface coating of the implant ; 2 ) the PTVs at the time of uncovering provide the best estimate of a clinical ly acceptable PTV for that bone-implant complex ; 3 ) while the PTVs for any bone-implant complex may fluctuate + /- 1.0 around the uncovering PTV during routine healing and loading of the implant , a consistent shift toward a positive PTV that approaches " 0 " should be cause for concern that the bone-implant complex may be at risk of failure ; 4 ) HA-coated implants became slightly less stable ( more positive PTVs ) over time , while the non-coated implants became more stable ( more negative PTVs ) ; and 5 ) until a " critical PTV " can be accurately identified , it is suggested that a consistent shift in recorded PTVs that exceeds the + 3.0 value on the PTV scale should be viewed with concern for possible deterioration at the bone-implant complex The aim of this prospect i ve r and omized controlled clinical trial was to evaluate and compare clinical aspects and satisfaction during the first year following treatment and consecutively the change in treatment during the next 4 years of follow-up . Patients were allocated to one of the following treatment modalities : an implant-retained overdenture ( IRO-group , 2 endosseous implants , n Output:	The observation of greater implant failure for removable over fixed protheses groups in the maxilla appeared likely due to deficient preoperative bone volume in the removable prosthesis groups . DISCUSSION There is little evidence that implant survival or success is affected directly by prosthesis type based on current design s studied for at least 5 years . Prosthesis maintenance does appear to vary with different prosthesis design s. CONCLUSION While this study suggests implant survival and success may not be affected by variation across the established types of implant prostheses , maintenance dem and s can vary with implant prosthesis type , especially with overdenture attachments .
MS21554	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The continued high mortality and morbidity rates for unintentional childhood injuries remain a public health concern . This article reports on the influence of a home visitation programme ( HVP ) on household hazards associated with unintentional childhood injuries in a South African low-income setting . METHODS A r and omised controlled trial ( n=211 households ) was conducted in a South African informal settlement . Community members were recruited and trained as paraprofessional visitors . Four intervention visits were conducted over 3 months , focusing on child development , and the prevention of burn , poison , and fall injuries . The HVP , a multi-component intervention , included educational inputs , provision of safety devices , and an implicit enforcement strategy . The intervention effect ( IE ) was measured with a st and ardised risk assessment index that compared post-intervention scores for intervention and control households . RESULTS A significant reduction was observed in the hazards associated with electrical and paraffin appliances , as well as in hazards related to poisoning . Non-significant changes were observed for burn safety household practice s and fall injury hazards . CONCLUSIONS This study confirmed that a multi-component HVP effectively reduced household hazards associated with electrical and paraffin appliances and poisoning among children in a low-income South African setting Objective : To access an underserved , mobile segment of a monolingual Spanish speaking population and to improve maternal self efficacy for home safety behaviors using a culturally appropriate intervention . Design : A pre- and post-test experimental design tested differences in maternal childhood injury health beliefs ( MCIHB ) and controllable safety hazards ( CHS ) . Participants were r and omly assigned to experimental and control groups . Baseline data assessed demographic and study variables comparability . The intervention included counseling , assessment of maternal safety practice s , and provision of safety items . Setting : A non-urban area in Texas where low income , largely migrant Hispanics represent the majority of residents . Participants : Eighty two mothers of 1–4 year old children . Results : The 95 % retention rate of an itinerant , hard to reach population suggests that minority participants may be receptive to culturally appropriate home visits . The intervention group demonstrated improved self efficacy for home safety behaviors ( F ( 2 , 77 ) = 7.50 , p = 0.01 ) . Mothers with stronger self efficacy and fewer perceived barriers had fewer accessible in-home hazards . Observed home hazard predictors were : ( a ) never being married ; ( b ) poor home repair , ( c ) lower self efficacy for safety behaviors ; and ( d ) control group status . Conclusions : Safety items coupled with a home visit tailored to child age and maternal culture was an effective intervention in a hard to reach population . This study contributes to design ing research for a monolingual population with limited local language proficiency and community residency . Injuries represent a major source of health disparities in these neglected population OBJECTIVE To determine whether educational baby books are an effective method for increasing low-income , first-time mothers ' safety practice s during their child 's first 18 months . METHODS Primiparous women ( n = 167 ) were r and omly assigned to 1 of 3 groups : an educational book group , a noneducational book group , or a no-book group . Home visits and interviews measured safety practice s when women were in their third trimester of pregnancy ( baseline ) and when their children were 2 , 4 , 6 , 9 , 12 , and 18 months of age . RESULTS Women in the educational book group had fewer risks in their homes and exercised more safety practice s than the no-book group ( - 20 % risk reduction ; effect size = -.30 ) . When the safety practice s involved little time or expense ( eg , putting away sharp objects ) , the educational book group was significantly more likely to engage in these behaviors than the no-book group ( 40 % higher practice s ; effect size = 0.19 ) or noneducational book group ( 27 % higher practice s ; effect size = 0.13 ) . However , no differences were found between groups for behaviors that required high effort in time , money , or hassle ( eg , installing latches on cabinets ) . CONCLUSIONS Educational baby books appear to be an easy and low-cost way to increase the safety practice s of new mothers , especially if the practice s involve little to no time , money , or hassle OBJECTIVE To test the efficacy of installing safety devices in the homes of young children on total injury rates and on injuries deemed a priori modifiable by the installation of these devices . DESIGN A nested , prospect i ve , r and omized controlled trial . SETTING Indoor environment of housing units . PARTICIPANTS Mothers and their children from birth to 3 years old participating in the Home Observation and Measures of the Environment study . Among 8878 prenatal patients , 1263 ( 14.2 % ) were eligible , 413 ( 32.7 % ) agreed to participate , and 355 were r and omly assigned to the intervention ( n = 181 ) or control ( n = 174 ) groups . INTERVENTION Installation of multiple passive measures ( eg , stair gates , cabinet locks , and smoke detectors ) to reduce exposure to injury hazards . Injury hazards were assessed at home visits by teams of trained research assistants using a vali date d survey . MAIN OUTCOME MEASURE Modifiable and medically attended injury ( ie , telephone calls , office visits , and emergency visits for injury ) . RESULTS The mean age of children at intervention was 6.3 months . Injury hazards were reduced in the intervention homes but not in the control homes at 1 and 2 years ( P < .004 ) . There was no difference in the rate for all medically attended injuries in intervention children compared with controls : 14.3 injuries ( 95 % confidence interval [ CI ] , 9.7 - 21.1 injuries ) vs 20.8 injuries ( 95 % CI , 14.4 - 29.9 injuries ) per 100 child-years ( P = .17 ) ; but there was a significant reduction in the rate of modifiable medically attended injuries in intervention children compared with controls : 2.3 injuries ( 95 % CI , 1.0 - 5.5 injuries ) vs 7.7 injuries ( 95 % CI , 4.2 - 14.2 injuries ) per 100 child-years ( P = .03 ) . CONCLUSION An intervention to reduce exposure to hazards in homes led to a 70 % reduction in the rate of modifiable medically attended injury . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00129324 OBJECTIVE To assess the effectiveness of an emergency department (ED)-based home safety intervention on caregivers ' behaviors and practice s related to home safety . METHODS We conducted a r and omized , clinical trial of 96 consecutive caregivers of children who were younger than 5 years and presented to an urban pediatric ED for evaluation of an acute unintentional injury sustained in the home . After completing a structured home safety question naire via face-to-face interview , caregivers were r and omly assigned to receive either comprehensive home safety education and free safety devices or focused , injury-specific ED discharge instructions . Participants were contacted by telephone 2 months after the initial ED visit for repeat administration of the safety question naire . The pretest and posttest question naires were scored such that the accrual of points correlated with reporting of safer practice s. Scores were then normalized to a 100-point scale . The overall safety score reflected performance on the entire question naire , and the 8 category safety scores reflected performance in single areas of home injury prevention ( fire , burn , poison , near-drowning , aspiration , cuts/piercings , falls , and safety device use ) . The main outcome was degree of improvement in safety practice s as assessed by improvement in safety scores . RESULTS The intervention group demonstrated a significantly higher average overall safety score at follow-up than the control group ( 73.3 % + /- 8.4 % vs 66.8 % + /-11.1 ) and significant improvements in poison , cut/piercing , and burns category scores . Caregivers in the intervention group also demonstrated greater improvement in reported use of the distributed safety devices . CONCLUSIONS This educational and device disbursement intervention was effective in improving the home safety practice s of caregivers of young children . Moreover , the ED was used effectively to disseminate home injury prevention information Objective : to evaluate the effectiveness of a school-based injury prevention program . Design : Cluster r and omised controlled trial . Setting : 20 primary schools in Nottingham , UK . Participants : 459 children aged 7 to 10 years . Intervention : The “ Risk Watch ” program delivered by teachers , aim ed at improving bike and pedestrian , falls , poisoning and fire and burns safety . Main outcome measures : Safety knowledge , observed safety skills and self-reported safety behaviour . Results : At follow-up , intervention group children correctly answered more fire and burn prevention knowledge questions than control group children ( difference between means 7.0 % ( 95 % CI 1.5 % to12.6 % ) ) . Children in intervention group schools were more likely to know the correct actions to take if clothes catch fire and the correct way to wear a cycle helmet ( difference between school means 35.3 % ( 95 % CI 22.7 % to 47.9 % ) and 6.3 % ( 95 % CI 1.4 % to 11.1 % ) respectively ) . They were also more likely to know the correct actions to take in a house fire and on finding tablets ( OR 2.80 ( 95 % CI 1.08 to 7.22 ) and OR 3.50 ( 95 % CI 1.18 to 10.38 ) respectively ) and correctly demonstrated more safety skills than control group children ( difference between means 11.9 % ( 95 % CI 1.4 % to 22.5 % ) ) . There was little evidence to suggest the first year of the program impacted on self-reported safety behaviours . Conclusions : The Risk Watch program delivered by teachers in primary schools increased some aspects of children ’s safety knowledge and skills and primary schools should consider delivering this program . Longer term , larger scale evaluations are required to examine retention of knowledge and skills and impact on safety behaviours and child injury rates Abstract Objective To assess the effectiveness of safety advice and safety equipment in reducing unintentional injuries for families with children aged under 5 years and living in deprived areas . Design R and omised controlled trial . Setting 47 general practice s in Nottingham . Participants 3428 families with children under 5 . Intervention A st and ardised safety consultation and provision of free and fitted stair gates , fire guards , smoke alarms , cupboard locks , and window locks . Main outcome measures Primary outcome measures were whether a child in the family had at least one injury that required medical attendance and rates of attendance in primary and secondary care and of hospital admission for injury over a two year period . Secondary outcome measures included possession of safety equipment and safety practice s. Results No significant difference was found in the proportion of families in which a child had a medically attended injury ( odds ratio 1.14 , 95 % confidence interval 0.98 to 1.50 ) or in the rates of attendance in secondary care ( incidence rate ratio 1.02 , 0.90 to 1.13 ) or admission to hospital ( 1.02 , 0.70 to 1.48 ) . However , children in the intervention arm had a significantly higher attendance rate for injuries in primary care ( 1.37 , 1.11 to 1.70 , P = 0.003 ) . At both one and two years ' follow up , families in the intervention arm were significantly more likely to have a range of safety practice s , but absolute differences in the percentages were relatively small . Conclusions The intervention result ed in significant improvements in safety practice s for up to two years but did not reduce injuries that necessitated medical attendance . Although equipment was provided and fitted free of charge , the observed changes in safety practice s may not have been large enough to affect injury rates Objective : To investigate the effectiveness of a paraprofessional home visitation program ( HVP ) to improve home safety and prevent injuries among children living in low-income setting s. Methods : The HVP was implemented in two low-income communities in South Africa . In each community , approximately 200 households were r and omly selected for the trial . Eligible households were those with children aged ⩽10 years . Intervention households received four visits , one every two weeks , by trained paraprofessionals that focused on a specific injury topic and consisted of : information dissemination about specific injury prevention practice s ; home inspection accompanied by information about home hazards ; and the supply of safety devices . The key outcomes to measure the presence of home hazards were scores for burns ( safety practice s , paraffin , and electrical ) , poisoning , and falls . Results : Significant reductions were found for injury risks related to burn safety practice s. For injury risks related to electrical burns , paraffin burns , and poisoning , a decline was also noted although this was not statistically significant . No decline was noted for fall-related risks . Conclusions : Subject to further replication and evaluation , home visits by paraprofessionals providing safety education , home inspection , and safety devices be considered for integration into a comprehensive child injury prevention strategy in low-income communities BACKGROUND During the 20-month period September 1993 to April 1995 , a health education injury prevention programme focusing on home injuries among the young ( < or = 18 years old ) and elderly ( > or = 65 years old ) on the Greek isl and of Naxos was undertaken , its effectiveness was evaluated by comparing the subsequent injury experience in sentinel population groups in Naxos as well as in Spetses , another isl and of similar sociodemographic profile , where no such intervention programme had been formally implemented . METHODS On the isl and -of Naxos an injury prevention campaign was initially undertaken involving virtually all opinion leaders and implemented through lectures , workshops and publicity in Output:	There was a lack of evidence that interventions reduced poisoning rates .
MS21555	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies We found that interval training provides an effective means to improve the cardiovascular fitness and health status of highly functional patients with coronary artery disease . We also revealed that interval training improves anaerobic tolerance to a greater extent than the traditional exercise training model without increasing the risk to the patient . This research supports the implementation of interval training for highly functional patients with coronary artery disease Background —Predicting the risk of cardiac and all-cause death in patients with established coronary heart disease is important in counseling the individual and design ing risk-stratified rehabilitation and secondary prevention programs . Cox proportional hazards and Kaplan-Meier survival curves were thus completed on initial assessment data obtained from patients referred to an outpatient cardiac rehabilitation center . Methods and Results —A single-center prospect i ve observational design took peak cardiorespiratory exercise test data for 12 169 male rehabilitation c and i date s aged 55.0±9.6 years ( 7096 myocardial infa rct ions [ MIs ] , 3077 coronary artery bypass grafts [ CABGs ] , and 1996 documented cases of ischemic heart disease [ IHD ] ) . A follow-up of 4 to 29 years ( median , 7.9 ) yielded 107 698 man-years of experience . Entry data were tested for associations with time to cardiac and all-cause death . We recorded 1336 cardiac deaths ( 953 MI , 225 CABG , and 158 IHD ) and 2352 all-cause deaths . A powerful predictor of cardiac and all-cause mortality was measured peak oxygen intake ( & OV0312;o2peak ) . For the overall sample , values of < 15 , 15 to 22 , and > 22 mL/kg per minute yielded respective multivariate adjusted hazard ratios of 1.00 , 0.62 , and 0.39 for cardiac and 1.00 , 0.66 , and 0.45 for all-cause deaths . For the separate diagnostic categories , apart from & OV0312;o2peak , the only other significant predictors of cardiac death common to all 3 were smoking and digoxin , and for all-cause death , age , smoking , digoxin , and diabetes . Conclusions —Exercise capacity , as determined by direct measurement of & OV0312;o2peak , exerts a major long-term influence on prognosis in men after MI , CABG , or IHD and can play a valuable role in risk stratification and counseling BACKGROUND High-intensity interval training has been shown to be superior to moderate continuous exercise training in improving exercise capacity and endothelial function in patients with coronary artery disease . The objective of this study was to evaluate this training model on in-stent restenosis following percutaneous coronary intervention for stable or unstable angina . METHODS AND RESULTS We prospect ively r and omized 40 patients after percutaneous coronary intervention with implantation of a bare metal stent ( n = 30 ) or drug eluting stent ( n = 32 ) to a 6-month supervised high-intensity interval exercise training program ( n = 20 ) or to a control group ( n = 20 ) . At six months , restenosis , measured as in-segment late luminal loss of the stented coronary area , was smaller in the training group 0.10 ( 0.52 ) mm compared to the control group 0.39 ( 0.38 ) mm ( P = .01 ) . Reduction of late luminal loss in the training group was consistent with both stent types . Peak oxygen uptake increased in the training and control group by 16.8 % and 7.8 % , respectively ( P < .01 ) . Flow-mediated dilation improved 5.2 % ( 7.6 ) in the training group and decreased -0.1 % ( 8.1 ) in the control group ( P = .01 ) . Levels of high-sensitivity C-reactive protein decreased by -0.4 ( 1.1 ) mg/L in the training group and increased by 0.1 ( 1.2 ) mg/L in the control group ( P = .03 for trend ) . CONCLUSIONS Regular high-intensity interval exercise training was associated with a significant reduction in late luminal loss in the stented coronary segment . This effect was associated with increased aerobic capacity , improved endothelium function , and attenuated inflammation Background Increased aerobic exercise capacity appears to reduce both all-cause mortality and cardiovascular disease mortality . Physical exercise to improve peak oxygen uptake ( VO2peak ) is thus strongly recommended , however evidence regarding the most efficient training intensity for patients with coronary artery disease ( CAD ) is still lacking . The purpose of this r and omized study was therefore to assess the effects of high intensity aerobic interval exercise compared to moderate intensity exercise , representing the same total training load , for increasing VO2peak in stable CAD- patients . Methods Twenty-one stable CAD- patients were r and omized to supervised treadmill walking at either high intensity ( 80–90 % of VO2peak ) or moderate intensity ( 50–60 % of VO2peak ) three times a week for 10 weeks . Results After training VO2peak increased by 17.9 % ( P = 0.012 ) in the high intensity group and 7.9 % ( P = 0.038 ) in the moderate intensity group . The training-induced adaptation was significantly higher in the high intensity group ( P = 0.011 ) . Conclusions High intensity aerobic interval exercise is superior to moderate exercise for increasing VO2peak in stable CAD- patients . As VO2peak seems to reflect a continuum between health and cardiovascular disease and death , the present data may be useful in design ing effective training programmes for improved health in the future The aim of this study was to evaluate the effectiveness of a novel group-based aerobic interval training of high intensity on functional capacity and quality of life in patients with chronic heart failure ( CHF ) and examine the relation between changes in functional capacity and quality of life . Eighty patients with stable CHF ( 63 men , 17 women ; mean age 70.1 + /- 7.9 [ SD ] years ; left ventricular ejection fraction 30 + /- 8.5 % ) on optimal medical treatment were r and omly assigned to either a 16-week group-based aerobic high-intensity interval training model twice weekly for 65 to 80 minutes/day ( n = 40 ) or a control group ( n = 40 ) that received st and ard care . Functional capacity was measured using the 6-minute walk test and cycle ergometer test . Quality of life was measured using the Minnesota Living with Heart Failure Question naire . After 16 weeks , functional capacity improved significantly in the exercise group compared with the control group measured using the 6-minute walk test ( + 58 vs -15 meters ; p < 0.001 ) and for both workload and time measured using the bicycle ergometer test ( + 10 vs -1 W ; p < 0.001 ; + 57 vs -8 seconds ; p < 0.001 ) . Quality of life improved significantly in the exercise group compared with the control group ( p = 0.03 ) , and a significant inverse correlation was found between quality of life and functional capacity ( r = -0.49 , p < 0.05 ) . In conclusion , our exercise model significantly improved functional capacity and quality of life compared with the control group in patients with CHF . Improvements in quality of life were significantly related to functional capacity Output:	IT prescribed in isolation or in combination with resistance training was shown to induce significant and clinical ly important physiological adaptations in cardiac patients . IT was also shown to improve cardiorespiratory fitness ( e.g. VO2max , VO2AT ) , endothelial function , left ventricle morphology and function ( e.g. ejection fraction ) to a significantly greater extent when compared with conventional MCT . No adverse cardiac or other life-threatening events occurred secondary to exercise participation in these studies .
MS21556	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Because several studies have suggested that beta blockers are effective in the prophylaxis of first variceal bleeding in cirrhosis , screening for oesophageal varices might be appropriate . We prospect ively studied 84 cirrhotic patients without obvious evidence of large oesophageal varices and previous bleeding during a mean follow up of 16 months . At entry to the study 41 patients had no oesophageal varices and in 43 these were grade 1 . The subsequent percentages of patients without large oesophageal varices were 74 % at one year and 52 % at two years . Univariate analysis showed that a longer duration of cirrhosis ( p less than 0.05 ) and grade 1 oesophageal varices at entry ( p less than 0.001 ) were predictive factors for the occurrence of large oesophageal varices , whereas , multivariate analysis showed that the initial size of the oesophageal varices ( p less than 0.001 ) , a high initial Child-Pugh score , and a smaller improvement in Child-Pugh score during the study were independent risk factors . Among patients with grade s 0 and 1 oesophageal varices at the start of the study the proportions with large oesophageal varices at two years were 31 % and 70 % respectively . We have calculated that , accepting a maximum risk of first bleeding of 10 % without prophylactic treatment , a patient without oesophageal varices should be screened endoscopically every other year , while a patient with grade 1 disease should benefit from one annual upper gastrointestinal endoscopy Background and aims : Risk factors for mortality and re-bleeding following acute variceal haemorrhage ( AVH ) are incompletely understood . The aim of this study was to determine risk factors for 6-week mortality , and re-bleeding within 5 days in patients with cirrhosis and AVH . Methods : Kaplan – Meier and Cox proportional hazards regression analyses were used to determine risk factors among 256 patients with AVH entered into a r and omised , prospect i ve trial . Results : Thirty-five patients ( 14 % ) died within 6 weeks of AVH ; 14 deaths ( 40 % ) occurred within 5 days . Only the Model for End-stage Liver Disease ( MELD ) score and units of packed red blood cells ( PRBCs ) transfused in the first 24 h were associated with 6-week mortality univariately ( HR 1.11 , p<0.001 ; HR 1.22 , p<0.001 ) and bivariately ( HR MELD = 1.10 , p<0.001 ; HR per unit of PRBCs transfused = 1.15 , p = 0.005 ) . Re-bleeding within 5 days occurred in 37 patients ( 15 % ) ; MELD score ( p = 0.01 ) and a clot on a varix ( p = 0.05 ) predicted re-bleeding . Patients with a MELD score ⩾18 ; both MELD score ⩾18 and ⩾4 units of PRBCs transfused ; both MELD score ⩾18 and active bleeding at index endoscopy ; and variceal re-bleeding had increased risk of death 6 weeks post-AVH ( HR = 7.4 , p<0.001 ; 11.3 , p<0.001 ; 9.9 , p<0.001 ; 10.2 , p<0.001 respectively ) . Conclusions : Patients with AVH and MELD score ⩾18 , requiring ⩾4 units of PRBCs within the first 24 h or with active bleeding at endoscopy are at increased risk of dying within 6 weeks . MELD score ⩾18 is also a strong predictor of variceal re-bleeding within the first 5 days Background Endoscopy ( esophagogastroduodenoscopy , EGD ) to screen for esophageal varices ( EV ) is recommended in patients with portal hypertension . Reports indicate that capsule endoscopy ( CE ) is capable of identifying large/medium varices ( L/MV ) when the varix comprises more than 25 % of the circumference of the field of view . Aims We evaluated the ability of CE to discriminate the size of EV using this grading scale . Methods Patients underwent CE and EGD on the same day . A blinded investigator interpreted capsule findings . CE labeled EV as L/MV if ≥25 % of the lumen circumference was occupied , and small/none for < 25 % . Results A total of 37 patients were enrolled in this prospect i ve , observational study at a single tertiary-care academic center . Three CE were excluded due to rapid esophageal transit time or technical malfunction . Using a 25 % threshold , the sensitivity , specificity , positive predictive value ( PPV ) , and negative predictive value ( NPV ) for EC to discriminate L/MV were 23.5 % , 88.2 % , 66.7 % , and 53.6 % , respectively ( κ = 0.12 ) . Reducing the threshold to 12.5 % result ed in sensitivity , specificity , PPV , and NPV of 88.2 % , 64.7 % , 71.4 % , and 84.6 % , respectively ( κ = 0.53 ) . A receiver-operator characteristic ( ROC ) curve showed a 15 % threshold to be optimal in discriminating EV size using CE , result ing in sensitivity , specificity , PPV , and NPV of 76.5 % , 82.4 % , 81.3 % , and 77.8 % , respectively ( κ = 0.59 ) . Conclusions This study indicates that discriminating EV size by the current capsule scale is unreliable . Lowering the grading threshold improved the ability to discriminate EV size by CE . In the proper context , CE is an alternative to EGD to screen for EV AIM To investigate the utility of esophageal capsule endoscopy in the diagnosis and grading of esophageal varices . METHODS Cirrhotic patients who were undergoing esophagogastroduodenoscopy ( EGD ) for variceal screening or surveillance underwent capsule endoscopy . Two separate blinded investigators read each capsule endoscopy for the following results : variceal grade , need for treatment with variceal b and ing or prophylaxis with beta-blocker therapy , degree of portal hypertensive gastropathy , and gastric varices . RESULTS Fifty patients underwent both capsule and EGD . Forty-eight patients had both procedures on the same day , and 2 patients had capsule endoscopy within 72 h of EGD . The accuracy of capsule endoscopy to decide on the need for prophylaxis was 74 % , with sensitivity of 63 % and specificity of 82 % . Inter-rater agreement was moderate ( kappa = 0.56 ) . Agreement between EGD and capsule endoscopy on grade of varices was 0.53 ( moderate ) . Inter-rater reliability was good ( kappa = 0.77 ) . In diagnosis of portal hypertensive gastropathy , accuracy was 57 % , with sensitivity of 96 % and specificity of 17 % . Two patients had gastric varices seen on EGD , one of which was seen on capsule endoscopy . There were no complications from capsule endoscopy . CONCLUSION We conclude that capsule endoscopy has a limited role in deciding which patients would benefit from EGD with b and ing or beta-blocker therapy . More data is needed to assess accuracy for staging esophageal varices , PHG , and the detection of gastric varices BACKGROUND Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage . Their effectiveness in preventing varices is unknown . METHODS We r and omly assigned 213 patients with cirrhosis and portal hypertension ( minimal hepatic venous pressure gradient [ HVPG ] of 6 mm Hg ) to receive timolol , a nonselective beta-blocker ( 108 patients ) , or placebo ( 105 patients ) . The primary end point was the development of gastroesophageal varices or variceal hemorrhage . Endoscopy and HVPG measurements were repeated yearly . RESULTS During a median follow-up of 54.9 months , the rate of the primary end point did not differ significantly between the timolol group and the placebo group ( 39 percent and 40 percent , respectively ; P=0.89 ) , nor were there significant differences in the rates of ascites , encephalopathy , liver transplantation , or death . Serious adverse events were more common among patients in the timolol group than among those in the placebo group ( 18 percent vs. 6 percent , P=0.006 ) . Varices developed less frequently among patients with a baseline HVPG of less than 10 mm Hg and among those in whom the HVPG decreased by more than 10 percent at one year and more frequently among those in whom the HVPG increased by more than 10 percent at one year . CONCLUSIONS Nonselective beta-blockers are ineffective in preventing varices in unselected patients with cirrhosis and portal hypertension and are associated with an increased number of adverse events . ( Clinical Trials.gov number , NCT00006398 . Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis . The aim of this multicenter , prospect i ve , cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis . A training set of 291 and a test set of 174 bleeding cirrhotic patients were included . Treatment was according to the preferences of each center and the follow-up period was 6 weeks . Predictive rules for 5-day failure ( uncontrolled bleeding , rebleeding , or death ) and 6-week mortality were developed by the logistic model in the training set and vali date d in the test set . Initial treatment controlled bleeding in 90 % of patients , including vasoactive drugs in 27 % , endoscopic therapy in 10 % , combined ( endoscopic and vasoactive ) in 45 % , balloon tamponade alone in 1 % , and none in 17 % . The 5-day failure rate was 13 % , 6-week rebleeding was 17 % , and mortality was 20 % . Corresponding findings for variceal versus nonvariceal bleeding were 15 % versus 7 % ( P = .034 ) , 19 % versus 10 % ( P = .019 ) , and 20 % versus 15 % ( P = .22 ) . Active bleeding on endoscopy , hematocrit levels , aminotransferase levels , Child-Pugh class , and portal vein thrombosis were significant predictors of 5-day failure ; alcohol-induced etiology , bilirubin , albumin , encephalopathy , and hepatocarcinoma were predictors of 6-week mortality . Prognostic re assessment including blood transfusions improved the predictive accuracy . All the developed prognostic models were superior to the Child-Pugh score . In conclusion , prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades . Initial treatment stops bleeding in 90 % of patients . Accurate predictive rules are provided for early recognition of high-risk patients OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials BACKGROUND / AIMS The incidence and natural history of small esophageal varices ( EV ) in cirrhotics may influence the frequency of endoscopies and the decision to start a pharmacological treatment in these patients . METHODS We prospect ively evaluated 206 cirrhotics , 113 without varices and 93 with small EV , during a mean follow-up of 37+/-22 months . Patients with previous gastrointestinal bleeding or receiving any treatment for portal hypertension were excluded . Endoscopy was performed every 12 months . RESULTS The rate Output:	We can not support the use of capsule endoscopy as a triage test in adults with cirrhosis , administered before oesophago-gastro-duodenoscopy , despite the low incidence of adverse events and participant reports of being better tolerated . Thus , we can not conclude that oesophago-gastro-duodenoscopy can be replaced by capsule endoscopy for the detection of oesophageal varices in adults with cirrhosis . We found no data assessing capsule endoscopy in children and in people with portal thrombosis
MS21557	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Regular exercise training is recognized as a powerful tool to improve work capacity , endothelial function and the cardiovascular risk profile in obesity , but it is unknown which of high-intensity aerobic exercise , moderate-intensity aerobic exercise or strength training is the optimal mode of exercise . In the present study , a total of 40 subjects were r and omized to high-intensity interval aerobic training , continuous moderate-intensity aerobic training or maximal strength training programmes for 12 weeks , three times/week . The high-intensity group performed aerobic interval walking/running at 85 - 95 % of maximal heart rate , whereas the moderate-intensity group exercised continuously at 60 - 70 % of maximal heart rate ; protocol s were isocaloric . The strength training group performed ' high-intensity ' leg press , abdominal and back strength training . Maximal oxygen uptake and endothelial function improved in all groups ; the greatest improvement was observed after high-intensity training , and an equal improvement was observed after moderate-intensity aerobic training and strength training . High-intensity aerobic training and strength training were associated with increased PGC-1alpha ( peroxisome-proliferator-activated receptor gamma co-activator 1alpha ) levels and improved Ca(2 + ) transport in the skeletal muscle , whereas only strength training improved antioxidant status . Both strength training and moderate-intensity aerobic training decreased oxidized LDL ( low-density lipoprotein ) levels . Only aerobic training decreased body weight and diastolic blood pressure . In conclusion , high-intensity aerobic interval training was better than moderate-intensity aerobic training in improving aerobic work capacity and endothelial function . An important contribution towards improved aerobic work capacity , endothelial function and cardiovascular health originates from strength training , which may serve as a substitute when whole-body aerobic exercise is contra-indicated or difficult to perform Exercise is an effective intervention for treating hypertension and arterial stiffness , but little is known about which exercise modality is the most effective in reducing arterial stiffness and blood pressure in hypertensive subjects . Our purpose was to evaluate the effect of continuous vs. interval exercise training on arterial stiffness and blood pressure in hypertensive patients . Sixty-five patients with hypertension were r and omized to 16 weeks of continuous exercise training ( n=26 ) , interval training ( n=26 ) or a sedentary routine ( n=13 ) . The training was conducted in two 40-min sessions a week . Assessment of arterial stiffness by carotid – femoral pulse wave velocity ( PWV ) measurement and 24-h ambulatory blood pressure monitoring ( ABPM ) were performed before and after the 16 weeks of training . At the end of the study , ABPM blood pressure had declined significantly only in the subjects with higher basal values and was independent of training modality . PWV had declined significantly only after interval training from 9.44±0.91 to 8.90±0.96 m s−1 , P=0.009 ( continuous from 10.15±1.66 to 9.98±1.81 m s−1 , P = ns ; control from 10.23±1.82 to 10.53±1.97 m s−1 , P = ns ) . Continuous and interval exercise training were beneficial for blood pressure control , but only interval training reduced arterial stiffness in treated hypertensive subjects Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies Aims : Exercise is recommended as prevention , management , and control of all stages of hypertension . There are still controversies about the optimal training dose , frequency , and intensity . We aim ed to study the effect of aerobic interval training on blood pressure and myocardial function in hypertensive patients . Methods and results : A total of 88 patients ( 52.0 ± 7.8 years , 39 women ) with essential hypertension were r and omized to aerobic interval training ( AIT ) ( > 90 % of maximal heart rate , correlates to 85–90 % of VO2max ) , isocaloric moderate intensity continuous training ( MIT ) ( ∼70 % of maximal heart rate , 60 % of VO2max ) , or a control group . Exercise was performed on a treadmill , three times per week for 12 weeks . Ambulatory 24-hour blood pressure ( ABP ) was the primary endpoint . Secondary endpoints included maximal oxygen uptake ( VO2max ) , mean heart rate/24 hour , flow mediated dilatation ( FMD ) , total peripheral resistance ( TPR ) , and myocardial systolic and diastolic function by echocardiography . Systolic ABP was reduced by 12 mmHg ( p < 0.001 ) in AIT and 4.5 mmHg ( p = 0.05 ) in MIT . Diastolic ABP was reduced by 8 mmHg ( p < 0.001 ) in AIT and 3.5 mmHg ( p = 0.02 ) in MIT . VO2max improved by 15 % ( p < 0.001 ) in AIT and 5 % ( p < 0.01 ) in MIT . Systolic myocardial function improved in both exercise groups , diastolic function in the AIT group only . TPR reduction and increased FMD were only observed in the AIT group . Conclusions : This study indicates that the blood pressure reducing effect of exercise in essential hypertension is intensity dependent . Aerobic interval training is an effective method to lower blood pressure and improve other cardiovascular risk factors BACKGROUND Peak oxygen uptake ( Vo(2peak ) ) strongly predicts mortality in cardiac patients . We compared the effects of aerobic interval training ( AIT ) versus moderate continuous training ( MCT ) on Vo(2peak ) and quality of life after coronary artery bypass grafting ( CABG ) . METHODS Fifty-nine CABG patients were r and omized to either AIT at 90 % of maximum heart rate or MCT at 70 % of maximum heart rate , 5 d/wk , for 4 weeks at a rehabilitation center . Primary outcome was Vo(2peak ) , at baseline , after rehabilitation ( 4 weeks ) , and after 6 months of home-based exercise ( 6 months ) . RESULTS Vo(2peak ) increased between baseline and 4 weeks in AIT ( 27.1 + /- 4.5 vs 30.4 + /- 5.5 mL.kg(-1).min(-1 ) , P < .001 ) and MCT ( 26.2 + /- 5.2 vs 28.5 + /- 5.6 mL.kg(-1).min(-1 ) , P < .001 ; group difference , not significant ) . Aerobic interval training increased Vo(2peak ) between 4 weeks and 6 months ( 30.4 + /- 5.5 vs 32.2 + /- 7.0 mL.kg(-1).min(-1 ) , P < .001 ) , with no significant change in MCT ( 28.5 + /- 5.6 vs 29.5 + /- 5.7 mL.kg(-1).min(-1 ) ) . Quality of life improved in both groups from baseline to 4 weeks , remaining improved at 6 months . There were no changes in echocardiographic systolic and diastolic left ventricular function . Adiponectin increased between 4 weeks and 6 months in both groups ( group differences , not significant ) . CONCLUSIONS Four weeks of intense training increased Vo(2peak ) significantly after both AIT and MCT . Six months later , the AIT group had a significantly higher Vo(2peak ) than MCT . The results indicate that AIT and MCT increase Vo(2peak ) similarly in the short term , but with better long-term effect of AIT after CABG We found that interval training provides an effective means to improve the cardiovascular fitness and health status of highly functional patients with coronary artery disease . We also revealed that interval training improves anaerobic tolerance to a greater extent than the traditional exercise training model without increasing the risk to the patient . This research supports the implementation of interval training for highly functional patients with coronary artery disease Background Prolonged oxygen uptake kinetics ( O2 kinetics ) , following the onset of a constant workload of exercise has been associated with a poor prognosis in patients with chronic heart failure . This study aim ed to determine both continuous and interval training effects on the different O2-kinetics phases in these patients . Design Twenty-one patients ( 60 ± 8 years ) with stable chronic heart failure participated in a 36-session exercise rehabilitation program ( three times weekly ) . Patients were r and omly assigned to interval training ( n = 11 ; 100 % of peak work rate for 30 s , alternating with 30s-rest ) and to continuous training ( n = 10 ; 50 % of peak work rate ) . Methods Before and after the completion of the program , all patients performed both incremental symptom-limited and constant workload submaximal cardiopulmonary exercise tests . Phase I O2-kinetics was evaluated by time ( t ) , from the start of exercise until the onset of decreased respiratory exchange ratio and phase II by the time constant ( τ ) of the response from the end of phase I until steady state . Results After training , there was a significant increase in peak oxygen uptake and peak work rate in both continuous ( 15.3 ± 4.4 vs. 16.6 ± 4.5 ml/kg per min ; P=0.03 and 81.8 ± 40.1 vs. 94.7 ± 46.1 W ; P=0.03 ) and interval training groups ( 14.2 ± 3.1 vs. 15.4 ± 4.2 ml/kg per min ; P=0.03 and 82.5 ± 24.1 vs. 93.7 ± 30.1 W ; P=0.04 ) . Patients who underwent interval training had a significant decrease in t ( 39.7 ± 3.7 to 36.1 ± 6.9s ; P=0.05 ) , but not τ ( 59.6 ± 9.4 to 58.9 ± 8.5 s ; P = ns ) , whereas those assigned to continuous training had a significant decrease in both t ( 40.6 ± 6.1 to 36.4 ± 5.4 s ; P=0.01 ) and τ ( 63.3 ± 23.6 to 42.5 ± 16.7 s ; P=0.03 ) . Conclusions Exercise training improves O2 kinetics in chronic heart failure patients . Both continuous and interval training improve phase I O2-kinetics , but continuous training results in superior improvement of the phase II O2-kinetics , an indirect index of muscle oxidative capacity Aerobic capacity , measured as the peak oxygen uptake , is a strong predictor of survival in cardiac patients . Aerobic interval training ( AIT ) , walking/running four times four minutes at 85–95 % of peak heart rate , has proven to be effective in increasing peak oxygen uptake in coronary heart disease patients . As some patients do not attend organized rehabilitation programs , home-based exercise should be an alternative . We investigated whether AIT could be performed effectively at home , and compared the effects on peak oxygen uptake with that observed after a st and ard care , four-week residential rehabilitation . Thirty patients undergoing coronary artery bypass surgery were r and omized to resident Output:	HIIT significantly increases CRF by almost double that of MICT in patients with lifestyle-induced chronic diseases
MS21558	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background and Objectives Femoral nerve block ( FNB ) , a commonly used postoperative pain treatment after total knee arthroplasty ( TKA ) , reduces quadriceps muscle strength essential for mobilization . In contrast , adductor canal block ( ACB ) is predominately a sensory nerve block . We hypothesized that ACB preserves quadriceps muscle strength as compared with FNB ( primary end point ) in patients after TKA . Secondary end points were effects on morphine consumption , pain , adductor muscle strength , morphine-related complications , and mobilization ability . Methods We performed a double-blind , r and omized , controlled study of patients scheduled for TKA with spinal anesthesia . The patients were r and omized to receive either a continuous ACB or an FNB via a catheter ( 30-mL 0.5 % ropivacaine given initially , followed by a continuous infusion of 0.2 % ropivacaine , 8 mL/h for 24 hours ) . Muscle strength was assessed with a h and held dynamometer , and we used the percentile change from baseline for comparisons . The trial was registered at clinical trials.gov ( Identifier : NCT01470391 ) . Results We enrolled 54 patients , of which 48 were analyzed . Quadriceps strength as a percentage of baseline was significantly higher in the ACB group compared with the FNB group : ( median [ range ] ) 52 % [ 31–71 ] versus 18 % [ 4–48 ] , ( 95 % confidence interval , 8–41 ; P = 0.004 ) . There was no difference between the groups regarding morphine consumption ( P = 0.94 ) , pain at rest ( P = 0.21 ) , pain during flexion of the knee ( P = 0.16 ) , or adductor muscle strength ( P = 0.39 ) ; neither was there a difference in morphine-related adverse effects or mobilization ability ( P > 0.05 ) . Conclusions Adductor canal block preserved quadriceps muscle strength better than FNB , without a significant difference in postoperative pain Purpose Providing effective analgesia for total knee arthroplasty ( TKA ) patients remains challenging . Femoral nerve block ( FNB ) offers targeted pain control ; however , its effect on motor function , related fall risk and impact on rehabilitation has been the source of controversy . Adductor canal block ( ACB ) potentially spares motor fibres of the femoral nerve , but the comparative effect of the two approaches has not yet been well defined due to considerable variability in pain perception . Our study compares both single-shot FNB and ACB , side to side , in the same patients undergoing bilateral TKA . Methods Sixty patients scheduled for bilateral TKA were r and omised to receive ultrasound-guided FNB on one leg and ACB on the other , in addition to combined spinal epidural anaesthesia . The primary outcome was comparative postoperative pain in either extremity at six to eight , 24 and 48 hours postoperatively . Secondary comparative outcomes included motor strength ( manually and via dynamometer ) , physical therapy milestones and patient satisfaction . Results While pain levels were lowest at six to eight hours postoperatively and increased thereafter ( P < 0.001 ) , no significant differences were seen between extremities at any time point with regard to pain in the quantitative comparison using visual analogue scale ( VAS ) scores ( P = 0.4154 ) , motor strength ( P = 0.7548 ) , physical therapy milestones or patient satisfaction . However , in the qualitative comparison , a significant proportion of patients reported the leg receiving ACB to be more painful than that receiving FNB at 24 h [ 50.9 % ( n = 30 ) vs 25.42 % ( n = 15 ) , P = 0.0168 ) ] . Conclusions Although we could not confirm a benefit in motor function between ACB and FNB , given the equivalent analgesic potency combined with its potentially lower overall impact if neuropraxia should occur , ACB may represent an attractive alternative to FNB Background There are several methods for postoperative analgesia for knee surgery . The commonly utilized method is multimodal analgesia based on continuous femoral nerve block . The aim of this study was to investigate the application of continuous adductor canal block for analgesia after total knee replacement and compare this method with continuous femoral nerve block . Methods Sixty patients scheduled for total knee replacement from June 2013 to March 2014 were r and omly divided into a femoral group and an adductor group . Catheters were placed under the guidance of nerve stimulation in the femoral group and under the guidance of ultrasound in the adductor group . Operations were performed under combined spinal and epidural anesthesia . After the operations , 0.2 % ropivacaine was given at a speed of 5 ml/h through catheters in all patients . Visual analogue scale ( VAS ) pain scores at rest and while moving were noted at 4 , 24 , and 48 hours after the operation , and quadriceps strength was also assessed at these time‐points . Secondary parameters such as doses of complementary analgesics and side effects were also recorded . Results There were no significant differences between the groups in VAS pain scores at rest or while moving , at 4 , 24 , or 48 hours after the operation ( P > 0.05 ) . At these time‐points , mean quadriceps strengths in the adductor group were 3.0 ( 2.75‐3.0 ) , 3.0 ( 3.0‐4.0 ) , and 4.0 ( 3.0‐4.0 ) , respectively , all of which were significantly stronger than the corresponding means in the femoral group , which were 2.0 ( 2.0‐3.0 ) , 2.0 ( 2.0‐3.0 ) , and 3.0 ( 2.0‐4.0 ) , respectively ( P < 0.05 ) . There were no significant differences between the groups in doses of complementary analgesics or side effects ( P > 0.05 ) . X‐ray images of some patients showed that local anesthetic administered into the adductor canal could diffuse upward and reach the femoral triangle . Conclusions Continuous adductor canal block with 0.2 % ropivacaine could be used effectively for analgesia after total knee replacement . Compared with continuous femoral nerve block , this analgesic method has similar analgesic effects and is associated with less weakness of quadriceps muscle Background and Objectives Adductor canal block ( ACB ) has been suggested as an analgesic alternative to femoral nerve block ( FNB ) for procedures on the knee , but its effect on quadriceps motor function is unclear . We performed a r and omized , blinded study to compare quadriceps strength following adductor canal versus FNB in volunteers . Our hypothesis was that quadriceps strength would be preserved following ACB , but not FNB . Secondary outcomes included relative preservation of hip adduction and degree of balance impairment . Methods The ACB was performed in one leg and the FNB in the contralateral leg in 16 volunteers using a r and omized block sequence . For all blocks , 15 mL of 3 % chloroprocaine was injected under ultrasonographic guidance . Maximal voluntary isometric contraction of knee extension and hip adduction was measured at baseline and at 30 and 60 minutes after block . After 60-minute assessment s were complete , the second block was placed . A test of balance ( Berg Balance Scale ) was performed 30 minutes after the first block only . Results Quadriceps strength and balance scores were similar to baseline following ACB . Following FNB , there was a significant reduction in quadriceps strength ( 95.1 % ± 17.1 % vs 11.1 % ± 14.0 % ; P < 0.0001 ) and balance scores ( 56 ± 0 vs 37 ± 17.2 ; P = 0.02 ) compared with baseline . There was no difference in hip adductor strength ( 97.0 % ± 10.8 % vs 91.8 % ± 9.6 % ; P = 0.17 ) . Conclusions Compared with FNB , ACB results in significant quadriceps motor sparing and significantly preserved balance The purpose of this study was to evaluate the functional outcomes of persons who underwent simultaneous bilateral total knee arthroplasty ( TKA ) compared to subjects who underwent unilateral TKA and a healthy control group . Fifteen subjects who underwent primary bilateral TKA and 15 sex , age , and body mass index-matched subjects who underwent primary unilateral TKA were observed prospect ively for 2 years . Subjects in both surgical groups showed significant improvement in Knee Outcome Scores , Short Form 36 physical component scores , Timed Up and Go , and stair-climbing tasks ( P < or= .004 ) . No differences in final outcomes were found between surgical groups . In addition , most 2-year clinical measures were no different between the surgical and control groups . Subjects medically appropriate for bilateral TKA should be afforded this option UNLABELLED Total knee arthroplasty is associated with intense , early post-operative pain . Femoral nerve block is known to provide optimal pain relief but reduces the strength of the quadriceps muscle and associated with the risk of falling . Adductor canal block is almost pure sensory blockade with minimal effect on quadriceps muscle strength . We prospect ively r and omized 100 patients in two groups ' continuous adductor and femoral block group . Ambulation ability ( Timed up go , 10-m walk , 30 s chair test ) , time to active SLR , quadsticks , staircase competency , ambulation distance was significantly better ( P value < 0.001 ) in adductor canal group whereas pain scores , opioid consumption showed no significant difference . Adductor canal block provided better ambulation and early functional recovery but without superior analgesia than femoral nerve block post TKA . LEVEL OF EVIDENCE Level III , therapeutic study Output:	Dear editors : We read with interest the manuscript by Li et al. [ 1 ] Adductor canal block provides better performance after total knee arthroplasty compared with femoral nerve block : a systematic review and meta- analysis ; however , the authors concluded that the meta- analysis suggested that ACB provide better ambulation ability , faster functional recovery , and better pain control at rest after TKA compared to FNB .
MS21559	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives : To examine the association between hormone therapy ( HT ) and cognitive performance or dementia , focusing on the duration and type of treatment used , as well as the timing of initiation of HT in relation to the menopause . Methods : Women 65 years and older were recruited in France as part of the Three City Study . At baseline and 2- and 4-year follow-up , women were administered a short cognitive test battery and a clinical diagnosis of dementia was made . Detailed information was also gathered relating to current and past HT use . Analysis was adjusted for a number of sociodemographic , behavioral , physical , and mental health variables , as well as APOE ε4 . Results : Among 3,130 naturally postmenopausal women , current HT users performed significantly better than never users on verbal fluency , working memory , and psychomotor speed . These associations varied according to the type of treatment and a longer duration of HT appeared to be more beneficial . However , initiation of HT close to the menopause was not associated with better cognition . HT did not significantly reduce dementia risk over 4 years but current treatment diminished the negative effect associated with APOE ε4 . Conclusions : Current hormone therapy ( HT ) was associated with better performance in certain cognitive domains but these associations are dependent on the duration and type of treatment used . We found no evidence that HT needs to be initiated close to the menopause to have a beneficial effect on cognitive function in later life . Current HT may decrease the risk of dementia associated with the APOE ε4 allele We estimated the remaining lifetime risks of developing Alzheimer 's disease ( AD ) and dementia from all causes , based on data from longitudinal population studies . The risk of developing AD during one 's lifetime depends on both disease incidence and life expectancy . Conventional estimates of cumulative incidence overestimate the risk when there is a substantial probability of mortality due to competing causes . A total of 2,611 cognitively intact subjects ( 1,061 men , 1,550 women ; mean age , 66± 7 years ) were prospect ively evaluated for the development of AD or other dementia . A modified survival analysis was used to estimate both cumulative incidence and the sex-specific remaining lifetime risk estimates for quinquennial age groups above age 65 years . Over a 20-year follow-up period , 198 subjects developed dementia ( 120 with AD ) . The remaining lifetime risk of AD or other dementia depended on sex , being higher in women , but varied little with age between 65 and 80 years . In a 65-year-old man , the remaining lifetime risk of AD was 6.3 % ( 95 % CI , 3.9 to 8.7 ) and the remaining lifetime risk of developing any dementing illness was 10.9 % ( 95 % CI , 8.0 to 13.8 ) ; corresponding risks for a 65-year-old woman were 12 % ( 95 % CI , 9.2 to 14.8 ) and 19 % ( 95 % CI , 17.2 to 22.5 ) . The cumulative incidence between age 65 and 100 years was much higher : for AD , 25.5 % in men and 28.1 % in women ; for dementia , 32.8 % in men and 45 % in women . The actual remaining lifetime risk of AD or dementia varies with age , sex , and life expectancy and is lower than the hypothetical risk estimated by a cumulative incidence in the same population CONTEXT Postmenopausal women have a greater risk than men of developing Alzheimer disease , but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent . On July 8 , 2002 , the study drugs , estrogen plus progestin , in the Women 's Health Initiative ( WHI ) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy . OBJECTIVE To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo . DESIGN , SETTING , AND PARTICIPANTS The Women 's Health Initiative Memory Study ( WHIMS ) , a r and omized , double-blind , placebo-controlled clinical trial , began enrolling participants from the Women 's Health Initiative ( WHI ) estrogen plus progestin trial in May 1996 . Of the 4894 eligible participants of the WHI study , 4532 ( 92.6 % ) postmenopausal women free of probable dementia , aged 65 years or older , and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS . INTERVENTION Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate ( n = 2229 ) , or a matching placebo ( n = 2303 ) . MAIN OUTCOME MEASURES Incidence of probable dementia ( primary outcome ) and mild cognitive impairment ( secondary outcome ) were identified through a structured clinical assessment . RESULTS The mean ( SD ) time between the date of r and omization into WHI and the last Modified Mini-Mental State Examination ( 3MSE ) for all WHIMS participants was 4.05 ( 1.19 ) years . Overall , 61 women were diagnosed with probable dementia , 40 ( 66 % ) in the estrogen plus progestin group compared with 21 ( 34 % ) in the placebo group . The hazard ratio ( HR ) for probable dementia was 2.05 ( 95 % confidence interval [ CI ] , 1.21 - 3.48 ; 45 vs 22 per 10 000 person-years ; P = .01 ) . This increased risk would result in an additional 23 cases of dementia per 10 000 women per year . Alzheimer disease was the most common classification of dementia in both study groups . Treatment effects on mild cognitive impairment did not differ between groups ( HR , 1.07 ; 95 % CI , 0.74 - 1.55 ; 63 vs 59 cases per 10 000 person-years ; P = .72 ) . CONCLUSIONS Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older . In addition , estrogen plus progestin therapy did not prevent mild cognitive impairment in these women . These findings , coupled with previously reported WHI data , support the conclusion that the risks of estrogen plus progestin outweigh the benefits OBJECTIVES The current study investigated the neurotrophic and neuroprotective action of the complex formulation of conjugated equine estrogens ( CEEs ) , the most frequently prescribed estrogen replacement therapy in the United States and the estrogen replacement therapy of the Women 's Health Initiative . METHODS Videomicroscopic , morphologic and biochemical analyses were conducted in primary cultures of hippocampal neurons to determine the neurotrophic and neuroprotective properties of CEEs . RESULTS Results of these analyses demonstrated that CEEs significantly increased hippocampal neuronal outgrowth , a cellular marker of memory formation . Dose response analyses indicated that the lowest effective concentration of CEEs exerted the maximal neurotrophic effect . Results of neuroprotection studies demonstrated that CEES induced highly significant neuroprotection against beta amyloid(25 - 35 ) , hydrogen peroxide and glutamate-induced toxicity . CONCLUSIONS CEEs induced cellular markers of memory function in neurons critical to memory and vulnerable to negative effects of aging and Alzheimer 's disease . In addition , CEEs significantly and potently protected neurons against toxic insults associated with Alzheimer 's disease . Because CEEs are the estrogen replacement therapy of the Women 's Health Initiative , results of the current study could provide cellular mechanisms for effects of CEEs on cognitive function and risk of Alzheimer 's disease derived from this prospect i ve clinical trial A prospect i ve analysis of risk factors for Alzheimer 's disease was a major objective of the Canadian Study of Health and Aging , a nationwide , population -based study . Of 6,434 eligible subjects aged 65 years or older in 1991 , 4,615 were alive in 1996 and participated in the follow-up study . All participants were cognitively normal in 1991 when they completed a risk factor question naire . Their cognitive status was reassessed 5 years later by using a similar two-phase procedure , including a screening interview , followed by a clinical examination when indicated . The analysis included 194 Alzheimer 's disease cases and 3,894 cognitively normal controls . Increasing age , fewer years of education , and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer 's disease . Use of nonsteroidal anti-inflammatory drugs , wine consumption , coffee consumption , and regular physical activity were associated with a reduced risk of Alzheimer 's disease . No statistically significant association was found for family history of dementia , sex , history of depression , estrogen replacement therapy , head trauma , antiperspirant or antacid use , smoking , high blood pressure , heart disease , or stroke . The protective associations warrant further study . In particular , regular physical activity could be an important component of a preventive strategy against Alzheimer 's disease and many other conditions Over the past two decades , there has been a significant amount of research investigating the risks and benefits of hormone replacement therapy ( HRT ) with regards to neurodegenerative disease . Here , we review basic science studies , r and omized clinical trials , and epidemiological studies , and discuss the putative neuroprotective effects of HRT in the context of Alzheimer 's disease , Parkinson 's disease , frontotemporal dementia , and HIV-associated neurocognitive disorder . Findings to date suggest a reduced risk of Alzheimer 's disease and improved cognitive functioning of postmenopausal women who use 17β-estradiol . With regards to Parkinson 's disease , there is consistent evidence from basic science studies for a neuroprotective effect of 17β-estradiol ; however , results of clinical and epidemiological studies are inconclusive at this time , and there is a paucity of research examining the association between HRT and Parkinson's-related neurocognitive impairment . Even less understood are the effects of HRT on risk for frontotemporal dementia and HIV-associated neurocognitive disorder . Limits to the existing research are discussed , along with proposed future directions for the investigation of HRT and neurodegenerative diseases CONTEXT Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions , particularly memory . OBJECTIVE The objective of this study was to determine whether hormone therapy influences changes in specific cognitive functions and affect in older women . DESIGN This study was a r and omized , double-blind , placebo-controlled clinical trial . SETTING Participants were women from 14 of 40 clinical centers of the Women 's Health Initiative ( WHI ) . PARTICIPANTS Postmenopausal women ( 1416 ) aged 65 yr and older , free of probable dementia , and enrolled in WHI and the WHI Memory Study ( WHIMS ) trial of combination estrogen and progestin for a mean of 3 yr and followed for a mean of 1.35 yr , were studied . INTERVENTION Intervention was conjugated equine estrogen ( CEE ; 0.625 mg ) with 2.5 mg medroxyprogesterone acetate ( MPA ) in one daily tablet ( CEE + MPA ) or placebo . MAIN OUTCOME MEASURES Annual rates of change in specific cognitive functions and affect , adjusted for time since r and omization , were measured . RESULTS CEE + MPA had a negative impact on verbal memory ( P < or= 0.01 ) and a trend to a positive impact on figural memory ( P = 0.012 ) over time compared with placebo , but other cognitive domains were not affected . Both effects on memory were evident only after long-term therapy . CEE + MPA did not significantly influence positive affect , negative affect , or depressive symptoms . CONCLUSIONS The effect of CEE + MPA on cognitive function varies across cognitive domains in older women , reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain . Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research Background : Cross-sectional studies suggest gender differences in cognitive function and risk of AD in older persons . However , longitudinal studies comparing change in cognitive function and risk of AD in men and women have had mixed results . The authors investigated gender differences in rate of decline for different cognitive systems and for risk of developing AD . Methods : Participants were from the Religious Orders Study , a longitudinal , clinical –pathologic study of aging and AD in older Catholic nuns , priests , and brothers . Longitudinal data were available from 577 older women and 271 older men , who completed an average of 5.8 annual evaluations with more than 95 % follow-up participation in survivors . The evaluations included 21 neuropsychological tests , from which summary measures of global cognitive function and 5 functional domains were formed , and clinical classification of AD . Results : R and om effects models were used to analyze change in cognitive function , and proportional hazards models were used to assess risk of incident AD . On average , men and women declined in all abilities during the 8-year period but did not differ in annual rates of change in analyses that controlled for age , education , and initial level of cognitive function . Risk of incident AD did not differ between men and women . Furthermore , results were unchanged after controlling for possession of the apolipoprotein- Output:	Our findings support current recommendations that hormone therapy should not be used for dementia prevention .
MS21560	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Adverse drug reactions ( ADR 's ) could be expected more frequently in pregnant women . This study was performed in order to identify ADR 's to tocolytic drugs in hospitalised pregnant women . Methods A prospect i ve cohort study was performed in two General Hospitals of the Instituto Mexicano del Seguro Social ( IMSS ) in Mexico City . Two hundred and seven women undergoing labor , premature labor , threatened abortion or suffering any obstetric related disease were included . Drug prescription and signs and symptoms of any potential ADR were registered daily during the hospital stay . Any potential ADR to tocolytic drugs was evaluated and classified by three of the authors using the Kramer 's algorithm . Results Of the 207 patients , an ADR was positively classified in 25 cases ( 12.1 % , CI95 % 8.1 to 17.5 % ) . All ADR 's were classified as minor reactions . Grouping patients with diagnosis of threatened abortion , premature labor or under labor ( n= 114 ) , 24 ADR 's were related to terbutaline , accounting for a rate of 21.1 ADR 's per 100 obstetric patients . Obstetric patients suffering an ADR were older than obstetric patients without any ADR . However , the former received less drugs/day × patient-1 and had a shorter hospital stay ( p < 0.05 ) whereas the dose of terbutaline was similar between the two groups . Terbutaline inhibited uterine motility in women with and without any ADR at a similar rate , 70 and 76 % respectively ( x2 = 0.07 ; p = 0.8 ) . Conclusion Terbutaline , used as a tocolytic drug , was related to a high frequency of minor ADRs and to a high rate of effcicacy Objectives : People in developing countries often seek medical advice for common ailments from pharmacies . As one example , pharmacists routinely diagnose and treat symptomatic sexually transmitted infections ( STIs ) . We aim ed to assess the quality of advice provided in Mexico City pharmacies by presenting hypothetical STI related syndromes and recording pharmacy attendants ’ suggested diagnoses and treatments . Methods : We interviewed the first available attendant in each of a 5 % r and om sample of Mexico City ’s pharmacies . We inquired about the training , age , and experience of the attendant and about the typical number of clients coming for treatment of suspected STIs . After considering three hypothetical case studies , attendants recommended diagnoses , treatments , and , sometimes , physician follow up . Results : Most Mexico City “ pharmacists ” are actually clerks , with trained pharmacists rarely available on the premises . The average pharmacy attendant was 32 years old , with a median of 5 years ’ experience at that pharmacy , but very limited ( if any ) training . 62 % reported seeing 10 or more clients with genital or vaginal infections per month . Depending on the case study , attendants provided appropriate diagnoses in 0–12 % of cases , recommended appropriate treatments in 12–16 % of cases , and suggested physician follow up for 26–67 % of cases . Conclusions : In general , surveyed pharmacy personnel were unable to diagnose accurately or offer appropriate treatment advice when presented with classic , common STI symptoms . Given the volume of clients seeking advice from this source , training pharmacy attendants could significantly help to reduce the burden of disease associated with STIs in Mexico City A prospect i ve cohort study was conducted to analyze factors associated with antibiotic noncompliance and waste among patients suffering acute respiratory infection ( ARI ) and acute diarrhea ( AD ) . The study took place in four primary health care clinics in Mexico City , two belonging to the Ministry of Health ( MoH ) and two to the Mexican Social Security Institute ( IMSS ) . Two hundred twenty-two patients with ARI and 155 with AD were included . Data about study variables and the assessment of compliance were obtained through patient interviews and direct observation . Factors associated with noncompliance were assessed through a multiple logistic regression procedure . Noncompliance was 60 % for ARI and 55.5 % for AD in both health care systems . Prescription of an antibiotic was justified only in 13.5 % of cases . Associated factors were : increased duration of illness ( OR 2.95 ; 95 % CI , 1.17 - 7.41 ) ; complexity of the treatment : 3 or more doses per day ( OR 2.47 ; 95 % CI , 1.56 - 3.92 ) , and treatment for more than 7 days ( OR 1.94 ; 95 % CI , 1.16 - 3.26 ) ; younger age of patient ( OR 1.89 ; 95 % CI , 1.18 - 3.02 ) ; and an inadequate physician-patient relationship ( OR 1.87 ; 95 % CI , 1.16 - 3.02 ) . Antibiotic waste was higher in IMSS ( ARI 39.3 % , AD 32.6 % ) , than in the MoH ( ARI 21.2 % , AD 16.4 % ) . Educational strategies to modify physician prescribing practice s and strengthen physician-patient relationships might improve compliance and decrease drug waste In developing countries , antibiotics are the most common drugs sold , and some data suggest that they are frequently misused . In order to describe the pattern of antibiotic use in a periurban community in Mexico City , 1659 r and omly-selected households were visited and an interview with the housewife was carried out . Six local drugstores also were selected at r and om . A social worker made six visits to each pharmacy , observed the events during the purchase of the drug and applied a structured question naire to the customer immediately after the transaction . Of 8279 individuals , 425 ( 5 % ) said that they had used at least one antimicrobial in the preceding 2 weeks and antibiotics were the majority ( 29 % ) of the drug sales . The main perceived reasons for drug use were acute respiratory tract ailments and gastroenteritis . Interviewees reported that antibiotic therapy was given in 27 % of respiratory diseases and in 37 % of all diarrheal episodes . The drugs most commonly reported were : penicillins , erythromycin , metronidazole , neomycin , cotrimoxazole and tetracyclines . While self-medication and drug purchases without medical prescription were common , the majority of antibiotics were prescribed by a physician . Approximately two thirds of individuals using an antibiotic said they had used it for less than 5 days and 72 % of the purchases were for insufficient quantities of drugs . Our data suggest that antibiotics are frequently misused and they support the need to assess the determinants of self-medication , health-seeking behavior and physician prescribing practice s. The need for effective educational programs to improve prescribers ' decisions is stressed CONTEXT In Mexico , oral contraceptives ( OCs ) are available to women over-the-counter in pharmacies . While past research has suggested that nonmedical providers , such as pharmacy workers , are capable of screening women for contraindications to OCs , little is known about their practice s. METHODS After selecting a 10 % r and om sample of all pharmacies in Mexico City ( n = 108 ) , we surveyed the first available pharmacy worker to learn more about pharmacy workers ' screening practice s when selling OCs over-the-counter to women . RESULTS While nearly all of the pharmacy workers surveyed had sold OCs without a prescription , only 31 % reported asking women any questions before selling pills . Among those who asked questions , the most commonly asked questions were about other medications a woman was taking , about blood pressure and about alcohol intake . Pharmacy workers did not ask these questions consistently to all clients . CONCLUSION Training pharmacy workers might be one strategy to improve screening of women for pill contraindications . However , pharmacy workers may lack the time and motivation to carry out such screening . An alternative strategy might be to better inform women to self-screen for pill contraindications To improve prescribing practice s for rhinopharyngitis , an interactive educational intervention and a managerial intervention were carried out in 18 primary care facilities in metropolitan Mexico City . Four family medicine clinics of the Mexican Social Security Institute ( IMSS ) and 14 health centres of the Ministry of Health ( SSA ) were included . A quasi-experimental design was employed . One hundred and nineteen physicians ( IMSS 68 , SSA 51 ) participated . Sixty-five physicians ( IMSS 32 , SSA 33 ) were in the study group , while 54 were in the control group ( IMSS 36 , SSA 18 ) . The study had four stages : ( I ) baseline , to evaluate the physicians ' prescribing behaviour for rhinopharyngitis ; ( II ) intervention , using an interactive educational workshop and a managerial peer review committee ; ( III ) post-intervention evaluation of short-term impact ; and ( IV ) follow-up evaluation of long-term effect 18 months after the workshop . The control group did not receive any intervention but was evaluated at the same time as the study group . At baseline , most patients in both institutions received antibiotic prescriptions ( IMSS 85.2 % , SSA 68.8 % ) . After the workshop , the percentage of patients receiving antibiotic prescriptions in the IMSS went from 85.2 % to 48.1 % , while in the SSA it went from 68.8 % to 49.1 % . Appropriateness of treatment was analyzed using the physician as the unit of analysis . At baseline , 30 % of IMSS physicians in the study group treated their patients appropriately . After the intervention , this percentage increased to 57.7 % , and at the 18-month follow-up it was 54.2 % . The SSA study group increased the appropriate use of antibiotics from 35.7 % to 46.2 % , with this percentage falling to 40.9 % after the 18-month follow-up period . In the control group there were no significant changes in prescribing patterns with respect to either the prescribing of antibiotics or the appropriateness of treatment . The intervention strategies were successful in both institutions . Forty per cent of physicians improved their prescribing practice s after the workshop , with this change remaining in 27.5 % of them throughout the follow-up period . On the other h and , 42.5 % of the physicians did not change their prescribing practice s after the intervention . The rest ( 17.5 % ) showed appropriate prescribing practice s during all the stages of the study . We conclude that it is possible to improve the physicians ' prescribing practice s through interactive educational strategies and managerial interventions . This type of intervention can be an affordable way to provide continuing medical education to primary care physicians who do not have access to continuing educational activities , and to improve the quality of care they provide BACKGROUND The impact of nosocomial infections and multidrug resistance on mortality is a topic of considerable controversy . METHODS A prospect i ve , nested case control study was conducted in four intensive care units ( ICUs ) in Mexico to measure the impact of antibiotic resistance on and identify the main risk factors for mortality in critically ill patients with nosocomial infections . RESULTS One hundred thirteen patients developed 119 nosocomial infections . Multivariate analysis identified two variables that were significantly and independently associated with mortality : ventilator-associated pneumonia ( p = 0.0041 , odds ratio [ OR ] = 7.7 ) and inadequate antibiotic treatment ( p < 0.0001 , OR = 70.5 ) . Although antibiotic resistance in Gram-negative rods was not an independent risk factor for mortality , there was a strong association between antibiotic resistance and inadequate treatment ( chi2 for linear trend = 29.3 , p < 0.00001 ) . For patients with ventilator-associated pneumonia , predicted mortality calculated by APACHE II score was 23 % compared to an observed mortality of 71 % . CONCLUSIONS In this study the major risk factors for mortality were inadequate antibiotic treatment and development of ventilator-associated pneumonia . Multidrug resistance significantly increased the probability of receiving inadequate antibiotic treatment . The striking differences between observed and predicted mortality in these four ICUs indicate the need for further research and a re assessment of the current programs for prevention and control of nosocomial infections in Mexico Based on previous community-oriented studies an irrational use of antibiotics , particularly in developing countries , has been suggested . In order to describe the pattern of antibiotic use in a periurban community in Mexico City , 1659 r and omly selected households were visited and an interview to the housewife was carried out . Of 8279 individuals 425 ( 5 % ) had used at least one antimicrobial in the preceding two weeks . Main perceived reasons for drug use were : respiratory tract ailments ( 58 % ) and acute diarrhea ( 25 % ) . Antibiotic therapy was given in 27 % of respiratory diseases and in 37 % of all diarrheal episodes . Most commonly used drugs were : penicillins ( 43 % ) , erythromycin ( 13 % ) , metronidazole ( 9 % ) , neomycin ( 6 % ) , cotrimoxazole ( 6 % ) and tetracyclines ( 6 % ) . While self-medication was common ( 19 % ) the majority of antibiotics were prescribed by a physician ( 81 % ) . Approximately two thirds of individuals using an antibiotic did it for less than five days . Our data suggest a frequent misuse of antibiotics and support the future assessment , in this community , of physician prescribing practice s , the determinants of self-medication as well as the impact of this drug use on the selection of resistant bacterial strains OBJECTIVE To evaluate if the histamine H2 Output:	This review identified two priorities for Mexico 's pharmaceutical policy and strategies : tackling the irrational use of medicines and the inadequate access of medicines .
MS21561	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background While integrated health care system has been proved an effective way to help improving patient health and system efficiency , the exact behaviour model and motivation approach are not so clear in poor rural areas where health human re sources and continuous service provision are urgently needed . To gather solid evidence , we initiated a comprehensive intervention project in Qianjiang District , southwest part of rural China in 2012 . And after one-year 's pilot , we developed an intervention package of team service , comprehensive pathway and prospect ive- and performance-based payment system . Methods To testify the potential influence of payment interventions , we use clustered r and omised controlled trial , 60 clusters are grouped into two treatment groups and one control group to compare the time and group differences . Difference-in-differences model and structural equation modelling will be used to analyse the intervention effects and pathway . The outcomes are : quality of care , disease burden , supplier cooperative behaviour and patient utilisation behaviour and system efficiency . Repeated multivariate variance analysis will be used to statistically examine the outcome differences . Discussion This is the first trial of its kind to prove the effects and efficiency of integrated care . Though we adopted r and omised controlled trial to gather the highest rank of evidence , still the fully r and omisation was hard to realise in health policy reform experiment . To compensate , the design er should take efforts on control for the potential confounders as much as possible . With this trial , we assume the effects will come from : ( 1 ) improvement on the quality of life through risk factors control and lifestyles change on patient 's behaviours ; ( 2 ) improvement on quality of care through continuous care and coordinated supplier behaviours ; ( 3 ) improvement on the system efficiency through active interaction between suppliers and patients . Conclusion The integrated care system needs collaborative work from different levels of caregivers . So it is extremely important to consider the supplier cooperative behaviour . In this trial , we introduced payment system to help the delivery system integration through providing financial incentives to motivate people to play their roles . Also , the multidisciplinary team , the multi-institutional pathway and system global budget and pay-for-performance payment system could afford as a solution RATIONALE , AIMS AND OBJECTIVES Acute myocardial infa rct ions ( MIs ) or heart attacks are the result of a complete or an incomplete occlusion of the lumen of the coronary artery with a thrombus . Prompt diagnosis and early coronary intervention results in maximum myocardial salvage , hence time to treat is of the essence . Adequate , accurate and complete information is vital during the early stages of admission of an MI patient and can impact significantly on the quality and safety of patient care . This study aim ed to record how clinical information between different clinical teams during the journey of a patient in the MI care pathway is captured and to review the flow of information within this care pathway . METHOD A prospect i ve , descriptive , structured observational study to assess ( i ) current clinical information systems ( CIS ) utilization and ( ii ) real-time information availability within an acute cardiac care setting was carried out . Completeness and availability of patient information capture across four key stages of the MI care pathway were assessed prospect ively . RESULTS Thirteen separate information systems were utilized during the four phases of the MI pathway . Observations revealed fragmented CIS utilization , with users accessing an average of six systems to gain a complete set of patient information . Data capture was found to vary between each pathway stage and in both patient cohort risk groupings . The highest level of information completeness ( 100 % ) was observed only in the discharge stage of the MI care pathway . The lowest level of information completeness ( 58 % ) was observed in the admission stage . CONCLUSION The study highlights fragmentation , CIS duplication , and discrepancies in the current clinical information capture and data transfer across the MI care pathway in an acute cardiac care setting . The development of an integrated and user-friendly electronic data capture and transfer system would reduce duplication and would facilitate efficient and complete information provision at the point of care Background Ten years on from the National Institute of Health and Clinical Excellence ’ technology appraisal guideline on haemodialysis in 2002 ; the clinical community is yet to rise to the challenge of providing home haemodialysis ( HHD ) to 10 - 15 % of the dialysis cohort . The renal registry report , suggests underutilization of a treatment type that has had a lot of research interest and several publications worldwide on its apparent benefit for both physical and mental health of patients . An underst and ing of the drivers to introducing and sustaining the modality , from organizational , economic , clinical and patient perspectives is fundamental to realizing the full benefits of the therapy with the potential to provide evidence base for effective care models . Through the BASIC-HHD study , we seek to underst and the clinical , patient and carer related psychosocial , economic and organisational determinants of successful uptake and maintenance of home haemodialysis and thereby , engage all major stakeholders in the process . Design and methods We have adopted an integrated mixed methodology ( convergent , parallel design ) for this study . The study arms include a. patient ; b. organization ; c. carer and d. economic evaluation . The three patient study cohorts ( n = 500 ) include pre-dialysis patients ( 200 ) , hospital haemodialysis ( 200 ) and home haemodialysis patients ( 100 ) from geographically distinct NHS sites , across the country and with variable prevalence of home haemodialysis . The pre-dialysis patients will also be prospect ively followed up for a period of 12 months from study entry to underst and their journey to renal replacement therapy and subsequently , before and after studies will be carried out for a select few who do commence dialysis in the study period . The process will entail quantitative methods and ethnographic interviews of all groups in the study . Data collection will involve clinical and biomarkers , psychosocial quantitative assessment s and neuropsychometric tests in patients . Organizational attitudes and dialysis unit practice s will be studied together with perceptions of healthcare providers on provision of home HD . Economic evaluation of home and hospital haemodialysis practice s will also be undertaken and we will apply scenario ( " what … if " ) analysis using system dynamics modeling to investigate the impact of different policy choices and financial models on dialysis technology adoption , care pathways and costs . Less attention is often given to the patient ’s carers who provide informal support , often of a complex nature to patients afflicted by chronic ailments such as end stage kidney disease . Engaging the carers is fundamental to realizing the full benefits of a complex , home-based intervention and a qualitative study of the carers will be undertaken to elicit their fears , concerns and perception of home HD before and after patient ’s commencement of the treatment . The data sets will be analysed independently and the findings will be mixed at the stage of interpretation to form a coherent message that will be informing practice in the future . Discussion The BASIC-HHD study is design ed to assemble pivotal information on dialysis modality choice and uptake , investigating users , care-givers and care delivery processes and study their variation in a multi-layered analytical approach within a single health care system . The study results would define modality specific service and patient pathway re design . Study Registration This study has been review ed and approved by the Greater Manchester West Health Research Authority National Research Ethics Service ( NRES ) The study is on the NIHR ( CLRN ) portfolio Background The worldwide human re source gap in anesthesia services often presents a barrier to accessing life-saving and life-improving surgeries . This paper assessed the impact of a ketamine anesthesia package , Every Second Matters-Ketamine ( ESM-Ketamine ) ™ , for use in emergency and life-improving surgeries by non-anesthetist clinicians in a re source -limited setting when no anesthetist was available . Methods We analyzed prospect ively collected data from 193 surgeries constituting a pilot implementation of the ESM-Ketamine package , among three sub-district hospitals in Western Kenya . The study population comprises patients who required emergency or life-improving surgery when no anesthetist was available . Non-anesthetist clinicians in three sub-district hospitals underwent a 5-day training course in ESM-Ketamine complemented by checklists and an ESM-Ketamine Kit . Data were collected prospect ively every time the ESM-Ketamine pathway was invoked . The training cases , although primarily tubal ligations , were included . The primary outcome measures centered on capturing the ability to safely support emergency and life-improving surgeries , when no anesthetist was available , through invoking the ESM-Ketamine pathway . The registry was critically examined using st and ard descriptive and frequency analysis . Results 193 surgical procedures were supported using the ESM-Ketamine package by five ESM-Ketamine trained providers . Brief ( < 30 s ) patient desaturation below 92 % and hallucinations occurred in 16 out of 186 ( 8.6 % ) and 23 out of 190 patients ( 12.1 % ) , respectively . There were no reported major adverse events such as death , prolonged desaturations ( over 30 s ) , or injury result ing from ketamine use . Conclusion This study provides promising initial evidence that the ESM-Ketamine package can support emergency and life-improving surgeries in re source -limited setting s when no anesthetist is available BACKGROUND Venous thromboembolism is common in cancer patients and requires anticoagulation with low-molecular-weight heparin ( LMWH ) . Current data recommend LMWH for anticoagulation as far as 6 months , yet guidelines recommend LMWH beyond 6 months in patients who have ongoing or active cancer . This recommendation , based on expert consensus , has not been evaluated in a clinical study . OBJECTIVES ( 1 ) To identify the most clinical ly and cost-effective length of anticoagulation with LMWH in the treatment of cancer-associated thrombosis ( CAT ) ; ( 2 ) to identify practicalities of conducting a full r and omised controlled trial ( RCT ) with regard to recruitment , retention and outcome measurement ; and ( 3 ) to explore the barriers for progressing to a full RCT . DESIGN The Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis ( ALICAT ) trial is a r and omised , multicentre , feasibility mixed- methods study with three components : ( 1 ) a RCT comparing ongoing LMWH treatment for CAT with cessation of LMWH at 6 months ' treatment ( current licensed practice ) in patients with locally advanced or metastatic cancer , consulted in three clinical setting s ( haematology out patients , oncology out patients and primary care ) ; ( 2 ) a nested qualitative study , including focus groups with clinicians to investigate attitudes for recruiting to the study and identify the challenges of progressing to a full RCT , and semistructured interviews with patients and relatives to explore their attitudes towards participating in the study , and potential barriers and concerns to participation ; and ( 3 ) a UK-wide survey exercise to develop a classification and enumeration system for the CAT models and pathways of care . SETTING A haematology out patients department , an oncology out patients department and primary care . PARTICIPANTS Patients with ongoing active or metastatic cancer who have received 6 months of LMWH for CAT . INTERVENTIONS Ongoing LMWH treatment for CAT versus cessation of LMWH at 6 months ' treatment in patients with locally advanced or metastatic cancer . MAIN OUTCOME MEASURES ( i ) The number of eligible patients over 12 months ; ( ii ) the number of recruited patients over 12 months ( target recruitment rate of 30 % of eligible patients ) ; and ( iii ) the proportion of r and omised participants with recurrent venous thromboembolisms ( VTEs ) during follow-up . RESULTS Following several delays in setting up the RCT component of the study , 5 out of 32 eligible patients consented to be r and omised to the RCT suggesting progression to a full RCT was not feasible . Reasons for non-consenting were primarily based on a fixed preference for continuing or discontinuing treatment after 6 months of anticoagulation , and a fear of r and omisation to their non-preferred option . Views were largely influenced by patients ' initial experience of CAT . Focus groups with clinicians revealed that they would be reticent to recruit to such a study as they had fixed views of best management despite the lack of evidence . Patient pathway modelling suggested that there is a broad heterogeneity of practice with respect to CAT management and co-ordination , with no consensus on which specialty should best manage such cases . CONCLUSIONS The results of the RCT reflect recruitment from the oncology site only and provide no recruitment data from haematology centres . However , it is unlikely that these other sites would have access to more eligible patients . The management of cancer-associated thrombosis beyond 6 months will remain a clinical challenge . As it is unlikely that a prospect i ve study will successfully recruit , other strategies to accrue relevant data are necessary . Currently the LONGHEVA ( Long-term treatment for cancer patients with deep-venous thrombosis or pulmonary embolism ) registry is in development to prospect ively evaluate this important and common clinical scenario . STUDY REGISTRATION This study is registered as clinical trials.gov number NCT01817257 and International St and ard R and omised Controlled Trial Number ( IS RCT N ) 37913976 . FUNDING DETAILS Funding for the ALICAT trial was provided by the Health Technology Assessment programme ( 10/145/01 ) in response to a themed funding call . The study was design ed in accordance with the initial funding brief and feedback from the review process Background Medical treatment in patient-centred care in oncology is broadly managed and regulated in terms of guideline development , cancer centres , and quality assurance by cancer registries . In contrast to this quality management cycle ( PDCA ) , there are no equal st and ards for patient-reported outcomes like quality of life ( QoL ) Output:	Oncology is particularly prevalent due to its already well-established processes of care .
MS21562	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Our previous work has identified that unmedicated volunteers with schizophrenia have regional cerebral blood flow ( rCBF ) activation patterns inappropriately related to the cognitive dem and of a task in anterior cingulate cortex ( ACC ) . Using positron emission tomography ( PET ) with 15O water , we compared task-induced rCBF patterns induced by haloperidol or clozapine in individuals with schizophrenia . We hypothesized that clozapine , given its superior clinical action , would tend to normalize the abnormal task-activated response in ACC more than haloperidol . Schizophrenia volunteers ( SVs ) ( n=6 ) and normal volunteers ( NVs ) ( n=12 ) were trained to perform a tone discrimination task with 70–80 % accuracy . They were then scanned during three task conditions : ( 1 ) Rest , ( 2 ) sensory motor control ( SMC ) task , and ( 3 ) decision task ( DEC ) . SVs were initially scanned after withdrawal of all psychotropic medication and again after treatment with therapeutic doses of haloperidol ( n=5 ) and /or clozapine ( n=5 ) . rCBF values , sample d in the grown maxima of the task-activated ACC cluster , were analyzed between groups and task conditions . Task performance was similar across the unmedicated , haloperidol- and clozapine-medicated SV groups . There was a reduction in accuracy in the haloperidol SV group compared to the NVs . Group and task conditions affected rCBF in the ACC . Clozapine , but not haloperidol , reversed the abnormal ACC rCBF pattern in unmedicated SV to normal . The clozapine-treated SV group showed a rCBF pattern similar to the NV group in that ACC activation was not observed during the control task but occurred during the decision condition . The pattern seen in the haloperidol-treated SV group was similar to the unmedicated SV group in that ACC activation was seen during the control task and no further activation was seen during the DEC . We report that clozapine , but not haloperidol , normalizes anterior cingulate rCBF patterns in schizophrenia during a cognitive task . Based on these preliminary data , we propose that this pattern may account for the superior therapeutic effect of clozapine and represents a surrogate marker of this action OBJECTIVE Studies have found that cau date volume increased after treatment with typical antipsychotics in patients with schizophrenia but decreased after treatment was changed to clozapine . In the current study the authors examined whether this volume decrease was related to clinical improvement . METHOD Twenty-eight patients with schizophrenia who had not responded to treatment with typical antipsychotics were included in the study ; 22 completed the study . Cau date volume was assessed by using magnetic resonance imaging during treatment with typical antipsychotics and after 24 weeks and 52 weeks of clozapine treatment . Symptoms were assessed just before clozapine treatment and once a month thereafter . RESULTS Clozapine treatment result ed in a significant reduction in left cau date volume in patients who responded to the drug but not in patients who did not respond to clozapine at 52 weeks of treatment . Overall , the degree of reduction in left cau date volume was significantly related to the extent of improvement in positive and general symptoms but not in negative symptoms . CONCLUSIONS These findings suggest that the cau date nucleus plays a role in the positive and general symptoms of schizophrenia BACKGROUND Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described . Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome . This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia . OBJECTIVE To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition . DESIGN Longitudinal , r and omized , controlled , multisite , double-blind study . Patients treated and followed up for up to 104 weeks . Neurocognitive and magnetic resonance imaging ( MRI ) assessment s performed at weeks 0 ( baseline ) , 12 , 24 , 52 , and 104 . Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI , psychopathologic , and neurocognitive outcomes . SETTING Fourteen academic medical centers ( United States , 11 ; Canada , 1 ; Netherl and s , 1 ; Engl and , 1 ) . PARTICIPANTS Patients with first-episode psychosis ( DSM-IV ) and healthy volunteers . INTERVENTIONS R and om allocation to a conventional antipsychotic , haloperidol ( 2 - 20 mg/d ) , or an atypical antipsychotic , olanzapine ( 5 - 20 mg/d ) . MAIN OUTCOME MEASURES Brain volume changes assessed by MRI . RESULTS Of 263 r and omized patients , 161 had baseline and at least 1 postbaseline MRI evaluation . Haloperidol-treated patients exhibited significant decreases in gray matter volume , whereas olanzapine-treated patients did not . A matched sample of healthy volunteers ( n = 58 ) examined contemporaneously showed no change in gray matter volume . CONCLUSIONS Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes . Haloperidol was associated with significant reductions in gray matter volume , whereas olanzapine was not . Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated . The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine BACKGROUND Little is known about the effects of antipsychotic medications on gray matter ( GM ) in schizophrenia . Although clozapine remains the most effective antipsychotic medication in treatment-refractory cases , it is unknown whether it has a differential effect on GM development . METHODS In an exploratory analysis , we used automated cortical thickness measurements and prospect ively scanned childhood-onset schizophrenia ( COS ) patients who were maintained on one medication . Two atypical antipsychotic medications , clozapine ( n=12 , 37 scans ) and olanzapine ( n=12 , 33 scans ) were compared with respect to effects on cortical development , in contrast to GM trajectories of matched controls . RESULTS There were no significant differences in the trajectories of cortical thickness between the two treatment groups with the exception of a small circumscribed area in the right prefrontal cortex , where the olanzapine group showed thicker cortex . As expected , both groups showed thinner GM compared to matched controls . CONCLUSIONS Although these analyses do not rule out effects of antipsychotic medications on GM development in schizophrenia , they show no differential effect between clozapine and olanzapine on GM trajectory Subtraction ictal single photon emission tomography ( SPET ) co-registered to magnetic resonance imaging ( SISCOM ) is an ictal-interictal brain perfusion SPET subtraction method , developed for evaluation of brain perfusion changes applied for the identification of epileptic foci . The aim of this study was to test whether regional cerebral blood flow ( rCBF ) alterations due to clozapine in schizophrenic patients could also be detected with SISCOM . We have studied the brain perfusion SPET data obtained both before ( pre-SPET ) and 8 weeks after ( post-SPET ) clozapine treatment , in 20 patients with schizophrenia . These data were used for SISCOM processing . In order to identify any alterations in the perfusion pattern using SISCOM , pre- and post-SPET data were subtracted from each other . Activation maps were created and merged on either pre- or post-SPET images . Visual interpretation of brain perfusion SPET studies were performed and compared with SISCOM findings . We found that final SISCOM images and visual evaluation of pre- and post-SPET studies were well concordant in 17/20 patients . Discordance was observed in 3 patients . In 1 of these 3 patients alterations observed with SISCOM were confirmed as subtle changes on visual re-evaluation of the images . In the remaining 2 of these 3 patients , SISCOM did not confirm the changes observed by visual analysis . Additionally , SISCOM depicted perfusion alteration in occipital cortex in 5 patients . In conclusion , the algorithm of SISCOM seemed to be useful and complementary to visual evaluation , to assess rCBF changes due to clopazine in outpatient schizophrenic patients who had treatment refractoriness or intolerance of previous antipsychotics and to provide additional information when both pre- and post-SPET data were subtracted from each other BACKGROUND Approximately 50 % of patients with schizophrenia or schizoaffective disorder attempt suicide , and approximately 10 % die of suicide . Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients . METHODS A multicenter , r and omized , international , 2-year study comparing the risk for suicidal behavior in patients treated with clozapine vs olanzapine was conducted in 980 patients with schizophrenia or schizoaffective disorder , 26.8 % of whom were refractory to previous treatment , who were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation . To equalize clinical contact across treatments , all patients were seen weekly for 6 months and then biweekly for 18 months . Subsequent to r and omization , unmasked clinicians at each site could make any interventions necessary to prevent the occurrence of suicide attempts . Suicidal behavior was assessed at each visit . Primary end points included suicide attempts ( including those that led to death ) , hospitalizations to prevent suicide , and a rating of " much worsening of suicidality " from baseline . Masked raters , including an independent suicide monitoring board , determined when end point criteria were achieved . RESULTS Suicidal behavior was significantly less in patients treated with clozapine vs olanzapine ( hazard ratio , 0.76 ; 95 % confidence interval , 0.58 - 0.97 ; P = .03 ) . Fewer clozapine-treated patients attempted suicide ( 34 vs 55 ; P = .03 ) , required hospitalizations ( 82 vs 107 ; P = .05 ) or rescue interventions ( 118 vs 155 ; P = .01 ) to prevent suicide , or required concomitant treatment with antidepressants ( 221 vs 258 ; P = .01 ) or anxiolytics or soporifics ( 301 vs 331 ; P = .03 ) . Overall , few of these high-risk patients died of suicide during the study ( 5 clozapine vs 3 olanzapine-treated patients ; P = .73 ) . CONCLUSIONS Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide . Use of clozapine in this population should lead to a significant reduction in suicidal behavior Typical antipsychotics have been reported to enlarge the cau date nucleus in schizophrenic patients . The atypical antipsychotic , clozapine , is associated with a decrease in cau date size in patients previously treated with typical antipsychotics . The present study investigates whether a change in cau date volume after switching from treatment with typical antipsychotics to treatment with clozapine is related to improvement in symptoms or tardive dyskinesia ( TD ) . Twenty-six schizophrenic patients participated in this open study . Cau date nucleus volume and TD were assessed before discontinuing typical antipsychotics and after 24 weeks of treatment with clozapine . After discontinuing typical antipsychotics , symptoms were assessed in a 3 days drug-free period and subsequently once a month . Treatment with clozapine result ed in a decrease in cau date volume , improvement in symptoms and amelioration of TD . However , no difference in cau date volume changes was found between responders and non-responders to clozapine and no correlations were found between cau date volume changes and reduction of TD . In conclusion , this study replicates earlier findings that clozapine decreases cau date volume in patients previously treated with typical antipsychotics and suggests that this effect is unrelated to treatment response or to amelioration of TD Typical antipsychotic drugs act on the dopaminergic system , blocking the dopamine type 2 ( D2 ) receptors . Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors , and a high degree of occupancy of the serotoninergic receptors 5-HT2A . Whether these different pharmacological actions produce different effects on brain structure remains unclear . We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based , nonr and omized sample of patients at the first psychotic episode . Subjects were recruited as part of a large epidemiological study ( ÆSOP : aetiology and ethnicity in schizophrenia and other psychoses ) . We evaluated 22 drug-free patients , 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics . We used high-resolution MRI and voxel-based methods of image analysis . The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes . However , typicals seem to affect more extensively the basal ganglia ( enlargement of the putamen ) and cortical areas ( reductions of lobulus para central is , anterior cingulate gyrus , superior Output:	In structural studies , the use of clozapine was associated with volume reductions in the basal ganglia , especially the cau date nucleus , where functional neuroimaging studies also found decreased perfusion . In the frontal lobe , clozapine treatment was associated with increased gray matter volume and reduced perfusion . CONCLUSION The results of the studies review ed suggest that the use of clozapine is associated with distinctive structural and functional neuroimaging findings that are not shared with other antipsychotics
MS21563	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To study the use and cost of bedside capillary glucose testing in a large teaching hospital . PATIENTS AND METHODS In a prospect i ve study of 40 inpatient units and 10 outpatient units at Massachusetts General Hospital , records were maintained by each unit of the date , time , operator , and results of patient and quality control tests . Cost analysis was performed using data from time studies , test tallies in logbooks , and hospital administration records . RESULTS The number of glucose meters in the hospital increased from 10 to 54 over a 2-year period . In 1992 , 67,596 tests were performed by the bedside method , representing 30.7 % of all glucose measurements performed in the institution . The majority of tests ( 94.7 % ) were performed on in patients , and 10.2 % of all hospital admissions underwent bedside glucose testing . The impact on the number of glucose tests performed in the clinical laboratories was minimal , indicating that bedside glucose testing was added as an extra test rather than as a substitute for laboratory-based glucose measurements . The cost of bedside glucose testing was $ 4.19 per test compared with $ 3.84 in the clinical laboratory . The cost varied from one unit to another ( median $ 5.52 , range $ 3.08 to $ 48.16 ) , an effect largely attributed to the difference in the volume of tests performed by different units . In seven high-volume units the cost per test was lower than the corresponding value in the laboratory . The cost of bedside glucose testing included labor ( 80.2 % ) and supplies ( 19.8 % ) . The percent of costs attributed directly to patient testing was 57.7 % , whereas the costs for all other related activities ( training , quality control , and quality assurance ) was 42.3 % . CONCLUSIONS Bedside capillary glucose testing is a rapidly exp and ing technology and is performed on a significant percentage of hospital admissions . Bedside glucose testing is not inherently more expensive than central ized laboratory measurements but implementation on inefficient care units with low utilization can add substantially to the cost . Much of the excess cost of the bedside method can be attributed to the high costs of quality control and quality assurance , training , and documentation Patients with active venous and arterial thromboembolic disorders are known to benefit from systemic anticoagulation with heparin . Clinical studies have shown , however , that therapeutic anticoagulation is rarely achieved rapidly and often is not maintained over time . Prolonged laboratory turnaround time of the activated partial thromboplastin time ( aPTT ) may contribute directly to these common problems . A total of 272 aPTT determinations were performed on 120 heparin-treated patients admitted to the coronary care unit . The time from sample collection to data availability was 126 + /- 84 minutes with st and ard laboratory aPTT testing . In contrast , a bedside coagulation device provided an aPTT within 3 minutes ( p < 0.001 ) . Subtherapeutic aPTT values ( < 65 seconds ) were documented in 21 % of all patients ; in each , the heparin dose was changed and a repeat aPTT was required . In a separate study of 33 heparinized patients r and omized to either bedside or central laboratory aPTT testing ( 264 aPTT determinations ) , the time to achieve a therapeutic state of systemic anticoagulation was 8.2 hours and 18.1 hours , respectively ( p < 0.005 ) . The time from aPTT determination to a decision regarding heparin titration adjustments was 14.5 minutes and 3 hours with bedside and laboratory testing , respectively ( p < 0.001 ) . Thus bedside coagulation monitoring provides a convenient , rapid , and accurate assessment of systemic anticoagulation among heparin-treated patients with active thromboembolic disease in the coronary care unit . This technology warrants further clinical investigation BACKGROUND Point-of-care testing ( POCT ) can provide rapid test results , but its impact on patient care is not well documented . We investigated the ability of POCT to decrease inpatient and outpatient waiting times for cardiovascular procedures . METHODS We prospect ively studied , over a 7-month period , 216 patients requiring diagnostic laboratory testing for coagulation ( prothrombin time/activated partial thromboplastin time ) and /or renal function ( urea nitrogen , creatinine , sodium , and potassium ) before elective invasive cardiac and radiologic procedures . Overall patient management and workflow were examined in the initial phase . In phase 2 , we implemented POCT but utilized central laboratory results for patient management . In phase 3 , therapeutic decisions were based on POCT results . The final phase , phase 4 , sought to optimize workflow around the availability of POCT . Patient wait and timing of phlebotomy , availability of laboratory results , and therapeutic action were monitored . Split sampling allowed comparability of POCT and central laboratory results throughout the study . RESULTS In phase 1 , 44 % of central laboratory results were not available before the scheduled time for procedure ( n = 135 ) . Mean waiting times ( arrival to procedure ) were 188 + /- 54 min for patients who needed renal testing ( phase 2 ; n = 14 ) and 171 + /- 76 min for those needing coagulation testing ( n = 24 ) . For patients needing renal testing , POCT decreased patient wait times ( phases 3 and 4 combined , 141 + /- 52 min ; n = 18 ; P = 0.02 ) . For patients needing coagulation testing , wait times improved only when systematic changes were made in workflow ( phase 4 , 109 + /- 41 min ; n = 12 ; P = 0.01 ) . CONCLUSIONS Although POCT has the potential to provide beneficial patient outcomes , merely moving testing from a central laboratory to the medical unit does not guarantee improved outcomes . Systematic changes in patient management may be required BACKGROUND R and omized trials have demonstrated the importance of achieving adequate heparinization early in the course of therapy . Recently , some authors reported a pooled analysis of selected studies in the literature that suggested that there is no convincing evidence that the risk of recurrent venous thromboembolism is critically dependent on achieving a therapeutic activated partial thromboplastin time result at 24 to 48 hours . METHODS We provide the analyses of patient groups entered into our series of 3 consecutive double-blind r and omized trials evaluating initial heparin therapy for proximal deep venous thrombosis . RESULTS Logistic regression analysis of the patient groups receiving the less intense initial intravenous heparin dose of 30,000 U/24 h demonstrated that subtherapy for 24 hours predicted the onset of venous thromboembolic events . Failure to achieve a therapeutic activated partial thromboplastin time by 24 hours was associated with a 23.3 % frequency of venous thromboembolism vs 4 % to 6 % for those whose activated partial thromboplastin time exceeded the therapeutic threshold by 24 hours ( P=.02 ) . Time-to-event analysis shows the increased frequency of recurrent venous thromboembolic events during the period of study in patients who were subtherapeutic for 24 hours compared with those who were therapeutic ( P=.001 ) . CONCLUSIONS Our findings reaffirm the clinical importance of rapidly achieving therapeutic levels of heparin . Patients who failed to achieve the therapeutic threshold by 24 hours were at an increased risk of subsequent recurrent venous thromboembolism . These findings are independently supported by the results of a r and omized trial comparing different intensities of initial heparin treatment by continuous infusion Objective : Two different point-of-care ( POC ) systems for the monitoring of coagulation variables at the bedside were evaluated with regard to practicability , accuracy and costs . Design : Prospect i ve , descriptive study . Setting : Single-institutional , clinical investigation on an intensive care unit ( ICU ) of an urban , university-affiliated hospital . Patients : Eighty cardiac surgery patients were studied postoperatively . Interventions : Arterial blood sample s were drawn postoperatively on the ICU at different data points . Measurements and results : Activated partial thromboplastin time ( aPTT ) and prothrombin time ( PT ) were measured using two POC systems ( Thrombolytic Assessment System [ TAS ] and CoaguCheck Plus ° ) . At the same time coagulation parameters were measured by the central laboratory of the hospital . Measurements were carried out at different data points after cardiac surgery on the ICU . The direct and indirect costs of measuring aPTT/PT were also assessed . Bias analyses revealed good agreement of the POC-based monitoring of aPTT/PT with laboratory-based monitoring of coagulation ( e. g. aPTT CoaguCheck : bias of − 2.8 s with ± 2 SD [ limits of agreement ] of + 13.7 and −19.1 s ) . Mean turn-around time ( TAT ; time from blood sampling until availability of data for the ICU physicians ) was significantly longer for the central laboratory-based coagulation monitoring ( 130 ± 38 min ) than for the two POC systems ( aPTT-TAS : 9.6 ± 2.7 min ; aPTT-CoaguCheck : 6.5 ± 1.9 min ) . Blood sampling at unfavorable times increased the TAT for laboratory-based measurements considerably . The direct costs for measuring aPPT and PT were significantly higher using both POC systems ( aPTT-TAS : $ 4.84 ; aPTT-CoaguCheck : $ 4.34 ) than for the central laboratory ( $ 1.59 ) . Costs for transportation increased the laboratory-based monitoring considerably ( $ 3.77 ) . Conclusions : Both POC analyzers may reduce the potential for pre-analytical errors associated with coagulation measurements at the central laboratory , hasten TAT significantly and may improve patient therapy by reducing inappropriate administration of blood products Individual aspects of heparin or protamine dosing have been better controlled than previously as useful tests have become available . Although many variables including drug potency , drug source , and individual patient response have been separately identified , there has not been an attempt to integrate them into a single management strategy . This study was undertaken to learn whether more precise control of drug variables and patient response would affect blood loss and transfusion requirements . Adult patients having primary cardiac operations were prospect ively r and omized into two groups . A control group received heparin and protamine by conventional methods . The test group received heparin and protamine according to in vitro predictive tests integrating drugs , tests , and patient response . Supplemental protamine was given in this group only if heparin was specifically found by testing . Anticoagulation in all patients was maintained at an activated coagulation time greater than 400 seconds , and any other treatment for bleeding was at the discretion of the clinical team caring for the patients . Testing and treatment for both groups followed routine practice after patient arrival in the intensive care unit . Test patients received slightly more heparin and a markedly lower dose of protamine than the control patients . Testing identified patients with decreased heparin sensitivity ( preoperative heparin therapy ) and correctly predicted the effective heparin dose . Supplemental protamine was given twice as often to control patients and frequently when no heparin was detectable ( retrospectively ) . Test patients exhibited less 24-hour chest tube drainage ( 671 ml versus 1298 ml ) and fewer patients received transfusion ( 9/22 versus 18/24 ) with fewer donor exposures ( 22/22 versus 101/24 ) . The management strategy used for heparin and protamine added accuracy and precision , which was associated with improved hemostasis . Although the observation is valid , the mechanism or mechanisms are not completely clear . Nevertheless , it is reasonable to apply basic pharmacologic principles and establishment of consistent , predictable protocol s that are beneficial . It is against this background that the efficacy of additional drugs or equipment should be assessed . It is quite possible that only marginal if any improvement in hemostasis may be found in patients having primary , uncomplicated cardiac operation with the addition of more costly drugs or equipment During 1966 to 1968 , 64 of 459 ( 13.9 % ) prospect ively monitored , digoxin‐treated patients at Massachusetts General Hospital suffered adverse reactions to the drug . Measurements of serum digoxin concentrations for therapeutic guidance began at Massachusetts General Hospital in 1969 , and trom Gctober , 1970 , to June , 1972 , they were performed on 40 % of all digoxin recipients . During that same period , only 15 of 2.53 ( 5.9 % ) monitored , digoxin‐treated patients became digitoxic . At 7 other monitored hospitals the frequency of adverse reactions to digoxin in 2,425 digoxin‐treated patients ranged from 13.1 % to 19.4 % . Detailed comparison of patients treated with digoxin during 1970 to 1972 at Massachusetts General Hospital and Peter Bent Brigham Hospital , 2 very similar Harvard Medical School teaching hospitals , showed the risk of aigitoxicity to be 2.12 times greater at the latter where serum digoxin assays were not commonly performed . These findings suggest that the use of serum digoxin determinations for ad;ustment of digoxin dosage reduces the frequency of digoxin toxicity Output:	All studies have incorporated point-of-care testing with changes in the way patient care is delivered and have shown significant improvements when this approach is taken . The cost of point-of-care testing is greater than traditional laboratory testing , but the increased cost may be offset by improvements in the management of patient care , improvements in patient outcomes , and decreased utilization of the healthcare system . Point-of-care testing has been used successfully by pharmacists in disease management programs . Various government regulations and legislation impact the use of point-of-care testing . : Limited data indicate that point-of-care testing , when combined with changes in healthcare delivery systems , may improve patient outcomes and decrease the overall cost of health care .
MS21564	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Nonselective systemic vasodilators worsen ventilation perfusion ( V/Q ) matching and gas exchange in patients with chronic obstructive pulmonary disease ( COPD ) . Inhaled iloprost has the potential to act preferentially in ventilated regions of the lung , thereby reducing pulmonary hypertension ( PH ) while alveolar ventilation is still maintained . Objectives : To investigate the acute effects of inhaled iloprost on V/Q matching in patients with COPD and PH . Methods : Ten males with COPD and PH on echocardiography were evaluated before and after inhaling 2 doses of iloprost ( 2.5 µg ) . Measurements included lung function , arterial blood gas , 6-min walk test ( 6MWT ) as well as ventilatory equivalents for oxygen ( VE/VO2 ) and carbon dioxide ( VE/VCO2 ) taken at baseline , 30 min following each dose of iloprost , and 2 h after the second dose . Results : Mean differences in VE/VCO2 and VE/VO2 were –13.3 ( 95 % CI –36.5 to –2.7 ; p = 0.002 ) and –15.0 ( 95 % CI –36.7 to –0.4 ; p = 0.02 ) , respectively , and the mean change in ( A-a ) gradient was –3.7 mm Hg ( 95 % CI –6.1 to –1.0 ; p = 0.01 ) after a single dose of iloprost , whereas mean improvement in 6MWT was 49.8 m ( 95 % CI 14.8 to 84.7 ; p = 0.02 ) . Arterial blood gas , venous admixture , dead space fraction and lung functions were maintained after iloprost . The effects of iloprost were reproducible after the second dose . All measurements returned to baseline 2 h after the last dose . No adverse effects on systemic blood pressure or oxygen saturation were seen . Conclusions : Iloprost inhalation was safe in patients with COPD and PH , and was associated with improved V/Q matching and exercise tolerance Abstract Rationale : Pulmonary hypertension with exercise is common in chronic obstructive pulmonary disease ( COPD ) and may contribute to exercise limitation in this disease . We aim ed to determine the effects of treatment with sildenafil on exercise capacity in patients with COPD and emphysema . Methods : We performed a r and omized , double-blind , placebo-controlled 2-period crossover trial of sildenafil thrice daily in ten adults with COPD and emphysema on CT scan without pulmonary hypertension . We r and omized study participants to 4 weeks of sildenafil ( or placebo ) followed by a 1-week washout and then 4 weeks of placebo ( or sildenafil ) . The 2 primary outcomes were the 6-minute walk distance and oxygen consumption at peak exercise . Results : Sildenafil had no effect on 6-minute walk distance ( placebo-corrected difference = -7.8 m , 95 % confidence interval , -23.2 to 7.5 m , p = 0.35 ) or oxygen consumption at peak exercise ( placebo-corrected difference = -0.1 ml/kg/min , 95 % confidence interval -2.1 to 1.8 ml/kg/min , p = 0.89 ) . Sildenafil increased the alveolar-arterial oxygen gradient ( p = 0.02 ) , worsened symptoms ( p = 0.04 ) , and decreased quality -of-life ( p = 0.03 ) . Adverse events were more frequent while receiving sildenafil ( p = 0.005 ) . Conclusions : Routine sildenafil administration did not have a beneficial effect on exercise capacity in patients with COPD and emphysema without pulmonary hypertension . Sildenafil significantly worsened gas exchange at rest and quality of life . ( clinical trials.gov NCT00104637 ) BACKGROUND Sildenafil inhibits phosphodiesterase type 5 , an enzyme that metabolizes cyclic guanosine monophosphate , thereby enhancing the cyclic guanosine monophosphate-mediated relaxation and growth inhibition of vascular smooth-muscle cells , including those in the lung . METHODS In this double-blind , placebo-controlled study , we r and omly assigned 278 patients with symptomatic pulmonary arterial hypertension ( either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to-pulmonary shunts ) to placebo or sildenafil ( 20 , 40 , or 80 mg ) orally three times daily for 12 weeks . The primary end point was the change from baseline to week 12 in the distance walked in six minutes . The change in mean pulmonary-artery pressure and World Health Organization ( WHO ) functional class and the incidence of clinical worsening were also assessed , but the study was not powered to assess mortality . Patients completing the 12-week r and omized study could enter a long-term extension study . RESULTS The distance walked in six minutes increased from baseline in all sildenafil groups ; the mean placebo-corrected treatment effects were 45 m ( + 13.0 percent ) , 46 m ( + 13.3 percent ) , and 50 m ( + 14.7 percent ) for 20 , 40 , and 80 mg of sildenafil , respectively ( P<0.001 for all comparisons ) . All sildenafil doses reduced the mean pulmonary-artery pressure ( P=0.04 , P=0.01 , and P<0.001 , respectively ) , improved the WHO functional class ( P=0.003 , P<0.001 , and P<0.001 , respectively ) , and were associated with side effects such as flushing , dyspepsia , and diarrhea . The incidence of clinical worsening did not differ significantly between the patients treated with sildenafil and those treated with placebo . Among the 222 patients completing one year of treatment with sildenafil monotherapy , the improvement from baseline at one year in the distance walked in six minutes was 51 m. CONCLUSIONS Sildenafil improves exercise capacity , WHO functional class , and hemodynamics in patients with symptomatic pulmonary arterial hypertension BACKGROUND Sildenafil has been found to improve exercise capacity and haemodynamic parameters in patients with various pulmonary disorders . This study was undertaken to evaluate its efficacy in severe chronic obstructive pulmonary disease ( COPD ) . METHODS In this double-blind , r and omised , placebo-controlled study , 37 patients with severe COPD received either sildenafil or placebo for 12 weeks . Distance covered in six-minute walk test ( 6MWD ) was taken as primary end-point . Pulmonary artery pressure ( PAP ) was measured as secondary end point . RESULTS Thirty-three patients ( 15 in sildenafil arm and 18 in placebo arm ) completed the study . Non-parametric tests were used for comparison . There was significant increase in 6MWD from baseline after three months of follow-up in sildenafil users ( median change in distance covered in six-minute walk test ( delta6MWD ) = 190 m ) as compared to placebo users ( delta6MWD = 0 m , p < 0.05 ) . The PAP decreased significantly ( chi2 = 14.94 , p < 0.05 ) in sildenafil group after three months , while it did not change significantly among placebo group ( chi2 = 3.84 , p > 0.05 ) . CONCLUSION Sildenafil improved 6MWD and PAP in patients with severe COPD Pulmonary hypertension is a life-threatening complication of lung fibrosis . Vasodilator therapy is difficult owing to systemic side effects and pulmonary ventilation-perfusion mismatch . We compared the effects of intravenous prostacyclin and inhaled NO and aerosolized prostacyclin in r and omized order and , in addition , tested for effects of oxygen and systemic calcium antagonists ( CAAs ) in eight patients with lung fibrosis and pulmonary hypertension . Aerosolized prostagl and in (PG)I(2 ) caused preferential pulmonary vasodilatation with a decrease in mean pulmonary arterial pressure from 44.1 + /- 4.2 to 31.6 + /- 3.1 mm Hg , and pulmonary vascular resistance ( RL ) from 810 + /- 226 to 386 + /- 69 dyn . s. cm(-)(5 ) ( p < 0.05 , respectively ) . Systemic arterial pressure , arterial oxygen saturation , and pulmonary right-to-left shunt flow , measured by multiple inert gas analysis , were not significantly changed . Inhaled NO similarly result ed in selective pulmonary vasodilatation , with RL decreasing from 726 + /- 217 to 458 + /- 81 dyn . s. cm(-)(5 ) . In contrast , both intravenous PGI(2 ) and CAAs were not pulmonary selective , result ing in a significant drop in arterial pressure . In addition , PGI(2 ) infusion caused a marked increase in shunt flow . Long-term therapy with aerosolized iloprost ( long-acting PGI(2 ) analog ) result ed in unequivocal clinical improvement from a state of immobilization and severe resting dyspnea in a patient with decompensated right heart failure . We concluded that , in pulmonary hypertension secondary to lung fibrosis , aerosolization of PGI(2 ) or iloprost causes marked pulmonary vasodilatation with maintenance of gas exchange and systemic arterial pressure . Long-term therapy with inhaled iloprost may be life saving in decompensated right heart failure from pulmonary hypertension secondary to lung fibrosis Pulmonary hypertension is a serious complication of chronic obstructive pulmonary disease ( COPD ) that currently has no established pharmacological treatment . This study aim ed to assess whether concomitant treatment with sildenafil would enhance the results of pulmonary rehabilitation in patients with COPD and increased pulmonary arterial pressure ( PAP ) . In this double-blind , r and omised controlled trial patients received 20 mg sildenafil or placebo three times daily and underwent pulmonary rehabilitation for 3 months . The primary end-point was the gain in the cycle endurance time at a constant work-rate . Secondary end-points included performance in the incremental exercise test , 6-min walk distance and quality of life . 63 patients with severe COPD and moderately increased PAP were r and omised . Cycle endurance time increased by 149 s ( 95 % CI 26–518 s ) in the sildenafil group and by 169 s ( 95 % CI 0–768 s ) in the placebo group ( median change difference -7 s , 95 % CI -540–244 s ; p=0.77 ) . Gains in the incremental exercise test , 6-min walk distance and quality of life at the end of the study did not differ between groups . Measurements of arterial oxygenation and adverse events were similar in both groups . In patients with severe COPD and moderately increased PAP , concomitant treatment with sildenafil does not improve the results of pulmonary rehabilitation in exercise tolerance . Sildenafil did not improve respiratory rehabilitation outcomes in patients with severe COPD and moderately increased PAP Pulmonary hypertension during exercise is common in severe chronic obstructive pulmonary disease ( COPD ) . It was hypothesised that the use of the endothelin-receptor antagonist bosentan can improve cardiopulmonary haemodynamics during exercise , thus increasing exercise tolerance in patients with severe COPD . In the present double-blind , placebo-controlled study , 30 patients with severe or very severe COPD were r and omly assigned in a 2:1 ratio to receive either bosentan or placebo for 12 weeks . The primary end-point was change in the 6-min walking distance . Secondary end-points included changes in health-related quality of life , lung function , cardiac haemodynamics , maximal oxygen uptake and pulmonary perfusion patterns . Compared with placebo , patients treated with bosentan during 12 weeks showed no significant improvement in exercise capacity as measured by the 6-min walking distance ( mean±sd 331±123 versus 329±94 m ) . There was no change in lung function , pulmonary arterial pressure , maximal oxygen uptake or regional pulmonary perfusion pattern . In contrast , arterial oxygen pressure dropped , the alveolar – arterial gradient increased and quality of life deteriorated significantly in patients assigned bosentan . The oral administration of the endothelin receptor antagonist bosentan not only failed to improve exercise capacity but also deteriorated hypoxaemia and functional status in severe chronic obstructive pulmonary disease patients without severe pulmonary hypertension at rest RATIONALE Sildenafil , a phosphodiesterase-5 inhibitor , could be useful for treating pulmonary hypertension ( PH ) in chronic obstructive pulmonary disease ( COPD ) . However , vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition . OBJECTIVES To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD -associated PH . METHODS We conducted a r and omized , dose comparison trial in 20 patients with COPD -associated PH . Eleven patients were assigned to 20 mg , and 9 patients to 40 mg , of sildenafil . Pulmonary hemodynamics Output:	In conclusion , PH specific drugs ( especially sildenafil ) could improve exercise capacity and decrease PAP in COPD patients with severe PH
MS21565	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND : We proposed a new chest physiotherapy ( CPT ) secretion clearance method to treat respiratory syncytial virus bronchiolitis in infants . Our new CPT method consists of 15 prolonged slow expirations , then 5 provoked cough maneuvers . METHODS : We r and omized 20 infants ( mean age 4.2 months ) into 2 groups : 8 patients received 27 sessions of nebulization of hypertonic saline ; 12 patients received 31 sessions of nebulization of hypertonic saline followed by our new CPT method . We used the Wang clinical severity scoring system ( which assesses wheezing , respiratory rate , retractions , and general condition ) and measured SpO2 and heart rate before each CPT session ( T0 ) , immediately after the 30-min session ( T30 ) , and 120 min after the session ( T150 ) . RESULTS : Within the groups : in the first group , Wang score was significantly lower at T150 than at T0 : 4.6 vs 5.0 ( P = .008 ) . In the new- method -CPT group , Wang score was significantly lower at T30 ( 3.6 vs 4.3 , P = .001 ) and at T150 ( 3.7 vs 4.3 , P = .002 ) . Wheezing score was significantly lower at T150 than at T0 ( 1.1 vs 1.2 , P = .02 ) in the first group , and in the new- method -CPT group at T30 than at T0 ( 0.8 vs 1.3 , P = .001 ) and at T150 than at T0 ( 0.9 vs 1.3 , P = .001 ) . Between the groups : at T30 the improvement was significantly better in the new- method -CPT group for overall Wang score ( P = .02 ) , retractions ( P = .05 ) , respiratory rate ( P = .001 ) , and heart rate ( P < .001 ) . At T150 the Wang score was not significantly different between the groups . At T30 ( versus T0 ) the difference in percent gain between the groups was significant for Wang score ( P = .004 ) , wheezing ( P = .001 ) , and heart rate ( P = .02 ) . Over 5-hospital days , the daily baseline ( T0 ) Wang score decreased significantly in the new- method -CPT group ( P = .002 ) , whereas it did not in the first group . There were no adverse events . Average hospital stay was not significantly different between the groups . CONCLUSIONS : Our new CPT method showed short-term benefits to some respiratory symptoms of bronchial obstruction in infants with acute respiratory syncytial virus bronchiolitis OBJECTIVE In previously well infants hospitalized with acute viral bronchiolitis , the effectiveness of repeated nebulized therapy with epinephrine ( EPI ) was compared with treatment with albuterol ( ALB ) or saline placebo ( PLAC ) . STUDY DESIGN In this r and omized , double-blind , parallel-group , controlled trial , infants received study nebulizations every 1 to 6 hours and were assessed twice daily by the research team . The primary outcome was length of hospital stay ( LOS ) . Secondary outcomes included the time from admission until the infant had normal hydration , oxygenation , and minimal respiratory distress . RESULTS A total of 149 infants were r and omized ; 50 were allocated to receive racemic EPI , 51 were given ALB , and 48 received PLAC . Baseline characteristics and pre-enrollment symptoms , signs , and therapy were similar between groups . There were no group differences in the primary outcome measure , mean LOS (hours)(+/- SD ) : EPI = 59.8 ( 62 ) , ALB = 61.4 ( 54 ) , and PLAC = 63.3 ( 47 ) ; P = .95 by intent-to-treat analysis . Group differences were not statistically significant in any of the secondary outcomes . CONCLUSIONS There were no group differences in the effectiveness of therapy for infants hospitalized with bronchiolitis . Based on these results , we do not recommend routine use of either nebulized EPI or ALB in this patient group Objective To compare the length of hospital stay ( primary ) and improvement in clinical severity scores ( secondary ) among children with bronchiolitis nebulized with 3 % hypertonic saline or 0.9 % saline . Design R and omized double blind controlled trial . Setting Tertiary care teaching hospital . Patients Hospitalized children ( 1–24 months ) with acute bronchiolitis of moderate severity . InterventionNebulization of 4 ml of 3 % hypertonic saline or 4 mL of 0.9 % saline , along with 2.5 mg salbutamol , at 4-hourly intervals till the patient was ready for discharge . Results Baseline characteristics were similar in two groups . Median clinical severity score at admission was 6 ( IQR-1 ) in both the groups . Clinical severity scores monitored afterwards 12-hourly till discharge ( 132 h ) did not show statistically significant differences in 3 % and 0.9 % saline groups . Mean length of hospital stay ( time to reach predefined clinical severity score<3 ) was 63.93 ± 22.43 h in 3 % saline group and 63.51 ± 21.27 h in 0.9 % saline group ( P=0.878 ) . No adverse events were reported by the parents , caregivers or treating medical attendants in both groups . Conclusion Nebulized 3 % saline is not superior to 0.9 % saline in infants with clinical ly diagnosed acute bronchiolitis OBJECTIVE To assess the efficacy and safety of inhaled nebulized hypertonic saline ( HS ) solution in infants with acute bronchiolitis . METHOD Totally 129 patients with acute bronchiolitis ( clinical severity score ≥ 4 , aged 2 - 18 months ) admitted to the Capital Institute of Pediatrics from November 2012 to January 2013 were enrolled . All the subjects were assigned to receive 1.5 ml compound ipratropium bromide solution for inhalation and 1 ml budesonide firstly , twice a day . Then , the subjects were r and omized to receive 2 ml doses of nebulized 5 % HS ( Group A ) , 3 % HS ( Group B ) or 0.9 % NS ( Group C ) , twice a day . The treatment lasted for 3 days . Clinical severity scores before treatment and 24 , 48 , 72 h after treatment were documented . Bronchospasm , nausea and emesis were recorded to assess safety . RESULT A total of 124 patients completed this research .Group A included 40 cases , Group B included 42 cases , Group C included 42 cases . Demographic characteristics , pre-treatment duration and clinical severity score before treatment were similar among the 3 group . Seventy-two hours after treatment , the clinical severity score of Group A , B , and C were 3.5 ( 1.0 ) , 4.0 ( 1.0 ) and 5.0 ( 0 ) . At 24 , 48 , and 72 h after treatment , the clinical severity score were significantly different among the three groups ( χ(2 ) = 36.000 , 51.200 , 50.800 , P < 0.05 ) .One patient in Group A got paroxysmal cough everytime as soon as he received 5 % HS ( 6 times).Other 3 patients in Group A got paroxysmal cough once . The incidence of adverse effect of Group A was 3.75 % ( 9/240 ) ; no adverse event occurred in other group . The incidence of adverse effect among this three group was significantly different ( χ(2 ) = 19.13 , P < 0.01 ) . CONCLUSION Inhalation of nebulized 5 % and 3 % hypertonic saline could decrease clinical symptoms of patient with acute bronchiolitis ; 5 % HS was superior to 3 % HS . But 2 ml dose of 5 % HS may induce paroxysmal cough Bronchiolitis is a common disorder in young children that often results in hospitalisation . Except for a possible effect of nebulised hypertonic saline ( sodium chloride ) , no evidence -based therapy is available . This study investigated the efficacy of nebulised 3 % and 6 % hypertonic saline compared with 0.9 % hypertonic saline in children hospitalised with viral bronchiolitis . In this multicentre , double-blind , r and omised , controlled trial , children hospitalised with acute viral bronchiolitis were r and omised to receive either nebulised 3 % , 6 % hypertonic saline or 0.9 % normal saline during their entire hospital stay . Salbutamol was added to counteract possible bronchial constriction . The primary endpoint was the length of hospital stay . Secondary outcomes were need for supplemental oxygen and tube feeding . From the 292 children included in the study ( median age 3.4 months ) , 247 completed the study . The median length of hospital stay did not differ between the groups : 69 h ( interquartile range 57 ) , 70 h ( IQR 69 ) and 53 h ( IQR 52 ) , for 3 % ( n=84 ) and 6 % ( n=83 ) hypertonic saline and 0.9 % ( n=80 ) normal saline , respectively , ( p=0.29 ) . The need for supplemental oxygen or tube feeding did not differ significantly . Adverse effects were similar in the three groups . Nebulisation with hypertonic saline ( 3 % or 6 % sodium chloride ) although safe , did not reduce the length of stay in hospital , duration of supplemental oxygen or tube feeding in children hospitalised with moderate-to-severe viral bronchiolitis . Hypertonic saline nebulisation did not reduce hospital stay for children with viral bronchiolitis Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged OBJECTIVE To determine the utility of inhaled hypertonic saline solution to treat ambulatory infants with viral bronchiolitis . DESIGN R and omized , double-blind , controlled trial . Sixty-five ambulatory infants ( mean + /- SD age , 12.5 + /- 6 months ) with viral bronchiolitis received either of the following : inhalation of 0.5 mL ( 5 mg ) terbutaline added to 2 mL of 0.9 % saline solution as a wet nebulized aerosol ( control ; group 1 ; n = 32 ) or 0.5 mL ( 5 mg ) terbutaline added to 2 mL of 3 % saline solution administered in the same manner as above ( treatment ; group 2 ; n = 33 ) . This therapy was repeated three times every day for 5 days . RESULTS The clinical severity ( CS ) scores at baseline on the first day of treatment were 6.4 + /- 1.8 in group 1 and 6.6 + /- 1.5 in group 2 ( not significant ) . After the first day , the CS score was significantly lower ( better ) in group 2 as compared to group 1 on each of the treatment days ( p < 0.005 ; Fig 1 ) . On the first day , the percentage decrease in the CS score after inhalation Output:	Cl aims that HS achieves small reductions in LoS must be treated with scepticism .
MS21566	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective To investigate the association between low functional health literacy ( ability to read and underst and basic health related information ) and mortality in older adults . Design Population based longitudinal cohort study based on a stratified r and om sample of households . Setting Engl and . Participants 7857 adults aged 52 or more who participated in the second wave ( 2004 - 5 ) of the English Longitudinal Study of Ageing and survived more than 12 months after interview . Participants completed a brief four item test of functional health literacy , which assessed underst and ing of written instructions for taking an aspirin tablet . Main outcome measure Time to death , based on all cause mortality through October 2009 . Results Health literacy was categorised as high ( maximum score , 67.2 % ) , medium ( one error , 20.3 % ) , or low ( more than one error , 12.5 % ) . During follow-up ( mean 5.3 years ) 621 deaths occurred : 321 ( 6.1 % ) in the high health literacy category , 143 ( 9.0 % ) in the medium category , and 157 ( 16.0 % ) in the low category . After adjusting for personal characteristics , socioeconomic position , baseline health , and health behaviours , the hazard ratio for all cause mortality for participants with low health literacy was 1.40 ( 95 % confidence interval 1.15 to 1.72 ) and with medium health literacy was 1.15 ( 0.94 to 1.41 ) compared with participants with high health literacy . Further adjustment for cognitive ability reduced the hazard ratio for low health literacy to 1.26 ( 1.02 to 1.55 ) . Conclusions A third of older adults in Engl and have difficulties reading and underst and ing basic health related written information . Poorer underst and ing is associated with higher mortality . The limited health literacy capabilities within this population have implication s for the design and delivery of health related services for older adults in Engl and OBJECTIVES This study analyzed whether inadequate functional health literacy is an independent risk factor for hospital admission . METHODS We studied a prospect i ve cohort of 3260 Medicare managed care enrollees . RESULTS Of the participants , 29.5 % were hospitalized . The crude relative risk ( RR ) of hospitalization was higher for individuals with inadequate literacy ( n = 800 ; RR = 1.43 ; 95 % confidence interval [ CI ] = 1.24 , 1.65 ) and marginal literacy ( n = 366 ; RR = 1.33 ; 95 % CI = 1.09 , 1.61 ) than for those with adequate literacy ( n = 2094 ) . In multivariate analysis , the adjusted relative risk of hospital admission was 1.29 ( 95 % CI = 1.07 , 1.55 ) for individuals with inadequate literacy and 1.21 ( 95 % CI = 0.97 , 1.50 ) for those with marginal literacy . CONCLUSIONS Inadequate literacy was an independent risk factor for hospital admission among elderly managed care enrollees Summary Background Patient education is essential for a safe and efficient oral anticoagulant treatment . We examined if a newly launched booklet with information on anticoagulant treatment with warfarin improved patient knowledge and the time spent in the therapeutic-range ( TTR ) . Methods St and ardized question naire was administered to 235 consecutive patients on warfarin to assess their baseline knowledge and readministered it 2 months after they received the booklet . A control group of 51 patients was interviewed only after the booklet had been distributed . Results Patient ’s knowledge at the baseline was unsatisfying ( mean question naire score : 11/16 ) and a substantial progress was achieved after the educational intervention ( mean question naire score : 13/16 , p = 0.001 ) . TTR is significantly increased after the intervention ( 63.4 ± 22.3 vs. 74.6 ± 23.8 % ; p < 0.01 ) . The mean question naire score and TTR after education were not different in the intervention and the control group . Conclusions Knowledge about oral anticoagulant treatment and TTR is increased after the issue of the booklet in the majority of patients . However , for a small group of patients with unimproved knowledge new forms of education are needed Background Effective and safe management of oral anticoagulant treatment ( OAT ) requires a high level of patient knowledge and adherence . The aim of this study was to assess patient knowledge about OAT and factors associated with patient knowledge . Methods This is a baseline survey of a cluster-r and omized controlled trial in 22 general practice s with an educational intervention for patients or their caregivers . We assessed knowledge about general information on OAT and key facts regarding nutrition , drug-interactions and other safety pre caution s of 345 patients at baseline . Results Participants rated their knowledge about OAT as excellent to good ( 56 % ) , moderate ( 36 % ) or poor ( 8 % ) . However , there was a discrepancy between self-rated knowledge and evaluated actual knowledge and we observed serious knowledge gaps . Half of the participants ( 49 % ) were unaware of dietary recommendations . The majority ( 80 % ) did not know which non-prescription analgesic is the safest and 73 % indicated they would not inform pharmacists about OAT . Many participants ( 35 - 75 % ) would not recognize important emergency situations . After adjustment in a multivariate analysis , older age and less than 10 years education remained significantly associated with lower overall score , but not with self-rated knowledge . Conclusions Patients have relevant knowledge gaps , potentially affecting safe and effective OAT . There is a need to assess patient knowledge and for structured education programs . Trial registration Deutsches Register Klinischer Studien ( German Clinical Trials Register ) : DRKS00000586.Universal Trial Number ( UTN U1111 - 1118 - 3464 ) BACKGROUND While limited literacy is common and its prevalence increases with age , no prospect i ve study has assessed whether limited literacy is associated with mortality in older adults . OBJECTIVE To assess the association of limited literacy with mortality . DESIGN AND SETTING Five-year prospect i ve study from 1999 to 2004 of community-dwelling elders from Memphis , TN , and Pittsburgh , PA , who were from the Health , Aging , and Body Composition study . Subjects ' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine . Scores were categorized into limited ( 0 to 8th grade reading level ) or adequate literacy ( > or = 9th grade reading level ) . PARTICIPANTS Two thous and five hundred and twelve black and white elders without baseline functional difficulties or dementia . MEASUREMENTS Time to death . RESULTS Participants ' mean age was 75.6 years , 48 % were male , 38 % were black , and 24 % had limited literacy ; the median follow-up time was 4.2 years . Compared with those with adequate literacy , those with limited literacy had a higher risk of death ( 19.7 % vs 10.6 % ) with a hazard ratio ( HR ) of 2.03 ( 95 % confidence intervals [ CI ] , 1.62 to 2.55 ) . After adjusting for demographics and socioeconomic status , co-morbid conditions , self-rated health status , health-related behaviors , health care access measures , and psychosocial status , limited literacy remained independently associated with mortality ( HR 1.75 ; 95 % CI , 1.27 to 2.41 ) . CONCLUSIONS Limited literacy is independently associated with a nearly 2-fold increase in mortality in the elderly . Given the growth of the aging population and the prevalence of chronic diseases , the mechanisms by which limited literacy is associated with mortality in the elderly warrant further investigation BACKGROUND Individuals with low levels of health literacy have less health knowledge , worse self-management of chronic disease , lower use of preventive services , and worse health in cross-sectional studies . We sought to determine whether low health literacy levels independently predict overall and cause-specific mortality . METHODS We design ed a prospect i ve cohort study of 3260 Medicare managed-care enrollees in 4 US metropolitan areas who were interviewed in 1997 to determine their demographic characteristics , chronic conditions , self-reported physical and mental health , and health behaviors . Participants also completed the shortened version of the Test of Functional Health Literacy in Adults . Main outcome measures included all-cause and cause-specific ( cardiovascular , cancer , and other ) mortality using data from the National Death Index through 2003 . RESULTS The crude mortality rates for participants with adequate ( n = 2094 ) , marginal ( n = 366 ) , and inadequate ( n = 800 ) health literacy were 18.9 % , 28.7 % , and 39.4 % , respectively ( P < .001 ) . After adjusting for demographics , socioeconomic status , and baseline health , the hazard ratios for all-cause mortality were 1.52 ( 95 % confidence interval , 1.26 - 1.83 ) and 1.13 ( 95 % confidence interval , 0.90 - 1.41 ) for participants with inadequate and marginal health literacy , respectively , compared with participants with adequate health literacy . In contrast , years of school completed was only weakly associated with mortality in bivariate analyses and was not significant in multivariate models . Participants with inadequate health literacy had higher risk-adjusted rates of cardiovascular death but not of death due to cancer . CONCLUSIONS Inadequate health literacy , as measured by reading fluency , independently predicts all-cause mortality and cardiovascular death among community-dwelling elderly persons . Reading fluency is a more powerful variable than education for examining the association between socioeconomic status and health Background : The ability to use printed material to function in society ( literacy ) and to h and le basic numerical concepts ( numeracy ) may have implication s in patients ’ ability to follow dosing schedules . We examined literacy and numeracy skills among patients on warfarin and explored their association with anticoagulation control . Methods and Results : Patients older than 50 years attending two anticoagulation management units were prospect ively enrolled . We measured literacy , numeracy , and international normalized ratio ( INR ) . During a 3-month follow-up period , we calculated the variability of the INR and the amount of time a patient ’s INR was within his or her therapeutic range , variables associated with bleeding and effectiveness . Among 143 patients , only 75 ( 52.4 % ) were able to read health-related words at the eighth grade level or less . Patients ’ self-reported grade completed was higher than the measured literacy grade level ( & kgr ; = 0.21 ) . While 79.0 % had completed at least eight grade s , only 47.6 % had a score at that grade level . Sixty-nine patients answered none or correctly answered fewer than two of the six numeracy questions ( 48.3 % ) . The INR variability was higher among patients with lower literacy ( P = 0.009 ) and lower numeracy skills ( P = 0.004 ) . The time in range was similar among patients at different literacy levels ( P = 0.9 ) . Patients with lower numeracy level spent more time above their therapeutic range ( P = 0.04 ) and had a trend of less time spent in range ( P = 0.10 ) . Conclusions : Low literacy was prevalent among study patients taking warfarin . Low literacy and numeracy were associated with measures of poor anticoagulation control OBJECTIVES With the aim to facilitate a more comprehensive review process in public health including patient safety , we established a tool that we have termed ICROMS ( Integrated quality Criteria for the Review Of Multiple Study design s ) , which unifies , integrates and refines current quality criteria for a large range of study design s including qualitative research . STUDY DESIGN Review , pilot testing and expert consensus . METHODS The tool is the result of an iterative four phase process over two years : 1 ) gathering of established criteria for assessing controlled , non-controlled and qualitative study design s ; 2 ) pilot testing of a first version in two systematic review s on behavioural change in infection prevention and control and in antibiotic prescribing ; 3 ) further refinement and adding of additional study design s in the context of the European Centre for Disease Prevention and Control funded project ' Systematic review and evidence -based guidance on organisation of hospital infection control programmes ' ( SIGHT ) ; 4 ) scrutiny by the pan-European expert panel of the SIGHT project , which had the objective of ensuring robustness of the systematic review . RESULTS ICROMS includes established quality criteria for r and omised studies , controlled before- and -after studies and interrupted time series , and incorporates criteria for non-controlled before- and -after studies , cohort studies and qualitative studies . The tool consists of two parts : 1 ) a list of quality criteria specific for each study design , as well as criteria applicable across all study design s by using a scoring system ; 2 ) a ' decision matrix ' , which specifies the robustness of the study by identifying minimum requirements according to the study type and the relevance of the study to the review question . The decision matrix directly determines inclusion or exclusion of a study in the review . ICROMS was applied to a series of systematic review s to test its feasibility and usefulness in the appraisal of multiple study design s. The tool was applicable across a wide range of study design s and outcome measures . CONCLUSION ICROMS is a comprehensive yet feasible appraisal of a large range of study design s to be included in systematic review s Output:	Our results suggest that in patients taking OAC treatments there is a positive relationship between HL and the level of knowledge . Lower HL level was associated with greater knowledge deficits and less adherence to treatment . Conclusion There is a paucity of research evaluating the effect of HL on diverse aspects of OAC treatments .
MS21567	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Erlotinib combined with gemcitabine has not been evaluated in Japanese patients with unresectable pancreatic cancer . This two‐step phase II study assessed the safety and pharmacokinetics of erlotinib 100 mg/day ( oral ) plus gemcitabine 1000 mg/m2 ( i.v . days 1 , 8 , 15 ) in a 28‐day cycle in the first step , and efficacy and safety in the second step . The primary end‐point was safety . One hundred and seven patients were enrolled ( first step , n = 6 ; second step , n = 101 ) . The most common adverse event was RASH ( compiled using the preferred terms rash , acne , exfoliative rash , dermatitis acneiform , erythema , eczema , dermatitis and pustular rash ) in 93.4 % of patients . One treatment‐related death occurred . While interstitial lung disease‐like events were reported in nine patients ( 8.5 % ; grade 1/2/3 , 3.8/2.8/1.9 % ) , all patients recovered or improved . The median overall survival , the 1‐year survival rate and median progression‐free survival were 9.23 months , 33.0 % and 3.48 months , respectively . The overall response and disease control rates were 20.3 % and 50.0 % , respectively . In Japanese patients with unresectable pancreatic cancer , erlotinib plus gemcitabine had acceptable toxicity and efficacy that was not inferior to that seen in Western patients . ( Cancer Sci 2011 ; 102 : 425–431 Objectives This retrospective study examined pancreatic cancer patients who received combination gemcitabine and erlotinib to determine if the association between rash and outcomes observed in clinical trials would be observed in ‘ real-world ’ community oncology setting s. Methods Medical records from 10 community oncology practice s were used to identify eligible patients . Rash severity was classified as High ( moderate/severe ) versus Low ( absent/mild ) based on medical record review . Kaplan-Meier analysis assessed progression-free survival ( PFS ) and overall survival ( OS ) by rash status from a l and mark of 42 days after treatment initiation . Cox regression with time-varying covariates tested whether high-severity rash predicted longer OS and PFS . Results The High Severity group ( n = 34 ) had longer median OS from the l and mark than the Low Severity group ( n = 134 ; 7.58 months vs 5.03 months , P = 0.0339 ) . Cox regression analysis ( n = 174 ) confirmed a reduced risk of death with High Rash Severity ( hazard ratio [ HR ] = 0.67 , P = 0.0389 ) . Progression-free survival results showed a similar pattern ( median PFS 2.37 months from l and mark vs 2.04 months for High vs Low Severity groups , P = 0.0485 ) . Conclusions Results from this community sample were consistent with findings from r and omized clinical trials , showing that longer OS is predicted by high-severity rash in erlotinib-treated pancreatic cancer patients BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group , as compared with 3.7 months in the gemcitabine group ( hazard ratio for disease progression or death , 0.69 ; 95 % CI , 0.58 to 0.82 ; P<0.001 ) ; the response rate according to independent review was 23 % versus 7 % in the two groups ( P<0.001 ) . The most common adverse events of grade 3 or higher were neutropenia ( 38 % in the nab-paclitaxel-gemcitabine group vs. 27 % in the gemcitabine group ) , fatigue ( 17 % vs. 7 % ) , and neuropathy ( 17 % vs. 1 % ) . Febrile neutropenia occurred in 3 % versus 1 % of the patients in the two groups . In the nab-paclitaxel-gemcitabine group , neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days . CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma , nab-paclitaxel plus gemcitabine significantly improved overall survival , progression-free survival , and response rate , but rates of peripheral neuropathy and myelosuppression were increased . ( Funded by Celgene ; Clinical Trials.gov number , NCT00844649 . ) Purpose To evaluate the feasibility , toxicity and efficacy of the combination regimen consisting of gemcitabine-FDR infusion plus erlotinib , in ACP patients . Methods Forty-two patients with histologically confirmed , locally advanced or metastatic pancreatic cancer were included in this phase II trial . Main objectives were to assess the efficacy and safety of this regimen . Therapeutic regimen consisted of gemcitabine 1,200 mg/m2 in 120-min infusion on days 1 , 8 and 15 , plus erlotinib 100 mg orally once daily . Cycles were repeated every 28 days . Results A total of 160 courses of gemcitabine-FDR erlotinib were administered ( median 3.8 courses per patient ) . The most common grade 3–4 AEs were neutropenia ( 21 % ) , thrombocytopenia ( 10 % ) , skin rash ( 10 % ) and asthenia ( 10 % ) . Complete response was achieved in one patient ( 2 % ) and 11 ( 26 % ) achieved a partial response . Stable disease and progression disease were observed in 11 patients ( 26 % ) and 19 ( 45 % ) , respectively . Median time to progression was 5 months ( 95%CI : 3.9–5.8 months ) and median overall survival was 8 months ( 95 % CI : 5.1–10.8 ) . One-year survival rate was 35 % . Conclusions A regimen consisting of gemcitabine-FDR infusion plus erlotinib is active and well tolerated in APC patients . However , the results do not justify the conduct of a Phase III trial Objective To analyze the efficacy of gemcitabine with or without erlotinib for pancreatic cancer , and to determine the predictive role of epidermal growth factor receptor ( EGFR ) and KRAS mutations in these patients . Methods This was a single-center , r and omized , open-label , prospect i ve trial . Eighty-eight chemotherapy-naïve metastatic pancreatic cancer patients were r and omized for treatment with gemcitabine or gemcitabine plus erlotinib . EGFR and KRAS mutations were analyzed , respectively . The primary endpoint was the disease control rate . Results Disease control rate ( 64 % vs. 25 % ; P < 0.001 ) , progression-free survival ( median 3.8 vs. 2.4 months ; P < 0.001 ) , and overall survival ( median 7.2 vs. 4.4 months ; P < 0.001 ) were better in the gemcitabine plus erlotinib group than in the gemcitabine alone group . In the gemcitabine plus erlotinib group , disease control ( 85 % vs. 33 % ; P = 0.001 ) , progression-free survival ( median 5.9 vs. 2.4 months ; P = 0.004 ) , and overall survival ( median 8.7 vs. 6.0 months ; P = 0.044 ) were better in patients with EGFR mutations than in those without EGFR mutations . KRAS mutation was not associated with treatment response or survival . Conclusions Gemcitabine plus erlotinib is more effective than gemcitabine alone for treating metastatic pancreatic cancer patients , especially those with EGFR mutations . Clinical Trials.gov number , NCT01608841 We report on the results of a prospect i ve treatment of 30 proven metastatic pancreatic cancer patients with the recently described combination of gemcitabine and erlotinib ( GEM+E ) ( 24 × 1st line therapy , 8 × 2nd line therapy ) . Eight of these patients received GEM+E for treatment of metastastic tumour recurrence after previous resective surgery , followed by adjuvant chemotherapy with gemcitabine . In 2 patients GEM+E was given as 1st line treatment and later , after complete response which was followed by a new recurrence , also as a second line therapy . The evaluation of RASH severity grade s , the course of the serum tumour marker CA19 - 9 were determined every 14 days and the evaluation of the imaging methods CT or MRT , evaluated every 6 - 8 weeks , revealed the following results : there was a tendency for RASH grade s to correlate with the tumour response , however , with observed exceptions . The decision for interruption or maintenance of GEM+E , therefore , should not be based on the RASH phenomenon , but on a detailed follow-up with imaging methods and Output:	Conclusion Skin rash was associated with better OS and PFS in APC patients treated with gemcitabine plus erlotinib .
MS21568	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Visual inspection with Acetic Acid ( VIA ) and Visual Inspection with Lugol ’s Iodine ( VILI ) are increasingly recommended in various cervical cancer screening protocol s in low-re source setting s. Although VIA is more widely used , VILI has been advocated as an easier and more specific screening test . VILI has not been well-vali date d as a st and -alone screening test , compared to VIA or vali date d for use in HIV-infected women . We carried out a r and omized clinical trial to compare the diagnostic accuracy of VIA and VILI among HIV-infected women . Women attending the Family AIDS Care and Education Services ( FACES ) clinic in western Kenya were enrolled and r and omized to undergo either VIA or VILI with colposcopy . Lesions suspicious for cervical intraepithelial neoplasia 2 or greater ( CIN2 + ) were biopsied . Between October 2011 and June 2012 , 654 were r and omized to undergo VIA or VILI . The test positivity rates were 26.2 % for VIA and 30.6 % for VILI ( p = 0.22 ) . The rate of detection of CIN2 + was 7.7 % in the VIA arm and 11.5 % in the VILI arm ( p = 0.10 ) . There was no significant difference in the diagnostic performance of VIA and VILI for the detection of CIN2 + . Sensitivity and specificity were 84.0 % and 78.6 % , respectively , for VIA and 84.2 % and 76.4 % for VILI . The positive and negative predictive values were 24.7 % and 98.3 % for VIA , and 31.7 % and 97.4 % for VILI . Among women with CD4 + count < 350 , VILI had a significantly decreased specificity ( 66.2 % ) compared to VIA in the same group ( 83.9 % , p = 0.02 ) and compared to VILI performed among women with CD4 + count ≥ 350 ( 79.7 % , p = 0.02 ) . VIA and VILI had similar diagnostic accuracy and rates of CIN2 + detection among HIV-infected women . Trial Registration Clinical Trials.gov Background Over 85 % of cervical cancer cases and deaths occur in developing countries . HIV-seropositive women are more likely to develop precancerous lesions that lead to cervical cancer than HIV-negative women . However , the literature on cervical cancer prevention in seropositive women in developing countries has not been review ed . The aim of this study is to systematic ally review cervical cancer prevention modalities available for HIV-seropositive women in developing countries . Methods / design This protocol was developed by following the Preferred Reporting Items for Systematic Review s and Meta-Analyses Protocol s ( PRISMA -P ) statement , and the systematic review will be reported in accordance with the PRISMA guidelines . Embase , MEDLINE , PubMed , CINAHL and Cochrane Library will be search ed from inception up to date of final search , and additional studies will be located through citation and reference list tracking . Eligible studies will be r and omised controlled trials , prospect i ve and retrospective cohort studies , case-control and cross-sectional studies carried out in developing countries . Studies will be included if they are published in English and examine cervical cancer prevention modalities in HIV-seropositive women . Results will be summarised in tables and , where appropriate , combined using meta- analysis . Discussion This review will address the gap in evidence by systematic ally review ing the published literature on the different prevention modalities being used to prevent cervical cancer in HIV-seropositive women in developing countries . The findings may be used to inform evidence -based guidelines for prevention of cervical cancer in seropositive women as well as future research . Systematic review registration PROSPERO CRD42017054678 OBJECTIVE To determine the factors influencing cervical cancer diagnosis and treatment in countries of East , Central and Southern Africa ( ECSA ) . METHODS Data were collected from r and omly selected primary health care centres , district and provincial hospitals , and tertiary hospitals in each participating country . Health care workers were interviewed , using a question naire ; the facilities for screening , diagnosing , and treating cervical cancer in each institution were recorded , using a previously design ed checklist . FINDINGS Although 95 % of institutions at all health care levels in ECSA countries had the basic infrastructure to carry out cervical cytology screening , only a small percentage of women were actually screened . Lack of policy guidelines , infrequent supply of basic material s , and a lack of suitable qualified staff were the most common reasons reported . CONCLUSIONS This study demonstrates that there is an urgent need for more investment in the diagnosis and treatment of cervical cancer in ECSA countries . In these , and other countries with low re sources , suitable screening programmes should be established BACKGROUND The objective of this study was to determine whether the 3-dose quadrivalent human papillomavirus ( HPV ) vaccine series ( HPV-6 , -11 , -16 , -18 ) is immunogenic and safe in young women infected with human immunodeficiency virus ( HIV ) . METHODS We enrolled 99 women aged 16 - 23 years in a phase 2 , open-label , multicenter trial , conducted from 2008 to 2011 by the Adolescent Medicine Trials Network for HIV/AIDS Interventions . Outcome measures were immunogenicity 4 weeks after dose 3 , measured by ( 1 ) geometric mean titers ( GMTs ) and ( 2 ) seroconversion rates for HPV-6 , -11 , -16 , and -18 , among those seronegative and HPV DNA negative for each type . Immune responses were compared to those of a historical comparison group of HIV-negative women ( n = 267 ) using univariate methods . Clinical and laboratory adverse events were assessed after each dose . RESULTS The mean age of subjects was 21.4 years ; 80 % were non-Hispanic black , 69 were not taking antiretroviral therapy ( ART ) , and 30 were taking ART . No differences in GMTs were noted among participants taking ART vs the comparison group , but GMTs were lower in participants not taking ART vs the comparison group for HPV-16 ( 2393 vs 3892 milli-Merck units per milliliter [ mMU/mL ] , P = .012 ) and HPV-18 ( 463 vs 801 mMU/mL , P = .003 ) . Seroconversion rates were 100 % for HPV-6 , -11 , -16 , and -18 among participants taking ART . Rates ranged from 92.3 % ( for HPV-18 ) to 100.0 % ( for HPV-6 ) among participants not taking ART . One severe adverse event ( fatigue ) was noted . CONCLUSIONS In a sample of HIV-infected women who were HPV DNA and HPV seronegative , immune responses to HPV vaccination were generally robust and the vaccine was well tolerated BACKGROUND Women infected with human immunodeficiency virus ( HIV ) are disproportionately affected by human papillomavirus (HPV)-related anogenital disease , particularly with increased immunosuppression . AIDS Clinical Trials Group protocol A5240 was a trial of 319 HIV-infected women in the United States , Brazil , and South Africa to determine immunogenicity and safety of the quadrivalent HPV vaccine in 3 strata based on screening CD4 count : > 350 ( stratum A ) , 201 - 350 ( stratum B ) , and ≤200 cells/µL ( stratum C ) . METHODS Safety and serostatus of HPV types 6 , 11 , 16 , and 18 were examined . HPV serological testing was performed using competitive Luminex immunoassay ( HPV-4 cLIA ) . HPV type-specific seroconversion analysis was done for participants who were seronegative for the given type at baseline . RESULTS Median age of patients was 36 years ; 11 % were white , 56 % black , and 31 % Hispanic . Median CD4 count was 310 cells/µL , and 40 % had undetectable HIV-1 load . No safety issues were identified . Seroconversion proportions among women at week 28 for HPV types 6 , 11,16 , and 18 were 96 % , 98 % , 99 % , and 91 % , respectively , for stratum A ; 100 % , 98 % , 98 % , and 85 % , respectively , for stratum B , and 84 % , 92 % , 93 % , and 75 % , respectively , for stratum C. CONCLUSIONS The quadrivalent HPV vaccine targeted at types 6 , 11 , 16 , and 18 was safe and immunogenic in HIV-infected women aged 13 - 45 years . Women with HIV RNA load > 10 000 copies/mL and /or CD4 count < 200 cells/µL had lower rates of seroconversion rates . Clinical Trials Registration . NCT00604175 Human papillomavirus ( HPV ) infection is highly prevalent and can lead to cancer ; the development of safe and efficacious vaccines for HPV is a major public health concern . The two licensed HPV vaccines contain recombinant virus-like particles of HPV 16 and 18 ; one of such vaccines also protects against HPV types 6 and 11 which cause genital warts . We determined safety and immunogenicity of quadrivalent HPV vaccine in HIV-infected and HIV-negative adolescents and young adults , aged 13 - 27 years . The seroconversion rate , assessed by antibody titers , 1 month after the administration of the third vaccine dose was 0.85 ( 95 % CI 0.75 - 0.95 ) in the HIV-infected group and 0.91 ( 0.83 - 0.99 ) in the HIV-negative subjects ( p=0.52 ) . The vaccine was generally safe and well tolerated ; the most common side effect was local pain and the most frequent systemic side effect was headache . This is the first report on response to HPV vaccination in both female and male HIV-infected adolescents and young adults and highlights that this population may benefit from HPV immunoprophylaxis . Further studies are needed to examine the long term efficacy of this vaccine in HIV-infected individuals Individuals infected with human immunodeficiency virus ( HIV ) have excess risk of developing human papillomavirus (HPV)-related disease . A substantial fraction of HPV-associated cancers is caused by HPV serotypes not included in the currently available vaccines . Among healthy women , both Cervarix ® ( HPV-16/18 , GlaxoSmithKline Biologicals , GSK ) and Gardasil ® ( HPV-6/11/16/18 , Merck ) have demonstrated partial cross-protection against certain oncogenic non-vaccine HPV-types . Currently , there are no available data on vaccine-induced cross-protection in men and little is known about cross-reactive immunity after HPV-vaccination of HIV-infected individuals . In an investigator-initiated trial , we r and omized 91 HIV-positive men and women to receive vaccination with Cervarix ® or Gardasil ® . The HPV-DNA status of the participants was determined with pcr before and after immunization . Cross-reactive antibody responses against HPV-31 , HPV-33 , and HPV-45 were evaluated for up to 12 months using a pseudovirion-based neutralization assay ( PBNA ) . Geometric mean antibody titers ( GMTs ) were compared among vaccine groups and genders at 7 and 12 months . Both vaccines induced anti-HPV-31 , -33 , and -45 neutralizing antibodies in participants who were seronegative and HPV-DNA negative for those types at study entry . Geometric mean antibody titers were comparable between vaccine groups . Interestingly , anti-HPV-31 and -33 antibody titers were higher among women compared with men at 7 and 12 months . In conclusion , both licensed HPV-vaccines induced cross-neutralizing antibodies against frequent oncogenic non-vaccine serotypes HPV-31 , HPV-33 , and HPV-45 in HIV-infected adults , and women had greater serological responses against HPV-31 and -33 compared with men BACKGROUND It is estimated that 1%-2 % of women develop cervical intraepithelial neoplasia grade 2 - 3 ( CIN 2 - 3 ) annually worldwide . The prevalence among women living with HIV is higher , at 10 % . If left untreated , CIN 2 - 3 can progress to cervical cancer . WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2 - 3 . METHODS Guidelines were developed using the WHO H and book for Guideline Development and the GRADE ( Grading of Recommendations , Assessment , Development and Evaluation ) approach . A multidisciplinary guideline panel was created . Systematic review Output:	The screening methods used for HIV-seropositive women are the same for HIV-negative women , with varying clinical performance and accuracy . HPV testing has a better accuracy/efficiency than other methods with a sensitivity of 80.0–97.0 % and specificity of 51.0–78.0 % . Sequential screening using VIA or visual inspection with Lugol ’s iodine ( VILI ) and HPV testing has shown better clinical performance in screening HIV-seropositive women .
MS21569	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: 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 This study attempts : ( 1 ) to verify that serum antimuscarinic activity is related to clozapine dose , and more importantly to clozapine plasma concentrations ; ( 2 ) to explore whether norclozapine has serum antimuscarinic activity ; ( 3 ) to explore whether antimuscarinic activity is related to clozapine side effects ; and ( 4 ) to compare the serum antimuscarinic activities of clozapine with those of antiparkinsonian drugs and other antipsychotics . In 39 patients participating in a double-blind clozapine study , the [3H]QNB assay was used to measure serum antimuscarinic activity : ( 1 ) on baseline medications ; ( 2 ) after a 4-week haloperidol trial ; ( 3 ) after a 16-week clozapine trial of either 100 , 300 , or 600 mg/d ; and ( 4 ) after 1 or 2 consecutive 16-week clozapine trials with remaining doses in nonresponders . Clozapine levels predicted serum antimuscarinic activity better than clozapine dose . At the end of the 1st clozapine trial , the correlation with the levels explained 69 % of the variance of serum antimuscarinic activity ( r = 0.83 , P < 0.001 , N = 34 ) . Clozapine levels were good predictors of serum antimuscarinic activity only in patients taking 300 or 600 mg/d . After correcting for clozapine levels , the within-subject correlation between norclozapine levels and serum antimuscarinic activity was relatively high and significant ( r = 0.54 , F = 26.7 , df = 1.65 , P < 0.001 ) . Constipation was significantly associated with higher serum antimuscarinic activity during the 1st clozapine trial . Clozapine was associated with clearly higher antimuscarinic activity than other antipsychotics or low doses of antiparkinsonians . In vitro studies and new clinical studies are needed to verify whether norclozapine may significantly contribute to antimuscarinic activity during clozapine treatment McEvoy et al. 's study in 1999 , which used cotinine levels but had limited power , suggested that clozapine treatment may be associated with a mild smoking decrease ( particularly when plasma clozapine levels are > 150 ng/ml ) . Some naturalistic studies also suggest that clozapine treatment may be associated with a mild smoking decrease . The present study included 38 schizophrenic daily smokers from a double-blind clozapine trial . Five analyses were tested for significant decreases in plasma cotinine levels from a haloperidol baseline to : ( 1 ) the end of clozapine trials regarding clozapine doses ( 100 , 300 or 600 mg/day ) , ( 2 ) the end of the clozapine trial where the highest plasma clozapine level was achieved , ( 3 ) the end of the clozapine trial where a clozapine level in the 150 - 450 ng/ml range was achieved , ( 4 ) the end of the first clozapine trial regardless of clozapine dose , and ( 5 ) the end of the last clozapine trial in the study . The first and straightforward analysis by dose showed no clozapine effects on smoking . The second and the third analyses ( an attempt to mimic the design by McEvoy et al. [ McEvoy , J.P. , Freudenreich , O. , Wilson , W.H. , 1999 . Smoking and therapeutic response to clozapine in patients with schizophrenia . Biol . Psychiat . 46 , 125 - 129 . ] ) also indicated that there was not a significant effect of clozapine on smoking . The fourth and five analyses were also negative . None of the five analyses in our clozapine trial demonstrated that clozapine had major effects on smoking . This study can not rule out that in some subjects , clozapine treatment may be associated with a small decrease in smoking . New prospect i ve longitudinal studies using repeated cotinine and clozapine levels are needed to explore whether clozapine may reduce smoking in some patients The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas BACKGROUND Clozapine is currently restricted to patients who have failed at least two trials of other antipsychotic medications because of concerns that its use as a first-line agent would lead to greater mortality , mainly through agranulocytosis . AIMS OF THE STUDY We sought to determine the cost-effectiveness of allowing clozapine to be a first-line treatment versus the current policy of restricting clozapine to third-line status . METHODS We performed a cost-effectiveness analysis using published data from r and omized controlled trials and epidemiologic studies . The target population was patients with schizophrenia in an acute psychotic episode , with a lifetime time horizon and societal perspective . Outcome measures included life expectancy , quality -adjusted life expectancy , costs , and cost-effectiveness ratios . RESULTS Using clozapine as a first agent would lead to modest gains in life-expectancy as well as quality -adjusted life expectancy , relative to restricting its use to patients who failed 2 conventional antipsychotics . The cost-effectiveness ratio of using clozapine first vs. using clozapine third would be $ 24,100 per quality -adjusted life year ( QALY ) . In 1-way and probabilistic sensitivity analyses , these findings were robust to a variety of assumptions . DISCUSSION Allowing clozapine to be a first-line agent may lead to small gains in life expectancy at moderate but acceptable costs . IMPLICATION S While these results do not shed light on whether clozapine should be the preferred first-line strategy , they do suggest that clozapine should be added to the armamentarium of possible treatments for treatment-sensitive as well as treatment-resistant schizophrenia Preliminary results of a double-blind clozapine study in a population of chronic psychotic patients at a state psychiatric facility are reported . Thirty " treatment-refractory " schizophrenic patients given a diagnosis according to DSM-III-R criteria ( mean age of 44 + /- 9.1 years and a duration of illness of 24.9 + /- 8.8 years ) who received 300 mg or 600 mg of clozapine and r and omized in a double-blind fashion were analyzed . Subjects were evaluated using the Brief Psychiatric Rating Scale ( BPRS ) and the Clinical Global Impression ( CGI ) Scale on a weekly basis for 16 weeks . Based on the changes in their CGI scores at week 16 of clozapine treatment , subjects were retrospectively categorized as " improvers " ( N = 12 ) and " nonimprovers " ( N = 18 ) . The two groups were compared for changes in total BPRS and BPRS factor scores . In terms of total BPRS scores , we expected a difference between the two groups because they were categorized based on changes in their CGI scores . However , the total BPRS scores in improvers showed a significant decrease by week 6 of clozapine treatment . On analyzing the four BPRS factors , the improvers showed improvement in the thinking disturbance factor by week 1 that remained steady from week 7 . On the hostility-suspiciousness factor , the improvers showed an improvement across time when compared with nonimprovers . The withdrawal-retardation factor showed improvement in both groups across time , whereas the anxiety-depression factor was least influenced by clozapine . These observations suggested that all BPRS symptom factors did not uniformly contribute to improvement in overall psychopathology , which was observed as a decrease in total BPRS scores The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge . Clozapine , an atypical antipsychotic drug , has long been of scientific interest , but its clinical development has been delayed because of an associated risk of agranulocytosis . This report describes a multicenter clinical trial to assess clozapine 's efficacy in the treatment of patients who are refractory to neuroleptics . DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospect i ve , single-blind trial of haloperidol ( mean dosage , 61 + /- 14 mg/d ) for six weeks . Patients whose condition remained unimproved were then r and omly assigned , in a double-blind manner , to clozapine ( up to 900 mg/d ) or chlorpromazine ( up to 1800 mg/d ) for six weeks . Two hundred sixty-eight patients were entered in the double-blind comparison . When a priori criteria were used , 30 % of the clozapine-treated patients were categorized as responders compared with 4 % of chlorpromazine-treated patients . Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale , Clinical Global Impression Scale , and Nurses ' Observation Scale for Inpatient Evaluation ; this improvement included " negative " as well as positive symptom areas . Although no cases of agranulocytosis occurred during this relatively brief study , in our view , the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients Steady-state blood clozapine concentrations in 58 schizophrenic patients varied more than 45-fold ( 40 - 1911 ng/mL ) after fixed-dose treatment ( 400 mg/day ) . Discriminant function analysis determined that a blood clozapine concentration of 420 ng/mL optimally distinguished responders from nonresponders . After 4 weeks of treatment , only 8 % of those patients with a blood clozapine concentration < 420 ng/mL responded compared with 60 % of those who had a blood clozapine concentration > 420 ng/mL. When plasma concentrations were increased above 420 ng/mL ( by a double-blind r and om assignment procedure ) , nonresponders increased their response rate to 73 % if their plasma concentrations at Week 12 exceeded 420 ng/mL compared with a response rate of 29 % if their Week 12 levels remained below 420 ng/mL ( chi 2 = 4.2 , p < .04 ) OBJECTIVE This study sought to determine the relationships between serum clozapine levels and therapeutic response . METHOD Fifty-six in patients who met the DSM-III-R criteria for chronic schizophrenia and who had not responded to extended treatment with classical antipsychotics were r and omly assigned to 12 weeks of double-blind treatment with clozapine at one of three serum level ranges : low ( 50 - 150 Output:	We found no evidence of effect on mental state between st and ard , low and very low dose regimes , but we did not identify any trials on high or very high doses of clozapine . There was limited evidence that the incidence of some adverse effects was greater at st and ard dose compared to lower dose regimes .
MS21570	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVE Neuroimaging studies have demonstrated dysfunction in the brain reward circuit in individuals with online gaming addiction ( OGA ) . We hypothesized that virtual reality therapy ( VRT ) for OGA would improve the functional connectivity ( FC ) of the cortico-striatal-limbic circuit by stimulating the limbic system . METHODS Twenty-four adults with OGA were r and omly assigned to a cognitive behavior therapy ( CBT ) group or VRT group . Before and after the four-week treatment period , the severity of OGA was evaluated with Young 's Internet Addiction Scale ( YIAS ) . Using functional magnetic resonance imaging , the amplitude of low-frequency fluctuation ( ALFF ) and FC from the posterior cingulate cortex ( PCC ) seed to other brain areas were evaluated . Twelve casual game users were also recruited and underwent only baseline assessment . RESULTS After treatment , both CBT and VRT groups showed reductions in YIAS scores . At baseline , the OGA group showed a smaller ALFF within the right middle frontal gyrus and reduced FC in the cortico-striatal-limbic circuit . In the VRT group , connectivity from the PCC seed to the left middle frontal and bilateral temporal lobe increased after VRT . CONCLUSION VRT seemed to reduce the severity of OGA , showing effects similar to CBT , and enhanced the balance of the cortico-striatal-limbic circuit Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Craving is a strong desire to consume that emerges in every case of substance addiction . Previous studies have shown that eliciting craving with an exposure cues protocol can be a useful option for the treatment of nicotine dependence . Thus , the main goal of this study was to develop a virtual platform in order to induce craving in smokers . Fifty-five undergraduate students were r and omly assigned to two different virtual environments : high arousal context ual cues and low arousal context ual cues scenarios ( 17 smokers with low nicotine dependency were excluded ) . An eye-tracker system was used to evaluate attention toward these cues . Eye fixation on smoking-related cues differed between smokers and nonsmokers , indicating that smokers focused more often on smoking-related cues than nonsmokers . Self-reports of craving are in agreement with these results and suggest a significant increase in craving after exposure to smoking cues . In sum , these data support the use of virtual environments for eliciting craving Previous studies have shown the efficacy of virtual reality ( VR ) environments that reproduce smoking-related stimuli for increasing self-reported craving and psychophysiological reactivity in smokers . However , no study to date has attempted to simulate smoking behavior itself by means of VR technology . The aim of this study was to assess the effect of smoking a virtual cigarette on self-reported craving levels and heart rate ( HR ) in a sample of smokers . Participants were 45 smokers r and omly assigned to three VR conditions built into a virtual pub : smoking a virtual cigarette , throwing virtual darts at a virtual dartboard or just being in the virtual pub . Results showed that smoking a virtual cigarette significantly increased self-reported craving and HR when compared to the other two conditions . These results reveal that simulation of smoking behavior in a VR environment functions as an efficacious proximal cue that can be used for triggering craving under the cue-exposure paradigm Traditional cue reactivity provides a methodology for examining drug triggers and stimuli in laboratory and clinical setting s. However , current techniques lack st and ardization and generalization across research setting s. Improved method ologies using virtual reality ( VR ) cue reactivity extend previous research st and ardizing exposure to stimuli and exploring reactions to drug cues in a controlled VR setting . In a controlled pilot trial , 13 nicotine-dependent participants were allowed to smoke ad libitum then exposed to VR smoking and VR neutral cues and compared on craving intensity . VR smoking cues significantly increased craving compared to VR neutral cues . On average , craving intensity increased 118 % during exposure to VR smoking cues . Implication s for substance abuse research and treatment using VR to assess cessation and anticraving medications are discussed Objective : Virtual reality (VR)-based cue reactivity has been successfully used for the assessment of drug craving . Going beyond assessment of cue reactivity , a novel VR-based treatment approach for smoking cessation was developed and tested for feasibility . Method : In a r and omized experiment , 10-week treatment feasibility trial , 46 nicotine-dependent adults , completed the10-week program . Virtual reality skills training ( VRST ) combined with nicotine replacement therapy ( NRT ) was compared to NRT alone . Participants were assessed for smoking behavior and coping skills during , at end of treatment , and at posttreatment follow-up . Results : Smoking rates and craving for nicotine were significantly lower for the VRST group compared to NRT-only group at the end of treatment . Self-confidence and coping skills were also significantly higher for the VRST group , and number of cigarettes smoked was significantly lower , compared to the control group at follow-up . Conclusions : Feasibility of VRST was supported in the current study Background : Educating physicians and other health care professionals about the identification and treatment of patients who drink more than recommended limits is an ongoing challenge . Methods : An educational r and omized controlled trial was conducted to test the ability of a st and -alone training simulation to improve the clinical skills of health care professionals in alcohol screening and intervention . The “ virtual reality simulation ” combined video , voice recognition , and nonbranching logic to create an interactive environment that allowed trainees to encounter complex social cues and realistic interpersonal exchanges . The simulation included 707 questions and statements and 1207 simulated patient responses . Results : A sample of 102 health care professionals ( 10 physicians ; 30 physician assistants or nurse practitioners ; 36 medical students ; 26 pharmacy , physican assistant , or nurse practitioner students ) were r and omly assigned to a no training group ( n = 51 ) or a computer-based virtual reality intervention ( n = 51 ) . Professionals in both groups had similar pretest st and ardized patient alcohol screening skill scores : 53.2 ( experimental ) vs 54.4 ( controls ) , 52.2 vs 53.7 alcohol brief intervention skills , and 42.9 vs 43.5 alcohol referral skills . After repeated practice with the simulation there were significant increases in the scores of the experimental group at 6 months after r and omization compared with the control group for the screening ( 67.7 vs 58.1 ; P < .001 ) and brief intervention ( 58.3 vs 51.6 ; P < .04 ) scenarios . Conclusions : The technology tested in this trial is the first virtual reality simulation to demonstrate an increase in the alcohol screening and brief intervention skills of health care professionals The urge to gamble is a psychological , physiological , and emotional state involved in the maintenance of pathological gambling . The ability of repeated exposure to a virtual gambling environment to modify the urge to gamble and perceived self-efficacy ( PSE ) is investigated . Ten video lottery players move throughout a virtual bar with five video lottery terminals five times . The urge to gamble and PSE do not significantly vary during exposure to the gambling environment . However , the desire to gamble significantly increases when passing from the practice environment to the gambling environment . These findings suggest that virtual reality is viable for use in exposure , but that a sole 20-minute session does not set the extinction process into motion . Future studies should be conducted on virtual exposure over the course of several sessions , with the addition of a cognitive restructuring intervention Virtual reality ( VR ) can be used in the treatment of gambling disorder to provide emotionally charged context s ( e.g. , induce cravings ) where patients can practice cognitive behavior therapy ( CBT ) techniques in the safety of the therapist ’s office . This raises practical questions , such as whether the cravings are sufficient to be clinical ly useful but also manageable enough to remain clinical ly safe . Pilot data are also needed to test the development of a treatment manual and prepare large r and omized control trials . This paper reports on three studies describing ( a ) cravings induced in VR compared to real gambling and a control game of skill with no money involved ( N = 28 frequent gamblers and 36 infrequent gamblers ) ; ( b ) the usefulness of a treatment protocol with only two CBT sessions using VR ( N = 34 pathological gamblers ) ; and ( c ) the safety of a four-session treatment program of CBT in VR ( N = 25 pathological gamblers ) . Study 1 reveals that immersions in VR can elicit desire and a positive anticipation to gamble in frequent gamblers that are ( a ) significantly stronger than for infrequent gamblers and for playing a control game of skill and ( b ) as strong as for gambling on a real video lottery terminal . Study 2 documents the feasibility of integrating VR in CBT , its usefulness in identifying more high-risk situations and dysfunctional thoughts , how inducing cravings during relapse prevention exercises significantly relates to treatment outcome , and the safety of the procedure in terms of cybersickness . Results from Study 3 confirm that , compared to inducing urges to gamble in imagination , using VR does not lead to urges that are stronger , last longer , or feel more out of control . Outcome data and effect sizes are reported for both r and omized control pilot trials conducted in inpatient setting s. Suggestions for future research are provided , including on increasing the number of VR sessions in the treatment program Pilot studies revealed promising results regarding crushing virtual cigarettes to reduce tobacco addiction . In this study , 91 regular smokers were r and omly assigned to two treatment conditions that differ only by the action performed in the virtual environment : crushing virtual cigarettes or grasping virtual balls . All participants also received minimal psychosocial support from nurses during each of 12 visits to the clinic . An affordable virtual reality system was used ( eMagin HMD ) with a virtual environment created by modifying a 3D game . Results revealed that crushing virtual cigarettes during 4 weekly sessions led to a statistically significant reduction in nicotine addiction ( assessed with the Fagerström test ) , abstinence rate ( confirmed with exhaled carbon monoxide ) , and drop-out rate from the 12-week psychosocial minimal-support treatment program . Increased retention in the program is discussed as a potential explanation for treatment success , and hypotheses are raised about self-efficacy , motivation , and learning Cigarette smokers , when confronted with cues associated with smoking , evidence strong reactions , including increased attentional bias toward those smoking-related cues . These reactions have not been extensively studied in young adult smokers , a group that research suggests may respond differently than adults or adolescent smokers . Furthermore , the impact of olfactory cues , such as cigarette smoke , on attentional bias has not been explored in young adult smokers . In this pilot study , 20 nicotine-dependent young adult smokers were r and omized to receive scent cues or no scent cues and were exposed to four virtual reality ( VR ) rooms containing sensory and social content , including smoking or neutral cues . Participants entered a neutral VR room , followed by two different smoking VR rooms , and closed with the same neutral room . Subjective attention to smoking cues and thoughts about smoking responses were recorded upon exiting each room . Significant increases in attention to cues and thoughts about smoking were found when young adult smokers were exposed to VR smoking environments , but the inclusion of olfactory cues did not result in significantly higher attention to cues or thoughts about smoking . Results suggest that while further research is necessary to underst and the impact of olfactory cues , VR appears to be an effective methodology for cue exposure studies exploring attentional bias in young adult smokers INTRODUCTION Cue-induced craving is a major motivator of smoking behavior , and , more importantly , a predictor of relapse . Previous studies demonstrated Output:	Conclusions : This overview suggest that VR provide benefits in the assessment and treatment of substance use disorders and behavior addictions and achieve high levels of ecological validity . While , craving provocation in VR is effective across addiction disorders , treatments based exclusively on virtual exposure to drug related cues as shown heterogenous results
MS21571	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND PURPOSE Diaspirin cross-linked hemoglobin ( DCLHb ) is a purified , cell-free human hemoglobin solution . In animal stroke models its use led to a significant reduction in the extent of brain injury . The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke . METHODS DCLHb or saline was administered to 85 patients with acute ischemic stroke in the anterior circulation , within 18 hours of onset of symptoms , in a multicenter , r and omized , single-blind , dose-finding , controlled safety trial , consisting of 3 parts : 12 doses of 25 , 50 , and 100 mg/kg DCLHb over 72 hours . RESULTS DCLHb caused a rapid rise in mean arterial blood pressure . The pressor effect was not accompanied by complications or excessive need for antihypertensive treatment . Two patients in the 100 mg/kg group had adverse events that were possibly drug related : one suffered fatal brain and pulmonary edema , the other transient renal and pancreatic insufficiency . Multivariate logistic regression analysis showed that a severe stroke at baseline and treatment with DCLHb ( OR , 4.0 ; CI , 1.4 to 12.0 ) were independent predictors of a worse outcome ( Rankin Scale score of 3 to 6 ) at 3 months . CONCLUSIONS Outcome scale scores were worse in the DCLHb group , and more serious adverse events and deaths occurred in DCLHb-treated patients than in control patients . We recommend that additional safety studies be performed , preferably with a second generation , genetically engineered hemoglobin BACKGROUND AND PURPOSE Reduction in infa rct volume is the st and ard measure of therapeutic success in animal stroke models . Reduction in infa rct volume has been advocated as a biological surrogate or auxiliary outcome measure for human stroke clinical trials to replace or supplement deficit , disability , and global clinical scales . However , few studies have investigated correlations between infa rct volume and clinical end points in acute ischemic stroke patients . METHODS CT scans at days 6 to 11 were acquired prospect ively in 191 fully eligible patients enrolled in the R and omized Trial of Tirilazad Mesylate in Patients With Acute Stroke ( RANTTAS ) . Patients were enrolled within 6 hours of onset of stroke in any vessel distribution . Infa rct volume was measured by operator-assisted computerized planimetry . RESULTS One hundred thirty-two patients had visible new supratentorial infa rcts , with median infa rct volume of 28.0 cm3 ( interquartile range , 9.0 to 93.0 cm3 ) . Fifty-nine patients had no visible new infa rct . Correlations with st and ard 3-month outcome scales and mortality were as follows : Barthel Index , r=0.43 ; Glasgow Outcome Scale , r=0.53 ; National Institutes of Health Stroke Scale , r=0.54 ; mortality , r=0.31 . For visible infa rcts alone , correlations were as follows : BI , r=0.46 ; GOS , r=0.59 ; NIHSS , r=0.56 ; mortality , r=0.32 . CONCLUSIONS Subacute CT infa rct volume correlates moderately with 3-month clinical outcome as assessed by widely used neurological and functional assessment scales . The modesty of this linkage constrains the use of infa rct volume as a surrogate end point in ischemic stroke clinical trials BACKGROUND In laboratory animals , cerebral ischaemia is worsened by hyperthermia and improved by hypothermia . Whether these observations apply to human beings with stroke is unknown . We therefore examined the relation between body temperature on admission with acute stroke and various indices of stroke severity and outcome . METHODS In a prospect i ve and consecutive study 390 stroke patients were admitted to hospital within 6 h after stroke ( median 2.4 h ) . We determined body temperature on admission , initial stroke severity , infa rct size , mortality , and outcome in survivors . Stroke severity was measured on admission , weekly , and at discharge on the Sc and inavian Stroke Scale ( SSS ) . Infa rct size was determined by computed tomography . Multiple logistic and linear regression outcome analyses included relevant confounders and potential predictors such as age , gender , stroke severity on admission , body temperature , infections , leucocytosis , diabetes , hypertension , atrial fibrillation , ischaemic heart disease , smoking previous stroke , and comorbidity . FINDINGS Mortality was lower and outcome better in patients with mild hypothermia on admission ; both were worse in patients with hyperthermia . Body temperature was independently related to initial stroke severity ( p < 0.009 ) , infa rct size ( p < 0.0001 ) , mortality ( p < 0.02 ) , and outcome in survivors ( SSS at discharge ) ( p < 0.003 ) . For each 1 degrees C increase in body temperature the relative risk of poor outcome ( death or SSS score on discharge < 30 points ) rose by 2.2 ( 95 % CI 1.4 - 3.5 ) ( p < 0.002 ) . INTERPRETATION We have shown that , in acute human stroke , an association exists between body temperature and initial stroke severity , infa rct size , mortality , and outcome . Only intervention trials of hypothermic treatment can prove whether this relation is causal BACKGROUND AND PURPOSE The great variability of outcome seen in stroke patients has led to an interest in identifying predictors of outcome . The combination of clinical and imaging variables as predictors of stroke outcome in a multivariable risk adjustment model may be more powerful than either alone . The purpose of this study was to determine the multivariable relationship between infa rct volume , 6 clinical variables , and 3-month outcomes in ischemic stroke patients . METHODS Included in the study were 256 eligible patients from the R and omized Trial of Tirilazad Mesylate in Acute Stroke ( RANTTAS ) . Six clinical variables and 1-week infa rct volume were the prespecified predictor variables . The National Institutes of Health Stroke Scale , Barthel Index , and Glasgow Outcome Scale were the outcomes . Multivariable logistic regression techniques were used to develop the model equations , and bootstrap techniques were used for internal validation . Predictive performance of the models was assessed for discrimination with receiver operator characteristic ( ROC ) curves and for calibration with calibration curves . RESULTS The predictive models had areas under the ROC curve of 0.79 to 0.88 and demonstrated nearly ideal calibration curves . The areas under the ROC curves were statistically greater ( P<0.001 ) with both clinical and imaging information combined than with either alone for predicting excellent recovery and death or severe disability . CONCLUSIONS Combined clinical and imaging variables are predictive of 3-month outcome in ischemic stroke patients . Demonstration of this relationship with acute clinical variables and 1-week infa rct information supports future attempts to predict 3-month outcome with all acute variables Background The 21-aminosteroids are a series of compounds design ed to inhibit lipid peroxidation in the cell , and , as such , may have cerebral protective effects . The current study was performed to evaluate the effect of a 21-aminosteroid , tirilazad mesylate ( U74006F ) , on cerebral blood flow , metabolism , and carbon dioxide reactivity . Methods Using a double-blind study design , eight volunteers received tirilazad mesylate , and eight others received only vehicle . The cerebral blood flow was measured by single photon emission computerized tomography using 133Xe inhalation in the resting condition at the beginning of the study and after infusion of tirilazad mesylate ( 1.5 mg/kg ) or vehicle . Cerebral oxygen metabolism was calculated from the cerebral blood flow and the measured cerebral arteriovenous oxygen content difference . After both of the above cerebral blood flow measurements , arterial carbon dioxide tension was decreased by voluntary hyperventilation , and , later , Increased by breathing an air/carbon dioxide mixture . The relative changes in cerebral blood flow Induced by the Paco2 , variations were estimated from the changes in the arteriovenous oxygen content difference . Results Blood pressure , pulse rate , and Paco2 , were similar before and after the infusion of tirilazad mesylate in both groups , and there was no difference between the groups . The cerebral blood flow and oxygen metabolism did not change after the tirilazad mesylate infusion . The slope of the regression line of relative change of estimated cerebral blood flow and Paco2 , ( regression coefficients in both groups , > 0.90 ) was unchanged after Infusion . Conclusions Tirilazad mesylate has no effect on cerebral blood flow , cerebral oxygen metabolism , or reactivity of cerebral blood flow to carbon dioxide in healthy volunteers CONTEXT Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset , but many patients present later after stroke onset and alternative treatments are needed . OBJECTIVE To determine the clinical efficacy and safety of intra-arterial ( IA ) recombinant prourokinase ( r-proUK ) in patients with acute stroke of less than 6 hours ' duration caused by middle cerebral artery ( MCA ) occlusion . DESIGN PROACT II ( Prolyse in Acute Cerebral Thromboembolism II ) , a r and omized , controlled , multicenter , open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998 . SETTING Fifty-four centers in the United States and Canada . PATIENTS A total of 180 patients with acute ischemic stroke of less than 6 hours ' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infa rct ion signs on computed tomographic scan . INTERVENTION Patients were r and omized to receive 9 mg of IA r-proUK plus heparin ( n = 121 ) or heparin only ( n = 59 ) . MAIN OUTCOME MEASURES The primary outcome , analyzed by intention-to-treat , was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less . Secondary outcomes included MCA recanalization , the frequency of intracranial hemorrhage with neurological deterioration , and mortality . RESULTS For the primary analysis , 40 % of r-proUK patients and 25 % of control patients had a modified Rankin score of 2 or less ( P = .04 ) . Mortality was 25 % for the r-proUK group and 27 % for the control group . The recanalization rate was 66 % for the r-proUK group and 18 % for the control group ( P<.001 ) . Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10 % of r-proUK patients and 2 % of control patients ( P = .06 ) . CONCLUSION Despite an increased frequency of early symptomatic intracranial hemorrhage , treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days CONTEXT Approved treatment options for acute ischemic stroke in the United States and Canada are limited at present to intravenous tissue-type plasminogen activator , but bleeding complications , including intracranial hemorrhage , are a recognized complication . OBJECTIVE To evaluate the efficacy and safety of the defibrinogenating agent ancrod in patients with acute ischemic stroke . DESIGN The Stroke Treatment with Ancrod Trial ( STAT ) , a r and omized , parallel-group , double-blind , placebo-controlled trial conducted between August 1993 and January 1998 . SETTING Forty-eight centers , primarily community hospitals , in the United States and Canada . PATIENTS A total of 500 patients with an acute or progressing ischemic neurological deficit were enrolled and included in the intent-to-treat analysis . INTERVENTIONS Patients were r and omly assigned to receive ancrod ( n=248 ) or placebo ( n = 252 ) as a continuous 72-hour intravenous infusion beginning within 3 hours of stroke onset , followed by infusions lasting approximately 1 hour at 96 and 120 hours . The ancrod regimen was design ed to decrease plasma fibrinogen levels to 1.18 to 2.03 micromol/L. MAIN OUTCOME MEASURES The primary efficacy end point was functional status , with favorable functional status defined as survival to day 90 with a Barthel Index of 95 or more or at least the prestroke value , compared by treatment group . Primary safety variables included symptomatic intracranial hemorrhage and mortality . RESULTS Favorable functional status was achieved by more patients in the ancrod group ( 42.2 % ) than in the placebo group ( 34.4 % ; P=.04 ) by the prespecified covariate-adjusted analysis . Mortality was not different between treatment groups ( at 90 days , 25.4 % for the ancrod group and 23 % for the placebo group ; P=.62 ) , and the proportion of severely disabled patients was less in the ancrod group than in the placebo group ( 11.8 % vs 19.8 % ; P=.01 ) . The favorable functional status observed with ancrod vs placebo was consistent in Output:	REVIEW ER 'S CONCLUSIONS Tirilazad mesylate increased the combined end-point of ' death or disability ' by about one-fifth , but did not alter case fatality , when given to patients with acute ischaemic stroke .
MS21572	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIM Epidural analgesia is considered to be the best method of pain relief after major surgery despite its side-effects , which include hypotension , respiratory depression , urinary retention , incomplete or failed block , and , in rare cases , paraplegia . Paravertebral block is an alternative technique that may offer a comparable analgesic effect and a better side-effect profile . This study measured postoperative pain and respiratory function in patients r and omized to receive either paravertebral block or epidural analgesia for pain control after thoracic surgery . METHODS Twenty-four adult patients undergoing thoracic surgery were enrolled in a prospect i ve and r and omized clinical study . Patients were r and omly allocated to receive either postoperative continuous paravertebral analgesia ( N=12 ) or epidural analgesia ( N=12 ) starting at pleura closure . Postoperative use of morphine , visual analogue scores , and spirometer data were collected for 72 hours after surgery as markers of pain relief . RESULTS There was a statistically significant ( P=0.003 ) increase in median ( 25th-75th percentiles ) patient-controlled use of morphine , with values of 36 ( 22 - 42 ) mg in the paravertebral group vs. 9 ( 2 - 22 ) mg in the epidural group . This increase in morphine usage in the paravertebral group was statistically significant at 6 , 24 , 48 , and 72 hours after surgery . Postoperative pain measured with the visual analogue score was not significantly different in the two groups . Spirometer values at 72 h were better in the epidural group than in the paravertebral group ( P=0.03 ) . CONCLUSIONS Epidural analgesia is more efficient than paravertebral continuous block at reducing pain after thoracic surgery OBJECTIVE To compare the results of continuous epidural bupivacaine analgesia with and without hydromorphone to continuous paravertebral analgesia with bupivcaine in patients with post-thoracotomy pain . DESIGN A prospect i ve , r and omized , double-blinded trial . SETTING A teaching hospital . PARTICIPANTS Patients at a tertiary care teaching hospital undergoing throracotomy for lung cancer . INTERVENTIONS Subjects were assigned r and omly to receive a continuous thoracic epidural or paravertebral infusion . Patients in the epidural group were r and omized to receive either bupivacaine alone or in combination with hydromorphone . Visual analog scores as well as incentive spirometery results were obtained before and after thoracotomy . METHODS AND MAIN RESULTS Seventy-five consecutive patients presenting for thoracotomy were enrolled in this institutional review board-approved study . On the morning of surgery , subjects were r and omized to either an epidural group receiving bupvicaine with and without hydromorphone or a paravertebral catheter-infused bupvicaine . Postoperative visual analog scores and incentive spirometry data were measured in the postanesthesia care unit , the evening of the first operative day , and daily thereafter until postoperative day 4 . Analgesia on all postoperative days was superior in the thoracic epidural group receiving bupivacaine plus hydromorphone . Analgesia was similar in the epidural and continuous paravertebral groups receiving bupivacaine alone . No significant improvement was noted by combining the continuous infusion of bupivacaine via the paravertebral and epidural routes . Incentive spirometry goals were best achieved in the epidural bupivacaine and hydromorphone group and equal in the group receiving bupivacaine alone either via epidural or continuous paravertebral infusion . CONCLUSIONS The current study provided data that fill gaps in the current literature in 3 important areas . First , this study found that thoracic epidural analgesia ( TEA ) with bupivacaine and a hydrophilic opioid , hydromorphone , may provide enhanced analgesia over TEA or continuous paravertebral infusion ( CPI ) with bupivacaine alone . Second , in the bupivacaine-alone group , the increased basal rates required to achieve analgesia result ed in hypotension more frequently than in the bupivacaine/hydromorphone combination group , underscoring the benefit of the synergistic activity . Finally , in agreement with previous retrospective studies , the current data suggest that CPI of local anesthetic appears to provide acceptable analgesia for post-thoracotomy pain Background : The aim of this prospect i ve , r and omized , blinded study was to compare analgesic efficacy of continuous paravertebral and epidural analgesia for post‐thoracotomy pain . Methods : Forty‐two ASA physical status II – III patients undergoing lung resection surgery were r and omly allocated to receive post‐thoracotomy analgesia with either a thoracic epidural ( group EPI , n = 21 ) or paravertebral ( group PVB , n = 21 ) infusion of 0.2 % ropivacaine ( infusion rate : 5–10 mL h−1 ) . The degree of pain at rest and during coughing , haemodynamic variables and blood gas analysis were recorded every 12 h for the first 48 h. Results : The area under the curve of the visual analogue pain score during coughing over time was 192 ( 60–444 ) cm h−1 in group EPI and 228 ( 72–456 ) cm h−1 in group PVB ( P = 0.29 ) . Rescue morphine analgesia was required in four patients of group EPI ( 19 % ) and five patients of group PVB ( 23 % ) ( P = 0.99 ) . The PaO2/FiO2 ratio reduced significantly from baseline values in both groups without between‐group differences . The median ( range ) percentage reduction of systolic arterial pressure from baseline was −9 ( 0 to −9)% in group PVB and −17 ( 0 to −38)% in group EPI ( P = 0.02 ) ; while clinical ly relevant hypotension ( systolic arterial pressure decrease > 30 % of baseline ) was observed in four patients of group EPI only ( 19 % ) ( P = 0.04 ) . Patient satisfaction with the analgesia technique was 8.5 ( 8–9.8 ) cm in group EPI and 9 ( 7.5–10 ) cm in group PVB ( P = 0.65 ) . Conclusions : Continuous thoracic paravertebral analgesia is as effective as epidural blockade in controlling post‐thoracotomy pain , but is associated with less haemodynamic effects This study was undertaken to evaluate the effectiveness of 0.5 % bupivacaine ( 360 mg/day ) as a continuous infusion through an indwelling intercostal catheter inserted intraoperatively in the management of pain after thoracotomy . Eighty-six patients were r and omized into three groups : group 1 = intercostal bupivacaine , group 2 = intercostal saline solution , and group 3 = fixed-schedule intramuscular buprenorphine . Supplementary buprenorphine was given as required . Pain and pulmonary function were assessed throughout the first 5 days after operation . Pain score was lower in group 1 than in group 2 for the first 8 hours after operation ( p < 0.02 ) . During the first 3 postoperative days , mean postoperative pain scores of 5 or more were recorded in 9 % of group 1 patients versus 40 % of group 2 patients ( p < 0.05 ) and 13 % of group 3 patients ( not significant ) . Total doses of buprenorphine were lower in groups 1 and 2 than in group 3 ( p < 0.001 ) . No between-group differences in pulmonary function were observed . Respiratory complications occurred in no patients in groups 1 and 3 versus 5 in group 2 ( p < 0.05 ) . Continuous intercostal bupivacaine provided similar early pain control as compared with fixed-schedule narcotics but induced better analgesia with fewer complications than on-dem and narcotics alone ( group 2 ) Context Thoracic epidural and paravertebral blocks provide adequate analgesia for postoperative thoracotomy pain . Both procedures are usually performed percutaneously with considerable failure rates . A subpleural catheter placed in the space posterior to the parietal pleura and alongside the paravertebral area may provide superior postoperative pain relief . Objective To compare subpleural analgesia with thoracic epidural analgesia in patients undergoing thoracotomy . Design R and omised , double-blind study . Setting A tertiary care University Medical Centre between 26 June 2008 and 21 March 2011 . Patients Forty-two patients scheduled for elective posterolateral thoracotomy . Patients with American Society of Anesthesiologists physical status ≥4 , with a previous history of thoracotomy , on chronic pain medications or with a contraindication to receiving local anaesthetics or thoracic epidural block were excluded from the study . Interventions Patients were r and omised to receive either subpleural analgesia or thoracic epidural analgesia for 24-h post-thoracotomy pain control . Main outcome measures A visual analogue scale was used to assess pain at rest and on coughing during the first 24 h postoperatively and the incidence of hypotension was recorded . Results Patients who received subpleural analgesia had higher visual analogue scores at rest and on coughing than those who received thoracic epidural analgesia . Seven patients who started with subpleural analgesia were treated with thoracic epidural analgesia at a mean ( SD ) of 3.9 ( 4.8 ) h. The remaining 14 patients had a median ( IQR [ range ] ) visual analogue score of 5 cm ( 4–5 [ 3–6 ] ) at rest and were maintained on subpleural analgesia until the end of the study . The visual analogue score at rest was < 7 cm in all 21 patients who received thoracic epidural analgesia and none was switched to subpleural analgesia during the study . None of the patients in the subpleural analgesia group experienced hypotension compared with five of the 21 patients in the thoracic epidural analgesia group ( P = 0.047 ) . Conclusion Thoracic epidural analgesia is superior to subpleural analgesia in relieving post-thoracotomy pain Background In order to assess the short term risks of pneumonectomy for lung cancer in contemporary practice a one year prospect i ve observational study of pneumonectomy outcome was made . Current UK practice for pneumonectomy was observed to note patient and treatment factors associated with major complications . Methods A multicentre , prospect i ve , observational cohort study was performed . All 35 UK thoracic surgical centres were invited to su bmi t data to the study . All adult patients undergoing pneumonectomy for lung cancer between 1 January and 31 December 2005 were included . Patients undergoing pleuropneumonectomy , extended pneumonectomy , completion pneumonectomy following previous lobectomy and pneumonectomy for benign disease , were excluded from the study .The main outcome measure was suffering a major complication . Major complications were defined as : death within 30 days of surgery ; treated cardiac arrhythmia or hypotension ; unplanned intensive care admission ; further surgery or inotrope usage . Results 312 pneumonectomies from 28 participating centres were entered . The major complication incidence was : 30-day mortality 5.4 % ; treated cardiac arrhythmia 19.9 % ; unplanned intensive care unit admission 9.3 % ; further surgery 4.8 % ; inotrope usage 3.5 % . Age , American Society of Anesthesiologists physical status ≥ P3 , pre-operative diffusing capacity for carbon monoxide ( DLCO ) and epidural analgesia were collectively the strongest risk factors for major complications . Major complications prolonged median hospital stay by 2 days . Conclusion The 30 day mortality rate was less than 8 % , in agreement with the British Thoracic Society guidelines . Pneumonectomy was associated with a high rate of major complications . Age , ASA physical status , DLCO and epidural analgesia appeared collectively most associated with major complications BACKGROUND Optimal management of pain after thoracotomy can be challenging . Continuous infusion of local anesthetic into the incision may help reduce the amount of narcotics required to control postoperative pain . To address this issue , we performed a r and omized , double-blinded , controlled trial of infusion of bupivacaine versus placebo through intercostal and subcutaneous catheters after thoracotomy . METHODS From April 2006 to June 2007 , 124 patients had intercostal catheters placed at thoracotomy and connected to continuous infusion pain pumps . Each patient had catheters placed in the intercostal space near the head of the rib and subcutaneously beneath the incision ; both were connected to an infusion pump through a Y connector . Patients were r and omly assigned to receive placebo ( normal saline solution ) or 0.25 % bupivacaine as a 4 cc per hour infusion for 100 hours after thoracotomy . All personnel caring for the patients were blinded to the content of the infusion . Demographic information , visual analog pain scores , and oral morphine equivalent usage was recorded for each patient . In addition to the infusion catheters , all patients had epidural analgesia that remained in place until postoperative day 3 . RESULTS There were 60 patients in the bupivacaine arm and 64 in the placebo group . Overall mean age was 64.7 years and 65 ( 52.4 % ) were men . Mean body mass index was 28.8 kg/m(2 Output:	So , we conclude that thoracic PVB may be as effective as thoracic epidural analgesia for post-thoracotomy pain relief and is also associated with fewer complications
MS21573	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives —To compare the therapeutic effect of two different exercise protocol s in athletes with jumper 's knee . Methods —R and omised clinical trial comparing a 12 week programme of either drop squat exercises or leg extension/leg curl exercises . Measurement was performed at baseline and after six and 12 weeks . Primary outcome measures were pain ( visual analogue scale 1–10 ) and return to sport . Secondary outcome measures included quadriceps and hamstring moment of force using a Cybex II isokinetic dynamometer at 30 ° /second . Differences in pain response between the drop squat and leg extension/curl treatment groups were assessed by 2 ( group ) × 3 ( time ) analysis of variance . Two by two contingency tables were used to test differences in rates of return to sport . Analysis of variance ( 2 ( injured versus non-injured leg ) × 2 ( group ) × 3 ( time ) ) was also used to determine differences for secondary outcome measures . Results —Over the 12 week intervention , pain diminished by 2.3 points ( 36 % ) in the leg extension/curl group and 3.2 points ( 57 % ) in the squat group . There was a significant main effect of both exercise protocol s on pain ( p<0.01 ) with no interaction effect . Nine of 10 subjects in the drop squat group returned to sporting activity by 12 weeks , but five of those subjects still had low level pain . Six of nine of the leg extension/curl group returned to sporting activity by 12 weeks and four patients had low level pain . There was no significant difference between groups in numbers returning to sporting activity . There were no differences in the change in quadriceps or hamstring muscle moment of force between groups . Conclusions —Progressive drop squats and leg extension/curl exercises can reduce the pain of jumper 's knee in a 12 week period and permit a high proportion of patients to return to sport . Not all patients , however , return to sport by that time Background : Conservative treatment of patellar tendinopathy has been minimally investigated . Effective vali date d treatment protocol s are required . Objectives : To investigate the immediate ( 12 weeks ) and long term ( 12 months ) efficacy of two eccentric exercise programmes for the treatment of patellar tendinopathy . Methods : This was a prospect i ve r and omised controlled trial of 17 elite volleyball players with clinical ly diagnosed and imaging confirmed patellar tendinopathy . Participants were r and omly assigned to one of two treatment groups : a decline group and a step group . The decline group were required to perform single leg squats on a 25 ° decline board , exercising into tendon pain and progressing their exercises with load . The step group performed single leg squats on a 10 cm step , exercising without tendon pain and progressing their exercises with speed then load . All participants completed a 12 week intervention programme during their preseason . Outcome measures used were the Victorian Institute of Sport Assessment ( VISA ) score for knee function and 100 mm visual analogue scale ( VAS ) for tendon pain with activity . Measures were taken throughout the intervention period and at 12 months . Results : Both groups had improved significantly from baseline at 12 weeks and 12 months . Analysis of the likelihood of a 20 point improvement in VISA score at 12 months revealed a greater likelihood of clinical improvements in the decline group than the step group . VAS scores at 12 months did not differ between the groups . Conclusions : Both exercise protocol s improved pain and sporting function in volleyball players over 12 months . This study indicates that the decline squat protocol offers greater clinical gains during a rehabilitation programme for patellar tendinopathy in athletes who continue to train and play with pain Background —There is no disease specific , reliable , and valid clinical measure of Achilles tendinopathy . Objective —To develop and test a question naire based instrument that would serve as an index of severity of Achilles tendinopathy . Methods —Item generation , item reduction , item scaling , and pretesting were used to develop a question naire to assess the severity of Achilles tendinopathy . The final version consisted of eight questions that measured the domains of pain , function in daily living , and sporting activity . Results range from 0 to 100 , where 100 represents the perfect score . Its validity and reliability were then tested in a population of non-surgical patients with Achilles tendinopathy ( n = 45 ) , presurgical patients with Achilles tendinopathy ( n = 14 ) , and two normal control population s ( total n = 87 ) . Results —The VISA-A question naire had good test-retest ( r = 0.93 ) , intrarater ( three tests , r = 0.90 ) , and interrater ( r = 0.90 ) reliability as well as good stability when compared one week apart ( r = 0.81 ) . The mean ( 95 % confidence interval ) VISA-A score in the non-surgical patients was 64 ( 59–69 ) , in presurgical patients 44 ( 28–60 ) , and in control subjects it exceeded 96 ( 94–99 ) . Thus the VISA-A score was higher in non-surgical than presurgical patients ( p = 0.02 ) and higher in control subjects than in both patient population s ( p<0.001 ) . Conclusions —The VISA-A question naire is reliable and displayed construct validity when means were compared in patients with a range of severity of Achilles tendinopathy and control subjects . The continuous numerical result of the VISA-A question naire has the potential to provide utility in both the clinical setting and research . The test is not design ed to be diagnostic . Further studies are needed to determine whether the VISA-A score predicts prognosis To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results AIM Prognosis and treatment of Achilles tendon pain ( achillodynia ) has been insufficiently studied . The purpose of the present study was to examine the long-term effect of eccentric exercises compared with stretching exercises on patients with achillodynia . METHODS Patients with achillodynia for at least 3 months were r and omly allocated to one of two exercise regimens . Exercise was performed daily for a 3-month period . Symptom severity was evaluated by tendon tenderness , ultrasonography , a question naire on pain and other symptoms , and a global assessment of improvement . Follow-up was performed at time points 3 , 6 , 9 , 12 weeks and 1 year . RESULTS Of 53 patients with achillodynia 45 patients were r and omized to either eccentric exercises or stretching exercises . Symptoms gradually improved during the 1-year follow-up period and were significantly better assessed by pain and symptoms after 3 weeks and all later visits . However , no significant differences could be observed between the two groups . Women and patients with symptoms from the distal part of the tendon had significantly less improvement . CONCLUSIONS Marked improvement in symptoms and findings could be gradually observed in both groups during the 1-year follow-up period . To that extent this is due to effect of both regimens or the spontaneous improvement is unsettled BACKGROUND AND PURPOSE Systematic review s and meta-analyses often include an evaluation of the method ological quality of the individual studies that have been included , and are usually conducted by at least 2 individuals . The objective of this study was to assess the method ological quality and reliability of a series of r and omized controlled trials ( RCTs ) of both pharmacological and nonpharmacological interventions by use of the 10-item Physiotherapy Evidence -Based Data base ( PEDro ) Scale . METHODS Two abstract ors independently review ed 81 RCTs assessing a variety of interventions . The Cohen kappa statistic and the intraclass correlation coefficient ( ICC ) were used to assess agreement between abstract ors . RESULTS The average total PEDro scores were 5.94 ( SD=1.43 ) for all studies combined , 6.88 ( SD=1.2 ) for pharmacological studies , and 5.29 ( SD=1.26 ) for nonpharmacological studies . The median score for pharmacological studies was significantly higher than that for nonpharmacological studies ( 7 versus 5 ) . Pair-wise kappa scores ranged from a low of .452 for concealed allocation among drug trials to perfect agreement ( 1.00 ) for r and omization and reporting of results from between-group comparisons . The ICCs associated with the cumulative PEDro score were .91 ( 95 % confidence interval [CI]=.83-.94 ) for all studies , .89 ( 95 % CI=.78-.95 ) for pharmacological studies , and .91 ( 95 % CI=.84-.952 ) for nonpharmacological studies . DISCUSSION AND CONCLUSION The method ological quality for pharmacological interventions was significantly higher than that for nonpharmacological interventions . There was good agreement between raters at an individual item level and in total PEDro scores . A lack of reporting clarity , poor organization of the report , or the failure to include salient details contributed to less-than-perfect agreement between raters Achilles tendinopathy is common and treatment with eccentric exercises seems promising . We design ed a prospect i ve r and omized clinical trial to test the hypothesis that eccentric calf muscle exercises reduce pain and improve function in patients with Achilles tendinopathy . Forty-four patients were recruited from primary care ( mean age : 45 years ; 23 women ; 65 % active in sports ) and r and omized to three treatment groups for 12 weeks : eccentric exercises , a night splint or a combination of both treatments . Pain and function were evaluated at 6 , 12 , 26 and 52 weeks by the Foot and Ankle Outcome Score . At 6 weeks , the eccentric group reported a significant pain reduction ( 27 % compared with baseline , P = 0.007 ) which lasted for 1 year ( 42 % , P = 0.001 ) . The two groups treated with a night splint also reported significant but less pain reduction than the eccentric group . Differences between all the three groups were not significant . At 12 weeks , the eccentric group reported significantly less pain than the splint-only group ( P = 0.04 ) . More patients in the eccentric group than in the splint group returned to sport after 12 weeks . We conclude that eccentric exercises seem to reduce pain and improve function in patients with Achilles tendinopathy . Our results are in line with previous studies and strengthen the recommendation that patients should undergo an eccentric exercise program prior to considering other treatments such as surgery Sclerosing injections targeting neovascularisation have been demonstrated to give promising clinical results in patients with chronic painful Achilles tendinosis . In this study , fifteen elite or recreational athletes ( 12 men and three women ) with the diagnosis patellar tendinosis/Jumper ’s knee in 15 patellar tendons were included . All the patients had a long duration of pain symptoms ( mean = 23 months ) from the patellar tendon , and ultra-sonography + colour doppler examination showed structural tendon changes with hypo-echoic areas and a neovascularisation , corresponding to the painful area . The patients were treated with ultrasound and colour doppler-guided injections of the sclerosing substance Polidocanol , targeting the area with neovascularisation . At follow-up ( mean = 6 months ) after a mean amount of three treatments , there was a good clinical result in 12/15 tendons . The patients were back to their previous ( before injury ) sport activity level , and the amount of pain recorded on a VAS-scale had decreased significantly ( VAS from 81 to 10 ) . Our findings indicate that treatment with sclerosing injections , targeting the area with neovessels in patellar tendinosis , has the potential to cure the pain in the tendons and also allow the patients to go back to full patellar-tendon loading activity Background : Little information is available on the long-term outcome of jumper 's knee , a common problem among athletes . Purpose : Our aim was to determine the 15-year prognosis of jumper 's knee . Study Design : Prospect i ve case control . Methods : The prognosis for jumper 's knee was studied using two groups : athletes with jumper 's knee and nonsymptomatic control athletes . At baseline , all subjects participated in st and ardized clinical examinations and measurements , and 15 years later they were asked to respond to a question naire . Results : Twenty athletes with jumper 's knee and 16 ath Output:	Similarly , the RCTs demonstrated that strength-related measures improved over time , but none revealed significant differences relative to the control treatment .
MS21574	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Two hundred Hausa primigravidae at Zaria were divided into five groups in a r and omized double-blind trial of antenatal oral antimalarial prophylaxis , and haematinic supplements . Group 1 received no active treatment . Groups 2 to 5 were given chloroquine 600 mg base once , followed by proguanil 100 mg per day . In addition , group 3 received iron 60 mg daily , group 4 folic acid 1 mg daily , and group 5 iron plus folic acid . Forty-five percent were anaemic ( haemoglobin ( Hb ) less than 11.0 g dl-1 ) at first attendance before 24 weeks of gestation , and malaria parasitaemia ( predominantly Plasmodium falciparum ) was seen in 27 % , of whom 60 % were anaemic . The mean Hb fell during pregnancy in group 1 , and seven patients in this group had to be removed from the trial and treated for severe anaemia ( packed cell volume ( PCV ) less than 0.26 ) . Only five patients in the other groups developed severe anaemia ( P = 0.006 ) , two of whom had malaria following failure to take treatment . Patients in group 1 had the lowest mean Hb at 28 and 36 weeks of gestation , and patients receiving antimalarials and iron ( groups 3 and 5 ) had the highest Hb at 28 weeks , but differences were not significant , possibly due to removal from the trial of patients with severe anaemia . Anaemia ( Hb less than 12.0 g dl-1 ) at six weeks after delivery was observed in 61 % of those not receiving active treatment ( group 1 ) , in 39 % of those protected against malaria but not receiving iron supplements ( groups 2 and 4 ) and in only 18 % of patients receiving both antimalarials and iron ( groups 3 and 5 ) . Folic acid had no significant effect on mean Hb . Proguanil was confirmed to be a highly effective causal prophylaxis . Prevention of malaria , without folic acid supplements , reduced the frequency of megaloblastic erythropoiesis from 56 % to 25 % . Folic acid supplements abolished megaloblastosis , except in three patients who were apparently not taking the treatment prescribed . Red cell folate ( RCF ) concentrations were higher in subjects with malaria , probably due to intracellular synthesis by plasmodia . Infants of mothers not receiving antimalarials appeared to have an erythroid hyperplasia . Maternal folate supplements raised infants ' serum folate and RCF . Fourteen per cent had low birth weight ( less than 2500 g ) , and the perinatal death rate was 11 % ; the greatest number were in group 1 , but not significantly . A regime is proposed for the prevention of malaria , iron deficiency , folate deficiency and anaemia in pregnancy in the guinea savanna of Nigeria Background Intermittent preventive treatment with sulphadoxine-pyrimethamine ( IPTp-SP ) is being implemented in most malaria endemic countries as a st and ard two-doses regimen as it reduces the risk of low birth weight ( LBW ) and the prevalence of maternal anaemia . Nevertheless , where the risk of infection close to delivery is high because of intense transmission , a third IPTp-SP dose may further reduce the negative effects of malaria on pregnancy outcome . Methods Pregnant women in the 2nd or 3rd trimester were r and omized to receive either 2 ( SP2 ) or 3 doses ( SP3 ) of SP . Trained field workers paid home visits to the women for drug administration according to a predefined drug delivery schedule . Women were encouraged to attend their scheduled ANC visits and to deliver at the health facilities where the new-born was weighed . The prevalence of LBW ( < 2500 g ) , severe anaemia ( Hb < 8 g/dL ) and premature birth was analysed using intention-to-treat ( ITT ) and per- protocol ( PP ) analysis . Results Data from 1274 singleton pregnancies were analysed ( 641 in the SP3 and 633 in the SP2 group ) . The uptake of the intervention appeared to be low . Though the prevalence of LBW in both intervention groups was similar ( adjusted Incident Rate Ratio , AIRR = 0.92 , 95%CI : 0.69 - 1.24 ) in the ITT analysis , the risk of severe anaemia was significantly lower in the SP3 group compared to the SP2 group ( AIRR = 0.38 , 95%CI : 0.16 - 0.90 ) . The PP analysis showed a trend of reduced risk of LBW , severe anaemia and premature delivery in the SP3 group , albeit the difference between two and three IPTp-SP did not reach statistical significance . Conclusion The risk of LBW and severe anaemia tended to be lower in the SP3 group , though this was not statistically significant , probably due to the low uptake of the intervention which reduced the power of the study . Further studies are needed for establishing whether a third SP dose has a real benefit in preventing the negative effects of malaria in pregnancy in setting s where transmission is markedly seasonal To determine the effect of chloroquine chemoprophylaxis during pregnancy on birth weights , a r and omized trial was carried out in 1987 and 1988 in Banfora , Burkina Faso ( West Africa ) . Seven hundred forty-five r and omly selected women treated with chloroquine sulfate were compared to with 719 controls who received no treatment . In spite of an un question able effect of chloroquine in preventing placental infection ( 4.1 % infected placentas in the treated group versus 19.0 % in the controls ) , the mean difference in birth weights between the two groups ( 6 g ) was not significant . The difference in the proportion of low birth weight ( LBW ) newborn babies in two groups ( 16.3 % versus 16.4 % ) was also not significant . However , there was a strong relationship between placental infection and birth weight ( the mean birth weight difference between infected and uninfected placentas was 113 g , and the proportion of LBW babies was 26.0 % in infected placentas versus 14.8 % in uninfected placentas ) . The small difference in birth weights observed between the two groups may be due to the fact that the prevalence rate of placental infection is low and that prophylaxis is effective only on a portion of the subjects in the treated group . It may also indicate that malaria is only one of several risk factors responsible for LBW . The relatively small increase in birth weight , the expected poor acceptance of mass prophylaxis , and the spreading of chloroquine-resistant Plasmodium strains should be considered before extending malaria chemoprophylaxis to all pregnant women . It might be worth considering to limit prophylaxis to primigravidae Background In the global context of a reduction of under-five mortality , neonatal mortality is an increasingly relevant component of this mortality . Malaria in pregnancy may affect neonatal survival , though no strong evidence exists to support this association . Methods In the context of a r and omised , placebo-controlled trial of intermittent preventive treatment ( IPTp ) with sulphadoxine-pyrimethamine ( SP ) in 1030 Mozambican pregnant women , 997 newborns were followed up until 12 months of age . There were 500 live borns to women who received placebo and 497 to those who received SP . Findings There were 58 infant deaths ; 60.4 % occurred in children born to women who received placebo and 39.6 % to women who received IPTp ( p = 0.136 ) . There were 25 neonatal deaths ; 72 % occurred in the placebo group and 28 % in the IPTp group ( p = 0.041 ) . Of the 20 deaths that occurred in the first week of life , 75 % were babies born to women in the placebo group and 25 % to those in the IPTp group ( p = 0.039 ) . IPTp reduced neonatal mortality by 61.3 % ( 95 % CI 7.4 % , 83.8 % ) ; p = 0.024 ] . Conclusions Malaria prevention with SP in pregnancy can reduce neonatal mortality . Mechanisms associated with increased malaria infection at the end of pregnancy may explain the excess mortality in the malaria less protected group . Alternatively , SP may have reduced the risk of neonatal infections . These findings are of relevance to promote the implementation of IPTp with SP , and provide insights into the underst and ing of the pathophysiological mechanisms through which maternal malaria affects fetal and neonatal health . Trial Registration Clinical Trials.gov Background New regimens for intermittent preventive treatment in pregnancy ( IPTp ) against malaria are needed as the effectiveness of the st and ard two-dose sulfadoxine-pyrimethamine ( SP ) regimen is under threat . Previous trials have shown that IPTp with monthly SP benefits HIV-positive primi- and secundigravidae , but there is no conclusive evidence of the possible benefits of this regimen to HIV-negative women , or to a population comprising of both HIV-positive and –negative women of different gravidities . Methods This study analyzed 484 sample s collected at delivery as part of a r and omized , partially placebo controlled clinical trial , conducted in rural Malawi between 2003 and 2007 . The study included pregnant women regardless of their gravidity or HIV-infection status . The participants received SP twice ( controls ) , monthly SP , or monthly SP and two doses of azithromycin ( AZI-SP ) . The main outcome was the prevalence of peripheral Plasmodium falciparum malaria at delivery diagnosed with a real-time polymerase chain reaction ( PCR ) assay . Findings Overall prevalence of PCR-diagnosed peripheral P. falciparum malaria at delivery was 10.5 % . Compared with the controls , participants in the monthly SP group had a risk ratio ( 95 % CI ) of 0.33 ( 0.17 to 0.64 , P<0.001 ) and those in the AZI-SP group 0.23 ( 0.11 to 0.48 , P<0.001 ) for malaria at delivery . When only HIV-negative participants were analyzed , the corresponding figures were 0.26 ( 0.12 to 0.57 , P<0.001 ) for women in the monthly SP group , and 0.24 ( 0.11 to 0.53 , P<0.001 ) for those in the AZI-SP group . Conclusions Our results suggest that increasing the frequency of SP administration during pregnancy improves the efficacy against malaria at delivery among HIV-negative women , as well as a population consisting of both HIV-positive and –negative pregnant women of all gravidities , in a setting of relatively low but holoendemic malaria transmission , frequent use of bed nets and high SP resistance . Trial Registration Clinical Trials.gov BACKGROUND In 2003 , Mali introduced intermittent preventive therapy in pregnancy ( ITPp ) with sulfadoxine-pyrimethamine ( SP ) for the control of malaria in pregnancy , consisting of 2 doses of SP given in the 2nd and 3rd trimester . This widely used regimen , although very effective , leaves many women unprotected from malaria during the last 4-to-8 weeks of gestation , which is a pivotal period for fetal weight gain . The aim of the study was to compare the efficacy and safety of 3-dose versus 2-dose IPTp-SP for the prevention of placental malaria and associated low birth weight ( LBW ) . METHODS We conducted a parallel-group , open-label , individually r and omized controlled superiority trial involving 814 women of all gravidity , enrolled from April 2006 through March 2008 . All women were seen at least 3 times and received either 2 ( n = 401 ) or 3 ( n = 413 ) doses of IPTp-SP . The primary endpoint measured was placental malaria , LBW , preterm births , and maternal anemia were secondary endpoints , and severe maternal skin reactions and neonatal jaundice were safety endpoints . RESULTS Among the 96 % of study subjects who were followed up until delivery , the prevalence of placental malaria was 2-fold lower in the 3-dose group ( 8.0 % ) than in the 2-dose group ( 16.7 % ) ; the adjusted prevalence ratio ( APR ) was 0.48 ( 95 % confidence interval [ CI ] , 0.32 - 0.71 ) . LBW and preterm births were also reduced ; the prevalence of LBW was 6.6 % in the 3-dose group versus 13.3 % in the 2-dose group ( APR , 0.50 ; 95 % CI , 0.32 - 0.79 ) , and the prevalence of preterm births was 3.2 % versus 8.9 % ( APR , 0.37 ; 95 % CI , 0.19 - 0.71 ) . No significant reductions in maternal anemia or differences in safety endpoints were observed . CONCLUSIONS Adding a third dose of ITPp-SP halved the risk of placental malaria , LBW , and preterm births in all gravidae , compared with the st and ard 2-dose regimen , in this area of highly seasonal transmission with low levels of SP resistance . CLINICAL TRIALS REGISTRATION IS RCT N 74189211 BACKGRO Output:	In trials giving chemoprevention to all pregnant women irrespective of parity , the average effects of chemoprevention measured in all women indicated it may prevent severe anaemia ( defined by authors , but at least < 8 g/L : RR 0.19 , 95 % CI 0.05 to 0.75 ; two trials , 1327 participants , low quality evidence ) , but consistent benefits have not been shown for other outcomes . Authors ' conclusions Routine chemoprevention to prevent malaria and its consequences has been extensively tested in RCTs , with clinical ly important benefits on anaemia and parasitaemia in the mother , and on birthweight in infants . 8 May 2019 No up date planned Review superseded The intervention is clearly effective .
MS21575	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging . However , evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning . OBJECTIVE To determine whether G. biloba slows the rates of global or domain-specific cognitive decline in older adults . DESIGN , SETTING , AND PARTICIPANTS The Ginkgo Evaluation of Memory ( GEM ) study , a r and omized , double-blind , placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years , conducted in 6 academic medical centers in the United States between 2000 and 2008 , with a median follow-up of 6.1 years . INTERVENTION Twice-daily dose of 120-mg extract of G. biloba ( n = 1545 ) or identical-appearing placebo ( n = 1524 ) . MAIN OUTCOME MEASURES Rates of change over time in the Modified Mini-Mental State Examination ( 3MSE ) , in the cognitive subscale of the Alzheimer Disease Assessment Scale ( ADAS-Cog ) , and in neuropsychological domains of memory , attention , visual-spatial construction , language , and executive functions , based on sums of z scores of individual tests . RESULTS Annual rates of decline in z scores did not differ between G. biloba and placebo groups in any domains , including memory ( 0.043 ; 95 % confidence interval [ CI ] , 0.034 - 0.051 vs 0.041 ; 95 % CI , 0.032 - 0.050 ) , attention ( 0.043 ; 95 % CI , 0.037 - 0.050 vs 0.048 ; 95 % CI , 0.041 - 0.054 ) , visuospatial abilities ( 0.107 ; 95 % CI , 0.097 - 0.117 vs 0.118 ; 95 % CI , 0.108 - 0.128 ) , language ( 0.045 ; 95 % CI , 0.037 - 0.054 vs 0.041 ; 95 % CI , 0.033 - 0.048 ) , and executive functions ( 0.092 ; 95 % CI , 0.086 - 0.099 vs 0.089 ; 95 % CI , 0.082 - 0.096 ) . For the 3MSE and ADAS-Cog , rates of change varied by baseline cognitive status ( mild cognitive impairment ) , but there were no differences in rates of change between treatment groups ( for 3MSE , P = .71 ; for ADAS-Cog , P = .97 ) . There was no significant effect modification of treatment on rate of decline by age , sex , race , education , APOE*E4 allele , or baseline mild cognitive impairment ( P > .05 ) . CONCLUSION Compared with placebo , the use of G. biloba , 120 mg twice daily , did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00010803 Soybean-derived phosphatidylserine ( Soy-PS ) is a phosphatidylserine made from soybean lecithin by enzymatic reaction with L-serine . A double-blind , r and omized controlled study was conducted to investigate the effects of Soy-PS on the cognitive functions of the elderly Japanese subjects with memory complaints . Seventy-eight elderly people with mild cognitive impairment ( 50–69 years old ) were r and omly allocated to take Soy-PS ( 100 mg , 300 mg/day ) or placebo for 6 months . As a result , there was no difference in blood markers and vital signs during Soy-PS treatment and any side effect caused by Soy-PS treatment was not observed . Neuropsychological test scores were similarly increased in all groups including placebo group . However , in the subjects with relatively low score at baseline , the memory scores in PS treated groups were significantly increased against the baseline , while those of placebo group remained unchanged . And the memory improvements in Soy-PS-treated groups were mostly attributed to the increase in delayed verbal recall , a memory ability attenuated in the earliest stage of dementia . In conclusion , Soy-PS used in this study is considered as safety food ingredient and 6 months of Soy-PS supplementation could improve the memory functions of the elderly with memory complaints BACKGROUND Despite widespread use of multivitamin supplements , their effect on cognitive health-a critical issue with aging-remains inconclusive . To date , no long-term clinical trials have studied multivitamin use and cognitive decline in older persons . OBJECTIVE To evaluate whether long-term multivitamin supplementation affects cognitive health in later life . DESIGN R and omized , double-blind , placebo-controlled trial of a multivitamin from 1997 to 1 June 2011 . The cognitive function sub study began in 1998 . Up to 4 repeated cognitive assessment s by telephone interview were completed over 12 years . ( Clinical Trials.gov : NCT00270647 ) SETTING : The Physicians ' Health Study II . PATIENTS 5947 male physicians aged 65 years or older . INTERVENTION Daily multivitamin or placebo . MEASUREMENTS A global composite score averaging 5 tests of global cognition , verbal memory , and category fluency . The secondary end point was a verbal memory score combining 4 tests of verbal memory , which is a strong predictor of Alzheimer disease . RESULTS No difference was found in mean cognitive change over time between the multivitamin and placebo groups or in the mean level of cognition at any of the 4 assessment s. Specifically , for the global composite score , the mean difference in cognitive change over follow-up was -0.01 SU ( 95 % CI , -0.04 to 0.02 SU ) when treatment was compared with placebo . Similarly , cognitive performance did not differ between the multivitamin and placebo groups on the secondary outcome , verbal memory ( mean difference in cognitive change over follow-up , -0.005 SU [ CI , -0.04 to 0.03 SU ] ) . LIMITATION Doses of vitamins may be too low or the population may be too well-nourished to benefit from a multivitamin . CONCLUSION In male physicians aged 65 years or older , long-term use of a daily multivitamin did not provide cognitive benefits . PRIMARY FUNDING SOURCE National Institutes of Health , BASF , Pfizer , and DSM Nutritional Products BACKGROUND Prior investigations have reported a link between poor status of antioxidants , folate , and cobalamin result ing in elevated total plasma homocysteine ( tHcy ) and methylmalonic acid ( MMA ) concentrations with an increased risk for reduced cognitive performance . The aim of the study was to evaluate the effect of a 6-month multivitamin supplementation on the cognitive performance of female seniors and to assess cognitive functioning in relation to vitamin status , tHcy , and MMA values at baseline . METHODS The study was performed as a r and omized placebo-controlled double-blind trial . 220 healthy , free-living women ( aged 60 - 91 years ) were included . Blood drawings and cognitive tests were performed at the Institute of Food Science of the University of Hanover , Germany . Vitamin and cognitive status have been evaluated prior to and 6 months after supplementation . Plasma ascorbic acid , serum concentrations of alpha-tocopherol , beta-carotene , and coenzyme Q10 , serum and erythrocyte folate as well as serum cobalamin , serum MMA , and plasma tHcy concentrations were measured . Activity coefficient of erythrocyte alpha aspartic aminotransferase was used as functional index for vitamin B(6 ) status . The cognitive performance was assessed by the Symbol Search test , a subtest of the Wechsler Adult Intelligence Scale ( WAIS-III ) and the pattern-recognition test . Intelligence as assessed by the ' Kurztest für Allgemeine Intelligenz ' ( KAI ) was a further variable . RESULTS No significant differences in pattern-recognition and intelligence score were observed between vitamin and placebo group prior to and after multivitamin supplementation . In the Symbol Search test , the vitamin group exhibited better test results than the placebo group at both measure points . One-way ANOVA showed a marginally significant linear trend between the baseline tHcy concentration and the pattern-recognition score ( P = 0.051 ) in the total sample . Multiple backward regression revealed only a significant influence of the school graduation on baseline cognitive function test results . A general linear model showed that the changes in cognitive function scores could not be explained by the type of treatment or blood parameters . CONCLUSIONS Our data indicate that 6 months supplementation of physiological dosages of antioxidants and B vitamins have no effect on cognitive performance in presumedly healthy and well-nourished female seniors . An intervention period of only 6 months may be too short for improving cognitive performance in well-educated elderly women without dementia Background Observational studies have frequently reported an association between cognitive function and nutrition in later life but r and omised trials of B vitamins and antioxidant supplements have mostly found no beneficial effect . We examined the effect of daily supplementation with 11 vitamins and 5 minerals on cognitive function in older adults to assess the possibility that this could help to prevent cognitive decline . Methods The study was carried out as part of a r and omised double blind placebo controlled trial of micronutrient supplementation based in six primary care health centres in North East Scotl and . 910 men and women aged 65 years and over living in the community were recruited and r and omised : 456 to active treatment and 454 to placebo . The active treatment consisted of a single tablet containing eleven vitamins and five minerals in amounts ranging from 50–210 % of the UK Reference Nutrient Intake or matching placebo tablet taken daily for 12 months . Digit span forward and verbal fluency tests , which assess immediate memory and executive functioning respectively , were conducted at the start and end of the intervention period . Risk of micronutrient deficiency at baseline was assessed by a simple risk question naire . Results For digit span forward there was no evidence of an effect of supplements in all participants or in sub-groups defined by age or risk of deficiency . For verbal fluency there was no evidence of a beneficial effect in the whole study population but there was weak evidence for a beneficial effect of supplementation in the two pre-specified subgroups : in those aged 75 years and over ( n 290 ; mean difference between supplemented and placebo groups 2.8 ( 95 % CI -0.6 , 6.2 ) units ) and in those at increased risk of micronutrient deficiency assessed by the risk question naire ( n 260 ; mean difference between supplemented and placebo groups 2.5 ( 95 % CI -1.0 , 6.1 ) units ) . Conclusion The results provide no evidence for a beneficial effect of daily multivitamin and multimineral supplements on these domains of cognitive function in community-living people over 65 years . However , the possibility of beneficial effects in older people and those at greater risk of nutritional deficiency deserves further attention Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer ’s disease ( AD ) ? One approach is to modify nongenetic risk factors , for instance by lowering elevated plasma homocysteine using B vitamins . In an initial , r and omized controlled study on elderly subjects with increased dementia risk ( mild cognitive impairment according to 2004 Petersen criteria ) , we showed that high-dose B-vitamin treatment ( folic acid 0.8 mg , vitamin B6 20 mg , vitamin B12 0.5 mg ) slowed shrinkage of the whole brain volume over 2 y. Here , we go further by demonstrating that B-vitamin treatment reduces , by as much as seven fold , the cerebral atrophy in those gray matter ( GM ) regions specifically vulnerable to the AD process , including the medial temporal lobe . In the placebo group , higher homocysteine levels at baseline are associated with faster GM atrophy , but this deleterious effect is largely prevented by B-vitamin treatment . We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine ( above the median , 11 µmol/L ) and that , in these participants , a causal Bayesian network analysis indicates the following chain of events : B vitamins lower homocysteine , which directly leads to a decrease in GM atrophy , thereby slowing cognitive decline . Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline . Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented Background — Cardiovascular factors are associated with cognitive decline . Antioxidants may be beneficial . Methods and Results — The Women ’s Antioxidant Cardiovascular Study was a trial of vitamin E ( 402 mg every other day ) , beta carotene ( 50 mg every other day ) , and vitamin C ( 500 mg daily ) for the secondary prevention of cardiovascular disease . From 19 Output:	Overall , studies provided low-strength evidence suggesting that -3 fatty acids do not improve cognitive performance in adults with normal cognition compared with placebo .
MS21576	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction Aging involves a progressive reduction of respiratory muscle strength as well as muscle strength . Purpose Compare the effects of resistance training volume on the maximum inspiratory pressure ( MIP ) , maximum expiratory pressure ( MEP ) , functional performance , and muscle strength in elderly women . Methods Thirty elderly women were r and omly assigned to a group performing either single sets ( 1-SET ) or three sets ( 3-SET ) of exercises . The sit-to-st and test , MIP , MEP , and muscle strength were assessed before and after 24 training sessions . Progressive resistance training was performed two times per week for a total of 8–12 repetitions , using the main muscle groups of the upper and lower limbs . Results The main results showed that the participants significantly increased their MEP ( P<0.05 ; 1-SET : 34.6 % ; 3-SET : 35.8 % ) and MIP ( P<0.05 ; 1-SET : 13.7 % ; 3-SET : 11.2 % ) . Both groups also improved in the sit-to-st and test ( P<0.05 ; 1-SET : 10.6 % ; 3-SET : 17.1 % ) . After 24 training sessions , muscle strength also significantly increased ( P<0.0001 ; 40%–80 % ) in both groups . An intergroup comparison did not show any statistically significant differences between the groups in any of the parameters analyzed . Conclusion Single- and multiple-set resistance training programs increased MIP , MEP , muscle strength , and sit-to-st and test performance in elderly women after 24 sessions of training . In conclusion , our results suggested that elderly women who are not in the habit of physical activity may start with single-set resistance training programs as a short-term strategy for the maintenance of health The strength training has been shown to be effective for attenuating the age-related physiological decline . However , the adequate volume of strength training volume adequate to promote improvements , mainly during the initial period of training , still remains controversial . Thus , the purpose of this study was to compare the effects of a short-term strength training program with single or multiple sets in elderly women . Maximal dynamic ( 1-RM ) and isometric strength , muscle activation , muscle thickness ( MT ) , and muscle quality ( MQ = 1-RM and MT quadriceps quotient ) of the knee extensors were assessed . Subjects were r and omly assigned into one of two groups : single set ( SS ; n = 14 ) that performed one set per exercise or multiple sets ( MS ; n = 13 ) that performed three-sets per exercise , twice weekly for 6 weeks . Following training , there were significant increases ( p ≤ 0.05 ) in knee extension 1-RM ( 16.1 ± 12 % for SS group and 21.7 ± 7.7 % for MS group ) , in all MT ( p ≤ 0.05 ; vastus lateralis , rectus femoris , vastus medialis , and vastus intermedius ) , and in MQ ( p ≤ 0.05 ) ; 15.0 ± 12.2 % for SS group and 12.6 ± 7.2 % for MS group ) , with no differences between groups . These results suggest that during the initial stages of strength training , single- and multiple-set training demonstrate similar capacity for increasing dynamic strength , MT , and MQ of the knee extensors in elderly women OBJECTIVE To determine the effect of frequency of resistive training on gain in muscle strength and neuromuscular performance in healthy older adults . DESIGN A r and omized controlled trial with subjects assigned either to high-intensity resistance training 1 ( EX1 ) , 2 ( EX2 ) , or 3 ( EX3 ) days per week for 24 weeks or to a control group ( CO ) . SETTING An exercise facility at an academic medical center . SUBJECTS Forty-six community-dwelling healthy men ( n = 29 ) and women ( n = 17 ) aged 65 to 79 years . INTERVENTION Progressive resistance training consisting of three sets of eight exercises targeting major muscle groups of the upper and lower body , at 80 % of one-repetition maximum ( 1-RM ) for eight repetitions , either 1 , 2 , or 3 days per week . MEASURES Dynamic muscle strength ( 1-RM ) using isotonic equipment every 4 weeks , bone mineral density and body composition by dual energy X-ray absorptiometry ( DXA ) , and neuromuscular performance by timed chair rise and 6-meter backward t and em walk . RESULTS For each of the eight exercises , muscle strength increased in the exercise groups relative to CO ( P < .01 ) , with no difference among EX1 , EX2 and EX3 groups at any measurement interval . Percent change averaged 3.9 + /- 2.4 ( CO ) , 37.0 + /- 15.2 ( EX1 ) , 41.9 + /- 18.2 ( EX2 ) , and 39.7 + /- 9.8 ( EX3 ) . The time to rise successfully from the chair 5 times decreased significantly ( P < .01 ) at 24 weeks , whereas improvement in the 6-meter backward t and em walk approached significance ( P = .10 ) in the three exercise groups compared with CO . Changes in chair rise ability were correlated to percent changes in quadriceps strength ( r = -0.40 , P < .01 ) and lean mass ( r = -0.40 , P < .01 ) . CONCLUSIONS A program of once or twice weekly resistance exercise achieves muscle strength gains similar to 3 days per week training in older adults and is associated with improved neuromuscular performance . Such improvement could potentially reduce the risk of falls and fracture in older adults Are meta-analyses the brave new world , or are the critics of such combined analyses right to say that the biases inherent in clinical trials make them uncombinable ? Negative trials are often unreported , and hence can be missed by meta-analysts . And how much heterogeneity between trials is acceptable ? A recent major criticism is that large r and omised trials do not always agree with a prior meta- analysis . Neither individual trials nor meta-analyses , reporting as they do on population effects , tell how to treat the individual patient . Here we take a more rounded approach to meta-analyses , arguing that their strengths outweigh their weaknesses , although the latter must not be brushed aside Age-related processes in the neuromuscular and the somatosensory system are responsible for decreases in maximal and explosive force production capacity and deficits in postural control . Thus , the objectives of this study were to investigate the effects of resistance training on strength performance and on postural control in seniors . Forty healthy seniors ( 67+/-1 yrs ) participated in this study . Subjects were r and omly assigned to a resistance training ( n=20 ) and a control group ( n=20 ) . Resistance training for the lower extremities lasted for 13 weeks at 80 % of the one repetition maximum . Pre and post tests included the measurement of maximal isometric leg extension force with special emphasis on the early part of the force-time-curve and the assessment of static ( functional reach test ) and dynamic ( t and em walk test , platform perturbation ) postural control . Resistance training result ed in an enhanced strength performance with increases in explosive force exceeding those in maximal strength . Improved performances in the functional reach and in the t and em walk test were observed . Resistance training did not have an effect on the compensation of platform perturbations . Increases in strength performance can primarily be explained by an improved neural drive of the agonist muscles . The inconsistent effect of resistance training on postural control may be explained by heterogeneity of testing methodology or by the incapability of isolated resistance training to improve postural control BACKGROUND To study the effects of resistance training on muscle strength and size in older people , we enrolled 8 men and 17 women ( mean age 68.2 + /- 1 SEM ) into a one-year exercise trial . METHODS Subjects were r and omly assigned to exercise or control groups . Muscle biopsies were obtained from 11 subjects ( 8 exercisers/3 controls ) at baseline and after 15 weeks ; exercisers underwent another biopsy at 30 weeks . After testing maximum strength using the 1-RM method , the exercisers began a 12-exercise circuit ( 3 sets of 8 repetitions at 75 % of 1-RM ) , 3 times a week . The controls repeated the strength testing every 15 weeks . They were asked to continue usual activities and not to start any exercise program . RESULTS With exercise , muscle strength increased , average increases ranging from 30 % ( hip extensors ) to 97 % ( hip flexors ) . Strength increased rapidly over 3 months , then plateaued for the duration of the experiment . No strength changes were observed in sedentary controls . Cross-sectional area of type 1 muscle fibers increased in exercisers by 15 weeks ( 29.4 + /- 1 % , p < .02 ) and after 30 weeks ( 58.5 + /- 13.7 % , p < .002 ) compared to baseline . Type 2 fiber area did not change at 15 weeks , but increased by 30 weeks of training ( 66.6 + /- 9.5 % , p < .0002 ) . CONCLUSIONS These results suggest that prolonged moderate to high intensity resistance training may be carried out by healthy older adults with reasonable compliance , and that such training leads to sustained increases in muscle strength . These improvements are rapidly achieved and are accompanied by hypertrophy of both type 1 and type 2 muscle fibers The purpose of this study was to determine whether a high intensity ( HI ) versus a moderate ( MI ) or low-intensity ( LI ) training program would be more effective in improving the isokinetic knee extension muscular performance in healthy inactive men and women . Sixty-four participants , men and women , were r and omly assigned to one of four groups : control group ( C ) , LI ( 50 % of 1RM ) , the MI group ( 70 % of 1RM ) and the HI ( 90 % of 1RM ) . Participants exercised on three resistance exercise machines : leg extension , leg curls and leg press . The isokinetic testing method ( concentric mode ) applied prior to and at the end of the training period ( 16 weeks , three 3 times per week ) to assess the knee muscular performance . MANOVA repeated measures revealed that the HI group demonstrated the most strength gains following a speed specificity pattern ( most considerable improvement occurred at or near slow speeds from 7.3 % to 11.2 % for male and from 2.3 % to 15.2 % for female ) . In addition , males demonstrated a greater improvement of knee extension power output than females . In conclusion , HI strength training is proposed for elderly men and women as the most effective protocol . Furthermore only at low-velocity testing , women of the HI showed a greater change than men ( p < 0.05 ) . Regarding strength increase in relation to various testing velocities , a greater increase was found in HI at low velocities , with the other training groups exhibiting almost similar strength increase at all tested speeds ZusammenfassungHINTERGRUND : I m Alter kommt es sowohl zu einer Reduktion der Muskelmasse als auch zu metabolischen Veränderungen i m Skelettmuskel . Ein Großteil dieser Veränderungen ist auf Bewegungsmangel zurückzuführen und kann durch ein Ausdauertraining ( ET ) und Krafttraining ( RT ) verhindert werden . FRAGESTELLUNG : Welche Trainings method e ist die effektivste , um die physische Leistungsfähigkeit i m Alter zu verbessern ? Das Ziel dieser Studie ist es festzustellen , ob ein systematisches ET auch die Muskelkraft steigern kann und/oder ob ein systematisches RT auch die aerobe Kapazität von gesunden alten Menschen verbessern kann . UNTERSUCHUNGEN/ METHOD EN : 42 Prob and en ( 32 Frauen , 10 Männer ) wurden für die Studie rekrutiert und in 3 Gruppen r and omisiert : 13 Prob and en führten ein 6-monatiges ET Programm durch , 15 Prob and en ein 6-monatiges RT Programm und 14 Prob and en wurden in die Kontrollgruppe gelost . Eine Belastungsspiroergometrie und eine Dynamometrie wurden zu Beginn und am Ende der Studie absolviert , um die aerobe Kapazität ( VO2max ) , die maximale Leistungsfähigkeit ( Wmax ) , sowie die Maximalkraft ( 1-RM ) zu testen . ERGEBNISSE : Die Maximalkraft verbesserte sich signifikant ( zwischen 15 % und 30 % ) nach 6 Monaten RT , während ET zu keiner signifikanten Veränderung der Maximalkraft führte . ET result ierte in einer hoch signifikanten Verbesserung der Wmax um 31 % , während RT nur eine moderate Verbesserung der Wmax um 6 % zeigte . ET result ierte zusätzlich in einer signifikanten Reduktion des Körperfettanteils , RT in einer Zunahme der fettfreien Magermasse . SCHLUSSFOLGERUNG : Sowohl ET , als auch RT wirken positiv auf die Gesundheit und Fitness gesunder alter Menschen , jedoch auf unterschiedliche Art und Weise : ET verbessert die aerobe Kapazität , jedoch nicht die Muskelkraft , und reduziert das kardiovaskuläre Risiko wahrscheinlich effektiver . RT verbessert die Muskelkraft und tendenziell das metabolische Risiko , das bei einer reduzierten Muskelmasse i m Alter erhöht ist . Wir empfehlen bei gesunden , alten Menschen vor allem ein Maximalkrafttraining mit einer Intensität von 60–80 % des EWM , 8–15 Wiederholungen pro Übung und einem Volumen von 3–6 Sätzen pro Muskelgruppe und Woche . ET sollte ergänzend 2-mal pro Woche mit einer Intensität von 60 % VO2max ( nach Karvonen ) und einer wöchentlichen Output:	No single training volume variable significantly predicted RT effects on measures of muscle morphology . While we were able to determine a dose – response relationship based on specific individual training variables with respect to muscle strength and morphology , it was not possible to ascertain any potential interactions between these variables . Conclusions This systematic literature review and meta- analysis confirmed the effectiveness of RT on specific measures of upper and lower extremity muscle strength and muscle morphology in healthy old adults . In addition , we were able to extract dose – response relationships for key training variables ( i.e. , volume , intensity , rest ) , informing clinicians and practitioners to design effective RTs for muscle strength and morphology . Training period , intensity , time under tension , and rest in between sets play an important role in improving muscle strength and morphology and should be implemented in exercise training programs targeting healthy old adults .
MS21577	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND More than 80 % of donor lungs are potentially injured and therefore not considered suitable for transplantation . With the use of normothermic ex vivo lung perfusion ( EVLP ) , the retrieved donor lung can be perfused in an ex vivo circuit , providing an opportunity to reassess its function before transplantation . In this study , we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP . METHODS In this prospect i ve , nonr and omized clinical trial , we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP . High-risk donor lungs were defined by specific criteria , including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen ( PO(2):FIO(2 ) ) less than 300 mm Hg . Lungs with acceptable function were subsequently transplanted . Lungs that were transplanted without EVLP during the same period were used as controls . The primary end point was primary graft dysfunction 72 hours after transplantation . Secondary end points were 30-day mortality , bronchial complications , duration of mechanical ventilation , and length of stay in the intensive care unit and hospital . RESULTS During the study period , 136 lungs were transplanted . Lungs from 23 donors met the inclusion criteria for EVLP ; in 20 of these lungs , physiological function remained stable during EVLP and the median PO(2):FIO(2 ) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion , respectively ( P<0.001 ) . These 20 lungs were transplanted ; the other 116 lungs constituted the control group . The incidence of primary graft dysfunction 72 hours after transplantation was 15 % in the EVLP group and 30 % in the control group ( P=0.11 ) . No significant differences were observed for any secondary end points , and no severe adverse events were directly attributable to EVLP . CONCLUSIONS Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs . ( Funded by Vitrolife ; Clinical Trials.gov number , NCT01190059 . ) Objective : Painful bladder syndrome/interstitial cystitis ( PBS/IC ) and recurrent urinary tract infections ( UTI ) are clinical ly challenging conditions to manage in patients . We evaluate the clinical use of intravesical sodium hyaluronate ( Cystistat ® ) in both these patient groups who have completed treatment . Patients and Methods : Thirteen patients with recurrent UTIs ( Group I ) and 8 patients with PBS/IC ( Group II ) received intravesical sodium hyaluronate ( Cystistat ® ) . Preinstallation demographic parameters were statically comparable in both groups . The mean age of presentation was 54.6 years in Group I and 57.5 years in Group II ( p = 0.9 ) . All 13 patients in Group I were on low dose antibiotics . The mean number of installations completed in both groups was 9 ( range 4–21 ) . Results : Data was collected prospect ively using a st and ard pre- and post-treatment question er with the pelvic pain and urinary/frequency patient symptom scale . At a mean follow-up of 21 months a significant improvement in bladder pain ( p = 0.05 ) , daytime frequency ( p = 0.03 ) and quality of life ( p = 0.02 ) was noted in patients in Group I. Two patients had breakthrough UTIs during treatment . Within Group I , 7 ( 53 % ) patients responded well to treatment . Patients in Group II had a significant improvement in bladder pain ( p = 0.02 ) , urgency ( p = 0.01 ) , nocturia ( p = 0.01 ) and quality of life ( p = 0.04 ) . Within Group II , 6 patients ( 75 % ) responded to treatment . Conclusion : Intravesical sodium hyaluronate ( Cystistat ® ) can be used with minimal side effects and good compliance in both groups of patients with PBS and recurrent UTIs . Longer follow-up and larger patient numbers in both groups will be required to confirm the long-term efficacy of these two clinical ly challenging groups of patients BACKGROUND The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts . The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital . We aim ed to assess the clinical outcomes of the Organ Care System compared with st and ard cold storage of human donor hearts for transplantation . METHODS We did this prospect i ve , open-label , multicentre , r and omised non-inferiority trial at ten heart-transplant centres in the USA and Europe . Eligible heart-transplant c and i date s ( aged > 18 years ) were r and omly assigned ( 1:1 ) to receive donor hearts preserved with either the Organ Care System or st and ard cold storage . Participants , investigators , and medical staff were not masked to group assignment . The primary endpoint was 30 day patient and graft survival , with a 10 % non-inferiority margin . We did analyses in the intention-to-treat , as-treated , and per- protocol population s. This trial is registered with Clinical Trials.gov , number NCT00855712 . FINDINGS Between June 29 , 2010 , and Sept 16 , 2013 , we r and omly assigned 130 patients to the Organ Care System group ( n=67 ) or the st and ard cold storage group ( n=63 ) . 30 day patient and graft survival rates were 94 % ( n=63 ) in the Organ Care System group and 97 % ( n=61 ) in the st and ard cold storage group ( difference 2·8 % , one-sided 95 % upper confidence bound 8·8 ; p=0·45 ) . Eight ( 13 % ) patients in the Organ Care System group and nine ( 14 % ) patients in the st and ard cold storage group had cardiac-related serious adverse events . INTERPRETATION Heart transplantation using donor hearts adequately preserved with the Organ Care System or with st and ard cold storage yield similar short-term clinical outcomes . The metabolic assessment capability of the Organ Care System needs further study . FUNDING TransMedics The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia – reperfusion injury . We present the first patients transplanted using a normothermic machine perfusion ( NMP ) device that transports and stores an organ in a fully functioning state at 37 ° C . In this Phase 1 trial , organs were retrieved using st and ard techniques , attached to the perfusion device at the donor hospital , and transported to the implanting center in a functioning state . NMP livers were matched 1:2 to cold‐stored livers . Twenty patients underwent liver transplantation after NMP . Median NMP time was 9.3 ( 3.5–18.5 ) h versus median cold ischaemia time of 8.9 ( 4.2–11.4 ) h. Thirty‐day graft survival was similar ( 100 % NMP vs. 97.5 % control , p = 1.00 ) . Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group ( 417 IU [ 84–4681 ] ) versus ( 902 IU [ 218–8786 ] , p = 0.03 ) . This first report of liver transplantation using NMP‐preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation , including transportation . NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs Ex vivo lung perfusion ( EVLP ) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation . Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were r and omly assigned to two groups . In the antibiotic group ( n = 8) , lungs underwent EVLP for 12 h with high‐dose antibiotics ( ciprofloxacin 400 mg or azithromycin 500 mg , vancomycin 15 mg/kg , and meropenem 2 g ) . In the control group ( n = 7 ) , lungs underwent EVLP for 12 h without antibiotics . A quantitative decrease in bacterial counts in bronchoalveolar lavage ( BAL ) was found in all antibiotic‐treated cases but in only two control cases . Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group . EVLP with broad‐spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance . Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α , IL‐1β and macrophage inflammatory proteins 1α and 1β at 12 h. In conclusion , EVLP treatment of infected donor lungs with broad‐spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function Output:	Local delivery of nanodrugs to organs such as the lung , rectum , or bladder may enhance the local drug concentration with less clearance via MPS . In transplant setting s , ex vivo organ perfusion provides a new route to repair injury of isolated organs in the absence of MPS . Based on a similar concept , chemotherapy with in vivo lung perfusion techniques and other isolated organ perfusion provides opportunities for cancer therapy
MS21578	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS To test the accuracy of four measures of peripheral diabetic neuropathy in a primary care population . METHODS Type 2 diabetic ( n = 544 ) and 544 non-diabetic participants aged 45 - 76 years were r and omly selected from general practice registers . Neuropathy was assessed using vibration threshold ( VT ) and scores for light touch , thermal sense and modified Michigan Neuropathy Screening Instrument question naire . These measures were assessed for variation with diabetes status , age , diabetes duration , HbA1c , and presence of retinopathy and nephropathy . Light touch , thermal sense and question naire scores were assessed against VT using ROC curve analysis . RESULTS Only VT and light touch were different between diabetic and non-diabetic groups ( P = 0.02 and < 0.0001 , respectively ) . All measures were significantly associated with diabetes duration and retinopathy , and all except question naire score ( P = 0.14 ) with age . None was associated with nephropathy and only question naire score was associated with HbA1c ( P = 0.033 ) . VT varied as expected across scores of light touch ( chi2 = 41.65 , P = 0.0001 ) , thermal sense ( chi2 = 15.86 , P = 0.015 ) and question naire ( chi2 = 21.22 , P = 0.047 ) . Area under the curve values for light touch , thermal and question naire scores were 0.72 ( 95 % confidence interval ( CI ) 0.63 , 0.82 ) , 0.63 ( 95 % CI 0.52 , 0.73 ) and 0.64 ( 95 % CI 0.53 , 0.74 ) , respectively . CONCLUSIONS All measures had associations with risk factors for neuropathy , but light touch score ( monofilament ) had the strongest association with vibration threshold ( the chosen gold st and ard ) and thus appeared the most appropriate tool for use in primary care , because of its validity and simplicity of use The Semmes-Weinstein pressure aesthesiometer , which measures cutaneous pressure sensation , was used for quantifying sensory loss in diabetic peripheral neuropathy . Eighty subjects comprising four groups were tested : nondiabetic controls ( Group C ) ; non-neuropathic , diabetic controls ( Group DC ) ; diabetic subjects with neuropathy and without a history of pedal ulcerations ( Group DN ) ; and , diabetic subjects with a history of or active pedal ulceration ( Group DU ) . Cutaneous pressure sensation of 10 dorsal and plantar sites on the foot were tested , using a method of interval comparison modeled after the two-alternative forced choice algorithm . The sensitivity threshold level was defined as the lightest probe in which the subject accurately chose the correct interval in at least 2 out of 3 trials . The mean sensitivity threshold level for Group DC was not significantly increased ( p greater than .05 ) compared to Group C. In contrast , patients with neuropathy ( Group DN or DU ) showed a significantly higher mean sensitivity threshold ( p less than .001 ) than either Group C or DC . In addition , this technique demonstrated that patients in Group DU had a mean sensitivity threshold that was statistically higher ( p less than .001 ) than Group DN , although both groups of patients had symptomatic neuropathy . This study provides a direct demonstration that decreased sensation of pressure occurs in the feet of diabetic patients with a history of ulceration . The best discrimination between groups is obtained by requiring that three of the six plantar forefoot sites have a sensitivity threshold level of greater than 5.07 log ( 0.1 mg ) force as the risk discriminator level . Semmes-Weinstein aesthesiometry should now be tested in a prospect i ve study to demonstrate its effectiveness in determining those patients at great risk of developing foot ulcers OBJECTIVE Little prospect i ve research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents . We prospect ively studied the effects of diabetes characteristics , foot deformity , behavioral factors , and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 lower limbs . RESEARCH DESIGN AND METHODS Eligible subjects included all diabetic enrollees of a general internal medicine clinic without foot ulcer , of whom 83 % agreed to participate . Baseline assessment included history and lower-limb physical examination , tests for sensory and autonomic neuropathy , and measurements of macro- and microvascular perfusion in the foot . Subjects were followed for the occurrence of a full thickness skin defect on the foot that took > 14 days to heal , with a mean follow-up of 3.7 years . RESULTS Using stepwise Cox regression analysis , the following factors were independently related to foot ulcer risk : foot insensitivity to the 5.07 monofilament ( relative risk [ 95 % CI ] ) 2.2 ( 1.5 - 3.1 ) , past history of amputation 2.8 ( 1.8 - 4.3 ) or foot ulcer 1.6 ( 1.2 - 2.3 ) , insulin use 1.6 ( 1.1 - 2.2 ) , Charcot deformity 3.5 ( 1.2 - 9.9 ) , 15 mmHg higher dorsal foot transcutaneous PO2 0.8 ( 0.7 - 0.9 ) , 20 kg higher body weight 1.2 ( 1.1 - 1.4 ) , 0.3 higher ankle-arm index 0.8 ( 0.7 - 1.0 ) , poor vision 1.9 ( 1.4 - 2.6 ) , and 13 mmHg orthostatic blood pressure fall 1.2 ( 1.1 - 1.5 ) . Higher ulcer risk was associated with hammer/claw toe deformity and history of laser photocoagulation in certain subgroups . Unrelated to foot ulcer risk in multivariate models were diabetes duration and type , race , smoking status , diabetes education , joint mobility , hallux blood pressure , and other foot deformities . CONCLUSIONS Certain foot deformities , reduced skin oxygenation and foot perfusion , poor vision , greater body mass , and both sensory and autonomic neuropathy independently influence foot ulcer risk , thereby providing support for a multifactorial etiology for diabetic foot ulceration OBJECTIVE To evaluate the effectiveness of the Semmes-Weinstein monofilament examination ( SWME ) for diabetic peripheral neuropathy ( DPN ) screening at an outpatient clinic . METHODS Eighty-two type 2 diabetic out patients were question ed about 13 subjective symptoms and tested for deep reflexes . They were examined using two types of quantitative sensory testing : SWME ( using 4.31/2 g and 5.07/10 g monofilaments ) and vibration testing ( using the C-64 quantitative tuning fork ) . The patients were diagnosed with DPN when two of the following three criteria from both legs were met : ( 1 ) the presence of either pain , numbness , or paraesthesia ; ( 2 ) a diminished or absent ankle reflex ; or ( 3 ) a scale below 4 for their vibration perception thresholds ( VPT ) . RESULTS The most common subjective symptoms were muscle cramps and numbness in the extremities . SWME 4.31/2 g at the great toe or the plantar aspect of the fifth metatarsal was the most useful diagnostic test for DPN , providing 60.0 % sensitivity and 73.8 % specificity . SWME 4.31/2 g was correlated with lower limb VPT ( P=.029 ) and three subjective symptoms including fainting . SWME 5.07/10 g was correlated with lower limb VPT ( P=.011 ) , the ankle reflex ( P=.013 ) , the knee reflex ( P=.031 ) , and two subjective symptoms . However , the sensitivity to diagnose DPN was low ( 30.0 % ) . CONCLUSIONS The abnormalities indicated by SWME correlated well with those identified by lower limb VPT . Moreover , SWME 4.31/2 g correlated with fainting , suggesting that it could detect abnormalities in the small fibers . Considering the minimal time for this examination , SWME 4.31/2 g is a useful examination in an outpatient setting along with lower limb VPT and ankle reflex testing OBJECTIVE The purpose of this study was to evaluate the effects of different testing sites and buckling strengths on the sensitivity and specificity of using the Semmes-Weinstein monofilament to detect patients with insensate foot . The impact on workload required to educate and follow up these high-risk individuals was estimated by modeling in our patient population with a documented status of neuropathy . RESEARCH DESIGN AND METHODS Using the 5.07/10-g monofilament , one observer tested 132 r and omly selected subjects with diabetes at five sites on the right foot . The sensitivity and specificity of each site and combinations of sites in detecting vibration perception threshold > 40 was calculated . In addition , two monofilaments , one with a buckling force of 5 g and the other with a force of 15 g , were compared by testing 200 r and omly selected patients . An estimate of the prevalence of insensate foot and workload was made by modeling the findings to the 5,270 patients with neuropathy status registered on our computerized data base . RESULTS Specificity of the 5.07/10-g monofilament to detect insensate foot at each of the five sites is high , at approximately 90 % , but there is considerably more variation and lower sensitivity , ranging from 44 - 71 % . Data derived from the use of different combinations of sites showed that more stringent criteria are associated with lower sensitivity but higher specificity . If the foot is considered insensate when either of sites 3 and 4 ( plantar aspect of the first and fifth metatarsal heads , respectively ) can not feel the monofilament , there is reasonable sensitivity and specificity ( 80 - 86 % , respectively ) . By modeling on our diabetes center population , it can be demonstrated that the choice of different method ologies leads to different conclusions about the prevalence of severe neuropathy , ranging from 3.4 to 29.3 % . CONCLUSIONS Using a combination of sites 3 and 4 for monofilament testing gives a reasonable compromise for time , sensitivity , and specificity . Minor changes in sensitivity and specificity can lead to major changes in the prevalence of neuropathy , with implication s for workload OBJECTIVE Diabetic foot ulceration is a preventable long-term complication of diabetes . A multicenter prospect i ve follow-up study was conducted to determine which risk factors in foot screening have a high association with the development of foot ulceration . RESEARCH DESIGN AND METHODS A total of 248 patients from 3 large diabetic foot centers were enrolled in a prospect i ve study . Neuropathy symptom score , neuropathy disability score ( NDS ) , vibration perception threshold ( VPT ) , Semmes-Weinstein monofilaments ( SWFs ) , joint mobility , peak plantar foot pressures , and vascular status were evaluated in all patients at the beginning of the study . Patients were followed-up every 6 months for a mean period of 30 months ( range 6 - 40 ) , and all new foot ulcers were recorded . The sensitivity , specificity , and positive predictive value of each risk factor were evaluated . RESULTS Foot ulcers developed in 95 feet ( 19 % ) or 73 patients ( 29 % ) during the study . Patients who developed foot ulcers were more frequently men , had diabetes for a longer duration , had nonpalpable pedal pulses , had reduced joint mobility , had a high NDS , had a high VPT , and had an inability to feel a 5.07 SWE NDS alone had the best sensitivity , whereas the combination of the NDS and the inability to feel a 5.07 SWF reached a sensitivity of 99 % . On the other h and , the best specificity for a single factor was offered by foot pressures , and the best combination was that of NDS and foot pressures . Univariate logistical regression analysis yielded a statistically significant odds ratio ( OR ) for sex , race , duration of diabetes , palpable pulses , history of foot ulceration , high NDSs , high VPTs , high SWFs , and high foot pressures . In addition , 94 ( 99 % ) of the 95 ulcerated feet had a high NDS and /or SWF which result ed in the highest OR of 26.2 ( 95 % CI 3.6 - 190 ) . Furthermore , in multivariate logistical regression analysis , the only significant factors were high NDSs , VPTs , SWFs , and foot pressures . CONCLUSIONS Clinical examination and a 5.07 SWF test are the two most sensitive tests in identifying patients at risk for foot ulceration , especially when the tests are used in conjunction with each other . VPT measurements are also helpful and can be used as an alternative . Finally , foot pressure measurements offer a substantially higher specificity and can be used as a postscreening test in conjunction with providing appropriate footwear Current recommendations for the prevention of foot ulceration and amputation include screening at-risk individuals by testing for loss of protective sensation at eight sites using 10-g ( 5.07 ) nylon monofilaments . Yet measurement of the cutaneous pressure threshold to differentiate one-point from two-point static touch stimuli may allow identification of these at-risk individuals earlier in the clinical course of diabetic neuropathy . The present study tested this hypothesis using a prospect i ve , cross-sectional , multicenter design that included sensibility testing of 496 patients with diabetic neurop Output:	However , current literature suggests that nerve conduction study ( NCS ) is the gold st and ard for diagnosing DPN . There is great variation in the current literature regarding the diagnostic value of SWME as a result of different method ologies .
MS21579	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To estimate the impact of the Integrated Management of Childhood Illness ( IMCI ) strategy on early-childhood mortality , we evaluated a malaria-control project in Benin that implemented IMCI and promoted insecticide-treated nets ( ITNs ) . METHODS We conducted a before- and -after intervention study that included a nonr and omized comparison group . We used the preceding birth technique to measure early-childhood mortality ( risk of dying before age 30 months ) , and we used health facility surveys and household surveys to measure process indicators . RESULTS Most process indicators improved in the area covered by the intervention . Notably , because ITNs were also promoted in the comparison area children 's ITN use increased by about 20 percentage points in both areas . Regarding early-childhood mortality , the trend from baseline ( 1999 - 2001 ) to follow-up ( 2002 - 2004 ) for the intervention area ( 13.0 % decrease ; P < .001 ) was 14.1 % ( P < .001 ) lower than was the trend for the comparison area ( 1.3 % increase ; P = .46 ) . CONCLUSIONS Mortality decreased in the intervention area after IMCI and ITN promotion . ITN use increased similarly in both study areas , so the mortality impact of ITNs in the 2 areas might have canceled each other out . Thus , the mortality reduction could have been primarily attributable to IMCI 's effect on health care quality and care-seeking Objective To determine the effect of implementation of the Integrated Management of Neonatal and Childhood Illness strategy on treatment seeking practice s and on neonatal and infant morbidity . Design Cluster r and omised trial . Setting Haryana , India . Participants 29 667 births in nine intervention clusters and 30 813 births in nine control clusters . Main outcome measures The pre-specified outcome was the effect on treatment seeking practice s. Post hoc exploratory analyses assessed morbidity , hospital admission , post-neonatal infant care , and nutritional status outcomes . Interventions The Integrated Management of Neonatal and Childhood Illness intervention included home visits by community health workers , improved case management of sick children , and strengthening of health systems . Outcomes were ascertained through interviews with r and omly selected caregivers : 6204 , 3073 , and 2045 in intervention clusters and 6163 , 3048 , and 2017 in control clusters at ages 29 days , 6 months , and 12 months , respectively . Results In the intervention cluster , treatment was sought more often from an appropriate provider for severe neonatal illness ( risk ratio 1.76 , 95 % confidence interval 1.38 to 2.24 ) , for local neonatal infection ( 4.86 , 3.80 to 6.21 ) , and for diarrhoea at 6 months ( 1.96 , 1.38 to 2.79 ) and 12 months ( 1.22 , 1.06 to 1.42 ) and pneumonia at 6 months ( 2.09 , 1.31 to 3.33 ) and 12 months ( 1.44 , 1.00 to 2.08 ) . Intervention mothers reported fewer episodes of severe neonatal illness ( risk ratio 0.82 , 0.67 to 0.99 ) and lower prevalence of diarrhoea ( 0.71 , 0.60 to 0.83 ) and pneumonia ( 0.73 , 0.52 to 1.04 ) in the two weeks preceding the 6 month interview and of diarrhoea ( 0.63 , 0.49 to 0.80 ) and pneumonia ( 0.60 , 0.46 to 0.78 ) in the two weeks preceding the 12 month interview . Infants in the intervention clusters were more likely to still be exclusively breast fed in the sixth month of life ( risk ratio 3.19 , 2.67 to 3.81 ) . Conclusion Implementation of the Integrated Management of Neonatal and Childhood Illness programme was associated with timely treatment seeking from appropriate providers and reduced morbidity , a likely explanation for the reduction in mortality observed following implementation of the programme in this study . Trial registration Clinical trials NCT00474981 ; ICMR Clinical Trial Registry CTRI/2009/091/000715 To assess the impact on child growth of the nutrition-counseling component of the Integrated Management of Childhood Illnesses ( IMCI ) strategy , a r and omized trial was implemented . All 28 government health centers in a Southern Brazil city were paired according to baseline nutritional indicators . One center from each pair was r and omly selected and its doctors received 20-h training in nutrition counseling . Thirty-three doctors were included and 12 - 13 patients < 18 mo of age from each doctor were recruited . The study included testing the knowledge of doctors , observing consultations and visiting the children at home 8 , 45 and 180 d after the initial consultation . Maternal knowledge , practice s and adherence to nutritional recommendations were assessed , and anthropometric measurements were taken . Day-long dietary intake was evaluated on a sub sample of children . Doctors in the intervention group had better knowledge of child nutrition and improved assessment and counseling practice s. Maternal recall of recommendations was higher in the intervention than in the control group , as was satisfaction with the consultation . Reported use of recommended foods was also increased . Daily fat intake was higher in the intervention than in the control group ; mean daily intakes of energy and zinc also tended to improve . Children 12 mo of age or older had improved weight gain and a positive but nonsignificant improvement in length . Nutrition-counseling training improved doctors ' performances , maternal practice s and the diets and weight gain of children . The r and omized design with blind outcome evaluation strongly supports a causal link . These results should be replicated in other setting Physician behavior and caregiver retention of nutrition advice were examined as potential mediating factors in the success of a nutrition counseling efficacy trial in Pelotas , Brazil , which reduced growth faltering in children 12 - 24 mo old . After pair-matching on socioeconomic status and nutrition indicators , municipal health centers were r and omly assigned to an intervention group , in which physicians were trained with an IMCI-derived ( Integrated Management of Childhood Illness ) nutrition counseling protocol , or to a control group , without continuing education in nutrition . In a sub study of the larger trial , direct observation of consultations , followed by home interviews with mothers , provided data on physician counseling behavior and mothers ' retention of nutrition advice . Trained providers were more likely to engage in nutrition counseling ( P < 0.013 ) and to deliver more extensive advice ( P < 0.02 ) . They also used communication skills design ed to improve rapport and ensure that mothers understood the advice ( P < 0.01 ) . Mothers who received advice from trained providers had high rates of recalling the messages on specific foods ( 95 vs.27 % ; P < 0.01 ) and feeding practice and food preparation recommendations ( 90 vs. 20 % ; P < 0.01 ) , whereas the proportions of the messages recalled on breast-feeding ( 60 % vs. 30 % ) did not differ significantly ( P < 0.20 ) . The training course contained several elements that may explain why intervention group mothers were better able to recall nutrition advice . These include locally appropriate messages , tools for assessing individual problems , and counseling skills BACKGROUND The Integrated Management of Childhood Illness ( IMCI ) strategy is design ed to address major causes of child mortality at the levels of community , health facility , and health system . We assessed the effectiveness of facility-based IMCI in rural Tanzania . METHODS We compared two districts with facility-based IMCI and two neighbouring comparison districts without IMCI , from 1997 to 2002 , in a non-r and omised study . We assessed quality of case-management for children 's illness , drug and vaccine availability , and supervision involving case-management , through a health-facility survey in 2000 . Household surveys were used to assess child-health indicators in 1999 and 2002 . Survival of children was tracked through demographic surveillance over a predefined 2-year period from mid 2000 . Further information on context ual factors was gathered through interviews and record review . The economic cost of health care for children in IMCI and comparison districts was estimated through interviews and record review at national , district , facility , and household levels . FINDINGS During the IMCI phase-in period , mortality rates in children under 5 years old were almost identical in IMCI and comparison districts . Over the next 2 years , the mortality rate was 13 % lower in IMCI than in comparison districts ( 95 % CI -7 to 30 or 5 to 21 , depending on how adjustment is made for district-level clustering ) , with a rate difference of 3.8 fewer deaths per 1000 child-years . Context ual factors , such as use of mosquito nets , all favoured the comparison districts . Costs of children 's health care with IMCI were similar to or lower than those for case-management without IMCI . INTERPRETATION Our findings indicate that facility-based IMCI is good value for money , and support widespread implementation in the context of health-sector reform , basket funding , good facility access , and high utilisation of health facilities Background Poverty , lack of female empowerment , and lack of education are major risk factors for childhood illness worldwide . Microcredit programs , by offering small loans to poor individuals , attempt to address the first two of these risk factors , poverty and gender disparity . They provide clients , usually women , with a means to invest in their businesses and support their families . This study investigates the health effects of also addressing the remaining risk factor , lack of knowledge about important health issues , through r and omization of members of a microcredit organization to receive a health education module based on the World Health Organization 's Integrated Management of Childhood Illness ( IMCI ) community intervention . Methods Baseline data were collected in February 2007 from clients of a microcredit organization in Pucallpa , Peru ( n = 1,855 ) and their children ( n = 598 ) . Loan groups , consisting of 15 to 20 clients , were then r and omly assigned to receive a health education intervention involving eight monthly 30-minute sessions given by the organization 's loan officers at monthly loan group meetings . In February 2008 , follow-up data were collected , and included assessment s of sociodemographic information , knowledge of child health issues , and child health status ( including child height , weight , and blood hemoglobin levels ) . To explore the effects of treatment ( i.e. , participation in the health education sessions ) on the key outcome variables , multivariate regressions were implemented using ordinary least squares . Results Individuals in the IMCI treatment arm demonstrated more knowledge about a variety of issues related to child health , but there were no changes in anthropometric measures or reported child health status . Conclusions Microcredit clients r and omized to an IMCI educational intervention showed greater knowledge about child health , but no differences in child health outcomes compared to controls . These results imply that the intervention did not have sufficient intensity to change behavior , or that microcredit organizations may not be an appropriate setting for the administration of child health educational interventions of this type . Trial Registration This study is registered with Clinical Trials.gov , NCT01047033 Background Pneumonia is a leading cause of death among children under five years of age . The Integrated Management of Childhood Illness strategy can improve the quality of care for pneumonia and other common illnesses in developing countries , but adherence to these guidelines could be improved . We evaluated an intervention in Benin to support health worker adherence to the guidelines after training , focusing on pneumonia case management . Methods We conducted a r and omized trial . After a health facility survey in 1999 to assess health care quality before Integrated Management of Childhood Illness training , health workers received training plus either study supports ( job aids , non-financial incentives and supervision of workers and supervisors ) or " usual " supports . Follow-up surveys were conducted in 2001 , 2002 and 2004 . Outcomes were indicators of health care quality for Integrated Management-defined pneumonia . Further analyses included a graphical pathway analysis and multivariable logistic regression modelling to identify factors influencing case-management quality . Results We observed 301 consultations of children with non-severe pneumonia that were performed by 128 health workers in 88 public and private health facilities . Although outcomes improved in both intervention and control groups , we found no statistically significant difference between groups . However , training proceeded slowly , and low- quality care from untrained health workers diluted intervention effects . Per- protocol analyses suggested that health workers with training plus study supports performed better than those with training plus usual supports ( 20.4 and 19.2 percentage-point improvements for recommended treatment [ p = 0.08 ] and " recommended or adequate " treatment [ p = 0.01 ] , respectively ) . Both groups tended to perform better than untrained health workers . Analyses of treatment errors revealed that incomplete assessment and difficulties processing clinical findings led to missed pneumonia diagnoses , and missed diagnoses led to inadequate treatment . Increased supervision frequency was associated with better care ( odds ratio for recommended treatment = 2.1 [ 95 % confidence interval : 1.1 - 3.9 ] per additional supervisory visit ) . Conclusion Integrated Management of Childhood Illness training was useful , but insufficient , to achieve high- quality pneumonia case management . Our study supports led to additional improvements , although large gaps in performance still remained . A simple graphical pathway analysis can identify specific , common errors that health workers make in the case-management process ; this information could be used to target quality improvement activities , such as supervision ( Clinical Trials.gov number N Output:	Therefore , we do not know whether IMCI impacts exclusive breast feeding . Implementing the integrated management of childhood illness strategy may reduce child mortality , and packages that include interventions for the neonatal period may reduce infant mortality . IMCI may have little or no effect on nutritional status and probably has little or no effect on vaccine coverage . Maternal care seeking behavior may be more appropriate with IMCI , but study results have been mixed , providing evidence of very low certainty about whether IMCI has effects on adherence to exclusive breast feeding . Key messages This review shows that use of the World Health Organization IMCI strategy may led to fewer deaths among children from birth to five years of age . This review showed that use of IMCI : • may lead to fewer deaths among children from birth to five years of age
MS21580	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : The objective of this work was to develop practice guidelines for the management of alcoholic liver disease . Method : A computerized search using the Medline Data Base from 1966–July 1997 was performed with the search headings ; alcohol , alcoholic hepatitis , alcoholic liver disease , liver transplant , diagnosis , epidemiology , human , and English only . All r and omized controlled trials , case-control studies , and meta-analyses were read in depth . A manual search was also done using references from each retrieved report , review articles , editorials , postgraduate course syllabi , and textbooks . In the subsequent review , evidence was evaluated using a hierarchical scale with r and omized , controlled trials given the most importance . Abstract s presented at national meetings were included only when unique data were obtained from those studies The efficacy of methylprednisolone ( 1 g daily or three days ) , which is effective in reversing transplant rejection , was assessed in a r and omised controlled trial of 55 patients with severe acute alcoholic hepatitis , 34 of whom had encephalopathy . The clinical progress , frequency of bleeding and sepsis , and cause of death were similar in the treatment ( 27 patients ) and control groups ( 28 patients ) . There was no significant difference in mortality rate between the two groups : 57 % of the control group and 63 % of the treatment group died during the study . Patients ' survival depended on the presence of absence of the following features : encephalopathy , serum bilirubin concentration more than 340 micromol/l , serum creatinine concentration more than 250 micromol/l , and histological evidence of cirrhosis as well as severe acute alcoholic hepatitis STUDY OBJECTIVE To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe alcoholic hepatitis . DESIGN R and omized , double-blind , placebo-controlled multicenter trial . SETTING Four university teaching hospitals . PATIENTS We enrolled 66 patients with alcoholic hepatitis and either spontaneous hepatic encephalopathy or a discriminant function value greater than 32 , calculated using the formula : 4.6 ( prothrombin time - control time ) + serum bilirubin [ in mumol/L]/17.1 . Fifty-nine patients ( 89 % ) completed the study . Two patients withdrew from the trial . The other 64 patients were hospitalized for the duration of the trial ; however , treatment was discontinued in 5 patients because of potential drug toxicity . INTERVENTIONS Patients were r and omly assigned to receive either methylprednisolone ( 32 mg ) or placebo within 7 days of admission . Treatment was given for 28 days . The doses were then tapered over 2 weeks and discontinued . MEASUREMENTS AND MAIN RESULTS The endpoint of the study was death . Of the 31 recipients of placebo , 11 ( 35 % ) died within 28 days of r and omization compared with 2 ( 6 % ) of the 35 patients given methylprednisolone ( P = 0.006 ) . The 95 % CI for the difference in mortality was 12 % to 70 % . In the patients with spontaneous hepatic encephalopathy at entry , 9 of 19 recipients of placebo died ( 47 % ) compared with 1 ( 7 % ) of the 14 patients given methylprednisolone ( P = 0.02 ) . The 95 % CI for the difference in mortality was 14 % to 66 % . The Cox proportional hazards regression model showed the advantage of methylprednisolone over placebo after adjustment for other potentially important prognostic variables ( P = 0.004 ) . CONCLUSIONS Methylprednisolone therapy decreases short-term mortality in patients with severe alcoholic hepatitis manifested either by spontaneous hepatic encephalopathy or a markedly elevated discriminant function value In a prospect i ve double-blind study , 27 patients with alcoholic hepatitis were r and omized for 6-methylprednisolone ( 12 patients ) or placebo treatment ( 15 patients ) . The mortality was 50 % among steroid treated patients and 47 % in the control group ( P less than .05 ) . The role of liver biopsy feasibility at selection is emphasized since the mortality in this group was 10 % as opposed to 71 % when the procedure was contraindicated ( P less than .01 ) . Complications in the steroid-treated subjects were similar quantitatively and qualitatively to those observed in the control series Steroids are recommended in severe alcohol-induced hepatitis , but some data suggest that artificial nutrition could also be effective . We conducted a r and omized trial comparing the short- and long-term effects of total enteral nutrition or steroids in these patients . A total of 71 patients ( 80 % cirrhotic ) were r and omized to receive 40 mg/d prednisolone ( n = 36 ) or enteral tube feeding ( 2,000 kcal/d ) for 28 days ( n = 35 ) , and were followed for 1 year or until death . Side effects of treatment occurred in 5 patients on steroids and 10 on enteral nutrition ( not significant ) . Eight enterally fed patients were prematurely withdrawn from the trial . Mortality during treatment was similar in both groups ( 9 of 36 vs. 11 of 35 , intention-to-treat ) but occurred earlier with enteral feeding ( median 7 vs. 23 days ; P = .025 ) . Mortality during follow-up was higher with steroids ( 10 of 27 vs. 2 of 24 intention-to-treat ; P = . 04 ) . Seven steroid patients died within the first 1.5 months of follow-up . In contrast to total enteral nutrition ( TEN ) , infections accounted for 9 of 10 follow-up deaths in the steroid group . In conclusion , enteral feeding does not seem to be worse than steroids in the short-term treatment of severe alcohol-induced hepatitis , although death occurs earlier with enteral nutrition . However , steroid therapy is associated with a higher mortality rate in the immediate weeks after treatment , mainly because of infections . A possible synergistic effect of both treatments should be investigated Abstract A prospect i ve , double-blind controlled pilot study in 20 subjects of the efficacy of glucocorticosteroids in the treatment of severe , life-threatening , alcoholic hepatitis failed to demons A cooperative study was conducted to determine the efficacy of 30 days of treatment with either a glucocorticosteroid ( prednisolone ) or an anabolic steroid ( ox and rolone ) in moderate or severe alcoholic hepatitis . One hundred thirty-two patients with moderate disease and 131 with severe disease were r and omly assigned to one of three treatments : prednisolone , ox and rolone , or placebo . During the 30 days , mortality in the groups receiving steroid therapy was not significantly different from mortality in the placebo group . Thirteen per cent of the moderately ill patients and 29 per cent of the severely ill patients died . Although neither steroid improved short-term survival , ox and rolone therapy was associated with a beneficial effect on long-term survival . This was especially true in patients with moderate disease : among those who survived for one or two months after the start of treatment the conditional six-month death rate was 3.5 per cent after ox and rolone and 19 to 20 per cent after placebo ( P = 0.02 ) . No consistent long-term effect was associated with prednisolone therapy Output:	Glucocorticosteroids significantly reduced mortality in the subgroup of trials with patients with Maddrey 's score of at least 32 or hepatic encephalopathy and with low-bias risk . Trial sequential analyses using heterogeneity-adjusted information size demonstrated no significant effect of glucocorticosteroids on mortality . Weighted logistic regression analyses taking prognostic factors at r and omization into consideration found no significant effect of glucocorticosteroids on mortality . CONCLUSIONS The current evidence base of mainly heterogeneous with high bias risk trials does not support the use of glucocorticosteroids in alcoholic hepatitis .
MS21581	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: 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 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 BACKGROUND Simple distribution of clinical practice guidelines to physicians does not change practice behavior . A low-cost , continuous peer review feedback method was used to promote resident physicians ' compliance with nine preventive care guidelines at the ambulatory care clinic at the Marshall University School of Medicine ( Huntington , West Virginia ) . METHODS Preventive care guidelines were distributed and a peer review feedback program was instituted in the resident physician primary care practice . The frequency of resident physician use of nine preventive care services was assessed and compared during three periods : pre guideline ( September 1 , 1993 , to March 1 , 1994 ; 148 patients ) , guideline ( September 1 , 1994 , to March 1 , 1995 ; 148 patients ) , and one-year follow-up ( September 1 , 1995 , to March 1 , 1996 ; 150 patients ) . The patients in the three periods were similar in age , gender , and risk for influenza and pneumococcal infection . RESULTS During the guideline period , resident physicians offered patients four preventive care services-tetanus toxoid immunization , clinical breast examination , Papanicolaou smear testing , and hemoccult testing significantly more often than during the pre guideline period . All services were offered significantly more often during the one-year follow-up period compared with the pre guideline period and as often as in the guideline period . CONCLUSION A low-cost , continuous peer review feedback program significantly and durably improves resident physician compliance with clinical practice guidelines on preventive care services . However , the effectiveness of the poor review feedback method may not generalize to private practice or other setting s. Research on other methods to promote compliance with clinical practice guidelines and to influence physician behavior in general should continue Many studies have tested the efficacy of intervention strategies for improving physicians ' performance of cancer screening tests . Less attention has been paid to the feasibility of strategy implementation . Three important dimensions of feasibility are acceptability to the targeted audience , logistical difficulties , and cost and cost-effectiveness . We assessed the relative feasibility along these dimensions of three intervention strategies shown previously to be efficacious among 62 internal medicine resident physicians . Two strategies , medical record audit with feedback and computerized cancer screening reminders were aim ed at physicians directly , and one , patient education , indirectly through their patients . While all three interventions were acceptable to the physicians , implementation of the audit with feedback intervention was logistically more difficult and more costly than either the cancer screening reminders or patient education interventions . The average cost per additional screening test ( beyond the number that would have been performed without intervention ) was $ 50.40 for audit with feedback , $ 18.19 for cancer screening reminders , and $ 51.20 for patient education . Overall , the cancer screening reminder intervention was the most feasible of the three strategies 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 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 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 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 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 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 Output:	Evidence in these review s indicates that provider assessment and feedback interventions can effectively increase screening by mammography , Pap test , and fecal occult blood test . Evidence was insufficient to determine the effectiveness of provider incentives in increasing use of any of these tests . Specific areas for further research are suggested in this report , including the need for additional research to determine whether provider incentives are effective in increasing use of any of these screening tests , and whether assessment and feedback interventions are effective in increasing other tests for colorectal cancer ( i.e. , flexible sigmoidoscopy , colonoscopy , or double-contrast barium enema )
MS21582	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Alzheimer ’s disease ( AD ) is the most common type of dementia affecting people over 65 years of age . The hallmarks of AD are the extracellular deposits known as amyloid β plaques and the intracellular neurofibrillary tangles , both of which are the principal players involved in synaptic loss and neuronal cell death . Tau protein and Aβ fragment 1–42 have been investigated so far in cerebrospinal fluid as a potential AD biomarkers . However , an urgent need to identify novel biomarkers which will capture disease in the early stages and with better specificity remains . High-throughput proteomic and pathway analysis of hippocampal tissue provides a valuable source of disease-related proteins and biomarker c and i date s , since it represents one of the earliest affected brain regions in AD . Results In this study 2954 proteins were identified ( with at least 2 peptides for 1203 proteins ) from both control and AD brain tissues . Overall , 204 proteins were exclusively detected in AD and 600 proteins in control sample s. Comparing AD and control exclusive proteins with cerebrospinal fluid ( CSF ) literature -based proteome , 40 out of 204 AD related proteins and 106 out of 600 control related proteins were also present in CSF . As most of these proteins were extracellular/secretory origin , we consider them as a potential source of c and i date biomarkers that need to be further studied and verified in CSF sample s. Conclusions Our semiquantitative proteomic analysis provides one of the largest human hippocampal proteome data bases . The lists of AD and control related proteins represent a panel of proteins potentially involved in AD pathogenesis and could also serve as prospect i ve AD diagnostic biomarkers Cognitive dysfunction is common in older persons suffering from a major depression . However , the degree to which this dysfunction is reversible with successful treatment of the depression remains uncertain . The present study examined the effects that treatment ( r and omized double-blind design ) with either an SSRI ( paroxetine ) or a tricyclic antidepressant ( nortriptyline ) had on cognition in older depressed patients . The patients ' performance was compared to that of a group of normal controls of similar age and education . Patients and controls were administered measures of working memory , information-processing speed , episodic memory and attention five times over the course of a 12 week trial . At baseline , the patients performed more poorly than the elderly controls on all cognitive measures . While the patients ' performance did improve over the course of their treatment , the magnitude of this improvement did not exceed that produced in the elderly controls by practice alone . The same pattern of results was evident in both intent-to-treat and responder analyses . Thus , there was no evidence that the depressed patients ' cognitive performance normalized after response to antidepressant therapy . Neither the patients ' age at onset nor their baseline level of cognitive functioning influenced the amount by which their performance improved over the 12 week trial . There was no difference between paroxetine and nortriptyline in the amount of cognitive change associated with treatment . The present results suggest that cognitive dysfunction persists in older depressed patients even after their mood disorder has responded to antidepressant medications Background MicroRNAs ( miRNAs ) mediate posttranscriptional regulation of protein-coding genes by binding to the 3 ' untranslated region of target mRNAs , leading to translational inhibition , mRNA destabilization or degradation , depending on the degree of sequence complementarity . In general , a single miRNA concurrently downregulates hundreds of target mRNAs . Thus , miRNAs play a key role in fine-tuning of diverse cellular functions , such as development , differentiation , proliferation , apoptosis and metabolism . However , it remains to be fully eluci date d whether a set of miRNA target genes regulated by an individual miRNA in the whole human microRNAome generally constitute the biological network of functionally-associated molecules or simply reflect a r and om set of functionally-independent genes . Methods The complete set of human miRNAs was downloaded from miRBase Release 16 . We explored target genes of individual miRNA by using the Diana-microT 3.0 target prediction program , and selected the genes with the miTG score ≧ 20 as the set of highly reliable targets . Then , Entrez Gene IDs of miRNA target genes were uploaded onto KeyMolnet , a tool for analyzing molecular interactions on the comprehensive knowledgebase by the neighboring network- search algorithm . The generated network , compared side by side with human canonical networks of the KeyMolnet library , composed of 430 pathways , 885 diseases , and 208 pathological events , enabled us to identify the canonical network with the most significant relevance to the extracted network . Results Among 1,223 human miRNAs examined , Diana-microT 3.0 predicted reliable targets from 273 miRNAs . Among them , KeyMolnet successfully extracted molecular networks from 232 miRNAs . The most relevant pathway is transcriptional regulation by transcription factors RB/E2F , the disease is adult T cell lymphoma/leukemia , and the pathological event is cancer . Conclusion The predicted targets derived from approximately 20 % of all human miRNAs constructed biologically meaningful molecular networks , supporting the view that a set of miRNA targets regulated by a single miRNA generally constitute the biological network of functionally-associated molecules in human cells OBJECTIVE Knowledge of the relationship between various clinical characteristics and cognitive functioning is advancing , but little is known about the cognitive response to treatment for geriatric depression . The purpose of this study was to examine the cognitive response to treatment for patients with late-life depression . METHOD Subjects included 45 nondemented , elderly depressed patients who achieved remission after 12 weeks of antidepressant treatment and 20 elderly comparison subjects . All subjects were administered a battery of clinical measures , including cognitive screening instruments , before and after treatment . RESULTS As a group , the elderly depressed patients showed a small improvement in overall cognitive functioning after treatment . Among depressed patients with concomitant cognitive impairment at baseline , performance on the Mattis Dementia Rating Scale domains of conceptualization and initiation/perseveration improved significantly relative to those of depressed patients with normal cognition . Despite the improvement following treatment , the overall level of cognitive functioning in the elderly depressed patients with cognitive impairment at baseline remained mildly impaired , especially in the memory and initiation/perseveration domains . CONCLUSIONS Elderly depressed patients with cognitive impairment may experience improvement in specific domains following antidepressant treatment but may not necessarily reach normal levels of performance , particularly in memory and executive functions . This subgroup of late-life depression patients is likely at high risk of developing progressive dementia Output:	CONCLUSION The current results suggest that the maintenance of genomic integrity , proteostasis control , immune-inflammatory regulation , and neurotrophic support are key neurobiologic links between these conditions .
MS21583	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Clinical practice involves measuring quantities for a variety of purpose s , such as aiding diagnosis , predicting future patient outcomes , and serving as endpoints in studies or r and omized trials . Measurements are almost always prone to various sorts of errors , which cause the measured value to differ from the true value ; accordingly , studies investigating measurement error frequently appear in this and other journals . The importance of measurement error depends upon the context in which the measurements in question are to be used . For example , a certain degree of measurement error may be acceptable if measurements are to be used as an outcome in a comparative study such as a clinical trial , but the same measurement errors may be unacceptably large to make measurements usable in individual patient management , such as screening or risk prediction . In the past 20 years many papers have been published advocating how studies of measurement error should be analyzed , with a paper by Bl and and Altman1 being one of the most cited and well known examples . There has been much controversy concerning the choice of parameter to be estimated and reported , and consequently confusion surrounding the meaning and interpretation of results from studies investigating measurement error . In this paper we first distinguish between the general concepts of agreement and reliability to aid research ers in considering which are relevant for their particular application . We then review the statistical methods that can be used to investigate and quantify agreement and reliability , dealing separately with the different types of measurement error study , while emphasizing the largely common techniques that should be used for data analysis . We reiterate that the judgment of whether agreement or reliability are acceptable must be related to the clinical application , and can not be proven by a statistical test . We highlight the fact that reliability depends on the population in which measurements are made , and not just on the measurement errors of the measurement method . We discuss the advantages of method comparison studies making at least two measurements with each measurement method on each subject . A key advantage is that the cause of a correlation between paired differences and means in the so-called Bl and –Altman plot can be determined , in contrast to when only a single measurement is made with each method . Throughout the paper , we try to emphasize that calculated values of agreement and reliability from measurement error studies are estimates of parameters , and as such we should report such estimates with CIs to indicate the uncertainty with which they have been estimated . We restrict our attention to measurements of a continuous quantity ; alternative methods are required for categorical data 2 The interaction between fascicle and tendinous tissues ( TT ) in short-contact drop jumps ( DJ ) with three different drop heights [ low ( Low ) , optimal ( OP ) , and high ( High ) ] was examined with 11 subjects . The ground reaction force ( F(z ) ) and ankle and knee joint angles were measured together with real-time ultrasonography ( fascicle length ) and electromyographic activities of the medial gastrocnemius ( MG ) and vastus lateralis ( VL ) muscles during the movement . With increasing drop height , the braking force and flight time increased from Low to OP ( P < 0.05 ) . In High , the braking force increased but the flight time decreased compared with OP ( P < 0.05 ) . During contact of Low and OP conditions , the length of muscle-tendon unit and TT underwent lengthening before shortening in both MG and VL muscles . However , the two muscles differed in the fascicle behaviors . The MG fascicles behaved isometrically or shortened , and the VL fascicles underwent lengthening before shortening during contact . In High , the TT lengthening in both muscles decreased compared with OP ( P < 0.05 ) . The rapid stretch occurred in the MG fascicles but not in VL fascicles during the braking phase . The elastic recoil ratio decreased in both muscles with increasing the intensity during DJ . These findings demonstrated that TT underwent lengthening before shortening during DJ . However , the efficacy of elastic recoil decreased with increasing the drop intensity . The effective catapult action in TT can be limited by the drop intensity . In addition , the measured muscles behaved differently during DJ , providing evidence that each muscle may have a specific means of fascicle-TT interaction The present study was design ed to examine fascicle-tendon interaction in the synergistic medial gastrocnemius ( MG ) and soleus ( Sol ) muscles during drop jumps ( DJ ) performed from different drop heights ( DH ) . Eight subjects performed unilateral DJ with maximal rebounds on a sledge apparatus from different DH . During the exercises , fascicle lengths ( using ultrasonography ) and electromyographic activities were recorded . The results showed that the fascicles of the MG and Sol muscles behaved differently during the contact phase , but the whole muscle-tendon unit and its tendinous tissue lengthened before shortening in both muscles . The Sol fascicles also lengthened before shortening during the ground contact in all conditions . During the braking phase , the Sol activation increased with increasing DH . However , the amplitude of Sol fascicle lengthening was not dependent on DH during the same phase . In the MG muscle , the fascicles primarily shortened during the braking phase in the lower DH condition . However , in the higher DH conditions , the MG fascicles either behaved isometrically or were lengthened during the braking phase . These results suggest that the fascicles of synergistic muscles ( MG and Sol ) can behave differently during DJ and that , with increasing DH , there may be specific length change patterns of the fascicles of MG but not of Sol Plantar flexor series elasticity can be used to dissociate muscle-fascicle and muscle-tendon behavior and thus afferent feedback during human walking . We used electromyography ( EMG ) and high-speed ultrasonography concomitantly to monitor muscle activity and muscle fascicle behavior in 19 healthy volunteers as they walked across a platform . On r and om trials , the platform was dropped ( 8 cm , 0.9 g acceleration ) or held at a small inclination ( up to + /-3 degrees in the parasagittal plane ) with respect to level ground . Dropping the platform in the mid and late phases of stance produced a depression in the soleus muscle activity with an onset latency of about 50 ms . The reduction in ground reaction force also unloaded the plantar flexor muscles . The soleus muscle fascicles shortened with a minimum delay of 14 ms . Small variations in platform inclination produced significant changes in triceps surae muscle activity ; EMG increased when stepping on an inclined surface and decreased when stepping on a declined surface . This sensory modulation of the locomotor output was concomitant with changes in triceps surae muscle fascicle and gastrocnemius tendon length . Assuming that afferent activity correlates to these mechanical changes , our results indicate that within-step sensory feedback from the plantar flexor muscles automatically adjusts muscle activity to compensate for small ground irregularities . The delayed onset of muscle fascicle movement after dropping the platform indicates that at least the initial part of the soleus depression is more likely mediated by a decrease in force feedback than length-sensitive feedback , indicating that force feedback contributes to the locomotor activity in human walking Fascicle curvature of human medial gastrocnemius muscle ( MG ) was determined in vivo by ultrasonography during isometric contractions at three ( distal , central , and proximal ) locations ( n = 7 ) and at three ankle angles ( n = 7 ) . The curvature significantly ( P < 0.05 ) increased from rest to maximum voluntary contraction ( MVC ) ( 0.4 - 5.2 m(-1 ) ) . In addition , the curvature at MVC became larger in the order dorsiflexed , neutral , plantar flexed ( P < 0.05 ) . Thus both contraction levels and muscle length affected the curvature . Intramuscular differences in neither the curvature nor the fascicle length were found . The direction of curving was consistent along the muscle : fascicles were concave in the proximal side . Fascicle length estimated from the pennation angle and muscle thickness , under the assumption that the fascicle was straight , was underestimated by ~6 % . In addition , the curvature was significantly correlated to pennation angle and muscle thickness . These findings are particularly important for underst and ing the mechanical functions of human skeletal muscle in vivo Architectural properties of the triceps surae muscles were determined in vivo for six men . The ankle was positioned at 15 degrees dorsiflexion ( -15 degrees ) and 0 , 15 , and 30 degrees plantar flexion , with the knee set at 0 , 45 , and 90 degrees . At each position , longitudinal ultrasonic images of the medial ( MG ) and lateral ( LG ) gastrocnemius and soleus ( Sol ) muscles were obtained while the subject was relaxed ( passive ) and performed maximal isometric plantar flexion ( active ) , from which fascicle lengths and angles with respect to the aponeuroses were determined . In the passive condition , fascicle lengths changed from 59 , 65 , and 43 mm ( knee , 0 degrees ; ankle , -15 degrees ) to 32 , 41 , and 30 mm ( knee , 90 degrees ankle , 30 degrees ) for MG , LG , and Sol , respectively . Fascicle shortening by contraction was more pronounced at longer fascicle lengths . MG had greatest fascicle angles , ranging from 22 to 67 degrees , and was in a very disadvantageous condition when the knee was flexed at 90 degrees , irrespective of ankle positions . Different lengths and angles of fascicles , and their changes by contraction , might be related to differences in force-producing capabilities of the muscles and elastic characteristics of tendons and aponeuroses Abstract Purpose The present study examined the effects of repetitive hopping training on muscle activation profiles and fascicle – tendon interaction in the elderly . Methods 20 physically active elderly men were r and omly assigned for training ( TG ) and control groups ( CG ) . TG performed supervised bilateral short contact hopping training with progressively increasing training volume . Measurements were performed before the training period ( BEF ) as well as after 2 weeks ( 2 W ) and 11 weeks ( 11 W ) of training . During measurements , the gastrocnemius medialis – muscle ( GaM ) fascicle and its outer Achilles tendon length changes during hopping were examined by ultrasonography together with electromyographic ( EMG ) activities of calf muscles , kinematics , and kinetics . Results At 2 W , the ankle joint stiffness was increased by 21.0 ± 19.3 % and contact time decreased by 9.4 ± 7.8 % in TG . Thereafter , from 2–11 W the jumping height increased 56.2 ± 18.1 % in TG . Simultaneously , tendon forces increased 24.3 ± 19.0 % but tendon stiffness did not change . GaM fascicles shifted to shorter operating lengths after training without any changes in their length modifications during the contact phase of hopping . Normalized EMG amplitudes during hopping did not change with training . Conclusions The present study shows that 11 W of hopping training improves the performance of physically active elderly men . This improvement is achieved with shorter GaM operating lengths and , therefore , increased fascicle stiffness and improved tendon utilization after training . Based on these results , hopping training could be recommended for healthy fit elderly to retain and improve rapid force production capacity Purpose Hamstring strain injury is a frequent and serious injury in competitive and recreational sports . While Nordic hamstring ( NH ) eccentric strength training is an effective hamstring injury-prevention method , the protective mechanism of this exercise is not understood . Strength training increases muscle strength , but also alters muscle architecture and stiffness ; all three factors may be associated with reducing muscle injuries . The purpose of this study was to examine the effects of NH eccentric strength training on hamstring muscle architecture , stiffness , and strength . Methods Twenty healthy participants were r and omly assigned to an eccentric training group or control group . Control participants performed static stretching , while experimental participants performed static stretching and NH training for 6 weeks . Pre- and post-intervention measurements included : hamstring muscle architecture and stiffness using ultrasound imaging and elastography , and maximal hamstring strength measured on a dynamometer . Results The experimental group , but not the control group , increased volume ( 131.5 vs. 145.2 cm3 , p < 0.001 ) and physiological cross-sectional area ( 16.1 vs. 18.1 cm2 , p = 0.032 ) . There were no significant changes to muscle fascicle length , stiffness , or eccentric hamstring strength . Conclusions The NH intervention was an effective training method for muscle hypertrophy , but , contrary to common literature findings for other modes of eccentric training , did not increase fascicle length . The data suggest that the mechanism behind NH eccentric strength training mitigating hamstring injury risk could be increasing volume rather than increasing muscle length . Future research is , therefore , warranted to determine if muscle hypertrophy induced by NH training lowers future hamstring strain injury risk Six men performed a single ankle plantar flexion exercise in the supine position with the maximal effort with counter movement ( CM , plantar flexion preceded by dorsiflexion ) and without counter movement ( NoCM , plantar flexion only ) produced by a sliding table that controlled applied load to the ankle ( 40 % of the maximal voluntary force ) . The reaction force at the foot and ankle joint angle were measured using a force plate and a goniometer , respectively . From real-time ultrasonography of the gastrocnemius medialis muscle during the movement , the fascicle length was determined . The estimated peak force , average power , and work at the Achilles ' tendon during the plantar flexion phase in CM were significantly greater than those in NoCM . In CM , in the dorsiflexion phase , fascicle length initially increased with little electromyographic activity , then remained constant while the whole muscle-tendon unit lengthened , before decreasing in the final plantar flexion phase . In NoCM , fascicle length decreased throughout the movement and the fascicle length at the onset of movement was longer than that of the corresponding phase in CM . It was concluded that during CM muscle fibres optimally work almost isometrically , by leaving the task of storing and releasing elastic energy for enhancing exercise performance to the tendon Muscle imaging is a promising field of research to underst and the biological and bioelectrical characteristics of muscles through the observation of muscle architectural Output:	B-mode ultrasound is a reliable method to quantify fascicle architecture during movement . Additionally , computational approaches can provide a reliable and valid estimation of fascicle architecture
MS21584	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose : Sorafenib , a multikinase inhibitor targeting Raf and VEGFR , has shown activity in unselected patients with non – small-cell lung cancer ( NSCLC ) . At present there are no vali date d biomarkers indicative of sorafenib activity . Experimental Design : Patients received sorafenib 400 mg BID daily to determine activity and tolerability and to measure its biological effects . KRAS mutation status ( N = 34 ) , angiogenesis markers ( VEGF , bFGF , FLT-1 , PLGF-1 ) and imaging with DCE-MRI ( dynamic contrast enhanced MRI ) to determine early changes in tumor vascular characteristics were evaluated . Three parameters Ktrans , Kep , and Ve were measured by DCE-MRI at baseline and day 14 of cycle 1 . Cytokine analysis was done on days 0 , 14 , 28 , and 54 . Results : Thirty-seven patients with previously treated stage IV NSCLC were enrolled in this single-center phase II trial . In 34 evaluable patients , 2 had partial responses and 20 had stable disease for 3 to 17 months , a disease control rate of 65 % . The median progression-free survival ( PFS ) was 3.4 months , and median overall survival ( OS ) was 11.6 months . Toxicity was consistent with the known side effects of sorafenib . KRAS ( 32 % ) and EGFR mutations ( 22 % ) showed no correlation with response , PFS , or OS . Kep , was significant in predicting an improvement in OS ( P = 0.035 ) and PFS ( P = 0.029 ) . Cytokine analysis demonstrated an improved OS for bFGF day 0 ( < 6 vs. > 6 pg/mL ; P = 0.042 ) , whereas a PFS benefit was seen with bFGF at day 28 ( < 6 vs. > 6 ; P = 0.028 ) . Conclusions : KRAS and EGFR mutational status showed no correlation with response , PFS , or OS . Radiologic and cytokine changes may act as biomarkers indicative of early angiogenesis inhibition . Clin Cancer Res ; 17(5 ) ; 1190–9 . © 2011 AACR Introduction : Avastin Biomarkers In lunG And 3D Innovative anaLysis ( ABIGAIL ) , which is a phase II , open-label , r and omized study , investigated correlations between biomarkers and best overall response to bevacizumab plus platinum-doublet chemotherapy for patients with advanced/recurrent non – small-cell lung cancer . Methods : Patients received bevacizumab ( 7.5 or 15 mg/kg , 3-weekly until disease progression/unacceptable toxicity ) plus carboplatin/gemcitabine or carboplatin/paclitaxel ( maximum six cycles ) . Plasma sample s ( baseline/throughout treatment ) were analyzed for vascular endothelial growth factor (VEGF)-A ( baseline only ) , VEGF receptors ( VEGFR-1/VEGFR-2 ) , basic fibroblast growth factor , E-selectin , intercellular adhesion molecule-1 , and placental growth factor ( baseline only ) . Tumor sample s ( primary specimen ) were analyzed for VEGF-A , VEGFR-1/VEGFR-2 , neuropilin ( NRP ) , and CD31 . Response was evaluated at baseline and every 6 weeks ( Response Evaluation Criteria in Solid Tumors ) . Results : Patients were r and omized to receive chemotherapy plus 7.5 mg/kg ( n = 154 ) or 15 mg/kg ( n = 149 ) bevacizumab . For the primary analysis , none of the baseline plasma biomarkers correlated with best overall response . Exploratory analyses showed that low VEGF-A levels were associated with longer progression-free survival ( 7.4 versus 6.1 months ; hazard ratio , 1.57 ; 95 % confidence intervals , 1.17 to 2.09 ; p = 0.002 ) and overall survival ( 19.8 versus 11.1 months ; hazard ratio , 1.57 ; 95 % confidence interval , 1.15–2.13 ; p = 0.004 ) compared with these in high baseline plasma VEGF-A levels . No plasma biomarkers changed significantly over time . No significant correlations were observed between tumor biomarkers and clinical outcomes . No new safety signals were observed . Conclusion : Baseline and /or dynamic changes in plasma basic fibroblast growth factor , E-selectin , intercellular adhesion molecule-1 , placental growth factor , VEGFR-1 and VEGFR-2 , and tumor biomarkers did not correlate statistically with treatment outcomes for bevacizumab plus chemotherapy . Only baseline plasma VEGF-A was significantly correlated with progression-free survival/overall survival PURPOSE To investigate the efficacy and safety of bevacizumab plus cisplatin and etoposide in patients with extensive-stage disease , small-cell lung cancer ( ED-SCLC ) . PATIENTS AND METHODS In this phase II trial , 63 patients were treated with bevacizumab 15 mg/kg plus cisplatin 60 mg/m(2 ) and etoposide 120 mg/m(2 ) , which was followed by bevacizumab alone until death or disease progression occurred . The primary end point was the proportion of patients alive at 6 months without disease progression ( ie , progression-free survival [ PFS ] ) . Secondary end points included overall survival ( OS ) , objective response rate , and toxicity . Correlative studies were performed to explore the relationship between baseline and changes in plasma vascular endothelial growth factor ( VEGF ) , soluble cell adhesion molecules ( ie , vascular cell adhesion molecule [ VCAM ] , intercellular cell adhesion molecule [ ICAM ] , and E-selectin ) and basic fibroblast growth factor and outcome . RESULTS The 6-month PFS was 30.2 % , the median PFS was 4.7 months , and OS was 10.9 months . The response rate was 63.5 % . The most common adverse event was neutropenia ( 57.8 % ) . Only one patient had grade 3 pulmonary hemorrhage . Patients who had high baseline VCAM had a higher risk of progression or death compared with those who had low baseline VCAM levels . No relationships between outcome and any other biomarkers were seen . CONCLUSION The addition of bevacizumab to cisplatin and etoposide in patients with ED-SCLC results in improved PFS and OS relative to historical controls who received this chemotherapy regimen without bevacizumab . This regimen appears to be well tolerated and has minimal increase in toxicities compared with chemotherapy alone . Baseline VCAM levels predicted survival , but no other relationships among treatment , biomarkers , and outcome were identified BACKGROUND The formation of new microvessels from the existing vascular bed is known as angiogenesis and is normally under the tight regulatory control of angiogenic factors . This control is lost in malignant tumours . Previous studies have correlated increased microvessel density with poor prognosis in patients with primary lung cancer . MATERIAL S AND METHODS Our group measured levels of vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) in sera from 68 patients with non-small cell lung cancer ( NSCLC ) and compared elevated levels of VEGF and bFGF with clinical outcome . Serum basic FGF and VEGF were measured using commercially available enzyme- linked immunosorbent assays ( R & D Systems Inc. , Minneapolis , MN USA ) . RESULTS In 26/68 ( 38 % ) patients we found that elevated circulating levels of bFGF and in 27/68 ( 39 % ) serum sample s levels of VEGF were elevated . Elevated bFGF values in sera was a statistically significant good prognostic factor , p- value = 0.048 , when adjusted to stage and there was a trend in that patients with elevated levels of bFGF had a higher fraction of adenocarcinomas compared with squamous epithelial carcinomas ( chi 2 = 2.0 ) . No significant correlations could be demonstrated when elevated levels of VEGF in serum was present . Elevated levels of both VEGF and bFGF was present in 45 % of the patients . CONCLUSIONS We found that elevated levels of bFGF is a good prognostic factor when measured in sera from NSCLC patients . As this result disagrees with earlier studies on other malignancies the results from our study needs to be further investigated in a prospect i ve study Basic fibroblast growth factor ( bFGF ) is a secreted multifunctional cytokine and a potent stimulator of angiogenesis . We measured bFGF concentrations from serum sample s taken from 103 patients with small cell lung cancer at the time of diagnosis . Serum concentration of bFGF ( S-bFGF ) ranged from undetectable to 54 pg/ml ( median , 6 pg/ml ) . S-bFGF was not associated with age , sex , performance status , or stage . A high pretreatment S-bFGF was associated with poor overall survival . The 1- and 2-year survival rates of the patients within the highest quartile of S-bFGF ( > or=17 pg/ml ) were only 26 % and 11 % , respectively , in contrast to the 49 % and 20 % 1- and 2-year survival rates of those patients with S-bFGF < 17 pg/ml ( P = 0.013 ) . The 1- and 2-year survival rates of the patients with extensive-stage disease were 33 % and 10 % , respectively ( P = 0.0091 ) . Interestingly , S-bFGF provided additional prognostic information to the stage because the 1- and 2-year survival rates of patients with extensive-stage disease and a high S-bFGF ( > or=17 pg/ml ) were as low as 16 % and 5 % , respectively ( P = 0.0026 ) . Similarly , in the multivariate model of survival analysis , patients with both extensive-stage disease and a high S-bFGF ( > or=17 pg/ml ) were found to have a particularly poor prognosis ( relative risk of death , 2.1 ; 95 % confidence interval , 1.2 - 3.6 ; P = 0.0057 ) . We conclude that a high S-bFGF at diagnosis is associated with poor outcome in small cell lung cancer , possibly reflecting active angiogenesis and rapid tumor growth , and may complement prognostic information obtained by staging Background : E4599 was a phase II/phase III trial , in which 878 patients with advanced non – small cell lung cancer were r and omized to carboplatin + paclitaxel ( PC arm ) or PC + bevacizumab ( BPC arm ) . Survival and progression-free survival were superior on the BPC arm . The rationale for markers used in this correlative study was based on elevated vascular endothelial growth factor ( VEGF ) , basic fibroblast growth factor ( bFGF ) , soluble intercellular adhesion molecule ( ICAM ) and E-selectin in a variety of malignances and changes in response to endothelial cell apoptosis . Material s and Methods : Prospect i ve correlates included measurements of pretreatment plasma VEGF , as well as pretreatment and week 7 , bFGF , ICAM , and E-selectin . Low and high levels were defined as less than or equal to or more than the median . Results : E-selectin ( P < 0.0001 ) showed a decrease and bFGF showed an increase ( P = 0.004 ) from baseline at week 7 , which were similar in both arms . Baseline ICAM showed significant associations with response and survival in both groups . Patients with low baseline ICAM had a higher response rate ( 32 % versus 14 % ; P = 0.02 ) , better overall survival ( P = 0.00005 ) , and better 1-year survival ( 65 % versus 25 % ) than those with high ICAM , respectively , regardless of treatment arm . Patients with high VEGF levels were more likely to respond to BPC compared with PC , but this was not predictive of survival . The results also suggest a benefit from bevacizumab for patients with low baseline ICAM levels ( 53 % reduction in the progression-free survival hazard rate ) . Conclusions : In this study , baseline ICAM levels were prognostic for survival and predictive of response to chemotherapy with or without bevacizumab . VEGF levels were predictive of response to bevacizumab but not survival Output:	There was no significant impact of bFGF expression on survival in advanced NSCLC . This meta- analysis showed that bFGF overexpression is a potential indicator of worse prognosis for patients with operable NSCLC and SCLC , but is not associated with outcome in advanced NSCLC . The data suggests that high bFGF expression is highly related to poor prognosis . Nevertheless , more high- quality studies should be performed in order to provide additional evidence for the prognostic value of bFGF in lung cancer
MS21585	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To examine antidepressant use before and after the diagnosis of diabetes . RESEARCH DESIGN AND METHODS This study was a longitudinal analysis of diabetic and nondiabetic groups selected from a prospect i ve cohort study of 151,618 men and women in Finl and ( the Finnish Public Sector Study , 1995–2005 ) . We analyzed the use of antidepressants in those 493 individuals who developed type 2 diabetes and their 2,450 matched nondiabetic control subjects for each year during a period covering 4 years before and 4 years after the diagnosis . For comparison , we undertook a corresponding analysis on 748 individuals who developed cancer and their 3,730 matched control subjects . RESULTS In multilevel longitudinal models , the odds ratio for antidepressant use in those who developed diabetes was 2.00 ( 95 % CI 1.57–2.55 ) times greater than that in nondiabetic subjects . The relative difference in antidepressant use between these groups was similar before and after the diabetes diagnosis except for a temporary peak in antidepressant use at the year of the diagnosis ( OR 2.66 [ 95 % CI 1.94–3.65 ] ) . In incident cancer case subjects , antidepressant use substantially increased after the cancer diagnosis , demonstrating that our analysis was sensitive for detecting long-term changes in antidepressant trajectories when they existed . CONCLUSIONS Awareness of the diagnosis of type 2 diabetes may temporarily increase the risk of depressive symptoms . Further research is needed to determine whether more prevalent use of antidepressants noted before the diagnosis of diabetes relates to effects of depression , side effects of antidepressant use , or a common causal pathway for depression and diabetes It has been hypothesized that coverage of diabetes-specific issues ( e.g. coping with complications , incapacity , pain ) during psychotherapy may optimize the likelihood of treatment success for depression in patients with diabetes . However , it is still unclear how often depression is confounded by diabetes-specific emotional problems . We aim to determine the levels of diabetes-specific emotional problems in diabetic individuals with high versus low levels of depression in a sample of 539 out patients with diabetes ( 202 Dutch , 185 Croatian and 152 English ) . Subjects completed the Center for Epidemiological Studies Depression and the Problem Areas in Diabetes scales . Percentages of patients with high depression scores were : 39 and 34 % ( Croatian men and women ) , 19 and 21 % ( Dutch men and women ) , 19 and 39 % ( English men and women ) . Moreover , 79 % ( Croatian ) , 47 % ( Dutch ) and 41 % ( English ) of the patients with a severe depression score reported to have four or more serious diabetes-specific emotional problems . For patients with low depression scores , these percentages were : 29 % ( Croatian ) , 11 % ( Dutch ) and 1 % ( English ) . Serious diabetes-specific emotional problems are particularly prevalent in depressed diabetes patients . R and omized controlled trials are warranted to test whether coverage of diabetes-specific issues during psychotherapy can further improve the treatment of depression in diabetes Objective : To investigate the association between diabetes and impaired fasting glucose ( IFG ) and cognition and risk of developing both dementia and mild cognitive impairment ( MCI ) in older women . Methods : The authors analyzed data from a 4-year r and omized trial of raloxifene among 7,027 osteoporotic postmenopausal women ( mean age , 66.3 years ) at 178 sites . Diabetes was defined by history , fasting blood glucose ≥7.0 mmol/L ( ≥126 mg/dL ) , or use of hypoglycemic agents ; IFG was defined as fasting glucose < 7.0 mmol/L but > 6.11 mmol/L ( 110 mg/dL ) ; all others were considered to have normal glucose ( NG ) . The main outcome was baseline and 4-year change on five st and ardized cognitive tests ( z scores with lower scores indicating worse performance ) and risk of developing clinical ly significant impairment ( dementia , mild cognitive impairment , or very low cognitive score ) . Results : A total of 267 ( 3.8 % ) women had diabetes and 297 ( 4.2 % ) had IFG . Women with IFG had worse baseline cognitive scores compared to women with NG but better scores than diabetics ( age-adjusted composite z score based on five tests : NG 0.40 , 95 % CI 0.30 to 0.49 ; IFG 0.14 , 95 % CI −0.36 to 0.64 ; diabetics −0.78 , 95 % CI −1.23 to −0.33 ; p < 0.001 ) . There was greater 4-year decline among diabetics ( age and treatment-adjusted composite z score : NG −0.05 , 95 % CI −0.16 to 0.05 ; IFG 0.11 , 95 % CI −0.53 to 0.75 ; diabetics −1.00 , 95 % CI −1.50 to −0.50 ; p = 0.001 ) . Further adjustment for education , race , and depression led to similar results . Risk of developing cognitive impairment among women with IFG or diabetes was increased by almost twofold ( age and treatment-adjusted OR = 1.64 ; 95 % CI 1.03 to 2.61 for IFG ; OR = 1.79 ; 95 % CI 1.14 to 2.81 for diabetics ) . Conclusions : Diabetic as well as pre-diabetic women have impaired cognitive performance and greater risk of developing cognitive impairment Output:	Results of this meta- analysis show that the risk of depression is similar for NGM , IGM , and UDD subjects . PDD subjects have an increased risk of depression relative to IGM and UDD subjects
MS21586	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Lactation is associated with improved glucose and insulin homeostasis , independent of weight change . OBJECTIVE To evaluate the association between lactation history and incidence of type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve observational cohort study of 83,585 parous women in the Nurses ' Health Study ( NHS ) and retrospective observational cohort study of 73,418 parous women in the Nurses ' Health Study II ( NHS II ) . MAIN OUTCOME MEASURE Incident cases of type 2 diabetes mellitus . RESULTS In the NHS , 5145 cases of type 2 diabetes were diagnosed during 1,239,709 person-years of follow-up between 1986 and 2002 , and in the NHS II , 1132 cases were diagnosed during 778,876 person-years of follow-up between 1989 and 2001 . Among parous women , increasing duration of lactation was associated with a reduced risk of type 2 diabetes . For each additional year of lactation , women with a birth in the prior 15 years had a decrease in the risk of diabetes of 15 % ( 95 % confidence interval , 1%-27 % ) among NHS participants and of 14 % ( 95 % confidence interval , 7%-21 % ) among NHS II participants , controlling for current body mass index and other relevant risk factors for type 2 diabetes . CONCLUSIONS Longer duration of breastfeeding was associated with reduced incidence of type 2 diabetes in 2 large US cohorts of women . Lactation may reduce risk of type 2 diabetes in young and middle-aged women by improving glucose homeostasis The incidence of breast cancer among Japanese women is substantially increasing . This population -based prospect i ve cohort study in Japan evaluated the associations of reproductive factors and exogenous female hormone use with breast cancer risk , both overall and separately among premenopausal and postmenopausal women . A total of 24,064 women aged 40–64 were followed from 1990 to 2003 . During 309,424 person-years of follow-up , 285 breast cancer cases were documented . In overall evaluation , nulliparity was significantly associated with an increased risk of breast cancer . There was a significant decrease in risk with increasing parity number among parous women ( trend P = 0.008 ) . No association was observed between age at menarche or age at first birth and breast cancer risk . Neither oral contraceptive ( OC ) use nor the use of exogenous female hormones other than OC was associated with breast cancer risk . The evaluation according to menopausal status revealed that nulliparity and parity number were significantly related to breast cancer risk only among postmenopausal women . Later age at natural menopause was associated with an increased risk of breast cancer among postmenopausal women ( trend P = 0.02 ) . Our findings suggest that parity number and age at menopause have great effects on breast cancer risk among Japanese women BACKGROUND Breast cancer has been increased in South East Asia countries , but there are limited data for breast cancer risk factors in these countries . To clarify the risk for breast cancer among the Malaysian women , a matched case-control study was conducted . METHOD Between October 2009 and April 2010 , a survey was prospect ively conducted among women admitted to clinics of Penang General Hospital for examination and /or treatment by using a question naire . Therefore , characteristics of patients diagnosed with breast cancer ( n=150 ) were compared with control cases ( n=150 ) admitted to hospital for non-neoplastic , non-hormone related diseases . RESULTS Family history of a distant relative with breast cancer ( OR=2.84 ) , history of first-degree relatives with breast cancer ( OR=2.95 ) , history of benign breast disease ( OR=2.43 ) , menstrual irregularity ( OR=4.24 ) , and use of oral contraceptive pills ( OCP ) ( OR=2.15 ) were found to be significant risk factors for breast cancer in our population . Furthermore , education more than 11 years ( OR=0.40 ) , breastfeeding ( OR=0.50 ) , being employed ( OR=0.45 ) and practicing low fat diet ( OR=0.53 ) were strongly protective against breast cancer development . CONCLUSION The results emphasize the importance of conducting a series of awareness campaigns that highlights the protective role of longer breastfeeding period against breast cancer and the negative relationships between OCP use and high fat diet with this disease A hospital-based case-control study of ovarian cancer was conducted in London and Oxford between October 1978 and February 1983 . Menstrual characteristics , reproductive and contraceptive history and history of exposure to various environmental factors were compared between 235 women with histologically diagnosed epithelial ovarian cancer and 451 controls . High gravidity , hysterectomy , female sterilisation and oral contraceptive use were associated with a reduced risk of ovarian cancer . Infertility and late age at menopause were associated with an increase in risk . While these factors were related , they were each found to be independently associated with ovarian cancer risk after adjusting for the effect of the other factors Background Breast cancer has been increased in developing countries , but there are limited data for breast cancer risk factors in these countries . To clarify the risk for breast cancer among the Turkish women , an university hospital based nested case-control study was conducted . Methods Between January 2000 and December 2006 , a survey was prospect ively conducted among women admitted to clinics of Istanbul Medical Faculty for examination and /or treatment by using a question naire . Therefore , characteristics of patients diagnosed with breast cancer ( n = 1492 ) were compared with control cases ( n = 2167 ) admitted to hospital for non-neoplastic , non-hormone related diseases . Results Breast cancer risk was found to be increased in women with age ( ≥ 50 ) [ 95 % confidence interval ( CI ) 2.42–3.18 ] , induced abortion ( 95 % CI 1.13–1.53 ) , age at first birth ( ≥ 35 ) ( 95 % CI 1.62–5.77 ) , body mass index ( BMI ≥ 25 ) ( 95 % CI 1.27–1.68 ) , and a positive family history ( 95 % CI 1.11–1.92 ) . However , decreased breast cancer risk was associated with the duration of education ( ≥ 13 years ) ( 95 % CI 0.62–0.81 ) , presence of spontaneous abortion ( 95 % CI 0.60–0.85 ) , smoking ( 95 % CI 0.61–0.85 ) , breast feeding ( 95 % CI 0.11–0.27 ) , nulliparity ( 95 % CI 0.92–0.98 ) , hormone replacement therapy ( HRT ) ( 95 % CI 0.26–0.47 ) , and oral contraceptive use ( 95 % CI 0.50–0.69 ) . On multivariable logistic regression analysis , age ( ≥ 50 ) years ( OR 2.61 , 95 % CI 2.20–3.11 ) , induced abortion ( OR 1.66 , 95 % CI 1.38–1.99 ) , and oral contraceptive use ( OR 0.60 , 95 % CI 0.48–0.74 ) were found to be associated with breast cancer risk as statistically significant independent factors . Conclusion These findings suggest that age and induced abortion were found to be significantly associated with increased breast cancer risk whereas oral contraceptive use was observed to be associated with decreased breast cancer risk among Turkish women in Istanbul BACKGROUND Findings from observational studies suggest an inverse association between lactation and premenopausal breast cancer risk , but results are inconsistent , and data from large prospect i ve cohort studies are lacking . METHODS We used information from 60,075 parous women participating in the prospect i ve cohort study of the Nurses ' Health Study II from 1997 to 2005 . Our primary outcome was incident premenopausal breast cancer . RESULTS We ascertained 608 incident cases of premenopausal breast cancer during 357,556 person-years of follow-up . Women who had ever breastfed had a covariate-adjusted hazard ratio ( HR ) of 0.75 ( 95 % confidence interval [ CI ] , 0.56 - 1.00 ) for premenopausal breast cancer compared with women who had never breastfed . No linear trend was found with duration of total lactation ( P = .95 ) , exclusive lactation ( P = .74 ) , or lactation amenorrhea ( P = .88 ) . The association between lactation and premenopausal breast cancer was modified by family history of breast cancer ( P value for interaction = .03 ) . Among women with a first-degree relative with breast cancer , those who had ever breastfed had a covariate-adjusted HR of 0.41 ( 95 % CI , 0.22 - 0.75 ) for premenopausal breast cancer compared with women who had never breastfed , whereas no association was observed among women without a family history of breast cancer . CONCLUSION In this large , prospect i ve cohort study of parous premenopausal women , having ever breastfed was inversely associated with incidence of breast cancer among women with a family history of breast cancer Lactational amenorrhea ( LA ) is associated with postpartum infertility and is known to be related to breast-feeding frequency and duration , but the exact role of complementary feeding of the infant has not been clearly defined . Data on LA were collected during and after a 2-mo intervention trial in which low-income Honduran women who had breast-fed fully for 4 mo were r and omly assigned to one of three groups : continued full breast-feeding until 6 mo ( FBF , n = 50 ) , introduction of complementary foods at 4 mo with ad libitum breast-feeding from 4 to 6 mo ( SF , n = 47 ) , or introduction of complementary foods at 4 mo with maintenance of baseline breast-feeding frequency from 4 to 6 mo ( SF-M , n = 44 ) . Women were followed up until the infant was 12 mo of age , or later if menses had not occurred by then . All but six of the women continued to breast-feed for > or = 12 mo . With the exclusion of those whose menses returned before 18 wk postpartum ( which could not have been due to the intervention ) , the proportion of women who were amenorrheic at 6 mo was 64.5 % in the SF group , 80.0 % in the FBF group , and 85.7 % in the SF-M group ( chi-square test = 4.13 , P = 0.02 ; one-tailed test with the latter two groups combined ) . The total duration of LA did not differ significantly among groups . The most significant determinant of LA was time spent breast-feeding ( min/d ) , which was in turn negatively associated ( P = 0.06 ) with the infant 's energy intake from complementary foods in regression analyses . These results indicate that there is a significant effect of introducing foods at 4 mo on the likelihood of amenorrhea at 6 mo postpartum , but not thereafter , and that this effect is not seen in mothers who maintain breast-feeding frequency The aim of this study was to evaluate the risk factors for invasive primary epithelial ovarian cancer among Japanese women . In 1990 - 1994 , 45,748 women aged 40 - 69 years were enrolled in the Japan Public Health Center-based Prospect i ve Study cohort . Only 86 epithelial ovarian cancer cases were diagnosed during follow-up through 2008 , reflecting the low ovarian cancer incidence rates in Japan . Cox proportional hazard models were used to estimate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) according to the exposure of interest . The median age at epithelial ovarian cancer diagnosis was 59 years , with a median follow-up before diagnosis of 7.6 years . There were no statistically significant associations for age at menarche or first birth , breastfeeding , use of exogenous hormones , menopausal status at cohort enrollment , height , body mass index , smoking status , second-h and smoke , alcohol consumption , physical activity and family history of cancer in a first-degree relative . The linear decrease in HR associated with each additional birth was 0.75 ( 95 % CI 0.56 - 0.99 ) . Among women who usually slept > 7 h per day , an HR of 0.4 ( 95 % CI 0.2 - 0.9 ) emerged compared to those who slept < 6 h. This study did not confirm risk factors for epithelial ovarian cancer among Japanese women that have been reported in studies carried out elsewhere . Usual sleep duration of > 7 h per day was inversely associated with epithelial ovarian cancer risk , which is a novel finding that needs to be confirmed in other studies Borderline ovarian tumors possess many of the same morphological features as their malignant counterparts , but they do not destructively invade the ovarian stroma , and the women in whom they develop generally have a favorable prognosis . Female residents of three urban counties of western Washington diagnosed with serous and mucinous borderline ovarian tumors between 1980 and 1985 ( n = 116 ) were interviewed regarding past reproductive events . A r and om sample of women from the same counties ( n = 158 ) was identified through r and om digit dialing and were interviewed . The risk of these ovarian tumors among women who had given birth to 1 or 2 children and to 3 Output:	No conclusive evidence of an association between breastfeeding and bone mineral density was found . Exclusive breastfeeding and predominant breastfeeding were associated with longer duration of amenorrhoea . Shorter duration of breastfeeding was associated with higher risk of postpartum depression . Evidence suggesting an association of breastfeeding with postpartum weight change was lacking . Conclusion This review supports the hypothesis that breastfeeding is protective against breast and ovarian carcinoma , and exclusive breastfeeding and predominant breastfeeding increase the duration of lactational amenorrhoea . There is evidence that breastfeeding reduces the risk of type 2 diabetes . However , an association between breastfeeding and bone mineral density or maternal depression or postpartum weight change was not evident
MS21587	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Eighteen long stay male patients ( diagnosis chronic schizophrenia ) were involved in a six month token economy prior to r and om assignment to one of three experimental groups to investigate the importance of social reinforcement and other token-related variables in maintaining improvements brought about by the token system . Assessment included st and ardised psychiatric rating scales , nurse rating scales , and behavioural measures . Analysis of variance suggests the full token economy system produced significant improvements , but that the social factors involved in token exchanges were not demonstrably important sources of reinforcement . and that none of the variables studies at the experimental phase were critical factors . Once patients returned to a complete token system , results indicate that this may have more value in the promotion of work activities rather than social responding . It is argued that the token system provides a necessary clear structure within which nurses can encourage continuous improvements with long stay patients In Experiment I , forty-five schizophrenics and forty-five normals were r and omly assigned to one of three conditions : information , non-social punishment and social punishment . A probability learning task with event ratio of 80:20 was employed . Punishment facilitated learning in schizophrenics but not in normals . Social and non-social punishment did not produce significant differences in response frequencies , but response latencies and question naire data were interpreted as evidence that social punishment produced more conflict and discomfort in schizophrenics than did the other two conditions . In Experiment II , thirty-nine schizophrenics were r and omly assigned to information , reward and punishment conditions . For the first 100 trials , the event ratio was 80:20 , after which it was reversed to 20:80 . After the shift , Ss receiving punishment learned the new ratio significantly better than Ss in the reward and information conditions . The results suggest that punishment is more effective than reward or information alone with schizophrenics Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration This is the second article from a study of the outcome of five different methods of treatment for schizophrenia ; patients were followed up over a period of two to five years after first admission and the first release . Patients who had been originally treated in hospital with psychotherapy alone stayed longer in hospital over the follow-up period than those who had received electroconvulsive therapy ( ECT ) , drug alone , or drug plus psychotherapy . Those who had been treated with milieu therapy also had a longer stay date d from the time of admission . Patients treated initially with drugs or ECT showed a trend toward spending less time in hospital after their release OBJECTIVES The study examined the effect of adding two employment specialists to the staff of a community mental health center ; their sole responsibility was to develop the skills and positive work attitudes that clients with severe mental illness need to enter the state vocational rehabilitation system or to seek employment . METHODS A total of 122 clients were r and omly assigned to a program with an employment specialist or to a control group with no specialized vocational services . Clients in the program were taught work skills and attitudes in group and individual sessions and through a trial work experience . A schedule of rewards reinforced positive changes . Outcomes measured were skill gains , changes in work attitudes , attainment of employment , and entry into the state vocational rehabilitation system . RESULTS At nine months , 34 of the 61 clients in the program achieved positive changes in vocational status that included competitive employment , participation in training and evaluation programs operated by the state vocational system , and formal referral to the system . Only one client in the control group was linked to the state system . Skill gains and positive changes in work attitudes were found for all program clients . Logistical regression suggested that program participation , rather than client characteristics , was an important predictor of a positive outcome . CONCLUSIONS Over a relatively short time period , targeted vocational programs can help clients with severe mental illness develop the skills and attitudes necessary to attain employment or entry into the vocational rehabilitation system . Vocational rehabilitation can be an integral part of the rehabilitation process for all mental health clients Response to a token economy was assessed in male chronic schizophrenic in- patients who were given , in a double-blind cross-over trial , pimozide ( up to 20 mg daily ) or chlorpromazine ) up to 1,000 mg daily ) , each for three months . After six months there was little change in the patients ' mental state , but general ward behaviour and token-rewarded " target " behaviours improved significantly . There were no statistically significant between-drug differences , but the trend was that general ward behaviour , but not token-rewarded behaviour , improved more on pimozide . The patients who showed initiative and cooperated best with staff were those whose token-rewarded behaviour was most satisfactory Abstract On a ward with extremely withdrawn and thought-disturbed schizophrenic patients it could be shown that introducing tokens contingent on the patients ' behaviour right from the beginning has no disadvantage compared with having a pre-period in which the patients learn to exchange the tokens and thereby establish their value as generalized reinforcers . Getting the tokens contingent on one 's own behaviour seems to heighten their subjective value over and above the pleasurable experience that one can exchange them for primary reinforcers . This might hold especially for long-stay patients who are used to getting noncontingent rewards as arbitrary presents , being extremely dependent on the behaviour of those who are in full control over the patients ' environment 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 paper discusses the effectiveness of an in-patient rehabilitation programme administered by nurses that combines life skills training , active encouragement , and a token economy . Fifty-two chronic schizophrenic patients with prominent negative symptoms who had been continuously in hospital for at least a year were r and omly assigned to the experimental or control group . The training and associated reinforcement schedule were administered daily to experimental subjects by two specially trained rehabilitation nurses . Control subjects did not receive training or reinforcement but were individually asked to perform the same daily tasks and participate in the same activities as the experimental-group subjects . Patients in both groups received their previous dosage of medication throughout the trial . After three months the severity of negative symptoms , as assessed by blind evaluators , decreased in both groups of subjects , but the improvement in the experimental group was much greater than that in the control group . These findings demonstrate the efficacy of behavioural interventions for chronic schizophrenic in- patients in China and highlight the importance of changing the role of Chinese psychiatric nurses from that of custodians who control patients ' behaviour to that of therapists who provide psychological and behavioural treatment Abstract Over 16 training sessions , 4 patients were exposed to a model and reinforced with pennies for talking about scenes depicted on 35 mm slides ; 4 patients were exposed to a model but received no reinforcements ; 4 patients were neither exposed to a model nor reinforced . Extended training over 14 additional sessions was given to 7 patients . A marked increase in verbal output occurred over training sessions , but the treatment effect did not generalize to the ward setting Abstract Schizophrenic patients in a token economy program residing on one ward in a state hospital were compared with control patients on other wards on a number of behavior rating scales . Results indicated an overall decrease in those scale factors most associated with psychotic behavior . The paper also suggests a means to shorten the time required to establish the effectiveness of the reinforcement contingencies in a token program Output:	REVIEW ER 'S CONCLUSIONS The token economy approach may have effects on negative symptoms but it is unclear if these results are reproducible , clinical ly meaningful and are maintained beyond the treatment programme .
MS21588	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE : To compare induction of labor at gestational age 41 weeks with expectant management in regard to neonatal morbidity . Secondary aims were to assess the effect of these managements on mode of delivery and maternal complications . METHODS : Between September 2002 and July 2004 , postterm women with singleton cephalic presentation and no prelabor rupture of membranes were r and omly assigned to induction of labor at 289 days or antenatal fetal surveillance every third day until spontaneous labor . Main outcome measures were neonatal morbidity , operative delivery rates , and maternal complications . RESULTS : Five hundred eight women were r and omly assigned , 254 in each group . No differences of clinical importance were observed in women in whom labor was induced compared with women who were expectantly managed with regard to the following outcomes : neonates whose 5-minute Apgar score was less than 7 ( three neonates in the induction group compared with four in the monitoring group , P=.72 ) ; neonates whose umbilical cord pH was less than 7 ( three compared with two , P=.69 ) ; prevalence of cesarean delivery ( 28 compared with 33 , P=.50 ) ; or prevalence of operative vaginal delivery ( 32 compared with 27 , P=.49 ) . In the induction group more women had precipitate labors ( 33 compared with 12 , P<.01 ; number needed to treat was 13 ) , and the duration of second stage of labor was more often less than 15 minutes ( 94 compared with 56 , P<.01 ; number needed to treat was 7 ) . CONCLUSION : No differences were found between the induced and monitored groups regarding neonatal morbidity or mode of delivery , and the outcomes were generally good . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00385229 LEVEL OF EVIDENCE : OBJECTIVE Management of the uncomplicated pregnancy prolonged beyond the estimated date of confinement is controversial , particularly when the cervix is unfavorable for induction . The benefit of reducing potential fetal risk with induction of labor must be balanced against the morbidity associated with this procedure . The objective of this study was to compare two strategies for managing postterm pregnancy ( i.e. , immediate induction and expectant management ) . STUDY DESIGN Four hundred forty patients with uncomplicated pregnancies at 41 weeks ' gestation were r and omized to either immediate induction of labor ( n = 265 ) or expectant management ( n = 175 ) . Patients with expectant management underwent nonstress testing and amniotic fluid volume assessment twice per week . Patients in the induction group underwent induction within 24 hours of r and omization . To evaluate the efficacy of intracervical prostagl and in E2 gel , patients in the induction group were r and omized in a 2:1 scheme to receive either 0.5 mg prostagl and in E2 gel or placebo gel intracervically 12 hours before induction of labor with oxytocin . RESULTS The incidence of adverse perinatal outcome ( neonatal seizures , intracranial hemorrhage , the need for mechanical ventilation , or nerve injury ) was 1.5 % in the induction group and 1 % in the expectant management group ( p > 0.05 ) . There were no fetal deaths in either group . There were no differences in mean birth weight or the frequency of macrosomia ( birth weight > or = 4000 gm ) between the two groups ( p > 0.05 ) . Regardless of parity , prostagl and in E2 intracervical gel was not more effective than placebo in ripening the cervix . The cesarean delivery rate was not significantly different in the expectant ( 18 % ) , prostagl and in E2 gel ( 23 % ) , or placebo gel ( 18 % ) groups . CONCLUSIONS Adverse perinatal outcome in otherwise uncomplicated pregnancies of > or = 41 weeks is very low with either of the management schemes described . Thus from the perspective of perinatal morbidity or mortality either management scheme is acceptable To compare labour and delivery outcomes in women undergoing induction and those having spontaneous onset for pregnancies past the estimated date of delivery , a prospect i ve study of 395 singleton , uncomplicated pregnancies was performed . Labour was induced in 175 women . Overall caesarean section rate was 9.4 % , with no significant difference between the 2 groups . Overall rate of assisted vaginal deliveries was 7 % , higher in the induction group than the spontaneous onset group but the difference was not significant . There was no significant difference in occurrence of intrapartum meconium , nor for maternal morbidity . No neonate needed intubation . No perinatal deaths occurred . Perinatal mortality and morbidity are preventable , and induction of labour before 42 weeks is justifiable to prevent adverse outcomes In a prospect i ve r and omized study , pregnancies with unfavorable cervix and well established gestational age of at least 42 weeks were selected for management by either antepartum fetal testing or prostagl and in gel induction of labor . Of the 108 pregnancies studied , 57 ( 53 % ) had labor induced and 51 ( 47 % ) continued without intervention . Comparison of the two groups showed no difference in meconium staining , fetal distress , length of first stage of labor , the need for intervention , or the mode of delivery . In terms of Apgar score the neonatal outcome was not significantly different but a greater proportion of the babies ( 7.8 % versus 1.8 % ) in the noninduced group required intubation . Our data show that there is no particular advantage in letting the pregnancy go beyond 42 completed weeks of gestation especially if prostagl and in is available for induction of labor OBJECTIVE To study the cesarean rate between expectant management and immediate induction in the otherwise uncomplicated postterm pregnancy with favorable cervix . STUDY DESIGN A total of 249 women with uncomplicated pregnancies at 41 weeks plus 3 days ( 290 days ) with favorable cervix ( Bishop score > or = 6 ) were r and omized to either expectant management ( n=125 ) or immediate induction of labor ( n=124 ) . The women in the induction group were sent to labor ward for induction by artificial rupture of membranes ( ARM ) and /or oxytocin infusion . The women with expectant management had nonstress test ( NST ) and amniotic fluid index ( AFI ) performed once a week and twice a week after 43 weeks of gestation until spontaneous labor . RESULTS The cesarean rate was not different between expectant management and immediate induction ( 21.6 % versus 26.6 % ; P=0.36 ) . Ninety-five percent of the expectant group delivered within 1 week after enrollment , and all of them delivered within 9 days after r and omization . Maternal and fetal complications in both groups were not different . There was also no difference in the mean birth weight ( P=0.24 ) and the frequency of macrosomia ( birth weight > or = 4000 g ) between the two groups ( P=0.23 ) . CONCLUSION Cesarean section rate between expectant management and immediate induction in the otherwise uncomplicated postterm pregnancy with favorable cervix was not different . Due to the very low adverse perinatal outcome , both expectant management and immediate induction are acceptable Objecfive To determine the proper management of pregnancy in uncomplicated cases going beyond 42 weeks OBJECTIVE Our purpose was to determine the optimal management of pregnancies beyond 41 week 's gestation with a cervix unfavorable for induction . MATERIAL AND METHOD All uncomplicated pregnancies that reached 41 weeks'gestation with a Bishop score of < or = 4 , were r and omly assigned to one of two groups RESULTS The duration of labor was shorter in the group " prépidil " compared with the control group ( P=0.002 ) . Identification of an unfavorable cervix at 41 weeks was unlikely to change by 42 weeks and cervical ripening was required in 40 % cases . There was no significant difference in caesarean section rates . Rates of admission into the neonatal unit and fetal outcomes were similar in the two groups . CONCLUSION Cervical ripening with prostagl and in gel at 41 week 's gestation for uncomplicated singleton pregnancies is safe and should be advocated Traditionally pregnancy has been considered ‘ post-term ’ at 42 completed weeks of gestation . At this gestation , if the cervix is unfavourable , debate over best practice has been between routine induction of labour and expectant management with some form of serial fetal monitoring . Popular wisdom seems to be that meta- analysis of the available r and omised controlled trials has settled the question in favour of routine induction . The largest included trial , containing over half the cases ( n 1⁄4 3407 ) , was carried out in Canada and published in 1992 . The results of the meta- analysis led the Society of Obstetricians and Gynaecologists of Canada ( SOGC ) to issue Clinical Practice Guidelines in 1997 . The guidelines recommended that : 1 . after 41 completed weeks of gestation , if the date s are certain , women should be offered elective delivery ; 2 . if the cervix is unfavourable , ripening should be undertaken ; and 3 . if expectant management is chosen , assessment of fetal health should be initiated . It is presumed that r and omised controlled trials or , even better , meta-analyses of r and omised trials , provide the best evidence to determine appropriate care . However , once information has been declared ‘ the best available evidence ’ , particularly if that assertion is used to justify clinical practice guidelines or ‘ consensus ’ , further inquiry may be inhibited . Since it is implied that ‘ the answers are all in ’ , mutation from clinical practice guideline to st and ard of care is prompt and uncomplicated , particularly if the labels ‘ consensus ’ or ‘ policy statement ’ are used between the two as conceptual mutagens . The st and ard of care in Canada now is assumed to be routine induction at 41 weeks . This commentary is intended to give pause to those who have accepted and adopted this st and ard BACKGROUND The two methods of management of prolonged pregnancy , induction of labour and expectant management with foetal surveillance , have pros and cons . Therefore , we compared the induction of labour with serial antenatal foetal monitoring in the management of post-term pregnancy . METHODS Seventy-four women with uncomplicated pregnancy at 41 weeks ( 287 days ) of gestation were r and omly assigned to undergo either induction of labour or serial antenatal foetal monitoring . Labour was induced in the latter group whenever there was evidence of foetal compromise . Antenatal monitoring consisted of the foetal kick count , non-stress test and biophysical profile . RESULTS Fifty-seven per cent of women went into spontaneous labour by 41 weeks and 4 days ( 291 days ) of gestation and only 14 % developed foetal compromise before that . However , when the gestational age was more than 41 weeks and 4 days ( 291 days ) , the incidence of meconium staining of amniotic fluid and evidence of uteroplacental insufficiency increased significantly . The rate of caesarean section , instrumental delivery , foetal distress and duration of labour did not differ significantly between the two groups . CONCLUSION The policy of inducing labour at 41 weeks and 4 days ( 291 days of gestation ) in uncomplicated pregnancies is justified in our population . However , foetal monitoring should begin at 41 weeks of gestation OBJECTIVE To compare the obstetric outcome of induction of labor at 41 weeks and of follow-up until 42 weeks and induction if the patient has still not given birth at 42 weeks . STUDY DESIGN Six hundred women at 287+/-1 days of gestation with definitely unfavorable cervical scores were r and omized to labor induction ( N=300 ) or spontaneous follow-up ( N=300 ) with twice-weekly nonstress testing and amniotic fluid measurement and once-weekly biophysical scoring . The treatments used in the induction group were ( 1 ) vaginal administration of 50 microg misoprostol ( n=100 ) , ( 2 ) oxytocin induction ( n=100 ) , and ( 3 ) transcervical insertion of a Foley balloon ( n=100 ) . The primary outcome measures were the cesarean delivery rate , whether or not the normal hospital stay had to be extended , and the neonatal outcomes . Secondary outcome measure included number of emergency cesarean deliveries performed for abnormalities of the fetal heart rate ( FHR ) . RESULTS The abdominal delivery rate was 19.3 % in the induction group and 22 % in the follow-up group ( p=0.4 ) . The mean length of hospital stay in the two main groups was 1.4+/-0.8 days and 1.3+/-1 days , respectively ( p=0.1 ) . Significantly higher rates of macrosomia and shoulder dystocia were seen in the follow-up group ( 24.6 and 2.3 % ) than in the induction group ( 7.6 % , p<0.001 ; 0.3 % , p=0.03 ) . Meconium-stained amniotic fluid and meconium aspiration syndrome were observed significantly less frequently in the induction group ( 9.3 and 1.3 % ) than in the follow-up group ( 20.3 % , p<0.001 ; 4 % , p=0.03 ) . Rates of emergency abdominal delivery in response to worrying FHR traces , neonatal intensive care unit admission , and low umblical artery pH were similar in the two groups . There was one intrauterine fetal death in the follow-up group . CONCLUSION Induction of labor at 41 weeks of gestation does not increase the cesarean delivery rate or cause a longer stay in hospital than follow-up Output:	Conclusions Induction of labour appears to be an effective way of reducing perinatal morbidity and mortality associated with post-term pregnancies .
MS21589	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Clinical and experimental studies have shown that a moderately increased physical activity level may have beneficial effects in terms of exercise conditioning , resistance to infection and decreased relative risk of cancer . Modulation of the innate and adaptive components of the immune system with a shift of cytokines and their antagonists to a more pro- and less anti-inflammatory response was found to be a prominent feature in non-tumor patients and healthy volunteers . As quantitative data concerning the cytokine/antagonist response following exercise are not available for tumor patients , we compared the effects of a post-operative rehabilitation program with moderate exercise ( ME ) intensity ( 0.55 - 0.65 x maximal aerobic power ) with a program with low exercise ( LE ) intensity ( 0.30 - 0.40 x maximal aerobic power ) in patients with curatively treated colorectal carcinoma ( UICC II and III ) measuring pro- ( IL-1beta , IL-6 , tumour necrosis factor ( TNF ) ) and anti-inflammatory cytokines ( IL-1 receptor antagonist , sTNF receptors I and II ) . Twenty-three patients participated in this prospect i ve trial , N = 13 in the ME group , N = 10 in the LE group . Exercise was performed daily 30 - 40 min for 2 weeks . Basal ( circulating ) and LPS-stimulated ( phasic ) cytokine and antagonist response was determined before exercise and after 1 and 2 weeks using appropriate ELISA tests . The LPS-stimulated interleukin-1 receptor antagonist ( IL-1ra ) response in the ME group gradually decreased from 31,532.6 ( 160.0 - 70,028.0 ) to 18,033.0 pg/ml ( 5040.0 - 52,570.0 ) after one and to 22,892.0 pg/ml ( 6376.0 - 34,726.0 ) after 2 weeks ( P < 0.05 ) with a concomitant decrease of the corresponding IL-1ra/IL-6 and IL-1ra/IL-1beta ratio : 2.51 - 1.41 and 4.1 - 3.1 , respectively . In contrast , in the LE group LPS-stimulated cytokines and antagonists did not significantly change during exercise . Circulating cytokines and antagonists remained unchanged in both groups . In providing quantitative data in patients with curatively-treated colorectal cancer , we demonstrated that a short-term rehabilitation program with moderate exercise leads to a decreased LPS-induced antagonist response with a shift to a more pro-inflammatory state ( decreased antagonist/cytokine ratio ) . Whether this change of the phasic immune response to moderate exercise may be clinical ly beneficial ( decreased rates of infection , relapses and /or second tumours ) is possible , but has to be investigated in long-term studies This pilot study examined the efficacy of two home-based exercise programs on alleviating fatigue and improving functional capacity in breast cancer survivors . Participants were r and omly assigned into one of three groups : aerobic exercise ( AE ) , resistance exercise ( RE ) , or usual care control ( CON ) . After receiving individualized instruction and training , participants assigned to the AE and RE groups were asked to perform the prescribed exercise(s ) 3 times per week for 12 weeks at home . Both groups were instructed to keep their perceived exercise intensity in the " fairly light " to " somewhat hard " range using the Borg Perceived Exertion Scale . All participants completed the revised Piper Fatigue Scale ( PFS ) and the 6-minute walk test ( 6MWT ) at baseline and 12-week post-exercise program . Analysis of pre- and post-training data revealed a significant reduction in fatigue levels on the PFS among participants in the AE group ( Z=2.521 , one-tailed P=0.006 ) , and a significant improvement in the distance of the 6MWT for the RE group ( Z=2.366 , one-tailed P=0.009 ) at the end of 12-week study period . No significant changes in fatigue or functional status were observed in the CON group . Findings provide preliminary support for RE as a viable strategy for improving functional capacity in breast cancer survivors , while AE may be more effective in attenuating cancer-related fatigue . Incorporating RE training for future research may help advance the growing body of knowledge in symptom management for breast cancer survivors Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials Few r and omized controlled trials have examined the effects of combined aerobic and resistance training in breast cancer survivors soon after completing adjuvant therapy . Breast cancer survivors ( N = 58 ) within 2 years of completing adjuvant therapy were r and omly assigned to an immediate exercise group ( IEG ; n = 29 ) or a delayed exercise group ( DEG ; n = 29 ) . The IEG completed 12 weeks of supervised aerobic and resistance exercise , three times per week . The DEG completed the program during the next 12 weeks . Participants completed patient-rated outcomes at baseline , 6 , 12 , 18 and 24 weeks . The primary endpoint was overall quality of life ( QoL ) measured by the Functional Assessment of Cancer Therapy-Breast scale . Secondary endpoints were fatigue , social physique anxiety , and physical fitness . Follow-up data was obtained on 97 % of participants and exercise adherence was 61.3 % . Repeated measures analyses of variance revealed a significant group by time interaction for overall QoL ( P < 0.001 ) . Specifically , QoL increased in the IEG from baseline to 12 weeks by 20.8 points compared to a decrease in the DEG of 5.3 points ( mean group difference = 26.1 ; 95 % CI = 18.3–32.7 ; P < 0.001 ) . From 12 to 24 weeks , QoL increased in the DEG by 29.5 points compared to an increase of 6.5 points in the IEG ( mean group difference = 23.0 ; 95 % CI = 16.3–29.1 ; P < 0.001 ) . Similar results were obtained for the secondary endpoints . Combined aerobic and resistance exercise soon after the completion of breast cancer therapy produces large and rapid improvements in health-related outcomes PURPOSE Self-directed and supervised exercise were compared with usual care in a clinical trial design ed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer . PATIENTS AND METHODS One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life , aerobic capacity , and body weight . Participants were r and omly allocated to one of three intervention groups : usual care ( control group ) , self-directed exercise , or supervised exercise . Quality of life , aerobic capacity , and body weight measures were repeated at 26 weeks . The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks . RESULTS Physical functioning in the control group decreased by 4.1 points , whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups , respectively ( P = .04 ) . Post hoc analysis showed a moderately large ( and clinical ly important ) difference between the self-directed and control groups ( 9.8 points ; P = .01 ) and a more modest difference between the supervised and control groups ( 6.3 points ; P = .09 ) . No significant differences between groups were observed for changes in quality of life scores . In a secondary analysis of participants stratified by type of adjuvant therapy , supervised exercise improved aerobic capacity ( + 3.5 mL/kg/min ; P = .01 ) and reduced body weight ( -4.8 kg ; P < .05 ) compared with usual care only in participants not receiving chemotherapy . CONCLUSION Physical exercise can blunt some of the negative side effects of breast cancer treatment , including reduced physical functioning . Self-directed exercise is an effective way to improve physical functioning compared with usual care . In participants not receiving chemotherapy , supervised exercise may increase aerobic capacity and reduce body weight compared with usual care The objective was to determine the effects of exercise training on changes in blood immune function in postmenopausal breast cancer survivors . Fifty-three postmenopausal breast cancer survivors were r and omly assigned to an exercise ( n=25 ) or control group ( n=28 ) . The exercise group trained on cycle ergometers three times per week for 15 wk . The control group did not train . The primary end point was change in natural killer cell cytotoxic activity in isolated peripheral blood mononuclear cells . Secondary end points were changes in st and ard hematological variables , whole blood neutrophil function , the phenotypes of isolated mononuclear cells , estimations of unstimulated and phytohemaglutinin-stimulated mononuclear cell function ( rate of [3H]thymidine uptake ) , and the production of proinflammatory [ interleukin (IL)-1alpha , tumor necrosis factor-alpha , IL-6 ] and anti-inflammatory cytokines ( IL-4 , IL-10 , transforming growth factor-beta1 ) . Statistical tests were two-sided ( alpha < 0.05 ) . Fifty-two participants completed the trial . Intention-to-treat analyses , which included the baseline value as a covariate , showed significant differences between groups for change in percent specific lysis of a target natural killer cell at all five effector-to-target ratios ( adjusted mean between-group change over all 5 effector-to-target ratios = + 6.34 % ; P < 0.05 for all comparisons ) , the lytic activity per cell ( adjusted mean between-group change = -2.72 lytic units ; P=0.035 ) , and unstimulated [3H]thymidine uptake by peripheral blood lymphocytes ( adjusted mean between-group change = + 218 per dpm x 10(6 ) cells ; P = 0.007 ) . There were no significant differences between groups for change in any other end point . Exercise training increased natural killer cell cytotoxic activity and unstimulated [3H]thymidine uptake by peripheral blood lymphocytes in postmenopausal breast cancer survivors Introduction Older breast cancer survivors ( BCS ) report more falls and functional limitations than women with no cancer history . Exercise training could reduce risk factors for future falls and disability . Methods We conducted a r and omized , controlled trial in 106 early-stage , postmenopausal BCS who were ≥50 years old at diagnosis and post-treatment . Women were r and omly assigned to a 1-year resistance + impact exercise program or a stretching placebo program . Endpoints were one repetition maximum bench press and leg press strength , timed five chair st and s , 4 m usual walk speed , timed stance tests , h and grip strength , self-report physical function , and fatigue . We also examined the influence of age , adjuvant hormone therapy use , and exercise adherence on study outcomes . Results Women in the resistance + impact training program significantly improved maximal leg ( p < 0 .02 ) and bench ( p < 0 .02 ) press strength compared to the stretching group . Women who attended 50 % or more of prescribed resistance training sessions had significantly better changes in maximal strength measures compared to less adherent women . Conclusions Resistance + impact exercise is superior to stretching at improving maximal muscle strength and exercise adherence contributes to the degree of improvement . Implication s for cancer survivorsOlder BCS can safely engage in resistance exercise that improves lower and upper body strength , thereby reducing a risk factor for falls and future disability . However , the ability of resistance training to shift other indices of fall and disability risk , i.e. , balance and function , is unclear . Strategies to promote adherence to resistance training could lead to greater improvements in strength Objectives To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer , with six month follow-up . Design Pragmatic r and omised controlled prospect i ve open trial . Setting Three National Health Service oncology clinics in Scotl and and community exercise facilities . Participants 203 women entered the study ; 177 completed the six month follow-up . Interventions Supervised 12 week group exercise programme in addition to usual care , compared with usual care . Main outcome measures Functional assessment of cancer therapy ( FACT ) question naire , Beck depression inventory , positive and negative affect scale , body mass index , seven day recall of physical activity , 12 minute walk test , and assessment of shoulder mobility . Results Mixed effects models with adjustment for baseline values , study site , treatment at baseline , and age gave intervention effect estimates ( intervention minus control ) at 12 weeks of 129 ( 95 % Output:	Meta-regression analysis revealed that exercise volume parameters are closely related with the effect estimates on CRF . Conclusions Supervised exercise reduces CRF and must be implemented in breast cancer rehabilitation setting s. High-volume exercises are safe and effective in improving CRF and overall quality of life in women with breast cancer .
MS21590	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: STUDY OBJECTIVE : To investigate whether neighbourhood characteristics are related to dietary patterns independently of individual level variables . DESIGN : A cross sectional analysis of the relation between neighbourhood median household income and food and nutrient intakes , before and after adjustment for individual level variables . SETTING : Four United States communities ( Washington Co , MD ; Suburban Minneapolis , MN ; Forsyth Co , NC , and Jackson , MS ) . PARTICIPANTS : 13,095 adults aged 45 to 64 years participating in the baseline examination of the Atherosclerosis Risk in Communities ( ARIC ) Study , a prospect i ve study of atherosclerosis . MEASUREMENTS AND MAIN RESULTS : Information on diet and individual level income was obtained from the baseline examination of the ARIC Study . Diet was assessed using a semi-quantitative food frequency question naire . Information on neighbourhood ( census defined block groups ) median household income was obtained from the 1990 US Census . Multilevel models were used to account for the multilevel structure of the data . Living in lower income neighbourhoods was generally associated with decreased energy adjusted intake of fruits , vegetables , fish , and increased intake of meat . Patterns generally persisted after adjustment for individual level income , but were often not statistically significant . Inconsistent associations were recorded for the intake of saturated fat , polyunsaturated fat , and cholesterol . Overall , individual level income was a more consistent predictor of diet than neighbourhood income . CONCLUSION : Despite limitations in the definition and characterisation of neighbourhoods , this study found consistent ( albeit small ) differences across neighbourhoods in food intake , suggesting that more in depth research into potential neighbourhood level determinants of diet is warranted The food frequency question naire ( FFQ ) has been used as an important dietary assessment tool in epidemiologic studies , but the usefulness of the FFQ has been debated in recent years . This study was performed to evaluate the relative validities of 3-day food records and the semi-quantitative FFQ . A total of 124 subjects finished 3-day food records ( FRs ) during each of the four seasons , as well as the FFQ from December 2002 to May 2004 . The FFQ was a food based semi-quantitative FFQ including 103 items . Three-day FRs from each season and a r and omly selected season were compared with the remaining 9-day FRs . The remaining 9-day FRs , as a reference measurement , were also compared with the FFQ . Pearson 's correlation coefficients between the 3-day FRs and the 9-day FRs were between 0.14 and 0.56 . Pearson 's correlation coefficients between the FFQ and the 9-day FRs ranged between 0.07 and 0.41 . Average proportions of classification into the same quartiles , adjacent quartiles , and distant quartiles between the 3-day FRs and the 9-day FRs were 35.8 % , 40.5 % , and 5.2 % , respectively . On average , the proportions of classification into the same quartiles , adjacent quartiles , and distant quartiles between the FFQ and the 9-day FRs were 31.1 % , 39.4 % , and 6.9 % , respectively . Three-day FRs showed higher correlations and higher agreement proportions of quartile classification with the 9-day FRs than did the FFQ , but both relative validities of 3-day FRs and the FFQ appear to be acceptable as dietary assessment tools . Further studies for validating food intake by reliable biomarkers are necessary Locational data , logged on portable GPS units and matched with accelerometer data , was used to examine associations of the built environment with physical activity and sedentary behaviors of adolescent females . In a sample of 293 adolescent females aged 15 to 18 years old in Minneapolis and San Diego , the built environment around each GPS point and its corresponding sedentary , light , and moderate-to-vigorous intensity physical activity was examined using r and om intercept multinomial logistic regression models . The odds of higher physical activity intensity ( 3-level outcome : sedentary , light , MVPA ) were higher in places with parks , schools , and high population density , during weekdays , and lower in places with more roads and food outlets . Underst and ing the places where physical activity and sedentary behaviors occur appears to be a promising strategy to clarify relationships and inform policy aim ed at increasing physical activity and reducing sedentary behaviors OBJECTIVES : To establish whether choice and availability of takeaway and restaurant food consumption are associated with increased obesity . DESIGN : Crossroads Undiagnosed Disease Study : a cross-sectional study undertaken between June 2001 and March 2003 . SETTING : A regional centre and six shire capitals of variables size in rural Victoria , Australia . PARTICIPANTS : In total , 1454 residents of r and omly selected households . MEASUREMENTS : Obesity ( by body mass index ( BMI ) or waist circumference ) , weekly recreational activity , self-reported frequency of takeaway consumption , number of local takeaway and restaurant food outlets in the area . RESULTS : The prevalence of obesity ranged from 25.5–30.8 % and was higher than the general Australian population among both men and women . Those in the regional centre were less likely than those in large and small shire capitals to participate in recreational activity of 150 min or more ( 39.7 vs 48.4 % , 46.0 % respectively , P=0.023 ) and yet reported better access to facilities and amenities for physical activity . Recreational activity of ≥150 min/week was associated with 0.75 ( 0.58–0.97 ) fold less risk of obesity . BMI was unrelated to takeaway consumption . Waist circumference was significantly lower among those eating no takeaways , but similar whether takeaways were consumed < 1/month or ≥1/week . Increased takeaway consumption was associated with increased consumption of higher fat preparations of dairy and meat products . Availability of takeaway outlets and restaurants was unrelated to obesity . CONCLUSION : The obesity epidemic exists among those without significant consumption of or availability to takeaway foods . In a setting of easy availability of food , the obesity epidemic relates strongly to reduced physical activity , but not to consumption of takeaway food OBJECTIVE The aim of this study was to examine the association between food prices and food outlet density and changes in the body mass index ( BMI ) among elementary school children in the USA . METHODS The Early Childhood Longitudinal Study followed a nationally representative sample of kindergarten children over 4 years . We merged individual-level data to ( a ) metropolitan data on food prices and ( b ) per capita number of restaurants , grocery stores and convenience stores in the child 's home and school zip code . The dependent variables were BMI changes over 1 and 3 years . We analysed mean changes with least-squares regression , and median changes and 85th percentile changes with quantile regression . We controlled for baseline BMI , age , real family income and sociodemographic characteristics . RESULTS Lower real prices for vegetables and fruits were found to predict a significantly lower gain in BMI between kindergarten and third grade ; half of that effect was found between kindergarten and first grade . Lower meat prices had the opposite effect , although this effect was generally smaller in magnitude and was insignificant for BMI gain over 3 years . Differences across subgroups were not statistically significant due to smaller sample sizes in subgroup analyses , but the estimated effects were meaningfully larger for children in poverty , children already at risk for overweight or overweight in kindergarten , and Asian and Hispanic children . There were no significant effects for dairy or fast-food prices , nor for outlet density , once we had controlled for individual characteristics and r and om intercepts to adjust st and ard errors for the sampling design . DISCUSSION The geographic variation in fruit and vegetable prices is large enough to explain a meaningful amount of the differential gain in BMI among elementary school children across metropolitan areas . However , as consumption information was not available , we can not confirm that this is the actual pathway . We found no effects of food outlet density at the neighbourhood level , possibly because availability is not an issue in metropolitan areas Output:	Associations between observed mobility patterns in the food environment and diet related outcomes were equivocal . Findings agreed that traditional food exposure measures overestimate the importance of the home food environment .
MS21591	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE Using self-refilling soup bowls , this study examined whether visual cues related to portion size can influence intake volume without altering either estimated intake or satiation . RESEARCH METHODS AND PROCEDURES Fifty-four participants ( BMI , 17.3 to 36.0 kg/m2 ; 18 to 46 years of age ) were recruited to participate in a study involving soup . The experiment was a between-subject design with two visibility levels : 1 ) an accurate visual cue of a food portion ( normal bowl ) vs. 2 ) a biased visual cue ( self-refilling bowl ) . The soup apparatus was housed in a modified restaurant-style table in which two of four bowls slowly and imperceptibly refilled as their contents were consumed . Outcomes included intake volume , intake estimation , consumption monitoring , and satiety . RESULTS Participants who were unknowingly eating from self-refilling bowls ate more soup [ 14.7+/-8.4 vs. 8.5+/-6.1 oz ; F(1,52)=8.99 ; p<0.01 ] than those eating from normal soup bowls . However , despite consuming 73 % more , they did not believe they had consumed more , nor did they perceive themselves as more sated than those eating from normal bowls . This was unaffected by BMI . DISCUSSION These findings are consistent with the notion that the amount of food on a plate or bowl increases intake because it influences consumption norms and expectations and it lessens one 's reliance on self-monitoring . It seems that people use their eyes to count calories and not their stomachs . The importance of having salient , accurate visual cues can play an important role in the prevention of unintentional overeating OBJECTIVE It is often believed that people overeat the foods they like . We investigated whether environmental cues such as packaging and container size are so powerful that they can increase our intake of foods that are less palatable . DESIGN , SETTING , AND PARTICIPANTS In a 2 x 2 between-subjects design , 158 moviegoers in Philadelphia ( 57.6 % male ; 28.7 years ) were r and omly given a medium ( 120 g ) or a large ( 240 g ) container of free popcorn that was either fresh or stale ( 14 days old ) . Following the movie , consumption measures were taken , along with measures of perceived taste . OUTCOME MEASURES AND RESULTS Moviegoers who were given fresh popcorn ate 45.3 % more popcorn when it was given to them in large containers . This container-size influence is so powerful that even when the popcorn was disliked , people still ate 33.6 % more popcorn when eating from a large container than from a medium-size container . CONCLUSIONS AND IMPLICATION S Even when foods are not palatable , large packages and containers can lead to overeating . The silver lining of these findings may be that portion size can also be used to increase the consumption of less preferred healthful foods , such as raw vegetables Young and Nestle suggested that the increase in the portion size of food products evident in the United States during the past 20 years may be responsible for the epidemic of overweight and obesity . They based their conclusion on statistical correlations . The purpose of the present study was to provide experimental evidence to support their proposal . Cornell undergraduate students were given access to a buffet lunch on Monday , Wednesday , and Friday and were told this was a test of flavor enhancers . They were instructed to eat as much or as little as they wanted . On the same days of the following week , the subjects were divided into 3 groups . Each group was served either 100 % , 125 % , or 150 % of the amount of food they had consumed the previous week . When larger amounts were served , significantly greater amounts of food were consumed . Each of the 4 foods that comprised the meal ( soup , pasta , breadsticks , ice cream ) increased significantly in proportion to the portion size . The data clearly support the hypothesis proposed by Young and Nestle and support the powerful role that environment plays in determining energy intake and potential increases in body weight Background While environmental and situational cues influence food intake , it is not always clear how they do so . We examine whether participants consume more when an eating occasion is associated with meal cues than with snack cues . We expect their perception of the type of eating occasion to mediate the amount of food they eat . In addition , we expect the effect of those cues on food intake to be strongest among those who are hungry . Methods One-hundred and twenty-two undergraduates ( 75 men , 47 women ; mean BMI = 22.8 , SD = 3.38 ) were r and omly assigned to two experimental conditions in which they were offered foods such as quesadillas and chicken wings in an environment that was associated with either meal cues ( ceramic plates , glasses , silverware , and cloth napkins at a table ) , or snack cues ( paper plates and napkins , plastic cups , and no utensils ) . After participants finished eating , they were asked to complete a question naire that assessed their hunger , satiety , perception of the foods , and included demographic and anthropometric questions . In addition , participants ' total food intake was recorded . Results Participants who were in the presence of meal-related cues ate 27.9 % more calories than those surrounded with snack cues ( 416 versus 532 calories ) . The amount participants ate was partially mediated by whether they perceived the eating occasion to be a meal or a snack . In addition , the effect of the environmental cues on intake was most pronounced among participants who were hungry . Conclusions The present study demonstrated that environmental and situational cues associated with an eating occasion could influence overall food intake . People were more likely to eat foods when they were associated with meal cues . Importantly , the present study reveals that the effect of these cues is uniquely intertwined with cognition and motivation . First , people were more likely to eat ambiguous foods when they perceived them as a meal rather than a snack . Second , the effect of the environmental cues on intake was only observed among those who were hungry The objective of this study was to test if proximity of a food or preference for a food influences food intake in a competitive food environment in which one low calorie/low fat ( apple slices ) and one higher calorie/higher fat ( buttered popcorn ) food was available in the same environment . The proximity of popcorn and apple slices was manipulated and 56 participants were r and omly assigned to groups . In Group Apples Near , apple slices were placed near ( within arms reach ) a participant and popcorn was placed far ( 2 m away ) . In Group Popcorn Near , buttered popcorn was placed near and apple slices were placed far . As a control for the absence of a proximity manipulation , Group Both Near had both test foods placed near . Although participants rated the popcorn as more liked than apples , the food that was placed closer to the participant was consumed most in the two experimental groups , regardless of preference ( R(2)=0.38 ) . Total energy intake was reduced most when popcorn was placed far from a participant compared to when it was placed near ( R(2)=0.24 ) . The effects reported here were not moderated by BMI and did not vary by sex . In all , the results support the hypothesis that making a low calorie food more proximate will reduce total energy intake and increase intake of a low calorie food , even when a higher calorie and more preferred food is also available , but less proximate In a cross-over study , participants ( n=59 ) were r and omly assigned to receive either 100 kcal packs or st and ard size packages of snacks for 1 week . After a minimum of a 1-week washout period , participants received the other form of the snack for 1 week . Snack consumption was recorded by participants in a diary . Participants consumed an average of 186.9 fewer grams of snacks per week when receiving 100 kcal snack packs compared to st and ard size packages of snacks . Post hoc comparisons revealed the effect of package size depended on both r and omization order and study week . Total grams of snacks consumed in week 1 differed significantly between the two r and omized groups . In week 2 , however , grams of snacks did not differ significantly between the two groups . This interaction was primarily due to a significantly lower consumption of snacks from st and ard size packages in the week following the portion-controlled packages . The results suggest that portion-controlled packaging reduce total intake from the provided snacks . Further , initial exposure to portion-controlled packages might have increased awareness of portion size such that less was consumed when larger packages were available Objective To assess the impact of fast food restaurants adding calorie labelling to menu items on the energy content of individual purchases . Design Cross sectional surveys in spring 2007 and spring 2009 ( one year before and nine months after full implementation of regulation requiring chain restaurants ’ menus to contain details of the energy content of all menu items ) . Setting 168 r and omly selected locations of the top 11 fast food chains in New York City during lunchtime hours . Participants 7309 adult customers interviewed in 2007 and 8489 in 2009 . Main outcome measures Energy content of individual purchases , based on customers ’ register receipts and on calorie information provided for all items in menus . Results For the full sample , mean calories purchased did not change from before to after regulation ( 828 v 846 kcal , P=0.22 ) , though a modest decrease was shown in a regression model adjusted for restaurant chain , poverty level for the store location , sex of customers , type of purchase , and inflation adjusted cost ( 847 v 827 kcal , P=0.01 ) . Three major chains , which accounted for 42 % of customers surveyed , showed significant reductions in mean energy per purchase ( McDonald ’s 829 v 785 kcal , P=0.02 ; Au Bon Pain 555 v 475 kcal , P<0.001 ; KFC 927 v 868 kcal , P<0.01 ) , while mean energy content increased for one chain ( Subway 749 v 882 kcal , P<0.001 ) . In the 2009 survey , 15 % ( 1288/8489 ) of customers reported using the calorie information , and these customers purchased 106 fewer kilocalories than customers who did not see or use the calorie information ( 757 v 863 kcal , P<0.001 ) . Conclusion Although no overall decline in calories purchased was observed for the full sample , several major chains saw significant reductions . After regulation , one in six lunchtime customers used the calorie information provided , and these customers made lower calorie choices Objectives : The supermarket industry now services many customers through online food shopping over the Internet . The Internet shopping process offers a novel opportunity for the modification of dietary patterns . The aim of this study was to evaluate the effects on consumers ' purchases of saturated fat of a fully automated computerised system that provided real-time advice tailored to the consumers ' specific purchases recommending foods lower in saturated fat . Design : This study was a blinded , r and omised controlled trial . Setting : The study was conducted in Sydney , New South Wales , Australia . Participants : The participants were consumers using a commercial online Internet shopping site between February and June 2004 . Interventions : Individuals assigned to intervention received fully automated advice that recommended specific switches from selected products higher in saturated fat to alternate similar products lower in saturated fat . Participants assigned to control received general non-specific advice about how to eat a diet lower in saturated fat . Outcome Measures : The outcome measure was the difference in saturated fat ( grams per 100 g of food ) in shopping baskets between the intervention and control groups . Results : There were 497 r and omised participants , mean age 40 y , each shopping for an average of about three people . The amount of saturated fat in the foods purchased by the intervention group was 0.66 % lower ( 95 % confidence interval 0.48–0.84 , p < 0.001 ) than in the control group . The effects of the intervention were sustained over consecutive shopping episodes , and there was no difference in the average cost of the food bought by each group . Conclusions : Fully automated , purchase-specific dietary advice offered to customers during Internet shopping can bring about changes in food purchasing habits that are likely to have significant public health implication s. Because implementation is simple to initiate and maintain , this strategy would likely be highly cost-effective Large food portions may be facilitating excess energy intake ( EI ) and adiposity among adults . The present study aim ed to assess the extent to which EI and amounts of foods consumed are influenced by the availability of different-sized food portions . A r and omised within-subject cross-over , fully residential design was used , where forty-three ( twenty-one men and twenty-two women ) normal-weight and overweight adults were r and omly allocated to two separate 4 d periods where they were presented with either ' st and ard ' or ' large ' food portions of the same foods and beverages . The main outcome measures were the amount of food ( g ) and EI ( MJ ) consumed throughout each study period . Mean EI over 4 d was significantly higher on the large portion condition compared with the st and ard condition in the total group ( 59.1 ( sd 6.6 ) v. 52.2 ( sd 14.3 ) MJ ; P = 0.020 ) ; men and women increased their EI by 17 % ( 10 ( sd 6.5 ) MJ ; P < 0.001 ) and 10 % ( 4 ( sd 6.5 ) MJ ; P = 0.005 ) respectively when served the large food portions relative to the st and ard food portions . The increased intakes were sustained over the 4 d in the large portion condition with little evidence of down-regulation of EI and food intake being made by subjects . Increased food portion size result ed in significant and sustained increases in EI in men Output:	Conclusions This analysis demonstrates Nudge holds promise as a public health strategy to combat obesity .
MS21592	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract . This prospect i ve r and omized intervention investigated whether training on a balance board could reduce the amount of traumatic injuries of the lower extremities in female soccer players . A total of 221 female soccer players from 13 different teams playing in the second and third Swedish divisions volunteered to participate in the study . Seven teams ( n=121 ) were r and omized to an intervention group and six teams ( n=100 ) to a control group and were followed during one outdoor season ( April – October ) . Before and after the season muscle flexibility and balance/postural sway of the lower extremities were measured in the players . There were no significant differences in age , height , weight , muscle flexibility and balance/postural sway of the lower extremities between the intervention and the control group . During the season the players in the intervention group performed a special training program consisting of 10–15 min of balance board training in addition to their st and ard soccer practice and games . After a 37 % drop-out the intervention group consisted of 62 players and the control group of 78 players . The results showed no significant differences between the groups with respect either to the number , incidence , or type of traumatic injuries of the lower extremities . The incidence rate of " major " injuries was higher in the intervention group than in the control group . Four of five anterior cruciate ligament injuries occurred in the intervention group , which means that we could not prevent severe knee injuries in female soccer players with balance board training . However , among the players who had been injured during the 3-month period prior to this investigation there were significantly more players from the control group than from the intervention group who sustained new injuries during the study period Background : Sport is the leading cause of injury requiring medical attention among adolescents . We studied the effectiveness of a home-based balance-training program using a wobble board in improving static and dynamic balance and reducing sports-related injuries among healthy adolescents . Methods : In this cluster r and omized controlled trial , we r and omly selected 10 of 15 high schools in Calgary to participate in the fall of 2001 . We then recruited students from physical education classes and r and omly assigned them , by school , to either the intervention ( n = 66 ) or the control ( n = 61 ) group . Students in the intervention group participated in a daily 6-week and then a weekly 6-month home-based balance-training program using a wobble board . Students at the control schools received testing only . The primary outcome measures were timed static and dynamic balance , 20-m shuttle run and vertical jump , which were measured at baseline and biweekly for 6 weeks . Self-reported injury data were collected over the 6-month follow-up period . Results : At 6 weeks , improvements in static and dynamic balance were observed in the intervention group but not in the control group ( difference in static balance 20.7 seconds , 95 % confidence interval [ CI ] 10.8 to 30.6 seconds ; difference in dynamic balance 2.3 seconds , 95 % CI 0.7 to 4.0 seconds ) . There was evidence of a protective effect of balance training in over 6 months ( relative risk of injury 0.2 , 95 % CI 0.05 to 0.88 ) . The number needed to treat to avoid 1 injury over 6 months was 8 ( 95 % CI 4 to 35 ) . Interpretation : Balance training using a wobble board is effective in improving static and dynamic balance and reducing sports-related injuries among healthy adolescents The purpose of this study was to determine the effect of a 4-week balance training program on specified functional tasks . Thirty-six subjects ( age = 22.7 ± 2.10 years ; height = 168.30 ± 9.55 cm ; weight = 71.15 ± 16.40 kg ) were r and omly placed into control ( C ; n = 19 ) and experimental groups ( Tx ; n = 17 ) . The Tx group trained using a commercially available balance training device ( BOSU ) . Postural limits ( displacement and sway ) and functional task ( time on ball , shuttle run , and vertical jump ) were assessed during a pretest ( T1 ) , a posttest ( T2 ) , and 2 weeks posttraining ( T3 ) . Multivariate repeated measures analysis ( a = 0.05 ) revealed significant differences in time on ball , shuttle run , total sway , and fore/aft displacement after the exercise intervention ( T2 ) . T3 assessment revealed that total sway and time on ball remained controlled ; however , no other measures were retained . Balance training improved performance of selected sport-related activities and postural control measures , although it is unclear whether the effect of training would transfer to general functional enhancement Balancing exercises on instable bases ( sensorimotor training [ SMT ] ) are often used in the rehabilitation process of an injured athlete to restore joint function . Recently it was shown that SMT was able to enhance rate of force development ( RFD ) in a maximal voluntary muscle contraction . The purpose of this study was to compare adaptations on strength capacity following ballistic strength training ( BST ) with those following an SMT during a training period of 1 microcycle ( 4 weeks ) . Maximum voluntary isometric strength ( MVC ) , maximum RFD ( RFDmax ) and the corresponding neural activation of M. soleus ( SOL ) , M. gastrocnemius ( GAS ) , and M. tibialis anterior ( TIB ) were measured during plantar flexion in 33 healthy subjects . The subjects were r and omly assigned to a SMT , BST , or control group . RFDmax increased significantly stronger following BST ( 48 ± 16 % ; p < 0.01 ) compared to SMT ( 14 ± 5 % ; p < 0.05 ) , whereas MVC remained unchanged in both groups . Median frequencies of the electromyographic power spectrum during the first 200 ms of contraction for GAS increased following both BST ( 45 ± 21 % ; p < 0.05 ) and SMT ( 45 ± 22 % ; p < 0.05 ) , but median frequencies for SOL increased only after SMT ( 13 ± 4 % ; p < 0.05 ) . Additionally , mean amplitude voltage increased following BST for SOL ( 38 ± 12 % ; p < 0.01 ) and for GAS ( 73 ± 23 % ; p < 0.01 ) during the first 100 ms , whereas it remained unchanged after SMT . It is concluded that BST and SMT may induce different neural adaptations that specifically affect recruitment and discharge rates of motor units at the beginning of voluntary contraction . Specific neural adaptations indicate that SMT might be used complementarily to BST , especially in sports that require contractile explosive properties in situations with high postural dem and s , e.g. , during jumps in ball sports Background : A number of studies have shown that proprioception training can reduce the risk of injuries in pivoting sports , but the mechanism is not clearly understood . Aim : To determine the contributing effects of propioception on knee joint position sense among team h and ball players . Study design : Prospect i ve cohort study . Methods : Two professional female h and ball teams were followed prospect ively for the 2005–6 season . 20 players in the intervention team followed a prescribed proprioceptive training programme while 19 players in the control team did not have a specific propioceptive training programme . The coaches recorded all exposures of the individual players . The location and nature of injuries were recorded . Joint position sense ( JPS ) was measured by a goniometer on both knees in three angle intervals , testing each angle five times . Assessment s were performed before and after the season by the same examiner for both teams . In the intervention team a third assessment was also performed during the season . Complete data were obtained for 15 subjects in the intervention team and 16 in the control team . Absolute error score , error of variation score and SEM were calculated and the results of the intervention and control teams were compared . Results : The proprioception sensory function of the players in the intervention team was significantly improved between the assessment s made at the start and the end of the season ( mean ( SD ) absolute error 9.78–8.21 ° ( 7.19–6.08 ° ) vs 3.61–4.04 ° (3.71–3.20 ° ) , p<0.05 ) . No improvement was seen in the sensory function in the control team between the start and the end of the season ( mean ( SD ) absolute error 6.31–6.22 ° (6.12–3.59 ° ) vs 6.13–6.69 ° (7.46–6.49 ° ) , p>0.05 ) . Conclusion : This is the first study to show that proprioception training improves the joint position sense in elite female h and ball players . This may explain the effect of neuromuscular training in reducing the injury rate The purpose of the present study was to investigate the effects of a soccer training session on the balance ability of the players and assess whether the effectiveness of a balance program is affected by its performance before or after the regular soccer training . Thirty-nine soccer players were r and omly divided into three subject groups ( n=13 each ) , one control group ( C group ) , one training group that followed a balance program ( 12 weeks , 3 times per week , 20 min per session ) before the regular soccer training ( TxB group ) , and one training group that performed the same balance program after the soccer training ( TxA group ) . St and ard testing balance boards and the Biodex Stability System were used to assess balance ability in the C , TxB , and TxA groups at baseline ( T0 ) and after completing the balance program ( T12 ) . The same tests and additional isokinetic knee joint moment measurements were carried out in the TxB and TxA groups pre- and post-soccer training . Two main results were obtained : ( 1 ) No differences ( p>0.05 ) were found in balance ability and knee joint moment production between pre- and post-soccer training . ( 2 ) The balance program increased ( p<0.01 ) the balance ability in the TxB and TxA groups , and the improvement in the TxA group was greater ( p<0.05 ) than that in the TxB group post-soccer training . Result ( 1 ) is in contrast to the notion of a link between fatigue induced by a soccer training session or game and injury caused by impaired balance , and result ( 2 ) has implication s for athletic training and rehabilitation The isolated effect of balance training on muscle strength of the flexors and extensors of the knee , without accompanying strength training , has not been addressed in the past . Effects of a balance training program alone were compared to a strength training program . Balance and strength training were performed by 15 persons each for 6 weeks including 12 training units of 25 min . Balance training was performed on instability training devices such as rolling board , mini trampoline and large rubber ball . The 15 persons of the strength training group trained on machines for leg curls and on leg presses for 25 min per unit . Measurements for balance were performed with one-leg balance on a narrow edge and a tilting stabilometer for 30 s ; maximum isometric strength was measured using an isokinetic device for each leg separately . The muscular balance between dominant and non-dominant leg was calculated . Strength gain was similar for the flexors and extensors in both groups . One-leg balance improved after balance training ( P < 0.01 ) with a 100 % increase over the strength training group ( P < 0.05 ) and the stabilometer test for each person in the balance ( P < 0.01 ) , but not in the strength training group . In the balance group the initial difference between right and left diminished . The results indicate balance training to be effective for gain in muscular strength , and secondly , in contrast to strength training , equalisation of muscular imbalances may be achieved after balance training Total sagittal knee laxity and postural control in the sagittal and frontal planes were measured in 25 patients at a mean of 36 months ( range , 27 to 44 ) after anterior cruciate ligament reconstruction and in a control group consisting of 20 uninjured age- and activity-matched subjects . Body sway was measured in the sagittal plane on a stable and on a sway-referenced force plate in single-legged stance , double-legged stance , or both , with the eyes open and closed . Postural reactions to perturbations in the sagittal and frontal planes were recorded in the single-legged stance with the eyes open . Total sagittal plane laxity was significantly greater in the anterior cruciate ligament-reconstructed knee ( 11.2 mm ; range , 6 to 15 ) than in the uninjured knee ( 8.9 mm ; range , 6 to 12 ) or in the control group ( 6.0 mm ; range , 5 to 8) . In spite of this , the patients , in comparison with the controls , exhibited normal postural control except in two variables — the reaction time and the latency between the start of force movement to maximal sway in the sagittal plane perturbations . This supports the hypothesis that rehabilitation , with proprioceptive and agility training , is an important component in restoring the functional stability in the anterior cruciate ligament-reconstructed knee Background Ankle sprains are the most common musculoskeletal injuries that occur in athletes , and they have a profound impact on health care costs and re sources . Hypothesis A balance training program can reduce the risk of ankle sprains in high school athletes . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Seven hundred and sixty-five high school soccer and basketball players ( 523 girls and 242 boys ) were r and omly assigned to either an intervention group ( 27 teams , 373 subjects ) that participated in a balance training program or to a control group ( 28 teams , 392 subjects ) that performed only st and ard conditioning exercises . On-site athletic trainers recorded athlete exposures and sprains . Results The rate of ankle sprains was significantly lower for subjects in the intervention group ( 6.1 % , 1.13 of 1000 exposures vs 9.9 % , 1.87 of 1000 exposures ; P = . Output:	Balance training was effective in improving postural sway and functional balance when compared with untrained control participants . Larger effect sizes were shown for training programs of longer duration . Although controversial findings were reported for jumping performance , agility , and neuromuscular control , there are indications for the effectiveness of balance training in these outcomes . When compared with plyometric or strength training , conflicting results or no effects of balance training were reported for strength improvements and changes in sprint performance . CONCLUSIONS We conclude that balance training can be effective for postural and neuromuscular control improvements .
MS21593	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : The aim of this study was to evaluate two interventions ( one reward-based and one exposure-based ) for increasing children 's acceptance of an unfamiliar vegetable compared with a no-treatment control . It was predicted that the exposure condition would increase liking for , and consumption of , the vegetable relative to either the reward or control group . Design : Using a r and omized controlled design , participants were assigned to one of two intervention groups ( exposure or reward ) or to a no-treatment control condition , for a 2 week period . Liking for , and consumption of , red pepper was assessed before and after the treatment period . Setting : The study was conducted in three primary schools in London . Subjects : Parental consent was obtained for 49 out of a possible 72 children . Interventions : Interventions comprised eight daily sessions during which participants in the exposure group were offered a taste of sweet red pepper and told that they could eat as much as they liked . Participants in the reward group were shown a sheet of cartoon stickers and told that they could choose one of them on condition that they ate at least one piece of the pepper . Results : The exposure-based intervention significantly increased both liking ( P=0.006 ) and consumption ( P=0.03 ) compared with the control group . The outcome of the reward intervention was intermediate and did not differ significantly from the exposure or control conditions . Conclusions : Repeated exposure to the taste of unfamiliar foods is a promising strategy for promoting liking of previously rejected foods in children . Sponsorship : This study was financed by Cancer Research UK OBJECTIVE To determine the influence of screen-based peer modeling on children 's vegetable consumption and preference . METHODS A total of 42 children aged 3 - 5 years were r and omly assigned to view individually a video segment of peers consuming a modeled vegetable ( bell pepper ) , vs a nonfood video segment or no video . Analysis of covariance models examined bell pepper preference and consumption during initial video exposure ( day 1 ) and without video exposure ( days 2 and 7 ) , adjusted for age , sex , body mass index , and initial bell pepper consumption . RESULTS Children in the vegetable condition ate more bell peppers ( 15.5 g ) than did those in the control condition ( 5.9 g ; P = .04 ; model η(2 ) = 0.85 ) on day 7 , with no differences on days 1 or 2 . Among children who ate the modeled vegetable , those in the vegetable DVD condition reported greater preference for eating the vegetable again ( P = .01 ) . CONCLUSIONS AND IMPLICATION S Screen-based peer modeling is a promising tool to influence children 's vegetable consumption Research suggests that repeatedly offering infants a variety of vegetables during weaning increases vegetable intake and liking . The effect may extend to novel foods . The present study aim ed to investigate the impact of advising parents to introduce a variety of single vegetables as first foods on infants ' subsequent acceptance of a novel vegetable . Mothers of 4- to 6-month-old infants in the UK , Greece and Portugal were r and omised to either an intervention group ( n 75 ) , who received guidance on introducing five vegetables ( one per d ) as first foods repeated over 15 d , or a control group ( n 71 ) who received country-specific ' usual care ' . Infant 's consumption ( g ) and liking ( maternal and research er rated ) of an unfamiliar vegetable were assessed 1 month post-intervention . Primary analyses were conducted for the full sample with secondary analyses conducted separately by country . No significant effect of the intervention was found for vegetable intake in the three countries combined . However , sub-group analyses showed that UK intervention infants consumed significantly more novel vegetable than control infants ( 32.8 ( SD 23.6 ) v. 16.5 ( sd 12.1 ) g ; P = 0.003 ) . UK mothers and research ers rated infants ' vegetable liking higher in the intervention than in control condition . In Portugal and Greece , there was no significant intervention effect on infants ' vegetable intake or liking . The differing outcome between countries possibly reflects cultural variations in existing weaning practice s. However , the UK results suggest in countries where vegetables are not common first foods , advice on introducing a variety of vegetables early in weaning may be beneficial for increasing vegetable acceptance BACKGROUND Research in humans and animal models suggests that acceptance of solid foods by infants during weaning is enhanced by early experiences with flavor variety . OBJECTIVE We tested the hypotheses that the acceptance of novel foods by formula-fed infants could be facilitated by providing the infants with a variety of flavors at the time when beikost is first introduced and that , contrary to medical lore , infants who had previously consumed fruit would be less likely to reject vegetables when first introduced than would infants without such an experience . DESIGN The infants ' acceptance of a novel vegetable ( puréed carrot ) and a novel meat ( puréed chicken ) was evaluated after a 9-d exposure period in 3 groups of infants , some of whom had previously consumed fruit . During the home-exposure period , one group was fed only carrots , the target vegetable ; a second group was fed only potatoes , a vegetable that differed in flavor from carrots ; and a third group was fed a variety of vegetables that did not include carrots . RESULTS Infants fed either carrots or a variety of vegetables , but not those fed potatoes , ate significantly more of the carrots after the exposure period . Exposure to a variety of vegetables also facilitated the acceptance of the novel food , puréed chicken , and daily experience with fruit enhanced the infants ' initial acceptance of carrots . CONCLUSION These findings are the first experimental evidence to indicate that exposure to a variety of flavors enhances acceptance of novel foods in human infants We examined associations between fruit and vegetable intake and the incidence of type 2 diabetes ( T2D ) in a population -based prospect i ve study of 64,191 women with no history of T2D or other chronic diseases at study recruitment and with valid dietary information . Dietary intake was assessed by in-person interviews using a vali date d FFQ . During 297,755 person-years of follow-up , 1608 new cases of T2D were documented . We used a Cox regression model to evaluate the association of fruit and vegetable intake ( g/d ) with the risk of T2D . Quintiles of vegetable intake and T2D were inversely associated . The relative risk for T2D for the upper quintile relative to the lower quintile of vegetable intake was 0.72 ( 95%CI : 0.61 - 0.85 ; P < 0.01 ) in multivariate analysis . Individual vegetable groups were all inversely and significantly associated with the risk of T2D . Fruit intake was not associated with the incidence of diabetes in this population . Our data suggest that vegetable consumption may protect against the development of T2D Background Governments worldwide recommend daily consumption of fruit and vegetables . We examine whether this benefits health in the general population of Engl and . Methods Cox regression was used to estimate HRs and 95 % CI for an association between fruit and vegetable consumption and all-cause , cancer and cardiovascular mortality , adjusting for age , sex , social class , education , BMI , alcohol consumption and physical activity , in 65 226 participants aged 35 + years in the 2001–2008 Health Surveys for Engl and , annual surveys of nationally representative r and om sample s of the non-institutionalised population of Engl and linked to mortality data ( median follow-up : 7.7 years ) . Results Fruit and vegetable consumption was associated with decreased all-cause mortality ( adjusted HR for 7 + portions 0.67 ( 95 % CI 0.58 to 0.78 ) , reference category < 1 portion ) . This association was more pronounced when excluding deaths within a year of baseline ( 0.58 ( 0.46 to 0.71 ) ) . Fruit and vegetable consumption was associated with reduced cancer ( 0.75 ( 0.59–0.96 ) ) and cardiovascular mortality ( 0.69 ( 0.53 to 0.88 ) ) . Vegetables may have a stronger association with mortality than fruit ( HR for 2 to 3 portions 0.81 ( 0.73 to 0.89 ) and 0.90 ( 0.82 to 0.98 ) , respectively ) . Consumption of vegetables ( 0.85 ( 0.81 to 0.89 ) per portion ) or salad ( 0.87 ( 0.82 to 0.92 ) per portion ) were most protective , while frozen/canned fruit consumption was apparently associated with increased mortality ( 1.17 ( 1.07 to 1.28 ) per portion ) . Conclusions A robust inverse association exists between fruit and vegetable consumption and mortality , with benefits seen in up to 7 + portions daily . Further investigations into the effects of different types of fruit and vegetables are warranted Background : What lactating mothers eat flavors breast milk and , in turn , modifies their infants ' acceptance of similarly flavored foods . Objective : We sought to determine the effects of the timing and duration of eating a variety of vegetables during breastfeeding on the liking of vegetables in both members of the dyad . Design : We conducted a r and omized controlled study of 97 mother-infant dyads . Lactating mothers drank vegetable , beet , celery , and carrot juices for 1 mo beginning at 0.5 , 1.5 , or 2.5 mo postpartum or for 3 mo beginning at 0.5 mo postpartum . The control group drank equal volumes of water and avoided drinking the juices . Mothers rated the tastes of the juices and self-reported dietary intakes at each monthly visit ( 0.5 - 4.5 mo ) . After weaning , when 7.9 mo of age , infants ' acceptance of plain , carrot-flavor ( exposed flavor ) , and broccoli-flavor ( nonexposed flavor ) cereals was assessed on separate days . Results : The timing of exposure affected the acceptance of the carrot flavor that did not generalize to the novel broccoli flavor . A relatively brief experience ( 1 mo ) with vegetable flavors in mothers ' milk , starting at 0.5 mo postpartum , was sufficient to shift the hedonic tone , which result ed in a faster rate of eating carrot-flavored cereal than that in infants who were exposed during subsequent months or not at all . One month of exposure had a greater effect than 3 mo of exposure or no exposure . Regardless of when exposure occurred , infants were less likely to display facial expressions of distaste initially when eating the carrot cereal . Over time , mothers liked the tastes of carrot , beet , and celery juices more , but no changes in dietary intake of vegetables were observed . Conclusions : Early life may be an optimum time for both infants and their mothers to learn to like the taste of healthy foods . More research is needed to facilitate the liking and eating of these foods by mothers , which will , in turn , increase the likelihood of their feeding these foods to their children . This trial was registered at clinical trials.gov as NCT01667549 BACKGROUND Laboratory and home-based research suggest that repeated exposure to vegetables may increase consumption among children . Effectiveness of repeated exposure to vegetables has not been tested in a community-based preschool setting . OBJECTIVE This r and omized controlled trial tested the hypotheses that children who are served unfamiliar vegetables repeatedly in the preschool lunch setting will increase consumption of them , and that consumption will be influenced by peer eating behaviors and parental feeding behaviors . SUBJECTS/ SETTING Data were collected in two private preschools in a small northeastern city in 2007 . Ninety-six children ( aged 3 to 6 years ) participated . DESIGN Schools were r and omly assigned to condition . During the first 6 weeks , Preschool A served three vegetables at lunch on 10 separate occasions ( ie , 30 days of exposure ) , while Preschool B continued routine practice . In the 7th week , schools reversed conditions and Preschool B served the vegetables for the next 6 weeks . Consumption data were collected daily in the intervention school and at baseline and post-intervention meals in the control school . PRIMARY OUTCOMES /STATISTICAL ANALYSES : Analysis of variance was used to examine the effect of vegetable exposure on vegetable intake ; multilevel models were used to examine the effect of peer eating behaviors and parental feeding practice s on vegetable intake . RESULTS Repeated exposure did not increase vegetable consumption . Greater consumption by tablemates was a significant predictor of greater vegetable consumption ; across the three vegetables , 1 g of peer intake was associated with roughly a 1/5-g intake increase among the subjects . Overall , children demonstrated wide fluctuation in vegetable consumption from day to day , creating as much variability within subjects as between them . CONCLUSIONS Further research should explore the conditions necessary for repeated exposure to increase vegetable consumption in preschool setting s. Creating opportunities for young children to serve as peer models has promise as a strategy to promote vegetable consumption The aim of the current study was to examine the effectiveness of different vegetable exposure methods ( variety versus single taste ) over a 9 day period in two groups of infants ; those introduced to solids prior to the age of 5.5 months , and those introduced after 5.5 months . Sixty parent-infant dyads were recruited in South Birmingham , UK . Infants ' acceptance of a novel vegetable ( pea puree ) was measured after a 9 day exposure period in the infants a week after they were first introduced to solid foods . During the exposure period half of each age group was given carrot every day , and the other half was given a variety pack of courgette , parsnip and sweet potato . A baseline measurement of the Output:	Our analyses demonstrate : 1 ) increased liking and intakes of the exposed vegetable after repeated exposure compared with no exposure ; 2 ) increased liking for the exposed vegetable after conditioning compared with repeated exposure , increased intakes after the use of rewards , and some suggestion of decreased intakes after flavor-nutrient conditioning ; and 3 ) increased liking and intakes of a novel vegetable after repeated exposure to a variety of other vegetables compared with no exposure or repeated exposure to one other vegetable . Effect sizes , however , are small , and limited evidence suggests long-term benefits . Conclusions Based on our findings , we recommend the use of repeated exposure to one and a variety of vegetables , and the use of rewards , for increasing vegetable liking and consumption .
MS21594	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The proximal femoral nail ( PFN ) is a recently introduced intramedullary system , design ed to improve treatment of unstable trochanteric fractures of the hip . In a multicentre prospect i ve clinical study , the intra-operative use , complications and outcome of treatment using the PFN ( n = 211 ) were compared with those using the gamma nail ( GN ) ( n = 213 ) . The intra-operative blood loss was lower with the PFN ( 220 ml v 287 ml , p = 0.001 ) . Post-operatively , more lateral protrusion of the hip screws of the PFN ( 7.6 % ) was documented , compared with the gamma nail ( 1.6 % , p = 0.02 ) . Most local complications were related to suboptimal reduction of the fracture and /or positioning of the implant . Functional outcome and consolidation were equal for both implants . Generally , the results of treatment of unstable trochanteric fractures were comparable for the PFN and GN . The pitfalls and complications were similar , and mainly surgeon- or fracture-related , rather than implant-related PURPOSE Asian patients with osteoporosis suffer from an increased incidence of hip fracture and a potentially increased risk of fixation failure due to anatomical differences compared to Caucasians . To cope with these differences , an Asian size- and geometry-adapted Proximal Femoral Nail Antirotation ( PFNA-II ) was developed . The objective of this prospect i ve multicenter study was to assess the risk of fracture fixation complications ( FFCs ) , the occurrence of mismatch and the quality of life status of patients treated with the PFNA-II . PATIENTS AND METHODS 176 Japanese patients with an isolated , unstable , closed trochanteric fracture were treated with the PFNA-II . Patients were prospect ively screened for anticipated complications and classified accordingly ; complications were central ly review ed by a complication review board to avoid bias by the treating surgeon , and categorized using a st and ardized reporting system . Outcome measurements included the occurrence and evaluation of FFCs , the radiological assessment of mismatch and quality of life measured with the EQ-5D score . RESULTS 3 Intraoperative and 15 postoperative complications were found in 16/176 patients . The risk of sustaining any intraoperative or postoperative FFC was 1.7 % ( 3/176 ; 95 % CI : 0.35 - 4.9 ) and 8 % ( 14/176 ; 95 % CI : 4.4 - 13 ) , respectively . The most likely cause for FFCs was the " bone/fracture " factor ( 9/14 patients ) . Radiologically detectable contact of the implant with the inner cortex ( " mismatch " ) was reported for 17/173 patients ( 10 % ) . CONCLUSIONS The reported complication risks and mismatches are reasonable for this patient cohort . The geometry- and size-adapted PFNA-II is relatively safe but requires st and ardized assessment in a larger target cohort Medical instructions for partial weight-bearing after lower limb surgery and fractures are commonly given . The techniques for instruction are mainly verbal cues . Our aim was to evaluate the efficiency of a new biofeedback device compared with traditional intervention for gait rehabilitation . After orthopedic surgery , 33 patients , r and omly divided into a study group ( n = 15 ) and a control group ( n = 18 ) , completed 10 days of a rehabilitation protocol . A significant difference ( P<.05 ) was found between the groups . Study subjects were able to follow weight-bearing instructions better . We suggest that gait rehabilitation is more efficient when biofeedback is used to instruct patients regarding partial weight-bearing The aim of this study was to compare two proximal femur nails with regard to the complication rate and midterm clinical outcome : the InterTAN nail ( ITN ) versus the third generation gamma nail ( GN ) . 78 patients older than 60 years with an unstable intertrochanteric femoral fracture ( AO/OTA 31 A2/A3 ) were r and omised over a 20 month period into either ITN ( n = 39 ) or GN ( n = 39 ) . The outcomes of interest were the perioperative implant-related complications and the functional status ( Harris Hip Score ) at 6 months postoperatively . In 14 of the ITN and in two of the GN procedures the surgeons rated the implant as cumbersome ( p = 0.002 ) . Functional outcome and complication rate did not differ between both groups . The mechanical failure correlated with the positioning of the lag screw independent on the used implant . The surgeon 's technique ( closed reduction , positioning of lag screw ) and not implant configuration , is of crucial importance in achieving successful outcome BACKGROUND Femoral intramedullary nailing is currently one of the most frequent surgical treatments for extracapsular hip-fracture fixation . Cutting-out of the lag screw is the main complication of this technique , but only few studies have approached the cutting-out focussed on femoral nailing . The aim of this study was to confirm in patients treated with intramedullary nailing not only with regard to previous reports about the association of cutting-out with technical factors , but also with regard to clinical factors not previously studied . METHODS Case-control study of all patients sustaining a cut-out of the femoral nail was carried out and a control sample was r and omly selected among all extracapsular hip-fracture patients during the study period ( 2005 - 2008 ) . All clinical and technical variables were collected from medical records . Orthopaedic Trauma Association ( AO/OTA ) fracture classification , Singh Osteoporosis Index of the contralateral hip and the American Society of Anaesthesiology ( ASA ) criteria for preoperative clinical status were used . Statistical assessment included bivariant analysis and multivariant logistic regression analysis . RESULTS A total of 916 hip-fracture cases were treated in the study period : 33 of them ( 3.6 % ) were identified as suffering cutting-out , and 315 controls fulfilling inclusion criteria were also recruited . No statistical differences were found in age , sex or other socio-demographic variables between the two groups . Bivariant analysis showed significant differences between groups in technical variables ( tip-apex distance , suboptimal placement of lag screw , fracture diastasis , inadequate fixation quality and distal static locking ) and in clinical variables ( osteoporosis severity , right hip affected , better previous ability for walking and better preoperative ASA status ) . Multivariant logistic regression analysis showed significant association only for tip-apex distance and inadequate fixation quality . Differences in distal static locking were close to statistical significance . CONCLUSIONS The strongest predictor of cutting-out in femoral nailing is tip-apex distance . This study suggests that distal static locking and other clinical conditions play an important role in this fixation failure ABSTRACT Purpose : The purpose was to study the performance of exp and able proximal femoral nails ( EPFNs ) for the treatment of unstable intertrochanteric fractures in elderly patients . Patients and methods : Eighty-four patients were treated with a newly design ed EPFN and followed up for one year . Results : The mean operating time was 50.1 ± 3.2 min and the mean blood loss was 112.3 ± 5.3 ml . Patients were treated with EPFNs of 220 mm ( n = 24 ) , 240 mm ( n = 59 ) , and 340 mm ( n = 1 ) length . At six months postoperatively , the Harris Hip Score was 74.5 ± 5.3 . At the end of follow up , 75 % of patients completely recovered their preoperative function and resumed their normal activities . Seven patients died within one year postoperatively . During the operation , one patient experienced proximal femoral diaphyseal slight crack fracture . This crack fracture was treated by using a long EPFN ( 340 mm ) . Two patient developed screw cut-outs , which were solved by reoperation . And one developed deep infection resolved favorably by the appropriate antibiotic treatment . Implant failure , deep venous thrombosis , fat embolism , secondary fracture , and nonunion were not encountered . Conclusions : In conclusion , the results of the EPFNs were satisfactory in most elderly patients with unstable intertrochanteric fracture . However , during the inflation period , the pressure on the nail must be monitored carefully in order to prevent a crack fracture 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 Unstable intertrochanteric fractures present a challenge to orthopaedic surgeons , with varied geometry of the fractures and a wide choice of implants and techniques . The patients are usually osteoporotic , with multiple co-morbidities and poor tolerance for complications and re-operations . Lateral wall reconstruction and stability of the trochanteric fragments are considered important in providing a better outcome of these difficult injuries . We present a technique of lateral wall and trochanteric reconstruction using Cerclage wires and lag screws in the greater trochanter in addition to intramedullary nailing , and the radiological and functional outcome of this technique of augmentation . MATERIAL S AND METHODS This prospect i ve study includes 154 patients from 2010 to 2015 presenting to the institute with an unstable intertrochanteric fracture . They were sequentially operated with intramedullary nailing ( IMN ) and augmentation with cerclage wire and /or Anteroposterior screw in greater trochanter , and 77 patients with IMN only . Operating time and need for blood transfusion post-surgery were documented . Patients were followed up for minimum of 12 months and radiological union time , complications and functional outcome using Harris Hip Score were noted at 1 year . Statistical analysis was performed to compare the results in both groups RESULTS : The mean union was 3.6 months in group A and 4.1 months in group B , with no statistically significant difference . The operating time needed for augmentation was 10 minutes more than IMN only . Blood transfusion was not required in any case . The incidence of complications like screw cut out , back out and non-union was lower in augmented group , and good functional outcome was greater in the augmented group which was statistically significant . The reoperation rate was lower in augmented group . CONCLUSIONS This new technique of augmentation of fixation of intramedullary nail in unstable trochanteric fractures using cerclage wires and lag screws for lateral wall reconstruction is useful in reducing complications of the procedure and provides good radiological and functional outcome . It requires little additional operating time with minimal blood loss and soft tissue injury Partial weight bearing is a generally accepted principle of rehabilitation following trauma or reconstructive surgery of the lower extremity . Individual dynamic loads during partial weight bearing to a given load level of 200 N were compared in 23 patients who had sustained a fracture of the lower extremity and 11 healthy volunteers using dynamic sole pressure measurements . Excessive dynamic loading compared with the statically pre-tested 200 N level was observed in all groups . Maximum force levels were up to 690 N in young patients and up to 580 N elderly patients beyond the prescribed static load . None of the healthy volunteers was able to keep within the given load of 200 N. The set load level was exceeded by at least 38 N ( 119 % ) in the elderly patient group . In comparison , elderly patients showed statistically significantly higher maximum forces than young patients during the first two test days ( p=0.007 and 0.013 ) . On the 3rd test day the maximum ground contact forces were on average 71 N higher than in the young patients group . Analysis of the force time integrals ( impulses transferred to the ground ) displayed higher values in the older again than in young patients . The differences were statistically significant during the first two test days ( p=0.006 and 0.037 ) . This study implies that the conventional concept of postoperative partial weight bearing starting from 200 N and a stepwise increase of the load level until full weight bearing is not valid during clinical practice Objectives : To compare the results between a new intramedullary Gamma nail and a compression hip screw in the treatment of trochanteric fractures . Design : Prospect i ve r and omized . Setting : Level 1 trauma center . Patients : Two hundred ten consecutive patients older than 65 years with trochanteric femoral fractures . Interventions : Treatment with a compression hip screw or a new design of the Trochanteric Gamma nail ( 180 mm in length with a mediolateral angle of 4 ° and available only with a proximal diameter of 17 mm and distal diameter of 11 mm ) . Main Outcome Measurements : Operative and fluoroscopy times , blood loss , functional outcome , complication rate , and failure of fixation . Results : The Trochanteric Gamma nail was used in 104 patients and the compression hip screw in 106 . The 2 groups were similar in terms of their preoperative data , with a median follow-up of 13.6 months ( range 12 - 30 ) . The results show no difference in operating time ( P = 0.21 ) , but the Trochanteric Gamma nail group had a significantly shorter fluoroscopy time ( P = 0.006 ) , and the number of patients transfused and the mean of units of blood transfused were significantly less in the Trochanteric Gamma nail group ( P = 0.013 , 0.046 , respectively ) . Mortality within 12 months was similar in both groups ( P = 0.83 ) . All fractures Output:	With evidence available to date , there is no clear agreement on the postoperative rehabilitation protocol following fixation of an unstable trochanteric fracture by cephalomedullary nail in the elderly
MS21595	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Subjects with obesity and elevated fasting blood glucose are at high risk of developing type 2 diabetes which may be reduced by a dietary intervention leading to an improvement of insulin resistance . We investigated the potential of a whole-grain based dietary product ( WG ) with reduced starch content derived from double-fermented wheat during a hypo-energetic diet to positively influence body weight , fasting blood glucose , insulin resistance and lipids in comparison to a nutrient-dense meal replacement product ( MR ) in a r and omized two-way cross-over study with two 4-week treatment periods separated by a 2-week wash-out . Subjects replaced at least two daily meals with WG and MR , respectively , targeting for a consumption of 200 g of either product per day . Total daily energy intake was limited to 7120 kJ. Thirty-one subjects ( BMI 33.9 ( SD 2.7 ) kg/m2 , fasting blood glucose 6.3 ( SD 0.8 ) mmol/l ) completed the study . In both treatment groups body weight ( -2.5 ( SD 2.0 ) v. - 3.2 ( SD 1.6 ) kg for WG v. MR ) , fasting blood glucose ( -0.4 ( SD 0.3 ) v. -0.5 ( SD 0.5 ) mmol/l ) , total cholesterol ( -0.5 ( SD 0.5 ) v. -0.6 ( SD 0.5 ) mmol/l ) , TAG ( -0.3 ( SD 0.9 ) v. -0.3 ( SD 1.2 ) mmol/l ) and homeostasis model assessment ( HOMA ) insulin resistance score ( -0.7 ( SD 0.8 ) v. -1.1 ( SD 1.7 ) microU/ml x mmol/l ) improved ( P < 0.05 ) with no significant differences between the treatments . After statistical adjustment for the amount of body weight lost , however , the comparison between both groups revealed that fasting serum insulin ( P = 0.031 ) and HOMA insulin resistance score ( P = 0.049 ) improved better with WG than with MR . We conclude that WG favourably influences metabolic risk factors for type 2 diabetes independent from the amount of body weight lost during a hypo-energetic diet Background Fibre-rich rye products have been shown to have superior effects on self-reported appetite compared to white wheat bread and some studies have shown lower energy intake after subsequent meal . The aim of the present study was to evaluate the effects of whole grain rye crisp bread ( RB ) versus refined wheat bread ( WB ) on appetite in two studies using different portion sizes and total energy intakes . Methods Two r and omised cross-over pre-load studies were conducted in 20 and 21 subjects , respectively . Appetite was rated by visual analogue scale ( VAS ) for 4 h. In both studies , participants were 39 ± 14 years old and had BMI 23 ± 3 . The studies differed in terms of energy content of the breakfasts and proportion of energy from the treatment product as well as amount of test products . Differences between treatments within the two studies were evaluated using mixed models with repeated measures appropriate for cross-over design s. Results In Study one , hunger and desire to eat were significantly lower ( P < 0.05 ) after RB compared with WB , but there were no difference for fullness or difference in energy intake at lunch served ad libitum . In Study two , the portion size was lower than in Study one and the test product constituted a larger proportion of the breakfast . Fullness was significantly higher after RB compared with WB ( P < 0.05 ) and hunger , desire to eat as well as energy intake at lunch were significantly lower ( P < 0.05 ) . Conclusions Whole grain rye crisp bread caused lower self-reported hunger , higher fullness and less desire to eat compared to refined wheat bread . It also led to a lower energy intake after an ad libitum lunch . Results were stronger and /or more consistent when the test meal portion was smaller and accounted for a larger proportion of the total energy intake of the breakfast abstract Objectives : Whole grain sorghum is a promising ingredient in foods , especially those targeting satiety and weight control . This study aim ed to test weight loss effects of a whole grain red sorghum product incorporated into an energy-restricted diet . Methods : Sixty subjects ( 46 females ) were r and omized to either a sorghum ( intervention ) or white wheat ( control ) group , receiving 45 g of flaked cereal biscuits to include daily in their prescribed diets for 12 weeks . Primary outcome was weight loss . Secondary outcomes included plasma glucose , glycosylated hemoglobin ( HbA1c ) , insulin , total cholesterol , high-density lipoprotein cholesterol ( HDL-c ) , low-density lipoprotein cholesterol ( LDL-c ) , triacylglycerides ( TAG ) , interleukin (IL)-1β , IL-6 , IL-8 , tumor necrosis factor alpha ( TNF-α ) , high-sensitivity C-reactive protein ( hs-CRP ) , and total antioxidant capacity ( TAC ; measured at 0 and 12 weeks ) . Results : After 12 weeks , there were no significant differences in weight loss or any clinical variables between a wheat control and sorghum cereal group in an energy-restricted diet . Equivalent amounts of weight were lost ( p = 0.369 ) in both groups , and the majority of clinical indices such as fasting glucose , insulin , cholesterol , and key inflammatory biomarkers showed significant beneficial changes over time ( p < 0.05 ) . Conclusions : Although both groups experienced significant weight loss and general improvement in a number of clinical measures , no effects appeared specifically related to sorghum consumption . Further clinical trials are necessary to establish an evidence base for weight loss effects from chronic sorghum intake . Sorghum represents a viable , gluten-free grain alternative in the formulation of novel food products BACKGROUND Epidemiologic studies that directly examine changes in whole-grain consumption in relation to weight gain are sparse , and characterization of this association has been obscured by method ologic inconsistencies in the assessment of whole grains . OBJECTIVE We aim ed to ascertain the associations between changes in new quantitative estimates of whole-grain intake and 8-y weight gain among US men . DESIGN The study was conducted in a prospect i ve cohort of 27 082 men aged 40 - 75 y at baseline in 1986 . Data on lifestyle factors were obtained periodically by using self-reported question naires , and participants measured and reported their body weight in 1986 and 1994 . RESULTS In multivariate analyses , an increase in whole-grain intake was inversely associated with long-term weight gain ( P for trend < 0.0001 ) . A dose-response relation was observed , and for every 40-g/d increment in whole-grain intake from all foods , weight gain was reduced by 0.49 kg . Bran that was added to the diet or obtained from fortified-grain foods further reduced the risk of weight gain ( P for trend = 0.01 ) , and , for every 20 g/d increase in intake , weight gain was reduced by 0.36 kg . Changes in cereal and fruit fiber were inversely related to weight gain . No associations were observed between changes in refined-grain or added germ consumption and body weight . CONCLUSIONS The increased consumption of whole grains was inversely related to weight gain , and the associations persisted after changes in added bran or fiber intakes were accounted for . This suggests that additional components in whole grains may contribute to favorable metabolic alterations that may reduce long-term weight gain BACKGROUND Alkylresorcinols ( ARs ) , phenolic lipids exclusively present in the outer parts of wheat and rye grains , have been proposed as specific dietary biomarkers of whole-grain wheat and rye intake . OBJECTIVE The objective was to vali date plasma ARs as a biomarker of whole-grain wheat and rye intakes by study ing the correlation between their plasma concentration and intake calculated from food records . DESIGN In a r and omized crossover study , 22 women and 8 men were given a defined amount of either whole-grain or refined-cereal-grain products to be included in their habitual diets for two 6-wk periods . Blood sample s were collected and food intakes were recorded before and after each intervention period . RESULTS Plasma AR concentrations were significantly higher after the whole-grain diet period than after the refined-grain period ( P < 0.0001 ) and were well correlated with average daily AR intake estimated by self-reported weighed food records ( Spearman 's r = 0.58 , P < 0.001 ) . CONCLUSION Plasma AR concentrations are correlated with intake assessed by food records , which suggests that ARs are selective nutritional biomarkers for the intake of whole-grain wheat and rye BACKGROUND Although increased consumption of dietary fiber and grain products is widely recommended to maintain healthy body weight , little is known about the relation of whole grains to body weight and long-term weight changes . OBJECTIVE We examined the associations between the intakes of dietary fiber and whole- or refined-grain products and weight gain over time . DESIGN In a prospect i ve cohort study , 74,091 US female nurses , aged 38 - 63 y in 1984 and free of known cardiovascular disease , cancer , and diabetes at baseline , were followed from 1984 to 1996 ; their dietary habits were assessed in 1984 , 1986 , 1990 , and 1994 with vali date d food-frequency question naires . Using multiple models to adjust for covariates , we calculated average weight , body mass index ( BMI ; in kg/m(2 ) ) , long-term weight changes , and the odds ratio of developing obesity ( BMI > or = 30 ) according to change in dietary intake . RESULTS Women who consumed more whole grains consistently weighed less than did women who consumed less whole grains ( P for trend < 0.0001 ) . Over 12 y , those with the greatest increase in intake of dietary fiber gained an average of 1.52 kg less than did those with the smallest increase in intake of dietary fiber ( P for trend < 0.0001 ) independent of body weight at baseline , age , and changes in covariate status . Women in the highest quintile of dietary fiber intake had a 49 % lower risk of major weight gain than did women in the highest quintile ( OR = 0.51 ; 95 % CI : 0.39 , 0.67 ; P < 0.0001 for trend ) . CONCLUSION Weight gain was inversely associated with the intake of high-fiber , whole-grain foods but positively related to the intake of refined-grain foods , which indicated the importance of distinguishing whole-grain products from refined-grain products to aid in weight control Introduction Epidemiological studies suggest three daily servings of whole-grain foods ( WGF ) might lower cardiovascular disease risk , at least partly by lowering serum lipid levels . We have assessed the effects of consuming three daily portions of wholegrain food ( provided as wheat or a mixture of wheat and oats ) on lipoprotein subclass size and concentration in a dietary r and omised controlled trial involving middle aged healthy individuals . Methods After a 4-week run-in period on a refined diet , volunteers were r and omly allocated to a control ( refined diet ) , wheat , or wheat + oats group for 12 weeks . Our servings were determined in order to significantly increase the intakes of non starch polysaccharides to the UK Dietary Reference Value of 18 g per day in the whole grain groups ( 18.5 g and 16.8 g per day in the wheat and wheat + oats groups respectively in comparison with 11.3 g per day in the control group ) . Outcome measures were serum lipoprotein subclasses ' size and concentration . Habitual dietary intake was assessed prior and during the intervention . Of the 233 volunteers recruited , 24 withdrew and 3 were excluded . Results At baseline , significant associations were found between lipoprotein size and subclasses ' concentrations and some markers of cardiovascular risk such as insulin resistance , blood pressure and serum Inter cellular adhesion molecule 1 concentration . Furthermore , alcohol and vitamin C intake were positively associated with an anti-atherogenic lipoprotein profile , with regards to lipoprotein size and subclasses ' distribution . However , none of the interventions with whole grain affected lipoprotein size and profile . Conclusion Our results indicate that three portions of wholegrain foods , irrelevant of the type ( wheat or oat-based ) do not reduce cardiovascular risk by beneficially altering the size and distribution of lipoprotein subclasses . Trial Registration www.Controlled-Trials.com IS RCT N 27657880 Whole grain rye products have previously been shown to increase feelings of satiety for up to 8h after intake under st and ardized conditions . This study was set out to investigate the sustainability of the satiating effect after regular consumption of breakfast meals with whole grain rye porridge or refined wheat bread . The study was r and omized , cross-over and double-blind . Healthy subjects ( n=24 ) were r and omly assigned to daily consumption of iso-caloric st and ardized breakfast meals with whole grain rye porridge or refined wheat bread for two 3-wk phases , separated by a wash out of 3 - 4weeks . Each inter Output:	The primary outcome was the effectiveness of whole grain food consumption in reducing body weight . This study suggests that whole grain food consumption can slightly reduce body weight and CRP in obese/overweight population
MS21596	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Fursultiamine ( TTFD ) , a derivative of thiamine , at an oral dose of 100 mg/day had a mild beneficial effect in patients with Alzheimer 's disease in a 12-week open trial . The improvement could be observed not only in their emotional or other mental symptoms but also in intellectual function . Only mildly impaired subjects showed cognitive improvement . Alzheimer patients ' blood levels of thiamine before the trial were within the normal range . No adverse reactions were observed and all patients tolerated the trial well . TTFD could afford an alternate treatment to large doses of thiamine hydrochloride in Alzheimer patients . However , further investigations of the therapeutic implication s of thiamine and its possible etiologic clues to Alzheimer 's disease are necessary 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 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 As a test of the significance of previously described biochemical abnormalities in thiamine-dependent enzymes in brains and other tissues in patients with Alzheimer 's disease , a double-blind , placebo-controlled , crossover , outpatient pilot study compared the effects of 3 g/d of oral thiamine hydrochloride for three months with those of a niacinamide placebo . Eleven moderately impaired patients with " probable Alzheimer 's disease " by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria completed the study . All patients were well nourished and had no stigmata of dietary thiamine deficiency . Their initial mean + /- SEM Mini-Mental State Examination score was 14.2 + /- 1.4 , and the mean age was 72 years . Global cognitive rating by the Mini-Mental State Examination was higher during three months with 3 g/d of oral thiamine hydrochloride than with niacinamide placebo . Behavioral ratings , however , did not differ significantly , nor did clinical state when it was judged subjectively Output:	The data were compatible with thiamine producing harm , no change or improvement . There was no statistically significant difference in the test of Verbal Fluency and the Boston Naming Test . REVIEW ER 'S CONCLUSIONS This review finds no evidence that thiamine is a useful treatment for the symptoms of Alzheimer 's disease . Thiamine can not be recommended for patients with Alzheimer 's disease
MS21597	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To report an exploratory subgroup analysis assessing the extent to which the overall benefit found in the Early Prostate Cancer program is dependent on lymph node status at r and omization . The program is ongoing , and the overall survival data are immature . The first combined analysis of the bicalutamide ( Casodex ) Early Prostate Cancer program at 3 years ' median follow-up showed that bicalutamide , 150 mg once daily , plus st and ard care ( radical prostatectomy , radiotherapy , or watchful waiting ) , significantly reduced the risk of objective progression and prostate-specific antigen ( PSA ) doubling in patients with localized/locally advanced prostate cancer . METHODS Men ( n = 8113 ) with localized/locally advanced disease received bicalutamide 150 mg or placebo once daily , plus st and ard care . The time to event data ( objective progression , PSA doubling ) was analyzed by lymph node status at r and omization . RESULTS Compared with st and ard care alone , bicalutamide significantly reduced the risk of objective progression , irrespective of lymph node status , with the most pronounced reduction in patients with N+ ( hazard ratio [ HR ] 0.29 ; 95 % confidence interval [ CI ] 0.15 to 0.56 ) compared with those with N0 ( HR 0.59 ; 95 % CI 0.48 to 0.73 ) and Nx ( HR 0.60 ; 95 % CI 0.50 to 0.72 ) disease . The largest decrease in risk of PSA doubling with bicalutamide was observed in N+ disease ( HR 0.16 ; 95 % CI 0.09 to 0.29 ) , with significantly reduced risks seen in N0 ( HR 0.45 ; 95 % CI 0.40 to 0.51 ) and Nx ( HR 0.38 ; 95 % CI 0.33 to 0.44 ) disease . CONCLUSIONS The greatest reduction in the risk of objective progression and PSA doubling with bicalutamide was seen in patients with N+ disease . However , bicalutamide also provided a statistically significant benefit in those with N0 and Nx disease PURPOSE To evaluate the effect of immediate and rogen suppression in conjunction with st and ard external beam irradiation vs. radiation alone on a group of pathologically staged lymph node-positive patients with adenocarcinoma of the prostate . METHODS AND MATERIAL S A national prospect i ve r and omized trial ( RTOG 85 - 31 ) of st and ard external beam irradiation plus immediate and rogen suppression vs. external beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate . One hundred seventy-three of the patients in this trial had biopsy-proven pathologically involved lymph nodes . Ninety-eight of these patients received radiation plus the immediate and rogen suppression ( LHRH agonist ) , while 75 received radiation alone with hormonal manipulation instituted at the time of relapse . RESULTS With a median followup of 4.9 years , estimated progression-free survival with PSA < 1.5 ng/ml at 5 years was 55 % for the patients who received radiation plus immediate LHRH agonist vs. 11 % of the patients who received radiation alone with hormonal manipulation at relapse ( p = 0.0001 ) . Because all of these patients had locally advanced disease ( i.e. , pathologically positive lymph nodes ) , stage does not explain this difference in outcome , and Gleason grade was not statistically different between the two groups . Estimated absolute survival at 5 years for the radiation and LHRH group was 73 vs. 65 % for the radiation alone group who received and rogen suppression at relapse . Estimated disease-specific survival at 5 years was 82 % for the radiation and immediate LHRH agonist group and 77 % for the radiation-alone group . CONCLUSION Patients with adenocarcinoma of the prostate and pathologically involved pelvic lymph nodes ( pN+ or clinical stage D1 ) should be seriously considered for external beam irradiation plus immediate hormonal manipulation over radiation alone with hormonal manipulation at the time of relapse Concepts regarding the surgical treatment of cancer of the prostate have changed significantly at the Mayo Clinic . Rather than emphasizing radical prostatectomy only for low- grade ( grade less than or equal to 2 ) and low-stage ( less than or equal to T1/B1 ) lesions -- which may be equally well treated at less than ten years , in regard to crude survival , by radiotherapy -- we believe that radical prostatectomy is particularly suitable for lesions of higher local stages , including those with regional node extension . This view is based on a large experience ( less than 2,000 cases ) with the radical surgical treatment of cancer of the prostate and on the realization that conservative single-modality treatment ( hormonal or radiotherapy ) for advanced local Stages ( C and D1 ) provides poor cause-specific survival and nonprogression rates and may lead to high local morbidity . The treatment of Stage D1 prostate cancer was thought to be not amenable to surgical treatment , and many have recommended observation only . In 266 patients ( mean age , 64 years ) followed one to twenty-one years ( mean , 4.7 years ) , immediate adjuvant orchiectomy at the time of radical prostatectomy performed in 162 patients ( 61 % ) result ed in a highly significant ( P less than 0.0001 ) decrease in progression compared with no immediate orchiectomy in 104 patients ( 39 % ) . The ten-year overall and local nonprogression rates for those undergoing immediate orchiectomy were 80 percent and 98 percent , respectively ; median time to progression for the no-immediate-orchiectomy group was less than 4.5 years , and the local recurrence rate was 25 percent at ten years . Of all the pathologic variables , only DNA ploidy pattern had a significant influence on progression and cause-specific survival . Also , in patients with D1 disease and a nuclear DNA diploid pattern , immediate adjuvant orchiectomy result ed in a nonprogression rate of 100 percent at ten years compared with virtually 0 percent in those with a nondiploid tumor and no immediate orchiectomy . Because 42 percent of the patients with D1 disease in the Mayo Clinic experience have DNA diploid tumors , adjuvant orchiectomy in this group results in no progression or prostate cancer death . Patients with Stage D1 prostate cancer and DNA nondiploid pattern undergoing prostatectomy should be entered in prospect i ve adjuvant innovative treatment protocol s since these tumors do not seem to respond to early hormonal manipulation PURPOSE In a r and omized study we compared the combination of orchiectomy and radiotherapy to radiotherapy alone as treatment for locally advanced prostate cancer . Patients who were treated only with radiotherapy initially underwent castration therapy at clinical progression , providing the opportunity to compare immediate vs deferred endocrine intervention . MATERIAL S AND METHODS In this prospect i ve study 91 patients with locally advanced prostate cancer were r and omized to receive external beam radiotherapy ( 46 ) or combined orchiectomy and radiotherapy ( 45 ) after surgical lymph node staging . Survival rates were calculated . RESULTS During 14 to 19 years of followup 87 % of the patients in the radiotherapy group and 76 % in the combined orchiectomy and radiotherapy group died ( log rank p = 0.03 ) . Prostate cancer mortality was 57 % and 36 % , respectively ( log rank p = 0.02 ) . The difference in favor of combined treatment was mainly caused by lymph node positive tumors . For node negative tumors there was no significant difference in the survival rates . CONCLUSIONS Immediate and rogen deprivation should be considered instead of deferred endocrine treatment started at clinical progression for prostate cancer with spread to regional lymph nodes . While awaiting evidence from r and omized trials , one should consider full dose radiotherapy for local control of locally advanced prostate cancer even when it is lymph node positive 4570 Purpose : We previously reported 7 year follow-up of men with clinical ly localized prostate cancer , who underwent radical prostatectomy ( RP ) and pelvic lymphadenectomy ( PLD ) and were found to have nodal metastases ( N+ ) , had significantly improved survival and disease-specific survival with immediate ( within 3 months of surgery ) and continuous hormonal monotherapy ( HT ) compared with those who had and rogen ablation withheld until distant metastases were identified ( NEJM 341:1781,1999 ) . To determine the durability of this effect , we up date results at 10 years median follow-up . METHODS 98 men were r and omized to receive Goserelin acetate or bilateral orchiectomy ( N=47 ) vs. observation ( N=51 ) until distant disease was documented . Patients were followed with semi-annual exams and laboratory tests , and annual bone scans . RESULTS Patients were well-matched for age ( mean 65.9 yrs ) , prostate size , local extent , and Gleason score . Only 20 % of men had detectable PSA 's following their surgery at the time of r and omization . At median follow-up of 10 years , 13 of 47 men who received immediate HT died ( 6 of prostate cancer , 7 of non-prostate cancer causes with undetectable PSA 's at the time of death ) vs 26 in the deferred arm ( 22 of prostate cancer , 4 of non-prostate cancer ) . The differences in both overall ( immediate 72.4 % ; deferred 49.0 % , p = .025 ) , and cause specific ( immediate : 87.2 % ; deferred : 56.9 % , p = .001 ) survivals , between the two arms were significant . Toxicities of treatment were tolerable , and at last follow-up , no immediately treated man had experienced an osteoporotic fracture or had discontinued HT . CONCLUSION 10 years , early HT in patients with N+ disease following RP+PLD continues to be associated with highly significant improvements in overall and disease-specific survival . The treatment has been generally well tolerated . Early HT 's role in other disease scenarios warrants testing in prospect i ve r and omized studies . No significant financial relationships to disclose 4628 Background : The Early Prostate Cancer ( EPC ) program is an ongoing study of the effect of adding bicalutamide ( CASODEX ) 150 mg to st and ard care ( radiotherapy [ RT ] , radical prostatectomy [ RP ] , or watchful waiting [ WW ] ) for men with localized or locally advanced prostate cancer . At a median 7.4 years ' follow-up , bicalutamide significantly improved objective progression-free survival ( PFS ) in men with locally advanced disease , irrespective of st and ard care , and improved overall survival in the RT setting . There was no PFS benefit in patients with localized disease . Lymph-node involvement is an established risk factor for progression , so we conducted an exploratory analysis among patients with locally advanced disease to assess the influence of this risk factor on PFS . METHODS The EPC program ( n = 8113 ) comprises 3 r and omized trials design ed for combined analysis . Patients with localized ( T1 - 2 , N0/Nx ) or locally advanced ( T3 - 4 , any N ; or any T , N+ ) non-metastatic prostate cancer received bicalutamide ( n = 4052 ) or placebo ( n = 4061 ) once daily plus st and ard care . This sub analysis studied the effect of nodal status ( N- , N+ , Nx ) in locally advanced disease . RESULTS In patients with locally advanced disease , PFS improvements were irrespective of nodal status . The treatment effect increased as the risk of progression increased from N- to Nx to N+ disease . The greatest reduction in risk was seen in RP patients with N+ disease . CONCLUSIONS The reduction in risk of progression with bicalutamide was seen irrespective of nodal status . The most significant reduction in risk of progression was in RP patients with N+ disease ; survival data by nodal status for these patients will be presented . [ Table : see text ] [ Table : see text ] BACKGROUND Appropriate timing of and rogen deprivation treatment ( ADT ) for prostate cancer is controversial . Our aim was to determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed . METHODS Eligible patients from 36 institutes in the USA were r and omly assigned in 1988 - 93 to receive immediate ADT ( n=47 ) or to be observed ( n=51 ) , with ADT to be given on detection of distant metastases or symptomatic recurrences . Patients were followed up every 3 months for the first year and every 6 months thereafter . The primary endpoint was progression-free survival ; secondary endpoints were overall and disease-specific survival . Analysis was by intention to treat . To ensure that the treatment groups were comparable , we did a retrospective central pathology review of slides and re grade d the Gleason scores for available sample s. This trial pre date s the requirement for clinical trial registration . FINDINGS At median follow-up of 11.9 years ( range 9.7 - 14.5 for surviving patients ) , men assigned immediate ADT had a significant improvement in overall survival ( hazard ratio 1.84 [ 95 % CI 1.01 - 3.35 ] , p=0.04 ) , prostate-cancer-specific survival ( 4.09 [ 1.76 - 9.49 ] , p=0.0004 ) , and progression-free Output:	Conclusions The data available suggest an improvement in survival and delayed disease progression but increased adverse events for patients with node-positive prostate cancer after local therapy treated with early and rogen suppression therapy versus deferred and rogen suppression therapy .
MS21598	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Physical activity can reduce the risk of hip fractures in older women , although the required type and duration of activity have not been determined . Walking is the most common activity among older adults , and evidence suggests that it can increase femoral bone density and reduce fracture risk . OBJECTIVE To assess the relationship of walking , leisure-time activity , and risk of hip fracture among postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve analysis begun in 1986 with 12 years of follow-up in the Nurses ' Health Study cohort of registered nurses within 11 US states . A total of 61,200 postmenopausal women ( aged 40 - 77 years and 98 % white ) without diagnosis of cancer , heart disease , stroke , or osteoporosis at baseline . MAIN OUTCOME MEASURES Incident hip fracture result ing from low or moderate trauma , analyzed by intensity and duration of leisure-time activity and by time spent walking , sitting , and st and ing , measured at baseline and up date d throughout follow-up . RESULTS From 1986 to 1998 , 415 incident hip fracture cases were identified . After controlling for age , body mass index , use of postmenopausal hormones , smoking , and dietary intakes in proportional hazards models , risk of hip fracture was lowered by 6 % ( 95 % confidence interval [ CI ] , 4%-9 % ; P<.001 ) for each increase of 3 metabolic equivalent (MET)-hours per week of activity ( equivalent to 1 h/wk of walking at an average pace ) . Active women with at least 24 MET-h/wk had a 55 % lower risk of hip fracture ( relative risk [ RR ] , 0.45 ; 95 % CI , 0.32 - 0.63 ) compared with sedentary women with less than 3 MET-h/wk . Even women with a lower risk of hip fracture due to higher body weight experienced a further reduction in risk with higher levels of activity . Risk of hip fracture decreased linearly with increasing level of activity among women not taking postmenopausal hormones ( P<.001 ) , but not among women taking hormones ( P = .24 ) . Among women who did no other exercise , walking for at least 4 h/wk was associated with a 41 % lower risk of hip fracture ( RR , 0.59 ; 95 % CI , 0.37 - 0.94 ) compared with less than 1 h/wk . More time spent st and ing was also independently associated with lower risks . CONCLUSION Moderate levels of activity , including walking , are associated with substantially lower risk of hip fracture in postmenopausal women Background . The effect of physical training on bone mineral density ( BMD ) in women with endometriosis treated with gonadotropin‐releasing hormone ( GnRH ) analogs was studied Summary The purpose of this study was to determine the optimal intensity of exercise necessary to prevent the postmenopausal bone loss on the basis of anaerobic threshold ( AT ) . Thirty-three postmenopausal women were r and omized to control ( group C : n=12 ) or two exercise groups ( group H and group M ) . All women performed a treadmill exercise test , and the AT was measured by expired gas analysis . The exercise regimen consisted mainly of walking at a speed that kept the exercise heart rate above the AT ( group H : n=12 ) or below the AT ( group M : n=9 ) . Exercise was performed for 30 minutes , three times a week for 7 months . The bone mineral density ( BMD ) of the lumbar vertebrae was measured using dual energy X-ray absorptiometry . The BMD level in group C decreased by 1.7±2.7 % , but there was a significant increase of 1.1±2.9 % in group H. In group M there was a decrease of 1.0±3.1 % which did not differ from group C. In group C , serum osteocalcin and urinary hydroxyproline excretion were significantly increased , but no changes were seen in either of the exercise groups . Urinary calcium significantly decreased in the exercise groups . We conclude that short-term ( 7 months ) exercise with intensity above the AT is safe and effective in preventing postmenopausal bone loss Abstract . Several meta-analyses confirm that physical exercise can slow down postmenopausal bone loss , but it is not clear whether physical exercise alone can increase bone mass . Our intent was to evaluate high-impact exercises ( including jumping ) and combined balance and leg-strength training , with and without raloxifene treatment , in three healthy elderly women , age 68–71 years . The 40-week study period consisted of two 17-week exercise periods with a 6-week rest period in between . The jumping exercises were performed both vertically and in different directions . Effects were measured in bone mineral density ( BMD ) , balance , maximal gait speed , and leg extensor strength . BMD ( g/cm2 ) was measured with dual-energy X-ray photon absorptiometry ( DXA ) at the proximal femur , lumbar spine , and total body . After the first exercise period , large losses of trochanteric BMD ( 8.1%–10.8 % ) were seen in all subjects . After both 6 weeks of rest and the second exercise period , which included both exercise and raloxifene , BMD increased in all subjects . During both exercise periods , the balance , gait speed , and leg extensor strength increased in all subjects . The results show that this kind of high-impact exercise had limited effects on BMD , but had large positive effects on balance , gait speed , and leg extensor strength . In conclusion , high-impact exercise in elderly women improves their fall risk factors , but , at least without raloxifene treatment , the trochanteric fracture risk might even increase because of reduction in the regional bone mass 1 . This study examined the influence of brisk walking on skeletal status in post-menopausal women . 2 . Subjects were 84 healthy women aged 60 - 70 years . Who were previously sedentary and at least 5 years post-menopausal . Subjects were r and omly assigned to walking ( n = 43 ) and control ( n = 41 ) groups . Walkers followed a 12-month , largely unsupervised programme of brisk walking . The bone mineral density of the lumbar spine , femoral neck and calcaneus and broadb and ultrasonic attention of the calcaneus were measured at baseline and after 12 months . 3 . Forty control subjects and 38 walkers completed the study . Walkers built up to 20.4 + /- 3.8 min/day ( mean + /- SD ) of brisk walking . Body mass increased in control subjects relative to walkers [ mean change ( SE ) + 0.9 ( 0.3 ) and -0.1 ( 0.3 ) kg respectively ; P = 0.04 ] . Predicted maximum oxygen uptake increased in walkers by 2.1 ( 0.9 ) ml min-1 kg-1 ( P = 0.02 ) . Bone mineral density in the lumbar spine and calcaneus fell in control subjects [ -0.005 ( 0.004 ) and -0.010 ( 0.004 ) g/cm2 , respectively ] but not in walkers [ + 0.006 ( 0.004 ) and + 0.001 ( 0.004 ) g/cm2 ] . The difference in response between groups was significant in the calcaneus ( P = 0.04 ) but not in the lumbar spine ( P = 0.08 ) . Mean femoral neck bone mineral density did not change significantly in either group , although changes in walkers were related to the amount of walking completed ( r = 0.51 , P = 0.001 ) . The change in broadb and ultrasonic attenuation of the calcaneus differed between groups [ control subjects , -3.7 ( 0.8 ) ; walkers , -0.7 ( 0.8 ) dB/MHz ; P = 0.01 ] . 4 . Walking decreased bone loss in the calcaneus and possibly in the lumbar spine . It also improved functional capacity and enabled walkers to avoid the increase in body mass seen in control subjects OBJECTIVE to evaluate the effects of brisk walking on bone mineral density in women who had suffered an upper limb fracture . DESIGN r and omized placebo-controlled trial . Assessment s of bone mineral density were made before and at 1 and 2 years after intervention . St and ardized and vali date d measures of physical capacity , self-rated health status and falls were used . SETTING district general hospital outpatient department . SUBJECTS 165 women drawn from local accident and emergency departments with a history of fracture of an upper limb in the previous 2 years . Women were r and omly allocated to intervention ( self-paced brisk walking ) or placebo ( upper limb exercises ) groups . INTERVENTION both groups were seen at 3-monthly intervals to assess progress , measure physical capacity and maintain enthusiasm . The brisk-walking group were instructed to progressively increase the amount and speed of walking in a manner that suited them . The upper limb exercise placebo group were asked to carry out a series of exercises design ed to improve flexibility and fine h and movements , appropriate for a past history of upper limb fracture . RESULTS drop-outs from both intervention and placebo groups were substantial ( 41 % ) , although there were no significant differences in bone mineral density , physical capacity or health status between drop-outs and participants . At 2 years , among those completing the trial , bone mineral density at the femoral neck had fallen in the placebo group to a greater extent than in the brisk-walking group [ mean net difference between intervention and placebo groups 0.019 g/cm2 , 95 % confidence interval ( CI ) -0.0026 to + 0.041 g/cm2 , P = 0.056 ] . Lumbar spine bone mineral density had increased to a similar extent ( + 0.017 g/cm2 ) in both groups . The cumulative risk of falls was higher in the brisk-walking group ( excess risk of 15 per 100 person-years , 95 % CI 1.4 - 29 per 100 person-years , P < 0.05 ) . There were no significant differences in clinical or spinal x-ray fracture risk or self-rated health status between intervention and placebo groups . CONCLUSION the promotion of exercise through brisk-walking advice given by nursing staff may have a small , but clinical ly important , impact on bone mineral density but is associated with an increased risk of falls . Self-paced brisk walking is difficult to evaluate in r and omized controlled trials because of drop-outs , placebo group exercise , limited compliance and lack of st and ardization of the duration and intensity of walking . Further work is needed to evaluate the best means of safely achieving increased activity levels in different groups , such as older women and those at high risk of fractures Abstract . Osteoporosis is one of the most common skeletal disorders affecting postmenopausal women . The purpose of this study was to investigate whether a 24-week program of aerobic high-impact loading exercise was beneficial for enhancing physical fitness and bone mineral density ( BMD ) in osteopenic postmenopausal women . Forty-three postmenopausal women aged 48–65 years participated in this study . The BMD of the spine ( L2–L4 ) and right femoral neck of each woman was below 1 SD of the mean of premenopausal women , as examined by dual X-ray absorptiometry . The assignment of subjects into exercise or control group was not r and omized but based on each subject 's anticipated compliance to the 6-month long exercise program . Twenty-two subjects joined the exercise group and attended the training programs and 21 served as the control group . Exercise programs included treadmill walking at an intensity above 70 % of maximal oxygen consumption ( VO2max ) for 30 minutes , followed by 10 minutes of stepping exercise using a 20-cm-high bench . The program was conducted three times per week for 24 weeks . Physical fitness measurements included testing of flexibility , muscular strength and endurance , body composition , and cardiopulmonary fitness . The results showed that the quadriceps strength , muscular endurance , and VO2max in the exercise group had significant improvements , whereas no improvement was found in any of the physical fitness parameters in the control group . The BMD of the L2–L4 and the femoral neck in the exercise group increased 2.0 % ( P > 0.05 ) and 6.8 % ( P < 0.05 ) and those in the control group decreased 2.3 % ( P < 0.05 ) and 1.5 % ( P > 0.05 ) , respectively . In conclusion , aerobics combined with high-impact exercise at a moderate intensity was effective in off setting the decline in BMD in osteopenic postmenopausal women The separate and combined effects of weight-bearing exercise and hormone replacement therapy ( HRT ) on bone mineral density ( BMD ) were studied in 32 women , 60 to 72 years of age . HRT consisted of continuous conjugated estrogens 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days . Exercise consisted of 2 months of low-intensity exercise followed by 9 months of more vigorous weight-bearing exercise approximately 45 minutes/day , > or = 3 days/week , at 65 - 85 % of maximal heart rate . Lumbar spine and proximal femur BMD were significantly increased in response to exercise and to HRT , and total body BMD was significantly increased in response to HRT ; neither exercise nor HRT had an effect on wrist BMD . The combination of exercise + HRT result ed in increased BMD at all sites except the wrist , with effects being additive for the Output:	We conclude that regular walking has no significant effect on preservation of BMD at the spine in postmenopausal women , whilst significant positive effects at femoral neck are evident . Other forms of exercise that provide greater targeted skeletal loading may be required to preserve bone mineral density in this population
MS21599	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The purpose of the study was to determine if the adjunctive administration of magnesium sulfate with ritodrine would result in decreased dosage requirements of ritodrine , and , therefore , decrease the incidence of ritodrine-associated side effects . C and i date s for tocolysis were prospect ively r and omized so that some received a uniform tocolytic dose of magnesium sulfate in a blinded protocol . All patients received a ritodrine infusion which was titrated in the st and ard manner to achieve cessation of labor . Evaluations included interval cumulative ritodrine dose , maximal ritodrine infusion rate , fluid balance , and blood chemistry studies . Contrary to our hypothesis , there were significantly more cardiovascular effects in the group that received ritodrine plus magnesium sulfate ( 11/24 ) than in the group that received ritodrine alone ( 1/17 ) ( p less than or equal to 0.02 ) . The predominant side effect was chest pain , frequently associated with electrocardiogram changes indicative of myocardial ischemia . These results are consistent with the current underst and ing of the regulatory mechanisms of these tocolytic agents . We conclude from the results of our prospect i ve , r and omized , blinded study that the adjunctive use of magnesium sulfate with ritodrine is associated with an unacceptable increase in serious side effects and probably does not improve efficacy BACKGROUND The efficacy and safety of repeat doses of prenatal corticosteroids remains uncertain . Our aim was to establish whether repeat prenatal corticosteroids given to women at risk of preterm birth can reduce neonatal morbidity without harm . METHODS In this hospital-based study , 982 women who remained at risk of preterm birth at less than 32 weeks ' gestation , 7 or more days after receiving a first course of prenatal corticosteroids , were r and omly assigned to receive a repeat intramuscular dose of either 11.4 mg betamethasone ( as Celestone Chronodose ) , or saline placebo . This was repeated every week the woman remained undelivered , at less than 32 weeks ' gestation , and at risk of preterm birth . Primary outcomes were occurrence and severity of neonatal respiratory distress syndrome , use and duration of oxygen and mechanical ventilation , and weight , length , and head circumference at birth and hospital discharge . Statistical analyses were on an intention to treat basis . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N48656428 . FINDINGS Fewer babies exposed to repeat corticosteroids had respiratory distress syndrome ( 33%vs 41 % ; relative risk 0.82 , 95 % CI 0.71 - 0.95 , p=0.01 ) and fewer had severe lung disease ( 12%vs 20 % ; relative risk 0.60 , 95 % CI 0.46 - 0.79 , p=0.0003 ) than those in the placebo group . In keeping with these benefits , babies exposed to repeat corticosteroids needed less oxygen therapy ( p=0.03 ) , and shorter duration of mechanical ventilation ( p=0.01 ) . Mean weight , length , and head circumference at birth and hospital discharge did not differ between treatment groups . Z-scores for weight ( p=0.04 ) and head circumference ( p=0.03 ) at birth were lower in the babies who received repeat corticosteroids although at the time of hospital discharge Z-scores did not differ between treatment groups ( p=0.29 for weight , p=0.48 for head circumference ) . INTERPRETATION Exposure to repeat doses of antenatal corticosteroids reduces neonatal morbidity . Pending long-term outcome results , the short-term benefits for the babies in our study support the use of repeat doses of corticosteroids in women who remain at risk of very preterm birth 7 or more days after an initial course The purpose of this study was to describe the course of preterm labor in patients receiving a st and ard intravenous infusion of the oxytocin antagonist atosiban . An open-labeled , non-r and omized study was conducted at 4 sites . Successful tocolysis was defined as delay of delivery larger than 48 hours from starting atosiban and no need for an alternate tocolytic . Atosiban was administered by continuous intravenous infusion at a rate of 300 micrograms per minute until uterine contractions were absent for 6 hours , or up to a maximum infusion time of 12 hours . Sixty-two patients of between 20 and 36 weeks ' gestation were enrolled over 6 months . One had rupture of membranes and was excluded . Successful tocolysis was noted in 43 of 61 ( 70.5 % ) . Four delivered spontaneously within 48 hours and 14 ( 23.0 % ) required an alternate tocolytic agent . The chance of successful tocolysis was related to the degree of cervical dilation at the start of therapy . Cessation of uterine contractions was noted in 38 patients ( 62.3 % ) . A decrease in uterine contraction frequency of 50 % or more was noted in 50 of 61 patients ( 82.0 % ) . Four patients reported side effects ( nausea , vomiting , headache , dysguesia , chest pain ) , but in no case did side effects require discontinuation of the medication . Intravenous administration of atosiban is associated with a delay in delivery comparable to that seen with other tocolytics . If this effect is confirmed in planned placebo-controlled trials , its favorable side effect profile may give it a place in the armamentarium The purpose of this r and omized study was to compare the efficacy of ritodrine alone ( 51 ) versus ritodrine plus magnesium gluconate ( 56 ) . We concluded that high oral doses of magnesium therapy ( 4 x 3 gr ) potentiate the effects of intravenous beta-agonists , allowing a reduction of the dosage needed and a better " tolerance " . Considering the low side effects , it seems reasonable to consider using magnesium in the treatment of premature labour Objectives . We evaluated the efficacy of magnesium sulfate as a second-line tocolysis for 48 hours . Material s and Methods . A multi-institutional , simple 2-arm r and omized controlled trial was performed . Forty-five women at 22 to 34 weeks of gestation were eligible , whose ritodrine did not sufficiently inhibit uterine contractions . After excluding 12 women , 33 were r and omly assigned to either magnesium alone or combination ( ritodrine and magnesium ) . The treatment was determined as effective if the frequency of uterine contraction was reduced by 30 % at 48 hours of the treatment . Results . After magnesium sulfate infusion , 90 % prolonged their pregnancy for > 48 hours . Combination therapy was effective in 95 % ( 18/19 ) , which was significantly higher than 50 % ( 7/14 ) for magnesium alone . Conclusion . This r and omized trial revealed that combination therapy significantly reduced uterine contractions , suggesting that adjuvant magnesium with ritodrine is recommended , rather than changing into magnesium alone , when uterine contractions are intractable with ritodrine infusion Objective . Red blood cell ( RBC ) deformability is an important factor in determining movement of red blood cells through the microcirculation . In preeclampsia and some cases of intrauterine growth restriction ( IUGR ) , RBC deformability and microcirculation are reduced . Magnesium is administered to reduce the risk of seizures . The aim of this study was first to detect the effect of intravenous magnesium application ( 2 g/h ) on the deformability of RBCs in pregnancies with normal RBC deformability , receiving magnesium as tocolytic agent . The second aim was to examine the effect of calcium-antagonists ( magnesium , nifedipin ) on the deformability of RBC of preeclamptic patients in vitro . Methods . Part 1 : magnesium ( 2 g/h ) , fenoterol ( 270 µg/h ) + verapamil ( 0.2 mg/h ) or placebo ( NaCl 0.9 % ) was administered intravenously to pregnant women with premature contractions to test the tocolytic effect . RBC-deformability was measured by laser diffractoscopy in all three groups . Blood sample s were taken before , after 1 h and after 24 h of administration . Magnesium-plasma-levels were measured . Part 2 : Blood sample s from patients with preeclampsia were incubated in vitro with magnesium ( 2 mmol ) , nifedipine ( 0.25 mg/ml ) , or placebo ( NaCl 0.9 % ) . RBC deformability was measured before and 15 min , 1h , 2h , 6h , and 10h after start of the incubation . Results . Part 1 : The initial RBC-deformability was the same in all groups ( E=0.232 ± 0.017 in NaCl , 0.232 ± 0.023 in fenoterol + verapamil , 0.232 ± 0.019 in magnesium ) . After 1 h of administration , RBC-deformability was significantly greater with magnesium ( 0.254 ± 0.020 ) and Fenoterol + Verapamil ( 0.238 ± 0.02 ) compared to placebo ( 0.231 ± 0.015 ) . After 24 h the effect on RBC deformability in the fenoterol + verapamil-group was gone ( 0.234 ± 0.021 compared to 0.234 ± 0.016 in placebo ) , while in the IV-magnesium-group RBC-deformability remained increased ( E=0.241 ± 0.019 ) . Statistical analysis of the influence of magnesium-plasma-levels showed the maximum effect at concentrations of 1.95–2.15mmol/l . Part 2 : RBC-deformability in preeclampsia was reduced as predicted by previous studies ( 0.120 + 0.0086 versus 0.232 in normal pregnancy ) . In vitro incubation with magnesium enhanced RBC-deformability in preeclampsia . Even after 15 min , a statistically significant effect was seen ( 0.127 ± 0.0091 versus 0.121 ± 0.0091 in placebo ) . Maximum effect was reached after 6 h of incubation ( 0.159 ± 0.0093 versus 0.133 ± 0.0091 ) . Incubation with Nifedipine also enhanced RBC deformability [ 0.127 ± 0.0091 after 15 min , 0.149 ± 0.010 after 6 h ( maximum effect ) ] , but the effect was less pronounced than with magnesium . Conclusion . Intravenous magnesium therapy over a 24-hour period increases RBC-deformability even in pregnancies with normal RBC-deformability . In vitro measurements show an increase of RBC-deformability in preeclampsia in response to magnesium , which could offer additional therapeutic benefit for the treatment of reduced blood flow seen in most cases of preeclampsia Seventeen patients in advanced premature labor ( cervical dilatation greater than or equal to 3 cm and effacement greater than or equal to 50 % ) were r and omized in a double-blind protocol to receive metoprolol ( a beta 1-adrenergic antagonist ) or a placebo in conjunction with intravenous and oral terbutaline ( a beta 2-agonist ) in an attempt to inhibit the side effects of terbutaline . Both groups of patients had a dose-related increase in heart rate and systolic blood pressure and a decrease in diastolic blood pressure . Laboratory studies revealed significant hyperglycemia , hypokalemia , hypocalcemia , and acidosis during the intravenous terbutaline infusion , all of which normalized during oral terbutaline therapy . There were no significant differences in the cardiovascular or metabolic responses to terbutaline between the metroprolol and placebo patients . The mean delay in delivery was 5.7 days , with 59 % of patients having delivery delayed for 48 hours or more . The mean prolongation time was shorter , but not statistically significant , for those patients receiving metroprolol . Despite the use of high-dose terbutaline , there were no significant complications of therapy . There was little efficacy of infusion dosages above 40 micrograms/min or repeated courses of intravenous tocolysis . Although recent reports do not recommend tocolysis in these patients , this study suggests that combined beta-mimetics and glucocorticoids may be the optimal care for patients in advanced premature labor , in particular , those with infants of very low birth weight A prospect i ve and double-blind study was undertaken to compare the effectiveness of two different treatments on two r and omized groups of patients with threatened preterm labor . The first treatment consisted of the administration of ritodrine and a placebo ; in the second , ritodrine was combined with indomethacin . 22 patients were evaluated in each group . The results obtained for gain in days , number of patients delivered at term , weight of newborns and number of recurrences in each group suggest that treatment with ritodrine and indomethacin is slightly but significantly more effective than treatment with ritodrine and placebo in prolonging pregnancy . No evidence has been found of possible unfavorable vascular effects of indomethacin in the fetus Output:	There were no significant differences between groups receiving IV ritodrine plus vaginal progesterone compared with IV ritodrine alone for most outcomes reported , although the latency period ( time from recruitment to delivery ) was increased in the group receiving the combination of tocolytics . For other combinations of tocolytic agents , primary outcomes were rarely reported and for secondary outcomes results did not demonstrate differences between groups .

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