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MS22000	*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 We examined the effect of a peer-delivered educational intervention , the Malawi Male Motivator intervention , on couples ' contraceptive uptake . We based the intervention design on the information-motivation-behavioral skills ( IMB ) model . METHODS In 2008 we recruited 400 men from Malawi 's Mangochi province who reported not using any method of contraception . We r and omized them into an intervention arm and a control arm , and administered surveys on contraceptive use at baseline and after the intervention . We also conducted in-depth interviews with a subset of intervention participants . RESULTS After the intervention , contraceptive use increased significantly within both arms ( P < .01 ) , and this increase was significantly greater in the intervention arm than it was in the control arm ( P < .01 ) . Quantitative and qualitative data indicated that increased ease and frequency of communication within couples were the only significant predictors of uptake ( P < .01 ) . CONCLUSIONS Our findings indicate that men facilitated contraceptive use for their partners . Although the IMB model does not fully explain our findings , our results show that the intervention 's content and its training in communication skills are essential mechanisms for successfully enabling men to help couples use a contraceptive The aim of this study was to determine the effect of health education on the knowledge and attitude regarding family planning and contraception ’s method among the women who obligatory attended the Premarital Counseling Center in Yasouj city , Iran . An experimental study was carried out and a total of 200 women were selected for the study using convenience sampling method among women who attended in the health centre in order to utilize the necessary premarital actions . Respondents were divided by two experimental and control groups r and omly . A pre-evaluation was done on the knowledge and attitude on family planning using a structured question naire . After which , the health education for experimental group was done within four educational sessions during 4 consecutive weeks and control group underwent traditional education method . Post evaluation was utilized for any changes regarding their knowledge and attitude among the respondents immediately after the intervention . Independent and paired t-test was used to evaluate the mean knowledge and attitude scores differences among both groups . Results showed that there was a significant improvement in respondents ’ knowledge and attitude after educational program in experimental group ( p<0.001 ) , while no significant difference was observed in knowledge and attitude of control group . The finding also indicated that age was significantly associated with the level of respondents ’ knowledge . These results deal the effectiveness of the educational method . In conclusion , the educational method is effective in increasing the knowledge and improving the attitude of women regarding family planning in Yasouj compared to current used educational method . Future educational programs need to incorporate the features that have been associated with successful interventions in the past , as well as including their own evaluation procedures This study tested the hypothesis that individual counselling in the third trimester would increase postpartum contraceptive use to a greater extent than only providing an educational leaflet . A total of 180 third trimester pregnant women of mean age 28.3 years who were attending Marmara University Hospital for prenatal care were enrolled . One-third were r and omly allocated to receive prenatal contraceptive counselling and the remaining two-thirds ( control group ) received an educational leaflet . Participants were followed-up at 6–9 months postpartum . The majority of subjects ( 91.5 % ) wanted to use contraception after delivery but 26.7 % did not know which method to use . At follow-up , 79.6 % of all women had begun a postpartum contraceptive regime and 68.7 % were using a modern contraceptive method . Overall , there was no statistically significant difference in postpartum contraception use between the control and intervention groups in this study population . It is , therefore , concluded that prenatal counselling was not superior to educational leaflets for increasing the use of effective and modern postpartum contraception Background A number of single case reports have suggested that the context within which intervention studies take place may challenge the assumptions that underpin r and omised controlled trials ( RCTs ) . However , the diverse ways in which context may challenge the central tenets of the RCT , and the degree to which this information is known to research ers or subsequently reported , has received much less attention . In this paper , we explore these issues by focusing on seven RCTs of interventions varying in type and degree of complexity , and across diverse context s. Methods This in-depth multiple case study using interviews , focus groups and documentary analysis was conducted in two phases . In phase one , a RCT of a nurse-led intervention provided a single exploratory case and informed the design , sampling and data collection within the main study . Phase two consisted of a multiple explanatory case study covering a spectrum of trials of different types of complex intervention . A total of eighty-four data sources across the seven trials were accessed . Results We present consistent empirical evidence across all trials to indicate that four key elements of context ( personal , organisational , trial and problem context ) are crucial to underst and ing how a complex intervention works and to enable both assessment s of internal validity and likely generalisability to other setting s. The ways in which context challenged trial operation was often complex , idiosyncratic , and subtle ; often falling outside of current trial reporting formats . However , information on such issues appeared to be available via first h and ‘ insider accounts ’ of each trial suggesting that improved reporting on the role of context is possible . Conclusions Sufficient detail about context needs to be understood and reported in RCTs of complex interventions , in order for the transferability of complex interventions to be assessed . Improved reporting formats that require and encourage the clarification of both general and project-specific threats to the likely internal and external validity need to be developed . In addition , a cultural change is required in which the open and honest reporting of such issues is seen as an indicator of study strength and research er integrity , rather than a symbol of a poor quality study or investigator ability OBJECTIVES This study was undertaken to determine the relative efficacy of home visitation with and without husb and participation on the use of modern contraception in Ethiopia . METHODS A r and omized field trial of a family planning education intervention using home visitation with and without husb and participation was conducted in Addis Ababa , Ethiopia , from August 1990 to December 1991 and included a 12-month postintervention follow-up . A total of 266 experimental and 261 control subjects were entered , of whom 91.7 % and 88.9 % , respectively , were followed through 12 months . RESULTS A greater proportion of couples in the experimental group were practicing modern contraception at 2 months ( 25 % vs 15 % ) and 12 months ( 33 % vs 17 % ) following the home visit intervention . By 12 months following the home visits , experimental subjects were less likely to have defaulted and more likely to have started using modern contraception following an initial delay . CONCLUSIONS The inclusion of husb and s in family planning programs will result in relevant increases in the use of modern contraception . However , there exists an important " sleeper " effect to the education intervention , reflected by a delay of greater than 2 months in the initiation of modern contraception for most couples A r and omized community trial of a family planning outreach program was conducted in Rakai District , Ug and a. Five communities received st and ard services ; six intervention communities received additional family planning information , counseling , and contraceptive methods from government service providers and community-based volunteer agents using social marketing and other strategies . Condom use was promoted in all of the communities . The community-based family planning outreach program was implemented in two phases--1999 - 2000 ( early ) and 2001(late)-- and its impact was evaluated by means of population surveys in 2002 - 03 . At follow-up , hormonal contraceptive prevalence was 23 percent in the intervention communities , compared with 20 percent in the control communities . The differential was greater in the early-intervention communities than the late-intervention communities . Pregnancy rates at follow-up were 15 percent in the control and 13 percent in the intervention communities . No differentials in condom use were found between study arms . Family planning outreach via social marketing can significantly increase hormonal contraceptive use and decrease pregnancy rates , but the impact of this outreach program was modest BACKGROUND The study was conducted to determine the impact of counseling and educational leaflets on contraceptive practice s of couples . STUDY DESIGN R and omization of 600 women was done in two groups matched for age , parity and socioeconomic status at the Department of Obstetrics and Gynaecology , Shifa Foundation Community Health Centre , Shifa International Hospital , Islamabad , Pakistan . In Group A , the intervention group was exposed to contraceptive counseling and educational leaflets in the postnatal ward after delivery , whereas in Group B , the nonintervention group was not given any formal contraceptive advice . Later on , both groups were assessed regarding their contraceptive practice s. RESULTS At their follow-up visit ( 8 - 12 weeks ) postpartum , 19 ( 6.3 % ) women in the nonintervention group had started contraceptive use , whereas 153 ( 50.8 % ) had decided to start contraception in the next 6 months , and 129 ( 42.8 % ) women were still undecided . The main contraceptive user was the male partner ( n=117 , 38.8 % ) , and the most common method used was coitus interruptus ( n=62 , 36.3 % ) . In the intervention group , 170 women ( 56.9 % ) had started using contraceptives , whereas 129 ( 43.1 % ) had decided to start contraceptive use in the next 6 months . The predominant contraceptive user was the females ( n=212 - 70.9 % ) , and the most popular method chosen was oral contraceptive pills ( n=111 , 37.1 % ) . CONCLUSION There is a definite increase in contraceptive uptake in women provided with educational leaflets and counseling session with a shift toward use of more reliable contraceptive methods The impact of antenatal counselling on couples ' knowledge and practice of contraception was investigated . An interview question naire was used before and after conducting counselling sessions with 200 pregnant women and 100 spouses . The participants were followed up immediately after delivery and 3 months later . Both the control and study groups displayed a lack of knowledge of contraception . Counselling sessions improved the couples ' knowledge and practice in the study group . Involving husb and s in family planning counselling sessions led to joint decisions being made and encouraged women 's use of contraception . The majority of couples retained most of the information given . Integrating family planning counselling into antenatal care in all facilities and involving the husb and are recommended BACKGROUND Group , rather than individual , family planning counseling has the potential to increase family planning knowledge and use through more efficient use of limited human re sources . STUDY DESIGN A r and omized , noninferiority study design was utilized to identify whether group family planning counseling is as effective as individual family planning counseling in Ghana . Female gynecology patients were enrolled from two teaching hospitals in Ghana in June and July 2008 . Patients were r and omized to receive either group or individual family planning counseling . The primary outcome in this study was change in modern contraceptive method knowledge . Changes in family planning use intention before and after the intervention and intended method type were also explored . RESULTS Comparisons between the two study arms suggest that r and omization was successful . The difference in change in modern contraceptive methods known from baseline to follow-up between the two study arms ( group-individual ) , adjusted for study site , was -0.21 , ( 95 % confidence interval : -0.53 to 0.12 ) suggesting no difference between the two arms . CONCLUSIONS Group family planning counseling was as effective as individual family planning counseling in increasing modern contraceptive knowledge among female gynecology patients in Ghana Output:	Dem and generation interventions contribute to increases in modern contraceptive methods use .
MS22001	*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 : Caregivers of people with chronic conditions are more likely than non-caregivers to have depression and emotional problems . Few studies have examined the effectiveness of mindfulness-based stress reduction ( MBSR ) in improving their mental well-being . Methods : Caregivers of persons with chronic conditions who scored 7 or above in the Caregiver Strain Index were r and omly assigned to the 8-week MBSR group ( n = 70 ) or the self-help control group ( n = 71 ) . Vali date d instruments were used to assess the changes in depressive and anxiety symptoms , quality of life , self-efficacy , self-compassion and mindfulness . Assessment s were conducted at baseline , post-intervention and at the 3-month follow-up . Results : Compared to the participants in the control group , participants in the MBSR group had a significantly greater decrease in depressive symptoms at post-intervention and at 3 months post-intervention ( p < 0.01 ) . The improvement in state anxiety symptoms was significantly greater among participants in the MBSR group than those of the control group at post-intervention ( p = 0.007 ) , although this difference was not statistically significant at 3 months post-intervention ( p = 0.084 ) . There was also a statistically significant larger increase in self-efficacy ( controlling negative thoughts ; p = 0.041 ) and mindfulness ( p = 0.001 ) among participants in the MBSR group at the 3-month follow-up compared to the participants in the control group . No statistically significant group effects ( MBSR vs. control ) were found in perceived stress , quality of life or self-compassion . Conclusions : MBSR appears to be a feasible and acceptable intervention to improve mental health among family caregivers with significant care burden , although further studies that include an active control group are needed to make the findings more conclusive BACKGROUND : Compared with other parents , mothers of children with autism spectrum disorder or other neurodevelopmental disabilities experience more stress , illness , and psychiatric problems . Although the cumulative stress and disease burden of these mothers is exceptionally high , and associated with poorer outcomes in children , policies and practice s primarily serve the identified child with disabilities . METHODS : A total of 243 mothers of children with disabilities were consented and r and omized into either Mindfulness-Based Stress Reduction ( mindfulness practice ) or Positive Adult Development ( positive psychology practice ) . Well-trained , supervised peer mentors led 6 weeks of group treatments in 1.5-hour weekly sessions , assessing mothers 6 times before , during , and up to 6 months after treatment . Mothers had children with autism ( 65 % ) or other disabilities ( 35 % ) . At baseline , 85 % of this community sample had significantly elevated stress , 48 % were clinical ly depressed , and 41 % had anxiety disorders . RESULTS : Using slopes-as- outcomes , mixed r and om effects models , both treatments led to significant reductions in stress , depression , and anxiety , and improved sleep and life satisfaction , with large effects in depression and anxiety . Mothers in Mindfulness-Based Stress Reduction versus Positive Adult Development had greater improvements in anxiety , depression , sleep , and well-being . Mothers of children with autism spectrum disorder improved less in anxiety , but did not otherwise differ from their counterparts . CONCLUSIONS : Future studies are warranted on how trained mentors and professionals can address the unmet mental health needs of mothers of children with developmental disabilities . Doing so improves maternal well-being and furthers their long-term caregiving of children with complex developmental , physical , and behavioral needs Objectives Research suggests that an 8-week Mindfulness-Based Stress Reduction ( MBSR ) program ( a structured form of meditation ) might be effective in the treatment of various health problems including chronic pain . Our objective was to compare the clinical effectiveness of the MBSR program with a multidisciplinary pain intervention ( MPI ) program in terms of pain intensity , pain-related distress , quality of life , and mood in patients with chronic pain . Methods A r and omized , comparative clinical trial was conducted , including 6-month posttreatment follow-up . Ninety-nine participants , aged 24 to 64 years , with pain for a minimum of 3 months , were recruited from community-based clinics , hospitals , and community service centers . Participants were r and omly allocated to either the MBSR program ( 51 participants ) or a MPI program ( 48 participants ) . The study used vali date d Chinese versions of self-reported question naires measuring pain , mood symptoms , and health-related quality of life . Results Thirty-nine participants ( 77 % ) completed the MBSR program and 44 ( 90 % ) completed the MPI program . Patients in both the groups were comparable with regard to demographical characteristics , pain intensity , mood symptoms , and health-related quality -of-life measures before intervention . In both the groups , patients who completed the trial demonstrated statistically significant improvements in pain intensity and pain-related distress . However , no statistically significant differences were observed in overall results between the MBSR and MPI groups . Conclusions This r and omized , clinical trial showed that both MBSR and MPI programs reduced pain intensity and pain-related distress although no statistically significant differences were observed between the 2 groups and the improvements were small CONTEXT The decision to institutionalize a patient with dementia is complex and is based on patient and caregiver characteristics and the sociocultural context of patients and caregivers . Most studies have determined predictors of nursing home placement primarily according to patient or caregiver characteristics alone . OBJECTIVE To develop and vali date a prognostic model to determine the comprehensive predictors of placement among an ethnically diverse population of patients with dementia . DESIGN , SETTING , AND PARTICIPANTS The Medicare Alzheimer 's Disease Demonstration and Evaluation study , a prospect i ve study at 8 sites in the United States , with enrollment between December 1989 and December 1994 of 5788 community-living persons with advanced dementia . MAIN OUTCOME MEASURES Time to nursing home placement throughout a 36-month follow-up period , assessed by interview and review of Medicare records , and its association with patient and caregiver characteristics , obtained by interview at enrollment . RESULTS Patients were divided into a development ( n = 3859 ) and validation ( n = 1929 ) cohort . In the development cohort , the Kaplan-Meier estimates of nursing home placement throughout 1 , 2 , and 3 years were 22 % , 40 % , and 52 % , respectively . After multivariate adjustment , patient characteristics that were associated with nursing home placement were as follows : black ethnicity ( hazard ratio , 0.60 ; 95 % confidence interval [ CI ] , 0.48 - 0.74 ) , Hispanic ethnicity ( HR , 0.40 ; 95 % CI , 0.28 - 0.56 ) ( both ethnicities were inversely associated with placement ) , living alone ( HR , 1.74 ; 95 % CI , 1.49 - 2.02 ) , 1 or more dependencies in activities of daily living ( HR , 1.38 ; 95 % CI , 1.20 - 1.60 ) , high cognitive impairment ( for Mini-Mental Status Examination score < or = 20 : HR , 1.52 ; 95 % CI , 1.33 - 1.73 ) , and 1 or more difficult behaviors ( HR , 1.30 ; 95 % CI , 1.11 - 1.52 ) . Caregiver characteristics associated with patient placement were age 65 to 74 years ( HR , 1.17 ; 95 % CI , 1.01 - 1.37 ) , age 75 years or older ( HR , 1.55 ; 95 % CI , 1.31 - 1.84 ) , and high Zarit Burden Scale score ( for highest quartile : HR , 1.73 ; 95 % CI , 1.49 - 2.00 ) . Patients were assigned to quartiles of risk based on this model . In the development cohort , patients in the first , second , third , and fourth quartile had a 25 % , 42 % , 64 % , and 91 % rate of nursing home placement at 3 years , respectively . In the validation cohort , the respective rates were 21 % , 50 % , 64 % , and 89 % . The C statistic for 3-year nursing home placement was 0.66 in the development cohort and 0.63 in the validation cohort . CONCLUSIONS Patient and caregiver characteristics are both important determinants of long-term care placement for patients with dementia . Interventions directed at delaying placement , such as reduction of caregiver burden or difficult patient behaviors , need to take into account the patient and caregiver as a unit OBJECTIVES The purpose of this study was to investigate the predictors of caregiver burden and depression , including objective stressors and mediation forces influencing caregiving outcomes . METHODS This investigation is based on the 1994 Canadian Study of Health and Aging ( CSHA ) data base . Participants were 613 individuals with dementia , living in either the community or an institution , and their informal caregivers . Participants for the CSHA were identified by screening a large r and om sample of elderly persons across Canada . Structural equation models representing four alternative pathways from caregiving stressors ( e.g. , functional limitations , disturbing behaviors , patient residence , assistance given to caregiver ) to caregiver burden and depression were compared . RESULTS The data provided the best fit to a model whereby the effects on the caregiver 's well-being are mediated by appraisal s of burden . A higher frequency of disturbing behavior , caring for a community-dwelling patient , and low informal support were related to higher burden , which in turn led to more depressive symptomatology . Caregivers of patients exhibiting more disturbing behaviors and functional limitations received less help from family and friends , whereas those whose care recipients resided in an institution received more informal support . DISCUSSION Our findings add to the preexisting literature because we tested alternative models of caregiver burden using an unusually large sample size of participants and after overcoming method ological limitations of past research . Results highlight the importance of the effective management of disturbing behaviors , the provision of formal services for caregivers with highly impaired patients and no informal support , and the improvement of coping skills in burdened caregivers OBJECTIVES The purpose of this study was to examine the effects of a structured , 8-week , Mindfulness-Based Stress Reduction ( MBSR ) program on perceived stress , mood , endocrine function , immunity , and functional health outcomes in individuals infected with the human immunodeficiency virus ( HIV ) . DESIGN This study used a quasiexperimental , nonr and omized design . METHODS Subjects were specifically recruited ( nonr and om ) for intervention ( MBSR ) or comparison group . Data were collected at pretest and post-test in the MBSR group and at matched times in the comparison group . t Tests where performed to determine within-group changes and between-group differences . RESULTS Natural killer cell activity and number increased significantly in the MBSR group compared to the comparison group . No significant changes or differences were found for psychological , endocrine , or functional health variables . CONCLUSIONS These results provide tentative evidence that MBSR may assist in improving immunity in individuals infected with HIV Behavioral interventions that support caregivers ' restful sleep may delay the onset or decrease the severity of debilitating depressive symptoms . This , in turn , may increase caregivers ' physical and psychological health and wellbeing . A repeated- measures experimental design was used to test the feasibility and effectiveness of a brief behavioral sleep intervention for family caregivers of persons with advanced stage cancer . The CAregiver Sleep Intervention ( CASI ) includes stimulus control , relaxation , cognitive therapy , and sleep hygiene elements . CASI is individualized and delivered to accommo date caregiver burden . Thirty adult caregivers participated . The Pittsburgh Sleep Quality Index ( PSQI ) , Center for Epidemiological Studies -Depression scale ( CES-D ) , and Caregiver Quality of Life-Cancer scale ( CQOLC ) were used to measure self-reported sleep quality , depressive symptoms , and quality of life . Actigraphs measured latency , duration , efficiency , and wake after sleep onset ( WASO ) scores . Data were collected at baseline , 3 and 5 weeks , 2 , 3 , and 4 months post baseline . Improvement was seen across groups ; however , intervention caregivers showed more improvement in PSQI and CES-D scores than control caregivers . The CASI appears to be effective in improving sleep quality and depressive symptoms in caregivers of persons with cancer . Improvements in quality of life scores were similar across groups . Sample size and homogeneity limit generalizeability This study aims to investigate the impact of caregiving on the health status and quality of life ( QOL ) of primary informal caregivers ( PCGs ) of elderly care recipients in Hong Kong . A total of 246 PCGs and 492 matched noncaregiver ( NCG ) controls were identified in a population -based cross-sectional study through r and om telephone dialing . Their health status and QOL were assessed based on structured question naires and Short Form 36 ( SF-36 ) Health Survey . Multiple conditional logistic regression analysis showed that compared with NCGs , PCGs had significantly increased risks for reporting worse health , more doctor visits , anxiety and depression , and weight loss . Female PCGs were more likely to report chronic diseases , symptoms , and insomnia . PCGs , particularly women , had significantly lower scores in all eight domains of Output:	There were improvements in the self-rated psychological symptoms , such as stress , depression , anxiety and mindfulness . To conclude , mindfulness-based stress reduction , as a safe and transportable approach , has potential to improve the psychological symptoms in the caregivers of patients with various conditions
MS22002	*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 Design . Single blind r and omized study . Objectives . To compare the effectiveness of lumbar instrumented fusion with cognitive intervention and exercises in patients with chronic low back pain and disc degeneration . Summary of Background Data . To the authors ’ best knowledge , only one r and omized study has evaluated the effectiveness of lumbar fusion . The Swedish Lumbar Spine Study reported that lumbar fusion was better than continuing physiotherapy and care by the family physician . Patients and Methods . Sixty-four patients aged 25–60 years with low back pain lasting longer than 1 year and evidence of disc degeneration at L4–L5 and /or L5–S1 at radiographic examination were r and omized to either lumbar fusion with posterior transpedicular screws and postoperative physiotherapy , or cognitive intervention and exercises . The cognitive intervention consisted of a lecture to give the patient an underst and ing that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it . This was reinforced by three daily physical exercise sessions for 3 weeks . The main outcome measure was the Oswestry Disability Index . Results . At the 1-year follow-up visit , 97 % of the patients , including 6 patients who had either not attended treatment or changed groups , were examined . The Oswestry Disability Index was significantly reduced from 41 to 26 after surgery , compared with 42 to 30 after cognitive intervention and exercises . The mean difference between groups was 2.3 ( −6.7 to 11.4 ) ( P = 0.33 ) . Improvements inback pain , use of analgesics , emotional distress , life satisfaction , and return to work were not different . Fear-avoidance beliefs and fingertip-floor distance were reduced more after nonoperative treatment , and lower limb pain was reduced more after surgery . The success rateaccording to an independent observer was 70 % after surgery and 76 % after cognitive intervention and exercises . The early complication rate in the surgical group was 18 % . Conclusion . The main outcome measure showed equal improvement in patients with chronic low back pain and disc degeneration r and omized to cognitive intervention and exercises , or lumbar fusion This study examines prospect ively the r and omised , long-term , clinical and radiological results of the treatment of spondylitis patients by ventro-dorsal or ventral spine fusion . Group 1 consisted of 12 patients who ( after ventral removal of the focus of infection and autologous bone grafting ) were treated by dorsal instrumentation . Group 2 consisted of ten patients who , after similar ventral removal and bone interposition , were stabilised by ventral instrumentation . The patients prospect ively underwent clinical and radiological studies . In addition , they were asked to fill in self- assessment question naires such as the short-form (SF)-36 health survey , the Oswestry question naire , and the visual analog scales ( VAS ) . The postoperative follow-ups were at 6 months , 2 years and 5.4 years . It proved possible to demonstrate clinical ly that patients with an isolated ventral spondylodesis feel significantly better and experience significantly less pain in the area of spinal fusion than patients with ventro-dorsal fusion 2 and 5.4 years after the operation . Over a number of years a stable fusion can be achieved through either operation . Ventral stabilisation yields more advantages than dorsal instrumentation in the long term . These advantages result in a clinical ly smoother course after the operation . If , in the individual case , ventral instrumentation is feasible , this method should be used . RésuméLa présente étude a pour but d’examiner de façon prospect i ve et r and omisée le devenir à long terme , clinique et radiologique , du traitement des spondylites après greffe antérieure ou greffe postérieure . Le groupe I a inclus 12 patients après abord antérieur , évacuation de l’abcès et greffe antérieure puis mise en place une instrumentation postérieure . Le groupe II ayant inclus 10 patients après un abord antérieur similaire , la greffe osseuse a été stabilisée par une instrumentation antérieure . Les patients ont été examinés rétrospectivement sur le plan clinique et radiologique . Ils ont répondu au question naire SF-36 , le question naire d’Oswestry et au VAS . Le suivi moyen post opératoire a été réalisé à six mois , deux ans et 5,4 ans . Cette étude a démontré de façon claire que les patients ayant bénéficié d’une greffe antérieure ont eu un résultat significativement plus intéressant en termes de douleur et de fusion que les patients ayant été traités par abord antérieur et une greffe postérieure . Si on la compare à l’instrumentation postérieure , cette stabilisation antérieure présente un certain nombre d’avantages à long terme . L’instrumentation antérieure est bien suffisante pour traiter ces pathologies BACKGROUND Management of degenerative spondylolisthesis with spinal stenosis is controversial . Surgery is widely used , but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials . METHODS Surgical c and i date s from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a r and omized cohort or an observational cohort . Treatment was st and ard decompressive laminectomy ( with or without fusion ) or usual nonsurgical care . The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey ( SF-36 ) bodily pain and physical function scores ( 100-point scales , with higher scores indicating less severe symptoms ) and the modified Oswestry Disability Index ( 100-point scale , with lower scores indicating less severe symptoms ) at 6 weeks , 3 months , 6 months , 1 year , and 2 years . RESULTS We enrolled 304 patients in the r and omized cohort and 303 in the observational cohort . The baseline characteristics of the two cohorts were similar . The one-year crossover rates were high in the r and omized cohort ( approximately 40 % in each direction ) but moderate in the observational cohort ( 17 % crossover to surgery and 3 % crossover to nonsurgical care ) . The intention-to-treat analysis for the r and omized cohort showed no statistically significant effects for the primary outcomes . The as-treated analysis for both cohorts combined showed a significant advantage for surgery at 3 months that increased at 1 year and diminished only slightly at 2 years . The treatment effects at 2 years were 18.1 for bodily pain ( 95 % confidence interval [ CI ] , 14.5 to 21.7 ) , 18.3 for physical function ( 95 % CI , 14.6 to 21.9 ) , and -16.7 for the Oswestry Disability Index ( 95 % CI , -19.5 to -13.9 ) . There was little evidence of harm from either treatment . CONCLUSIONS In nonr and omized as-treated comparisons with careful control for potentially confounding baseline factors , patients with degenerative spondylolisthesis and spinal stenosis treated surgically showed substantially greater improvement in pain and function during a period of 2 years than patients treated nonsurgically . ( Clinical Trials.gov number , NCT00000409 [ Clinical Trials.gov ] . ) 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 CONTEXT Lumbar diskectomy is the most common surgical procedure performed for back and leg symptoms in US patients , but the efficacy of the procedure relative to nonoperative care remains controversial . OBJECTIVE To assess the efficacy of surgery for lumbar intervertebral disk herniation . DESIGN , SETTING , AND PATIENTS The Spine Patient Outcomes Research Trial , a r and omized clinical trial enrolling patients between March 2000 and November 2004 from 13 multidisciplinary spine clinics in 11 US states . Patients were 501 surgical c and i date s ( mean age , 42 years ; 42 % women ) with imaging-confirmed lumbar intervertebral disk herniation and persistent signs and symptoms of radiculopathy for at least 6 weeks . INTERVENTIONS St and ard open diskectomy vs nonoperative treatment individualized to the patient . MAIN OUTCOME MEASURES Primary outcomes were changes from baseline for the Medical Outcomes Study 36-item Short-Form Health Survey bodily pain and physical function scales and the modified Oswestry Disability Index ( American Academy of Orthopaedic Surgeons MODEMS version ) at 6 weeks , 3 months , 6 months , and 1 and 2 years from enrollment . Secondary outcomes included sciatica severity as measured by the Sciatica Bothersomeness Index , satisfaction with symptoms , self-reported improvement , and employment status . RESULTS Adherence to assigned treatment was limited : 50 % of patients assigned to surgery received surgery within 3 months of enrollment , while 30 % of those assigned to nonoperative treatment received surgery in the same period . Intent-to-treat analyses demonstrated substantial improvements for all primary and secondary outcomes in both treatment groups . Between-group differences in improvements were consistently in favor of surgery for all periods but were small and not statistically significant for the primary outcomes . CONCLUSIONS Patients in both the surgery and the nonoperative treatment groups improved substantially over a 2-year period . Because of the large numbers of patients who crossed over in both directions , conclusions about the superiority or equivalence of the treatments are not warranted based on the intent-to-treat analysis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000410 From August 1981 to February 1982 postoperative infections due to different strains of penicillin-resistant Staphylococcus aureus occurred in 20 of 467 patients ( 4.3 % ) undergoing elective cranial and spinal operations . These infections were not attributable to defects in procedures or the theatre environment , therefore chemoprophylaxis was instituted . In the following 8 months , when patients were given penicillin G and sulphadiazine for 5 days commencing immediately postoperatively , S. aureus infections occurred in five of 579 patients ( 0.9 % ) . In a subsequent r and omized uncontrolled study , infections occurred in six of 265 patients receiving penicillin ( 2.3 % ) , three of 270 receiving penicillin and sulphadiazine ( 1.1 % ) and one of 45 receiving erythromycin ( 2.2 % ) immediately postoperatively for 5 days . In a further study in which 587 patients received penicillin for 5 days commencing immediately preoperatively , infections due to S. aureus occurred in six ( 1.1 % ) . Infections due to gram-negative organisms were seen in five ( 0.4 % ) of 1167 patients in the two uncontrolled studies BACKGROUND Lumbar-disk surgery often is performed in patients who have sciatica that does not resolve within 6 weeks , but the optimal timing of surgery is not known . METHODS We r and omly assigned 283 patients who had had severe sciatica for 6 to 12 weeks to early surgery or to prolonged conservative treatment with surgery if needed . The primary outcomes were the score on the Rol and Disability Question naire , the score on the visual-analogue scale for leg pain , and the patient 's report of perceived recovery during the first year after r and omization . Repeated- measures analysis according to the intention-to-treat principle was used to estimate the outcome curves for both groups . RESULTS Of 141 patients assigned to undergo early surgery , 125 ( 89 % ) underwent microdiskectomy after a mean of 2.2 weeks . Of 142 patients design ated for conservative treatment , 55 ( 39 % ) were treated surgically after a mean of 18.7 weeks . There was no significant overall difference in disability scores during the first year ( P=0.13 ) . Relief of leg pain was faster for patients assigned to early surgery ( P<0.001 ) . Patients assigned to early surgery also reported a faster rate of perceived recovery ( hazard ratio , 1.97 ; 95 % confidence interval , 1.72 to 2.22 ; P<0.001 ) . In both groups , however , the probability of perceived recovery after 1 year of follow-up was 95 % . CONCLUSIONS The 1-year outcomes were similar for patients assigned to early surgery and those assigned to conservative treatment Output:	The only intervention that receives strong evidence is discectomy for faster relief in carefully selected patients due to lumbar disc prolapse with sciatica .
MS22003	*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 A prospect i ve review was performed on 60 consecutive patients with hip hemiarthroplasty after femoral neck fractures . METHODS Twenty-two patients underwent Austin Moore hemiarthroplasty with an intramedullary corticocancellous bone plug at the tip of the prosthesis ( group A ) and 38 patients underwent Austin Moore hemiarthroplasty alone ( group B ) . The patients were evaluated clinical ly and radiographically at 3 and 6 months postoperatively and annually thereafter . RESULTS There was no statistically significant difference in thigh pain score between the two groups . At 3- and 6-month follow-up , 88 % and 83 % of group A patients experienced no pain or mild thigh pain , compared with 72 % and 76 % in group B , respectively . The radiographs revealed more stem subsidence and calcar osteolysis in group B than in group A ( p < 0.01 and p < 0.05 , respectively ) . Furthermore , in both groups there was a correlation between calcar atrophy , stem subsidence , and early clinical thigh pain score ( p < 0.05 ) . CONCLUSION Our data suggest that , whereas the radiologic findings in both groups may be related to thigh pain , they had little effect on the rate of femoral stem revision . We believe that the application of a corticocancellous bone plug in uncemented hip hemiarthroplasty for treatment of femoral neck fractures can decrease the incidence of early thigh pain in the first 6 months Publisher Summary This chapter focuses on the bias in analytic research . Case-control studies are attractive . They can be executed quickly and at low cost , even when the disorders of interest are rare . The execution of pilot case-control studies is becoming automated ; strategies have been devised for the “ computer scanning ” of large files of hospital admission diagnoses and prior drug exposures , with detailed analyses carried out in the same data set on an ad hoc basis . As evidence of their growing popularity , when one original article was r and omly selected from each issue of The New Engl and Journal of Medicine , The Lancet , and the Journal of the American Medical Association for the years 1956 , 1966 , and 1976 , the proportion that reported case-control analytic studies increased fourfold over these two decades ; however , the proportion reporting cohort analytic studies fell by half ; a general trend toward fewer study subjects but more study authors was also noted Blinding embodies a rich history spanning over two centuries . Most research ers worldwide underst and blinding terminology , but confusion lurks beyond a general comprehension . Terms such as single blind , double blind , and triple blind mean different things to different people . Moreover , many medical research ers confuse blinding with allocation concealment . Such confusion indicates misunderst and ings of both . The term blinding refers to keeping trial participants , investigators ( usually health-care providers ) , or assessors ( those collecting outcome data ) unaware of the assigned intervention , so that they will not be influenced by that knowledge . Blinding usually reduces differential assessment of outcomes ( information bias ) , but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment ( sometimes called co-intervention ) . Many investigators and readers naïvely consider a r and omised trial as high quality simply because it is double blind , as if double-blinding is the sine qua non of a r and omised controlled trial . Although double blinding ( blinding investigators , participants , and outcome assessors ) indicates a strong design , trials that are not double blinded should not automatically be deemed inferior . Rather than solely relying on terminology like double blinding , research ers should explicitly state who was blinded , and how . We recommend placing greater credence in results when investigators at least blind outcome assessment s , except with objective outcomes , such as death , which leave little room for bias . If investigators properly report their blinding efforts , readers can judge them . Unfortunately , many articles do not contain proper reporting . If an article cl aims blinding without any accompanying clarification , readers should remain sceptical about its effect on bias reduction We report a r and omised , prospect i ve study comparing a st and ard sliding hip screw and the intramedullary hip screw for the treatment of unstable intertrochanteric fractures in the elderly . One hundred and two patients were r and omised on admission to two treatment groups . Fifty-two patients were treated with a compression hip screw ( CHS ) , and fifty had intramedullary fixation with an intramedullary hip screw ( IMHS ) . Patients were followed for 1 year and had a clinical and radiological review at 3 , 6 and 12 months . The mean duration of operation and fluoroscopy screening time was significantly greater for insertion of the intramedullary hip screw . There was no difference between the groups with regard to transfusion requirements or time to mobilise after surgery . There were two technical complications in the CHS group and three in the IMHS group . There was no significant difference between the two groups in radiological or functional outcome at 12 months . It remains to be shown whether the theoretical advantages of intramedullary fixation of extracapsular hip fractures bring a significant improvement in eventual outcome R and omized controlled trials are the gold st and ard for the evaluation of new therapies and surgical procedures and as such require strict attention to study design and statistical analysis . There are , however , multiple challenges in conducting a well- design ed clinical trial . This article describes the difficulties encountered at a single institution participating in a multicenter drug study and review s the challenges involved in developing a high- quality r and omized controlled study BACKGROUND Intramedullary nailing of the femur without reaming of the medullary canal has been advocated as a method to reduce marrow embolization to the lungs and the rate of infection after open fractures . The use of nailing without reaming , however , has been associated with lower rates of fracture-healing . The purpose of this prospect i ve study was to compare the rate of union of femoral shaft fractures following intramedullary nailing with and without reaming . METHODS Two hundred and twenty-four patients were enrolled in a multicenter , prospect i ve , r and omized clinical trial to compare nailing without reaming and nailing with reaming . One hundred and six patients with 107 femoral shaft fractures were treated with a smaller diameter nail without reaming of the canal , and 118 patients with 121 fractures had reaming of the canal and insertion of a relatively larger diameter nail . Patients were followed at six-week intervals until union occurred or a nonunion was diagnosed . RESULTS The two groups were comparable with regard to the measured patient and injury characteristics . Eight ( 7.5 % ) of the 107 fractures in the group without reaming had a nonunion compared with two ( 1.7 % ) of 121 fractures in the group with reaming ( p = 0.049 ) . The relative risk of nonunion was 4.5 times greater ( 95 % confidence interval = 1 to 20 ) without reaming and with use of a relatively small-diameter nail . CONCLUSION Intramedullary nailing of femoral shaft fractures without reaming results in a significantly higher rate of nonunion compared with intramedullary nailing with reaming The ability of a small-scale r and om-control clinical trial comprising less than 500 patients to disclose clinical ly important differences between treatment groups depends on the event rate in the control group . The high rate of wound infection after abdominal operations has attracted many trials of methods of antibiotic prophylaxis . We review ed all of the pertinent English literature recorded in Index Medicus in 1980 and 1981 . We examined 45 articles for defects in design , analysis , and presentation . Of the 45 articles , 25 reported statistically significant differences between treatment groups and 20 , no significant differences . Unsatisfactory methods of r and omization were used in four trials , ethics were question able in 22 , statistical methods were incorrect in 31 , and presentation was inadequate in 40 . We concluded that there is room for improvement in the conduct of clinical trials Considerable effort is often expended to adjudicate outcomes in clinical trials , but little has been written on the administration of the adjudication process and its possible impact on study results . As a case study , we describe the function and performance of an adjudication committee in a large r and omized trial of two diagnostic approaches to potentially operable lung cancer . Up to five independent adjudicators independently determined two primary outcomes : tumor status at death or at final follow-up and the cause of death . Patients for whom there was any disagreement were discussed in committee until a consensus was achieved . We describe the pattern of agreement among the adjudicators and with the final consensus result . Additionally , we model the adjudication process and predict the results if a smaller committee had been used . We found that reducing the number of adjudicators from five to two or three would probably have changed the consensus outcome in less than 10 % of cases . Correspondingly , the effect on the final study results ( comparing primary outcomes in both r and omized arms ) would have been altered very little . Even using a single adjudicator would not have affected the results substantially . About 90 minutes of person-time per patient was required for activities directly related to the adjudication process , or approximately 6 months of full time work for the entire study . This level of effort could be substantially reduced by using fewer adjudicators with little impact on the results . Thus , we suggest that when high observer agreement is demonstrated or anticipated , adjudication committees should consist of no more than three members . Further work is needed to evaluate if smaller committees are adequate to detect small but important treatment effects or if they compromise validity when the level of adjudicator agreement is lower This paper presents the short term results of an ongoing prospect i ve r and omized trial comparing a cemented unipolar with a cemented bipolar hemiarthroplasty for the treatment of displaced femoral neck fractures in the elderly . Forty-seven patients with an average age of 77 years completed 6-month followup . Outcomes at 6 weeks , 3 months and 6 months were assessed by completion of a patient oriented hip outcome instrument and by functional tests of walking speed and endurance . No differences in the postoperative complication rates or lengths of hospitalization were seen between the two groups . Patients treated with a bipolar hemiarthroplasty had greater range of hip motion in rotation and abduction and had faster walking speeds . However , no differences in hip rating outcomes were found . These early results suggest that use of the less expensive unipolar prosthesis for hemiarthroplasty after femoral neck fracture may be justified in the elderly Output:	Trials in orthopaedic trauma typically measure many outcomes requiring judgment , but the individuals assessing those outcomes are seldom blinded .
MS22004	*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 Sexually transmitted infections ( STIs ) such as herpes simplex virus (HSV)-2 are associated with an increased risk of HIV infection . Human papillomavirus ( HPV ) is a common STI , but little is know about its role in HIV transmission . The objective of this study was to determine whether cervico-vaginal HPV infection increases the risk of HIV acquisition in women independent of other common STIs . Methods and Findings This prospect i ve cohort study followed 2040 HIV-negative Zimbabwean women ( average age 27 years , range 18–49 years ) for a median of 21 months . Participants were tested quarterly for 29 HPV types ( with L1 PCR primers ) and HIV ( antibody testing on blood sample s with DNA or RNA PCR confirmation ) . HIV incidence was 2.7 per 100 woman-years . Baseline HPV prevalence was 24.5 % , and the most prevalent HPV types were 58 ( 5.0 % ) , 16 ( 4.7 % ) , 70 ( 2.4 % ) , and 18 ( 2.3 % ) . In separate regression models adjusting for baseline variables ( including age , high risk partner , positive test for STIs , positive HSV-2 serology and condom use ) , HIV acquisition was associated with having baseline prevalent infection with HPV 58 ( aHR 2.13 ; 95 % CI 1.09–4.15 ) or HPV 70 ( aHR 2.68 ; 95 % CI 1.08–6.66 ) . In separate regression models adjusting for both baseline variables and time-dependent variables ( including HSV-2 status , incident STIs , new sexual partner and condom use ) , HIV acquisition was associated with concurrent infection with any non-oncogenic HPV type ( aHR 1.70 ; 95 % CI 1.02–2.85 ) , any oncogenic HPV type ( aHR 1.96 ; 95 % CI 1.16–3.30 ) , HPV 31 ( aHR 4.25 ; 95 % CI 1.81–9.97 ) or HPV 70 ( aHR 3.30 ; 95 % CI 1.50–7.20 ) . Detection of any oncogenic HPV type within the previous 6 months was an independent predictor of HIV acquisition , regardless of whether HPV status at the HIV acquisition visit was included ( aHR 1.95 ; 95 % CI 1.19–3.21 ) or excluded ( aHR 1.96 ; 95 % CI 1.02–2.85 ) from the analysis . Conclusions / Significance Cervico-vaginal HPV infection was associated with an increased risk of HIV acquisition in women , and specific HPV types were implicated in this association . The observational nature of our study precludes establishment of causation between HPV infection and HIV acquisition . However , given the high prevalence of HPV infection in women , further investigation of the role of HPV in HIV transmission is warranted Background Human papillomaviruses are the most common sexually transmitted infections , and genital warts , caused by HPV-6 and 11 , entail considerable morbidity and cost . The natural history of genital warts in relation to HIV-1 infection has not been described in African women . We examined risk factors for genital warts in a cohort of high-risk women in Burkina Faso , in order to further describe their epidemiology . Methods A prospect i ve study of 765 high-risk women who were followed at 4-monthly intervals for 27 months in Burkina Faso . Logistic and Cox regression were used to identify factors associated with prevalent , incident and persistent genital warts , including HIV-1 serostatus , CD4 + count , and concurrent sexually transmitted infections . In a subset of 306 women , cervical HPV DNA was tested at enrolment . Results Genital wart prevalence at baseline was 1.6 % ( 8/492 ) among HIV-uninfected and 7.0 % ( 19/273 ) among HIV-1 seropositive women . Forty women ( 5.2 % ) experienced at least one incident GW episode . Incidence was 1.1 per 100 person-years among HIV-uninfected women , 7.4 per 100 person-years among HIV-1 seropositive women with a nadir CD4 + count > 200 cells/μL and 14.6 per 100 person-years among HIV-1 seropositive women with a nadir CD4 + count ≤200 cells/μL. Incident genital warts were also associated with concurrent bacterial vaginosis , and genital ulceration . Antiretroviral therapy was not protective against incident or persistent genital warts . Detection of HPV-6 DNA and abnormal cervical cytology were strongly associated with incident genital warts . Conclusions Genital warts occur much more frequently among HIV-1 infected women in Africa , particularly among those with low CD4 + counts . Antiretroviral therapy did not reduce the incidence or persistence of genital warts in this population Background While infections with human papillomavirus ( HPV ) are highly prevalent among sexually active young women in Ug and a , information on incidence , clearance and their associated risk factors is sparse . To estimate the incidence , prevalence and determinants of HPV infections , we conducted a prospect i ve follow-up study among 1,275 women aged 12 - 24 years at the time of recruitment . Women answered a question naire and underwent a pelvic examination at each visit to collect exfoliated cervical cells . The presence of 42 HPV types was evaluated in exfoliated cervical cells by a polymerase chain based ( PCR ) assay ( SPF10-DEIA LiPA ) . Results Three hundred and eighty ( 380 ) of 1,275 ( 29.8 % ) women were followed up for a median time of 18.5 months ( inter-quartile range 9.7 - 26.6 ) . Sixty-nine ( 69 ) women had incident HPV infections during 226 person-years of follow-up reflecting an incidence rate of 30.5 per 100 person-years . Incident HPV infections were marginally associated with HIV positivity ( RR = 2.8 , 95 % CI : 0.9 - 8.3 ) . Clearance for HPV type-specific infections was frequent ranging between 42.3 % and 100.0 % for high- and 50 % and 100 % for low-risk types . Only 31.2 % of women cleared all their infections . Clearance was associated with HIV negativity ( Adjusted clearance = 0.2 , 95 % CI : 0.1 - 0.7 ) but not with age at study entry , lifetime number of sexual partners and multiplicity of infections . The prevalence of low- grade squamous intraepithelial lesions ( LSILs ) was 53/365 ( 14.5 % ) . None of the women had a high- grade cervical lesion ( HSIL ) or cancer . Twenty-two ( 22 ) of 150 ( 14.7 % ) HPV negative women at baseline developed incident LSIL during follow-up . The risk for LSIL appeared to be elevated among women with HPV 18-related types compared to women not infected with those types ( RR = 3.5 , 95 % CI : 1.0 - 11.8 ) . Conclusions Incident HPV infections and type-specific HPV clearance were frequent among our study population of young women . These results underscore the need to vaccinate pre-adolescent girls before initiation of sexual activity BACKGROUND Male circumcision could provide substantial protection against acquisition of HIV-1 infection . Our aim was to determine whether male circumcision had a protective effect against HIV infection , and to assess safety and changes in sexual behaviour related to this intervention . METHODS We did a r and omised controlled trial of 2784 men aged 18 - 24 years in Kisumu , Kenya . Men were r and omly assigned to an intervention group ( circumcision ; n=1391 ) or a control group ( delayed circumcision , 1393 ) , and assessed by HIV testing , medical examinations , and behavioural interviews during follow-ups at 1 , 3 , 6 , 12 , 18 , and 24 months . HIV seroincidence was estimated in an intention-to-treat analysis . This trial is registered with Clinical Trials.gov , with the number NCT00059371 . FINDINGS The trial was stopped early on December 12 , 2006 , after a third interim analysis review ed by the data and safety monitoring board . The median length of follow-up was 24 months . Follow-up for HIV status was incomplete for 240 ( 8.6 % ) participants . 22 men in the intervention group and 47 in the control group had tested positive for HIV when the study was stopped . The 2-year HIV incidence was 2.1 % ( 95 % CI 1.2 - 3.0 ) in the circumcision group and 4.2 % ( 3.0 - 5.4 ) in the control group ( p=0.0065 ) ; the relative risk of HIV infection in circumcised men was 0.47 ( 0.28 - 0.78 ) , which corresponds to a reduction in the risk of acquiring an HIV infection of 53 % ( 22 - 72 ) . Adjusting for non-adherence to treatment and excluding four men found to be seropositive at enrollment , the protective effect of circumcision was 60 % ( 32 - 77 ) . Adverse events related to the intervention ( 21 events in 1.5 % of those circumcised ) resolved quickly . No behavioural risk compensation after circumcision was observed . INTERPRETATION Male circumcision significantly reduces the risk of HIV acquisition in young men in Africa . Where appropriate , voluntary , safe , and affordable circumcision services should be integrated with other HIV preventive interventions and provided as expeditiously as possible BACKGROUND Studies analyzing the impact of combination antiretroviral therapy ( cART ) on cervical infection with high-risk human papillomavirus ( HR-HPV ) have generated conflicting results . We assessed the long-term impact of cART on persistent cervical HR-HPV infection in a very large cohort of 652 women who underwent follow-up of HIV infection for a median duration of 104 months . METHODS Prospect i ve cohort of HIV-infected women undergoing HIV infection follow-up who had HR-HPV screening and cytology by Papanicolaou smear performed yearly between 2002 and 2011 . RESULTS At baseline , the median age was 38 years , the race/ethnic origin was sub-Sarahan Africa for 84 % , the median CD4(+ ) T-cell count was 426 cells/µL , 79 % were receiving cART , and the HR-HPV prevalence was 43 % . The median interval of having had an HIV load of < 50 copies/mL was 40.6 months at the time of a HR-HPV-negative test result , compared with 17 months at the time of a HR-HPV-positive test result ( P < .0001 , by univariate analysis ) . The median interval of having had a CD4(+ ) T-cell count of > 500 cells/µL was 18.4 months at the time of a HR-HPV-negative test result , compared with 4.45 months at the time of a HR-HPV-positive test result ( P < .0001 ) . In multivariate analysis , having had an HIV load of < 50 copies/mL for > 40 months ( odds ratio [ OR ] , 0.81 ; 95 % confidence interval [ CI ] , .76-.86 ; P < .0001 ) and having had a CD4(+ ) T-cell count of > 500 cells/µL for > 18 months ( OR , 0.88 ; 95 % CI , .82-.94 ; P = .0002 ) were associated with a significantly decreased risk of HR-HPV infection . CONCLUSION Sustained HIV suppression for > 40 months and a sustained CD4(+ ) T-cell count of > 500 cells/µL for > 18 months are independently and significantly associated with a decreased risk of persistent cervical HR-HPV infection BACKGROUND High rates of persistence of human papillomavirus ( HPV ) infection have been reported for adult women with human immunodeficiency virus ( HIV ) infection . Although most women are first infected with HPV during adolescence , persistence of specific HPV types has not been carefully examined among HIV-infected adolescents . The objective of this study was to examine the rates of and risk factors for persistence of HPV types among HIV-infected and -uninfected adolescent girls . METHODS This is a prospect i ve cohort study of female adolescents , aged 13 - 18 years , participating in the Reaching for Excellence in Adolescent Care and Health project , a national study of HIV-infected and -uninfected adolescents . The main outcome measured was type-specific loss of initial HPV DNA detected . Loss of HPV DNA was defined for the following categories of HP Output:	There was more evidence of publication bias in review 2 , and somewhat greater risk of confounding in studies included in review 1 . There was some evidence that adjustment for key confounders strengthened the associations for review 2 . Misclassification bias by HIV/HPV exposure status could also have biased estimates toward the null . These results provide evidence for synergistic HIV and HPV interactions of clinical and public health relevance . Although observational studies can never perfectly control for residual confounding , the evidence presented here lends further support for the presence of biological interactions between HIV and HPV that have a strong plausibility
MS22005	*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 determine the reliability and validity of a patient outcome question naire for chronic heart failure , a r and omized , double-blind , placebo-controlled , 3-month trial of pimobendan , an investigational medication with inotropic and vasodilator activities , was performed . Evaluated were 198 ambulatory patients with primarily New York Heart Association ( NYHA ) class III heart failure from 20 referral centers . Baseline therapy included digoxin , diuretics and , in 80 % , a converting enzyme inhibitor . Oral pimobendan at 2.5 ( n = 49 ) , 5.0 ( n = 51 ) , or 10 ( n = 49 ) mg daily or matching placebo ( n = 49 ) was administered . The Minnesota Living with Heart Failure ( LIhFE ) question naire was a primary outcome measure , along with an exercise test . Interitem correlations identified subgroups of questions representing physical and emotional dimensions . Repeated baseline scores were highly correlated ( r = 0.93 ) , as were the physical ( r = 0.89 ) and emotional ( r = 0.88 ) dimension scores . Placebo did not have a significant effect with median ( 25th , 75th percentile ) changes from baseline scores of 1 ( -3 , 5 ) , 1 ( -2 , 3 ) , and 0 ( -1 , 2 ) , respectively ( all p values greater than 0.10 ) . The 5 mg dose significantly improved the total score , 7.5 ( 0 , 18 ; p = 0.01 ) and the physical dimension , 4 ( 0 , 8 ; p = 0.01 ) , compared with placebo . Changes in the total ( r = 0.33 ; p less than 0.01 ) and physical ( r = 0.35 ; p less than 0.01 ) scores were weakly related to changes in exercise times , but corresponded well with changes in patients ' ratings of dyspnea and fatigue . ( ABSTRACT TRUNCATED AT 250 WORDS Objective We examine prospect ively the role of specific forms of self-efficacy in the physical and role function for patients with coronary heart disease after controlling for the effects of anxiety and depression . Methods A 6-month prospect i ve cohort study was conducted after cardiac catheterization of 198 HMO members , demonstrating clinical ly significant coronary disease . Coronary disease severity was assessed through cardiac catheterization ; physical function , role function , anxiety , depression , and self-efficacy were assessed through question naires . Results The Cardiac Self-Efficacy Scale had two factors ( maintain function and control symptoms ) with high internal consistency and good convergent and discriminant validity . In multiple regression models , the self-efficacy scales significantly predicted physical function , social function , and family function after controlling for baseline function , baseline anxiety , and other significant correlates . Conclusions Self-efficacy to maintain function and to control symptoms helps predict the physical function and role function , after accounting for coronary disease severity , anxiety , and depression in patients with clinical ly significant coronary disease . Interventions to improve self-efficacy may have a broader applicability in the heart disease population than previously appreciated Purpose We examined whether changes in health-related quality of life ( HRQL ) predict subsequent mortality among the Spanish elderly . Methods Prospect i ve cohort study of 2,373 persons , representative of the Spanish population aged 60 and older . HRQL was measured in 2001 and 2003 using the SF-36 health question naire . Cox regression models were used to examine the association of changes in the physical and mental component summary ( PCS and MCS ) scores of HRQL from 2001 to 2003 with all-cause mortality through 2007 . Results Two hundred twelve deaths were ascertained from 2003 to 2007 . The hazard ratios for mortality across categories of PCS change were as follows : 2.12 ( 95 % confidence interval [ CI ] 1.39–3.24 ) for a > 10-point decline ; 1.51 ( 1.01–2.28 ) for a 6- to 10-point decline ; 1 for the reference category , a change of −5 to + 5 points ; 0.83 ( 0.51–1.34 ) for a 6- to 9-point improvement and 0.68 ( 0.42–1.09 ) for a > 10-point improvement ; P for linear trend < 0.001 . The associations between changes in the MCS and mortality showed the same direction , but were of a lower magnitude and attained statistical significance ( P < 0.05 ) only for a > 10-point decline in MCS . Conclusions Changes in HRQL predict mortality in the older adults . A decline in HRQL should alert to a worse vital prognosis and stimulate the search for the possible determinants of such decline BACKGROUND The application of health-related quality of life ( HRQOL ) as a pediatric population health measure may facilitate risk assessment and re source allocation , the tracking of community health , the identification of health disparities , and the determination of health outcomes from interventions and policy decisions . OBJECTIVE To determine the feasibility , reliability , and validity of the 23-item PedsQL 4.0 ( Pediatric Quality of Life Inventory ) Generic Core Scales as a measure of pediatric population health for children and adolescents . DESIGN Mail survey in February and March 2001 to 20 031 families with children ages 2 - 16 years throughout the State of California encompassing all new enrollees in the State 's Children 's Health Insurance Program ( SCHIP ) for those months and targeted language groups . METHODS The PedsQL 4.0 Generic Core Scales ( Physical , Emotional , Social , School Functioning ) were completed by 10 241 families through a statewide mail survey to evaluate the HRQOL of new enrollees in SCHIP . RESULTS The PedsQL 4.0 evidence d minimal missing responses , achieved excellent reliability for the Total Scale Score ( alpha = .89 child;.92 parent report ) , and distinguished between healthy children and children with chronic health conditions . The PedsQL 4.0 was also related to indicators of health care access , days missed from school , days sick in bed or too ill to play , and days needing care . CONCLUSION The results demonstrate the feasibility , reliability , and validity of the PedsQL 4.0 as a pediatric population health outcome . Measuring pediatric HRQOL may be a way to evaluate the health outcomes of SCHIP Output:	Self-efficacy – HRQOL associations were similar in strength across age groups , regardless of presence of cardiovascular surgery , and among patients diagnosed with different forms of CVD . Conclusions / Implication s : General and exercise-specific self-efficacy are moderately related with HRQOL among people with CVD after surgery or during rehabilitation .
MS22006	*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: Pathological formation of reactive oxygen species within the coronary circulation has been hypothesized to mediate some clinical manifestations of ischemic heart disease ( IHD ) by interfering with physiological regulation of coronary tone . To determine the degree to which coronary tone responds to acute changes in ambient levels of oxidants and antioxidants in vivo in a clinical setting , we measured the effect of an acute oxidative stress ( breathing 100 % oxygen ) on coronary capacitance artery diameter ( quantitative angiography ) and blood flow velocity through the coronary microcirculation ( intracoronary Doppler ultrasonography ) before and after treatment with the antioxidant vitamin C ( 3-g intravenous infusion ) in 12 IHD patients undergoing a clinical coronary interventional procedure . Relative to room air breathing , 100 % oxygen breathing promptly reduced coronary blood flow velocity by 20 % and increased coronary resistance by 23 % , without significantly changing the diameter of capacitance arteries . Vitamin C administration promptly restored coronary flow velocity and resistance to a slightly suprabasal level , and it prevented the reinduction of coronary constriction with rechallenge with 100 % oxygen . This suggests that acute oxidative stress produces prompt and substantial changes in coronary resistance and blood flow in a clinical setting in patients with IHD , and it suggests that these changes are mediated by vitamin C-quenchable substances acting on the coronary microcirculation . This observation may have relevance for clinical practice BACKGROUND Administration of supplemental oxygen in the perioperative period is controversial , as it may increase long-term mortality . Our aim was to assess the association between 80 % oxygen and occurrence of subsequent cancer in patients undergoing abdominal surgery in a post hoc analysis of the PROXI trial . METHODS The 1386 patients in the PROXI trial underwent elective or emergency laparotomy between 2006 and 2008 with r and omization to either 80 % or 30 % oxygen during and for 2 h after surgery . We retrieved follow-up status regarding vital status , new cancer diagnoses , and new histological cancer specimens . Data were analysed using the Cox proportional hazards model . RESULTS Follow-up was complete in 1377 patients ( 99 % ) after a median of 3.9 yr . The primary outcome of new cancer diagnosis or new malignant histological specimen occurred in 140 of 678 patients ( 21 % ) in the 80 % oxygen group vs 150 of 699 patients ( 21 % ) assigned to 30 % oxygen ; hazards ratio 1.06 [ 95 % confidence interval ( CI ) 0.84 , 1.34 ] , P=0.62 . Cancer-free survival was significantly shorter in the 80 % oxygen group ; hazards ratio 1.19 ( 95 % CI 1.01 , 1.42 ) , P=0.04 , as was the time between surgery and new cancer , median 335 vs. 434 days in the 30 % oxygen group . In patients with localized disease , non-significant differences in cancer and cancer-free survival were found with hazard ratios of 1.31 and 1.29 , respectively . CONCLUSIONS Although new cancers occurred at similar rate , the cancer-free survival was significantly shorter in the 80 % oxygen group , but this did not appear to explain the excess mortality in the 80 % oxygen group . CLINICAL TRIAL REGISTRATION Clinical Trials.gov ( NCT01723280 ) BACKGROUND Perioperative supplemental oxygen has been proposed to decrease the incidence of surgical site infection ( SSI ) in colorectal surgery with controversial results . We have assessed the influence of hyperoxygenation on SSI by using the most homogeneous study population . METHODS We studied , in a prospect i ve r and omized study , 81 patients , who underwent elective open infraperitoneal anastomosis for rectal cancer . Patients were assigned r and omly to an oxygen/air mixture with a fraction of inspired oxygen ( FiO2 ) of 30 % ( n = 41 ) or 80 % ( n = 40 ) . Administration was commenced after induction of anesthesia and maintained for 6 hours after surgery . RESULTS The overall wound infection rate was 21 % : 11 patients ( 26.8 % ) had wound infections in the 30 % FiO2 group and 6 ( 15 % ) in the 80 % FiO2 group ( P < .05 ) . The risk of SSI was 41 % lower in the 80 % FiO2 group . CONCLUSION Supplemental 80 % FiO2 reduced postoperative SSI with few risks to the patient and little associated cost OBJECTIVE The purpose of this study was to investigate whether supplemental oxygen during and for 2 hours after cesarean delivery reduces the incidence of postcesarean infectious morbidity . STUDY DESIGN We conducted a r and omized , controlled trial from 2008 - 2010 . Women who underwent cesarean delivery were r and omly assigned to receive either 2 L of oxygen by nasal cannula during cesarean delivery only ( st and ard care ) or 10 L of oxygen by nonrebreather mask ( intervention group ) during and for 2 hours after cesarean delivery . Women who underwent scheduled or intrapartum cesarean delivery were eligible and were observed for 1 month after the procedure . The primary composite outcome was maternal infectious morbidity , which included endometritis and wound infection . RESULTS Five hundred eighty-five women were included in the final analysis . Infectious morbidity occurred in 8.8 % of patients in the st and ard care group and in 12.2 % of patients in the supplemental oxygen group . There was no significant difference in the rate of infectious morbidity between the st and ard care and intervention groups ( relative risk , 1.4 ; 95 % confidence interval , 0.9 - 2.3 ) . CONCLUSION Supplemental oxygen does not reduce the rate of postcesarean delivery infectious morbidity , including endometritis and wound infection BACKGROUND : A high perioperative inspiratory oxygen fraction ( 80 % ) has been recommended to prevent postoperative wound infections . However , the most recent and one of the largest trials , the PROXI trial , found no reduction in surgical site infection , and 30-day mortality was higher in patients given 80 % oxygen . In this follow-up study of the PROXI trial we assessed the association between long-term mortality and perioperative oxygen fraction in patients undergoing abdominal surgery . METHODS : From October 8 , 2006 , to October 6 , 2008 , 1386 patients underwent elective or emergency laparotomy and were r and omized to receive either 80 % or 30 % oxygen during and for 2 hours after surgery . The follow-up date was February 24 , 2010 . Survival was analyzed using Kaplan-Meier statistics and the Cox proportional hazards model . RESULTS : Vital status was obtained in 1382 of 1386 patients after a median follow-up of 2.3 years ( range 1.3 to 3.4 years ) . One hundred fifty-nine of 685 patients ( 23.2 % ) died in the 80 % oxygen group compared to 128 of 701 patients ( 18.3 % ) assigned to 30 % oxygen ( HR , 1.30 [ 95 % confidence interval , 1.03 to 1.64 ] , P = 0.03 ) . In patients undergoing cancer surgery , the HR was 1.45 ; 95 % confidence interval , 1.10 to 1.90 ; P = 0.009 ; and after noncancer surgery , the HR was 1.06 ; 95 % confidence interval , 0.69 to 1.65 ; P = 0.79 . CONCLUSIONS : Administration of 80 % oxygen in the perioperative period was associated with significantly increased long-term mortality and this appeared to be statistically significant in patients undergoing cancer surgery but not in noncancer patients This explicit and strong recommendation has caused considerable concern in the anaesthesia community because it directly contradicts the results of many trials ( and a meta- analysis of those trials ) which showednobenefitof supplemental oxygen . The use of an increased inspired oxygen fraction ( FiO2 ) has a long history in anaesthesia , intensive care , and emergency medicine . Planned induction and extubation of anaesthesia are conducted with 100 % oxygen to enhance safety in the case of airwaydifficulty . Extra oxygen is alsogivenduringgeneral anaesthesia as 21 % is rarely sufficient , with concentrations ranging from 30 % to nearly 100 % depending on case factors and anaesthesiologist preference . There is considerable reason to expect that supplemental oxygen might reduce the risk of surgical site infection [ 21 ] . All surgical wounds become contaminated , and the primary defence against bacterial contamination isoxidativekillingbyneutrophils , a process that requires molecular oxygen and depends on the partial pressureofoxygenintissueovertheentire physiological range . Consistent with this theory , Hopf et al. [ 11 ] showed that surgical wound infection risk was inversely related to tissue oxygenation . Based on these observational data , the Outcomes Research Consortium r and omized 500 patients having colorectal resection to either 80%or30 % inspiredoxygen [ 9 ] . The incidence of SSI was halved from 11.2 AIM An association has been proposed between perioperative administration of 80 % oxygen and a lower incidence of wound infection after colorectal surgery . The present study was conducted to assess this hypothesis . METHODS Thirty-eight patients ( ASA classification 1 and 2 ) undergoing elective colorectal cancer surgery were allocated at r and om to 2 groups . Group 1 consisted of 19 patients who received an admixture of 80 % oxygen and 20 % nitrogen during anesthesia through an orotracheal tube and during the 2 first hours in the recovery room through a tight facemask with reservoir . Group 2 consisted of 19 patients who received an admixture of 70 % nitrous oxide and 30 % oxygen during anesthesia , followed by administration of 30 % oxygen delivered by a blender through a tight facemask with reservoir in the same manner than group 1 , during the first 2 hours in the recovery room . Wound infection was evaluated daily during hospital stay and after 7 days , 2 weeks , and 1 month . RESULTS The incidence of wound infection was 12.5 % in group 1 and 17.6 % in group 2 ( p=0.53 ) . CONCLUSIONS The results of this study showed no reduction in the incidence of wound infection following elective colorectal surgery in patients receiving 80 % oxygen during the perioperative period Background : Benefits and limitations of supplementation with 80 % fraction of inspired oxygen for preventing surgical site infections have not yet been clearly defined . Some studies have reported benefits in colorectal surgery , whereas trials in abdominal and gynecologic surgery have reported either no effect or a deleterious effect . Methods : Controlled , r and omized , assessor-blind multicenter trial , the ISO2 study , comparing the effects of hyperoxygenation ( fraction of inspired oxygen , 80 % ) with those of 30 % oxygen on the frequency of surgical site infections in routine abdominal , gynecologic , and breast surgery on 434 patients . Patients not seen in consultation after discharge were contacted . Results : In total , 208 patients received 30 % perioperative oxygen and 226 received 80 % . There was no difference between the two groups for baseline , intraoperative , and postoperative characteristics , except for oxygen saturation at closure , higher in the 80 % group ( P = 0.01 ) . The frequency of 30-day surgical site infections was 7.2 % ( 15/208 ) in the 30 % group and 6.6 % ( 15/226 ) in the 80 % group ( relative risk , 0.92 ; 95 % CI [ 0.46–1.84 ] , P = 0.81 ) . Frequency of adverse events ( nausea and vomiting , sternal pain , cough , hypotension ) was similar in the two groups . Desaturation and bradycardia were more frequent in the 30 % group . In an up date d meta- analysis including the result of this trial and those of eight published r and omized trials , the overall relative risk was 0.97 ; 95 % CI ( 0.68–1.40 ) , I2 ( inconsistency degree ) = 73 % , ( P = 0.88 ) . Conclusions : The routine use of hyperoxygenation throughout abdominal , gynecologic , and breast surgery had no effect on the frequency of 30-day surgical site infections and was not accompanied by more frequent adverse effects Background A high perioperative inspiratory oxygen fraction ( FiO2 ) may reduce the frequency of surgical site infection . Perioperative atelectasis is caused by absorption , compression and reduced function of surfactant . It is well accepted , that ventilation with 100 % oxygen for only a few minutes is associated with significant formation of atelectasis . However , it is still not clear if a longer period of 80 % oxygen results in more atelectasis compared to a low FiO2.Our aim was to assess Output:	Conclusions No definite signal of harm with 80 % FiO2 in adult surgical patients undergoing general anaesthesia was demonstrated and there is little evidence on safety‐related issues to discourage its use in this population
MS22007	*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 Peritoneal dialysis ( PD ) requires patients to take an active role in their adherence to fluid restrictions . Although fluid non-adherence had been identified among this patient group , no specific interventions have been research ed or published with in the PD population . The current study sought to investigate whether an applied cognitive behavioural therapy ( CBT-based intervention ) used among haemodialysis patients would improve fluid adherence among PD patients ; utilizing clinical indicators used in practice . METHODS Fifteen PD patients identified as fluid non-adherent were r and omly assigned to an intervention group ( IG ) or a deferred-entry control group ( CG ) . The study ran for a total of 21 weeks , with five data collection points ; at baseline , post-intervention and at three follow-up points ; providing a RCT phase and a combined longitudinal analysis phase . The content of the group intervention encompassed educational , cognitive and behavioural components , aim ed to assist patients ' self-management of fluid . RESULTS No significant differences in weight ( kg ) reduction were found in either phase and undesirable changes in blood pressure ( BP ) were observed . However , in the longitudinal phase , a statistically significant difference in oedematous status was observed at 6-week follow-up ; which may be indicative of fluid adherence . Positive and significant differences were observed in the desired direction for measures of psychological well-being , quality of life and health beliefs ; areas correlated with enhanced fluid adherence in other research . CONCLUSIONS This study reveals encouraging and significant changes in predictors of fluid adherence . Although there were no significant changes in weight as a crude clinical measure of fluid intake , significant reductions in oedematous status were observed as a consequence of this CBT-based group intervention Objective The purpose of this study is to evaluate the efficacy of a behavioral self-regulation intervention vs. active control condition using a parallel-group r and omized clinical trial with a sample of center hemodialysis patients with chronic kidney disease . Method Participants were recruited from 8 hemodialysis treatment centers in the Midwest . Eligible patients were ( a ) fluid nonadherent as defined by an interdialytic weight gain > 2.5 kg over a 4-week period , ( b ) > 18 years of age , ( c ) English-speaking without severe cognitive impairment , ( d ) treated with center-based hemodialysis for > 3 months , and ( e ) not living in a care facility in which meals were managed . Medical records were used to identify eligible patients . Patients were r and omly assigned to either a behavioral self-regulation intervention or active control condition in which groups of 3–8 patients met for hour-long , weekly sessions for 7 weeks at their usual hemodialysis clinic . Primary analyses were intention-to-treat . Results Sixty-one patients were r and omized to the intervention while 58 were assigned to the attention-placebo support and discussion control . Covariate-adjusted between-subjects analyses demonstrated no unique intervention effect for the primary outcome , interdialytic weight gain ( β = 0.13 , p = 0.48 ) . Significant within-subjects improvement over time was observed for the intervention group ( β = −0.32 , p = 0.014 ) . Conclusions The present study found that participation in a behavioral self-regulation intervention result ed in no unique intervention effect on a key indicator of adherence for those with severe chronic kidney disease . There was , however , modest within-subjects improvement in interdialytic weight gain for the intervention group which meshes with other evidence showing the utility of behavioral interventions in this patient population . Clinical Trials.gov Identifier : This research examined the relative efficacies of three intervention strategies design ed to increase compliance to medical regimens in a group of ambulatory hemodialysis patients . The interventions examined included behavioral contracting ( with or without the involvement of a family member or friend ) and weekly telephone contacts with patients . Compliance was assessed with regard to following dietary restrictions and limiting fluid intake . Data were collected from 116 patients drawn from two outpatient clinics . Within clinics , patients were r and omly assigned either to an intervention program or to a control group . The study employed a pretest-posttest control group design . Patients were interviewed before the intervention programs began ( T1 ) , after a 6-week intervention period ( T2 ) , and 3 months after completion of the intervention period ( T3 ) . Results showed that the interventions achieved substantial reductions in patients ' serum potassium levels and in weight gains between dialysis treatments between T1 and T2 . In general , however , these program effects tapered off to preintervention levels between T2 and T3 . The findings thus indicate a need for long-term intervention programs OBJECTIVE This study aim ed to assess the effectiveness of Benson 's relaxation technique in improving the hemodialysis patients ' dietary and fluid adherence and biomedical markers . DESIGN This r and omized controlled trial with a pre-post test design was conducted on 86 hemodialysis patients r and omly divided into an intervention ( receiving Benson 's relaxation technique ) and a control group ( usual care ) . SETTING The setting of the study was two hemodialysis units affiliated to Shiraz University of Medical Sciences , Shiraz , Iran . INTERVENTION The patients listened to the audiotape of Benson 's relaxation technique twice a day each time for 20min for 8 weeks . MAIN OUTCOME MEASURES Dietary and fluid adherence and some biomedical markers were measured in both the intervention and the control group at baseline and at the 8th week after the intervention . RESULTS The results showed significant differences between the two groups regarding blood urea nitrogen and phosphate as dietary adherence and interdialytic weight gain as fluid adherence in the 8th week of the intervention ( P<0.05 ) . Also , a significant difference was found between the two groups concerning blood glucose level after the intervention ( P<0.05 ) . CONCLUSIONS This study highlighted the importance of Benson 's relaxation technique in improvement of adherence and some biomedical markers in hemodialysis patients . Thus , Benson 's relaxation therapy could be used as a part of the nursing care practice for hemodialysis patients and those suffering from chronic diseases OBJECTIVE To examine the effect of self-management dietary counselling ( SMDC ) on adherence to dietary management of hyperphosphatemia among haemodialysis patients . DESIGN An eight-week cluster based r and omised control trial . PARTICIPANTS 122 stable adult patients were recruited from an HD unit in Sidon , Lebanon . Study groups were : full intervention ( A ) ( n = 41 ) , partial intervention ( B ) ( n = 41 ) and control ( C ) ( n = 40 ) . INTERVENTION Group ( A ) received SMDC , Group ( B ) received educational games only and Group ( C ) did not receive any research intervention . MAIN OUTCOME MEASURES Serum phosphorus ( P ) , Calcium Phosphate product ( Ca × P ) and two question naires : patient knowledge ( PK ) and dietary non-adherence ( PDnA ) to P reduced diet . RESULTS Group A experienced a significant improvement in mean ( ± SD ) P ( 6.54 ± 2.05 - 5.4 ± 1.97 mg/dl ) , Ca × P ( 58 ± 17 - 49 ± 12 ) , PK scores ( 50 ± 17 - 69 ± 25 % ) and PDnA scores ( 21.4 ± 4.0 - 18.3 ± 2.0 ) . Group B experienced a significant improvement in Ca × P ( 52 ± 14 - 45 ± 16 ) . Group C did not experience any significant change post intervention . CONCLUSION Our findings demonstrate the importance of patient-tailored counselling on serum P management Background / Aims . One of the causes of uncontrolled secondary hyperparathyroidism ( sHPT ) is patient 's poor drug adherence . We evaluated the clinical benefits of an integrated care approach on the control of sHPT by cinacalcet . Methods . Prospect i ve , r and omized , controlled , multicenter , open-label study . Fifty hemodialysis patients on a stable dose of cinacalcet were r and omized to an integrated care approach ( IC ) or usual care approach ( UC ) . In the IC group , cinacalcet adherence was monitored using an electronic system . Results were discussed with the patients in motivational interviews , and drug prescription adapted accordingly . In the UC group , drug adherence was monitored , but results were not available . Results . At six months , 84 % of patients in the IC group achieved recommended iPTH targets versus 55 % in the UC group ( P = 0.04 ) . The mean cinacalcet taking adherence improved by 10.8 % in the IC group and declined by 5.3 % in the UC group ( P = 0.02 ) . Concomitantly , the mean dose of cinacalcet was reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group ( P = 0.03 ) . Conclusions . The use of a drug adherence monitoring program in the management of sHPT in hemodialysis patients receiving cinacalcet improves drug adherence and iPTH control and allows a reduction in the dose of cinacalcet 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 Poor compliance with the dietary prescriptions is quite common in dialysis patients . We believe that most of the noncompliance is caused by the patient 's poor underst and ing of the dietary prescription . Therefore , in the present study , we tried to investigate the role of menu suggestion in improving the patient 's compliance with the dietary prescription . DESIGN AND SETTING A longitudinal cohort study conducted at an outpatient dialysis clinic . PATIENTS Seventy clinical ly stable patients on peritoneal dialysis were included in this prospect i ve study during April 1 , 2004 , to November 31 , 2004 , in a single center . Patients who had significant cognitive impairment and thus did not underst and the food contents during the training course were not eligible for enrollment . INTERVENTION All the patients were r and omly assigned to 1 of 2 groups . Group 1 patients received the traditional patient education method . Group 2 patients additionally received individualized menu suggestions based on their food preferences and education on how to exchange the foods at equivalent amounts according to the exchange list . MAIN OUTCOME MEASURES At present , there are no clear optimal dietary protein intake levels for peritoneal dialysis patients . Our experience is that a dietary protein intake level of 0.8 to 1.2 g/kg/d can maintain our patients in a good nutritional status . Thereafter , in this study we prescribed the dietary protein intake level at 0.8 to 1.2 g/kg/d and defined compliance as meeting this target protein intake level . RESULTS There were 35 patients in each group . The compliance was 22.9 % in group 1 and 57.1 % in group 2 ( P < .05 ) . CONCLUSIONS Our study suggests that menu suggestion may be an effective way of improving the compliance with the diet in peritoneal dialysis patients . It improves the patient 's underst and ing of the dietary prescription CONTEXT High dietary phosphorus intake has deleterious consequences for renal patients and is possibly harmful for the general public as well . To prevent hyperphosphatemia , patients with end-stage renal disease limit their intake of foods that are naturally high in phosphorus . However , phosphorus-containing additives are increasingly being added to processed and fast foods . The effect of such additives on serum phosphorus levels is unclear . OBJECTIVE To determine the effect of limiting the intake of phosphorus-containing food additives on serum phosphorus levels among patients with end-stage renal disease . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized controlled trial at 14 long-term hemodialysis facilities in northeast Ohio . Two hundred seventy-nine patients with elevated baseline serum phosphorus levels ( > 5.5 mg/dL ) were recruited between May and October 2007 . Two shifts at each of 12 large facilities and 1 shift at each of 2 small facilities were r and omly assigned to an intervention or control group . INTERVENTION Intervention participants ( n=145 ) received education on avoiding foods with phosphorus additives when purchasing groceries or visiting fast food restaurants . Control participants ( n=134 ) continued to receive usual care . MAIN OUTCOME MEASURE Change in serum phosphorus level after 3 months . RESULTS At baseline , there was no significant difference in serum phosphorus levels between the 2 groups . After 3 months , the decline in serum phosphorus levels was 0.6 mg/dL larger among intervention vs control participants ( 95 % confidence interval , -1.0 to -0.1 mg/dL ) . Intervention participants also had statistically significant increases in reading ingredient lists ( P<.001 ) and nutrition facts labels ( P = .04 ) but no significant increase in food knowledge scores ( P = .13 ) . CONCLUSION Educating end-stage renal disease patients to avoid phosphorus-containing food additives result ed in modest improvements in hyperphosphatemia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00583570 CONTEXT Mortality rates among US hemodialysis patients are the highest in the industrialized world at 23 % per year . Measures of dialysis do Output:	A majority of ( 28/36 ) RCTs showed improvement in some reported outcomes . CONCLUSIONS Interventions to improve treatment adherence result in modest short-term benefits in surrogate outcome measures in dialysis patients , but significant improvements in trial design and outcome reporting are warranted to identify strategies that would achieve meaningful and sustainable clinical benefits .
MS22008	*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 long-term physiological effects of refined carbohydrates on appetite and mood remain unclear . Reported effects when subjects are not blind may be due to expectations and have rarely been studied for more than 24 h. The present study compared the effects of supplementary soft drinks added to the diet over 4 weeks on dietary intake , mood and BMI in normal-weight women ( n 133 ) . Subjects were categorised as ' watchers ' or ' non-watchers ' of what they ate then received sucrose or artificially sweetened drinks ( 4 x 250 ml per d ) . Expectancies were varied by labelling drinks ' sugar ' or ' diet ' in a counter-balanced design . Sucrose supplements provided 1800 kJ per d and sweetener supplements provided 67 kJ per d. Food intake was measured with a 7 d diary and mood with ten single Likert scales . By 4 weeks , sucrose supplements significantly reduced total carbohydrate intake ( F(1,129 ) = 53.81 ; P<0.001 ) , fat ( F(2,250 ) = 33.33 ; P<0.001 ) and protein intake ( F(2,250 ) = 28.04 ; P<0 - 001 ) compared with sweetener supplements . Mean daily energy intake increased by just under 1000 kJ compared with baseline ( t ( 67 df ) = 3.82 ; P < 0.001 ) and was associated with a non-significant trend for those receiving sucrose to gain weight . There were no effects on appetite or mood . Neither dietary restraint status as measured by the Dutch Eating Behaviour Question naire nor the expectancy procedure had effects . Expectancies influenced mood only during baseline week . It is concluded that sucrose satiates , rather than stimulates , appetite or negative mood in normal-weight subjects BACKGROUND The consumption of beverages that contain sugar is associated with overweight , possibly because liquid sugars do not lead to a sense of satiety , so the consumption of other foods is not reduced . However , data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain . METHODS We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age . Participants were r and omly assigned to receive 250 ml ( 8 oz ) per day of a sugar-free , artificially sweetened beverage ( sugar-free group ) or a similar sugar-containing beverage that provided 104 kcal ( sugar group ) . Beverages were distributed through schools . At 18 months , 26 % of the children had stopped consuming the beverages ; the data from children who did not complete the study were imputed . RESULTS The z score for the body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group ; the 95 % confidence interval ( CI ) of the difference was -0.21 to -0.05 . Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group ( 95 % CI for the difference , -1.54 to -0.48 ) . The skinfold-thickness measurements , waist-to-height ratio , and fat mass also increased significantly less in the sugar-free group . Adverse events were minor . When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study , the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group ( P=0.06 ) . CONCLUSIONS Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children . ( Funded by the Netherl and s Organization for Health Research and Development and others ; DRINK Clinical Trials.gov number , NCT00893529 . ) BACKGROUND Increased intake of sugar-sweetened beverages and fruit juice has been associated with overweight in children . OBJECTIVE This study prospect ively assessed beverage consumption patterns and their relationship with weight status in a cohort of children born at different risk for obesity . METHODS AND PROCEDURES Participants were children born at low risk ( n = 27 ) or high risk ( n = 22 ) for obesity based on maternal prepregnancy BMI ( kg/m(2 ) ) . Daily beverage consumption was generated from 3-day food records from children aged 3 - 6 years and coded into seven beverage categories ( milk , fruit juice , fruit drinks , caloric and non-caloric soda , soft drinks including and excluding fruit juice ) . Child anthropometric measures were assessed yearly . RESULTS High-risk children consumed a greater percentage of daily calories from beverages at age 3 , more fruit juice at ages 3 and 4 , more soft drinks ( including fruit juice ) at ages 3 - 5 , and more soda at age 6 compared to low-risk children . Longitudinal analyses showed that a greater 3-year increase in soda intake was associated with an increased change in waist circumference , whereas a greater increase in milk intake was associated with a reduced change in waist circumference . There was no significant association between change in intake from any of the beverage categories and change in BMI z-score across analyses . DISCUSSION Children 's familial predisposition to obesity may differentially affect their beverage consumption patterns . Future research should examine the extent to which dietary factors may play a role in pediatric body fat deposition over time BACKGROUND During the nutrition transition in Chile , dietary changes were marked by increased consumption of high-energy , nutrient-poor products , including sugar-sweetened beverages ( SSBs ) . Obesity is now the primary nutritional problem in posttransitional Chile . OBJECTIVE We conducted a r and omized controlled trial to examine the effects on body composition of delivering milk beverages to the homes of overweight and obese children to displace SSBs . DESIGN We r and omly assigned 98 children aged 8 - 10 y who regularly consumed SSBs to intervention and control groups . During a 16-wk intervention , children were instructed to drink 3 servings/d ( approximately 200 g per serving ) of the milk delivered to their homes and to not consume SSBs . Body composition was measured by dual-energy X-ray absorptiometry . Data were analyzed by multiple regression analysis according to the intention-to-treat principle . RESULTS For the intervention group , milk consumption increased by a mean ( + /- SEM ) of 452.5 + /- 37.7 g/d ( P < 0.0001 ) , and consumption of SSBs decreased by -711.0 + /- 33.7 g/d ( P < 0.0001 ) . For the control group , milk consumption did not change , and consumption of SSBs increased by 71.9 + /- 33.6 g/d ( P = 0.04 ) . Changes in percentage body fat , the primary endpoint , did not differ between groups . Nevertheless , the mean ( + /- SE ) accretion of lean body mass was greater ( P = 0.04 ) in the intervention ( 0.92 + /- 0.10 kg ) than in the control ( 0.62 + /- 0.11 kg ) group . The increase in height was also greater ( P = 0.01 ) in the intervention group ( 2.50 + /- 0.21 cm ) than in the control group ( 1.77 + /- 0.20 cm ) for boys but not for girls . CONCLUSION Replacing habitual consumption of SSBs with milk may have beneficial effects on lean body mass and growth in children , despite no changes in percentage body fat . This trial was registered at clinical trials.gov as NCT00149695 To examine whether artificial sweeteners aid in the control of long-term food intake and body weight , we gave free-living , normal-weight subjects 1150 g soda sweetened with aspartame ( APM ) or high-fructose corn syrup ( HFCS ) per day . Relative to when no soda was given , drinking APM-sweetened soda for 3 wk significantly reduced calorie intake of both females ( n = 9 ) and males ( n = 21 ) and decreased the body weight of males but not of females . However , drinking HFCS-sweetened soda for 3 wk significantly increased the calorie intake and body weight of both sexes . Ingesting either type of soda reduced intake of sugar from the diet without affecting intake of other nutrients . Drinking large volumes of APM-sweetened soda , in contrast to drinking HFCS-sweetened soda , reduces sugar intake and thus may facilitate the control of calorie intake and body weight BACKGROUND High consumption of sugar-sweetened drinks has been associated with weight gain and obesity in the United States . This trend may also be affecting population s with different eating patterns who increasingly are adopting typical US dietary patterns . OBJECTIVE We assessed whether the consumption of sweetened drinks and other food items increased the likelihood of weight gain in a Mediterranean population . DESIGN This was a prospect i ve cohort analysis of 7194 men and women with a mean age of 41 y who were followed-up for a median of 28.5 mo with mailed question naires . Dietary exposure was assessed with a previously vali date d semiquantitative food-frequency question naire . RESULTS During follow-up , we observed that 49.5 % of the participants increased their weight ( x weight gain : 0.64 kg ; 95 % CI : 0.55 , 0.73 kg ) . In the participants who had gained > or =3 kg in the 5 y before baseline , the adjusted odds ratio of subsequent weight gain for the fifth quintile compared with the first quintile of sugar-sweetened soft drink consumption was 1.6 ( 95 % CI : 1.2 , 2.1 ; P for trend = 0.02 ) . This association was absent in the participants who had not gained weight in the 5-y period before baseline . The consumption of hamburgers , pizza , and sausages ( as a proxy for fast-food consumption ) was also independently associated with weight gain ( adjusted odds ratio for the fifth compared with the first quintile = 1.2 ; 95 % CI : 1.0 , 1.4 ; P for trend = 0.05 ) . We also found a significant , but weaker , association between weight gain and both red meat and sweetened fruit juice consumption . CONCLUSION In a Mediterranean cohort , particularly in the participants who had already gained weight , an increased consumption of sugar-sweetened soft drinks and of hamburgers , pizza , and sausages was associated with a higher risk of additional subsequent weight gain BACKGROUND Consumption of liquid calories from beverages has increased in parallel with the obesity epidemic in the US population , but their causal relation remains unclear . OBJECTIVE The objective of this study was to examine how changes in beverage consumption affect weight change among adults . DESIGN This was a prospect i ve study of 810 adults participating in the PREMIER trial , an 18-mo r and omized , controlled , behavioral intervention trial . Measurements ( weight , height , and 24-h dietary recall ) were made at baseline , 6 mo , and 18 mo . RESULTS Baseline mean intake of liquid calories was 356 kcal/d ( 19 % of total energy intake ) . After potential confounders and intervention assignment were controlled for , a reduction in liquid calorie intake of 100 kcal/d was associated with a weight loss of 0.25 kg ( 95 % CI : 0.11 , 0.39 ; P < 0.001 ) at 6 mo and of 0.24 kg ( 95 % CI : 0.06 , 0.41 ; P = 0.008 ) at 18 mo . A reduction in liquid calorie intake had a stronger effect than did a reduction in solid calorie intake on weight loss . Of the individual beverages , only intake of sugar-sweetened beverages ( SSBs ) was significantly associated with weight change . A reduction in SSB intake of 1 serving/d was associated with a weight loss of 0.49 kg ( 95 % CI : 0.11 , 0.82 ; P = 0.006 ) at 6 mo and of 0.65 kg ( 95 % CI : 0.22 , 1.09 ; P = 0.003 ) at 18 mo . CONCLUSIONS These data support recommendations to limit liquid calorie intake among adults and to reduce SSB consumption as a means to accomplish weight loss or avoid excess weight gain . This trial was registered at clinical trials.gov as NCT00000616 BACKGROUND Type 2 diabetes mellitus is an increasingly serious health problem among African American women . Consumption of sugar-sweetened drinks was associated with an increased risk of diabetes in 2 studies but not in a third ; however , to our knowledge , no data are available on African Americans regarding this issue . Our objective was to examine the association between consumption of sugar-sweetened beverages , weight gain , and incidence of type 2 diabetes mellitus in African American women . METHODS A prospect i ve follow-up study of 59,000 African American women has been in progress since 1995 . Participants reported on food and beverage consumption in 1995 and 2001 . Biennial follow-up question Output:	Sensitivity analyses of RCTs in children showed more pronounced benefits in preventing weight gain in SSB substitution trials ( compared with school-based educational programs ) and among overweight children ( compared with normal-weight children ) . Our systematic review and meta- analysis of prospect i ve cohort studies and RCTs provides evidence that SSB consumption promotes weight gain in children and adults
MS22009	*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 Cardiac shock wave therapy ( CSWT ) improves cardiac function in patients with severe coronary artery disease ( CAD ) . We aim ed to evaluate the clinical outcomes of a new CSWT treatment regimen . Methods The 55 patients with severe CAD were r and omly divided into 3 treatment groups . The control group ( n = 14 ) received only medical therapy . In group A ( n = 20 ) , CSWT was performed 3 times within 3 months . In group B ( n = 21 ) , patients underwent 3 CSWT sessions/week , and 9 treatment sessions were completed within 1 month . Primary outcome measurement was 6-minute walk test ( 6MWT ) . Other measurements were also evaluated . Results The 6MWT , CCS grading of angina , dosage of nitroglycerin , NYHA classification , and SAQ scores were improved in group A and B compared to control group . Conclusions A CSWT protocol with 1 month treatment duration showed similar therapeutic efficacy compared to a protocol of 3 months duration . Clinical trial registryWe have registered on Clinical Trials.gov , the protocol ID is CSWT IN CHINA OBJECTIVE The aim of this study was to evaluate the effect of cardiac shock wave therapy ( CSWT ) on microvolt T wave alternans ( MTWA ) in patients with coronary artery disease ( CAD ) . METHODS 87 patients with old myocardial infa rct ion ( OMI ) were enrolled in this study . Sixty-two patients were r and omized into the CSWT group , 32 patients into the regular treatment group ( Group A ) according to different shock wave procedure , and 30 into the exp and ing scope treatment group ( Group B ) , and 25 patients were r and omized into the control group ( Group C ) . But the shock wave ( SW ) energy was only applied to the patients in the CSWT group and not to the patients in the control group . Three months was a treatment course , thus patients received a total of 9 CSWT treatment sessions . RESULTS Technetium-99 m sestamibi myocardial perfusion , fluorine-18 fluorodeoxyglucose myocardial metabolism single-photon emission computed tomography ( SPECT ) were performed to identify segments of myocardial ischemia , myocardial viability , and microvolt T wave alternans ( MTWA ) before and after CSWT . After CSWT , the rehospitalization rates of CSWT group were lower than control group ( P<0.05 ) . The myocardial ischemic segments , metabolism abnormal segments , total radioactive score of perfusion imaging and metabolism imaging , MTWA , and MTWA/HR in CSWT group were reduced significantly ( P<0.05 ) . And the heart rate of maximum MTWA , exercise time were increased significantly ( P<0.05 ) . All of the parameters in the control group did not change significantly even worsen after the treatment ( P>0.05 ) . CONCLUSIONS CSWT can reduce the MTWA value , improve the heart chronotropic function and increase the threshold of frequency which causes MTWA Background Ultrasound guided cardiac shock wave therapy ( CSWT ) is a noninvasive therapeutic option in the treatment of chronic-refractory angina . Clinical trials have shown that CSWT reduces angina symptoms , improves regional systolic function , LV ejection fraction , myocardial perfusion and quality of life parameters . Absolute measurements of myocardial perfusion before and after CSWT have not been performed so far . Methods and results We studied a total of 21 CCS III patients with history of CAD and multiple interventions who suffered from disabling angina despite individually optimized medical therapy . An N-13 NH3 PET perfusion scan under adenosine was performed before and after CSWT treatment . CSWT was well tolerated in all patients . Absolute perfusion under adenosine of the global left-ventricular myocardium did not change under therapy or minimal coronary resistance . The treated segments , however , showed in terms of both perfusion and resistance a mild but significant improvement , by 11 and 15 % , respectively , whereas no change could be observed in the remote segments . Considering a threshold of increased perfusion of 5 % , 10 ( 77 % ) out of 13 patients with a better target perfusion improved in their CCS class , whereas 3 ( 43 % ) out of 7 patients without improved target perfusion improved in their CCS class too . ConclusionS t and ard CSWT has the potential to improve myocardial perfusion of the therapy zone and clinical CAD symptomatology without affecting global myocardial perfusion . As a noninvasive and well tolerated therapeutic option , these data suggest the use of CSWT in patients with end-stage CAD Our aim was to evaluate the safety and effectiveness of extracorporeal cardiac shock wave therapy ( CSWT ) for the patients with coronary heart disease ( CHD ) using a r and omized , double-blind , controlled clinical trial design . Twenty-five patients with CHD were enrolled in this study . Fourteen of the patients were r and omized into the CSWT group and 11 into the control group . We applied the CSWT procedure to each patient by using nine shock treatments during 3 months , but the shock wave ( SW ) energy was only applied to the patients in the CSWT group and not to the patients in the control group . Technetium-99 m sestamibi myocardial perfusion , fluorine-18 fluorodeoxyglucose myocardial metabolism single-photon emission computed tomography ( SPECT ) , and two-dimensional echocardiography were performed to identify segments of myocardial ischemia , myocardial viability , and ejection fraction before and after CSWT . We also followed the patients to evaluate adverse effects . After CSWT , the New York Heart Association class , the Canadian Cardiovascular Society angina scale , nitroglycerin dosage , myocardial perfusion and myocardial metabolic imaging scores of dual-isotope SPECT in the CSWT group were reduced significantly ( P = 0.019 , 0.027 , 0.039 , 0.000 , 0.001 , respectively ) , and the Seattle Angina Question naire scale , 6-min walking test , and left ventricular ejection fraction were increased significantly ( P = 0.021 , 0.024 , 0.016 , respectively ) compared with those before the SW treatment . All of the parameters in the control group did not change significantly after the treatment ( all P > 0.05 ) . No serious adverse effects of CSWT were observed . Cardiac shock wave therapy is a safe and effective treatment for CHD patients 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 AIMS An increasing number of patients with severe coronary artery disease ( CAD ) are not c and i date s for traditional revascularization and experience angina in spite of excellent medical therapy . Despite limited data regarding the natural history and predictors of adverse outcome , these patients have been considered at high risk for early mortality . METHODS AND RESULTS The OPtions In Myocardial Ischemic Syndrome Therapy ( OPTIMIST ) program at the Minneapolis Heart Institute offers traditional and investigational therapies for patients with refractory angina . A prospect i ve clinical data base includes detailed baseline and yearly follow-up information . Death status and cause were determined using the Social Security Death Index , clinical data , and death certificates . Time to death was analysed using survival analysis methods . For 1200 patients , the mean age was 63.5 years ( 77.5 % male ) with 72.4 % having prior coronary artery bypass grafting , 74.4 % prior percutaneous coronary intervention , 72.6 % prior myocardial infa rct ion , 78.3 % 3-vessel CAD , 23.0 % moderate-to-severe left-ventricular ( LV ) dysfunction , and 32.6 % congestive heart failure ( CHF ) . Overall , 241 patients died ( 20.1 % : 71.8 % cardiovascular ) during a median follow-up 5.1 years ( range 0 - 16 , 14.7 % over 9 ) . By Kaplan-Meier analysis , mortality was 3.9 % ( 95 % CI 2.8 - 5.0 ) at 1 year and 28.4 % ( 95 % CI 24.9 - 32.0 ) at 9 years . Multivariate predictors of all-cause mortality were baseline age , diabetes , angina class , chronic kidney disease , LV dysfunction , and CHF . CONCLUSION Long-term mortality in patients with refractory angina is lower than previously reported . Therapeutic options for this distinct and growing group of patients should focus on angina relief and improved quality of life Background Cardiac shockwave therapy ( CSWT ) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium . This prospect i ve study was performed to evaluate the feasibility and safety of CSWT . Methods We included 33 patients ( mean age 70 ± 7 years , mean left ventricular ejection fraction 55 ± 12 % ) with end-stage coronary artery disease , chronic angina pectoris and reversible ischaemia on myocardial scintigraphy . CSWT was applied to the ischaemic zones ( 3–7 spots/session , 100 impulses/spot , 0.09 mJ/mm2 ) in an echocardiography-guided and ECG-triggered fashion . The protocol included a total of 9 treatment sessions ( 3 treatment sessions within 1 week at baseline , and after 1 and 2 months ) . Clinical assessment was performed using exercise testing , angina score ( CCS class ) , nitrate use , myocardial scintigraphy , and cardiac magnetic resonance ( CMR ) 1 and 4 months after the last treatment session . Results One and 4 months after CSWT , sublingual nitrate use decreased from 10/week to 2/week ( p < 0.01 ) and the angina symptoms diminished from CCS class III to CCS class II ( p < 0.01 ) . This clinical improvement was accompanied by an improved myocardial uptake on stress myocardial scintigraphy ( 54.2 ± 7.7 % to 56.4 ± 9.4 % , p = 0.016 ) and by increased exercise tolerance at 4-month follow-up ( from 7.4 ± 2.8 to 8.8 ± 3.6 min p = 0.015 ) . No clinical ly relevant side effects were observed . Conclusion CSWT improved symptoms and reduced ischaemia burden in patients with end-stage coronary artery disease without relevant side effects . The study provides a solid basis for a r and omised multicentre trial to establish CSWT as a new treatment option in end-stage coronary artery disease Objectives The usefulness and safety of percutaneous myocardial laser therapy in selected patients have been identified in previous 1-year r and omized trial reports , including that from a double-blind , sham-controlled trial we independently conducted . We aim ed to determine whether the 1-year effects are maintained through a long-term , longitudinal follow-up . Methods Patients ( n=77 ) with chronic , stable , medically refractory angina ( class III or IV ) not amenable to conventional revascularization and with evidence of reversible ischemia , ejection fraction ≥25 % , and myocardial wall thickness ≥8 mm were treated with percutaneous myocardial laser . After the 1-year follow-up and disclosure of all r and omized assignments as prespecified in the respective study protocol , patients were followed up longitudinally for a mean of 3 years for angina class , left ventricular ejection fraction , medication usage , and adverse events . Results No procedural mortality , myocardial infa rct ion , or cerebral embolism occurred . Pericardiocentesis was required in two patients ( 2.6 % ) . Cardiac event-free survival was 88 % at 1 year and 66 % at late follow-up . Mean Canadian Cardiovascular Society angina class was significantly improved from baseline ( 3.2±0.4 ) at 1 year ( 2.2±1.1 , P<0.001 ) and at a mean of 3 years ( 1.9±1.2 , P<0.001 ) . Nitrate usage was significantly reduced at late follow-up ; however , ejection fraction did not change over time . In a multivariate analysis , angina improvement at 1 year was found to be a significant independent predictor of both survival and angina improvement at late follow-up . Conclusion We conclude that percutaneous myocardial laser therapy in selected patients with severe , medically refractory angina not treatable with conventional revascularization induces significant and sustained symptomatic benefit Objectives . To investigate the effectiveness of extracorporeal shock wave therapy ( ESWT ) for symptoms alleviation in chronic pelvic pain syndrome ( CPPS ) . Material s and Methods . 40 patients with CPPS were r and omly allocated into either the treatment or sham group . In the first group , patients were treated by ESWT once a week for 4 weeks by a defined protocol . In the sham group , the same protocol was applied but with the probe being turned off . The follow-up assessment s were done at 1 , 2 , 3 , and 12 weeks by Visual Analogue Scale ( VAS ) for pain and NIH-developed Chronic Prostatitis Symptom Index ( NIH-CPSI ) . Results . Pain domain scores at follow-up points in both treatment and sham groups were reduced , more so in the treatment group , which were significant at weeks 2 , 3 , and 12 . Urinary scores became significantly different at weeks 3 and 12 . Also , quality of life ( QOL ) and total NIH-CPSI scores at all four Output:	All selected studies demonstrated significant improvement in subjective measures of angina symptoms and /or quality of life , in the majority of studies left ventricular function and myocardial perfusion improved . Conclusions Systematic review of CSWT studies in stable coronary artery disease ( CAD ) demonstrated consistent improvement of clinical variables . Meta- analysis showed a moderate improvement of exercise capacity . Overall , CSWT is a promising non-invasive option for patients with end-stage CAD , but evidence is limited to small sample single-center studies .
MS22010	*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 aim of the study was to analyse the toxicity and health related quality of life ( HRQoL ) of breast cancer patients treated with FAC ( 5-fluorouracil , doxorubicin , cyclophosphamide ) and TAC ( docetaxel , doxorubicin , cyclophosphamide ) with and without primary prophylactic G-CSF ( PPG ) . PATIENTS AND METHODS This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients . After the entry of the first 237 patients , the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia . A total of 1047 evaluable patients from 49 centres in Spain , two in Pol and and four in Germany were included in the trial . Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 question naires were compared in the three groups ( FAC , TAC pre-amendment and TAC post-amendment ) . RESULTS The addition of PPG to TAC significantly reduced the incidence of neutropenic fever , grade 2 - 4 anaemia , asthenia , anorexia , nail disorders , stomatitis , myalgia and dysgeusia . Patient QoL decreased during chemotherapy , more with TAC than FAC , but returned to baseline values afterwards . The addition of PPG to TAC significantly reduced the percentage of patients with clinical ly relevant Global Health Status deterioration ( 10 or more points over baseline value ) at the end of chemotherapy ( 64 % versus 46 % , P<0.03 ) . CONCLUSIONS The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects . The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG , particularly in the final part of chemotherapy treatment Introduction There are few studies on the effect on quality of life ( QL ) of cancer-related illness and treatment in elderly patients . The aim of this work was to evaluate prospect ively QL in a sample of elderly patients with stages I – III breast cancer who started radiotherapy treatment and compare their QL with that of a sample of younger patients . Material s and methods Forty-eight patients , ≥ 65 years of age completed the European Organization for Research and Treatment of Cancer ( EORTC ) QL question naires QLQ-C30 and QLQ-BR23 , and the Interview for Deterioration in Daily Living Activities in Dementia ( IDDD ) daily activities scale three times throughout treatment and follow-up periods . Clinical and demographic data were also recorded . Fifty patients ages 40–64 years with the same disease stage and treatment modality had previously completed the QL question naires . QL scores , changes in them among the three assessment s , differences between groups based on clinical factors , and differences between the two sample s were calculated . Results QL scoring was good and stable ( > 70/100 points ) in most areas , in line with clinical data . Light and moderate limitations occurred in global QL and some emotional , sexual , and treatment-related areas . Moderate decreases ( 10–20 ) appeared in some toxicity-related areas , which recovered during the follow-up period . Breast-conservation and sentinel-node patients presented higher scores in emotional areas . There were few QL differences among age-based sample s. Conclusions QL and clinical data indicate radiotherapy was well tolerated . Age should not be the only factor evaluated when deciding upon treatment for breast cancer patients Quality of life ( QOL ) assessment s of women entering a UK r and omised trial of adjuvant radiotherapy ( START ) were investigated to estimate the independent effects on QOL of age , time since surgery , type of breast surgery , chemotherapy and endocrine therapy . QOL was evaluated using the EORTC general cancer QOL scale ( EORTC QLQ-C30 ) , breast cancer module ( BR23 ) , the Body Image Scale ( BIS ) and the Hospital Anxiety and Depression Scale ( HADS ) . Independent effects of age and clinical factors were tested using multiple regression analysis . A total of 2208 ( mean age 56.9 years , range 26 - 87 ) consented to the QOL study prior to radiotherapy ; 17.1 % had undergone mastectomy ( Mx ) and the remainder had undergone a wide local excision ( WLE ) . 33.3 % had received adjuvant chemotherapy ( CT ) and 56.7 % were taking endocrine therapy ( ET ) . Age had significant effects on QOL with older and younger subgroups predicting poorer QOL for different domains . CT affected most QOL domains and result ed in worse body image , sexual functioning , breast and arm symptoms ( < 0.001 ) . Mx was associated with greater body image concerns ( p<0.001 ) , and WLE with more arm symptoms ( p=0.01 ) . There were no effects of ET on QOL . Women < 50 years ( proxy pre-menopausal ) had worse QOL in respect of anxiety , body image and breast symptoms but age and clinical factors had no effect on depression . Overall , QOL and mental health were favourable for most women about to start RT , but younger age and receiving CT were significant risk factors for poorer QOL , and so patients in these subgroups warrant further monitoring . Surgery had a limited impact and ET had no effect on QOL OBJECTIVE To evaluate a single cycle of adjuvant chemotherapy compared with longer duration chemotherapy for premenopausal women or chemoendocrine therapy for postmenopausal women with operable breast cancer using a quality -of-life-oriented end point , Q-TWiST ( quality -adjusted analysis of TWiST : Time Without Symptoms and Toxicity ) . DESIGN Multicenter r and omized clinical trial -- International Breast Cancer Study Group ( IBCSG : formerly Ludwig Group ) Trial V. SETTING IBCSG participating centers in Sweden , Switzerl and , Australia , Yugoslavia , Spain , New Zeal and , Italy , Germany , and South Africa . PATIENTS Data were available for 1229 eligible patients with node-positive breast cancer who were r and omized to receive one of three adjuvant treatments after at least a total mastectomy and axillary clearance . INTERVENTIONS Patients received either a single cycle of perioperative chemotherapy consisting of cyclophosphamide , methotrexate , fluorouracil , and leucovorin ; or six cycles ( 6 months ) of a conventionally timed chemotherapy consisting of cyclophosphamide , methotrexate , fluorouracil , and prednisone for premenopausal women or this combination plus tamoxifen for postmenopausal women ; or both perioperative and conventionally timed chemotherapy for a 7-month course of adjuvant therapy . RESULTS At 5 years of median follow-up , patients who received the longer duration therapies had an improved 5-year disease-free survival percentage ( 53 % compared with 36 % ; P less than 0.001 ) and 5-year overall survival percentage ( 73 % compared with 63 % ; P = 0.001 ) compared with those who received the single perioperative cycle alone . By 3.5 years , the greater burden of toxic effects associated with the longer duration treatments was balanced by their superior control of disease . Within 5 years of follow-up , even after subtracting time with adjuvant treatment toxicity , patients gained an average of 2.2 months of Q-TWiST if treated with the longer duration therapies compared with the single cycle ( P = 0.03 ) . The gain for premenopausal patients was 2.8 months ( P = 0.05 ) , whereas the gain for postmenopausal women was 1.5 months ( P greater than 0.2 ) . CONCLUSIONS Six or seven months of adjuvant chemotherapy or chemoendocrine therapy improve both the quantity and quality of life for patients with node-positive breast cancer compared with a single short course of perioperative combination chemotherapy BACKGROUND Quality of life has increasingly become an important issue in breast cancer treatment . One of the impetuses for sentinel lymph node biopsy or selective axillary lymph node dissection ( ALND ) is the assumed decreased incidence of lymphedema compared with st and ard ALND . This is based on the assumption that ALND is associated with a clinical ly significant incidence of lymphedema and that this lymphedema decreases the quality of life of these patients . However , few data exist on this issue . This study attempts to define the incidence and effect on quality of life of postoperative lymphedema in breast cancer patients . METHODS To determine the incidence of postoperative lymphedema , the Breast Cancer Registry at Henry Ford Hospital was accessed to obtain information on all patients who underwent ALND in the management of breast cancer over a 7-year period . The registry is a prospect ively gathered data base to include the development of various complications , such as lymphedema . To determine the effects of lymphedema on quality of life , 101 consecutive , unselected patients who underwent breast surgery were asked to complete the SF-36 , a generic quality of life instrument . The SF-36 measures eight domains of quality of life . Patients were then divided into three groups : ( 1 ) breast surgery without ALND ( -ALND ) , ( 2 ) breast surgery with ALND but no lymphedema ( -LE ) , and ( 3 ) breast surgery with ALND and lymphedema ( + LE ) . RESULTS In all , 827 patients with ALND were identified in the registry . Of these , 8.3 % developed clinical ly apparent lymphedema . Patients in -ALND and -LE groups had similar scores in all domains of the SF-36 . However , patients in the + LE group had significantly lower scores in the domains of role-emotional and bodily pain . A significantly higher percentage of patients in the + LE group had scores below one st and ard deviation compared with national norms in the domains of bodily pain ( P = 0.005 ) , mental health ( P = 0.01 ) , and general health ( P = 0.04 ) . CONCLUSIONS Although postoperative lymphedema occurs in a minority of patients , when it does occur it can produce demonstrable diminutions in quality of life . Therefore , efforts to reduce the incidence of lymphedema , such as sentinel lymph node biopsy or selective ALND , would benefit breast cancer patients PURPOSE The r and omized study aim ed to determine the efficacy of psychological intervention consisting of relaxation and guided imagery to reduce anxiety and depression in gynecologic and breast cancer patients undergoing brachytherapy during hospitalization . METHODS AND MATERIAL S Sixty-six patients programmed to receive brachytherapy in two hospitals in Barcelona ( Spain ) were included in this study . The patients were r and omly allocated to either the study group ( n=32 ) or the control group ( n=34 ) . Patients in both groups received training regarding brachytherapy , but only study group patients received training in relaxation and guided imagery . After collection of sociodemographic data , all patients were given a set of question naires on anxiety and depression : the Hospital Anxiety and Depression Scale ( HADS ) , and on quality of life : Cuestionario de Calidad de Vida QL-CA-AFex ( CCV ) , prior to , during and after brachytherapy . RESULTS The study group demonstrated a statistically significant reduction in anxiety ( p=0.008 ) , depression ( p=0.03 ) and body discomfort ( p=0.04 ) compared with the control group . CONCLUSIONS The use of relaxation techniques and guided imagery is effective in reducing the levels of anxiety , depression and body discomfort in patients who must remain isolated while undergoing brachytherapy . This simple and inexpensive intervention enhances the psychological wellness in patients undergoing brachytherapy . State : This study has passed Ethical Committee review PURPOSE / OBJECTIVES To describe the side-effects burden experienced over time by 53 women who were receiving treatment for breast cancer and to describe the association of side-effects burden with psychological adjustment and life quality . DESIGN Data were drawn from the Self-Help Intervention Project ( SHIP ) , an intervention study design ed to test the effectiveness of nursing interventions for women receiving treatment for breast cancer . SETTING Subjects were interviewed in their homes or treatment locations three times over a period of four to five months . SAMPLE 53 women r and omly assigned to the control group of the SHIP . METHODS The research ers collected data after treatment was initiated , six to eight weeks later , and three months after that . MAIN RESEARCH VARIABLES Side-effects burden , psychological adjustment , and life quality . FINDINGS Fatigue was the most problematic side effect over time . Other problematic side effects included sore arm(s ) , difficulty sleeping , hair loss , and skin irritation . Significant associations were evident for psychological adjustment with symptom extension and number of side effects at Time 2 and Time 3 . Depression burden and anxiety burden were associated significantly with psychological adjustment at all three times . Overall life quality and present life quality was associated negatively with symptom extension and number of side effects at all three times . Fatigue burden was associated negatively with life quality at Time 2 and Time 3 with depression burden and anxiety burden negatively associated with life quality at all three times . CONCLUSIONS Over time , evidence showed that negative feelings , in particular depression burden and anxiety burden , persist . Depression burden and anxiety burden each were negatively associated with overall and present life quality at all three times . IMPLICATION S FOR NURSING PRACTICE A need exists for clinical ly individualized nursing interventions that will reduce the side effects burden of women receiving treatment for breast cancer . Interventions can do much Output:	Few differences were detected by type of chemotherapy , with the single exception of worse results among younger women treated with radiotherapy . In the short term , better results were reported for all HRQL components by women undergoing conservative rather than radical surgery . Presence of lymphedema was associated with worse HRQL . Psychosocial disorder and level of depression and anxiety , regardless of treatment or disease stage , worsened HRQL . One study found that breast cancer patients scored worse than did healthy women on almost all SF-12 scales .
MS22011	*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: Heart failure ( HF ) is the leading cause of rehospitalization in older adults . The purpose of this pilot study was to examine whether telemonitoring by an advanced practice nurse reduced subsequent hospital readmissions , emergency department visits , costs , and risk of hospital readmission for patients with HF . One hundred two patient/caregiver dyads were r and omized into 2 groups postdischarge ; 84 dyads completed the study . Hospital readmissions , emergency department visits , costs , and days to readmission were abstract ed from medical records . Participants were interviewed soon after discharge and 3 months later about effects of telemonitoring on depressive symptoms , quality of life , and caregiver mastery . There were no significant differences due to telemonitoring for any outcomes . Caregiver mastery , informal social support , and electronic home monitoring were not significant predictors for risk of hospital readmission . Further studies should address the interaction between the advanced practice nurse and follow-up intervention with telemonitoring of patients with HF to better target those who are most likely to benefit OBJECTIVES We sought to identify whether home telemonitoring ( HTM ) improves outcomes compared with nurse telephone support ( NTS ) and usual care ( UC ) for patients with heart failure who are at high risk of hospitalization or death . BACKGROUND Heart failure is associated with a high rate of hospitalization and poor prognosis . Telemonitoring could help implement and maintain effective therapy and detect worsening heart failure and its cause promptly to prevent medical crises . METHODS Patients with a recent admission for heart failure and left ventricular ejection fraction ( LVEF ) < 40 % were assigned r and omly to HTM , NTS , or UC in a 2:2:1 ratio . HTM consisted of twice-daily patient self-measurement of weight , blood pressure , heart rate , and rhythm with automated devices linked to a cardiology center . The NTS consisted of specialist nurses who were available to patients by telephone . Primary care physicians delivered UC . The primary end point was days dead or hospitalized with NTS versus HTM at 240 days . RESULTS Of 426 patients r and omly assigned , 48 % were aged > 70 years , mean LVEF was 25 % ( SD , 8) and median plasma N-terminal pro-brain natriuretic peptide was 3,070 pg/ml ( interquartile range 1,285 to 6,749 pg/ml ) . During 240 days of follow-up , 19.5 % , 15.9 % , and 12.7 % of days were lost as the result of death or hospitalization for UC , NTS , and HTM , respectively ( no significant difference ) . The number of admissions and mortality were similar among patients r and omly assigned to NTS or HTM , but the mean duration of admissions was reduced by 6 days ( 95 % confidence interval 1 to 11 ) with HTM . Patients r and omly assigned to receive UC had higher one-year mortality ( 45 % ) than patients assigned to receive NTS ( 27 % ) or HTM ( 29 % ) ( p = 0.032 ) . CONCLUSIONS Further investigation and refinement of the application of HTM are warranted because it may be a valuable role for the management of selected patients with heart failure Background — Assessment of the quality of care for out patients with heart failure ( HF ) has focused on the development and use of process-based performance measures , with the supposition that these care process measures are associated with clinical outcomes . However , this association has not been evaluated for current and emerging outpatient HF measures . Methods and Results — Performance on 7 HF process measures ( 4 current and 3 emerging ) and 2 summary measures was assessed at baseline in patients from 167 US outpatient cardiology practice s with patients prospect ively followed up for 24 months . Participants included 15 177 patients with reduced left ventricular ejection fraction ( ⩽35 % ) and chronic HF or post – myocardial infa rct ion . Multivariable analyses were performed to assess the process- outcome relationship for each measure in eligible patients . Vital status was available for 11 621 patients . The mortality rate at 24 months was 22.1 % . Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use , & bgr;-blocker use , anticoagulant therapy for atrial fibrillation , cardiac resynchronization therapy , implantable cardioverter-defibrillators , and HF education for eligible patients were each independently associated with improved 24-month survival , whereas aldosterone antagonist use was not . The all-or-none and composite care summary measures were also independently associated with improved survival . Each 10 % improvement in composite care was associated with a 13 % lower odds of 24-month mortality ( adjusted odds ratio , 0.87 ; 95 % confidence interval , 0.84 to 0.90 ; P<0.0001 ) . Conclusions — Current and emerging outpatient HF process measures are positively associated with patient survival . These HF measures may be useful for assessing and improving HF care . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00303979 OBJECTIVE To study the impact of remote patient monitoring ( RPM ) upon the most frequent diagnosis in hospitalized patients over 65 years of age-heart failure ( HF ) . We examined the effect of RPM on hospital utilization and Medicare costs of HF patients receiving home care . MATERIAL S AND METHODS Two studies were simultaneously conducted : A r and omized and a matched-cohort study . In the r and omized study , 168 subjects were r and omly assigned ( after hospitalization ) to home care utilizing RPM ( live nursing visits and video-based nursing visits ) or to home care receiving live nursing visits only . In the matched-cohort study , 160 subjects receiving home care with RPM ( live nursing visits and video-based nursing visits ) were matched with home care subjects receiving live nursing visits only . RESULTS Regardless of whether outcomes were being analyzed for all subjects ( intention to treat ) or for hospitalized subjects only , hospitalization rates , time to first admission , length of stay , and costs to Medicare did not differ significantly between groups in either study at 30 or 90 days after enrollment . A notable trend , however , emerged across studies : Although time to hospitalization was shorter in the RPM groups than the control groups , RPM groups had lower hospitalization costs . CONCLUSIONS RPM , when utilized in conjunction with a robust management protocol , was not found to significantly differ from live nursing visits in the management of HF in home care . Shorter hospitalization times and lower associated costs may be due to earlier identification of exacerbation . These trends indicate the need for further study Background — Trials investigating efficacy of disease management programs ( DMP ) in heart failure reported contradictory results . Features rendering specific interventions successful are often ill defined . We evaluated the mode of action and effects of a nurse-coordinated DMP ( HeartNetCare-HF , HNC ) . Methods and Results — Patients hospitalized for systolic heart failure were r and omly assigned to HNC or usual care ( UC ) . Besides telephone-based monitoring and education , HNC addressed individual problems raised by patients , pursued networking of health care providers and provided training for caregivers . End points were time to death or rehospitalization ( combined primary ) , heart failure symptoms , and quality of life ( SF-36 ) . Of 1007 consecutive patients , 715 were r and omly assigned ( HNC : n=352 ; UC : n=363 ; age , 69±12 years ; 29 % female ; 40 % New York Heart Association class III-IV ) . Within 180 days , 130 HNC and 137 UC patients reached the primary end point ( hazard ratio , 1.02 ; 95 % confidence interval , 0.81–1.30 ; P=0.89 ) , since more HNC patients were readmitted . Overall , 32 HNC and 52 UC patients died ( 1 UC patient and 4 HNC patients after dropout ) ; thus , uncensored hazard ratio was 0.62 ( 0.40–0.96 ; P=0.03 ) . HNC patients improved more regarding New York Heart Association class ( P=0.05 ) , physical functioning ( P=0.03 ) , and physical health component ( P=0.03 ) . Except for HNC , health care utilization was comparable between groups . However , HNC patients requested counseling for noncardiac problems even more frequently than for cardiovascular or heart-failure – related issues . Conclusions — The primary end point of this study was neutral . However , mortality risk and surrogates of well-being improved significantly . Quantitative assessment of patient requirements suggested that besides (tele)monitoring individualized care considering also noncardiac problems should be integrated in efforts to achieve more sustainable improvement in heart failure outcomes . Clinical Trial Registration — URL : http://www.controlled-trials.com . Unique identifier : IS RCT N23325295 The evidence base of what works in chronic care management programs is underdeveloped . To fill the gap , we pooled and reanalyzed data from ten r and omized clinical trials of heart failure care management programs to discern how program delivery methods contribute to patient outcomes . We found that patients enrolled in programs using multi-disciplinary teams and in programs using in-person communication had significantly fewer hospital readmissions and readmission days than routine care patients had . Our study offers policymakers and health plan administrators important guideposts for developing an evidence base on which to build effective policy and programmatic initiatives for chronic care management BACKGROUND Small studies suggest that telemonitoring may improve heart-failure outcomes , but its effect in a large trial has not been established . METHODS We r and omly assigned 1653 patients who had recently been hospitalized for heart failure to undergo either telemonitoring ( 826 patients ) or usual care ( 827 patients ) . Telemonitoring was accomplished by means of a telephone-based interactive voice-response system that collected daily information about symptoms and weight that was review ed by the patients ' clinicians . The primary end point was readmission for any reason or death from any cause within 180 days after enrollment . Secondary end points included hospitalization for heart failure , number of days in the hospital , and number of hospitalizations . RESULTS The median age of the patients was 61 years ; 42.0 % were female , and 39.0 % were black . The telemonitoring group and the usual-care group did not differ significantly with respect to the primary end point , which occurred in 52.3 % and 51.5 % of patients , respectively ( difference , 0.8 percentage points ; 95 % confidence interval [ CI ] , -4.0 to 5.6 ; P=0.75 by the chi-square test ) . Readmission for any reason occurred in 49.3 % of patients in the telemonitoring group and 47.4 % of patients in the usual-care group ( difference , 1.9 percentage points ; 95 % CI , -3.0 to 6.7 ; P=0.45 by the chi-square test ) . Death occurred in 11.1 % of the telemonitoring group and 11.4 % of the usual care group ( difference , -0.2 percentage points ; 95 % CI , -3.3 to 2.8 ; P=0.88 by the chi-square test ) . There were no significant differences between the two groups with respect to the secondary end points or the time to the primary end point or its components . No adverse events were reported . CONCLUSIONS Among patients recently hospitalized for heart failure , telemonitoring did not improve outcomes . The results indicate the importance of a thorough , independent evaluation of disease-management strategies before their adoption . ( Funded by the National Heart , Lung , and Blood Institute ; Clinical Trials.gov number , NCT00303212 . ) BACKGROUND Clinical registries are used increasingly to analyze quality and outcomes , but the generalizability of findings from registries is unclear . METHODS We linked data from the Acute Decompensated Heart Failure National Registry ( ADHERE ) to 100 % fee-for-service Medicare cl aims data . We compared patient characteristics and inpatient mortality of linked and unlinked ADHERE hospitalizations ; patient characteristics , readmission , and postdischarge mortality of linked ADHERE patients to a r and om 20 % sample of Medicare beneficiaries hospitalized for heart failure ; and characteristics of Medicare sites participating and not participating in ADHERE . RESULTS Among 135,667 ADHERE records for eligible patients ≥ 65 years , we matched 104,808 ( 77.3 % ) records to fee-for-service Medicare cl aims , representing 82,074 patients . Linked hospitalizations were more likely than unlinked hospitalizations to involve women and white patients ; there were no meaningful differences in other patient characteristics . In-hospital mortality was identical for linked and unlinked hospitalizations . In Medicare , ADHERE patients had slightly lower unadjusted mortality ( 4.4 % vs 4.9 % in-hospital , 11.2 % vs 12.2 % at 30 days , 36.0 % vs 38.3 % at 1 year [ P < .001 ] ) and all-cause readmission ( 22.1 % vs 23.7 % at 30 days , 65.8 % vs 67.9 % at 1 year [ P < .001 ] ) . After risk adjustment , modest but statistically significant differences remained . ADHERE hospitals were more likely than non-ADHERE hospitals to be teaching hospitals , have higher volumes of heart failure discharges , and offer advanced cardiac services . CONCLUSION Elderly patients in ADHERE are similar to Medicare beneficiaries hospitalized with heart failure . Differences related to selective en Output:	Several studies found that access to a specialist heart failure team/service reduced hospital readmissions and mortality . In primary care , a collaborative model of care where the primary physician shared the care with a cardiologist , improved patient outcomes compared to a primary physician only . During hospitalisation , quality improvement programs improved the quality of inpatient care result ing in reduced hospital readmissions and mortality . In the transitional care phase , heart failure programs , nurse-led clinics , and early outpatient follow-up reduced hospital readmissions . Conclusion Re design ing systems of care aim ed at improving the translation of evidence into clinical practice and transitional care can potentially improve patient outcomes in a cohort of patients known for high readmission rates and mortality
MS22012	*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 Centers for Disease Control and Prevention has recommended using a nucleic acid amplification test ( NAAT ) for diagnosing pulmonary tuberculosis ( TB ) but there is a lack of data on NAAT cost-effectiveness . Methods We conducted a prospect i ve cohort study that included all patients with an AFB smear-positive respiratory specimen at Grady Memorial Hospital in Atlanta , GA , USA between January 2002 and June 2008 . We determined the sensitivity , specificity , and positive and negative predictive value of a commercially available and FDA -approved NAAT ( amplified MTD , Gen-Probe ) compared to the gold st and ard of culture . A cost analysis was performed and included costs related to laboratory tests , hospital charges , anti-TB medications , and contact investigations . Average cost per patient was calculated under two conditions : ( 1 ) using a NAAT on all AFB smear-postive respiratory specimens and ( 2 ) not using a NAAT . One-way sensitivity analyses were conducted to determine sensitivity of cost difference to reasonable ranges of model inputs . Results During a 6 1/2 year study period , there were 1,009 patients with an AFB smear-positive respiratory specimen at our public urban hospital . We found the NAAT to be highly sensitive ( 99.6 % ) and specific ( 99.1 % ) on AFB smear-positive specimens compared to culture . Overall , the positive predictive value ( PPV ) of an AFB smear-positive respiratory specimen for culture-confirmed TB was 27 % . The PPV of an AFB smear-positive respiratory specimen for culture-confirmed TB was significantly higher for HIV-uninfected persons compared to those who were HIV-seropositive ( 152/271 [ 56 % ] vs. 85/445 [ 19 % ] ; RR = 2.94 , 95 % CI 2.36–3.65 , p<0.001 ) . The cost savings of using the NAAT was $ 2,003 per AFB smear-positive case . Conclusions Routine use of the NAAT on AFB smear-positive respiratory specimens was highly cost-saving in our setting at a U.S. urban public hospital with a high prevalence of TB and HIV because of the low PPV of an AFB smear for culture-confirmed TB Background To investigate the ability of rESAT6 to identify different mycobacteria-sensitized guinea pigs and its safety in pre clinical and phase I clinical study . Material / Methods Guinea pigs were sensitized with different Mycobacteria . After sensitization , all animals were intradermally injected with rESAT6 and either PPD or PPD-B. At 24 h after the injection , the erythema of the injection sites were measured using a double-blind method . For the pre clinical safety study , different doses of rESAT6 and BSA were given 3 times intramuscularly to guinea pigs . On day 14 after the final immunization , the guinea pigs were intravenously injected with the same reagents in the hind legs and the allergic reactions were observed . A single-center , r and omized , open phase I clinical trial was employed . The skin test was conducted in 32 healthy volunteers aged 19–65 years with 0.1 μg , 0.5 μg , and 1 μg rESAT6 . Physical examination and laboratory tests were performed before and after the skin test and adverse reactions were monitored . The volunteers ’ local and systemic adverse reactions and adverse events were recorded for 7 days . Results Positive PPD or PPD-B skin tests were observed in all Mycobacteria-sensitized guinea pigs ; the diameters of erythema were all > 10 mm . The rESAT6 protein induced a positive skin test result in the guinea pigs sensitized with MTB , M. bovis , M. africanum and M. kansasii ; the diameters of erythema were 14.7±2.0 , 9.3±3.8 , 18.7±2.4 , and 14.8±4.2 mm , respectively . A negative skin test result was detected in BCG-vaccinated and other NTM-sensitized guinea pigs . The rESAT6 caused no allergic symptoms , but many allergic reactions , such as cough , dyspnea , and even death , were observed in the guinea pigs who were administered BSA . During the phase I clinical trial , no adverse reactions were found in the 0.1 μg rESAT6 group , but in the 0.5 μg rESAT6 group 2 volunteers reported pain and 1 reported itching , and in the 1 μg rESAT6 group there was 1 case of pain , 1 case of itching , and 1 case of blister . No other local or systemic adverse reactions or events were reported . Conclusions The rESAT6 can differentiate effectively among MTB infection , BCG vaccination , and NTM infection and is safe in healthy volunteers Background This study aim ed to determine the efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis ( TB ) . Material / Methods A phase II trial was performed in 158 patients with pulmonary TB ( 145 initially-treated and 13 re-treated ) and 133 healthy subjects . Skin testing was carried out by injecting purified protein derivative ( PPD ) ( on left forearm ) or recombinant ESAT-6 protein at a dosage of 2 , 5 , or 10 μg/mL ( on the right forearm ) in each subject . Reaction activity and adverse events were monitored at 24 , 48 , and 72 h following the injection . Receiver operating characteristic curves were plotted to determine the areas under the curves ( AUCs ) and the cut-off in duration diameters for the optimal diagnostic performance . Results The reaction activity was significantly increased upon recombinant ESAT-6 injection in pulmonary TB patients compared with healthy subjects . In pulmonary TB patients , the reaction was dose-dependent , and at 48 h , 10 μg/mL recombinant ESAT-6 produced a reaction similar to that produced by PPD . The AUCs for a 10 μg/mL dosage were 0.9823 , 0.9552 , and 0.9266 for 24 h , 48 h , and 72 h , respectively , and the in duration diameters of 4.5–5.5 mm were the optimal trade-off values between true positive rates and false positive rates . No serious adverse events occurred in any subjects . Conclusions Recombinant ESAT-6 protein is efficacious and safe for diagnosing pulmonary TB . Based on the reaction , performance , safety , and practicability , we recommend that 10 μg/mL at 48 h with an in duration cut-off value of 5.0 mm be used OBJECTIVE The goal of this study was to determine the optimal number of aspirations per lymph node ( LN ) station during endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration ( TBNA ) for maximum diagnostic yield in mediastinal staging of non-small cell lung cancer ( NSCLC ) in the absence of rapid on-site cytopathologic examination . METHODS EBUS-TBNA was performed in potentially operable NSCLC patients with mediastinal LNs accessible by EBUS-TBNA ( 5 to 20 mm ) . Every target LN station was punctured four times . RESULTS We performed EBUS-TBNA in 163 mediastinal LN stations in 102 NSCLC patients . EBUS-TBNA confirmed malignancy in 41 LN stations in 30 patients . Two malignant LN stations were missed in two patients . The sensitivity , specificity , positive predictive value , negative predictive value ( NPV ) , and accuracy of EBUS-TBNA in predicting mediastinal metastasis were 93.8 % , 100 % , 100 % , 96.9 % , and 97.9 % , respectively . Sample adequacy was 90.1 % for one aspiration , and it reached 100 % for three aspirations . The sensitivity for differentiating malignant from benign LN stations was 69.8 % , 83.7 % , 95.3 % , and 95.3 % for one , two , three , and four aspirations , respectively . The NPV was 86.5 % , 92.2 % , 97.6 % , and 97.6 % for one , two , three , and four aspirations , respectively . Maximum diagnostic values were achieved in three aspirations . When at least one tissue core was obtained by the first or second aspiration , the sensitivity and NPV of the first two aspirations were 91.9 % and 96.0 % , respectively . CONCLUSIONS Optimal results can be obtained in three aspirations per LN station in EBUS-TBNA for mediastinal staging of potentially operable NSCLC . When at least one tissue core specimen is obtained by the first or second aspiration , two aspirations per LN station can be acceptable RATIONALE Patients with isolated mediastinal lymphadenopathy ( IML ) are a common presentation to physicians , and mediastinoscopy is traditionally considered the " gold st and ard " investigation when a pathological diagnosis is required . Endobronchial ultrasound-guided transbronchial needle aspiration ( EBUS-TBNA ) is established as an alternative to mediastinoscopy in patients with lung cancer . OBJECTIVE To determine the efficacy and health care costs of EBUS-TBNA as an alternative initial investigation to mediastinoscopy in patients with isolated IML . METHODS Prospect i ve multicenter single-arm clinical trial of 77 consecutive patients with IML from 5 centers between April 2009 and March 2011 . All patients underwent EBUS-TBNA . If EBUS-TBNA did not provide a diagnosis , then participants underwent mediastinoscopy . MEASUREMENTS AND MAIN RESULTS EBUS-TBNA prevented 87 % of mediastinoscopies ( 95 % confidence interval [ CI ] , 77 - 94 % ; P < 0.001 ) but failed to provide a diagnosis in 10 patients ( 13 % ) , all of whom underwent mediastinoscopy . The sensitivity and negative predictive value of EBUS-TBNA in patients with IML were 92 % ( 95 % CI , 83 - 95 % ) and 40 % ( 95 % CI , 12 - 74 % ) , respectively . One patient developed a lower respiratory tract infection after EBUS-TBNA , requiring inpatient admission . The cost of the EBUS-TBNA procedure per patient was £ 1,382 ( $ 2,190 ) . The mean cost of the EBUS-TBNA strategy was £ 1,892 ( $ 2,998 ) per patient , whereas a strategy of mediastinoscopy alone was significantly more costly at £ 3,228 ( $ 5,115 ) per patient ( P < 0.001 ) . The EBUS-TBNA strategy is less costly than mediastinoscopy if the cost per EBUS-TBNA procedure is less than £ 2,718 ( $ 4,307 ) per patient . CONCLUSIONS EBUS-TBNA is a safe , highly sensitive , and cost-saving initial investigation in patients with IML . Clinical trial registered with Clinical Trials.gov ( NCT00932854 ) Background Tuberculin skin test ( TST ) has been used for years as an aid in diagnosing latent tuberculosis infection ( LTBI ) but it suffers from a number of well-documented performance and logistic problems . Quantiferon-TB Gold In Tube test ( QFT-GIT ) has been reported to have better sensitivity and specifity than TST . In this study , it was aim ed to compare the performance of a commercial IFN-γ release assay ( QFT-GIT ) with TST in the diagnosis of HCWs at risk for latent TB infection in BCG vaccinated population . Material / Methods Hundred healthy volunteer health care workers were enrolled . All were subjected to TST and QFT-GIT . Results were compared among Health Care Workers ( HCWs ) groups in terms of profession , workplace , working duration . Results TST is affected by previous BCG vaccinations and number of cases with QFT-GIT positivity is increased in accordance with the TST in duration diameter range . QFT-GIT result was negative in 17 of 32 TST positive ( ≥15 mm ) cases and positive in 4 of 61 cases whose TST diameters are between 6–14 mm , that is attritutable to previous BCG vaccination(s ) . It was negative in all cases with TST diameters between 0–5 mm . HCWs with positive QFT-GIT results were significantly older than the ones with negative results . Furthermore duration of work was significantly longer in QFT-GIT positive than in negative HCWs . Conclusions There was a moderate concordance between QFT-GIT and TST , when TST result was defined as positive with a ≥15 mm diameter of in duration . We suggest that QFT-GIT can be used as an alternative to TST for detection of LTBI , especially in groups with high risk of LTBI and in population with routine BCG vaccination program STUDY OBJECTIVES Although various techniques are available for obtaining pathology specimens from the mediastinal lymph nodes , including conventional bronchoscopic transbronchial needle aspiration ( TBNA ) , transesophageal ultrasonography-guided needle aspiration , and mediastinoscopy , there are limitations to these techniques , which include low yield , poor access , need for general anesthesia , or complications . To overcome these problems Output:	EBUS-TBNA appears to be an efficacious and safe procedure and should be used as an initial diagnostic tool for mediastinal TBLA
MS22013	*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 determine if photodynamic therapy with verteporfin ( Visudyne ; Novartis AG , Bülach , Switzerl and ) , termed verteporfin therapy , can safely reduce the risk of vision loss compared with a placebo ( with sham treatment ) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration who were identified with a lesion composed of occult with no classic choroidal neovascularization , or with presumed early onset classic choroidal neovascularization with good visual acuity letter score . METHODS This was a double-masked , placebo-controlled ( sham treatment ) , r and omized , multicenter clinical trial involving 28 ophthalmology practice s in Europe and North America . The study population was patients with age-related macular degeneration , with subfoveal choroidal neovascularization lesions measuring no greater than 5400 microm in greatest linear dimension with either 1 ) occult with no classic choroidal neovascularization , best-corrected visual acuity score of at least 50 ( Snellen equivalent approximately 20/100 ) , and evidence of hemorrhage or recent disease progression ; or 2 ) evidence of classic choroidal neovascularization with a best-corrected visual acuity score of at least 70 ( better than a Snellen equivalent of approximately 20/40 ) ; assigned r and omly ( 2:1 ) to verteporfin therapy or placebo therapy . Verteporfin ( 6 mg per square meter of body surface area ) or placebo ( 5 % dextrose in water ) was administered by means of intravenous infusion of 30 ml over 10 minutes . Fifteen minutes after the start of the infusion , a laser light at 689 nm delivered 50 J/cm(2 ) by application of an intensity of 600 mW/cm(2 ) over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the choroidal neovascularization lesion on the retina . At follow-up examinations every 3 months , retreatment with the same regimen was applied if angiography showed fluorescein leakage . The main outcome measure was at least moderate vision loss , that is , a loss of at least 15 letters ( approximately 3 lines ) , adhering to an intent-to-treat analysis with the last observation carried forward to impute for missing data . RESULTS Two hundred ten ( 93 % ) and 193 ( 86 % ) of the 225 patients in the verteporfin group compared with 104 ( 91 % ) and 99 ( 87 % ) of the 114 patients in the placebo group completed the month 12 and 24 examinations , respectively . On average , verteporfin-treated patients received five treatments over the 24 months of follow-up . The primary outcome was similar for the verteporfin-treated and the placebo-treated eyes through the month 12 examination , although a number of secondary visual and angiographic outcomes significantly favored the verteporfin-treated group . Between the month 12 and 24 examinations , the treatment benefit grew so that by the month 24 examination , the verteporfin-treated eyes were less likely to have moderate or severe vision loss . Of the 225 verteporfin-treated patients , 121 ( 54 % ) compared with 76 ( 67 % ) of 114 placebo-treated patients lost at least 15 letters ( P = .023 ) . Likewise , 67 of the verteporfin-treated patients ( 30 % ) compared with 54 of the placebo-treated patients ( 47 % ) lost at least 30 letters ( P = .001 ) . Statistically significant results favoring verteporfin therapy at the month 24 examination were consistent between the total population and the subgroup of patients with a baseline lesion composition identified as occult choroidal neovascularization with no classic choroidal neovascularization . This subgroup included 166 of the 225 verteporfin-treated patients ( 74 % ) and 92 of the 114 placebo-treated patients ( 81 % ) . In these patients , 91 of the verteporfin-treated group ( 55 % ) compared with 63 of the placebo-treated group ( 68 % ) lost at least 15 letters ( P = .032 ) , whereas 48 of the verteporfin-treated group ( 29 % ) and 43 of the placebo-treated group ( 47 % ) lost at least 30 letters ( P = .004 ) . Other secondary outcomes , including visual acuity letter score worse than 34 ( approximate Snellen equivalent of 20/200 or worse ) , mean change in visual acuity letter score , development of classic choroidal neovascularization , progression of classic choroidal neovascularization and size of lesion , favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire study group and the subgroup of cases with occult with no classic choroidal neovascularization at baseline . Subgroup analyses of lesions composed of occult with no classic choroidal neovascularization at baseline suggested that the treatment benefit was greater for patients with either smaller lesions ( 4 disc areas or less ) or lower levels of visual acuity ( letter score less than 65 , an approximate Snellen equivalent of 20/50(-1 ) or worse ) at baseline . Prospect ively planned multivariable analyses confirmed that these two baseline variables affected the magnitude of treatment benefit . ( ABSTRACT TRUNCATED OBJECTIVE The 2-year , phase III trial design ated Anti-vascular endothelial growth factor ( VEGF ) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization ( CNV ) in Age-related Macular Degeneration ( ANCHOR ) compared ranibizumab with verteporfin photodynamic therapy ( PDT ) in treating predominantly classic CNV . DESIGN Multicenter , international , r and omized , double-masked , active-treatment-controlled clinical trial . PARTICIPANTS Patients with predominantly classic , subfoveal CNV not previously treated with PDT or antiangiogenic drugs . INTERVENTION Patients were r and omized 1:1:1 to verteporfin PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus monthly intravitreal ranibizumab ( 0.3 mg or 0.5 mg ) injection . The need for PDT ( active or sham ) retreatment was evaluated every 3 months using fluorescein angiography ( FA ) . MAIN OUTCOME MEASURES The primary , intent-to-treat efficacy analysis was at 12 months , with continued measurements to month 24 . Key measures included the percentage losing < 15 letters from baseline visual acuity ( VA ) score ( month 12 primary efficacy outcome measure ) , percentage gaining > or=15 letters from baseline , and mean change over time in VA score and FA-assessed lesion characteristics . Adverse events were monitored . RESULTS Of 423 patients ( 143 PDT , 140 each in the 2 ranibizumab groups ) , the majority ( > or=77 % in each group ) completed the 2-year study . Consistent with results at month 12 , at month 24 the VA benefit from ranibizumab was statistically significant ( P<0.0001 vs. PDT ) and clinical ly meaningful : 89.9 % to 90.0 % of ranibizumab-treated patients had lost < 15 letters from baseline ( vs. 65.7 % of PDT patients ) ; 34 % to 41.0 % had gained > or=15 letters ( vs. 6.3 % of PDT group ) ; and , on average , VA was improved from baseline by 8.1 to 10.7 letters ( vs. a mean decline of 9.8 letters in PDT group ) . Changes in lesion anatomic characteristics on FA also favored ranibizumab ( all comparisons P<0.0001 vs. PDT ) . Overall , there was no imbalance among groups in rates of serious ocular and nonocular adverse events . In the pooled ranibizumab groups , 3 of 277 ( 1.1 % ) patients developed presumed endophthalmitis in the study eye ( rate per injection = 3/5921 [ 0.05 % ] ) . CONCLUSIONS In this 2-year study , ranibizumab provided greater clinical benefit than verteporfin PDT in patients with age-related macular degeneration with new-onset , predominantly classic CNV . Rates of serious adverse events were low . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references Purpose This prospect i ve multi-center pilot study compares the use of half-fluence photodynamic therapy combined with ranibizumab with ranibizumab monotherapy for the treatment of neovascular age-related macular degeneration . Methods All patients presenting with untreated subfoveal neovascular age-related macular degeneration were considered for inclusion . Patients were r and omized to receive either ranibizumab with half-fluence photodynamic therapy or ranibizumab alone . Patients in the ranibizumab alone group were given three consecutive monthly ranibizumab injections and were followed monthly . They were treated with ranibizumab as needed , based on clinical discretion , using vision and optical coherence tomography . Patients in the combined group were given one same-day combined ranibizumab and half-fluence ( 25 j/cm2 ) photodynamic therapy treatment and were treated monthly as needed . Outcomes included changes in st and ardized visual acuity , optical coherence tomography foveal thickness , and percentage of as-needed injections to maintenance examinations . Results Fifty-six out of 60 enrolled patients completed the twelve month primary outcome visit ; this consisted of 27 patients receiving ranibizumab alone and 29 receiving combined treatment . The average age was 79.1 for the ranibizumab alone group and 79.3 for the combined group . The mean visual acuity in the ranibizumab alone group improved from 52.9 Early Treatment of Diabetic Retinopathy letters initially to 62.8 letters at twelve months . The mean visual acuity in the combined group improved from 49.2 letters to 51.8 letters at twelve months . The differences in visual acuity improvements were not statistically significant based on a two-tailed t-test ( P = 0.2 ) . Due to the presence of outliers in each group , a Mann – Whitney U test was performed to confirm the results ( U = 325 ; P = 0.28 ) . The mean optical coherence tomography foveal thickness improved 92.5 microns and 106.7 microns in the ranibizumab alone and the combined group , respectively . The difference was not significant based on a two-tailed t-test ( P = 0.6 ) . The ranibizumab alone group received an average of 6.8 injections , while the combined group received an average of three injections . This difference was not significant based on a chi-square test ( P = 0.11 ) . Conclusion The groups appeared similar based on statistical analysis , but larger studies are needed to determine possible small differences between combination therapy and monotherapy Purpose Combination verteporfin photodynamic therapy ( vPDT ) and antivascular endothelial growth factor ( anti-VEGF ) therapy may decrease the need for injections while maintaining visual acuity in exudative age-related macular degeneration . This pilot study was design ed to determine the threshold fluence dose of vPDT ( the dose required to demonstrate an effect on choroidal perfusion ) combined with ranibizumab . Methods Seven patients were r and omized to sham vPDT ( two patients ) , 20 % fluence vPDT ( two patients ) , or 40 % fluence vPDT ( three patients ) in combination with three-monthly intravitreal 0.5 mg ranibizumab injections . Intravitreal ranibizumab was reinjected if disease activity was seen on fluorescein angiography , optical coherence tomography , or clinical examination . Indocyanine green-determined choroidal hypoperfusion was grade d in a masked fashion . Results Patients with 20 % vPDT had mild hypoperfusion defects at seven days that resolved by week 4 ( threshold dose ) ; patients with 40 % fluence vPDT had marked hypoperfusion at seven days that persisted as long as 12 months . Recruitment was stopped after limited efficacy was observed . One patient with 20 % fluence vPDT lost 19 letters at one year ; no other patient lost or gained > 10 letters . Central retinal thickness decreased in six of seven patients , but ranibizumab injections did not decrease . Conclusion This pilot study shows that the threshold fluence dose of vPDT ( when combined with ranibizumab ) is approximately 20 % st and ard fluence , and that mild and transient choroidal hypoperfusion can occur . Forty percent fluence vPDT causes a more prolonged and striking hypoperfusion . Despite hypoperfusion , no decrease in visual acuity or injections required was noted , suggesting that even higher fluence levels of vPDT may be necessary to decrease the number of anti-VEGF injections OBJECTIVE To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin ( Visudyne ; CIBA Vision Corp , Duluth , Ga ) in patients with subfoveal choroidal neovascularization ( CNV ) caused by age-related macular degeneration ( AMD ) . DESIGN Two multicenter , double-masked , place Output:	As major adverse events , the differences in the number of eye pain , endophthalmitis , hypertension and arterial thromboembolic events were not significant between the two groups , and the incidence of serious adverse events in the two groups was very low . For the maintenance of vision , the comparison of the combination of ranibizumab with PDT vs ranibizumab monotherapy shows no apparent difference . Compared with the combination of ranibizumab and PDT , patients treated with ranibizumab monothearpy may gain more visual acuity ( VA ) improvement . The combination treatment group had a tendency to reduce the number of ranibizumab retreatment . Both the two treatment strategies were well tolerated
MS22014	*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 incidence of brain metastases secondary to small cell lung cancer ( SCLC ) is about 35 % and the treatment strategy of brain irradiation with respect to dose and fractionation is controversial . In order to evaluate treatment outcome of brain irradiation in SCLC patients with brain relapse , we retrospectively evaluated all patients treated with brain irradiation in the eastern part of Denmark from 1988 to 1992 ( PCI patients excluded ) . During this 5-year period , 101 evaluable patients were included ( 44 females , 57 males ) ( median age 61 years ; range , 39 - 75 years ) . Forty-four patients , of whom 43 were in extracerebral complete remission ( CR ) , received extended course ( EC ) brain irradiation ( > 45 Gy , treatment schedule > 4 weeks ) . Fifty-seven patients received short course ( SC ) brain irradiation ( < 30 Gy , treatment schedule < 1 week ) . Among the SC treated patients , 14 were in CR , 20 had partial remission or stable disease and 23 had progressive extracerebral disease . The median survival ( from diagnosis of brain metastases ) in the group receiving irradiation with EC ( 44 patients ) was 160 days ( range , 74 - 2021 days ) , while the 57 patients treated with SC had a median survival of 88 days ( range , 20 - 948 days ) ( P = 0.00001 , Log-Rank analysis ) . In a subgroup of 14 patients in extracerebral CR , receiving SC irradiation , the median survival was 83 days ( range , 15 - 948 days ) . When the latter patients were compared to the 43 patients in CR in the group treated with EC , a statistically significant difference was shown ( P = 0.034 , Log-Rank analysis ) . Using Cox-hazard regression analysis with backward elimination , liver metastases and poor performance status were adverse prognostic signs , although the only significant parameters of survival were gender ( female vs. male , relative risk of dying 1 and 1.52 , P = 0.05 ) and schedule of brain irradiation ( extended course vs. short course , relative risk of dying , 0.36 and 1 , P < 0.001 ) . Extended course irradiation of brain relapse secondary to SCLC seems in general to be of limited value , although a significant prolonged survival at approximately 7 weeks , was obtained . The prolongation of survival does not seem worthwhile considering the length of treatment time ( 5 - 6 weeks ) compared to SC treatment ( 1 week ) . However , the data do not permit evaluation of the quality of life of the patients . This retrospective evaluation suggests the need for r and omized trials with carefully planned quality -of-life assessment Output:	From the limited evidence available , survival appeared to increase when patients were selected by performance status ( survival increasing from approximately three to seven months in high performance status groups , as defined by Karnofsky performance status or Recursive Partitioning Analysis classification ) . The evidence suggests no survival benefit when patients with poor performance status were treated with whole brain radiotherapy . WBRT appears to be of benefit in higher performance status patients but not in low performance status patients .
MS22015	*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 effectiveness of resistance training in improving cognitive function in older adults is well demonstrated . In particular , unconventional high-speed resistance training can improve muscle power development . In the present study , the effectiveness of 12 weeks of elastic b and -based high-speed power training ( HSPT ) was examined . METHODS Participants were r and omly assigned into a HSPT group ( n = 14 , age 75.0 ± 0.9 years ) , a low-speed strength training ( LSST ) group ( n = 9 , age 76.0 ± 1.3 years ) and a control group ( CON ; n = 7 , age 78.0 ± 1.0 years ) . A 1-h exercise program was provided twice a week for 12 weeks for the HSPT and LSST groups , and balance and tone exercises were carried out by the CON group . RESULTS Significant increases in levels of cognitive function , physical function , and muscle strength were observed in both the HSPT and LSST groups . In cognitive function , significant improvements in the Mini-Mental State Examination and Montreal Cognitive Assessment were seen in both the HSPT and LSST groups compared with the CON group . In physical functions , Short Physical Performance Battery scores were increased significantly in the HSPT and LSST groups compared with the CON group . In the 12 weeks of elastic b and -based training , the HSPT group showed greater improvements in older women with mild cognitive impairment than the LSST group , although both regimens were effective in improving cognitive function , physical function and muscle strength . CONCLUSIONS We conclude that elastic b and -based HSPT , as compared with LSST , is more efficient in helping older women with mild cognitive impairment to improve cognitive function , physical performance and muscle strength . Geriatr Gerontol Int 2017 ; 17 : 765 - 772 Objective The purpose of this study was to test the effects of a 6-month Wheelchair-bound Senior Elastic B and ( WSEB ) exercise program on the activities of daily living ( ADL ) and functional fitness of wheelchair-bound older adults with cognitive impairment . Design Cluster r and omized controlled trial was used . A convenience sample of 138 wheelchair-bound older adults with cognitive impairment were recruited from 8 nursing homes in southern Taiwan and were r and omly assigned based on the nursing homes they lived to the experimental ( 4 nursing homes ; n = 73 ) or the control group ( 4 nursing homes ; n = 65 ) . The experimental group performed WSEB exercises 3 times per week and 40 minutes per session for 6 months . The ADL and functional fitness ( cardiopulmonary function , body flexibility , range of joint motion , and muscle strength and endurance ) were examined at baseline , 3 months , and the end of 6-month study . Results The ADL and functional fitness indicators of participants in the experimental group showed significant improvements compared to the control group ( all P < 0.05 ) . Conclusions The WSEB exercises have positive benefits for the ADL and functional fitness of wheelchair-bound older adults with cognitive impairment . It is suggested that WSEB exercises be included as a routine activity in nursing homes . To Cl aim CME Credits : Complete the self- assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME Objectives : Upon completion of this article the reader should be able to : ( 1 ) Underst and the risk factors for functional decline in older adults with dementia ; ( 2 ) Articulate the benefits of structured activities and exercises in the older adult with dementia ; and ( 3 ) Incorporate elastic b and exercises into the treatment plan of wheelchair bound older adults with dementia . Level : Advanced Accreditation : The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians . The Association of Academic Physiatrists design ates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s) ™ . Physicians should only cl aim credit commensurate with the extent of their participation in the activity This study aim ed to investigate the effects of a long-term resistance exercise intervention on executive functions in healthy elderly males , and to further underst and the potential neurophysiological mechanisms mediating the changes . The study assessed forty-eight healthy elderly males r and omly assigned to exercise ( n = 24 ) or control ( n = 24 ) groups . The assessment included neuropsychological and neuroelectric measures during a variant of the oddball task paradigm , as well as growth hormone ( GH ) , insulin-like growth factor-1 ( IGF-1 ) , and homocysteine levels at baseline and after either a 12 month intervention of resistance exercise training or control period . The results showed that the control group had a significantly lower accuracy rate and smaller P3a and P3b amplitudes in the oddball condition after 12 months . The exercise group exhibited improved reaction times ( RTs ) , sustained P3a and P3b amplitudes , increased levels of serum IGF-1 , and decreased levels of serum homocysteine . The changes in IGF-1 levels were significantly correlated with the changes in RT and P3b amplitude of the oddball condition in the exercise group . In conclusion , significantly enhanced serum IGF-1 levels after 12 months of resistance exercise were inversely correlated with neurocognitive decline in the elderly . These findings suggest that regular resistance exercise might be a promising strategy to attenuate the trajectory of cognitive aging in healthy elderly individuals , possibly mediated by IGF-1 Background There is limited research about beneficial effects of physical activity in older adults suffering from mild cognitive impairment ( MCI ) . Aim The aim of the study was to provide preliminary evidence on the effects of two types of non-aerobic training on cognitive functions in older women suffering from MCI . Methods Twenty-eight participants aged 66–78 years with MCI were r and omly assigned to a combined balance and core resistance training group ( n = 14 ) or to a Pilates group ( n = 14 ) . Results Following completion of the 8-week exercise programme , both groups showed significant improvements in global and specific cognitive domains . Conclusion Findings suggest that non-aerobic training should be further explored as a beneficial intervention for older adults suffering from MCI BACKGROUND Cognitive decline among seniors is a pressing health care issue . Specific exercise training may combat cognitive decline . We compared the effect of once-weekly and twice-weekly resistance training with that of twice-weekly balance and tone exercise training on the performance of executive cognitive functions in senior women . METHODS In this single-blinded r and omized trial , 155 community-dwelling women aged 65 to 75 years living in Vancouver were r and omly allocated to once-weekly ( n = 54 ) or twice-weekly ( n = 52 ) resistance training or twice-weekly balance and tone training ( control group ) ( n = 49 ) . The primary outcome measure was performance on the Stroop test , an executive cognitive test of selective attention and conflict resolution . Secondary outcomes of executive cognitive functions included set shifting as measured by the Trail Making Tests ( parts A and B ) and working memory as assessed by verbal digit span forward and backward tests . Gait speed , muscular function , and whole-brain volume were also secondary outcome measures . RESULTS Both resistance training groups significantly improved their performance on the Stroop test compared with those in the balance and tone group ( P < or = .03 ) . Task performance improved by 12.6 % and 10.9 % in the once-weekly and twice-weekly resistance training groups , respectively ; it deteriorated by 0.5 % in the balance and tone group . Enhanced selective attention and conflict resolution was significantly associated with increased gait speed . Both resistance training groups demonstrated reductions in whole-brain volume compared with the balance and tone group at the end of the study ( P < or = .03 ) . CONCLUSION Twelve months of once-weekly or twice-weekly resistance training benefited the executive cognitive function of selective attention and conflict resolution among senior women . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00426881 Background Mild cognitive impairment ( MCI ) represents a critical window to intervene against dementia . Exercise training is a promising intervention strategy , but the efficiency ( i.e. , relationship of costs and consequences ) of such types of training remains unknown . Thus , we estimated the incremental cost-effectiveness of resistance training or aerobic training compared with balance and tone exercises in terms of changes in executive cognitive function among senior women with probable MCI . Methods Economic evaluation conducted concurrently with a six-month three arm r and omized controlled trial including eighty-six community dwelling women aged 70 to 80 years living in Vancouver , Canada . Participants received twice-weekly resistance training ( n = 28 ) , twice weekly aerobic training ( n = 30 ) or twice-weekly balance and tone ( control group ) classes ( n = 28 ) for 6 months . The primary outcome measure of the Exercise for Cognition and Everyday Living ( EXCEL ) study assessed executive cognitive function , a test of selective attention and conflict resolution ( i.e. , Stroop Test ) . We collected healthcare re source utilization costs over six months . Results Based on the bootstrapped estimates from our base case analysis , we found that both the aerobic training and resistance training interventions were less costly than twice weekly balance and tone classes . Compared with the balance and tone group , the resistance-training group had significantly improved performance on the Stroop Test ( p = 0.04 ) . Conclusions Resistance training and aerobic training result in health care cost saving and are more effective than balance and tone classes after only 6 months of intervention . Resistance training is a promising strategy to alter the trajectory of cognitive decline in seniors with MCI . Trial Registration Clinical Trials.gov NCT00958867 Background Older adults are encouraged to participate in regular physical activity to counter the age-related declines in physical and cognitive health . Literature on the effect of different exercise training modalities ( aerobic vs resistance ) on these health-related outcomes is not only sparse , but results are inconsistent . In general , it is believed that exercise has a positive effect on executive cognitive function , possibly because of the physiological adaptations through increases in fitness . Indications are that high-intensity interval training is a potent stimulus to improve cardiovascular fitness , even in older adults ; however , its effect on cognitive function has not been studied before . Therefore , the purpose of this study was to compare the effects of resistance training , high-intensity aerobic interval training and moderate continuous aerobic training on the cognitive and physical functioning of healthy older adults . Methods Sixty-seven inactive individuals ( 55 to 75 years ) were r and omly assigned to a resistance training ( RT ) group ( n = 22 ) , high-intensity aerobic interval training ( HIIT ) group ( n = 13 ) , moderate continuous aerobic training ( MCT ) group ( n = 13 ) and a control ( CON ) group ( n = 19 ) for a period of 16 weeks . Cognitive function was assessed with a Stroop task and physical function with the Timed-Up- and -Go ( TUG ) and submaximal Bruce treadmill tests . Results No significant GROUP x TIME interaction was found for Stroop reaction time ( P > .05 ) . The HIIT group showed the greatest practical significant improvement in reaction time on the information processing task , i.e. Stroop Neutral ( ES = 1.11 ) . MCT group participants had very large practical significant improvements in reaction time on the executive cognitive tasks , i.e. Stroop Incongruent and Interference ( ES = 1.28 and 1.31 , respectively ) . The HIIT group showed the largest practically significant increase in measures of physical function , i.e. walking endurance ( ES = 0.91 ) and functional mobility ( ES = 0.36 ) . Conclusions MCT and RT proved to be superior to HIIT for the enhancement of older individuals ’ executive cognitive function ; whereas HIIT were most beneficial for improvement in information processing speed . HIIT also induced the largest gains in physical function Objective : To investigate the effects of a 12-week resistance exercise program with an elastic b and on electroencephalogram ( EEG ) patterns and cognitive function in elderly patients with mild cognitive impairment ( MCI ) . Design : R and omized controlled trial . Setting : Community center . Participants : Twenty-two subjects with MCI and 25 healthy volunteer subjects were r and omly assigned to 1 of 4 groups : subjects with MCI who undertook the exercise program ( MCI-EX ; n = 10 ) , an MCI control group ( MCI-Con ; n = 12 ) , a healthy volunteer exercise group ( NG-EX ; n = 12 ) , and a healthy volunteer control group ( NG-Con ; n = 13 ) . Intervention : The exercise group engaged in a 15-repetition maximum ( 15RM ; 65 % of 1RM ) resistance exercise program for 12 weeks . Main Outcome Measures : Electroencephalograms , neuropsychological tests , and Senior Fitness Test . Results : The 12-week 15RM ( 65 % of 1RM ) resistance exercise program significantly improved variables related to the physical fitness of the elderly subjects . Furthermore , for the EEG test , the MCI and NG groups showed significant differences at baseline in relative beta waves on electrodes Fp1 ( P < 0.05 ) and F3 ( P < 0.05 ) , as well as in relative beta2 waves on F3 ( P < 0.05 ) . In addition , after the 12-week exercise intervention , differences in a region that benefits from exercise were observed between ( 1 ) the MCI-EX group in the relative theta power on F3 ( P < 0.05 ) and the relative alpha power on T3 ( P < 0.05 ) and in ( 2 ) the NG Output:	Main results showed that resistance training had positive effects on the executive function and global cognitive function of the elderly , and short-term interventions had little positive effect on memory and attention . Secondary results demonstrated that there was a significant benefit of triweekly resistance training in global cognitive function and biweekly in executive function of the elderly . Conclusions Resistance training had positive effects on the executive cognitive ability and global cognitive function among the elderly ; however , it had a weak-positive impact on memory . No significant improvement was found in attention . Triweekly resistance training has a better effect on general cognitive ability than biweekly .
MS22016	*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 1990 , 215 patients with operable breast cancer were entered into a prospect i ve study of the prognostic significance of five biochemical markers and 15 other factors ( pathological/chronological/patient ) . After a median follow-up of 6.6 years , there were 77 recurrences and 77 deaths ( 59 breast cancer-related ) . By univariate analysis , patient outcome related significantly to 13 factors . By multivariate analysis , the most important of nine independent factors were : number of nodes involved , steroid receptors ( for oestrogen or progestogen ) , age , clinical or pathological tumour size and grade . Receptors and grade exerted their influence only in the first 3 years . Progestogen receptors ( immunohistochemical ) and oestrogen receptors ( biochemical ) were of similar prognostic significance . The two receptors were correlated ( r=+0.50 , P=0.001 ) and displaced each other from the analytical model but some evidence for the additivity of their prognostic values was seen when their levels were discordant Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Objective Accurately predicting the prognosis of young patients with breast cancer ( < 40 years ) is uncertain since the literature suggests they have a higher mortality and that age is an independent risk factor . In this cohort study we considered two prognostic tools ; Nottingham Prognostic Index and Adjuvant Online ( Adjuvant ! ) , in a group of young patients , comparing their predicted prognosis with their actual survival . Setting North East Engl and Participants Data was prospect ively collected from the breast unit at a Hospital in Grimsby between January 1998 and December 2007 . A cohort of 102 young patients with primary breast cancer was identified and actual survival data was recorded . The Nottingham Prognostic Index and Adjuvant ! scores were calculated and used to estimate 10-year survival probabilities . Pearson 's correlation coefficient was used to demonstrate the association between the Nottingham Prognostic Index and Adjuvant ! scores . A constant yearly hazard rate was assumed to generate 10-year cumulative survival curves using the Nottingham Prognostic Index and Adjuvant ! predictions . Results Actual 10-year survival for the 92 patients who underwent potentially curative surgery for invasive cancer was 77.2 % ( CI 68.6 % to 85.8 % ) . There was no significant difference between the actual survival and the Nottingham Prognostic Index and Adjuvant ! 10-year estimated survival , which was 77.3 % ( CI 74.4 % to 80.2 % ) and 82.1 % ( CI 79.1 % to 85.1 % ) , respectively . The Nottingham Prognostic Index and Adjuvant ! results demonstrated strong correlation and both predicted cumulative survival curves accurately reflected the actual survival in young patients . Conclusions The Nottingham Prognostic Index and Adjuvant ! are widely used to predict survival in patients with breast cancer . In this study no statistically significant difference was shown between the predicted prognosis and actual survival of a group of young patients with breast cancer A prognostic index , previously derived in a group of 387 patients with primary breast cancer , has been recalculated for the same patients with over 5 years further follow-up and shown to be unchanged . The prognostic index has also been applied prospect ively to a further group of 320 patients and shown to be similarly effective in identifying patients with either a very good or a very poor prognosis . It has been verified that the index applies to patients with primary breast cancer . Patients have now been divided into 5 prognostic groups , predicting 11 % of patients with an almost normal survival and a further 10 % with a very poor prognosis . The index is used to stratify patients to study the effects of treatment regimes within groups of similar patients PURPOSE Our objective was to develop a nomogram to predict individual overall survival ( OS ) for primary breast cancer , based on pathological and biological tumor parameters . METHODS A retrospective study in a cohort of 180 patients with primary breast cancer was used to build the nomogram . Pathological factors and tumor proteases measured prospect ively in primary tumors were used . A multivariate Cox proportional hazards model was used to explore the relationship with OS , and regression coefficients were used to build the nomogram . The nomogram was internally vali date d with 200 bootstrap re- sample s. RESULTS The final variables included in the nomogram comprised tumor size ( P = 0.04 ) , nodal pathological status ( P = 0.01 ) , estrogen receptor status ( P = 0.04 ) , urokinase plasminogen activator inhibitor-1 ( PAI-1 ; P = 0.02 ) , thymidine kinase ( P = 0.03 ) , and cathepsin D ( P = 0.004 ) . The predictive accuracy of the nomogram at estimating the probability of OS , at both 2 and 5 years , was respectively 0.874 and 0.832 before and after calibration . CONCLUSION A nomogram to predict 2- and 5-year OS in BC , using histological and biological parameters was successfully developed . This prognostic tool should prove useful in decision-making and therapeutic research Abstract Web-based prognostication tools may provide a simple and economically feasible option to aid prognostication and selection of chemotherapy in early breast cancers . We vali date Output:	Overall , the models performed well in the development cohorts but less accurately in some independent population s , particularly in patients with high risk and young and elderly patients . An exception is the Nottingham Prognostic Index , which retains its predicting ability in most independent population s. Conclusions Many prognostic models have been developed for breast cancer , but only a few have been vali date d widely in different setting s. Importantly , their performance was suboptimal in independent population s , particularly in patients with high risk and in young and elderly patients
MS22017	*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 Geriatric evaluation and management has become st and ard care for community dwelling older adults following an acute admission to hospital . It is unclear whether this approach is beneficial for the frailest older adults living in permanent residential care . This study was undertaken to evaluate ( 1 ) the feasibility and consumer satisfaction with a geriatrician-led supported discharge service for older adults living in residential care facilities ( RCF ) and ( 2 ) its impact on the uptake of Advanced Care Planning ( ACP ) and acute health care service utilisation . Methods In 2002–4 a r and omised controlled trial was conducted in Melbourne , Australia comparing the geriatrician – led outreach service to usual care for RCF residents . Patients were recruited during their acute hospital stay and followed up at the RCF for six months . The intervention group received a post-discharge home visit within 96 hours , at which a comprehensive geriatric assessment was performed and a care plan developed . Participants and their families were also offered further meetings to discuss ACPs and document Advanced Directives ( AD ) . Additional review s were made available for assessment and management of intercurrent illness within the RCF . Consumer satisfaction was surveyed using a postal question naire . Results The study included 116 participants ( 57 intervention and 59 controls ) with comparable baseline characteristics . The service was well received by consumers demonstrated by higher satisfaction with care in the intervention group compared to controls ( 95 % versus 58 % , p = 0.006).AD were completed by 67 % of participants /proxy decision makers in the intervention group compared to 13 % of RCF residents prior to service commencement . At six months there was a significant reduction in outpatient visits ( intervention 21 ( 37 % ) versus controls 45 ( 76 % ) , ( p < 0.001 ) , but no difference in readmissions rates ( 39 % intervention versus 34 % control , p = 0.6 ) . There was a trend towards reduced hospital bed-day utilisation ( intervention 271 versus controls 372 days ) . Conclusion It is feasible to provide a supported discharge service that includes geriatrician assessment and care planning within a RCF . By exp and ing the service there is the potential for acute health care cost savings by decreasing the dem and for outpatient consultation and further reducing acute care bed-days Objective : To investigate the impact of an in-reach rehabilitation team for patients admitted after road trauma . Design : R and omised control trial of usual care versus early involvement of in-reach rehabilitation team . Telephone follow-up was conducted by a blind assessor at three months for those with minor/moderate injuries and six months for serious/severe injuries . Setting : Four participating trauma services in New South Wales , Australia . Subjects : A total of 214 patients admitted during 2012 - 2015 with a length of stay of at least five days . Intervention : Provision of rehabilitation services in parallel with ward based therapy using an in-reach team for the intervention group . The control group could still access the ward based therapy ( usual care ) . Main measures : The primary outcome was acute length of stay . Secondary outcomes included percentage requiring inpatient rehabilitation , function ( Functional Independence Measure and Timed Up and Go Test ) , psychological status ( Depression Anxiety and Stress Score 21 ) , pain ( Orebro Musculoskeletal Pain Question naire ) and quality of life ( Short Form-12 v2 ) . Results : Median length of stay in acute care was 13 days ( IQR 8 - 21 ) . The intervention group , compared to the control group , received more physiotherapy and occupational therapy sessions ( median number of sessions 16.0 versus 11.5 , P=0.003 ) . However , acute length of stay did not differ between the intervention and control groups ( median 15 vs 12 days , P=0.37 ) . There were no significant differences observed in the secondary outcomes at hospital discharge and follow-up . Conclusion : No additional benefit was found from the routine use of acute rehabilitation teams for trauma patients over and above usual care Background Despite growing emphasis on transitional care to reduce costs and improve quality , few studies have examined transitional care improvements in socioeconomically disadvantaged adults . It is important to consider these patients separately as many are high-utilizers , have different needs , and may have different responses to interventions . Objective To evaluate the impact of a multicomponent transitional care improvement program on 30-day readmissions , emergency department ( ED ) use , transitional care quality , and mortality . Design Clustered r and omized controlled trial conducted at a single urban academic medical center in Portl and , Oregon . Participants Three hundred eighty-two hospitalized low-income adults admitted to general medicine or cardiology who were uninsured or had public insurance . InterventionMulticomponent intervention including ( 1 ) transitional nurse coaching and education , including home visits for highest risk patients ; ( 2 ) pharmacy care , including provision of 30 days of medications after discharge for those without prescription drug coverage ; ( 3 ) post-hospital primary care linkages ; ( 4 ) systems integration and continuous quality improvement . Measurements Primary outcomes included 30-day inpatient readmission and ED use . Readmission data were obtained using state-wide administrative data for all participants ( insured and uninsured ) . Secondary outcomes included quality ( 3-item Care Transitions Measure ) and mortality . Research staff administering question naires and assessing outcomes were blinded . Results There was no significant difference in 30-day readmission between C-TraIn ( 30/209 , 14.4 % ) and control patients ( 27/173 , 16.1 % ) , p = 0.644 , or in ED visits between C-TraIn ( 51/209 , 24.4 % ) and control ( 33/173 , 19.6 % ) , p = 0.271 . C-TraIn was associated with improved transitional care quality ; 47.3 % ( 71/150 ) of C-TraIn patients reported a high quality transition compared to 30.3 % ( 36/119 ) control patients , odds ratio 2.17 ( 95 % CI 1.30–3.64 ) . Zero C-TraIn patients died in the 30-day post-discharge period compared with five in the control group ( unadjusted p = 0.02 ) . Conclusions C-TraIn did not reduce 30-day inpatient readmissions or ED use ; however , it improved transitional care quality Background Intermediate care is a health care model developed to optimize the coordination of health care services and functional independence . In Central Norway , an intermediate care hospital ( ICH ) was established in a municipality to improve hospital discharge and follow-up among elderly patients with chronic conditions and comprehensive care needs . The aim of this study was to investigate the effectiveness of hospital discharges to a municipality with an ICH compared to discharges to a municipality without an ICH . Methods This was a non-r and omized controlled observational study of hospitalized patients aged 60 years and older from two municipalities . Patients ( n = 328 ) admitted to a general hospital from February 2010 through September 2011 were included in the study and followed for 12 months . The data were analyzed using descriptive statistics , analysis of covariance ( ANCOVA ) and Cox proportional hazard regression . Results Each patient discharged from the general hospital to the municipality with an ICH had a shorter length of stay and used on average 4.2 ( p = 0.046 ) fewer hospital days during 1 year compared to patients from the municipality without an ICH . Otherwise , no statistical significant differences were found between the municipalities in terms of hospital readmissions , admissions , mortality , activities of daily living , primary health care utilization or total care days . A post hoc analysis of patients discharged to the ICH compared to the municipality without an ICH , showed that the ICH patients were older and frailer , but the outcome was similar to the main analysis . Conclusions Having an ICH in the municipality facilitated shorter length of hospital stay and kept the risk of readmissions , mortality and post-hospitalization care needs at the same level as without an ICH Background One of the reasons physiotherapy services are provided to emergency departments ( EDs ) and emergency extended care units ( EECUs ) is to review patients ' mobility to ensure they are safe to be discharged home . Aim To investigate whether a physiotherapy service to an EECU altered the rate of hospital admission , rate of re-presentation to the ED , visits to community healthcare practitioners , return to usual work/home/leisure activities and patient satisfaction . Methods A r and omised trial with concealed allocation , assessor blinding and intention-to-treat analysis was undertaken in an EECU . The sample comprised 186 patients ( mean age 70 years , 123 ( 66 % ) female patients , 130 ( 70 % ) trauma ) who were referred for physiotherapy assessment /intervention . Referral occurred at any stage of the patients ' EECU admission . All participants received medical/nursing care as required . The physiotherapy group also received physiotherapy assessment /intervention . Results The physiotherapy group had a 4 % ( 95 % CI −18 % to 9 % ) lower rate of admission to hospital than the control group and a 4 % ( 95 % CI −6 % to 13 % ) higher rate of re-presentation to the ED , which were statistically non-significant ( p≥0.45 ) . Differences between groups for use of community healthcare re sources , return to usual work/home/leisure activities and satisfaction with their EECU care were small and not significant . Conclusion A physiotherapy service for EECU patients , as provided in this study , did not reduce the rate of hospital admission , rate of re-presentation to the ED , use of community healthcare re sources , or improve the rate of return to usual work/home/leisure activities or patient satisfaction . Trial registration number ANZCTRN12609000106235 IMPORTANCE Hospital readmissions are common and costly , and no single intervention or bundle of interventions has reliably reduced readmissions . Virtual wards , which use elements of hospital care in the community , have the potential to reduce readmissions , but have not yet been rigorously evaluated . OBJECTIVE To determine whether a virtual ward-a model of care that uses some of the systems of a hospital ward to provide interprofessional care for community-dwelling patients -can reduce the risk of readmission in patients at high risk of readmission or death when being discharged from hospital . DESIGN , SETTING , AND PATIENTS High-risk adult hospital discharge patients in Toronto were r and omly assigned to either the virtual ward or usual care . A total of 1923 patients were r and omized during the course of the study : 960 to the usual care group and 963 to the virtual ward group . The first patient was enrolled on June 29 , 2010 , and follow-up was completed on June 2 , 2014 . INTERVENTIONS Patients assigned to the virtual ward received care coordination plus direct care provision ( via a combination of telephone , home visits , or clinic visits ) from an interprofessional team for several weeks after hospital discharge . The interprofessional team met daily at a central site to design and implement individualized management plans . Patients assigned to usual care typically received a typed , structured discharge summary , prescription for new medications if indicated , counseling from the resident physician , arrangements for home care as needed , and recommendations , appointments , or both for follow-up care with physicians as indicated . MAIN OUTCOMES AND MEASURES The primary outcome was a composite of hospital readmission or death within 30 days of discharge . Secondary outcomes included nursing home admission and emergency department visits , each of the components of the primary outcome at 30 days , as well as each of the outcomes ( including the composite primary outcome ) at 90 days , 6 months , and 1 year . RESULTS There were no statistically significant between-group differences in the primary or secondary outcomes at 30 or 90 days , 6 months , or 1 year . The primary outcome occurred in 203 of 959 ( 21.2 % ) of the virtual ward patients and 235 of 956 ( 24.6 % ) of the usual care patients ( absolute difference , 3.4 % ; 95 % CI , -0.3 % to 7.2 % ; P = .09 ) . There were no statistically significant interactions to indicate that the virtual ward model of care was more or less effective in any of the prespecified subgroups . CONCLUSIONS AND RELEVANCE In a diverse group of high-risk patients being discharged from the hospital , we found no statistically significant effect of a virtual ward model of care on readmissions or death at either 30 days or 90 days , 6 months , or 1 year after hospital discharge . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01108172 Residents of long-term care facilities have highly complex care needs and quality of care is of international concern . Maintaining resident wellness through proactive assessment and early intervention is key to decreasing the need for acute hospitalization . The Residential Aged Care Integration Program ( RACIP ) is a quality improvement intervention to support residential aged care staff and includes on-site support , education , clinical coaching , and care coordination provided by gerontology nurse specialists ( GNSs ) employed by a large district health board . The effect of the outreach program was evaluated through a r and omized comparison of hospitalization 1 year before and after program implementation . The sample included 29 intervention facilities ( 1,425 residents ) and 25 comparison facilities ( 1,128 residents ) receiving usual care . Acute hospitalization rate unexpectedly increased for both groups after program implementation , although the rate of increase was significantly less for the intervention facilities . The hospitalization rate after the intervention increased 59 % for the comparison group and 16 % for the intervention group ( rate ratio ( RR ) = 0.73 , 95 % confidence interval ( CI ) Output:	Mixed results were found regarding the effectiveness of many types of interventions . Interventions exclusively delivered in the acute hospital pre-discharge and those involving education were most common but their effectiveness was limited in avoiding (re)admission . Successful pre- and post-discharge interventions focused on multidisciplinary approaches . Post-discharge interventions exclusively delivered at home reduced hospital stay and contributed to patient satisfaction . Existing systematic review s on tele-health and long-term care interventions suggest insufficient evidence for admission avoidance . The most effective interventions to avoid inappropriate re-admission to hospital and promote early discharge included integrated systems between hospital and the community care , multidisciplinary service provision , individualization of services , discharge planning initiated in hospital and specialist follow-up
MS22018	*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 There were higher rates of revision , complication , non-union , delayed union , and poorer functional outcomes reported in super-aged patients of undisplaced femoral neck fractures treated with internal fixation . Therefore , we design ed this r and omized comparative study aim ing to compare the effectiveness and long-term follow-up results of hemiarthroplasty ( HA ) with that of multiple cannulated screws ( MCS ) . Material s and methods Eligible participants were r and omly assigned into two groups for different methods of operation ( hemiarthroplasty group and internal fixation group ) . The related indexes and data of two groups were collected for comparative analysis during the average follow-up period of 38.68 ± 28.24 months . Results There were only two patients performed reoperation in HA group , and the reoperation rate of HA group ( 5.41 % , 2/37 ) was significantly lower than that of IF group ( 21.4 % , 9/41 ) ( P value = 0.000 ) . The comparison of survival curves for reoperation showed significant differences between two groups ( P value = 0.031).The results of Cox proportional hazards model suggested that only operation method significantly affected the occurrence of reoperation ( P value = 0.049 ) . The results of survival analysis showed that there was no significant difference in survival time between two groups ( P value = 0.682 ) . And in the Cox proportional hazards model , only age significantly affected the occurrence of death ( P value = 0.000 ) . The average Harris scores of two groups were all above 75 points , and there was no significant difference in Harris scores between the two groups ( P value greater than 0.05 ) . But in the early term follow-up , the excellent and good rate of hip joint function in HA group was significantly higher than that in IF group ( P value less than 0.05 ) . Conclusions Hemiarthroplasty with less postoperative complications , low reoperation rate and better function recovery in early stage provide a good choice for the treatment of super-aged patients with nondisplaced femoral neck fracture BACKGROUND Arthroplasty is now widely used to treat intra-capsular proximal femoral fractures ( PFFs ) in older patients , even when there is little or no displacement . However , whether arthroplasty is associated with lower mortality and complication rates in non-displaced or mildly displaced PFFs is unknown . The objectives of this prospect i ve study were : ( 1 ) to evaluate early mortality rates with the two treatment methods , ( 2 ) to identify risk factors for complications , ( 3 ) and to identify predictors of functional decline . HYPOTHESIS Arthroplasty and internal fixation produce similar outcomes in non-displaced fractures of patients older than 80 years with PFFs . MATERIAL AND METHODS This multicentre prospect i ve study included consecutive patients older than 80 years who were managed for intra-capsular PFFs at eight centres in 2014 . Biometric data and geriatric assessment scores ( Parker Mobility Score , Katz Index of Independence , and Mini-Nutritional Assessment [ MNA ] score ) were collected before and 6 months after surgery . Independent risk factors were sought by multivariate analysis . We included 418 females and 124 males with a mean age of 87±4years . The distribution of Garden stages was stage I , n=56 ; stage II , n=33 ; stage III , n=130 ; and stage IV , n=323 . Arthroplasty was performed in 494 patients and internal fixation in 48 patients with non-displaced intra-capsular PFFs . RESULTS Mortality after 6 months was 16.4 % overall , with no significant difference between the two groups . By multivariate analysis , two factors were significantly associated with higher mortality , namely , male gender ( odds ratio [ OR ] , 3.24 ; 95 % confidence interval [ 95 % CI ] , 2.0 - 5.84 ; P<0.0001 ) and high ASA score ( OR , 1.56 ; 95 % CI , 1.07 - 2.26 ; P=0.019 ) . Two factors were independently associated with lower mortality , with 75 % predictive value , namely , high haematocrit ( OR , 0.8 ; 95 % CI , 0.7 - 0.9 ; P=0.001 ) and better Parker score ( OR , 0.5 ; 95 % CI , 0.3 - 0.8 ; P=0.01 ) . The cut-off values associated with a significant risk increase were 2 for the Parker score ( OR , 1.8 ; 95 % CI , 1.1 - 2.3 ; P=0.001 ) and 37 % for the haematocrit ( OR , 3.3 ; 95 % CI , 1.9 - 5.5 ; P=0.02 ) . Complications occurred in 5.5 % of patients . Surgical site infections were seen in 1.4 % of patients , all of whom had had arthroplasty . Blood loss was significantly greater with arthroplasty ( 311±197mL versus 201±165mL , P<0.0002 ) . Dependency worsened in 39 % of patients , and 31 % of patients lost self-sufficiency . A higher preoperative Parker score was associated with a lower risk of high postoperative dependency ( OR , 0.86 ; 95 % CI , 0.76 - 0.97 ; P=0.014 ) . DISCUSSION Neither treatment method was associated with decreased mortality or better function after intra-capsular PFFs in patients older than 80 years . Early mortality rates were consistent with previous reports . Among the risk factors identified in this study , age , preoperative self-sufficiency , and gender are not amenable to modification , in contrast to haematocrit and blood loss . CONCLUSION Internal fixation remains warranted in patients older than 80 years with non-displaced intra-capsular PFFs . LEVEL OF EVIDENCE III , prospect i ve case-control study Introduction : Although the preferred treatment for displaced femoral neck fractures in the elderly is hip arthroplasty , the treatment for impacted or undisplaced femoral neck fractures ( UFNF ) is still a subject of controversy . Our purpose was to systematic ally review studies of elderly patients with UFNF treated with internal fixation using screws : ( i ) what is the reported mortality ; ( ii ) what is the reoperation rate ; ( iii ) what are the clinical and radiological outcomes ; and ( iv ) what is the method ological quality of the included studies ? Methods : This systematic review was performed through a search of PubMed and the Cochrane data base using a structured search algorithm including studies enrolling patients older than 60 years old , with UFNF treated with internal fixation using screws . Our literature search returned 950 studies and 11 were selected for final abstract ion . Results : 6 studies reported mortality rate . At 1-year follow-up mortality was reported by 3 studies : 18.8 % ; 22 % , and 19 % . At 5 years , 1 study reported mortality rate of 42 % . Overall reoperation rate was reported by 9 studies and ranged from 8%-19 % , while conversion to hip arthroplasty was performed in the range between 8 % and 16 % according to 6 studies . Conclusions : Internal fixation with cannulated screws for UFNF in the elderly is a valuable option , although it has substantial reoperation and mortality rates . Further prospect i ve high- quality , r and omised controlled trials are required to establish the optimal approach for the treatment of UFNF INTRODUCTION The objective of this study was to identify indications and predictors for subsequent surgeries in the same hip and to evaluate life expectancy following screw fixation of undisplaced femoral neck fractures ( FNF ) . The study further aim ed to determine the necessary follow-up time for future studies aim ing to evaluate the treatment of such fractures . MATERIAL S AND METHODS This is a single-center retrospective cohort study with prospect ively collected data including skeletally mature patients with undisplaced FNFs operated between 2005 and 2013 . Gender , age at fracture , American Society of Anesthesiologists score , smoking status and excess use of alcohol were retrieved from electronical medical records . Further , complications leading to all consecutive reoperations were registered along with time from primary operation to all reoperations , type of procedure during subsequent surgeries and time of death . RESULTS 383 patients with a median ( range ) follow-up of 77 ( 23 - 125 ) months were identified . Within 1 , 2 and 5 years from primary surgery , 8 % , 17 % and 21 % respectively , had at least one subsequent surgery in the same hip . 10 % of the patients underwent salvage arthroplasty , however , in long time survivors ; conversion to arthroplasty was estimated in one out of four . Posterior tilt of the femoral head was a predictor for new surgeries due to instability of the bone-implant construct , but not for later avascular necrosis . For patients 70 years or older , the one-year mortality in men was 32 % with an expected survival of approx . 2.5 years , compared to 17 % and 5.5 years in women . CONCLUSIONS Screw fixation of undisplaced femoral neck fractures appears to be a safe procedure in particular in the absence of a posterior tilt of the femoral head . Conversion to arthroplasty was estimated to occur in one out of four of long time survivors . Men have a particularly poor medical prognosis and should receive careful medical attention . In order to capture 80 % of reoperations , clinical studies and register studies must have a follow-up time of at least two years Background Reported revision of internal fixation for undisplaced intracapsular hip fractures is between 12 and 17 % at 1 year . This risk is greater for elderly patients , for whom mortality after such a fracture is also higher . Our purpose was to identify predictors of fixation failure and mortality for elderly patients sustaining undisplaced intracapsular hip fractures , and to assess whether their socioeconomic status affected their outcome . Methods During a 3-year period we prospect ively compiled a consecutive series of 162 elderly ( ≥65 years old ) patients who underwent internal fixation for an undisplaced ( Garden stage I or II ) intracapsular hip fracture . Patient demographics , American Society of Anesthesiologists ( ASA ) grade , and posterior tilt ( measured on the lateral radiograph ) were recorded pre-operatively . All patients were followed up for a minimum of 1 year . Each patient ’s socioeconomic status was assigned by use of the Scottish Index of Multiple Deprivation . Patient mortality was established by use of the General Register Office for Scotl and . Results There were 28 failures of fixation during the study period . In Cox regression analysis , ASA grade and the presence of posterior tilt ( p < 0.0001 ) were significant independent predictors of fixation failure . Overall unadjusted mortality at 1 year was 19 % ( n = 30/162 ) . Cox regression analysis also affirmed ASA grade to be the only significant independent predictor of 1-year mortality ( p = 0.003 ) . The st and ardised mortality rate for the cohort was 2.3 ( p < 0.001 ) , and was significantly greater for patients less than 80 years of age ( p = 0.004 ) . Socioeconomic status did not affect outcome , but the most deprived patients sustain their fracture at a significantly younger age ( p = 0.001 ) . Conclusion We have demonstrated that ASA grade and posterior tilt of the femoral neck are independent predictors of fixation failure of undisplaced intracapsular hip fractures in elderly patients , and ASA grade was also an independent predictor of mortality Abstract Hemiarthroplasty is the most commonly used treatment for displaced femoral neck fractures in the elderly . There is limited evidence in the literature of improved functional outcome with cemented implants , although serious cement-related complications have been reported . We performed a r and omized , controlled trial in patients 70 years and older comparing a cemented implant ( 112 hips ) with an uncemented , hydroxyapatite-coated implant ( 108 hips ) , both with a bipolar head . The mean Harris hip score showed equivalence between the groups , with 70.9 in the cemented group and 72.1 in the uncemented group after 3 months ( mean difference , 1.2 ) and 78.9 and 79.8 after 12 months ( mean difference , 0.9 ) . In the uncemented group , the mean duration of surgery was 12.4 minutes shorter and the mean intraoperative blood loss was 89 mL less . The Barthel Index and EQ-5D scores did not show any differences between the groups . The rates of complications and mortality were similar between groups . Both arthroplasties may be used with good results after displaced femoral neck fractures . Level of Evidence : Level I , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 1 Output:	Conclusions Compared with the internal fixation group , patients that underwent hemiarthroplasty had a lower reoperation rate and an equivalent overall mortality rate . Our meta- analysis suggests that hemiarthroplasty might be a better treatment choice than internal fixation in treating elderly patients with an undisplaced femoral neck fracture
MS22019	*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 : Cocaine use is common in opioid-dependent HIV-infected patients , but its impact on treatment outcomes in these patients receiving buprenorphine/naloxone is not known . Methods : We conducted a prospect i ve study in 299 patients receiving buprenorphine/naloxone who provided baseline cocaine data and a subset of 266 patients who remained in treatment for greater than or equal to one quarter . Assessment s were conducted at baseline and quarterly for 1 year . We evaluated the association between baseline and in-treatment cocaine use on buprenorphine/naloxone retention , illicit opioid use , antiretroviral adherence , CD4 counts , HIV RNA , and risk behaviors . Results : Sixty-six percent ( 197 of 299 ) of patients reported baseline cocaine use and 65 % ( 173 of 266 ) of patients with follow-up data reported in-treatment cocaine use . Baseline and in-treatment cocaine use did not impact buprenorphine/naloxone retention , antiretroviral adherence , CD4 lymphocytes , or HIV risk behaviors . However , baseline cocaine use was associated with a 14.8 ( 95 % confidence interval [ CI ] , 9.0 - 24.2 ) times greater likelihood of subsequent cocaine use ( 95 % CI , 9.0 - 24.2 ) , a 1.4 ( 95 % CI , 1.02 - 2.00 ) times greater likelihood of subsequent opioid use , and higher log10 HIV RNA ( P < 0.016 ) over time . In-treatment cocaine use was associated with a 1.4 ( 95 % CI , 1.01 - 2.00 ) times greater likelihood of concurrent opioid use . Conclusions : Given cocaine use negatively impacts opioid and HIV treatment outcomes , interventions to address cocaine use in HIV-infected patients receiving buprenorphine/naloxone treatment are warranted This study was design ed to compare the neonatal abstinence syndrome ( NAS ) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial . This r and omized , double-blind , double-dummy , flexible dosing , parallel-group controlled trial was conducted in a comprehensive drug-treatment facility that included residential and ambulatory care . Participants were opioid-dependent pregnant women and their neonates . Treatment involved daily administration of either sublingual buprenorphine or oral methadone using flexible dosing of 4 - 24 mg or 20 - 100 mg , respectively . Primary a priori outcome measures were : ( 1 ) number of neonates treated for NAS ; ( 2 ) amount of opioid agonist medication used to treat NAS ; ( 3 ) length of neonatal hospitalization ; and ( 4 ) peak NAS score . Two of 10 ( 20 % ) buprenorphine-exposed and 5 of 11 ( 45.5 % ) methadone-exposed neonates were treated for NAS ( p=.23 ) . Total amount of opioid-agonist medication administered to treat NAS in methadone-exposed neonates was three times greater than for buprenorphine-exposed neonates ( 93.1 versus 23.6 ; p=.13 ) . Length of hospitalization was shorter for buprenorphine-exposed than for methadone-exposed neonates ( p=.021 ) . Peak NAS total scores did not significantly differ between groups ( p=.25 ) . Results suggest that buprenorphine is not inferior to methadone on outcome measures assessing NAS and maternal and neonatal safety when administered starting in the second trimester of pregnancy Background : Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes . Methods : HIV-infected , opioid-dependent subjects ( N = 295 ) recruited from 10 clinical sites initiated buprenorphine/naloxone ( BUP/NX ) and were assessed at baseline and quarterly for 12 months . Primary outcomes included receiving antiretroviral therapy ( ART ) , HIV-1 RNA suppression , and mean changes in CD4 lymphocyte count . Analyses were stratified for the 119 subjects not on ART at baseline . Generalized estimating equations were deployed to examine time-dependent correlates for each outcome . Results : At baseline , subjects on ART ( N = 176 ) were more likely than those not on ART ( N = 119 ) to be older , heterosexual , have lower alcohol addiction severity scores , and lower HIV-1 RNA levels ; they were less likely to be homeless and report sexual risk behaviors . Subjects initiating BUP/NX ( N = 295 ) were significantly more likely to initiate or remain on ART and improve CD4 counts over time compared with baseline ; however , these improvements were not significantly improved by longer retention on BUP/NX . Retention on BUP/NX for three or more quarters was , however , significantly associated with increased likelihood of initiating ART ( β = 1.34 [ 1.18 , 1.53 ] ) and achieve viral suppression ( β = 1.25 [ 1.10 , 1.42 ] ) for the 64 of 119 ( 54 % ) subjects not on ART at baseline compared with the 55 subjects not retained on BUP/NX . In longitudinal analyses , being on ART was positively associated with increasing time of observation from baseline and higher mental health quality of life scores ( β = 1.25 [ 1.06 , 1.46 ] ) and negatively associated with being homo- or bisexual ( β = 0.55 [ 0.35 , 0.97 ] ) , homeless ( β = 0.58 [ 0.34 , 0.98 ] ) , and increasing levels of alcohol addiction severity ( β = 0.17 [ 0.03 , 0.88 ] ) . The strongest correlate of achieving viral suppression was being on ART ( β = 10.27 [ 5.79 , 18.23 ] ) . Female gender ( β = 1.91 [ 1.07 , 3.41 ] ) , Hispanic ethnicity ( β = 2.82 [ 1.44 , 5.49 ] ) , and increased general health quality of life ( β = 1.02 [ 1.00,1.04 ] ) were also independently correlated with viral suppression . Improvements in CD4 lymphocyte count were significantly associated with being on ART and increased over time . Conclusions : Initiating BUP/NX in HIV clinical care setting s is feasible and correlated with initiation of ART and improved CD4 lymphocyte counts . Longer retention on BPN/NX was not associated with improved prescription of ART , viral suppression , or CD4 lymphocyte counts for the overall sample in which the majority was already prescribed ART at baseline . Among those retained on BUP/NX , HIV treatment outcomes did not worsen and were sustained . Increasing time on BUP/NX , however , was especially important for improving HIV treatment outcomes for those not on ART at baseline , the group at highest risk for clinical deterioration . Retaining subjects on BUP/NX is an important goal for sustaining HIV treatment outcomes for those on ART and improving them for those who are not . Comorbid substance use disorders ( especially alcohol ) , mental health problems , and quality -of-life indicators independently contributed to HIV treatment outcomes among HIV-infected persons with opioid dependence , suggesting the need for multidisciplinary treatment strategies for this population Substance abuse is associated with poor medical and quality -of-life outcomes among HIV-infected individuals . Although drug treatment may reduce these negative consequences , for many patients , options are limited . Buprenorphine/naloxone , an opioid agonist treatment that can be prescribed in the United States in office-based setting s , can be used to exp and treatment capacity and integrate substance abuse services into HIV care . Recognizing this potential , the US Health Re sources and Services Administration funded the development and implementation of demonstration projects that integrated HIV care and buprenorphine/naloxone treatment at 10 sites across the country . An Evaluation and Technical Assistance Center provided programmatic and clinical support as well as oversight for an evaluation that examined the processes for and outcomes of integrated care . The evaluation included patient-level self-report and chart abstract ions as well as provider and site level data collected through surveys and in-depth interviews . Although multisite demonstrations pose implementation and evaluation challenges , our experience demonstrates that these can , in part , be addressed through ongoing communication and technical assistance as well as a comprehensive evaluation design that incorporates multiple research methods and data sources . Although limitations to evaluation findings persist , they may be balanced by the scope and “ real-world ” context of the initiative Background : Opioid dependence and HIV infection are associated with poor health-related quality of life ( HRQOL ) . Buprenorphine/naloxone ( bup/nx ) provided in HIV care setting s may improve HRQOL . Methods : We surveyed 289 HIV-infected opioid-dependent persons treated with clinic-based bup/nx about HRQOL using the Short Form Health Survey ( SF-12 ) administered at baseline , 3 , 6 , 9 , and 12 months . We used normalized SF-12 scores , which correspond to a mean HRQOL of 50 for the general US population ( SD 10 , possible range 0 - 100 ) . We compared mean normalized mental and physical composite and component scores in quarters 1 , 2 , 3 , and 4 with baseline scores using generalized estimating equation models . We assessed the effect of clinic-based bup/nx prescription on HRQOL composite scores using mixed effects regression with site as r and om effect and time as repeated effect . Results : Baseline normalized SF-12 scores were lower than the general US population for all HRQOL domains . Average composite mental HRQOL improved from 38.3 ( SE 12.5 ) to 43.4 ( SE 13.2 ) [ β 1.13 ( 95 % CI : 0.72 to 1.54 ) ] and composite physical HRQOL remained unchanged [ β 0.21 ( 95 % CI : −0.16 to 0.57 ) ] over 12 months follow-up . Continued bup/nx treatment across all 4 quarters was associated with improvements in both physical [ β 2.38 ( 95 % CI : 0.63 to 4.12 ) ] and mental [ β 2.51 ( 95 % CI : 0.42 to 4.60 ) ] HRQOL after adjusting for other contributors to HRQOL . Conclusions : Clinic-based bup/nx maintenance therapy is potentially effective in ameliorating some of the adverse effects of opioid dependence on HRQOL for HIV-infected population IMPORTANCE Buprenorphine opioid agonist treatment ( OAT ) has established efficacy for treating opioid dependency among persons seeking addiction treatment . However , effectiveness for out-of-treatment , hospitalized patients is not known . OBJECTIVE To determine whether buprenorphine administration during medical hospitalization and linkage to office-based buprenorphine OAT after discharge increase entry into office-based OAT , increase sustained engagement in OAT , and decrease illicit opioid use at 6 months after hospitalization . DESIGN , SETTING , AND PARTICIPANTS From August 1 , 2009 , through October 31 , 2012 , a total of 663 hospitalized , opioid-dependent patients in a general medical hospital were identified . Of these , 369 did not meet eligibility criteria . A total of 145 eligible patients consented to participation in the r and omized clinical trial . Of these , 139 completed the baseline interview and were assigned to the detoxification ( n = 67 ) or linkage ( n = 72 ) group . INTERVENTIONS Five-day buprenorphine detoxification protocol or buprenorphine induction , intrahospital dose stabilization , and postdischarge transition to maintenance buprenorphine OAT affiliated with the hospital 's primary care clinic ( linkage ) . MAIN OUTCOMES AND MEASURES Entry and sustained engagement with buprenorphine OAT at 1 , 3 , and 6 months ( medical record verified ) and prior 30-day use of illicit opioids ( self-report ) . RESULTS During follow-up , linkage participants were more likely to enter buprenorphine OAT than those in the detoxification group ( 52 [ 72.2 % ] vs 8 [ 11.9 % ] , P < .001 ) . At 6 months , 12 linkage participants ( 16.7 % ) and 2 detoxification participants ( 3.0 % ) were receiving buprenorphine OAT ( P = .007 ) . Compared with those in the detoxification group , participants r and omized to the linkage group reported less illicit opioid use in the 30 days before the 6-month interview ( incidence rate ratio , 0.60 ; 95 % CI , 0.46 - 0.73 ; P < .01 ) in an intent-to-treat analysis . CONCLUSIONS AND RELEVANCE Compared with an inpatient detoxification protocol , initiation of and linkage to buprenorphine treatment is an effective means for engaging medically hospitalized patients who are not seeking addiction treatment and reduces illicit opioid use 6 months after hospitalization . However , Output:	Medication-assisted treatment more effectively reduces opioid use than behavioral treatment alone ( 5 , 6 ) . Office-based opioid treatment may be particularly advantageous for reaching persons with OUD who are already engaged in primary care and offers an alternative for patients who can not access methadone treatment programs . Challenges include a variable scope of psychosocial services and structure required for management of complex patients .
MS22020	*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 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 Although electrical stimulation of the pre central gyrus ( MCS ) is emerging as a promising technique for pain control , its mechanisms of action remain obscure , and its application largely empirical . Using positron emission tomography ( PET ) we studied regional changes in cerebral flood flow ( rCBF ) in 10 patients undergoing motor cortex stimulation for pain control , seven of whom also underwent somatosensory evoked potentials and nociceptive spinal reflex recordings . The most significant MCS-related increase in rCBF concerned the ventral-lateral thalamus , probably reflecting cortico-thalamic connections from motor areas . CBF increases were also observed in medial thalamus , anterior cingulate/orbitofrontal cortex , anterior insula and upper brainstem ; conversely , no significant CBF changes appeared in motor areas beneath the stimulating electrode . Somatosensory evoked potentials from SI remained stable during MCS , and no rCBF changes were observed in somatosensory cortex during the procedure . Our results suggest that descending axons , rather than apical dendrites , are primarily activated by MCS , and highlight the thalamus as the key structure mediating functional MCS effects . A model of MCS action is proposed , whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in pain-related structures receiving afferents from these nuclei , including the medial thalamus , anterior cingulate and upper brainstem . MCS could influence the affective-emotional component of chronic pain by way of cingulate/orbitofrontal activation , and lead to descending inhibition of pain impulses by activation of the brainstem , also suggested by attenuation of spinal flexion reflexes . In contrast , the hypothesis of somatosensory cortex activation by MCS could not be confirmed by our results OBJECTIVE There is growing interest in neuropsychiatry for repetitive transcranial magnetic stimulation ( rTMS ) as a neuromodulatory treatment . However , there are limitations in interpreting rTMS effects as a real consequence of physiological brain changes or as placebo-mediated unspecific effects , which may be particularly strong in psychiatric patients . This is due to the fact that existing sham rTMS procedures are less than optimal . A new placebo tool is introduced here , called real electro-magnetic placebo ( REMP ) device , which can simulate the scalp sensation induced by the real TMS , while leaving both the visual impact and acoustic sensation of real TMS unaltered . METHODS Physical , neurophysiological and behavioural variables of monophasic and biphasic single-pulse TMS and biphasic 1Hz and 20Hz rTMS procedures ( at different intensities ) were tested in subjects who were expert or naïve of TMS . Results of the real TMS were compared with those induced by the REMP device and with two other currently used sham procedures , namely the commercially available Magstim sham coil and tilting the real coil by 90 degrees . RESULTS The REMP device , besides producing scalp sensations similar to the real TMS , attenuated the TMS-induced electric field ( as measured by a dipole probe ) to a biologically inactive level . Behaviourally , neither expert nor naïve TMS subjects identified the " coil at 90 degrees " or the " Magstim sham coil " as a real TMS intervention , whilst naïve subjects were significantly more likely to identify the REMP-attenuated TMS as real . CONCLUSIONS The " goodness of sham " of the REMP device is demonstrated by physical , neurophysiological , and behavioural results . SIGNIFICANCE Such placebo TMS is superior to the available sham procedures when applied on subjects naïve to TMS , as in case of patients undergoing a clinical rTMS trial Background Many double-blind clinical trials of transcranial direct current stimulation ( tDCS ) use stimulus intensities of 2 mA despite the fact that blinding has not been formally vali date d under these conditions . The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding . Methods A r and omised double blind crossover trial . 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory . Participants attended for two separate sessions . In each session , they completed a word memory task , then received active or sham tDCS ( order r and omised ) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task . They then judged whether they believed they had received active stimulation and rated their confidence in that judgement . The blinded assessor noted when red marks were observed at the electrode sites post-stimulation . Results tDCS at 2 mA was not effectively blinded . That is , participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session ( kappa level of agreement ( κ ) 0.28 , 95 % confidence interval ( CI ) 0.09 to 0.47 p = 0.005 ) and the second session ( κ = 0.77 , 95%CI 0.64 to 0.90 ) , p = < 0.001 ) indicating inadequate participant blinding . Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation ( session one , κ = 0.512 , 95%CI 0.363 to 0.66 , p<0.001 ; session two , κ = 0.677 , 95%CI 0.534 to 0.82 ) indicating inadequate assessor blinding . Conclusions Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate . Positive results from such studies should be interpreted with caution OBJECTIVE Brain polarization in the form of transcranial direct current stimulation ( tDCS ) , which influences motor function and learning processes , has been proposed as an adjuvant strategy to enhance training effects in Neurorehabilitation . Proper testing in Neurorehabilitation requires double-blind sham-controlled study design s. Here , we evaluated the effects of tDCS and sham stimulation ( SHAM ) on healthy subjects and stroke patients ' self-report measures of attention , fatigue , duration of elicited sensations and discomfort . METHODS tDCS or SHAM was in all cases applied over the motor cortex . Attention , fatigue , and discomfort were self rated by study participants using visual analog scales . Duration of perceived sensations and the ability to distinguish tDCS from Sham sessions were determined . Investigators question ing the patients were blind to the intervention type . RESULTS tDCS and SHAM elicited comparably minimal discomfort and duration of sensations in the absence of differences in attention or fatigue , and could not be distinguished from SHAM by study participants nor investigators . CONCLUSIONS Successful blinding of subjects and investigators and ease of application simultaneously with training protocol s supports the feasibility of using tDCS in double-blind , sham-controlled r and omized trials in clinical Neurorehabilitation . SIGNIFICANCE tDCS could evolve into a useful tool , in addition to TMS , to modulate cortical activity in Neurorehabilitation Output:	We did not find evidence that rTMS improved disability . We found no evidence relating to the effectiveness of CES on disability . We found evidence of small study bias in the tDCS analyses . We did not find evidence that tDCS improved disability . We did not find evidence that low-frequency rTMS , rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain .
MS22021	*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 determine the safety and efficacy of induction with rabbit antithymocyte globulin ( RATG ) compared with interleukin-2 receptor antagonists in a racially diverse kidney transplant patient population under modern immunosuppression . Background : The optimal induction therapy in patients at risk for rejection , particularly black recipients , in the modern era of immunosuppression with flow cytometry-based cross-matching is unclear . Methods : This was a prospect i ve , risk-stratified , r and omized , single-center , open-label study of 200 consecutively enrolled patients in a large academic teaching center . Patients were r and omized to receive either daclizumab or basiliximab versus RATG for induction in combination with tacrolimus , mycophenolate mofetil , and corticosteroids . Patients were stratified between groups to ensure equal numbers of black , retransplants , high panel reactive antibodies ( PRAs ) ( > 20 % ) , and prolonged cold ischemic times ( > 24 hours ) in each group . Primary outcome measure is treatment efficacy defined as the incidence of biopsy-proven acute rejection and estimated creatinine clearance . Patients were followed up for 12 months . Renal transplant recipients were included if they were adult ( ≥18 years old ) and received an allograft from a deceased , living unrelated , or nonhuman leukocyte antigen identical living-related donor . Results : A total of 200 patients ( n = 98 in the interleukin-2 receptor antagonists , and n = 102 in the RATG ) were enrolled from February 2009 through July 2011 . One-year acute rejection rates were low and similar between groups ( 10 % in the interleukin-2 receptor antagonist group vs 6 % in the RATG group ; P = 0.30 ) . Creatinine clearance was also similar between groups ( interleukin-2 receptor antagonist group 56 ± 20 mL/min per 1.73 m2 vs RATG group 55 ± 22 mL/min per 1.73 m2 ; P = 0.73 ) . Sub analysis of recipient race revealed that in blacks only RATG was protective against 6- and 12-month acute rejection , without an increased risk of infection . Induction did not affect rejection rates according to recipient calculated PRAs ; however , RATG was associated with an increased risk of BK virus in low-PRA patients . Conclusions and Relevance : RATG induction provides improved protection against early acute rejection in black renal transplant recipients , whereas sensitized patients do not seem to demonstrate a similar benefit from this therapy . This study is registered at Clinical trials.gov ( NCT00859131 ) We conducted a single-center prospect i ve double-arm open-labeled study on kidney transplant patients from 2010 to 2011 to evaluate the efficacy of induction therapy using low , single-dose rabbit-antithymocyte globulin ( r-ATG ) , 1.5 mg/kg on Day 0 ( n = 80 , 60 males , mean age 35.9 years ) , versus basiliximab ( Interleukin-2 blocker ) 20 mg on Days 0 and 4 ( n = 20 , 12 males , mean age 45.1 years ) on renal allograft function in terms of serum creatinine ( SCr ) , rejection and infection episodes and patient/graft survival and cost . Demographic and post-transplant follow-up including immunosuppression was similar in both groups . In the r-ATG group , donors were unrelated ( spouse , n = 25 ) , deceased ( n = 31 ) and parents/siblings ( others ) , with a mean HLA match of 1.58 . Donors in the basiliximab group were living unrelated ( spouse , n = 15 ) and deceased ( n = 5 ) , with a mean HLA match of 1.56 . No patient/graft was lost in the r-ATG group over a mean of one year follow-up , and the mean SCr was 1.28 mg/dL with 7.5 % acute rejection ( AR ) episodes ; infections were also not observed . In the basiliximab group , over the same period of follow-up , there was 95 % death-censored graft survival , and the mean SCr was 1.23 mg/dL with 10 % AR episodes . One patient died due to bacterial pneumonia and one succumbed to coronary artery disease ; one graft was lost due to uncontrolled acute humoral and cellular rejection . The cost of r-ATG and basiliximab were $ 600 and $ 2500 , respectively . We conclude that induction immunosuppressive therapy with a low-dose r-ATG may be a better option as compared with basiliximab in terms of graft function , survival and cost benefit in kidney transplant patients BACKGROUND Induction therapy reduces the frequency of acute rejection and delayed graft function after transplantation . A rabbit antithymocyte polyclonal antibody or basiliximab , an interleukin-2 receptor monoclonal antibody , is most commonly used for induction . METHODS In this prospect i ve , r and omized , international study , we compared short courses of antithymocyte globulin and basiliximab in patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor . Patients taking cyclosporine , mycophenolate mofetil , and prednisone were r and omly assigned to receive either rabbit antithymocyte globulin ( 1.5 mg per kilogram of body weight daily , 141 patients ) during transplantation ( day 0 ) and on days 1 through 4 or basiliximab ( 20 mg , 137 patients ) on days 0 and 4 . The primary end point was a composite of acute rejection , delayed graft function , graft loss , and death . RESULTS At 12 months , the incidence of the composite end point was similar in the two groups ( P=0.34 ) . The antithymocyte globulin group , as compared with the basiliximab group , had lower incidences of acute rejection ( 15.6 % vs. 25.5 % , P=0.02 ) and of acute rejection that required treatment with antibody ( 1.4 % vs. 8.0 % , P=0.005 ) . The antithymocyte globulin group and the basiliximab group had similar incidences of graft loss ( 9.2 % and 10.2 % , respectively ) , delayed graft function ( 40.4 % and 44.5 % ) , and death ( 4.3 % and 4.4 % ) . Though the incidences of all adverse events , serious adverse events , and cancers were also similar between the two groups , patients receiving antithymocyte globulin had a greater incidence of infection ( 85.8 % vs. 75.2 % , P=0.03 ) but a lower incidence of cytomegalovirus disease ( 7.8 % vs. 17.5 % , P=0.02 ) . CONCLUSIONS Among patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor , induction therapy consisting of a 5-day course of antithymocyte globulin , as compared with basiliximab , reduced the incidence and severity of acute rejection but not the incidence of delayed graft function . Patient and graft survival were similar in the two groups . ( Clinical Trials.gov number , NCT00235300 [ Clinical Trials.gov ] . ) Background / Aims : The long-term evaluation of basiliximab induction therapy has not been addressed yet . We aim to evaluate its long-term effects in living related donor kidney transplantation . Methods : 100 adult recipients with their first kidney allograft were r and omized into two treatment groups – one group received basiliximab and the second served as a control . All patients received a maintenance triple immunosuppressive therapy ( steroids , cyclosporine microemulsion and azathioprine ) and were closely followed for 5 years . Results : Basiliximab significantly reduced the proportion of patients who experienced an acute rejection in the first year ( 18/50 ) when compared to the control group ( 31/50 ) and in 5 years ( 27/50 ) when compared to ( 36/50 ) the controls . The cumulative steroid dose used throughout the study was significantly lower in the basiliximab group . The overall incidence of post-transplant complications was comparable between the two treatment groups . There was no significant difference in patients and graft survival ; 5-year patient and graft survival were 100 and 86 % for basiliximab , and 96 and 88 % for the control group respectively . Conclusion : Although routine basiliximab induction significantly reduces the incidence of acute rejection , its beneficial long-term effects on graft function and patient and graft survival are not yet evident Background . Sequential anti-thymocyte globulins (ATG)/cyclosporine immunosuppression has two main advantages : delayed introduction of the nephrotoxic drug cyclosporine and prevention of acute rejection . Basiliximab , a recently developed chimeric monoclonal antibody that selectively depletes the minor sub population of activated T lymphocytes , has been shown to reduce the incidence of acute rejection when used with cyclosporine introduced on day 1 . Methods . This open , r and omized , multicenter study was undertaken to compare the safety and efficacy of ATG versus basiliximab induction therapy ( IT ) with delayed introduction of cyclosporine for microemulsion ( Neoral ) in 105 low immunologic risk renal-transplant patients receiving mycophenolate mofetil and steroids . Results . One-year patient and graft survival rates were 98.1 % and 94.2 % , respectively , in the basiliximab group ( n=52 ) , and 98.1 % and 96.2 % in the ATG group ( n=53 ) . The incidence of biopsy-confirmed acute rejection was comparable ( basiliximab 9.6 % , ATG 9.4 % ) , as were key parameters of renal function , notably serum creatinine levels , time-to-nadir serum creatinine , and the number of patients requiring posttransplantation dialysis ( basiliximab 28.8 % , ATG 30.2 % ) . However , significantly fewer patients in the basiliximab group experienced cytomegalovirus ( CMV ) infection , leukopenia , and thrombocytopenia , and this without any significant difference in any other key safety parameters ( including the incidences of serum sickness , fever , lymphoma , and infections in general ) . Conclusions . Both ATG and basiliximab , when used for IT in a sequential protocol , are equally effective in terms of graft and patient survival as well as at preventing acute rejection . However , basiliximab is associated with a lower incidence of certain key adverse events , namely CMV infection , leukopenia , and thrombocytopenia Background . The aim of this prospect i ve r and omized study was to examine the effect of induction immunosuppression and low initial cyclosporine ( CsA ) on the onset of graft function and its long-term consequences . Methods . During 1999–2001 , 155 patients were r and omized to single 9 mg/kg dose antithymocyte globulin (ATG)-Fresenius ( group A ) or two 20-mg doses of basiliximab ( group B ) with reduced dose CsA or conventional CsA triple therapy without induction ( group C ) . Results . Delayed function ( DGF ) was lower in group A than in groups B or C ( 5.7 % vs. 24.1 % and 15.9 % , P<0.025 ) and need of dialysis was less in groups A and B compared to C ( 10.3 and 10.4 vs. 20.0 days , P<0.05 ) . Acute rejections occurred in 11.3 % , 12.1 % and 20.5 % , and the mean ( median ) time to rejection was 16 ( 13 ) , 97 ( 46 ) and 101 ( 35 ) days in groups A , B , and C , respectively ( P<0.005 ) . One- and 5-year graft survivals ( GS ) were 98.1 % and 90.6 % ( group A ) , 96.6 % and 96.6 % ( group B ) , and 93.2 % and 84.1 % ( group C ) . Five-year GS was significantly better in group B than in group C ( P<0.05 ) . The death censored 5-year GS in groups A , B , and C were 94.3 % , 96.6 % , and 90.0 % ( P = NS ) . Single high-dose ATG induction was associated with hemodynamic and pulmonary disturbances without , however , serious or long-term consequences . Conclusions . ATG induction significantly reduced DGF . Both induction regimens together with low initial CsA led to significantly less posttransplant dialysis and excellent survival . The high dose ATG was associated with significant hemodynamic and pulmonary side effects during drug infusion Background . The purpose of this study was to determine the impact of antilymphocyte globulin (ALG)-induction on long-term outcomes of postrenal transplantation . Methods . Between January 1985 and January 1986 Output:	Conclusion Induction therapy of basiliximab has similar short-time effects on the recipients in renal transplantation compared with that of ATG . However , regarding the long-term effect , as represented by the rate of neoplasm , basiliximab has a significant advantage
MS22022	*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 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 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 of incidence of EV was 5 % ( 95%CI : 0.8 - 8.2 % ) at 1 year and 28 % ( 21.0 - 35.0 % ) at 3 years . The rate of EV progression was 12 % ( 5.6 - 18.4 % ) at 1 year and 31 % ( 21.2 - 40.8 % ) at 3 years . Post-alcoholic origin of cirrhosis , Child-Pugh 's class ( B or C ) and the finding of red wale marks at first examination were predictors for the variceal progression . The two-years risk of bleeding from EV was higher in patients with small varices upon enrollment than in those without varices : 12 % ( 95 % CI : 5.2 - 18.8 % ) vs. 2 % ( 0.1 - 4.1 % ) ; ( P<0.01 ) . Predictor for bleeding was the presence of red wale marks at first endoscopy . CONCLUSIONS In patients with no or small EV , endoscopy surveillance should be planned taking into account cause and degree of liver dysfunction This is one of a series of statements discussing the utilization of GI endoscopy in common clinical situations . The St and ards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text . In preparing this guideline , a MEDLINE literature search was performed and additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants . When little or no data exist from well design ed prospect i ve trials , emphasis is given to results from large series and reports from recognized experts . Guidelines for appropriate utilization of endoscopy are based on a critical review of the available data and expert consensus . Further controlled clinical studies are needed to clarify aspects of this statement , and revision may be necessary as new data appear . Clinical consideration may justify a course of action at variance to these recommendations . This document is intended to provide the principles by which credentialing organizations may create policy and practical guidelines for granting privileges to perform capsule endoscopy . For information on credentialing for other endoscopic procedures , please refer to ‘ ‘ Guidelines for Credentialing and Granting Privileges for Gastrointestinal Endoscopy . ’ BACKGROUND AND STUDY AIMS Esophagogastroduodenoscopy ( EGD ) is the most effective method for examining the upper gastrointestinal tract , and particularly for evaluating portal hypertension in cirrhotic patients , especially for screening purpose s. The aim of this study was to assess the feasibility , safety , accuracy , and tolerance of PillCam ESO capsule endoscopy for this indication . PATIENTS AND METHODS In this prospect i ve study , unse date d EGD and capsule endoscopy examinations were conducted on the same day in cirrhotic patients at the time of diagnosis . The patients quantified the tolerability ( relative to pain , nausea , choking sensations , etc . ) of the two procedures using a 100-mm visual analogue scale . The time required for the recording and for diagnosis with the capsule examination were documented , as were the patients ' preferences in comparison with EGD . Two independent endoscopists blinded to the EGD diagnoses assessed the diagnostic accuracy of the images obtained . RESULTS Twenty-one patients were included in the study ( mean age 62 , mean Model for End-Stage Liver Disease score 10.5 , mean Child-Pugh score 7.3 ) . The procedure was safe . One patient was unable to swallow the capsule . The mean recording time was 213 s ( range 6 - 1200 s ) ; the procedure accurately assessed the presence or absence of esophageal varices in 16 of 19 patients ( 84.2 % ) ; and it correctly indicated a need for primary prophylaxis ( esophageal varices of grade 2 or more and /or red signs ) in 100 % of cases . The tolerability of the capsule endoscopy examination was significantly better , and all of the patients preferred capsule endoscopy to EGD ( which was transnasal in 11 patients ) . CONCLUSIONS Capsule endoscopy was feasible , safe , accurate , highly acceptable , and preferred by cirrhotic patients undergoing screening for portal hypertension . This new technique requires further and more extensive evaluation , as well as assessment of its cost-effectiveness OBJECTIVES : Esophagogastroduodenoscopy ( EGD ) is the st and ard method for the diagnosis of esophago-gastric varices . The aim of this prospect i ve multicenter study was to evaluate the PillCam esophageal capsule endoscopy ( ECE ) for this indication . METHODS : Patients presenting with cirrhotic or noncirrhotic portal hypertension underwent ECEfollowed by EGD at the time of diagnosis . Capsule recordings were blindly read by two endoscopists . RESULTS : A total of 120 patients ( 72 males , mean age : 58 years ; mean Child – Pugh score : 7.2 ) were included . Esophageal varices were detected in 74 patients . No adverse event was observed after either EGD or ECE . Seven ( 6 % ) patients were unable to swallow the capsule . The mean recording time was 204 s ( range 1–876 ) . Sensitivity , specificity , negative predictive value , and positive predictive value of ECE for the detection of esophageal varices were 77 % , 86 % , 69 % , and 90 % , respectively . Sensitivity , specificity , negative and positive predictive Output:	Discussion : Wireless esophageal capsule endoscopy is well tolerated and safe in patients with liver cirrhosis and suspicion of portal hypertension . The sensitivity of capsule endoscopy is not currently sufficient to replace EGD as a first exploration in these patients , but given its high accuracy , it may have a role in cases of refusal or contraindication to EGD
MS22023	*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 Trastuzumab , an anti-HER2/neu monoclonal antibody , is thought to promote HER2/neu receptor internalization and /or turnover . This study was design ed to investigate the kinetics of trastuzumab treatment on tumor cells with varying levels of HER2/neu expression and to determine the effect of trastuzumab on HER2/neu-specific cytotoxic T lymphocyte – mediated lysis . Methods Three cell lines with varying levels of HER2/neu expression were incubated with varying doses of trastuzumab at multiple time points . Trastuzumab binding and HER2/neu expression were determined . Peripheral blood mononuclear cells from three HLA-A2 + healthy donors and four E75 peptide – vaccinated patients were stimulated with HER2/neu-derived peptides and tested in st and ard chromium release cytotoxicity assays with HER2/neu+ tumor cells pretreated with trastuzumab . Results Treatment of tumor cells with 10 μg/mL of trastuzumab in an overnight incubation result ed in saturation of cell-surface HER2/neu receptors . At higher doses , trastuzumab staining and HER2/neu expression decreased in a time-dependent manner . Pretreatment of tumor cells with trastuzumab result ed in increases in specific cytotoxicity by peptide-stimulated cytotoxic T lymphocytes from HLA-A2 + donors over untreated cells by an average of 5.6 % and 15.3 % ( P = .0002 ) for doses of 10 and 50 μg/mL , respectively . In similar experiments involving peripheral blood mononuclear cells obtained from immunized patients , the average specific cytotoxicity for untreated cells was 34.2 % ± 1.3 % vs. 40.6 % ± 2.5 % ( P = .035 ) and 40.7 % ± 1.6 % ( P = .0005 ) for those treated with 10 and 50 μg/mL , respectively . Conclusions Our data suggest that pretreatment of breast cancer cells with trastuzumab induces turnover of the HER2/neu protein and enhanced killing by HER2/neu peptide – stimulated CTLs . This increased lysis occurs regardless of the degree of HER2/neu expression and seems more pronounced in vaccinated patients . These findings support further investigation into the use of combination immunotherapy with trastuzumab and HER2/neu peptide – based vaccines Purpose : HER2/neu , a source of immunogenic peptides , is expressed in > 75 % of breast cancer patients . We have conducted clinical trials with the HER2/neu E75 peptide vaccine in breast cancer patients with varying levels of HER2/neu expression . Vaccine response based on HER2/neu expression level was analyzed . Experimental Design : Patients were stratified by HER2/neu expression . Low expressors ( n = 100 ) were defined as HER2/neu immunohistochemistry ( IHC ) 1 + to 2 + or fluorescence in situ hybridization < 2.0 . Overexpressors ( n = 51 ) were defined as IHC 3 + or fluorescence in situ hybridization ≥ 2.0 . Additional analyses were done stratifying by IHC status ( 0 - 3 + ) . St and ard clinocopathlogic factors , immunologic response ( in vivo delayed-type hypersensitivity reactions ; ex vivo human leukocyte antigen A2:immunoglobulin G dimer assay ) , and clinical responses ( recurrence ; mortality ) were assessed . Results : Low-expressor ( control , 44 ; vaccinated , 56 ) versus overexpressor patients ( control , 22 ; vaccinated , 29 ) were assessed . Low expressors , overexpressors , and most IHC-status vaccinated groups responded immunologically . Vaccinated low-expressor patients had larger maximum immunologic responses compared with overexpressor patients ( P = 0.04 ) , and vaccinated IHC 1 + patients had increased long-term immune response ( P = 0.08 ) . More importantly , compared with controls , low-expressor patients had a mortality reduction ( P = 0.08 ) . The largest decrease in mortality was seen in IHC 1 + patients ( P = 0.05 ) . In addition , a subset of overexpressor patients ( n = 7 ) received trastuzumab before vaccination , and this combination seems safe and immunologically beneficial . Conclusions : Most patients with various levels of HER2/neu expression responded immunologically and seemed to benefit from vaccination . The low expressors , specifically IHC 1 + patients , had more robust immunologic responses and may derive the greatest clinical benefit from the E75 vaccine Ideally , vaccines should be design ed to elicit long-lived immunity . The goal of this study was to determine whether HER-2/neu peptide-specific CD8 + T-cell immunity could be elicited using an immunodominant HER-2/neu-derived HLA-A2 peptide alone in the absence of exogenous help . Granulocyte macrophage colony-stimulating factor ( GM-CSF ) was used as adjuvant . Six HLA-A2 patients with HER-2/neu-overexpressing cancers received 6 monthly vaccinations with a vaccine preparation consisting of 500 microg of HER-2/neu peptide , p369 - 377 , admixed with 100 microg of GM-CSF . The patients had either stage III or IV breast or ovarian cancer . Immune responses to the p369 - 377 were examined using an IFN-gamma enzyme-linked immunosorbent spot assay . Before vaccination , the median precursor frequency ( range ) , defined as precursors per 10(6 ) peripheral blood mononuclear cell , to p369 - 377 was 0 ( no range ) . After vaccination , the median precursor frequency to p369 - 377 in four evaluable patients was 0 ( 0 - 116 ) . Overall , HER-2/neu peptide-specific precursors developed to p369 - 377 in two of four evaluable subjects . The responses were short-lived and not detectable at 5 months after the final vaccination . Immunocompetence was evident , because patients had detectable enzyme-linked immunosorbent spot responses to tetanus toxoid and influenza . These results demonstrate that HER-2/neu MHC class I epitopes can induce HER-2/neu peptide-specific IFN-gamma-producing CD8 + T cells . However , the magnitude of the responses were low , as well as short-lived , suggesting that CD4 + T-cell help is required for lasting immunity to this epitope E75 , a HER‐2/neu‐derived peptide , was administered as a preventive vaccine with granulocyte‐macrophage – colony‐stimulating factor ( GM‐CSF ) in disease‐free lymph node‐positive ( NP ) and lymph node‐negative ( NN ) breast cancer ( BCa ) patients . The optimal biologic dose ( OBD ) was determined based on toxicity and immunologic response PURPOSE E75 is an immunogenic peptide from the HER2/neu protein that is highly expressed in breast cancer . We are conducting a clinical trial of an E75 + granulocyte-macrophage colony-stimulating factor vaccine to assess safety , immunologic response , and the prevention of clinical recurrences in patients with disease-free , node-positive breast cancer ( NPBC ) . PATIENTS AND METHODS Fifty-three patients with NPBC were enrolled and HLA typed . HLA-A2 + patients ( n = 24 ) were vaccinated , and HLA-A2- patients ( n = 29 ) are observed prospect ively as clinical controls . Local/systemic toxicities , immunologic responses , and time to recurrence are being measured . RESULTS Only minor toxicities have occurred ( one grade 3 [ 4 % ] ) . All patients have demonstrated clonal expansion of E75-specific CD8+T cells that lysed HER2/neu-expressing tumor cells . An optimal dosage and schedule have been established . Patients have developed delayed-type hypersensitivity reactions to E75 postvaccination compared with controls ( 33 v 7 mm ; P < .01 ) . HLA-A2 + patients have been found to have larger , more poorly differentiated , and more hormonally insensitive tumors compared to HLA-A2- patients . Despite this , the only two deaths have occurred in the control group . The disease-free survival in the vaccinated group is 85.7 % compared to 59.8 % in the controls at 22 months ' median follow-up with a recurrence rate of 8 % compared to 21 % , respectively ( P < .19 ) . Median time to recurrence in the vaccinated patients was prolonged ( 11 v 8 months ) , and recurrence correlated with a weak delayed-type hypersensitivity response . CONCLUSION This HER2/neu ( E75 ) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo . Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC The authors conducted exploratory phase 1‐2 clinical trials vaccinating breast cancer patients with E75 , a human leukocyte antigen ( HLA ) A2/A3–restricted HER‐2/neu ( HER2 ) peptide , and granulocyte‐macrophage colony‐stimulating factor . The vaccine is given as adjuvant therapy to prevent disease recurrence . They previously reported that the vaccine is safe and effective in stimulating expansion of E75‐specific cytotoxic T cells . Here , they report 24‐month l and mark analyses of disease‐free survival ( DFS ) Background E75 , a HER2/neu immunogenic peptide , is expressed in breast cancer ( BCa ) . We have performed clinical trials of E75 + GM-CSF vaccine in disease-free , node-positive and node-negative BCa patients at high recurrence risk and recurrences were noted in both control and vaccine groups . Methods Among the 186 BCa patients enrolled , 177 completed the study . Patients were HLA typed ; the HLA-A2+/A3 + patients were vaccinated ; HLA-A2−/A3− patients were followed as controls . St and ard clinicopathological factors , immunologic response to the vaccine , and recurrences were collected and assessed . Results The control group recurrence rate was 14.8 and 8.3 % in the vaccinated group ( P = 0.17 ) . Comparing the 8 vaccinated recurrences ( V-R ) to the 88 vaccinated nonrecurrent patients ( V-NR ) , the V-R group had higher nodal stage ( ≥N2 : 75 vs. 5 % , P = 0.0001 ) and higher grade tumors ( % grade 3 : 88 vs. 31 % , P = 0.003 ) . The V-R group did not fail to respond immunologically as noted by equivalent dimer responses and post-DTH responses . Compared to control recurrent patients ( C-R ) , V-R patients trended toward higher- grade tumors and hormone-receptor negativity . C-R patients had 50 % bone-only recurrences , compared to V-R patients with no bone-only recurrences ( P = 0.05 ) . Lastly , V-R mortality rate was 12.5 % compared with 41.7 % for the C-R group ( P = 0.3 ) . Conclusions The vaccinated patients who recurred had more aggressive disease compared to V-NR patients . V-R patients had no difference in immune response to the vaccine either in vitro or in vivo . V-R patients , when compared to C-R patients , trended towards more aggressive disease , decreased recurrence rates , decreased mortality , and no bone-only recurrences We used the Luminex assay to compare serum cytokine profiles of breast cancer patients ( BCa ) to healthy controls , node-positive ( NP ) patients to node-negative ( NN ) , and pre- and post-vaccination serum of BCa vaccinated with a HER2/neu E75 peptide vaccine . Sera from 36 pre- and post-vaccination BCa , ( 12 NP and 24 NN ) and 13 healthy , female donors , were evaluated using Luminex technology . Levels of 22 cytokines consisting of interleukin (IL)-1alpha , -1beta , -2 , -4 , -5 , -6 , -7 , -8 , -10 , -12 , -13 , -15 , -17 , IFN-gamma , G-CSF , GM-CSF , TNF-alpha , IP-10 , MIP-1alpha , RANTES , eotaxin and monocyte chemotactic protein-1 ( MCP-1 ) were assessed . Six of 22 cytokines showed significant differences between BCa and healthy controls . MCP-1 , eotaxin , RANTES and GM-CSF levels were significantly elevated in BCa ( P<0.009 ) and IL-1alpha and IL-4 levels were significantly decreased in BCa ( P<0.015 ) . Cytokine levels were generally elev Output:	Meta‐ analysis of delayed‐type hypersensitivity)DTH ( reactions and CD8+‐T cell levels , as immune responses , displayed the significant differences in the vaccinated groups compared to their non‐vaccinated counterparts . In addition , the recurrence , and the overall and the disease‐free survival were significantly different in the vaccinated subjects versus the control . Evaluation of the local and systemic toxicity of the E75 peptide vaccine demonstrated the minimal side effects .
MS22024	*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 : Although sexual dysfunction has been reported in patients with hepatitis C virus ( HCV ) infection , little is known about this association . The aims of this study were to determine the prevalence of sexual dysfunction among men with chronic HCV infection and to evaluate the impact of sexual dysfunction on health-related quality of life ( HRQOL ) . METHODS : We prospect ively enrolled 112 HCV positive men and 239 HCV negative controls , and all patients completed vali date d question naires to assess sexual function ( Brief Male Sexual Function Inventory [ BMSFI ] ) , depression ( Beck Depression Inventory ) , and HRQOL ( Medical Outcomes Study Short Form-36 ) . The BMSFI assessed sexual drive , erection , ejaculation , sexual problem assessment , and overall sexual satisfaction . RESULTS : HCV positive men had significantly more sexual dysfunction than control subjects across all five domains of the BMFSI . In addition , HCV-infected men were significantly more likely than controls to not be sexually satisfied ( 53.6 % vs 28.9 % , p < 0.001 ) and this remained statistically significant after adjusting for age , race , and other potential confounding variables ( OR = 3.36 ; 95 % CI , 1.59–7.13 ) . In the 241 individuals without depression , HCV positive men were significantly more likely to not be sexually satisfied as compared with control subjects ( 47.5 % vs 11.0 % , p < 0.001 ) . HCV-infected men who were not sexually satisfied scored significantly worse in six of eight domains of HRQOL as compared with HCV-infected men who were sexually satisfied . CONCLUSIONS : Sexual dysfunction is highly prevalent in men with chronic HCV infection , is independent of depression , and is associated with a marked reduction in HRQOL The effects of interferon-alpha ( IFN-alpha ) , given at a dosage of 6 MU thrice weekly for 12 months , on gonadal function were investigated in 18 males affected by chronic hepatitis C. Periodically , all patients were clinical ly monitored and question ed about sexual function . Gonadotropin and serum and rogen concentrations ( follicle-stimulating hormone , luteinizing hormone , total testosterone , free testosterone , and rostenedione , dehydroepi and rosterone , dehydroepi and rosterone sulfate , and sex hormone binding globulin ) were tested every 3 months . Ten of 18 patients ( 55 % ) responded to IFN-alpha therapy . Serum total testosterone and sex hormone binding globulin values decreased slightly at the third month of treatment , then returned to baseline values . Serum free testosterone and other sex hormones remained essentially unchanged during IFN-alpha therapy . Four patients ( 22.2 % ) complained of sexual dysfunction ( impaired libido , erectile failure , and impaired ejaculation ) , which was unrelated to any significant hormonal change and resolved after IFN therapy was stopped . Serum sex hormones values did not differ between responders and nonresponders to IFN-alpha . This study indicates that 12 months treatment with 6 MU of IFN-alpha thrice weekly does not significantly affect gonadal function in men with chronic hepatitis C. The sexual dysfunction observed could be ascribed to such other side effects of IFN as asthenia , fatigue , or anxiety , or it could have a psychologic basis OBJECTIVE Recombinant human interferon alpha ( rhIFN-alpha ) is used therapeutically in malignant disorders and chronic hepatitis . The present study was assessed to study the effects of rhIFN-alpha on the hypothalamic-pituitary-testicular ( HPT ) axis . DESIGN AND METHODS We performed a saline-controlled cross-over study in six healthy men , sequentially measuring the serum concentrations of gonadotropins , testosterone , the free and rogen index ( FAI ) and sex hormone-binding globulin ( SHBG ) after a bolus subcutaneous injection of rhIFN-alpha . RESULTS rhIFN-alpha induced a sustained decrease of both testosterone ( from 19.5+/-1.88 to a nadir of 5.49+/-0.51nmol/l at the end of the study ) and FAI ( from 98.7+/-14.7 to a nadir of 32 . 1+/-5.3 at the end of the study ) , whereas concentrations of LH , FSH and SHBG were not different between the two studies . CONCLUSIONS Our results suggest that rhIFN-alpha affects the HPT axis at the testicular level , either directly or indirectly , and changes feedback relationships between the pituitary and the testis INTRODUCTION In men , erectile dysfunction ( ED ) is an important issue . Data concerning ED in men with end-stage liver disease ( ESLD ) is limited , and the risk factors for ED in this population are still unknown . AIMS To determine the prevalence , timescale , and risk factors for ED in ESLD patients c and i date s to liver transplantation . METHODS Patients c and i date s for a liver transplantation were asked to participate in a mailed survey about sexual function . Among the 123 eligible men , 98 ( 84 % ) agreed to complete the question naire . MAIN OUTCOME MEASURES The quality of erection was evaluated using the five-item International Index of Erectile Function ( IIEF-5 ) score , and satisfaction for sexuality , using the patient-baseline Treatment-Satisfaction Scale ( TSS ) score . Other questions also focused on patient perception of changes over time . RESULTS On the overall population , 28 patients ( 29 % ) were nonsexually active . Among the 70 patients who were sexually active , 52 patients ( 74 % ) had ED . Regarding the development of ED , 50 % of the patients perceived that a deterioration of erectile function occurred within the six previous months . The absence of sexual activity was more frequent in hepatitis B or C patients ( P = 0.02 ) . The risk factors for ED were alcohol intake ( P = 0.03 ) , tobacco use ( P = 0.03 ) , and cardiovascular disease ( P = 0.004 ) . The significant risk factors for having a low TSS score were having viral hepatitis ( P = 0.01 ) , and cardiovascular disease ( P = 0.01 ) . CONCLUSION Population of men with ESLD who are c and i date s for a liver transplantation is characterized by a high frequency of lack of sexual activity , and by a high prevalence of ED and should be targeted by interventions to improve sexual functioning . These preliminary data need further validation in prospect i ve trial using more comprehensive question naires BACKGROUND & AIMS Compared with Caucasian Americans ( CA ) , African Americans ( AA ) with chronic hepatitis C are less likely to respond to interferon-based antiviral therapy . METHODS In a multicenter treatment trial , 196 AA and 205 CA treatment-naive patients with hepatitis C virus ( HCV ) genotype 1 infection were treated with peginterferon alfa-2a ( 180 microg/wk ) and ribavirin ( 1000 - 1200 mg/day ) for up to 48 weeks . The primary end point was sustained virologic response ( SVR ) . RESULTS Baseline features were similar among AA and CA , including HCV-RNA levels and histologic severity , but AA had higher body weights , a higher prevalence of diabetes and hypertension , and lower alanine transaminase levels ( P < .001 for all ) . The SVR rate was 28 % in AA and 52 % in CA ( P < .0001 ) . Racial differences in viral responses were evident as early as treatment week 4 . Breakthrough viremia was more frequent among AA than CA ( 13 % vs 6 % , P = .05 ) ; relapse rates were comparable ( 32 % vs 25 % , P = .30 ) . Proportions of patients with serious adverse events and dose modifications and discontinuations were similar among AA and CA . In multiple regression analyses , CA had a higher SVR rate than AA ( relative risk , 1.96 ; 95 % confidence interval , 1.48 - 2.60 ; P < .0001 ) . Other factors independently associated with higher SVR included female sex , lower baseline HCV-RNA level , less hepatic fibrosis , and more peginterferon taken . CONCLUSIONS AA with chronic hepatitis C genotype 1 have lower rates of virologic response to peginterferon and ribavirin than CA . These differences are not explained by disease characteristics , baseline viral levels , or amount of medication taken OBJECTIVE OF THE STUDY To report on the results of two projects on chronic hepatitis B in Western Balkans lead by Ioannina , Northwest Greece and Tirana , Albania . METHODS In two prospect i ve projects , HEPAGA I and HEPAGA II which lasted 4 years . In HEPAGA I , serum sample s from 410 Albanians were tested for HBV . In HEPAGA II , health care consumption was recorded in hospitalized patients with chronic hepatitis B. RESULTS HEPAGA I showed that 11.89 % of the Albanians was HBsAg(+ ) and only 21.19 % had HBV immunoprotection . HEPAGA II study included 101 patients . There was a significant difference in hospitalization costs per patient between centers . The Greek patients were significantly older ( p=0.027 ) and there was a significant correlation between age > 50 years and hospitalization costs ( p=0.035 ) . In Greece , hospitalization costs , number of patients admitted and number of hospitalization days per patient were in a remarkable position compared to other causes of hospitalization . CONCLUSIONS The HEPAGA I study showed a decrease in the prevalence of chronic HBV infection in Albania compared to that of the previous decade . The HEPAGA II study demonstrated that health care consumption due to HBV infection is still an important determinant of the overall health consumption in Western Balkans The prevalence and course of sexual dysfunction was evaluated in 221 alcoholic cirrhotic men participating in a double-blind , placebo-controlled study on the effect of oral testosterone treatment on liver disease . At entry , 67 % ( 95 % confidence limits , 61%-74 % ) complained of sexual dysfunction . Sexual dysfunction was significantly ( p less than 0.05 ) associated with lower serum concentrations of testosterone , non-protein-bound testosterone , and non-sex hormone-binding globulin-bound testosterone . The significant associations between sexual dysfunction and non-protein-bound and non-sex hormone-binding globulin-bound testosterone concentrations disappeared , however , when age , ethanol consumption , and severity of liver disease were included as covariates in the analysis . During follow-up ( median 30 mo , range 1 - 48 mo ) sexual dysfunction improved significantly ( p less than 0.05 ) at 6 , 12 , and 24 mo . Furthermore , the reported libido and erectile and ejaculatory function improved significantly at the end of the follow-up period ( p less than 0.01 ) . However , the testosterone-treated patients did not differ significantly from the placebo-treated patients regarding any of the changes in sexual function . In conclusion , oral testosterone treatment does not significantly influence the type or course of sexual dysfunction in alcoholic cirrhotic men . However , sexual function improved after reduction of ethanol consumption in these patients Decrease of libido and erectile dysfunction are reported by male patients during antiviral therapy of chronic hepatitis C , but therapy-associated underlying factors for sexual dysfunction are not well defined . To assess putative contributions of interferon-induced sex hormone changes to sexual dysfunction , we prospect ively investigated changes in free testosterone , total testosterone , dehydroepi and rosterone sulfate , prolactin , sex hormone-binding globulin , FSH and LH levels and psychometric self- assessment scores in 34 male patients treated with interferon alfa-2b ( 5 MIU three times weekly ) (n=19)+ ribavirin ( n=15 ) for 6 - 12 months . Depression was measured by the Hospital Anxiety and Depression Scale . Sexual dysfunction was evaluated by the Symptom Checklist 90 Item Revised and a five-point rating scale assessing sexual arousal disorder . Free and total testosterone decreased significantly during antiviral therapy in close correlation with libido/sexual function . Depression scores increased during therapy and were also significantly associated with sexual dysfunction . However , and rogen levels displayed no significant correlation with depression . These results suggest that interferon-induced decrease in sexual function is associated - but not causally related -with both and rogen reduction and increased depressive symptoms . These findings may affect care for male hepatitis C patients during interferon therapy PURPOSE We assessed the change in confidence , relationships and self-esteem , and its correlation with erectile function in men with ED treated with sildenafil citrate in the first United States based , double-blind , placebo controlled , r and omized trial assessed by the vali date d SEAR . MATERIAL S AND METHODS This 12-week flexible dose ( 25 , 50 or 100 mg ) trial determined change scores from baseline to end of treatment for the 5 SEAR components ( Sexual Relationship domain , Confidence domain , Self-Esteem subscale [ prespecified as the primary end point ] , Overall Relationship subscale and Overall score ) , and their correlations with the IIEF and event log data , as well as correlations between SEAR components and a general efficacy question at the end of treatment . RESULTS Compared with the place Output:	EXPERT OPINION The results of this review have led to the following main observations : i ) there is scarce documentation on the association between CVH and sexual dysfunction ; ii ) hormonal impairment seems to be a major component in the development of erectile dysfunction in CVH ; however , published evidence concerning the contribution of other pathogenetic factors is rare and inconclusive and iii ) available treatment options for CVH potentially contribute to the development of sexual dysfunction in these patients .
MS22025	*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 Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism . There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment . Furthermore , the incidence of such events in these patients is dependent on the achieved International Normalized Ratio ( INR ) . The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR . PATIENTS AND METHODS In a retrospective analysis , the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy . Eligible patients participated in two multicenter , r and omized clinical trials on the initial treatment of venous thromboembolism . Patients were initially treated with heparin ( st and ard or low-molecular weight ) . Treatment with vitamin K antagonists was started within 1 day and continued for 3 months , with a target INR of 2.0 to 3.0 . RESULTS In 1,303 eligible patients ( 264 with malignancy ) , 35 recurrences and 12 bleeds occurred . Patients with malignancy , compared with nonmalignant patients , had a clinical ly and statistically significantly increased overall incidence of recurrence ( 27.1 v 9.0 , respectively , per 100 patient-years ) as well as bleeding ( 13.3 v 2.1 , respectively , per 100 patient-years ) . In both groups of patients , the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0 . CONCLUSION Although adequately dosed vitamin K antagonists are effective in patients with malignant disease , the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy Cancer patients are at high risk for venous thromboembolism ( VTE ) . Laboratory parameters with a predictive value for VTE could help stratify patients into high- or low-risk groups . The cell adhesion molecule P-selectin was recently identified as risk factor for VTE . To investigate soluble P-selectin ( sP-selectin ) in cancer patients as risk predictor for VTE , we performed a prospect i ve cohort study of 687 cancer patients and followed them for a median ( IQR ) of 415 ( 221 - 722 ) days . Main tumor entities were malignancies of the breast ( n = 125 ) , lung ( n = 86 ) , gastrointestinal tract ( n = 130 ) , pancreas ( n = 42 ) , kidney ( n = 19 ) , prostate ( n = 72 ) , and brain ( n = 80 ) ; 91 had hematologic malignancies ; 42 had other tumors . VTE occurred in 44 ( 6.4 % ) patients . In multivariable analysis , elevated sP-selectin ( cutoff level , 53.1 ng/mL , 75th percentile of study population ) was a statistically significant risk factor for VTE after adjustment for age , sex , surgery , chemotherapy , and radiotherapy ( hazard ratio = 2.6 , 95 % confidence interval , 1.4 - 4.9 , P = .003 ) . The cumulative probability of VTE after 6 months was 11.9 % in patients with sP-selectin above and 3.7 % in those below the 75th percentile ( P = .002 ) . High sP-selectin plasma levels independently predict VTE in cancer patients . Measurement of sP-selectin at diagnosis of cancer could help identify patients at increased risk for VTE Summary Background Data : The epidemiology of venous thromboembolism ( VTE ) after cancer surgery is based on clinical trials on VTE prophylaxis that used venography to screen deep vein thrombosis ( DVT ) . However , the clinical relevance of asymptomatic venography-detected DVT is unclear , and the population of these clinical trials is not necessarily representative of the overall cancer surgery population . Objective : The aim of this study was to evaluate the incidence of clinical ly overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and to identify risk factors for VTE . Methods : @RISTOS was a prospect i ve observational study in patients undergoing general , urologic , or gynecologic surgery . Patients were assessed for clinical ly overt VTE occurring up to 30 ± 5 days after surgery or more if the hospital stay was longer than 35 days . All outcome events were evaluated by an independent Adjudication Committee . Results : A total of 2373 patients were included in the study : 1238 ( 52 % ) undergoing general , 685 ( 29 % ) urologic , and 450 ( 19 % ) gynecologic surgery . In-hospital prophylaxis was given in 81.6 % and postdischarge prophylaxis in 30.7 % of the patients . Fifty patients ( 2.1 % ) were adjudicated as affected by clinical ly overt VTE ( DVT , 0.42 % ; nonfatal pulmonary embolism , 0.88 % ; death 0.80 % ) . The incidence of VTE was 2.83 % in general surgery , 2.0 % in gynecologic surgery , and 0.87 % in urologic surgery . Forty percent of the events occurred later than 21 days from surgery . The overall death rate was 1.72 % ; in 46.3 % of the cases , death was caused by VTE . In a multivariable analysis , 5 risk factors were identified : age above 60 years ( 2.63 , 95 % confidence interval , 1.21–5.71 ) , previous VTE ( 5.98 , 2.13–16.80 ) , advanced cancer ( 2.68 , 1.37–5.24 ) , anesthesia lasting more than 2 hours ( 4.50 , 1.06–19.04 ) , and bed rest longer than 3 days ( 4.37 , 2.45–7.78 ) . Conclusions : VTE remains a common complication of cancer surgery , with a remarkable proportion of events occurring late after surgery . In patients undergoing cancer surgery , VTE is the most common cause of death at 30 days after surgery Deep venous thrombosis ( DVT ) and pulmonary embolism ( PE ) are well recognized complications of cancer . However , our current knowledge of this association is derived from studies conducted more than a decade ago . In light of the changes in medical practice and the improvement in cancer care in recent years , a re-evaluation of the relationship between malignancy and venous thrombosis is in order . Of a total of 1041 patients with solid tumors admitted to 3 major medical centers , there were 81 ( 7.8 % ) diagnosed with DVT/PE . Patients were more likely to develop DVT/PE during chemotherapy ( p = .0001 ) . Advanced malignancies ( p = .001 ) , renal carcinoma ( p = .005 ) , pancreatic ( p = .001 ) , gastric ( p = .014 ) and brain tumors ( p = .001 ) were independent variables strongly associated with the occurrence of venous thrombosis . The occurrence of thrombotic events in the population tested in this study did not adversely affect survival ( p = .082 ) . The study identifies subset of patients with cancer at high risk for venous thrombosis . Early prophylaxis with anticoagulants in these patients may be warranted . Most importantly , further clinical trials are desperately awaited to detect possible new trends in the frequency and types of thrombotic events and to better define prevention strategies in cancer patients at risk for thrombosis . The association between venous thromboembolic disease ( VTD ) and malignant neoplastic disorders is well known and has been the subject of several reports for more than a century . There is a general agreement among investigators that thrombotic complications in patients with cancer occur at a rather high frequency , and that other circumstantial factors such as surgery or chemotherapy potentiates this risk . However , several important considerations pertaining to cancer and thrombosis continue to be shrouded in controversy . For example , there are inexplicable differences in the proportion of patients with cancer diagnosed with deep venous thrombosis ( DVT ) or pulmonary embolism ( PE ) reported in the literature . In the absence of large well-controlled studies , one may only postulate on the reasons that contributed to these differences . The inclusion of different types of VTD such as superficial , venous , arterial or vascular access device-induced thrombosis may have led to overestimation of the incidence of these events in patients with underlying malignancy . Another possible explanation for this discrepancy relates to the use of a variety of diagnostic and method ological criteria ranging from observation and clinical suspicion to more invasive procedures result ing in considerable differences in the rate of reported clotting events . Along the same line of discussion , one may argue whether VTD is a r and om event or constitutes a complication that occurs more commonly in patients with distinct characteristics and certain tumor types . To further investigate the association between malignancy and thrombosis , we evaluated 1041 patients with solid tumors for the risk of DVT/PE . The main objectives of the study were to determine the frequency of DVT/PE based on vali date d diagnostic criteria and to identify patients with cancer at high risk for developing these thrombotic episodes . Also , we evaluated the impact of VTD on the survival of these patients BACKGROUND The B-20 study of the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) was conducted to determine whether chemotherapy plus tamoxifen would be of greater benefit than tamoxifen alone in the treatment of patients with axillary lymph node-negative , estrogen receptor-positive breast cancer . METHODS Eligible patients ( n = 2306 ) were r and omly assigned to one of three treatment groups following surgery . A total of 771 patients with follow-up data received tamoxifen alone ; 767 received methotrexate , fluorouracil , and tamoxifen ( MFT ) ; and 768 received cyclophosphamide , methotrexate , fluorouracil , and tamoxifen ( CMFT ) . The Kaplan-Meier method was used to estimate disease-free survival , distant disease-free survival , and survival . Reported P values are two-sided . RESULTS Through 5 years of follow-up , chemotherapy plus tamoxifen result ed in significantly better disease-free survival than tamoxifen alone ( 90 % for MFT versus 85 % for tamoxifen [ P = .01 ] ; 89 % for CMFT versus 85 % for tamoxifen [ P = .001 ] ) . A similar benefit was observed in both distant disease-free survival ( 92 % for MFT versus 87 % for tamoxifen [ P = .008 ] ; 91 % for CMFT versus 87 % for tamoxifen [ P = .006 ] ) and survival ( 97 % for MFT versus 94 % for tamoxifen [ P = .05 ] ; 96 % for CMFT versus 94 % for tamoxifen [ P = .03 ] ) . Compared with tamoxifen alone , MFT and CMFT reduced the risk of ipsilateral breast tumor recurrence after lumpectomy and the risk of recurrence at other local , regional , and distant sites . Risk of treatment failure was reduced after both types of chemotherapy , regardless of tumor size , tumor estrogen or progesterone receptor level , or patient age ; however , the reduction was greatest in patients aged 49 years or less . No subgroup of patients evaluated in this study failed to benefit from chemotherapy . CONCLUSIONS Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria , regardless of age , lymph node status , tumor size , or estrogen receptor status , are c and i date s for chemotherapy PURPOSE A substantial clinical need exists for an alternative to vitamin K antagonists for treating deep-vein thrombosis in cancer patients who are at high risk of both recurrent venous thromboembolism and bleeding . Low-molecular-weight heparin , body-weight adjusted , avoids anticoagulant monitoring and has been shown to be more effective than vitamin-K-antagonist therapy . SUBJECTS AND METHODS Subjects were patients with cancer and acute symptomatic proximal-vein thrombosis . We performed a multi-centre r and omized , open-label clinical trial using objective outcome measures comparing long-term therapeutic tinzaparin subcutaneously once daily with usual-care long-term vitamin-K-antagonist therapy for 3 months . Outcomes were assessed at 3 and 12 months . RESULTS Of 200 patients , 100 received tinzaparin and 100 received usual care . At 12 months , the usual-care group had an excess of recurrent venous thromboembolism ; 16 of 100 ( 16 % ) versus 7 of 100 ( 7 % ) receiving low-molecular-weight heparin ( P=.044 ; risk ratio=.44 ; absolute difference -9.0 ; 95 % confidence interval [ CI ] , -21.7 to -0.7 ) . Bleeding , largely minor , occurred in 27 patients ( 27 % ) receiving tinzaparin and 24 patients ( 24 % ) receiving usual care ( absolute difference -3.0 ; 95 % CI , -9.1 to 15.1 ) . In patients without additional risk factors for bleeding at Output:	There is convincing evidence to recommend the use of heparins or fondaparinux for prevention of VTE in selected cancer patients , and , especially in some particular types of malignancies and cancer treatments . Management of VTE in patients with cancer is more challenging and bleeding complications associated with the use of anticoagulants are significantly higher in cancer patients than in those without malignancy .
MS22026	*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 efficacy of a distance treatment delivered through Internet and telephone for pediatric recurrent pain . METHODS Forty-seven participants ( 9 - 16 years of age ) were r and omly assigned to either an Internet-based treatment or a st and ard medical care waitlist . Treatment employed a Web-based manual for children and parents with weekly therapist contact by telephone or e-mail . At 1- and 3-month follow-ups , participants were assessed on the outcome variables of pain and quality of life . A 50 % reduction in diary pain scores was considered clinical ly significant . RESULTS Significant between-group differences were found : 71 and 72 % of the treatment group achieved clinical ly significant improvement at the 1- and 3-month follow-ups , respectively , whereas only 19 and 14 % of the control group achieved the criterion . No significant differences were found on the quality of life variable . CONCLUSIONS Distance methods have considerable potential for making effective treatments more accessible with lower associated costs Recurrent abdominal pain ( RAP ) affects 10 % to 18 % of school-age children and is caused by obvious organic pathology in fewer than 10 % of cases . Two recent studies do not support previous beliefs that most RAP is psychogenic . Studies have shown disorders of bowel motility in children with RAP similar to those of adult irritable bowel syndrome ( IBS ) ; controlled trials of additional dietary fiber in adult IBS have shown beneficial results . We did a r and omized , double-blind , placebo-controlled study in 52 children with RAP and demonstrated a clinical ly and statistically significant decrease in pain attacks ( at least 50 % fewer ) in almost twice as many children who were given additional fiber as placebo . Compliance was excellent in both groups and side effects were few . Although the cause of RAP is poorly understood , it is hypothesized that the beneficial effect of added fiber is due to its effect on shortening transit time , as in IBS Objectives Recurrent abdominal pain ( RAP ) is a common childhood complaint rarely associated with organic disease . Recently , the Pediatric Rome Criteria were developed to st and ardize the classification of pediatric functional gastrointestinal disorders ( FGIDs ) using a symptom-based approach . The authors tested the hypothesis that most patients with childhood RAP could be classified into one or more of the symptom subtypes defined by the Pediatric Rome Criteria . Methods Using a prospect i ve longitudinal design , new patients with RAP ( n = 114 ) were studied at a tertiary care children 's medical center . Before the medical evaluation , parents completed a question naire about their child , assessing symptoms defined by the Pediatric Rome Criteria . Results Of the 107 children for whom medical evaluation revealed no organic etiology for pain , 73 % had symptom profiles consistent with the Pediatric Rome Criteria for one of the FGIDs associated with abdominal pain ( irritable bowel syndrome , 44.9 % ; functional dyspepsia,15.9 % ; functional abdominal pain , 7.5 % ; abdominal migraine , 4.7 % ) Conclusions This study provides the first systematic empirical evidence that RAP , originally defined by Apley , includes children whose symptoms are consistent with the symptom criteria for several FGIDs defined by the Rome criteria . The pediatric Rome criteria may be useful in clinical research to ( 1 ) describe the symptom characteristics of research participants who meet Apley 's broad criteria for RAP , and ( 2 ) select patients with particular symptom profiles for investigation of potential biologic and psychosocial mechanisms associated with pediatric FGIDs OBJECTIVE To assess whether parental psychological and physical factors and child factors measured in the first year of life were associated with recurrent abdominal pain ( RAP ) in children at age 6(3/4 ) years . METHOD A longitudinal cohort study ( the Avon Longitudinal Study of Parents and Children ) , followed 8,272 children from pregnancy to age 6(3/4 ) years . Parental reports of child and parent functioning were gathered . Associations between parental and child functioning assessed at 6 to 8 months postpartum , and RAP measured at age 6(3/4 ) years were investigated . RESULTS The prevalence of RAP in this sample was 11.8 % . Both maternal anxiety ( adjusted odds ratio = 1.53 ; 95 % confidence interval 1.24 - 1.89 ) and paternal anxiety ( adjusted odds ratio = 1.38 ; 95 % confidence interval 1.12 - 1.71 ) in the first year of a child 's life were associated with later childhood RAP . Parent reports of child temperament features such as irregular feeding and sleeping were also associated with later RAP . CONCLUSIONS This is the first evidence from a prospect i ve study that anxiety in both mothers and fathers and child temperament features pre date the occurrence of RAP in children . These findings highlight the potential importance of addressing parental anxiety in families in which children present with RAP , although some caution should be exercised in their interpretation because of possible reporting bias To determine the benefit of using an H2-receptor antagonist in children with abdominal pain and dyspepsia , 25 such children were enrolled in a double-blind , placebo-controlled trial of famotidine . Global and quantitative pain assessment s were done before and after each treatment period . The quantitative assessment was calculated based on the abdominal pain score that was the sum of three components . Based on the global evaluation , there was a clear benefit of famotidine over placebo ( 68 % vs 12 % ) . Using the quantitative assessment , however , the mean improvement of the score using famotidine versus placebo was not statistically significant ( 3.37+/-3.53 vs 1.66+/-2.7 ) . There was a significant improvement in this score during the first treatment period regardless of medication used ( period effect : P = 0.05 ) . A subset of patients with peptic symptoms demonstrated a significant drug effect that outweighed the period effect ( drug effect : P = 0.01 ; period effect : P = 0.02 ) . We conclude that famotidine subjectively improves the symptoms of children with recurrent abdominal pain but not objective ly using the derived score . However , famotidine is significantly more effective than placebo among children with peptic symptoms . The use of this simple scoring scale may facilitate selecting those children who will benefit from H2-receptor antagonist therapy We sought to prospect ively characterize and compare the symptoms of children ≥ 5 years of age with recurrent abdominal pain to previously established criteria for irritable bowel syndrome ( IBS ) in adults . For all eligible subjects , a detailed question naire concerning characteristics of abdominal pain and defecatory pattern was completed at presentation . In addition , a battery of screening tests was performed and additional evaluation was done at the discretion of their physician . In all , 227 subjects fulfilled the entrance criteria , but 56 were sub-sequently excluded because of diagnoses of inflammatory bowel disease ( nine cases ) , lactose malabsorption ( 46 cases ) , or celiac disease ( one case ) . Of the remaining 171 patients , 117 had IBS symptoms . In the IBS subjects , lower abdominal discomfort ( p < 0.001 ) , cramping pain ( p < 0.0009 ) , and increased flatus ( p < 0.0003 ) were more common , whereas dyspeptic symptoms such as epigastric discomfort ( p < 0.003 ) , pain radiating to the chest ( p < 0.009 ) , and regurgitation ( p < 0.02 ) were more common in the non-IBS subjects . Our study not only confirms the clinical heterogeneity of children with recurrent abdominal pain but also concomitantly demonstrates that most children with this disorder have symptoms that fulfill the st and ardized criteria for IBS in adults . The identification of subgroups of children with recurrent abdominal pain can provide a framework for the diagnosis of functional bowel disease as well as establish the need for invasive and expensive tests 93 % of 88 children with severe frequent migraine recovered on oligoantigenic diets ; the causative foods were identified by sequential re introduction , and the role of the foods provoking migraine was established by a double-blind controlled trial in 40 of the children . Most patients responded to several foods . Many foods were involved , suggesting an allergic rather than an idiosyncratic ( metabolic ) pathogenesis . Associated symptoms which improved in addition to headache included abdominal pain , behaviour disorder , fits , asthma , and eczema . In most of the patients in whom migraine was provoked by non-specific factors , such as blows to the head , exercise , and flashing lights , this provocation no longer occurred while they were on the diet The association of lactase deficiency with recurrent abdominal pain was investigated . One hundred three white children between the ages of 6 to 14 years with recurrent abdominal pain were evaluated . Sixty-nine underwent lactose tolerance tests and 26 had intestinal biopsies with lactase determinations ; 21 of 69 ( 30.4 % ) had abnormal lactose tolerance tests and eight of 26 ( 31 % ) were lactase deficient . However , 16 of 61 ( 26.4 % ) control subjects matched for age and ethnic background exhibited lactase deficiency . Thus , a similar prevalence of lactase deficiency was found in the control and the recurrent abdominal pain groups . Thirty-eight patients with recurrent abdominal pain completed three successive six-week diet trials conducted in a double-blind fashion . An increase above base line value in pain frequency was seen in ten of 21 ( 48 % ) lactose malabsorbers and four of 17 ( 24 % ) lactose absorbers . After a 12-month milk elimination diet , six of 15 ( 40 % ) malabsorbers and five of 13 ( 38 % ) absorbers had elimination of their pain . This result compared with improvement occurring in five of 12 ( 42 % ) absorbers with recurrent abdominal pain who received a regular diet for one year and suggests that the elimination of lactose will not affect the overall frequency of improvement in recurrent abdominal pain . In addition , the recovery rate from recurrent abdominal pain is similar in both lactose absorbers and nonabsorbers independent of dietary restrictions spread metastases and died two months later , having remained normocalcaemic and swallowed normally until death . Case 2-A 50 year old man developed lymphadenopathy in the left supraclavicular fossa due to squamous carcinoma secondary to a symptomless primary tumour of the left main bronchus . The nodes were treated with palliative radiotherapy , but two months later he developed total dysphagia for solids , anorexia , and nausea . Examination showed some residual lymphadenopathy but was otherwise unremarkable ; a chest x ray film , however , showed a primary carcinoma in the left hilar region and multiple bone metastases . Barium swallow showed free flow of barium with no mechanical hold up but some slight muscular incoordination in the pharynx . A biochemical profile showed calcium concentration 3 - 8 mmol/l ( 15 ng/100 ml ) , alkaline phosphatase activity 200 IU/1 , urea concentration 17 - 9 mmol/l ( 108 mg/100 ml ) ( normal 2 - 0 - 8 - 1 mmol/l ( 12 - 49 mg/100 ml ) ) , and glutamic oxaloacetic transaminase activity 315 IU/l ( normal 5 - 45 IU/1 ) . Treatment with intravenous fluids , high dose steroids , and mithramycin corrected the hypercalcaemia , and his dysphagia had gone completely after five days and he was discharged home . He had no further problems with dysphagia . but died a month later from generalised disease . Postmortem examination confirmed a squamous cell carcinoma of the left main bronchus with widespread metastases but with a normal oesophagus that was not obstructed Output:	In spite of these method ological weaknesses and the clinical heterogeneity , the consistency and magnitude of the effects reported provides some evidence that cognitive behavioural therapy may be a useful intervention for children with recurrent abdominal pain although most children , particularly in primary care , will improve with reassurance and time
MS22027	*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 Regular physical exercise may improve a variety of physiological and psychological factors in depressive persons . However , there is little experimental evidence to support this assumption for adolescent population s. We conducted a r and omized controlled trial to investigate the effect of physical exercise on depressive state , the excretions of stress hormones and physiological fitness variables in adolescent females with depressive symptoms . METHODS Forty-nine female volunteers ( aged 18 - 20 years ; mean 18.8 + /- 0.7 years ) with mild-to-moderate depressive symptoms , as measured by the Centre for Epidemiologic Studies Depression ( CES-D ) scale , were r and omly assigned to either an exercise regimen or usual daily activities for 8 weeks . The subjects were then crossed over to the alternate regimen for an additional 8-week period . The exercise program consisted of five 50-min sessions per week of a group jogging training at a mild intensity . The variables measured were CES-D rating scale , urinary cortisol and epinephrine levels , and cardiorespiratory factors at rest and during exercise endurance test . RESULTS After the sessions of exercise the CES-D total depressive score showed a significant decrease , whereas no effect was observed after the period of usual daily activities ( ANOVA ) . Twenty-four hour excretions of cortisol and epinephrine in urine were reduced due to the exercise regimen . The training group had a significantly reduced resting heart rate and increased peak oxygen uptake and lung capacity . CONCLUSIONS The findings of this study suggest that a group jogging exercise may be effective in improving depressive state , hormonal response to stress and physiological fitness of adolescent females with depressive symptoms PURPOSE The objective of this study is to test the feasibility and impact of a 10-wk after-school exercise program for children with attention deficit hyperactivity disorder and /or disruptive behavior disorders living in an urban poor community . METHODS Children were r and omized to an exercise program ( n = 19 ) or a comparable but sedentary attention control program ( n = 16 ) . Cognitive and behavioral outcomes were collected pre-/posttest . Intent-to-treat mixed models tested group-time and group-time-attendance interactions . Effect sizes were calculated within and between groups . RESULTS Feasibility was evidence d by 86 % retention , 60 % attendance , and average 75 % maximum HR . Group-time results were null on the primary outcome , parent-reported executive function . Among secondary outcomes , between-group effect sizes favored exercise on hyperactive symptoms ( d = 0.47 ) and verbal working memory ( d = 0.26 ) , and controls on visuospatial working memory ( d = -0.21 ) and oppositional defiant symptoms ( d = -0.37 ) . In each group , within-group effect sizes were moderate to large on most outcomes ( d = 0.67 to 1.60 ) . A group-time-attendance interaction emerged on visuospatial working memory ( F[1,33 ] = 7.42 , P < 0.05 ) , such that attendance to the control program was related to greater improvements ( r = 0.72 , P < 0.01 ) , whereas attendance to the exercise program was not ( r = 0.25 , P = 0.34 ) . CONCLUSIONS Although between-group findings on the primary outcome , parent-reported executive function , were null , between-group effect sizes on hyperactivity and visuospatial working memory may reflect adaptations to the specific challenges presented by distinct formats . Both groups demonstrated substantial within-group improvements on clinical ly relevant outcomes . Findings underscore the importance of programmatic features , such as routines , engaging activities , behavior management strategies , and adult attention , and highlight the potential for after-school programs to benefit children with attention deficit hyperactivity disorder and disruptive behavior disorder living in urban poverty where health needs are high and services re sources few This study was conducted to determine the effect of acute aerobic exercise on executive function in children with attention deficit hyperactivity disorder ( ADHD ) . Forty children with ADHD were r and omly assigned into exercise or control groups . Participants in the exercise group performed a moderate intensity aerobic exercise for 30 min , whereas the control group watched a running/exercise-related video . Neuropsychological tasks , the Stroop Test and the Wisconsin Card Sorting Test ( WCST ) , were assessed before and after each treatment . The results indicated that acute exercise facilitated performance in the Stroop Test , particularly in the Stroop Color-Word condition . Additionally , children in the exercise group demonstrated improvement in specific WCST performances in Non-perseverative Errors and Categories Completed , whereas no influences were found in those performances in the control group . Tentative explanations for the exercise effect postulate that exercise allocates attention re sources , influences the dorsolateral prefrontal cortex , and is implicated in exercise-induced dopamine release . These findings are promising and additional investigations to explore the efficacy of exercise on executive function in children with ADHD are encouraged Self-control problems commonly manifest as temper outbursts and repetitive/rigid/impulsive behaviors , in children with autism spectrum disorders ( ASD ) , which often contributes to learning difficulties and caregiver burden . The present study aims to compare the effect of a traditional Chinese Chan-based mind-body exercise , Nei Yang Gong , with that of the conventional Progressive Muscle Relaxation ( PMR ) technique in enhancing the self-control of children with ASD . Forty-six age- and IQ-matched ASD children were r and omly assigned to receive group training in Nei Yang Gong ( experimental group ) or PMR ( control group ) twice per week for four weeks . The participants ’ self-control was measured by three neuropsychological tests and parental rating on st and ardized question naires , and the underlying neural mechanism was assessed by the participants ’ brain EEG activity during an inhibitory-control task before and after intervention . The results show that the experimental group demonstrated significantly greater improvement in self-control than the control group , which concurs with the parental reports of reduced autistic symptoms and increased control of temper and behaviors . In addition , the experimental group showed enhanced EEG activity in the anterior cingulate cortex , a region that mediates self-control , whereas the PMR group did not . The present findings support the potential application of Chinese Chan-based mind-body exercises as a form of neuropsychological rehabilitation for patients with self-control problems . Chinese Clinical Trial Registry ; Registration No. : ChiCTR-TRC-12002561 ; URL : www.chictr.org Attention Deficit Hyperactivity Disorder ( ADHD ) mainly affects the academic performance of children and adolescents . In addition to bringing physical and mental health benefits , physical activity has been used to prevent and improve ADHD comorbidities ; however , its effectiveness has not been quantified . In this study , the effect of physical activity on children 's attention was measured using a computer game . Intense physical activity was promoted by a relay race , which requires a 5-min run without a rest interval . The proposed physical stimulus was performed with 28 volunteers : 14 with ADHD ( GE-EF ) and 14 without ADHD symptoms ( GC-EF ) . After 5 min of rest , these volunteers accessed the computer game to accomplish the tasks in the shortest time possible . The computer game was also accessed by another 28 volunteers : 14 with ADHD ( GE ) and 14 without these symptoms ( GC ) . The response time to solve the tasks that require attention was recorded . The results of the four groups were analyzed using D'Agostino statistical tests of normality , Kruskal-Wallis analyses of variance and post-hoc Dunn tests . The groups of volunteers with ADHD who performed exercise ( GE-EF ) showed improved performance for the tasks that require attention with a difference of 30.52 % compared with the volunteers with ADHD who did not perform the exercise ( GE ) . The ( GE-EF ) group showed similar performance ( 2.5 % difference ) with the volunteers in the ( GC ) group who have no ADHD symptoms and did not exercise . This study shows that intense exercise can improve the attention of children with ADHD and may help their school performance Background Exercise has been shown to be effective in treating depression , but trials testing the effect of exercise for depressed adolescents utilising mental health services are rare . The aim of this study was to determine the effectiveness of a preferred intensity exercise intervention on the depressive symptoms of adolescents with depression . Methods We r and omly assigned 87 adolescents who were receiving treatment for depression to either 12 sessions of aerobic exercise at preferred intensity alongside treatment as usual or treatment as usual only . The primary outcome was depressive symptom change using the Children ’s Depression Inventory 2nd Version ( CDI-2 ) at post intervention . Secondary outcomes were health-related quality of life and physical activity rates . Outcomes were taken at baseline , post intervention and at six month follow up . Results CDI-2 score reduction did not differ significantly between groups at post-intervention ( est . 95 % CI −6.82 , 1.68 , p = 0.23 ) . However , there was a difference in CDI-2 score reduction at six month follow-up in favour of the intervention of −4.81 ( est . 95 % CI −9.49 , −0.12 , p = 0.03 ) . Health-related quality of life and physical activity rates did not differ significantly between groups at post-intervention and follow-up . Conclusions There was no additional effect of preferred intensity exercise alongside treatment as usual on depressive reduction immediately post intervention . However , effects were observed at six months post-intervention , suggesting a delayed response . However , further trials , with larger sample s are required to determine the validity of this finding . Trial registration Clinical Trials.gov NCT01474837 , March 16 The Depressed Adolescents Treated with Exercise ( DATE ) study evaluated a st and ardized aerobic exercise protocol to treat nonmedicated adolescents that met DSM-IV-TR criteria for major depressive disorder . From an initial screen of 90 individuals , 30 adolescents aged 12 - 18 years were r and omized to either vigorous exercise ( EXER ) ( > 12 kg/kcal/week [ KKW ] ) or a control stretching ( STRETCH ) activity ( < 4 KKW ) for 12 weeks . The primary outcome measure was the blinded clinician rating of the Children 's Depression Rating Scale - Revised ( CDRS-R ) to assess depression severity and Actical ( KKW ) accelerometry 24hr/7days a week to assess energy expenditure and adherence . Follow-up evaluations occurred at weeks 26 and 52 . The EXER group averaged 77 % adherence and the STRETCH group 81 % for meeting weekly target goals for the 12 week intervention based on weekly sessions completed and meeting KKW requirements . There was a significant increase in overall weekly KKW expenditures ( p < .001 ) for both groups with the EXER group doubling the STRETCH group in weekly energy expenditure . Depressive symptoms were significantly reduced from baseline for both groups with the EXER group improving more rapidly than STRETCH after six weeks ( p < .016 ) and nine weeks ( p < .001 ) . Both groups continued to improve such that there were no group differences after 12 weeks ( p = .07 ) . By week 12 , the exercise group had a 100 % response rate ( 86 % remission ) , whereas the stretch group response rate was 67 % ( 50 % remission ) ( p = .02 ) . Both groups had improvements in multiple areas of psychosocial functioning related to school and relationships with parents and peers . Anthropometry reflected decreased waist , hip and thigh measurements ( p = .02 ) , more so for females than males ( p = .05 ) , but there were no weight changes for either gender . The EXER group sustained 100 % remission at week 26 and 52 . The STRETCH group had 80 % response and 70 % remission rates at week 26 and by week 52 only one had not fully responded . The study provides support for the use of exercise as a non-medication intervention for adolescents with major depressive disorders when good adherence and energy expenditure ( KKW ) are achieved OBJECTIVE To test the dose-response effects of an exercise program on depressive symptoms and self-worth in children . METHOD Overweight , sedentary children ( N = 207 , 7 - 11 years , 58 % male , 59 % Black ) were r and omly assigned to low or high dose ( 20 or 40 min/day ) aerobic exercise programs ( 13 + /- 1.6 weeks ) , or control group . Children completed the Reynolds Child Depression Scale and Self-Perception Profile for Children at baseline and posttest . RESULTS A dose-response benefit of exercise was detected for depressive symptoms . A race x group interaction showed only White children 's global self-worth ( GSW ) improved . There was some evidence that increased self-worth mediated the effect on depressive symptoms . CONCLUSIONS This study shows dose-response benefits of exercise on depressive symptoms and self-worth in children . However , Blacks did not show increased GSW in response to the intervention . Results provide some support for mediation of the effect of exercise on depressive symptoms via self-worth Aerobic moderate-intensity continuous exercise ( MCE ) can improve executive function ( EF ) acutely , potentially through the activation of both physiological and psychological factors . Recently , high-intensity interval exercise ( HIIE ) has been reported to be more beneficial for physical adaptation than MCE . Factors for EF improvement can potentially be more enhanced by HIIE than by MCE ; but the effects of HIIE on EF remain unknown . Therefore , we aim ed to examine to what extent HIIE impacts post-exercise EF immediately after exercise and during post-exercise recovery , compared with traditional MCE . Twelve healthy male subjects performed cycle ergometer exercise based on either HIIE or MCE protocol s in a r and omized and counterbalanced order . The HIIE protocol consisted Output:	Conclusion : Although additional research is warranted to further underst and the mechanisms by which PA affects behavioral and cognitive outcome measures in children with SEBDs , PA offers a safe and alternative form of treatment for this population
MS22028	*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 aim was to prove the low identification rate of sentinel lymph node biopsy ( SNB ) and to determine the feasibility of replacing axillary lymph node dissection ( AND ) in axillary lymph node positive patients after chemotherapy . Methods From October 2001 to July 2005 , 875 consecutive patients with primary operable breast cancer underwent SNB and AND . Among them , 238 received pre-operative chemotherapy . We compared the identification rate , false negative rate ( FNR ) , negative predictive value ( NPV ) , and accuracy of SNB in clinical ly node-positive patients with or without chemotherapy . Results The identification rate was significantly lower in patients received chemotherapy ( 77.6 % ) than in those not received it ( 97.0 % ) ( P < 0.001 ) . In those received the therapy , the FNR was 5.6 % , the NPV was 86.8 % , and the accuracy was 95.9 % . In those not received therapy , the FNR was 7.4 % and the accuracy was 92.6 % ( differences not statistically significant ) . Conclusion The identification rate in confirmed axillary lymph node-positive patients was significantly lower in patients received pre-operative chemotherapy , but accuracy did not differ significantly between the two groups . Thus , for patients who achieve complete axillary clearance by chemotherapy , SNB could replace AND PURPOSE Multicentric breast cancer has been considered to be a contraindication for sentinel node ( SN ) biopsy ( SNB ) . In this prospect i ve multi-institutional trial , SNB-feasibility and accuracy was evaluated in 142 patients with multicentric cancer from the Austrian Sentinel Node Study Group ( ASNSG ) and compared with data from 3,216 patients with unicentric cancer . PATIENTS AND METHODS Between 1996 and 2004 , 3,730 patients underwent SNB at 15 ASNSG-affiliated hospitals . Patient data were entered in a multicenter data base . One hundred forty-two patients presented with multicentric invasive breast cancer and underwent SNB . RESULTS Intraoperatively , a mean number of 1.67 SNs were excised ( identification -rate , 91.5 % ) . The incidence of SN metastases was 60.8 % ( 79 of 130 ) . This was confirmed by axillary lymph node dissection ( ALND ) in 125 patients . Of patients with positive SNs , 60.8 % ( 48 of 79 ) showed involvement of nonsentinel nodes ( NSNs ) , as did three patients with negative SNs ( false-negative rate , 4.0 ) . Sensitivity , negative predictive value , and overall accuracy were 96.0 % , 93.3 % , and 97.3 % , respectively . Ninety-one percent of the patients underwent mastectomy , and 9 % were treated with breast conserving surgery . None of the patients have shown axillary recurrence so far ( mean follow-up , 28.8 months ) . Compared with 3,216 patients with unicentric cancer , there was a significantly higher rate of SN metastases as well as in NSNs , whereas there was no difference in detection and false-negative rates . CONCLUSION Multicentric breast cancer is a new indication for SNB without routine ALND in controlled trials . Given adequate quality control and an interdisciplinary teamwork of surgical , nuclear medicine , and pathology units , SNB is both feasible and accurate in this disease entity PURPOSE Sentinel lymph node ( SLN ) biopsy has proved to be an accurate method for detecting nodal micrometastases in previously untreated patients with early-stage breast cancer . We investigated the accuracy of this technique for patients with more advanced breast cancer after neoadjuvant chemotherapy . PATIENTS AND METHODS Patients with stage II or III breast cancer who had undergone doxorubicin-based neoadjuvant chemotherapy before breast surgery were eligible . Intraoperative lymphatic mapping was performed with peritumoral injections of blue dye alone or in combination with technetium-labeled sulfur colloid . All patients were offered axillary lymph node dissection . Negative sentinel and axillary nodes were subjected to additional processing with serial step sectioning and immunohistochemical staining with an anticytokeratin antibody to detect micrometastases . RESULTS Fifty-one patients underwent SLN biopsy after neoadjuvant chemotherapy from 1994 to 1999 . The SLN identification rate improved from 64.7 % to 94.1 % . Twenty-two ( 51.2 % ) of the 43 successfully mapped patients had positive SLNs , and in 10 of those 22 patients ( 45.5 % ) , the SLN was the only positive node . Three patients had false-negative SLN biopsy ; that is , the sentinel node was negative , but at least one nonsentinel node contained metastases . Additional processing revealed occult micrometastases in four patients ( three in sentinel nodes and one in a nonsentinel node ) . CONCLUSION SLN biopsy is accurate after neoadjuvant chemotherapy . The SLN identification improved with experience . False-negative findings occurred at a low rate throughout the series . This technique is a potential way to guide the axillary treatment of patients who are clinical ly node negative after neoadjuvant chemotherapy PURPOSE To develop a guideline for the use of sentinel node biopsy ( SNB ) in early stage breast cancer . METHODS An American Society of Clinical Oncology ( ASCO ) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer . The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB . The guideline was review ed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors . RESULTS The literature review identified one published prospect i ve r and omized controlled trial in which SNB was compared with axillary lymph node dissection ( ALND ) , four limited meta-analyses , and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND ( completion axillary dissection ) . There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer . However , a review of the available evidence demonstrates that , when performed by experienced clinicians , SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes . CONCLUSION SNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinical ly negative axillary nodes . Completion ALND remains st and ard treatment for patients with axillary metastases identified on SNB . Appropriately identified patients with negative results of SNB , when done under the direction of an experienced surgeon , need not have completion ALND . Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance . Although such specialized techniques are often used , they are not a required part of SLN evaluation for breast cancer at this time . Data suggest that SNB is associated with less morbidity than ALND , but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown BACKGROUND Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from r and omized trials on morbidity and mortality outcomes . We conducted a multicenter r and omized trial to compare quality -of-life outcomes between patients with clinical ly node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received st and ard axillary treatment . METHODS The primary outcome measures were arm and shoulder morbidity and quality of life . From November 1999 to October 2003 , 1031 patients were r and omly assigned to undergo sentinel lymph node biopsy ( n = 515 ) or st and ard axillary surgery ( n = 516 ) . Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy ( depending on the protocol at the treating institution ) . Intention-to-treat analyses of data at 1 , 3 , 6 , and 12 months after surgery are presented . All statistical tests were two-sided . RESULTS The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the st and ard axillary treatment group at 12 months were 0.37 ( 95 % confidence interval [ CI ] = 0.23 to 0.60 ; absolute rates : 5 % versus 13 % ) and 0.37 ( 95 % CI = 0.27 to 0.50 ; absolute rates : 11 % versus 31 % ) , respectively . Drain usage , length of hospital stay , and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group ( all P < .001 ) , and axillary operative time was reduced ( P = .055 ) . Overall patient-recorded quality of life and arm functioning scores were statistically significantly better in the sentinel lymph node biopsy group throughout ( all P < or = .003 ) . These benefits were seen with no increase in anxiety levels in the sentinel lymph node biopsy group ( P > .05 ) . CONCLUSION Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than st and ard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinical ly negative nodes BACKGROUND The optimum timing of sentinel-lymph-node biopsy for breast cancer patients treated with neoadjuvant chemotherapy is uncertain . The SENTINA ( SENTinel NeoAdjuvant ) study was design ed to evaluate a specific algorithm for timing of a st and ardised sentinel-lymph-node biopsy procedure in patients who undergo neoadjuvant chemotherapy . METHODS SENTINA is a four-arm , prospect i ve , multicentre cohort study undertaken at 103 institutions in Germany and Austria . Women with breast cancer who were scheduled for neoadjuvant chemotherapy were enrolled into the study . Patients with clinical ly node-negative disease ( cN0 ) underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy ( arm A ) . If the sentinel node was positive ( pN1 ) , a second sentinel-lymph-node biopsy procedure was done after neoadjuvant chemotherapy ( arm B ) . Women with clinical ly node-positive disease ( cN+ ) received neoadjuvant chemotherapy . Those who converted to clinical ly node-negative disease after chemotherapy ( ycN0 ; arm C ) were treated with sentinel-lymph-node biopsy and axillary dissection . Only patients whose clinical nodal status remained positive ( ycN1 ) underwent axillary dissection without sentinel-lymph-node biopsy ( arm D ) . The primary endpoint was accuracy ( false-negative rate ) of sentinel-lymph-node biopsy after neoadjuvant chemotherapy for patients who converted from cN1 to ycN0 disease during neoadjuvant chemotherapy ( arm C ) . Secondary endpoints included comparison of the detection rate of sentinel-lymph-node biopsy before and after neoadjuvant chemotherapy , and also the false-negative rate and detection rate of sentinel-lymph-node biopsy after removal of the sentinel lymph node . Analyses were done according to treatment received ( per protocol ) . FINDINGS Of 1737 patients who received treatment , 1022 women underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy ( arms A and B ) , with a detection rate of 99.1 % ( 95 % CI 98.3 - 99.6 ; 1013 of 1022 ) . In patients who converted after neoadjuvant chemotherapy from cN+ to ycN0 ( arm C ) , the detection rate was 80.1 % ( 95 % CI 76.6 - 83.2 ; 474 of 592 ) and false-negative rate was 14.2 % ( 95 % CI 9.9 - 19.4 ; 32 of 226 ) . The false-negative rate was 24.3 % ( 17 of 70 ) for women who had one node removed and 18.5 % ( 10 of 54 ) for those who had two sentinel nodes removed ( arm C ) . In patients who had a second sentinel-lymph-node biopsy procedure after neoadjuvant chemotherapy ( arm B ) , the detection rate was 60.8 % ( 95 % CI 55.6 - 65.9 ; 219 of 360 ) and the false-negative rate was 51.6 % ( 95 % CI 38.7 - 64.2 ; 33 of 64 ) . INTERPRETATION Sentinel-lymph-node biopsy is a reliable diagnostic method before neoadjuvant chemotherapy . After systemic treatment or early sentinel-lymph-node biopsy , the procedure has a lower detection rate and a higher false-negative rate compared with sentinel-lymph-node biopsy done before neoadjuvant chemotherapy . These limitations should be considered if biopsy is planned after neoadjuvant chemotherapy . FUNDING Brustkrebs Deutschl and , Output:	Conclusion Women without sentinel lymph node ( SLN ) metastases should not receive axillary lymph node dissection ( ALND ) . Women with one to two metastatic SLNs who are planning to undergo breast-conserving surgery with whole-breast radiotherapy should not undergo ALND ( in most cases ) . Women who have large or locally advanced invasive breast cancer ( tumor size T3/T4 ) , inflammatory breast cancer , or ductal carcinoma in situ ( when breast-conserving surgery is planned ) or are pregnant should not undergo SNB
MS22029	*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 training and follow-up effects of combined aerobic and strength training versus aerobic-only training on cognitive and motor function in institutionalized patients with dementia and to explore whether improved motor function mediates improved cognitive function . METHODS Using a 9-week , parallel , three-group , single-blind , r and omized , controlled trial with a follow-up assessment at week 18 , we assessed 109 patients with dementia ( age 85.5 ± 5.1 years ) in a psycho-geriatric nursing home . Each 9-week intervention consisted of 36 , 30-minute sessions . A combined group ( N = 37 ) received and completed two strength and two walking sessions per week , an aerobic group ( N = 36 ) completed four walking sessions , and a social group ( N = 36 ) completed four social visits per week . Cognitive and motor functions were assessed at baseline , after the 9-week intervention , and after a consecutive 9 weeks of usual care . RESULTS Baseline corrected post-test scores in the combined versus the social group were higher for global cognition , visual memory , verbal memory , executive function , walking endurance , leg muscle strength , and balance . Aerobic versus social group scores were higher for executive function . Follow-up effects reversed toward baseline values . Motor improvement did not significantly mediate cognitive improvement . CONCLUSION Compared with a nonexercise control group , a combination of aerobic and strength training is more effective than aerobic-only training in slowing cognitive and motor decline in patients with dementia . No mediating effects between improvements in cognitive function via improved motor function were found . Future research into the underlying mechanistic associations is needed Background About one-third of people older than 65 years fall at least once a year . Physical exercise has been previously demonstrated to improve gait , enhance physical fitness , and prevent falls . Nonetheless , the addition of cognitive training components may potentially increase these effects , since cognitive impairment is related to gait irregularities and fall risk . We hypothesized that simultaneous cognitive – physical training would lead to greater improvements in dual-task ( DT ) gait compared to exclusive physical training . Methods Elderly persons older than 70 years and without cognitive impairment were r and omly assigned to the following groups : 1 ) virtual reality video game dancing ( DANCE ) , 2 ) treadmill walking with simultaneous verbal memory training ( MEMORY ) , or 3 ) treadmill walking ( PHYS ) . Each program was complemented with strength and balance exercises . Two 1-hour training sessions per week over 6 months were applied . Gait variables , functional fitness ( Short Physical Performance Battery , 6-minute walk ) , and fall frequencies were assessed at baseline , after 3 months and 6 months , and at 1-year follow-up . Multiple regression analyses with planned comparisons were carried out . Results Eighty-nine participants were r and omized to three groups initially ; 71 completed the training and 47 were available at 1-year follow-up . DANCE/MEMORY showed a significant advantage compared to PHYS in DT costs of step time variability at fast walking ( P=0.044 ) . Training-specific gait adaptations were found on comparing DANCE and MEMORY : DANCE reduced step time at fast walking ( P=0.007 ) and MEMORY reduced gait variability in DT and DT costs at preferred walking speed ( both trend P=0.062 ) . Global linear time effects showed improved gait ( P<0.05 ) , functional fitness ( P<0.05 ) , and reduced fall frequency ( −77 % , P<0.001 ) . Only single-task fast walking , gait variability at preferred walking speed , and Short Physical Performance Battery were reduced at follow-up ( all P<0.05 or trend ) . Conclusion Long-term multicomponent cognitive – physical and exclusive physical training programs demonstrated similar potential to counteract age-related decline in physical functioning This study aim ed to evaluate the effects of different types of exercise on cognition . Eighty participants , 32 males and 48 females , aged 66.96 ± 11.73 , volunteered for this study . The participants were r and omly divided into the four following groups : Resistance Group ( RG ; n=20 ) , involved in high intensity strength training ; Cardiovascular Group ( CVG ; n=20 ) , involved in high intensity cardiovascular training ; Postural Group ( PG ; n=20 ) involved in low intensity training , based on postural and balance exercises ; and Control Group ( CG ; n=20 ) . Exercises were performed over the course of 12 weeks . All participants were tested for their cognitive functions pre- and post-intervention using the following neurocognitive tests : the Attentive Matrices Test , Raven 's Progressive Matrices , Stroop Color and Word Interference Test , Trail Making Test and Drawing Copy Test . Statistical analysis showed that the CVG group improved significantly in the Attentive Matrices Test and Raven 's Progressive Matrices ( both p=<0.05 ) , whereas the RG group improved in Drawing Copy Test time ( p=<0.05 ) . These results confirm that different types of exercise interventions have unique effects on cognition . Cardiovascular training is effective in improving performance attentive and analytic tasks , whereas resistance training is effective in improving praxis . Further investigation is necessary to evaluate the combination of the two exercise types in order to ascertain if their respective effects can be summated when performed together This study examined transfer effects of fall training on fear of falling ( Falls Efficacy Scale-International [ FES-I ] ) , balance performance , and spatiotemporal gait characteristics in older adults . Eighteen community-dwelling older adults ( ages 65 - 85 ) were r and omly assigned to an intervention or control group . The intervention group completed 12 training sessions ( 60 min , 6 weeks ) . During pre- and posttesting , we measured FES-I , balance performance ( double limb , closed eyes ; single limb , open eyes ; double limb , open eyes with motor-interfered task ) , and gait parameters ( e.g. , velocity ; cadence ; stride time , stride width , and stride length ; variability of stride time and stride length ) under single- and motor-interfered tasks . Dual tasks were applied to appraise improvements of cognitive processing during balance and gait . FES-I ( p = .33 ) and postural sway did not significantly change ( 0.36 < p < .79 ) . Trends toward significant interaction effects were found for step width during normal walking and stride length variability during the motor dual task ( p = .05 , ηp 2 = .22 ) . Fall training did not sufficiently improve fear of falling , balance , or gait performance under single- or dual-task conditions in healthy older adults Background Stepping impairments are associated with physical and cognitive decline in older adults and increased fall risk . Exercise interventions can reduce fall risk , but adherence is often low . A new exergame involving step training may provide an enjoyable exercise alternative for preventing falls in older people . Purpose To assess the feasibility and safety of unsupervised , home-based step pad training and determine the effectiveness of this intervention on stepping performance and associated fall risk in older people . Design Single-blinded two-arm r and omized controlled trial comparing step pad training with control ( no-intervention ) . Setting / Participants Thirty-seven older adults residing in independent-living units of a retirement village in Sydney , Australia . Intervention Intervention group ( IG ) participants were provided with a computerized step pad system connected to their TVs and played a step game as often as they liked ( with a recommended dose of 2–3 sessions per week for 15–20 minutes each ) for eight weeks . In addition , IG participants were asked to complete a choice stepping reaction time ( CSRT ) task once each week . Main Outcome Measures CSRT , the Physiological Profile Assessment ( PPA ) , neuropsychological and functional mobility measures were assessed at baseline and eight week follow-up . Results Thirty-two participants completed the study ( 86.5 % ) . IG participants played a median 2.75 sessions/week and no adverse events were reported . Compared to the control group , the IG significantly improved their CSRT ( F31,1 = 18.203 , p<.001 ) , PPA composite scores ( F31,1 = 12.706 , p = 0.001 ) , as well as the postural sway ( F31,1 = 4.226 , p = 0.049 ) and contrast sensitivity ( F31,1 = 4.415 , p = 0.044 ) PPA sub-component scores . In addition , the IG improved significantly in their dual-task ability as assessed by a timed up and go test/verbal fluency task ( F31,1 = 4.226 , p = 0.049 ) . Conclusions Step pad training can be safely undertaken at home to improve physical and cognitive parameters of fall risk in older people without major cognitive and physical impairments . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12611001081909 Different types of exercise training have the potential to induce structural and functional brain plasticity in the elderly . Thereby , functional brain adaptations were observed during cognitive tasks in functional magnetic resonance imaging studies that correlated with improved cognitive performance . This study aim ed to investigate if exercise training induces functional brain plasticity during challenging treadmill walking and elicits associated changes in cognitive executive functions . Forty-two elderly participants were recruited and r and omly assigned to either interactive cognitive-motor video game dancing ( DANCE ) or balance and stretching training ( BALANCE ) . The 8-week intervention included three sessions of 30 min per week and was completed by 33 participants ( mean age 74.9 ± 6.9 years ) . Prefrontal cortex ( PFC ) activity during preferred and fast walking speed on a treadmill was assessed applying functional near infrared spectroscopy pre- and post-intervention . Additionally , executive functions comprising shifting , inhibition , and working memory were assessed . The results showed that both interventions significantly reduced left and right hemispheric PFC oxygenation during the acceleration of walking ( p < 0.05 or trend , r = 0.25–0.36 ) , while DANCE showed a larger reduction at the end of the 30-s walking task compared to BALANCE in the left PFC [ F(1 , 31 ) = 3.54 , p = 0.035 , r = 0.32 ] . These exercise training induced modulations in PFC oxygenation correlated with improved executive functions ( p < 0.05 or trend , r = 0.31–0.50 ) . The observed reductions in PFC activity may release cognitive re sources to focus attention on other processes while walking , which could be relevant to improve mobility and falls prevention in the elderly . This study provides a deeper underst and ing of the associations between exercise training , brain function during walking , and cognition in older adults Background Although basic research has uncovered biological mechanisms by which exercise could maintain and enhance adult brain health , experimental human studies with older adults have produced equivocal results . Purpose This r and omized clinical trial aim ed to investigate the hypotheses that ( a ) the effects of exercise training on the performance of neurocognitive tasks in older adults is selective , influencing mainly tasks with a substantial executive control component and ( b ) performance in neurocognitive tasks is related to cardiorespiratory fitness . Methods Fifty-seven older adults ( 65–79 years ) participated in aerobic or strength- and -flexibility exercise training for 10 months . Neurocognitive tasks were selected to reflect a range from little ( e.g. , simple reaction time ) to substantial ( i.e. , Stroop Word – Color conflict ) executive control . Results Performance in tasks requiring little executive control was unaffected by participating in aerobic exercise . Improvements in Stroop Word – Color task performance were found only for the aerobic exercise group . Changes in aerobic fitness were unrelated to changes in neurocognitive function . Conclusions Aerobic exercise in older adults can have a beneficial effect on the performance of speeded tasks that rely heavily on executive control . Improvements in aerobic fitness do not appear to be a prerequisite for this beneficial effect Strength training has been reported as a potentially useful exercise to improve psychological aspects in the elderly , but its effects remain controversial . This study investigated the effectiveness of strength training conducted twice a week for 12 weeks for improving health-related quality of life ( HRQOL ) and executive cognitive function . The study was a single-blind r and omized controlled trial with assessment s before and after intervention . HRQOL and executive function were assessed using the SF-36 Health Status Survey and a computerized neuro-cognitive assessment using task-switch reaction time trials , respectively . Subjects comprised 119 participants > or = 65 years old , r and omized to either strength training ( n=65 ) or health education classes ( controls , n=54 ) . The strength training program was design ed to strengthen the large muscle groups most important for functional activities and to improve balance . The effects of the intervention on the eight dimensions of the SF-36 in the control and training groups were analyzed . Only the mental health scale of the SF-36 was significantly improved for the training group compared with controls after 12 weeks . Task-switch reaction time and correct response rate remained unchanged . Short-term strength training might have modest positive effects on HRQOL , although this training period may not be sufficient to affect executive function in relatively healthy older people Background Physical activity ( PA ) for older adults has well-documented physical and cognitive benefits , but most seniors do not meet recommended guidelines for PA , and interventions are lacking . Objectives This study evaluated the efficacy of a 12-week Internet intervention to help sedentary older adults over 55 years of age adopt and maintain an exercise regimen . Methods A total of 368 sedentary men and women ( M=60.3 ; SD 4.9 ) were recruited , screened , and assessed online . They were r and omized into treatment and control groups and assessed at pretest , at 12 weeks , Output:	The current systematic review will focus mainly on behavioral studies that look into the dual effects of different types of physical training ( e.g. , balance training , aerobic training , strength training , group sports , etc . ) Overall , observations from the 19 included studies conclude that improvements on both motor and cognitive functions were found , mainly in interventions that adopt physical-cognitive training or combined exercise training .
MS22030	*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 The influence of a 12-week-proprioceptive training on functional ankle stability was investigated in young speed skaters . Twenty-eight speed skaters were r and omly divided into an intervention ( n = 14 ) and into a control group ( n = 14 ) . A 15-min circle training was performed 5 times per week over a 12-week period . Measurements were taken prior to the training , after 6 and 12 weeks of training . Kinaesthesia was evaluated with the Isomed2000 in all movements of the ankle joint . Dynamic balance was tested with the Biodex Stability System at the stable level 8 and at the unstable level 2 , measuring the overall stability index , the anterior/posterior and the medial/lateral scores . Static single-leg stance was evaluated using the Kistler force platform . Kinaesthesia of the intervention group improved significantly for plantarflexion of the right foot ( P = 0.001 ) after 12 weeks . Dynamic balance showed significant differences in the intervention group after 12 weeks in comparison with the first measurement for each foot in the overall stability index , the anterior/posterior and the medial/lateral scores ( P ≤ 0.017 , respectively ) at the unstable level 2 . Functional ankle stability improved in terms of dynamic balance after 12 weeks of proprioceptive training . Therefore , inclusion of proprioceptive exercises in the daily training programme is recommended for young speed skaters 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 Typically , balance training has been used as an intervention paradigm either as static or as reactive balance training . Possible differences in functional outcomes between the two modalities have not been profoundly studied . The objective of the study was to investigate the specificity of neuromuscular adaptations in response to two balance intervention modalities within test and intervention paradigms containing characteristics of both profiles : classical sensorimotor training ( SMT ) referring to a static ledger pivoting around the ankle joint vs. reactive balance training ( RBT ) using externally applied perturbations to deteriorate body equilibrium . Thirty-eight subjects were assigned to either SMT or RBT . Before and after four weeks of intervention training , postural sway and electromyographic activities of shank and thigh muscles were recorded and co-contraction indices ( CCI ) were calculated . We argue that specificity of training interventions could be transferred into corresponding test setting s containing properties of SMT and RBT , respectively . The results revealed that i ) postural sway was reduced in both intervention groups in all test paradigms ; magnitude of changes and effect sizes differed dependent on the paradigm : when training and paradigm coincided most , effects were augmented ( P<0.05 ) . ii ) These specificities were accompanied by segmental modulations in the amount of CCI , with a greater reduction within the CCI of thigh muscles after RBT compared to the shank muscles after SMT ( P<0.05 ) . The results clearly indicate the relationship between test and intervention specificity in balance performance . Hence , specific training modalities of postural control cause multi-segmental and context -specific adaptations , depending upon the characteristics of the trained postural strategy . In relation to fall prevention , perturbation training could serve as an extension to SMT to include the proximal segment , and thus the control of structures near to the body ’s centre of mass , into training The objective of this study was to determine the relationship between specific performance measures and hockey skating speed . Thirty competitive secondary school and junior hockey players were timed for skating speed . Off-ice measures included a 40-yd ( 36.9-m ) sprint , concentric squat jump , drop jump , 1 repetition maximum leg press , flexibility , and balance ratio ( wobble board test ) . Pearson product moment correlations were used to quantify the relationships between the variables . Electromyographic ( EMG ) activity of the dominant vastus lateralis and biceps femoris was monitored in 12 of the players while skating , stopping , turning , and performing a change-of-direction drill . Significant correlations ( p < 0.005 ) were found between skating performance and the sprint and balance tests . Further analysis demonstrated significant correlations between balance and players under the age of 19 years ( r = −0.65 ) but not those over 19 years old ( r = −0.28 ) . The significant correlations with balance suggested that stability may be associated with skating speed in younger players . The low correlations with drop jumps suggested that short contact time stretch-shortening activities ( i.e. , low amplitude plyometrics ) may not be an important factor . Electromyographic activities illustrated the very high activation levels associated with maximum skating speed 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 BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . Objectives : To compare the effect of a neuromuscular training program and a basic exercise program on postural control in figure skaters . Design : Two groups ; parallel design ; prospect i ve , r and omized controlled trial . Setting : Postural control laboratory , arenas , September 2001 to December 2002 . Participants : Forty-four young , healthy figure skaters ( 18 years ± 3 years ) . Interventions : Participants were r and omly assigned to receive a neuromuscular training program ( n = 22 ) or a basic exercise training program ( n = 22 ) . Both programs were completed 3 times per week for 4 weeks , and each session was supervised . Main Outcome Measurements : Participants completed baseline and postintervention measures of postural control on a force plate . Postural control was quantified as the center of pressure ( CoP ) path length during tests of single-limb st and ing balance that mimicked figure skating skills and challenged the postural control system to varying degrees . The primary outcome measure was the CoP path length observed during a l and ing jump test completed with eyes closed . Results : The post intervention CoP path lengths during the more challenging tests were significantly ( P < 0.05 ) lower ( indicating better postural control ) for the neuromuscular trained group than for the basic exercise-trained group . For the l and ing jump test completed with eyes closed , the percent improvement in the neuromuscular trained group was significantly greater ( mean = 21.0 ± 22.0 % ) than the basic exercise trained group ( mean = −4.9 ± 24.9 % ; P < 0.05 ) . The magnitude of improvement in the neuromuscular-trained group ranged from approximately 1 % to 21 % , depending on the specific postural control test used . Conclusions : The results suggest that off-ice neuromuscular training can significantly improve postural control in figure skaters , whereas basic exercise training does not Sensory motor training programs are used in the rehabilitation and prevention of injuries among soccer players . Inconsistencies are found in the literature regarding the duration of the protocol s and the exercises and equipment used . OBJECTIVE To evaluate the benefits of a five-week sensory motor training program on the functional performance and postural control of young soccer players . METHODS The study sample comprised 22 young male soccer players who were evaluated using : the Figure-of-Eight Test ( F8 ) , Side Hop Test ( SHT ) , Star Excursion Balance Test ( SEBT ) , and a force platform . The players were r and omly divided into a control group ( N = 10 ) , who continued their soccer practice sessions and an intervention group ( N = 12 ) , who continued their soccer practice sessions and were also enrolled in a supervised five-week sensory motor training program . RESULTS After the five-week training program , the intervention group obtained significant results in the F8 , SHT and SEBT , as well as in the following parameters : area of pressure of sway center ( COP ) , mean velocity and mean frequency of COP . CONCLUSION The five-week sensory motor training program , carried out with easily available and low cost equipment , was effective at improving functional performance and postural control in young soccer players In young elite athletes the influence of a sensorimotor training ( SMT = balance training ) on strength , jump height and spinal reflex excitability was compared with adaptations induced by strength training ( ST ) . Seventeen athletes were r and Output:	However , our subgroup analyses did not reveal any statistically significant effects of the moderator variables age , sex , training status , setting and testing method on overall balance ( i.e. aggregation of static and dynamic balance ) . BT-related effects in adolescents were moderate to large for measures of static ( SMDwm = 0.61 ) and dynamic ( SMDwm = 0.86 ) balance . Conclusions BT is a highly effective means to improve balance performance with moderate to large effects on static and dynamic balance in healthy youth irrespective of age , sex , training status , setting and testing method . The examined training modalities did not have a moderating effect on balance performance in healthy adolescents . Thus , we conclude that an additional but so far unidentified training modality may have a major effect on balance performance that was not assessed in our analysis .
MS22031	*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: Ventilator-associated pneumonia ( VAP ) , an infection of the lower respiratory tract which occurs in association with mechanical ventilation , is one of the most common causes of nosocomial infection in the intensive care unit ( ICU ) . VAP causes significant morbidity and mortality in critically ill patients including increased duration of mechanical ventilation , ICU stay and hospitalization . Current knowledge for its prevention , diagnosis and management is therefore important clinical ly and is the basis for this review . We discuss recent changes in VAP surveillance nomenclature incorporating ventilator-associated conditions and ventilator-associated events , terms recently proposed by the Centers for Disease Control . To the extent possible , we rely predominantly on data from r and omized control trials ( RCTs ) and meta-analyses BACKGROUND A study was undertaken to assess the diagnostic value of different clinical criteria and the impact of microbiological testing on the accuracy of clinical diagnosis of suspected ventilator associated pneumonia ( VAP ) . METHODS Twenty five deceased mechanically ventilated patients were studied prospect ively . Immediately after death , multiple bilateral lung biopsy specimens ( 16 specimens/patient ) were obtained for histological examination and quantitative lung cultures . The presence of both histological pneumonia and positive lung cultures was used as a reference test . RESULTS The presence of infiltrates on the chest radiograph and two of three clinical criteria ( leucocytosis , purulent secretions , fever ) had a sensitivity of 69 % and a specificity of 75 % ; the corresponding numbers for the clinical pulmonary infection score ( CPIS ) were 77 % and 42 % . Non-invasive as well as invasive sampling techniques had comparable values . The combination of all techniques achieved a sensitivity of 85 % and a specificity of 50 % , and these values remained virtually unchanged despite the presence of previous treatment with antibiotics . When microbiological results were added to clinical criteria , adequate diagnoses originating from microbiological results which might have corrected false positive and false negative clinical judgements ( n = 5 ) were countered by a similar proportion of inadequate diagnoses ( n = 6 ) . CONCLUSIONS Clinical criteria had reasonable diagnostic values . CPIS was not superior to conventional clinical criteria . Non-invasive and invasive sampling techniques had diagnostic values comparable to clinical criteria . An algorithm guiding antibiotic treatment exclusively by microbiological results does not increase the overall diagnostic accuracy and carries the risk of undertreatment BACKGROUND The Centers for Disease Control and Prevention has shifted policy away from using ventilator-associated pneumonia ( VAP ) and toward using ventilator-associated conditions ( VACs ) as a marker of ICU quality . To date , limited prospect i ve data regarding the incidence of VAC among medical and surgical ICU patients , the ability of VAC criteria to capture patients with VAP , and the potential clinical preventability of VACs are available . METHODS This study was a prospect i ve 12-month cohort study ( January 2013 to December 2013 ) . RESULTS We prospect ively surveyed 1,209 patients ventilated for ≥ 2 calendar days . Sixty-seven VACs were identified ( 5.5 % ) , of which 34 ( 50.7 % ) were classified as an infection-related VAC ( IVAC ) with corresponding rates of 7.0 and 3.6 per 1,000 ventilator days , respectively . The mortality rate of patients having a VAC was significantly greater than that of patients without a VAC ( 65.7 % vs 14.4 % , P < .001 ) . The most common causes of VACs included IVACs ( 50.7 % ) , ARDS ( 16.4 % ) , pulmonary edema ( 14.9 % ) , and atelectasis ( 9.0 % ) . Among IVACs , 44.1 % were probable VAP and 17.6 % were possible VAP . Twenty-five VACs ( 37.3 % ) were adjudicated to represent potentially preventable events . Eighty-six episodes of VAP occurred in 84 patients ( 10.0 of 1,000 ventilator days ) during the study period . The sensitivity of the VAC criteria for the detection of VAP was 25.9 % ( 95 % CI , 16.7%-34.5 % ) . CONCLUSIONS Although relatively uncommon , VACs are associated with greater mortality and morbidity when they occur . Most VACs represent nonpreventable events , and the VAC criteria capture a minority of VAP episodes Background Ventilator-associated pneumonia ( VAP ) surveillance is time consuming , subjective , inaccurate , and inconsistently predicts outcomes . Shifting surveillance from pneumonia in particular to complications in general might circumvent the VAP definition 's subjectivity and inaccuracy , facilitate electronic assessment , make interfacility comparisons more meaningful , and encourage broader prevention strategies . We therefore evaluated a novel surveillance paradigm for ventilator-associated complications ( VAC ) defined by sustained increases in patients ' ventilator setting s after a period of stable or decreasing support . Methods We assessed 600 mechanically ventilated medical and surgical patients from three hospitals . Each hospital contributed 100 r and omly selected patients ventilated 2–7 days and 100 patients ventilated > 7 days . All patients were independently assessed for VAP and for VAC . We compared incidence-density , duration of mechanical ventilation , intensive care and hospital lengths of stay , hospital mortality , and time required for surveillance for VAP and for VAC . A subset of patients with VAP and VAC were independently review ed by a physician to determine possible etiology . Results Of 597 evaluable patients , 9.3 % had VAP ( 8.8 per 1,000 ventilator days ) and 23 % had VAC ( 21.2 per 1,000 ventilator days ) . Compared to matched controls , both VAP and VAC prolonged days to extubation ( 5.8 , 95 % CI 4.2–8.0 and 6.0 , 95 % CI 5.1–7.1 respectively ) , days to intensive care discharge ( 5.7 , 95 % CI 4.2–7.7 and 5.0 , 95 % CI 4.1–5.9 ) , and days to hospital discharge ( 4.7 , 95 % CI 2.6–7.5 and 3.0 , 95 % CI 2.1–4.0 ) . VAC was associated with increased mortality ( OR 2.0 , 95 % CI 1.3–3.2 ) but VAP was not ( OR 1.1 , 95 % CI 0.5–2.4 ) . VAC assessment was faster ( mean 1.8 versus 39 minutes per patient ) . Both VAP and VAC events were predominantly attributable to pneumonia , pulmonary edema , ARDS , and atelectasis . Conclusions Screening ventilator setting s for VAC captures a similar set of complications to traditional VAP surveillance but is faster , more objective , and a superior predictor of outcomes Objectives : Correct classification of the source of infection is important in observational and interventional studies of sepsis . Centers for Disease Control and Prevention criteria are most commonly used for this purpose , but the robustness of these definitions in critically ill patients is not known . We hypothesized that in a mixed ICU population , the performance of these criteria would be generally reduced and would vary among diagnostic subgroups . Design : Prospect i ve cohort . Setting : Data were collected as part of a cohort of 1,214 critically ill patients admitted to two hospitals in The Netherl and s between January 2011 and June 2011 . Patients : Eight observers assessed a r and om sample of 168 of 554 patients who had experienced at least one infectious episode in the ICU . Each patient was assessed by two r and omly selected observers who independently scored the source of infection ( by affected organ system or site ) , the plausibility of infection ( rated as none , possible , probable , or definite ) , and the most likely causative pathogen . Assessment s were based on a post hoc review of all available clinical , radiological , and microbiological evidence . The observed diagnostic agreement for source of infection was classified as partial ( i.e. , matching on organ system or site ) or complete ( i.e. , matching on specific diagnostic terms ) , for plausibility as partial ( 2-point scale ) or complete ( 4-point scale ) , and for causative pathogens as an approximate or exact pathogen match . Interobserver agreement was expressed as a concordant percentage and as a kappa statistic . Interventions : None . Measurements and Main Results : A total of 206 infectious episodes were observed . Agreement regarding the source of infection was 89 % ( 183/206 ) and 69 % ( 142/206 ) for a partial and complete diagnostic match , respectively . This result ed in a kappa of 0.85 ( 95 % CI , 0.79–0.90 ) . Agreement varied from 63 % to 91 % within major diagnostic categories and from 35 % to 97 % within specific diagnostic subgroups , with the lowest concordance observed in cases of ventilator-associated pneumonia . In the 142 episodes for which a complete match on source of infection was obtained , the interobserver agreement for plausibility of infection was 83 % and 65 % on a 2- and 4-point scale , respectively . For causative pathogen , agreement was 78 % and 70 % for an approximate and exact pathogen match , respectively . Conclusions : Interobserver agreement for classifying sources of infection using Centers for Disease Control and Prevention criteria was excellent overall . However , full concordance on all aspects of the diagnosis between independent observers was rare for some types of infection , in particular for ventilator-associated pneumonia Purpose Early hyperoxia may be an independent risk factor for mortality in mechanically ventilated intensive care unit ( ICU ) patients . We examined the relationship between early arterial oxygen tension ( PaO2 ) and in-hospital mortality . Method We retrospectively assessed arterial blood gases ( ABG ) with ‘ worst ’ alveolar-arterial ( A-a ) gradient during the first 24 h of ICU admission for all ventilated adult patients from 150 participating ICUs between 2000 and 2009 . We used multivariate analysis in all patients and defined subgroups to determine the relationship between PaO2 and mortality . We also studied the relationship between worst PaO2 , admission PaO2 and peak PaO2 in a r and om cohort of patients . Results We studied 152,680 patients . Their mean PaO2 was 20.3 kPa ( SD 14.6 ) and mean inspired fraction of oxygen ( FiO2 ) was 62 % ( SD 26 ) . Worst A-a gradient ABG identified that 49.8 % ( 76,110 ) had hyperoxia ( PaO2 > 16 kPa ) . Nineteen per cent of patients died in ICU and 26 % in hospital . After adjusting for site , Simplified Acute Physiology Score II ( SAPS II ) , age , FiO2 , surgical type , Glasgow Coma Scale ( GCS ) below 15 and year of ICU admission , there was an association between progressively lower PaO2 and increasing in-hospital mortality , but not with increasing levels of hyperoxia . Similar findings were observed with a sensitivity analysis of PaO2 derived from high FiO2 ( ≥50 % ) versus low FiO2 ( < 50 % ) and in defined subgroups . Worst PaO2 showed a strong correlation with admission PaO2 ( r = 0.98 ) and peak PaO2 within 24 h of admission ( r = 0.86 ) . Conclusion We found there was an association between hypoxia and increased in-hospital mortality , but not with hyperoxia in the first 24 h in ICU and mortality in ventilated patients . Our findings differ from previous studies and suggest that the impact of early hyperoxia on mortality remains uncertain Objectives : Centers for Disease Control and Prevention built up new surveillance paradigms for the patients on mechanical ventilation and the ventilator-associated events , comprising ventilator-associated conditions and infection-related ventilator-associated complications . We assess 1 ) the current epidemiology of ventilator-associated event , 2 ) the relationship between ventilator-associated event and ventilator-associated pneumonia , and 3 ) the impact of ventilator-associated event on antimicrobials consumption and mechanical ventilation duration . Design : Inception cohort study from the longitudinal prospect i ve French multicenter OUTCOME REA data base ( 1996 - 2012 ) . Patients : Patients on mechanical ventilation for greater than or equal to 5 consecutive days were classified as to the presence of a ventilator-associated event episode , using slightly modified Centers for Disease Control and Prevention definitions . Intervention : None . Measurements and Main Results : Among the 3,028 patients , 2,331 patients ( 77 % ) had at least one ventilator-associated condition , and 869 patients ( 29 % ) had one infection-related ventilator-associated complication episode . Multiple causes , or the lack of identified cause , were frequent . The leading causes associated with ventilator-associated condition and infection-related ventilator-associated complication were nosocomial infections ( 27.3 % and 43.8 % ) , including ventilator-associated pneumonia ( 14.5 % and 27.6 % ) . Sensitivity and specificity of diagnosing ventilator-associated pneumonia were 0.92 and 0.28 for ventilator-associated condition and 0.67 and 0 Output:	Conclusions VAE surveillance missed many cases of VAP , and the population characteristics identified by the two surveillance paradigms differed . VAE surveillance does not accurately detect cases of traditional VAP in ICUs
MS22032	*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 Kaiser Sunnyside Medical Center has participated in the American College of Surgeons National Surgical Quality Improvement Program ( NSQIP ) since January 2006 . Data on general and colorectal surgical site infections ( SSIs ) demonstrated a need for improvement in SSI rates . OBJECTIVE To evaluate application of a " care bundle " for patients undergoing colorectal operations , with the goal of reducing overall SSI rates . METHODS We prospect ively implemented multiple interventions , with retrospective analysis of data using the NSQIP data base . The overall , superficial , deep , and organ/space SSI rates were compared before and after implementation of this colorectal care bundle . RESULTS Between January 2006 and December 2009 , there were 430 colorectal cases in our NSQIP report with 91 infections , an overall rate of 21.16 % . Between January 2010 , when the colorectal care bundle was implemented , and June 2011 , there were 195 cases and 13 infections , a 6.67 % overall rate . The absolute decrease of 14.49 % is significant ( p < 0.0001 ) . The rate of superficial SSI decreased from 15.12 % to 3.59 % ( p < 0.0001 ) . The rates for deep and organ/space SSI also showed a decrease ; however , this was not statistically significant . The NSQIP observed-to-expected ratio for colorectal SSI decreased from a range of 1.27 to 1.83 before implementation to 0.54 after implementation ( fiscal year 2010 ) . CONCLUSIONS Our institution was a NSQIP high outlier in general surgery SSIs and had a high proportion of these cases represented in colorectal cases . By instituting a care bundle composed of core and adjunct strategies , we significantly decreased our rate of colorectal SSIs Background Wound-edge protection devices ( WEPDs ) have been used in surgery for more than 40 years to reduce surgical site infection ( SSI ) . No economic evaluation of WEPDs against any comparator has ever been conducted . The aim of the paper was to assess whether WEPDs are cost-effective in reducing SSI compared to st and ard care alone in the United Kingdom . Methods and Findings An economic evaluation was conducted alongside the ROSSINI trial . The study perspective was that of the UK National Health Service and the time horizon was 30 days post-operatively . The study was conducted in 21 UK hospitals . 760 patients undergoing laparotomy were r and omised to either WEPD or st and ard care and 735 were included in the primary analysis . The main economic outcome was cost-effectiveness based on incremental cost ( £ ) per quality adjusted life year ( QALY ) gained . Patients in the WEPD arm accessed health care worth £ 5,420 on average and gained 0.02131 QALYs , compared to £ 5,130 and 0.02133 QALYs gained in the st and ard care arm . The WEPD strategy was more costly and equally effective compared to st and ard care , but there was significant uncertainty around incremental costs and QALYs . The findings were robust to a range of sensitivity analyses . Conclusions There is no evidence to suggest that WEPDs can be considered a cost effective device to reduce SSI . Their continued use is a waste of limited health care re sources Objective To determine the clinical effectiveness of wound edge protection devices in reducing surgical site infection after abdominal surgery . Design Multicentre observer blinded r and omised controlled trial . Participants Patients undergoing laparotomy at 21 UK hospitals . Interventions St and ard care or the use of a wound edge protection device during surgery . Main outcome measures Surgical site infection within 30 days of surgery , assessed by blinded clinicians at seven and 30 days and by patient ’s self report for the intervening period . Secondary outcomes included quality of life , duration of stay in hospital , and the effect of characteristics of the patient and operation on the efficacy of the device . Results 760 patients were enrolled with 382 patients assigned to the device group and 378 to the control group . Six patients in the device group and five in the control group did not undergo laparotomy . Fourteen patients , seven in each group , were lost to follow-up . A total of 184 patients experienced surgical site infection within 30 days of surgery , 91/369 ( 24.7 % ) in the device group and 93/366 ( 25.4 % ) in the control group ( odds ratio 0.97 , 95 % confidence interval 0.69 to 1.36 ; P=0.85 ) . This lack of benefit was consistent across wound assessment s performed by clinicians and those reported by patients and across all secondary outcomes . In the secondary analyses no subgroup could be identified in which there was evidence of clinical benefit associated with use of the device . Conclusions Wound edge protection devices do not reduce the rate of surgical site infection in patients undergoing laparotomy , and therefore their routine use for this role can not be recommended . Trial registration Current Controlled Trials IS RCT N A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Aim Surgical site infection ( SSI ) remains a common postoperative morbidity , particularly in colorectal resections , and poses a significant financial burden to the healthcare system . The omission of mechanical bowel preparation , as is performed in enhanced recovery after surgery programmes , appears to further increase the incidence . Various wound protection methods have been devised to reduce the incidence of SSIs . However , there are few r and omized controlled trials assessing their efficacy . The aim of this study is to investigate whether ALEXIS wound retractors with reinforced O‐rings are superior to conventional wound protection methods in preventing SSIs in colorectal resections Introduction Surgical site infections ( SSIs ) are frequent complications in colorectal surgery and may lead to burst abdomen , incisional hernia , and increased perioperative costs . Plastic wound ring drapes ( RD ) were introduced some decades ago to protect the abdominal wound from bacteria and reduce SSIs . There have been no controlled trials examining the benefit of RD in laparoscopic colorectal surgery . The Reduction of wound infections in laparoscopic assisted colorectal resections by plastic wound ring drapes ( REDWIL ) trial was thus design ed to assess their effectiveness in preventing SSIs after elective laparoscopic colorectal resections . Material s/ methods REDWIL is a r and omized controlled monocenter trial with two parallel groups ( experimental group with RD and control group without RD ) . Patients undergoing elective laparoscopic colorectal resection were included . The primary endpoint was SSIs . Secondary outcomes were colonization of the abdominal wall with bacteria , reoperations/readmissions , early/late postoperative complications , and cost of hospital stay . The duration of follow-up was 6 months . Results Between January 2008 and October 2010 , 109 patients were r and omly assigned to the experimental or control group ( with or without RD ) . Forty-six patients in the RD group and 47 patients in the control group completed follow-up . SSIs developed in ten patients with RD ( 21.7 % ) and six patients without RD ( 12.8 % ) ( p = 0.28 ) . An intraoperative swab taken from the abdominal wall was positive in 66.7 % of patients with RD and 57.5 % without RD ( p = 0.46 ) . The number of species cultured within one swab was significantly higher in those without RD ( p = 0.03 ) . The median total inpatient costs including emergency readmissions were 3,402 ± 4,038 € in the RD group and 3,563 ± 1,735 € in the control group ( p = 0.869 ) . Conclusions RD do not reduce the rate of SSIs in laparoscopic colorectal surgery . The inpatient costs are similar with and without RD A controlled , r and omized study of the efficacy of a plastic wound ring drape ( Opdrape , Triplus ) to prevent contamination and infection in elective colorectal operations is reported . Seventy patients were operated upon with the wound ring drape and 70 patients without . All patients received preoperative systemic antibiotic prophylaxis . Abdominal wound infection was observed in seven of 70 ( 10 per cent ) patients with the wound ring drape and six of 70 ( 9 per cent ) without ( N.S. ) . An operative swab for bacteriologic evaluation was obtained from 85 per cent of the wounds . There was no evidence that the drape protected the wound from contamination with intestinal bacterial flora . It was concluded that the wound ring drape prevents neither contamination nor infection PURPOSE : Surgical site infection following colorectal surgery is a frequent and costly problem . Barrier protection at the time of this form of surgery has been used with varying results . The aim of this r and omized study was to examine the efficacy of barrier retractional wound protection in the prevention of surgical site infections in open , elective colorectal surgery . METHODS : One hundred thirty consecutive patients undergoing open elective colorectal resectional surgery were r and omly assigned to have either barrier retractional wound protection or st and ard wound retraction . Patients were then followed up for a minimum of 30 days postoperatively . The primary end point was surgical site infection as defined by the Centers for Disease Control and Prevention . The secondary end point was performance of the wound protector as assessed by operating surgeons . RESULTS : There was a significant reduction in the incidence of incisional surgical site infections when the wound protector was used : 3 of 64 ( 4.7 % ) vs 15 of 66 ( 22.7 % ) ; P = .004 . Most surgical site infections were diagnosed after discharge from the hospital ( 78 % ) , and there was no difference in the rates of reoperation , readmission , or formal wound drainage between the 2 groups . Surgeons found the wound protector to be helpful with retraction during surgery , with 88 % ( 7/8 ) adopting it as part of their st and ard setup . CONCLUSIONS : In this study the use of barrier wound protection in elective open colorectal resectional surgery result ed in a clinical ly significant reduction in incisional surgical site infections . Barrier wound protection of this nature should be considered routine in this type of surgery Introduction Surgical site infections ( SSIs ) remain a major problem in colorectal surgery . Method In this prospect i ve , r and omised study , we compared two kinds of wound protection , namely , “ plastic ring drape ” versus “ st and ard cloth towels ” . One hundred one patients were r and omised to the control group ( wet cloth towels ) and 98 to the study cohort ( ring drape ) . SSIs were classified according to Centers for Disease Control and Prevention recommendations . Discussion In the control group , 30 patients had an SSI , whereas 20 did so in the study group . This difference was not significant ( p = 0.131 ) . Conclusion Plastic ring drape for wound protection does not guard against SSIs in colorectal surgery Surgical site infections ( SSIs ) after cesarean section appear to be more common than generally believed . We prospect ively evaluated 231 consecutive pregnant women who underwent elective or emergency cesarean section , and were assigned to have either the Alexis wound retractor ( study group ) or a conventional Doyen retractor ( control group ) during the operation . There was no evidence of SSI , defined as wound dehiscence , pain or tenderness in the lower abdomen , localized swelling , redness , heat or purulent discharge from the wound in any woman in the study group . Moreover , no endometritis occurred in this patient collective . There were three SSI in the control group , but no endometritis . Our preliminary data show excellent protection of wound infections with an additive protective effect to that given by antibiotic cover . After a short learning curve , the h and ling of the Alexis device became easier and the median insertion time was 18 A study is reported of the influence of plastic wound protectors on the incidence of wound infection in patients having abdominal operations involving the opening of the alimentary tract or biliary system BACKGROUND We prospect ively investigated whether the wound-protective Alexis ( Applied Medical , Rancho Santa Margarita , CA ) wound retractor was effective in preventing surgical site infection ( SSI ) . METHODS We examined the actual condition of SSI in a 12-month r and omized , controlled trial consisting of 221 patients who had undergone nontraumatic gastrointestinal surgery . The patients were divided into a With Alexis retractor group ( n = 111 ) and a Without Alexis retractor group ( n = 110 ) . We also analyzed SSI separately on the basis of Output:	WEPD seems to be an effective intervention to reduce the risk of post-operative SSI in patients undergoing abdominal surgery
MS22033	*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 studies were conducted to investigate the effects of red pepper ( capsaicin ) on feeding behaviour and energy intake . In the first study , the effects of dietary red pepper added to high-fat ( HF ) and high-carbohydrate ( HC ) meals on subsequent energy and macronutrient intakes were examined in thirteen Japanese female subjects . After the ingestion of a st and ardized dinner on the previous evening , the subjects ate an experimental breakfast ( 1883 kJ ) of one of the following four types : ( 1 ) HF ; ( 2 ) HF and red pepper ( 10 g ) ; ( 3 ) HC ; ( 4 ) HC and red pepper . Ad libitum energy and macronutrient intakes were measured at lunch-time . The HC breakfast significantly reduced the desire to eat and hunger after breakfast . The addition of red pepper to the HC breakfast also significantly decreased the desire to eat and hunger before lunch . Differences in diet composition at breakfast time did not affect energy and macronutrient intakes at lunch-time . However , the addition of red pepper to the breakfast significantly decreased protein and fat intakes at lunch-time . In Study 2 , the effects of a red-pepper appetizer on subsequent energy and macronutrient intakes were examined in ten Caucasian male subjects . After ingesting a st and ardized breakfast , the subjects took an experimental appetizer ( 644 kJ ) at lunch-time of one of the following two types : ( 1 ) mixed diet and appetizer ; ( 2 ) mixed diet and red-pepper ( 6 g ) appetizer . The addition of red pepper to the appetizer significantly reduced the cumulative ad libitum energy and carbohydrate intakes during the rest of the lunch and in the snack served several hours later . Moreover , the power spectral analysis of heart rate revealed that this effect of red pepper was associated with an increase in the ratio sympathetic : parasympathetic nervous system activity . These results indicate that the ingestion of red pepper decreases appetite and subsequent protein and fat intakes in Japanese females and energy intake in Caucasian males . Moreover , this effect might be related to an increase in sympathetic nervous system activity in Caucasian males BACKGROUND Capsinoids-nonpungent capsaicin analogs-are known to activate brown adipose tissue ( BAT ) thermogenesis and whole-body energy expenditure ( EE ) in small rodents . BAT activity can be assessed by [¹⁸F]fluorodeoxyglucose-positron emission tomography ( FDG-PET ) in humans . OBJECTIVES The aims of the current study were to examine the acute effects of capsinoid ingestion on EE and to analyze its relation to BAT activity in humans . DESIGN Eighteen healthy men aged 20 - 32 y underwent FDG-PET after 2 h of cold exposure ( 19 ° C ) while wearing light clothing . Whole-body EE and skin temperature , after oral ingestion of capsinoids ( 9 mg ) , were measured for 2 h under warm conditions ( 27 ° C ) in a single-blind , r and omized , placebo-controlled , crossover design . RESULTS When exposed to cold , 10 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions ( BAT-positive group ) , whereas the remaining 8 subjects ( BAT-negative group ) showed no detectable uptake . Under warm conditions ( 27 ° C ) , the mean ( ±SEM ) resting EE was 6114 ± 226 kJ/d in the BAT-positive group and 6307 ± 156 kJ/d in the BAT-negative group ( NS ) . EE increased by 15.2 ± 2.6 kJ/h in 1 h in the BAT-positive group and by 1.7 ± 3.8 kJ/h in the BAT-negative group after oral ingestion of capsinoids ( P < 0.01 ) . Placebo ingestion produced no significant change in either group . Neither capsinoids nor placebo changed the skin temperature in various regions , including regions close to BAT deposits . CONCLUSION Capsinoid ingestion increases EE through the activation of BAT in humans . This trial was registered at http://www.umin.ac.jp/ctr/ as UMIN 000006073 The aim of the present study was to investigate whether capsaicin assists weight maintenance by limiting weight regain after weight loss of 5 to 10 % . In this r and omized double-blind placebo-controlled study , ninety-one moderately overweight subjects were r and omly assigned to an intensive group that underwent all the measurements , and an extensive group that underwent the same measurements except the metabolism measurements . After a 4-week very-low-energy diet ( VLED ) intervention , a 3-month weight-maintenance period followed . During weight maintenance , subjects were divided into a capsaicin ( 135 mg capsaicin/d ) and a placebo group . Body mass was measured before and after the VLED and after 1 , 2 and 3 months of weight maintenance . The mean body-mass loss during the VLED was 6.6 ( SD 2.0 ) kg ( 7.8 ( SD 1.8 ) % initial body mass ) , and was not different between the subsequent treatment and placebo group . During weight maintenance , mean % regain during treatment was not significantly different compared with placebo ( 33.3 ( SD 35.7 ) v. 19.2 ( SD 41.8 ) % , P=0.09 ) . RQ was significantly less increased during weight maintenance in the treatment group compared with placebo ( 0.04 ( SD 0.06 ) v. 0.07 ( SD 0.05 ) , P<0.05 ) , indicating a relatively more sustained fat oxidation . Fat oxidation ( g/h ) after weight maintenance was higher in the capsaicin group compared with placebo ( 4.2 ( SD 1.1 ) v. 3.5 ( SD 0.9 ) , P<0.05 ) . These results indicate that capsaicin treatment caused sustained fat oxidation during weight maintenance compared with placebo . However , capsaicin treatment has no limiting effect on 3-month weight regain after modest weight loss Background Dihydrocapsiate ( DCT ) is a natural safe food ingredient which is structurally related to capsaicin from chili pepper and is found in the non-pungent pepper strain , CH-19 Sweet . It has been shown to elicit the thermogenic effects of capsaicin but without its gastrointestinal side effects . Methods The present study was design ed to examine the effects of DCT on both adaptive thermogenesis as the result of caloric restriction with a high protein very low calorie diet ( VLCD ) and to determine whether DCT would increase post-pr and ial energy expenditure ( PPEE ) in response to a 400 kcal/60 g protein liquid test meal . Thirty-three subjects completed an outpatient very low calorie diet ( 800 kcal/day providing 120 g/day protein ) over 4 weeks and were r and omly assigned to receive either DCT capsules three times per day ( 3 mg or 9 mg ) or placebo . At baseline and 4 weeks , fasting basal metabolic rate and PPEE were measured in a metabolic hood and fat free mass ( FFM ) determined using displacement plethysmography ( BOD POD ) . Results PPEE normalized to FFM was increased significantly in subjects receiving 9 mg/day DCT by comparison to placebo ( p < 0.05 ) , but decreases in resting metabolic rate were not affected . Respiratory quotient ( RQ ) increased by 0.04 in the placebo group ( p < 0.05 ) at end of the 4 weeks , but did not change in groups receiving DCT . Conclusions These data provide evidence for postpr and ial increases in thermogenesis and fat oxidation secondary to administration of dihydrocapsiate . Trial registration clinical Dietary red pepper suppresses energy intake and modifies macronutrient intake . We have investigated whether a stimulus in the mouth and the sensation of spiciness are necessary for red pepper-induced changes in energy and macronutrient intake in human volunteers . In a preliminary test , sixteen Japanese male volunteers tasted sample s of a soup with grade d doses of red pepper in order to define a moderate and a maximum tolerable ( strong ) dose of red pepper . On the day of the experiment , a st and ardised breakfast was given to the volunteers . At lunchtime , the subjects ingested one of four experimental soups containing either a placebo , a moderate or a strong dose of red pepper plus placebo capsules , or a placebo soup plus capsules delivering a strong dose of red pepper . The rest of the meal was given ad libitum to all subjects . The amount of food , protein and carbohydrate ingested was similar for all conditions . Energy and fat intake were similar after the ingestion of the moderate soup compared with placebo . However , the strong soup significantly lowered fat intake compared with placebo ( P=0.043 ) , and ingestion of strong capsules also tended to suppress it ( P=0.080 ) . Moreover , energy intake after strong soup and capsules tended to be lower than placebo ( P=0.089 and 0.076 , respectively ) . The present results indicate that the maximum tolerable dose is necessary to have a suppressive effect of red pepper on fat intake . The main site of the action of red pepper is not in the mouth BACKGROUND : Decreased appetite and increased energy expenditure after oral consumption of red pepper has been shown . OBJECTIVE : The aim of the present study was to assess the relative oral and gastrointestinal contribution to capsaicin-induced satiety and its effects on food intake or macronutrient selection . METHODS : For 24 subjects ( 12 men and 12 women ; age : 35±10 y ; BMI : 25.0±2.4 kg/m2 ; range 20–30 ) , 16 h food intake was assessed four times during 2 consecutive days by offering macronutrient-specific buffets and boxes with snacks , in our laboratory restaurant . At 30 min before each meal , 0.9 g red pepper ( 0.25 % capsaicin ; 80 000 Scoville Thermal Units ) or a placebo was offered in either tomato juice or in two capsules that were swallowed with tomato juice . Hunger and satiety were recorded using Visual Analogue Scales . RESULTS : Average daily energy intake in the placebo condition was 11.5±1.0 MJ/d for the men and 9.4±0.8 MJ/d for the women . After capsaicin capsules , energy intake was 10.4±0.6 and 8.3±0.5 MJ/d ( P<0.01 ) ; after capsaicin in tomato juice , it was 9.9±0.7 and 7.9±0.5 MJ/d , respectively ( compared to placebo : P<0.001 ; compared to capsaicin in capsules : P<0.05 ) . En % from carbohydrate/protein/fat ( C/P/F ) : changed from 46±3/15±1/39±2 to 52±4/15±1/33±2 en% ( P<0.01 ) in the men , and from 48±4/14±2/38±3 to 42±4/14±2/32±3 en% ( P<0.01 ) in the women , in both capsaicin conditions . Satiety ( area under the curve ) increased from 689 to 757 mmh in the men and from 712 to 806 mmh in the women , both ( P<0.01 ) . Only in the oral exposure condition was the reduction in energy intake and the increase in satiety related to perceived spiciness . CONCLUSION : In the short term , both oral and gastrointestinal exposure to capsaicin increased satiety and reduced energy and fat intake ; the stronger reduction with oral exposure suggests a sensory effect of capsaicin The biochemical and physiological indices were monitored in 44 subjects after 4-week capsinoids ( capsaicin analogues with low pungency ) intake . The subjects were r and omly assigned to 3 groups : CSNs3 ( 3 mg/kg of capsinoids ) , CSNs10 ( 10 mg/kg of capsinoids ) and the control ( placebo ) . Measurements were performed in the morning on overnight-fasted subjects . The oxygen consumption ( VO2 ) , resting energy expenditure ( REE ) and fat oxidation increased slightly compared to pre-administration values without any adverse effects , although the increase was not significant . The increase in fat oxidation was positively and significantly correlated with the body mass index ( BMI ) . A meta- analysis was therefore conducted on a subgroup consisting of subjects with BMI ≥ 25 ( n=28 ) . As a result , not only VO2 increased significantly ( p<0.05 ) in the CSNs10 group , but also REE in the CSNs10 group and fat oxidation in the CSNs3 and CSNs10 groups tended to increase ( p<0.1 ) . Consequently , a capsinoids intake would be able to enhance the energy expenditure and fat burning in humans , particularly those with high BMI BACKGROUND & AIMS Bioactive ingredients have been shown to reduce appetite and energy intake . The magnitude of these effects might depend on energy balance why it was investigated how capsaicin , green tea , CH-19 sweet pepper as well as green tea and capsaicin affect appetite and energy intake during respectively negative and positive energy balance . METHODS 27 subjects were r and omized to three weeks of negative and Output:	It was observed that consumption of capsaicinoids increases energy expenditure by approximately 50 kcal/day , and that this would produce clinical ly significant levels of weight loss in 1 - 2 years . It was also observed that regular consumption significantly reduced abdominal adipose tissue levels and reduced appetite and energy intake . The mechanism of action is not presently fully understood , although it is well accepted much of the effects are caused by stimulation of the TRPV1 receptor . While capsaicinoids are not a magic bullet for weight loss , the evidence is that they could play a beneficial role , as part of a weight management program
MS22034	*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 whether ballistic resistance training would increase the vertical jump ( VJ ) performance of already highly trained jump athletes . METHODS Sixteen male volleyball players from a NCAA Division I team participated in the study . A Vertec was used to measure st and ing vertical jump and reach ( SJR ) and jump and reach from a three-step approach ( AJR ) . Several types of vertical jump tests were also performed on a Plyometric Power System and a forceplate to measure force , velocity , and power production during vertical jumping . The subjects completed the tests and were then r and omly divided into two groups , control and treatment . All subjects completed the usual preseason volleyball on-court training combined with a resistance training program . In addition , the treatment group completed 8 wk of squat jump training while the control group completed squat and leg press exercises at a 6RM load . Both groups were retested at the completion of the training period . RESULTS The treatment group produced a significant increase in both SJR and AJR of 5.9+/-3.1 % and 6.3+/-5.1 % . respectively . These increases were significantly greater than the pre- to postchanges produced by the control group , which were not significant for either jump . Analysis of the data from the various other jump tests suggested increased overall force output during jumping , and in particular increased rate of force development were the main contributors to the increased jump height . CONCLUSIONS These results lend support to the effectiveness of ballistic resistance training for improving vertical jump performance in elite jump athletes The purpose of this study was to compare the effects of combined strength and plyometric training with strength training alone on power-related measurements in professional soccer players . Subjects in the intervention team were r and omly divided into 2 groups . Group ST ( n = 6 ) performed heavy strength training twice a week for 7 weeks in addition to 6 to 8 soccer sessions a week . Group ST+P ( n = 8) performed a plyometric training program in addition to the same training as the ST group . The control group ( n = 7 ) performed 6 to 8 soccer sessions a week . Pretests and posttests were 1 repetition maximum ( 1RM ) half squat , countermovement jump ( CMJ ) , squat jump ( SJ ) , 4-bounce test ( 4BT ) , peak power in half squat with 20 kg , 35 kg , and 50 kg ( PP20 , PP35 , and PP50 , respectively ) , sprint acceleration , peak sprint velocity , and total time on 40-m sprint . There were no significant differences between the ST+P group and ST group . Thus , the groups were pooled into 1 intervention group . The intervention group significantly improved in all measurements except CMJ , while the control group showed significant improvements only in PP20 . There was a significant difference in relative improvement between the intervention group and control group in 1RM half squat , 4BT , and SJ . However , a significant difference between groups was not observed in PP20 , PP35 , sprint acceleration , peak sprinting velocity , and total time on 40-m sprint . The results suggest that there are no significant performance-enhancing effects of combining strength and plyometric training in professional soccer players concurrently performing 6 to 8 soccer sessions a week compared to strength training alone . However , heavy strength training leads to significant gains in strength and power-related measurements in professional soccer players Functional performance of lower limb muscles and contractile properties of chemically skinned single muscle fibers were evaluated before and after 8 wk of maximal effort stretch-shortening cycle ( SSC ) exercise training . Muscle biopsies were obtained from the vastus lateralis of eight men before and after the training period . Fibers were evaluated regarding their mechanical properties and subsequently classified according to their myosin heavy chain content ( SDS-PAGE ) . After training , maximal leg extensor muscle force and vertical jump performance were improved 12 % ( P<0.01 ) and 13 % ( P<0.001 ) , respectively . Single-fiber cross-sectional area increased 23 % in type I ( P<0.01 ) , 22 % in type IIa ( P<0.001 ) , and 30 % in type IIa/IIx fibers ( P<0.001 ) . Peak force increased 19 % in type I ( P<0.01 ) , 15 % in type IIa ( P<0.001 ) , and 16 % in type IIa/IIx fibers ( P<0.001 ) . When peak force was normalized with cross-sectional area , no changes were found for any fiber type . Maximal shortening velocity was increased 18 , 29 , and 22 % in type I , IIa , and hybrid IIa/IIx fibers , respectively ( P<0.001 ) . Peak power was enhanced in all fiber types , and normalized peak power improved 9 % in type IIa fibers ( P<0.05 ) . Fiber tension on passive stretch increased in IIa/IIx fibers only ( P<0.05 ) . In conclusion , short-term SSC exercise training enhanced single-fiber contraction performance via force and contraction velocity in type I , IIa , and IIa/IIx fibers . These results suggest that SSC exercises are an effective training approach to improve fiber force , contraction velocity , and therefore power The present study investigates the effects of power training on mechanical efficiency ( ME ) in jumping . Twenty-three subjects , including ten controls , volunteered for the study . The experimental group trained twice a week for 15 weeks performing various jumping exercises such as drop jumps , hurdle jumps , hopping and bouncing . In the maximal jumping test , the take-off velocity increased from 2.56 ( 0.24 ) m·s−1 to 2.77 ( 0.18 ) m·s−1 ( P<0.05 ) . In the submaximal jumping of 50 % of the maximum , energy expenditure decreased from 660 ( 110 ) to 502 ( 68 ) J·kg−1·min−1 ( P<0.001 ) while , simultaneously , ME increased from 37.2 (8.4)% to 47.4 (8.2)% ( P<0.001 ) . Some muscle enzyme activities of the gastrocnemius muscle increased during the training period : citrate synthase from 35 ( 8) to 39 ( 7 ) μmol·g−1 dry mass·min−1 ( P<0.05 ) and β-hydroxyacyl CoA dehydrogenase from 21 ( 4 ) to 23 ( 5 ) μmol·g−1 dry mass·min−1 ( P<0.05 ) , whereas no significant changes were observed in phosphofructokinase and lactate dehydrogenase . In the control group , no changes in ME or in enzyme activities were observed . In conclusion , the enhanced performance capability of 8 % in maximal jumping as a result of power training was characterized by decreased energy expenditure of 24 % . Thus , the increased neuromuscular performance , joint control strategy , and intermuscular coordination ( primary factors ) , together with improved aerobic capacity ( secondary factor ) , may result in reduced oxygen dem and s and increased ME Thomas , K , French , D , and Hayes , PR . The effect of two plyometric training techniques on muscular power and agility in youth soccer players . J Strength Cond Res 23(1 ) : 332 - 335 , 2009-The aim of this study was to compare the effects of two plyometric training techniques on power and agility in youth soccer players . Twelve males from a semiprofessional football club 's academy ( age = 17.3 ± 0.4 years , stature = 177.9 ± 5.1 cm , mass = 68.7 ± 5.6 kg ) were r and omly assigned to 6 weeks of depth jump ( DJ ) or countermovement jump ( CMJ ) training twice weekly . Participants in the DJ group performed drop jumps with instructions to minimize ground-contact time while maximizing height . Participants in the CMJ group performed jumps from a st and ing start position with instructions to gain maximum jump height . Posttraining , both groups experienced improvements in vertical jump height ( p < 0.05 ) and agility time ( p < 0.05 ) and no change in sprint performance ( p > 0.05 ) . There were no differences between the treatment groups ( p > 0.05 ) . The study concludes that both DJ and CMJ plyometrics are worthwhile training activities for improving power and agility in youth soccer players This study was performed to determine which of three theoretically optimal resistance training modalities result ed in the greatest enhancement in the performance of a series of dynamic athletic activities . The three training modalities included 1 ) traditional weight training , 2 ) plyometric training , and 3 ) explosive weight training at the load that maximized mechanical power output . Sixty-four previously trained subjects were r and omly allocated to four groups that included the above three training modalities and a control group . The experimental groups trained for 10 wk performing either heavy squat lifts , depth jumps , or weighted squat jumps . All subjects were tested prior to training , after 5 wk of training and at the completion of the training period . The test items included 1 ) 30-m sprint , 2 ) vertical jumps performed with and without a countermovement , 3 ) maximal cycle test , 4 ) isokinetic leg extension test , and 5 ) a maximal isometric test . The experimental group which trained with the load that maximized mechanical power achieved the best overall results in enhancing dynamic athletic performance recording statistically significant ( P < 0.05 ) improvements on most test items and producing statistically superior results to the two other training modalities on the jumping and isokinetic tests OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity The purpose of this study was to evaluate the effects of sprint training on muscle function and dynamic athletic performance and to compare them with the training effects induced by st and ard plyometric training . Male physical education students were assigned r and omly to 1 of 3 groups : sprint group ( SG ; n = 30 ) , plyometric group ( PG ; n = 30 ) , or control group ( CG ; n = 33 ) . Maximal isometric squat strength , squat- and counter-movement jump ( SJ and CMJ ) height and power , drop jump performance from 30-cm height , and 3 athletic performance tests ( st and ing long jump , 20-m sprint , and 20-yard shuttle run ) were measured prior to and after 10 weeks of training . Both experimental groups trained 3 days a week ; SG performed maximal sprints over distances of 10–50 m , whereas PG performed bounce-type hurdle jumps and drop jumps . Participants in the CG group maintained their daily physical activities for the duration of the study . Both SG and PG significantly improved drop jump performance ( 15.6 and 14.2 % ) , SJ and CMJ height ( ∼10 and 6 % ) , and st and ing long jump distance ( 3.2 and 2.8 % ) , whereas the respective effect sizes ( ES ) were moderate to high and ranged between 0.4 and 1.1 . In addition , SG also improved isometric squat strength ( 10 % ; ES = 0.4 ) and SJ and CMJ power ( 4 % ; ES = 0.4 , and 7 % ; ES = 0.4 ) , as well as sprint ( 3.1 % ; ES = 0.9 ) and agility ( 4.3 % ; ES = 1.1 ) performance . We conclude that short-term sprint training produces similar or even greater training effects in muscle function and athletic performance than does conventional plyometric training . This study provides support for the use of sprint training as an applicable training method of improving explosive performance of athletes in general Among sport conditioning coaches , there is considerable discussion regarding the efficiency of training methods that improve lower-body power . Heavy resistance training combined with vertical jump ( VJ ) training is a well-established training method ; however , there is a lack of information about its combination with Olympic weightlifting Output:	Change in VJ height was not different for OW versus plyometric training . CONCLUSIONS OW is an effective training method to improve VJ height . The similar effects observed for OW and plyometric training on VJ height suggests that either of these methods would be beneficial when devising training programmes to improve VJ height
MS22035	*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 Contrast media ( CM ) injection protocol s should be customized to the individual patient . Aim of this study was to determine if software tailored CM injections result in diagnostic enhancement of the coronary arteries in computed tomography angiography ( CTA ) and if attenuation values were comparable between different weight categories . MATERIAL S AND METHODS 265 consecutive patients referred for routine coronary CTA were scanned on a 2nd generation dual- source CT . Group 1 ( n=141 ) received an individual CM bolus based on weight categories ( 39 - 59 kg ; 60 - 74 kg ; 75 - 94 kg ; 95 - 109 kg ) and scan duration ( ' high-pitch : 1s ; " dual-step prospect i ve triggering " : 7s ) , as determined by contrast injection software ( Certegra ™ P3 T , Bayer , Berlin , Germany ) . Group 2 ( n=124 ) received a st and ard fixed CM bolus ; Iopromide 300 mgI/ml ; volume : 75 ml ; flow rate : 7.2 ml/s . Contrast enhancement was measured in all proximal and distal coronary segments . Subjective and objective image quality was evaluated . Statistical analysis was performed using SPSS ( IBM , version 20.0 ) . RESULTS For group 1 , mean attenuation values of all segments were diagnostic ( > 325 HU ) without statistical significant differences between different weight categories ( p>0.17 ) , proximal vs. distal : 449 ± 65 - 373 ± 58 HU ( 39 - 59 kg ) ; 443 ± 69 - 367 ± 81 HU ( 60 - 74 kg ) ; 427 ± 59 - 370 ± 61 HU ( 75 - 94 kg ) ; 427 ± 73 - 347 ± 61 HU ( 95 - 109 kg ) . Mean CM volumes were : 55 ± 6 ml ( 39 - 59 kg ) ; 61 ± 7 ml ( 60 - 74 kg ) ; 71 ± 8 ml ( 75 - 94 kg ) ; 84 ± 9 ml ( 95 - 109 kg ) . For group 2 , mean attenuation values were not all diagnostic with differences between weight categories ( p<0.01 ) , proximal vs. distal : 611 ± 142 - 408 ± 69 HU ( 39 - 59 kg ) ; 562 ± 135 - 389 ± 98 HU ( 60 - 74 kg ) ; 481 ± 83 - 329 ± 81 HU ( 75 - 94 kg ) ; 420 ± 73 - 305 ± 35 HU ( 95 - 109 kg ) . Comparable image noise and image quality were found between groups ( p ≥ 0.330 ) . CONCLUSIONS Individually tailored CM injection protocol s yield diagnostic attenuation and a more homogeneous enhancement pattern between different weight groups . CM volumes could be reduced for the majority of patients utilizing individualized CM bolus application Objective : To compare patient-weight-adjusted and fixed iodine-dose protocol s at coronary computed tomography angiography ( CTA ) using a 64-detector scanner and computer-assisted bolus tracking . Material s and Methods : Approval from our institutional review board and patient prior informed consent were obtained before entering 60 patients with suspected coronary disease in this study . The patients were r and omly assigned to one of 2 protocol s. In the fixed iodine-dose protocol , they received a fixed dose of 80 mL Iopamidol-370 ; the injection duration was 20 seconds . In the weight-adjusted iodine-dose protocol , the dose was tailored to the patient body weight ; this group received 1.0 mL/kg and the injection duration was shorter , ie , 15 seconds . Imaging was on a 64-detector CT scanner using a computer-assisted bolus tracking technique . A radiologist blinded to the protocol used measured the Hounsfield density number of the large vessels and coronary arteries . CT attenuation in the aortic root was compared in patients whose weight was less than 58 kg ( group 1 ) or 58 kg or more ( group 2 ) . The st and ard deviation ( SD ) of CT attenuation in the aortic root and the myocardium was compared with evaluate image noise . Using a 3-point scale , 2 radiologists independently evaluated beam-hardening artifacts and coronary enhancement . Statistical analysis was with the two-tailed Student t test and the Mann-Whitney U test . Results : There was no significant difference between the protocol s with respect to CT attenuation of the ascending aorta and coronary arteries . Under the fixed-iodine-dose protocol , mean CT attenuation in the aortic root was 421.3 ± 51.5 Hounsfield unit ( HU ) in the lighter- , and 397.2 ± 42.3 HU in the heavier weight group , respectively ; the difference was statistically significant ( P = 0.03 ) . Under the weight-adjusted iodine-dose protocol , these values were 407.6 ± 85.1 and 409.2 ± 47.9 HU , respectively and the difference was not statistically significant ( P = 0.17 ) . The SD of the ascending aorta and myocardium was significantly higher for the fixed- than the weight-adjusted iodine-dose protocol . The mean visual score for beam-hardening artifacts was significantly lower in the weight-adjusted- than the fixed-iodine-dose protocol ( P < 0.01 ) , however , there was no significant difference in the enhancement of the coronary arteries ( P = 0.82 ) . Conclusion : At 64-detector CTA of the heart , the patient weight-tailored dose protocol with the 15-second injection duration yielded significantly better image quality than the fixed-dose , 20-second injection duration protocol PURPOSE An extensive number of protocol s have been suggested to allow for functional diagnostics ; however , no data is available about the minimal amount of contrast medium to achieve reliable imaging properties . None of the plethora of existing studies report a rational why the specific concentration was chosen . MATERIAL S AND METHODS A total of 40 patients were included in this prospect i ve , controlled study . They were divided up into four equal groups getting a different concentration ( 10 % , 20 % , 30 % or 40 % ) of a second contrast medium bolus . Corresponding septal and right ventricular ROIs were compared . A visual score was established . Coronary attenuation was measured in the right and left coronary artery . Streak artifacts in the right atrium/ventricle were assessed . RESULTS In the 10 % contrast medium ( CM ) group only in 5/10 ( 50 % ) patients full septal delineation was reached . In all other groups full septal visualization was obtained . No group showed a relevant difference of mean density measured in HU units of the left ventricle or the coronary arteries . All study groups except of group 1 ( 10 % CM ) showed streak artifacts in the right atrium . CONCLUSION The dual flow protocol with a minimum concentration of 20 % improves septal visualization as basis for left ventricular functional assessment , however , does not allow for reliable right ventricular or atrial visualization . There is no significant difference between the different concentration protocol s in terms of coronary attenuation Purpose Pain sensation and extravasation are potential drawbacks of contrast media ( CM ) injection during computed tomographic angiography . The purpose was to evaluate safety and patient comfort of higher flow rates in different CM protocol s during coronary computed tomographic angiography . Methods Two hundred consecutive patients of a double-blind r and omized controlled trial ( NCT02462044 ) were analyzed . Patients were r and omized to receive 94 mL of prewarmed iopromide 240 mg I/mL at 8.3 mL/s ( group I ) , 75 mL of 300 mg I/mL at 6.7 mL/s ( group II ) , or 61 mL of 370 mg I/mL at 5.4 mL/s ( group III ) , respectively . Iodine delivery rate ( 2.0 g I/s ) and total iodine load ( 22.5 g I ) were kept identical . Outcome was defined as intravascular enhancement , patient comfort during injection , and injection safety , expressed as the occurrence of extravasation . Patients completed a question naire for comfort , pain , and stress during CM injection . Comfort was grade d using a 5-point scale , 1 representing “ very bad ” and 5 “ very well . ” Pain was grade d using a 10-point scale , 0 representing “ no pain ” and 10 “ severe pain . ” Stress was grade d using a 5-point scale , 1 representing “ no stress ” and 5 “ unsustainable stress . ” Results Mean enhancement levels within the coronary arteries were as follows : 437 ± 104 Hounsfield units ( HU ) ( group I ) , 448 ± 111 HU ( group II ) , and 447 ± 106 HU ( group III ) , with P ≥ 0.18 . Extravasation occurred in none of the patients . Median ( interquartile range ) for comfort , pain , and stress was , respectively , 4 ( 4–5 ) , 0 ( 0–0 ) , and 1 ( 1–2 ) , with P ≥ 0.68 . Conclusions High flow rates of prewarmed CM were safely injected without discomfort , pain , or stress . Therefore , the use of high flow rates should not be considered a drawback for CM administration in clinical practice OBJECTIVE Because an increase in body mass index ( weight in kilograms divided by height squared in meters ) confers higher image noise at coronary CT angiography , we evaluated a body mass index-adapted scanning protocol for low-dose 64-MDCT coronary angiography with prospect i ve ECG triggering . SUBJECTS AND METHODS One hundred one consecutively registered patients underwent coronary CTA with prospect i ve ECG triggering with a fixed contrast protocol ( 80 mL of iodixanol , 50-mL saline chaser , flow rate of 5 mL/s ) . Tube voltage ( range , 100 - 120 kV ) and current ( range , 450 - 700 mA ) were adapted to body mass index . Attenuation was measured , and contrast-to-noise ratio was calculated for the proximal right coronary artery and left main coronary artery . Image noise was determined for each patient as the SD of attenuation in the ascending aorta . RESULTS Body mass index ranged from 18.2 to 38.8 , and mean effective radiation dose from 1.0 to 3.2 mSv . There was no correlation between body mass index and image noise ( r = 0.11 , p = 0.284 ) , supporting the validity of the body mass index-adapted scanning protocol . However , body mass index was inversely correlated with vessel attenuation ( right coronary artery , r = -0.45 , p < 0.001 ; left main coronary artery , r = -0.47 , p < 0.001 ) and contrast-to-noise ratio ( right coronary artery , r = -0.39 , p < 0.001 ; left main coronary artery , r = -0.37 , p < 0.001 ) . CONCLUSION Use of the proposed body mass index-adapted scanning parameters results in similar image noise regardless of body mass index . Increased bolus dilution due to larger blood volume may account for the decrease in contrast-to-noise ratio and vessel attenuation in patients with higher body mass index , but the contrast bolus was not adapted to body mass index in this study Objective To prospect ively investigate the influence of contrast material concentration on enhancement in cardiac CT by using a biphasic single-injection protocol . Methods Sixty-four-row multidetector cardiac CT angiography was performed in 159 patients r and omised to a moderate or high contrast medium concentration . Contrast material injection included a first phase for enhancement of the coronary arteries and a second phase , at half the iodine flux , targeted at enhancement of the right ventricle . Contrast medium injection was followed by a saline flush . For both concentrations , injection duration ( and thus total iodine dose ) was adapted to the duration of the CT data acquisition and iodine flux was adjusted to patient weight . Attenuation was measured at various levels in the heart and vessels and the two concentrations compared , overall and per weight group . Results Enhancement of the aorta and left ventricle was significantly greater with the moderate than with the high concentration contrast medium . This remained true for the two higher weight groups . No difference was found in the lowest weight group or in the right ventricle and pulmonary outflow tract . Conclusion With a biphasic injection protocol , enhancement of the aorta and left ventricle was weaker with the higher concentration of contrast material To individually optimize contrast medium protocol for high-pitch prospect i ve ECG-triggering coronary CT angiography using body weight . Ninety patients undergoing high-pitch coronary CT angiography were r and omly assigned to 3 contrast medium injection protocol s with bolus tracking technique : Group A , 0.7 ml CM per kg patient weight ( ml/kg ) ; Group B , 0.6 ml/kg ; Group C , 0.5 ml/kg . Each group had 30 patients . The CT values of superior vena cava ( SVC ) , pulmonary artery ( PA ) , ascending aorta ( Output:	Based on the extracted data , it remains unclear which of the injection parameters is the most important determinant for adequate attenuation .
MS22036	*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 a large Swedish multicenter r and omized controlled trial ( RCT ) on intra partum fetal monitoring with automatic analysis of fetal ECG waveform ( STAN ) in combination with cardiotocography ( CTG ) ( 4966 parturients , 300 obstetricians and midwives managing the patients ) , interim analysis revealed protocol violations . By a post hoc analysis of the results over time , factors affecting the acceptance of the new technique were analyzed . Methods . The rates of primary and secondary outcome measures ( fetal outcome , operative deliveries ) were compared in the two study groups ( CTG + ST and CTG only ) . Changes over time were statistically evaluated using a test for homogeneity between the two periods . Results . After retraining , the CTG + ST group showed the lowest rates of operative delivery for fetal distress , fetal blood sampling and admissions to neonatal intensive care unit . Operative deliveries ( p = 0.02 ) and the number of fetal blood sampling decreased significantly over time ( p = 0.001 ) . Conclusions . Training and education probably predisposed the clinicians to a change and reinforced it when it occurred as a result of increased personal experience . The audit and feedback together with the influence of opinion leaders and inter-collegial interactions seem to have been of importance for the successively increasing acceptance of the new method during the RCT Abstract Objective : The aim of this study was to investigate the possible relationship between cord bloodalpha-fetoprotein ( AFP ) level and development of subsequent neonatal hyperbilirubinemia . Study design : The term newborns born between March 2005 and October 2005 were included in the study . Infants with Coombs-positive ABO and /or Rh incompatibility and /or hemolytic jaundice , asphyxia , congenital anomaly and signs of bleeding were excluded from the study . Cord blood AFP levels were measured in 504 full term newborns in this period . Infants were followed-up for possible neonatal hyperbilirubinemia . The capillary bilirubin level ( CBL ) was examined expeditiously in newborns developing jaundice and in other infants at the time discharge while the screening test was being performed . Results : The mean umbilical cord AFP level was 49.1 ± 44.9 mg/L ( range 1.1–396.2 mg/L ) , mean CBL was 5.8 ± 3.1 mg/dL ( range 1–19.4 mg/dL ) , and the mean bilirubin detection time was 37 ± 23.2 hours ( range 12–144 h ) of age . Although a significant positive correlation was found between umbilical cord AFP and CBL levels , it was weak ( r = 0.187 , p < 0.001 ) . Comparison of AFP levels in terms of bilirubin percentile values appropriate for postnatal age also showed a significant weak positive correlation ( r = 0.113 , p < 0.001 ) . Conclusion : The umbilical cord AFP levels may not be used as a strong predictor for the determination of newborns at risk for hyperbilirubinemia Objective . To undertake a renewed analysis of data from the previously published Swedish r and omized controlled trial on intrapartum fetal monitoring with cardiotocography ( CTG‐only ) vs. CTG plus ST analysis of fetal electrocardiogram ( CTG+ST ) , using current st and ards of intention‐to‐treat ( ITT ) analysis and to compare the results with those of the modified ITT ( mITT ) and per protocol analyses . Methods . Renewed extraction of data from the original data base including all cases r and omized according to primary case allocation ( n=5 049 ) . Main outcome measure . Metabolic acidosis in umbilical artery at birth ( pH < 7.05 , base deficit in extracellular fluid > 12.0mmol/l ) including sample s of umbilical vein blood or neonatal blood if umbilical artery blood was missing . Results . The metabolic acidosis rates were 0.66 % ( 17 of 2 565 ) and 1.33 % ( 33 of 2 484 ) in the CTG+ST and CTG‐only groups , respectively [ relative risk ( RR ) 0.50 ; 95 % confidence interval ( CI ) 0.28–0.88 ; p=0.019 ] . The original mITT gave RR 0.47 , 95%CI 0.25–0.86 ( p=0.015 ) , mITT with correction for 10 previously misclassified cases RR 0.48 , 95%CI 0.24–0.96 ( p=0.038 ) and per protocol analysis RR 0.40 , 95%CI 0.20–0.80 ( p=0.009 ) . The level of significance of the difference in metabolic acidosis rates between the two groups remained unchanged in all analyses . Conclusion . Re‐ analysis of data according to the ITT principle showed that regardless of the method of analysis , the Swedish r and omized controlled trial maintained its ability to demonstrate a significant reduction in metabolic acidosis rate when using CTG+ST analysis for fetal surveillance in labor OBJECTIVE Cardiotocography plus automatic ST analysis of the fetal electrocardiography has been shown recently to reduce both the operative delivery rate for fetal distress and the cord artery metabolic acidosis rate . The purpose of this study was to analyze findings that were related to cases with a complicated/adverse neonatal outcome in the Swedish r and omized controlled trial . STUDY DESIGN Of the 4966 term fetuses that were included in the trial , all 351 newborn infants who required special neonatal care were identified . Cases of perinatal death , neonatal encephalopathy , or metabolic acidosis at birth were review ed . RESULTS Of the 29 fetuses with adverse/complicated neonatal outcome , 22 fetuses had cardiotocography and ST patterns that indicated a need for intervention , according to the cardiotocography plus ST clinical guidelines . The number of live-born with moderate or severe neonatal encephalopathy showed a significant decrease from 0.33 % ( 8/2447 fetuses ) in the cardiotocography-only group to 0.04 % ( 1/2519 fetuses ) in the cardiotocography plus ST group . CONCLUSION Cardiotocography plus ST analysis provides accurate information about intrapartum hypoxia and may prevent intrapartum asphyxia and neonatal encephalopathy by giving a clear alert to the staff members who are in charge OBJECTIVE : To estimate the effectiveness of intrapartum fetal monitoring by cardiotocography plus ST analysis using a strict protocol for performance of fetal blood sampling . METHODS : We performed a multicenter r and omized trial among laboring women with a high-risk singleton pregnancy in cephalic presentation beyond 36 weeks of gestation . Participants were assigned to monitoring by cardiotocography with ST analysis ( index ) or cardiotocography only ( control ) . Primary outcome was metabolic acidosis , defined as an umbilical cord artery pH below 7.05 combined with a base deficit calculated in the extracellular fluid compartment above 12 mmol/L. Secondary outcomes were metabolic acidosis in blood , operative deliveries , Apgar scores , neonatal admissions , and hypoxic – ischemic encephalopathy . RESULTS : We r and omly assigned 5,681 women to the two groups ( 2,832 index , 2,849 control ) . The fetal blood sampling rate was 10.6 % in the index compared with 20.4 % in the control group ( relative risk 0.52 ; 95 % [ CI ] 0.46–0.59 ) . The primary outcome occurred 0.7 % in the index compared with 1.1 % in the control group ( relative risk 0.70 ; 95 % CI 0.38–1.28 ; number needed to treat 252 ) . Using metabolic acidosis calculated in blood , these rates were 1.6 % and 2.6 % , respectively ( relative risk 0.63 ; 95 % CI 0.42–0.94 ; number needed to treat 100 ) . The number of operative deliveries , low Apgar scores , neonatal admissions , and newborns with hypoxic – ischemic encephalopathy was comparable in both groups . CONCLUSION : Intrapartum monitoring by cardiotocography combined with ST analysis does not significantly reduce the incidence of metabolic acidosis calculated in the extracellular fluid compartment . It does reduce the incidence of metabolic acidosis calculated in blood and the need for fetal blood sampling without affecting the Apgar score , neonatal admissions , hypoxic – ischemic encephalopathy , or operative deliveries . CLINICAL TRIAL REGISTRATION : IS RCT N Register , www.is rct n.org , IS RCT N95732366 . LEVEL OF EVIDENCE : BACKGROUND It is unclear whether using fetal electrocardiographic ( ECG ) ST-segment analysis as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring modifies intrapartum and neonatal outcomes . METHODS We performed a multicenter trial in which women with a singleton fetus who were attempting vaginal delivery at more than 36 weeks of gestation and who had cervical dilation of 2 to 7 cm were r and omly assigned to " open " or " masked " monitoring with fetal ST-segment analysis . The masked system functioned as a normal fetal heart-rate monitor . The open system displayed additional information for use when uncertain fetal heart-rate patterns were detected . The primary outcome was a composite of intrapartum fetal death , neonatal death , an Apgar score of 3 or less at 5 minutes , neonatal seizure , an umbilical-artery blood pH of 7.05 or less with a base deficit of 12 mmol per liter or more , intubation for ventilation at delivery , or neonatal encephalopathy . RESULTS A total of 11,108 patients underwent r and omization ; 5532 were assigned to the open group , and 5576 to the masked group . The primary outcome occurred in 52 fetuses or neonates of women in the open group ( 0.9 % ) and 40 fetuses or neonates of women in the masked group ( 0.7 % ) ( relative risk , 1.31 ; 95 % confidence interval , 0.87 to 1.98 ; P=0.20 ) . Among the individual components of the primary outcome , only the frequency of a 5-minute Apgar score of 3 or less differed significantly between neonates of women in the open group and those in the masked group ( 0.3 % vs. 0.1 % , P=0.02 ) . There were no significant between-group differences in the rate of cesarean delivery ( 16.9 % and 16.2 % , respectively ; P=0.30 ) or any operative delivery ( 22.8 % and 22.0 % , respectively ; P=0.31 ) . Adverse events were rare and occurred with similar frequency in the two groups . CONCLUSIONS Fetal ECG ST-segment analysis used as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring did not improve perinatal outcomes or decrease operative-delivery rates . ( Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Neoventa Medical ; Clinical Trials.gov number , NCT01131260 . ) OBJECTIVE To determine the possibilities of ST analysis of fetal ECG ( STAN ) in premature deliveries between 30th to 36th week of pregnancy . To compare the results of a group of premature deliveries monitored by ST analysis with a control group of premature deliveries monitored by means of cardiotocography ( CTG ) and intrapartum fetal pulse oxymetry ( IFPO ) . TYPE OF STUDY A prospect i ve study . SETTING Department of Gynecology-Obstetrics , Masaryk University and Faculty Hospital Brno . METHODS The authors evaluated 39 women with premature delivery between 30th and 36th week of pregnancy from a total cohort of 239 high-risk pregnant women , who had been monitored by means of ST analysis of fetal ECG . The control group included 229 pregnant women who gave birth between 30th and 36th week of pregnancy under the monitoring with CTG and IFPO . The allocation into individual groups was at r and om order . The authors evaluated the duration and way of termination of delivery , pH in arterial umbilical blood , Apgar score in the first , fifth and tenth minute , total duration of hospitalization , necessity and duration of stay at the Neonatologic Intensive Care Unit , Intermediatry Intensive Care Unit , the presence of sepsis , hyperbilirubinemia and neurological state of the newborn . The statistical analysis was performed by means of the Fisher 's exact test , Kruskal-Wallis test , chi2 test and the parametric test Anova . RESULTS Almost none of the observed parameters in both categories of premature deliveries ( STAN vs. CTG+IFPO ) exhibited a statistically significant difference except a mild neurological affection of the newborn . In the group of premature deliveries monitored by ST analysis there are only 33.3 % of newborns with signs of light neurological damage as compared with the control group , where 56.3 % subjects were so affected ( p<0.01 ) . CONCLUSION It has become obvious that the ST analysis of fetal ECG in premature deliveries between 30th and 36th week of pregnancy provides the same results as the so far used monitoring by CTG and IFPO . In the group of premature deliveries monitored by the ST analysis , there Output:	There was little evidence that monitoring by PR interval analysis conveyed any benefit of any sort . The modest benefits of fewer fetal scalp samplings during labour ( in setting s in which this procedure is performed ) and fewer instrumental vaginal births have to be considered against the disadvantages of needing to use an internal scalp electrode , after membrane rupture , for ECG waveform recordings . We found little strong evidence that ST waveform analysis had an effect on the primary outcome measures in this systematic review .There was a lack of evidence showing that PR interval analysis improved any outcomes ; and a larger future trial may possibly demonstrate beneficial effects . There is little information about the value of fetal ECG waveform monitoring in preterm fetuses in labour .
MS22037	*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: Low serum 25-hydroxyvitamin D ( 25(OH)D ) has been shown to correlate with increased risk of type 2 diabetes . Small , observational studies suggest an action for vitamin D in improving insulin sensitivity and /or insulin secretion . The objective of the present study was to investigate the effect of improved vitamin D status on insulin resistance ( IR ) , utilising r and omised , controlled , double-blind intervention administering 100 microg ( 4000 IU ) vitamin D(3 ) ( n 42 ) or placebo ( n 39 ) daily for 6 months to South Asian women , aged 23 - 68 years , living in Auckl and , New Zeal and . Subjects were insulin resistant - homeostasis model assessment 1 (HOMA1)>1.93 and had serum 25(OH)D concentration < 50 nmol/l . Exclusion criteria included diabetes medication and vitamin D supplementation > 25 microg ( 1000 IU)/d . The HOMA2 computer model was used to calculate outcomes . Median ( 25th , 75th percentiles ) serum 25(OH)D(3 ) increased significantly from 21 ( 11 , 40 ) to 75 ( 55 , 84 ) nmol/l with supplementation . Significant improvements were seen in insulin sensitivity and IR ( P = 0.003 and 0.02 , respectively ) , and fasting insulin decreased ( P = 0.02 ) with supplementation compared with placebo . There was no change in C-peptide with supplementation . IR was most improved when endpoint serum 25(OH)D reached > or = 80 nmol/l . Secondary outcome variables ( lipid profile and high sensitivity C-reactive protein ) were not affected by supplementation . In conclusion , improving vitamin D status in insulin resistant women result ed in improved IR and sensitivity , but no change in insulin secretion . Optimal vitamin D concentrations for reducing IR were shown to be 80 - 119 nmol/l , providing further evidence for an increase in the recommended adequate levels . Registered Trial No. ACTRN12607000642482 Abstract Aims /hypothesisThe objective of this prevention programme was to study whether combining pioglitazone with lifestyle modification would enhance the efficacy of lifestyle modification in preventing type 2 diabetes in Asian Indians with impaired glucose tolerance . Methods In a community-based , placebo-controlled 3 year prospect i ve study , 407 participants with impaired glucose tolerance ( mean age 45.3 ± 6.2 years , mean BMI 25.9 ± 3.3 kg/m2 ) were sequentially grouped to receive either : lifestyle modification plus pioglitazone , 30 mg ( n = 204 ) or lifestyle modification plus placebo ( n = 203 ) . The participants and investigators were blinded to the assignment . The primary outcome was development of diabetes . Results At baseline , both groups had similar demographic , anthropometric and biochemical characteristics . At year 3 , the response rate was 90.2 % . The cumulative incidence of diabetes was 29.8 % with pioglitazone and 31.6 % with placebo ( unadjusted HR 1.084 [ 95 % CI 0.753–1.560 ] , p = 0.665 ) . Normoglycaemia was achieved in 40.9 % and 32.3 % of participants receiving pioglitazone and placebo , respectively ( p = 0.109 ) . In pioglitazone group , two deaths and two non-fatal hospitalisations occurred due to cardiac problems ; in the placebo group there were two occurrences of cardiac disease . Conclusions /interpretationDespite good adherence to lifestyle modification and drug therapy , no additional effect of pioglitazone was seen above that achieved with placebo . The effectiveness of the intervention in both groups was comparable with that of lifestyle modification alone , as reported from the Indian Diabetes Prevention Programme-1 . The results are at variance with studies that showed significant relative risk reduction in conversion to diabetes with pioglitazone in Americans with IGT . An ethnicity-related difference in the action of pioglitazone in non-diabetic participants may be one explanation . Trial registration : Clinical Trials.gov NCT00276497 Funding : This study was funded by the India Diabetes Research Background Expert bodies and health organisations recommend that adults undertake at least 150 min.week−1 of moderate-intensity physical activity ( MPA ) . However , the underpinning data largely emanate from studies of population s of European descent . It is unclear whether this level of activity is appropriate for other ethnic groups , particularly South Asians , who have increased cardio-metabolic disease risk compared to Europeans . The aim of this study was to explore the level of MPA required in South Asians to confer a similar cardio-metabolic risk profile to that observed in Europeans undertaking the currently recommended MPA level of 150 min.week−1 . Methods Seventy-five South Asian and 83 European men , aged 40–70 , without cardiovascular disease or diabetes had fasted blood taken , blood pressure measured , physical activity assessed objective ly ( using accelerometry ) , and anthropometric measures made . Factor analysis was used to summarise measured risk biomarkers into underlying latent ‘ factors ’ for glycaemia , insulin resistance , lipid metabolism , blood pressure , and overall cardio-metabolic risk . Age-adjusted regression models were used to determine the equivalent level of MPA ( in bouts of ≥10 minutes ) in South Asians needed to elicit the same value in each factor as Europeans undertaking 150 min.week−1 MPA . Findings For all factors , except blood pressure , equivalent MPA values in South Asians were significantly higher than 150 min.week−1 ; the equivalent MPA value for the overall cardio-metabolic risk factor was 266 ( 95 % CI 185 - 347 ) min.week−1 . Conclusions South Asian men may need to undertake greater levels of MPA than Europeans to exhibit a similar cardio-metabolic risk profile , suggesting that a conceptual case can be made for ethnicity-specific physical activity guidance . Further study is needed to extend these findings to women and to replicate them prospect ively in a larger cohort Background — Body mass index ( BMI ) is widely used to assess risk for cardiovascular disease and type 2 diabetes . Cut points for the classification of obesity ( BMI > 30 kg/m2 ) have been developed and vali date d among people of European descent . It is unknown whether these cut points are appropriate for non-European population s. We assessed the metabolic risk associated with BMI among South Asians , Chinese , Aboriginals , and Europeans . Methods and Results — We r and omly sample d 1078 subjects from 4 ethnic groups ( 289 South Asians , 281 Chinese , 207 Aboriginals , and 301 Europeans ) from 4 regions in Canada . Principal components factor analysis was used to derive underlying latent or “ hidden ” factors associated with 14 clinical and biochemical cardiometabolic markers . Ethnic-specific BMI cut points were derived for 3 cardiometabolic factors . Three primary latent factors emerged that accounted for 56 % of the variation in markers of glucose metabolism , lipid metabolism , and blood pressure . For a given BMI , elevated levels of glucose- and lipid-related factors were more likely to be present in South Asians , Chinese , and Aboriginals compared with Europeans , and elevated levels of the blood pressure – related factor were more likely to be present among Chinese compared with Europeans . The cut point to define obesity , as defined by distribution of glucose and lipid factors , is lower by ≈6 kg/m2 among non-European groups compared with Europeans . Conclusions — Revisions may be warranted for BMI cut points to define obesity among South Asians , Chinese , and Aboriginals . Using these revised cut points would greatly increase the estimated burden of obesity-related metabolic disorders among non-European population High prevalence of type 2 diabetes ( T2D ) is seen in some immigrant groups in Western countries , particularly in those from the Indian subcontinent . Our aims were to increase the physical activity ( PA ) level in a group of Pakistani immigrant men , and to see whether any increase was associated with reduced serum glucose and insulin concentrations . The intervention was developed in collaboration with the Pakistani community . It used a social cognitive theory framework and consisted of structured supervised group exercises , group lectures , individual counselling and telephone follow-up . One- hundred and fifty physically inactive Pakistani immigrant men living in Oslo , Norway , were r and omised to either a control group or an intervention group . The 5-month intervention focused on increasing levels of PA , which were assessed by use of accelerometer ( Actigraph MTI 7164 ) recordings . Risk of diabetes was assessed by serum glucose and insulin concentrations determined in a fasted state , and after an oral glucose tolerance test ( OGTT ) . ANCOVA was used to assess differences between groups . There was a mean difference in PA between the two groups of 49 counts per minute per day , representing a 15 % ( 95 % CI = 8.7–21.2 ; P = 0.01 ) higher increase in total PA level in the intervention group than in the control group . Insulin values taken 2 h after an OGTT were reduced in the intervention group by 27 % ( 95 % CI = 18.9–35.0 ; P = 0.02 ) more than those in the control group . There were no differences in fasting or postpr and ial glucose values between the groups at the follow-up test . This type of intervention can increase PA and reduce serum insulin in Pakistani immigrant men , thereby presumably reducing their risk of T2D Introduction Type 2 diabetes ( T2D ) is a major health concern among population s of South Asian ethnicity . Although dietary and physical activity interventions may reduce the risk of T2D , the effectiveness has been moderate among South Asians . This might ( in part ) be because this subgroup follows strategies that were originally developed for interventions among other population s. Therefore , this review aims to assess the evidence for the current dietary and physical activity strategies recommended in T2D prevention intervention studies and guidelines for South Asians . Methods and analysis Included will be all studies and guidelines on dietary and /or physical activity strategies to prevent T2D in adult South Asians . Two review ers will search online data bases from their start until the present date for published and unpublished experimental/quasiexperimental studies , with at least an abstract in English . References of identified articles and key review s will be screened for additional studies . Guidelines will be identified by search es in online data bases and websites of public organisations . Finally , expert consultations will be held to supplement any missing information . Trial quality will be assessed with the Quality Assessment Tool for Quantitative Studies Data , and guidelines with the Appraisal of Guidelines for Research & Evaluation II . Data on the strategies recommended , targeting and evidence on effectiveness will be extracted by two review ers and presented in tabular and narrative forms . Recommendations will be compared with the National Institute for Health and Care Excellence guidelines [ PH35 ] . Overall findings on dietary and physical activity recommendations , as well as findings for specific subgroups ( eg , by sex ) , will be discussed . Ethics and dissemination Ethics assessment is not required . Start date : 1 January 2016 , finishing and reporting date 31 July 2016 . Results will be published in a peer- review ed scientific journal , the project report of EuroDHYAN ( www.eurodhyan.eu ) and in a PhD dissertation . Trial registration number The protocol is registered with the International Prospect i ve Register of Systematic Review s ( PROSPERO ) registration number CRD42015027067 AIMS To assess the beneficial effects of the components of lifestyle intervention in reducing incidence of diabetes in Asian Indian men with impaired glucose tolerance ( IGT ) in India . METHODS This analysis was based on a 2 year prospect i ve , r and omized controlled primary prevention trial in a cohort of Asian Indian men with IGT ( n=537 ) ( Clinical Trial No : NCT00819455 ) . Intervention and control groups were given st and ard care advice at baseline . Additionally , the intervention group received frequent , mobile phone based text message reminders on healthy lifestyle principles . Dietary intake and physical activity habits were recorded by vali date d question naires . The lifestyle goals were : reductions in consumption of carbohydrates , oil , portion size and body mass index of at least 1 unit ( 1 kg/m(2 ) ) from baseline and maintenance of good physical activity . The association between diabetes and lifestyle goals achieved was assessed using multiple logistic regression analyses . Changes in insulin sensitivity ( Matsuda 's insulin sensitivity index ) and oral disposition index during the follow-up were assessed . RESULTS At the end of the study , 123 ( 23.8 % ) participants developed diabetes . The mean lifestyle score was higher in the intervention group compared with control ( 2.59 ± 1.13 vs. 2.28 ± 1.17 ; P=0.002 ) . Among the 5 lifestyle variables , significant improvements in the 3 dietary goal were seen with intervention . Concomitant improvement in insulin sensitivity and oral disposition index was noted . Higher lifestyle score was associated with lower risk of developing diabetes ( odds ratio : 0.54 [ 95 % CI : 0.44 - 0.70 ] ; P Output:	Intervention studies and guidelines did not reference evidence to support the effectiveness of components included in the intervention for South Asian population s in particular .
MS22038	*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: Renal tissue hypoxia is a final pathway in the development and progression of chronic kidney disease ( CKD ) , but whether renal oxygenation predicts renal function decline in humans has not been proven . Therefore , we performed a prospect i ve study and measured renal tissue oxygenation by blood oxygenation level-dependent magnetic resonance imaging ( BOLD-MRI ) in 112 patients with CKD , 47 with hypertension without CKD , and 24 healthy control individuals . Images were analyzed with the twelve-layer concentric objects method that divided the renal parenchyma in 12 layers of equal thickness and reports the mean R2 * value of each layer ( a high R2 * corresponds to low oxygenation ) , along with the change in R2 * between layers called the R2 * slope . Serum creatinine values were collected to calculate the yearly change in estimated glomerular function rate ( MDRD eGFR ) . Follow up was three years . The change in eGFR in CKD , hypertensive and control individuals was -2.0 , 0.5 and -0.2 ml/min/1.73m2/year , respectively . In multivariable regression analysis adjusted for age , sex , diabetes , RAS-blockers , eGFR , and proteinuria the yearly eGFR change correlated negatively with baseline 24 hour proteinuria and the mean R2 * value of the cortical layers , and positively with the R2 * slope , but not with the other covariates . Patients with CKD and high outer R2 * or a flat R2 * slope were three times more likely to develop an adverse renal outcome ( renal replacement therapy or over a 30 % increase in serum creatinine ) . Thus , low cortical oxygenation is an independent predictor of renal function decline . This finding should stimulate studies exploring the therapeutic impact of improving renal oxygenation on renal disease progression BACKGROUND AND OBJECTIVES Atherosclerotic renal artery stenosis ( ARAS ) can reduce renal blood flow , tissue oxygenation , and GFR . In this study , we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function , pressor hormones , and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Nonr and omized inpatient studies were performed in patients with unilateral ARAS ( > 60 % occlusion ) before and 3 months after revascularization ( n=10 ) or medical therapy ( n=20 ) or patients with essential hypertension ( n=32 ) under identical conditions . The primary study outcome was change in single-kidney GFR . Individual kidney hemodynamics and volume were measured using multidetector computed tomography . Tissue oxygenation ( using R(2 ) * as a measure of deoxyhemoglobin ) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin ( NGAL ) , monocyte chemoattractant protein-1 ( MCP-1 ) , and plasma renin activity were measured . RESULTS Total GFR did not change over 3 months in either group , but the stenotic kidney ( STK ) GFR rose over time in the stent compared with the medical group ( + 2.2[-1.8 to 10.5 ] versus -5.3[-7.3 to -0.3 ] ml/min ; P=0.03 ) . Contralateral kidney ( CLK ) GFR declined in the stent group ( 43.6±19.7 to 36.6±19.5 ml/min ; P=0.03 ) . Fractional tissue hypoxia fell in the STK ( fraction R(2 ) * > 30/s : 22.1%±20 % versus 14.9%±18.3 % ; P<0.01 ) after stenting . Renal vein biomarkers correlated with the degree of hypoxia in the STK : NGAL(r=0.3 ; P=0.01 ) and MCP-1(r=0.3 ; P=0.02 ; more so after stenting ) . Renal vein NGAL was inversely related to renal blood flow in the STK ( r=-0.65 ; P<0.001 ) . Biomarkers were highly correlated between STK and CLK , NGAL ( r=0.94 ; P<0.001 ) , and MCP-1 ( r=0.96 ; P<0.001 ) . CONCLUSIONS These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR . Furthermore , they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS . Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines PURPOSE To prospect ively determine the 3-year stability and potential changes of functional parameters in renal allograft recipients obtained from diffusion-weighted imaging ( DWI ) and blood oxygenation level-dependent ( BOLD ) MRI . MATERIAL S AND METHODS Nine renal allograft recipients underwent DWI and BOLD-MRI twice , once 7 ± 3 months after transplantation , and again 32 ± 2 months after the first MRI . DWI yielded an apparent diffusion coefficient ( ADC ) and the perfusion contribution ( F(P ) ) . BOLD imaging yielded R2 , providing an estimation of renal oxygenation . Coefficients of variation between ( CV(b ) ) and within subjects ( CV(w ) ) were calculated . RESULTS The parameters were stable after 32 months in eight of the nine patients , who had well-functioning allografts . Mean diffusion values were very similar in the first and second scan . CV(w ) and CV(b ) for ADC values were less than 3.5 % and 5.9 % , respectively , in cortex and medulla , but were higher for F(P ) ( 15%-18 % ) . CV(w ) and CV(b ) of R2 were also low ( medulla : CV(w ) = 10.8 % , CV(b ) = 11.4 % ; cortex : CV(w ) and CV(b ) = 7.2 % ) . R2 increased significantly ( P = 0.035 ) in cortex but not in medulla , suggesting reduced cortical oxygen content . One subject with decreased glomerular filtration rate demonstrated strongly altered parameters . CONCLUSION In the absence of graft dysfunction , DWI and BOLD imaging yield consistent results over 3 years in stable human renal allograft recipients Background — Atherosclerotic renal artery stenosis reduces renal blood flow ( RBF ) and amplifies stenotic kidney hypoxia . Revascularization with percutaneous transluminal renal angioplasty ( PTRA ) and stenting often fails to recover renal function , possibly because of ischemia/reperfusion injury developing after PTRA . Elamipretide is a mitochondrial-targeted peptide that binds to cardiolipin and stabilizes mitochondrial function . We tested the hypothesis that elamipretide plus PTRA would improve renal function , oxygenation , and RBF in patients with atherosclerotic renal artery stenosis undergoing PTRA . Methods and Results — Inpatient studies were performed in patients with severe atherosclerotic renal artery stenosis scheduled for PTRA . Patients were treated before and during PTRA with elamipretide ( 0.05 mg/kg per hour intravenous infusion , n=6 ) or placebo ( n=8 ) . Stenotic kidney cortical/medullary perfusion and RBF were measured using contrast-enhanced multidetector CT , and renal oxygenation by 3-T blood oxygen level−dependent magnetic resonance imaging before and 3 months after PTRA . Age and basal glomerular filtration rate did not differ between groups . Blood oxygen level−dependent imaging demonstrated increased fractional hypoxia 24 hours after angiography and stenting in placebo ( + 47 % ) versus elamipretide ( −6 % ) . These were reverted to baseline 3 months later . Stenotic kidney RBF rose ( 202±29–262±115 mL/min ; P=0.04 ) 3 months after PTRA in the elamipretide-treated group only . Over 3 months , systolic blood pressure decreased , and estimated glomerular filtration rate increased ( P=0.003 ) more in the elamipretide group than in the placebo group ( P=0.11 ) . Conclusions — Adjunctive elamipretide during PTRA was associated with attenuated postprocedural hypoxia , increased RBF , and improved kidney function in this pilot trial . These data support a role for targeted mitochondrial protection to minimize procedure-associated ischemic injury and to improve outcomes of revascularization for human atherosclerotic renal artery stenosis . Clinical Trial Registration — URL : https://www . clinical trials.gov . Unique identifier : NCT01755858 PURPOSE To prospect ively assess the oxygenation state of renal transplants and determine the feasibility of using blood oxygen level-dependent ( BOLD ) magnetic resonance ( MR ) imaging to differentiate between acute tubular necrosis ( ATN ) , acute rejection , and normal function . MATERIAL S AND METHODS This HIPAA-compliant study had institutional human subjects review committee approval , and written informed consent was obtained from all patients . BOLD MR imaging was performed in 20 patients ( age range , 21 - 70 years ) who had recently received renal transplants . Six patients had clinical ly normal functioning transplants , eight had biopsy-proved rejection , and six had biopsy-proved ATN . R2 * ( 1/sec ) measurements were obtained in the medulla and cortex of transplanted kidneys . R2 * is a measure of the rate of signal loss in a specific region and is related to the amount of deoxyhemoglobin present . Statistical analysis was performed by using a two- sample t test . Threshold R2 * values were identified to discriminate between transplanted kidneys with ATN , those with acute rejection , and those with normal function . RESULTS R2 * values for the medulla were significantly lower in the acute rejection group ( R2 * = 15.8/sec + /- 1.5 ) than in normally functioning transplants ( R2 * = 23.9/sec + /- 3.2 ) and transplants with ATN ( R2 * = 21.3/sec + /- 1.9 ) . The differences between the acute rejection and normal function groups ( P = .001 ) , as well as between the acute rejection and ATN groups ( P < .001 ) , were significant . Acute rejection could be differentiated from normal function and ATN in all cases by using a threshold R2 * value of 18/sec . R2 * values for the cortex were higher in ATN ( R2 * = 14.2/sec + /- 1.4 ) than for normally functioning transplants ( R2 * = 12.7/sec + /- 1.6 ) and transplants with rejection ( R2 * = 12.4/sec + /- 1.2 ) . The difference in R2 * values in the cortex between ATN and rejection was statistically significant ( P = .034 ) , although there was no threshold value that enabled differentiation of all cases of ATN from cases of normal function or acute rejection . CONCLUSION R2 * measurements in the medullary regions of transplanted kidneys with acute rejection were significantly lower than those in normally functioning transplants or transplants with ATN . These results suggest that marked changes in intrarenal oxygenation occur during acute transplant rejection Acute experimental reduction of renal blood flow decreases the renal blood oxygenation level – dependent ( BOLD ) MRI signal in animals . Angiotensin II also reduces renal blood flow , but the ability of BOLD MRI to dynamically detect this response has not yet been investigated in humans . Six healthy male volunteers underwent an individual dose-finding study to identify the intravenous doses of angiotensin II , norepinephrine , and sodium nitroprusside necessary to induce a 15-mm Hg peak mean arterial blood pressure change . MRI studies followed within 3 weeks , when angiotensin II ( 8.8±1.4 ng/kg ) , norepinephrine ( 52±12 ng/kg ) , and sodium nitroprusside ( 2.0±0.3 & mgr;g/kg ) were given twice in an unblocked , r and omized sequence while imaging experiments were performed on a 1.5-T Siemens Sonata . A multiecho echo-planar imaging sequence was used to acquire T2 * maps with a temporal resolution of 1 respiratory cycle . Averaged over a renal cortex dominated region of interest , angiotensin II caused a shortening of T2 * between 6 % and 10 % . Sodium nitroprusside and norepinephrine , although of equal potency concerning blood pressure responses , did not alter the renal BOLD signal . The renal BOLD response to angiotensin II appeared with short onset latency ( as early as 10 seconds after peripheral intravenous angiotensin II bolus administration ) suggesting that this response is a consequence of altered perfusion rather than increased renal oxygen consumption . The methods described here are suitable to assess renal responsiveness to angiotensin II and may , thus , be of great value in human hypertension research Blood oxygenation level-dependent ( BOLD ) MRI was shown to allow non-invasive observation of renal oxygen Output:	Increases in its outcome measure R2 * ( transverse relaxation rate expressed as per second ) correspond to higher deoxyhaemoglobin concentrations and suggest lower oxygenation , whereas decreases in R2 * indicate higher oxygenation . BOLD-MRI has shown that patients suffering from chronic kidney disease ( CKD ) or kidneys with severe renal artery stenosis have lower tissue oxygenation than controls . Additionally , CKD patients with the lowest cortical oxygenation have the worst renal outcome .
MS22039	*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 YKL-40 , a chitinase-like glycoprotein associated with inflammation and tissue remodeling , is produced by joint tissues and recognized as a c and i date auto-antigen in rheumatoid arthritis ( RA ) . In the present study , we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aim ing for early remission . Methods Ninety-nine patients with early DMARD-naïve RA participated in the NEO-RACo study . For the first four weeks , the patients were treated with the combination of sulphasalazine , methotrexate , hydroxychloroquine and low dose prednisolone ( FIN-RACo DMARD combination ) , and subsequently r and omized to receive placebo or infliximab added on the treatment for further 22 weeks . Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay . Results At the baseline , plasma YKL-40 concentration was 57 ± 37 ( mean ± SD ) ng/ml . YKL-40 was significantly associated with the disease activity score , interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks ’ treatment . The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment , and there was no further reduction when the tumour necrosis factor-α antagonist infliximab was added on the combination treatment . Conclusions High YKL-40 levels were found to be associated with disease activity in early DMARD-naïve RA and during intensive treat-to-target therapy . The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission Output:	This study indicates that OSAHS patients have higher serum YKL-40 level , which may serve as a potential biomarker for OSAHS diagnosis and monitoring
MS22040	*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 Colonoscopy may be associated with discomfort when performed without sedation . A study was conducted to determine whether instillation of water into the colon at the beginning of the procedure reduces intubation time as well as patient discomfort and pain . METHODS Colonoscopy was performed in 259 patients by 3 endoscopists-in-training with limited experience . Patients were r and omly allocated to 2 groups . In one , a technique was used in which 500 to 1000 mL of water is instilled into the colon by enema at the beginning of the procedure ( instillation group , n = 130 ) . In the other , patients underwent a conventional colonoscopy ( control group , n = 129 ) . Intubation time was measured and compared between the groups , and subjective discomfort experienced by the patients was measured upon completion of the examination . RESULTS Success rates for insertion to the cecum were similar , ( 95.4 % , instillation group ; 96.1 % , control group ) . Detection rates for any colorectal diseases were not different between the groups ( 30.0 % vs. 32.6 % ) . Mean time to cecal intubation was 10.5 minutes in the instillation group and 16.2 minutes in the control group ( p < 0.0001 ) . The proportion of patients who complained of abdominal pain during the procedure was 17.1 % in the instillation group and 33.3 % in the control group ( p < 0.001 ) . CONCLUSIONS When used by endoscopists-in-training , the water-instillation colonoscopy technique was associated with less discomfort and faster cecal intubation with no decrease in the rate of detection of colorectal diseases Objective . The volume of colonoscopies performed is increasing and differences in colonoscopy practice over time and between centres have been reported . Examination of current practice is important for benchmarking quality . The objective of this study was to examine variations in colonoscopy practice in endoscopy centres internationally . Material and methods . This observational study prospect ively included consecutive patients referred for colonoscopy from 21 centres in 11 countries . Patient , procedure and centre characteristics were collected through question naires . Descriptive statistics were performed and the variation between centres while controlling for case-mix was examined . Results . A total of 6004 patients were included in the study . Most colonoscopies ( 93 % ; range between centres 70–100 % ) were performed for diagnostic purpose s. The proportion of main indications for colonoscopy showed wide variations between centres , the two most common indications , surveillance and haematochezia , ranging between 7–24 % and 5–38 % , respectively . High- quality cleansing occurred in 74 % ( range 51–94 % ) of patients , and 30 % ( range 0–100 % ) of patients received deep sedation . Three-quarters ( range 0–100 % ) of the patients were monitored during colonoscopy , and one-quarter ( range 14–35 % ) underwent polypectomy . Colonoscopy was complete in 89 % ( range 69–98 % ) of patients and the median total duration was 20 min ( range of centre medians 15–30 min ) . The variation between centres was not reduced when case-mix was controlled for . Conclusions . This study documented wide variations in colonoscopy practice between centres . Controlling for case-mix did not remove these variations , indicating that centre and procedure characteristics play a role . Centres generally were within the existing guidelines , although there is still some work to be done to ensure that all centres attain the goal of providing high- quality colonoscopy BACKGROUND Pilot studies using a novel water method to perform screening colonoscopy allowed patients to complete colonoscopy without sedation medications and also significantly increased the cecal intubation success rate . OBJECTIVE To perform a r and omized , controlled trial comparing air insufflation ( conventional method ) and water infusion in lieu of air insufflation ( study method ) colonoscopy in minimally se date d patients . HYPOTHESIS Compared with the conventional method , patients examined by the study method had lower pain scores and required less medication but had a similar cecal intubation rate and willingness to undergo colonoscopy in the future . SETTING Outpatient colonoscopy in a single Veterans Affairs hospital . METHODS After informed consent and st and ard bowel preparation , patients received premedications administered as 0.5-increments of fentanyl ( 25 microg ) and 0.5-increments of Versed ( midazolam ) ( 1 mg ) plus 50 mg of diphenhydramine . The conventional and the study methods for colonoscopy were implemented as previously described . Additional pain medications were administered at the patients ' request . MAIN OUTCOME MEASUREMENTS Increments of medications , pain scores , cecal intubation , and willingness to repeat colonoscopy . RESULTS Increments of medications used before reaching the cecum ( 1.6 + /- 0.2 vs 2.4 + /- 0.2 , P < .0027 ) , total increments used ( 1.8 + /- 0.2 vs 2.5 + /- 0.2 , P < .014 ) , and the maximum pain scores ( 1.3 + /- 0.3 vs 4.1 + /- 0.6 , P < .0002 ) were significantly lower with the water method . Cecal intubation rate ( 100 % ) and willingness to undergo a repeat colonoscopy ( 96 % ) were similar . LIMITATIONS Single Veterans Affairs hospital , older male population . CONCLUSION Water infusion in lieu of air insufflation is superior to air insufflation during colonoscopy in the minimally se date d patients ( Clinical Trials.gov Identifier NCT00785889 ) BACKGROUND & AIMS Several studies have indicated that water infusion , instead of air insufflation , enhances cecal intubation in selected patients undergoing unse date d colonoscopy . We performed a prospect i ve , r and omized , controlled trial to investigate whether the water technique increases the proportion of patients that are able to complete unse date d colonoscopy . METHODS We analyzed data from 116 consecutive out patients who were willing to start colonoscopy without sedation ; 58 were each r and omly assigned to groups given water infusion or air insufflation during the insertion phase . Sedation and analgesia were administered on dem and . RESULTS Fewer patients requested sedation in the water group ( 8.6 % ) than in the air group ( 34.5 % ; P = .003 ) and their maximum pain scores were lower ( 2.8 ± 1.9 vs 4.2 ± 2.3 in the air group ; P = .011 ) . However , differences in percentages of patients who received complete , unse date d colonoscopy between the water group ( 74.1 % ) and air group ( 62.1 % ) did not reach statistical significance ( P = .23 ) ; the percentage of successful cecal intubations was lower in the water group ( 82.8 % ) than in the air group ( 96.5 % ; P = .03 ) because of poor visibility . Failed procedures in the water group were completed successfully after air insufflation . The cecal intubation time was shorter in the air group ( 6.2 ± 3.4 min ) than in the water group ( 8.1 ± 3.0 min ; P = .01 ) . CONCLUSIONS In patients willing to undergo unse date d colonoscopy , water infusion improves patient tolerance for cecal intubation , compared with air insufflation . However , it does not increase the overall percentage of successful cecal intubations because suboptimal bowel preparation interferes with visibility BACKGROUND : The increasing dem and for colonoscopy has renewed the interest for unse date d procedures . Alternative techniques , such as carbon dioxide insufflation and warm-water infusion , have been advocated to improve patient tolerance for colonoscopy in comparison with air insufflation . OBJECTIVE : The aim of this study was to evaluate the benefits of carbon dioxide insufflation and warm-water irrigation over air insufflation in unse date d patients . DESIGN : This study was a r and omized , controlled trial . SETTING : This study was conducted at a nonacademic single center . PATIENTS : Consecutive out patients agreeing to start colonoscopy without premedication were included . INTERVENTIONS : Patients were assigned to either carbon dioxide insufflation , warm-water irrigation , or air insufflation colonoscopy insertion phase . Sedation/analgesia were administered on patient request if significant pain or discomfort occurred . MAIN OUTCOME MEASURES : The primary outcome measured was the percentage of patients requiring sedation/analgesia . Pain and tolerance scores were assessed at discharge by using a 100-mm visual analog scale . RESULTS : Three hundred forty-one subjects ( 115 in the carbon dioxide , 113 in the warm-water , and 113 in the air group ) were enrolled . Intention-to-treat analysis showed that the proportion of patients requesting sedation/analgesia during colonoscopy was 15.5 % in the carbon dioxide group , 13.2 % in the warm-water group , and 25.6 % in the air group ( p = 0.04 carbon dioxide vs air ; p = 0.03 warm water vs air ) . Median ( interquartile range ) scores for pain were 30 ( 10–50 ) , 28 ( 15–50 ) , and 46 ( 22–62 ) in the carbon dioxide , warm-water , and air groups ( carbon dioxide vs air , p < 0.01 ; warm water vs air , p < 0.01 ) ; corresponding figures for tolerance were 20 ( 5–30 ) , 19 ( 5–36 ) , and 28 ( 10–50 ) ( carbon dioxide vs air , p < 0.01 ; warm water vs air , p < 0.01 ) . LIMITATIONS : This investigation was limited because it was a single-center study and the endoscopists were not blinded to r and omization . CONCLUSIONS : Carbon dioxide insufflation was associated with a decrease in the proportion of patients requesting on-dem and sedation , improved patient tolerance , and decreased colonoscopy-related pain in comparison with air insufflation . The findings regarding warm-water irrigation confirmed the previously reported advantages , so that warm-water irrigation and carbon dioxide insufflation could represent competitive strategies for colonoscopy in unse date d patients BACKGROUND AND STUDY AIMS Water immersion is an alternative colonoscopy technique that may reduce discomfort and facilitate insertion of the instrument . This was a prospect i ve study to compare the success of colonoscopy with minimal sedation using water immersion and conventional air insufflation . PATIENTS AND METHODS A total of 229 patients were r and omized to either water immersion or the st and ard air insertion technique . The primary outcome was success of minimal sedation colonoscopy , which was defined as reaching the cecum without additional sedation , exchange of the adult colonoscope or h and s-on assistance for trainees . Patient comfort and satisfaction were also assessed . RESULTS Successful minimal-sedation colonoscopy was achieved in 51 % of the water immersion group compared with 28 % in the st and ard air group ( OR , 2.66 ; 95 % CI 1.48 - 4.79 ; P = 0.0004 ) . Attending physicians had 79 % success with water immersion compared with 47 % with air insufflation ( OR , 4.19 ; 95 % CI 1.5 - 12.17 ; P = 0.002 ) , whereas trainees had 34 % success with water compared with 16 % using air ( OR , 2.75 ; 95 % CI 1.15 - 6.86 ; P = 0.01 ) . Using the water method , endoscopists intubated the cecum faster and this was particularly notable for trainees ( 13.0 + /- 7.5 minutes with water vs. 20.5 + /- 13.9 minutes with air ; P = 0.0001 ) . Total procedure time was significantly shorter with water for both experienced and trainee endoscopists ( P < 0.05 ) . Patients reported less intraprocedural pain with water compared with air ( 4.1 + /- 2.7 vs. 5.3 + /- 2.7 ; P = 0.001 ) , with a similar level of satisfaction . There was no difference in the neoplasm detection rates between the groups . CONCLUSION Colonoscopy insertion using water immersion increases the success rate of minimal sedation colonoscopy . Use of the technique leads to a decrease in discomfort , time to reach the cecum , and the amount of sedative and analgesic used , without compromising patient satisfaction OBJECTIVES : Completion rates , pain , and difficulties during the exam are still problems in colonoscopy . New methods of lubrication , rarely considered a matter of study , may help in this respect . Our aim was to compare an oil-assisted technique with a modified warm water method applied during colonoscopy . METHODS : A prospect i ve , r and omized , and controlled study was planned in which three groups of patients were su bmi tted to colonoscopy : a st and ard lubricating method ( water-soluble jelly : group A , 170 patients ) was adopted in a control group , whereas the st and ard method plus injection into the colon of corn seed oil ( group B , 170 patients ) or warm water ( group C , 170 patients ) were employed in the other groups . The main variables evaluated were : the success rate for total intubation , the time required to reach the cecum and the time needed to examine the colon at withdrawal , and the level of pain and degree of difficulty associated with the examination Output:	Qualitative analysis suggests that water infusion colonoscopy was not associated with a markedly increased rate of adverse events compared with the st and ard procedure . Completeness of colonoscopy , that is cecal intubation rate , was not improved by water infusion compared with st and ard air insufflation colonoscopy . However , adenoma detection , assessed with two different measures ( that is adenoma detection rate and number of detected adenomas per procedure ) , was slightly augmented by the water infusion colonoscopy . Improved adenoma detection might be due to the cleansing effects of water infusions on the mucosa . Detection of premalignant lesions during st and ard colonoscopy is suboptimal , and so improvements in adenoma detection by water infusion colonoscopy , although small , may help to reduce the risk of interval colorectal carcinoma . The most obvious benefit of water infusion colonoscopy was reduction of procedure-related abdominal pain , which may enhance the acceptance of screening/surveillance colonoscopy
MS22041	*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 Concomitant injuries to secondary structures have been proposed as a major cause of failure of anterior cruciate ligament reconstruction . Purpose Our purpose was to determine the relationship between meniscal status at the time of anterior cruciate ligament reconstruction and ultimate long-term function and stability . Study Design Prospect i ve cohort study . Methods We prospect ively studied 63 patients for an average of 10.4 years after arthroscopically assisted bone-patellar tendon-bone anterior cruciate reconstruction . All surgeries were performed between 1988 and 1991 ; concomitant meniscal surgery was performed if necessary . Subjects were divided into subgroups relative to the integrity of their menisci at the end of the reconstruction procedure ( intact meniscus , partial meniscectomy , complete meniscectomy ) . Results Patients who had undergone any degree of meniscal resection reported significantly more subjective complaints and activity limitations than those with intact menisci . Subjective International Knee Documentation Committee and Lysholm scores were lower in the meniscectomy subgroups than in the meniscus-intact group . Objective testing revealed a significantly lower ability to perform the single-legged hop in the meniscectomy subgroups . Ligament stability based on instrumented laxity measurements was not significantly different between the subgroups . Radiographic abnormalities were also more common in the subgroups that had undergone meniscectomy . Conclusions The menisci should be repaired if at all possible , especially in the setting of anterior cruciate ligament reconstruction , for optimal functional outcome and patient satisfaction BACKGROUND There are no controlled , prospect i ve studies comparing the 10-year outcomes of anterior cruciate ligament ( ACL ) reconstruction using patellar tendon ( PT ) and 4-str and hamstring tendon ( HT ) autografts . HYPOTHESIS Comparable results are possible with HT and PT autografts . STUDY DESIGN Cohort study ; Level of evidence , 2 . METHODS One hundred eighty ACL-deficient knees that met inclusion criteria underwent ACL reconstruction ( 90 HT autograft , 90 PT autograft ) by one surgeon and were treated with an accelerated rehabilitation program . All knees were observed in a prospect i ve fashion with subjective , objective , and radiographic evaluation at 2 , 5 , 7 , and 10-year intervals . RESULTS At 10 years , there were no differences in graft rupture rates ( 7/90 PT vs. 12/90 HT , P = .24 ) . There were 20 contralateral ACL ruptures in the PT group , compared with 9 in the HT group ( P = .02 ) . In all patients , graft rupture was associated with instrumented laxity > 2 mm at 2 years ( P = .001 ) . Normal or near-normal function of the knee was reported in 97 % of patients in both groups . In the PT group , harvest-site symptoms ( P = .001 ) and kneeling pain ( P = .01 ) were more common than in the HT group . More patients reported pain with strenuous activities in PT knees than in HT knees ( P = .05 ) . Radiographic osteoarthritis was more common in PT knees than the HT-reconstructed knees ( P = .04 ) . The difference , however , was composed of patients with mild osteoarthritis . Other predictors of radiographic osteoarthritis were < 90 % single-legged hop test at 1 year and the need for further knee surgery . An " ideal " outcome , defined as an overall International Knee Documentation Committee grade of A or B and a radiographic grade of A at 10 years after ACL reconstruction , was associated with <3 mm of instrumented laxity at 2 years , the absence of additional surgery in the knee , and HT grafts . CONCLUSIONS It is possible to obtain excellent results with both HT and PT autografts . We recommend HT reconstructions to our patients because of decreased harvest-site symptoms and radiographic osteoarthritis We used single-photon emission computed tomography ( SPECT ) to determine the long-term risk of degenerative change after reconstruction of the anterior cruciate ligament ( ACL ) . Our study population was a prospect i ve series of 31 patients with a mean age at injury of 27.8 years ( 18 to 47 ) and a mean follow-up of ten years ( 9 to 13 ) after bone-patellar tendon-bone reconstruction of the ACL . The contralateral normal knee was used as a control . All knees were clinical ly stable with high clinical scores ( mean Lysholm score , 93 ; mean Tegner activity score , 6 ) . Fifteen patients had undergone a partial meniscectomy and ACL reconstruction at or before reconstruction of their ACL . In the group with an intact meniscus , clinical symptoms of osteoarthritis ( OA ) were found in only one patient ( 7 % ) , who was also the only patient with marked isotope uptake on the SPECT scan compatible with OA . In the group which underwent a partial meniscectomy , clinical symptoms of OA were found in two patients ( 13 % ) , who were among five ( 31 % ) with isotope uptake compatible with OA . Only one patient ( 7 % ) in this group had evidence of advanced OA on plain radiographs . The risk of developing OA after ACL reconstruction in this series is very low and lower than published figures for untreated ACL-deficient knees . There is a significant increase ( p < 0.05 ) in degenerative change in patients who had a reconstruction of their ACL and a partial meniscectomy compared with those who had a reconstruction of their ACL alone Objective To compare , in young active adults with an acute anterior cruciate ligament ( ACL ) tear , the mid-term ( five year ) patient reported and radiographic outcomes between those treated with rehabilitation plus early ACL reconstruction and those treated with rehabilitation and optional delayed ACL reconstruction . Design Extended follow-up of prospect i ve r and omised controlled trial . Setting Orthopaedic departments at two hospitals in Sweden . Participants 121 young , active adults ( mean age 26 years ) with acute ACL injury to a previously uninjured knee . One patient was lost to five year follow-up . Intervention All patients received similar structured rehabilitation . In addition to rehabilitation , 62 patients were assigned to early ACL reconstruction and 59 were assigned to the option of having a delayed ACL reconstruction if needed . Main outcome measure The main outcome was the change from baseline to five years in the mean value of four of the five subscales of the knee injury and osteoarthritis outcome score ( KOOS4 ) . Other outcomes included the absolute KOOS4 score , all five KOOS subscale scores , SF-36 , Tegner activity scale , meniscal surgery , and radiographic osteoarthritis at five years . Results Thirty ( 51 % ) patients assigned to optional delayed ACL reconstruction had delayed ACL reconstruction ( seven between two and five years ) . The mean change in KOOS4 score from baseline to five years was 42.9 points for those assigned to rehabilitation plus early ACL reconstruction and 44.9 for those assigned to rehabilitation plus optional delayed reconstruction ( between group difference 2.0 points , 95 % confidence interval −8.5 to 4.5 ; P=0.54 after adjustment for baseline score ) . At five years , no significant between group differences were seen in KOOS4 ( P=0.45 ) , any of the KOOS subscales ( P≥0.12 ) , SF-36 ( P≥0.34 ) , Tegner activity scale ( P=0.74 ) , or incident radiographic osteoarthritis of the index knee ( P=0.17 ) . No between group differences were seen in the number of knees having meniscus surgery ( P=0.48 ) or in a time to event analysis of the proportion of meniscuses operated on ( P=0.77 ) . The results were similar when analysed by treatment actually received . Conclusion In this first high quality r and omised controlled trial with minimal loss to follow-up , a strategy of rehabilitation plus early ACL reconstruction did not provide better results at five years than a strategy of initial rehabilitation with the option of having a later ACL reconstruction . Results did not differ between knees surgically reconstructed early or late and those treated with rehabilitation alone . These results should encourage clinicians and young active adult patients to consider rehabilitation as a primary treatment option after an acute ACL tear . Trial registration Current Controlled Trials IS RCT N84752559 Background The choice of different graft types and surgical techniques used when reconstructing a torn anterior cruciate ligament may influence the long-term prevalence of osteoarthritis and functional outcomes . Hypothesis There are no differences in the prevalence of knee osteoarthritis or knee function in patients undergoing reconstruction of a torn anterior cruciate ligament with 4-str and hamstring autograft versus patellar tendon — bone autograft . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Seventy-two patients with subacute or chronic rupture of the anterior cruciate ligament were r and omly assigned to autograft reconstruction with 4-str and gracilis and semitendinosus tendon ( HAM ) ( N = 37 ) or with patellar tendon — bone ( PTB ) ( N = 35 ) from the ipsilateral side . Outcome measurements were the Cincinnati knee score , single-legged hop tests , isokinetic muscle strength tests , pain , knee joint laxity test ( KT-1000 arthrometer ) , and a radiologic evaluation ( Kellgren and Lawrence ) at 10-year follow-up . Results At 10 years , 57 patients ( 79 % ) were eligible for evaluation—29 in the HAM group and 28 in the PTB group . No differences were found between the 2 graft groups with respect to the Cincinnati knee score , the single-legged hop tests , pain , muscle strength measurements , or knee joint laxity . Fifty-five percent and 64 % of the patients had osteoarthritis corresponding to Kellgren and Lawrence grade 2 or more in the HAM and the PTB groups , respectively ( P = .27 ) . For the uninvolved knee , the corresponding numbers were 28 % and 22 % ( P = .62 ) . Conclusion At 10 years postoperatively , no statistically significant differences in clinical outcome between the 2 graft types were found . The prevalence of osteoarthritis was significantly higher in the operated leg than in the contralateral leg , but there were no significant differences between the 2 groups . The results indicate that the choice of graft type after an anterior cruciate ligament injury has minimal influence on the prevalence of osteoarthritis 10 years after surgery There is little evidence examining the relationship between anatomical l and marks , radiological placement of the tunnels and long-term clinical outcomes following anterior cruciate ligament ( ACL ) reconstruction . The aim of this study was to investigate the reproducibility of intra-operative l and marks for placement of the tunnels in single-bundle reconstruction of the ACL using four-str and hamstring tendon autografts . Isolated reconstruction of the ACL was performed in 200 patients , who were followed prospect ively for seven years with use of the International Knee Documentation Committee forms and radiographs . Taking 0 % as the anterior and 100 % as the posterior extent , the femoral tunnel was a mean of 86 % ( sd 5 ) along Blumensaat 's line and the tibial tunnel was 48 % ( sd 5 ) along the tibial plateau . Taking 0 % as the medial and 100 % as the lateral extent , the tibial tunnel was 46 % ( sd 3 ) across the tibial plateau and the mean inclination of the graft in the coronal plane was 19 degrees ( sd 5.5 ) . The use of intra-operative l and marks result ed in reproducible placement of the tunnels and an excellent clinical outcome seven years after operation . Vertical inclination was associated with increased rotational instability and degenerative radiological changes , while rupture of the graft was associated with posterior placement of the tibial tunnel . If the osseous tunnels are correctly placed , single-bundle reconstruction of the ACL adequately controls both anteroposterior and rotational instability The aims of the study were to analyse the change in knee laxity over time after anterior cruciate ligament ( ACL ) reconstruction , using either bone – patellar – tendon – bone ( BPTB ) or hamstring ( HS ) tendon autografts , and to compare the knee laxity measurements between the study groups both pre-operatively and on multiple follow-up occasions . Another aim was to compare the radiographic findings in terms of degenerative changes between the study groups . A r and omised series of 71 patients , who underwent ACL reconstruction using BPTB or HS tendon autografts and interference screw fixation , were included in the study . Of these patients , 47/71 ( 66 % ) attended a clinical examination , including laxity measurements using the KT-1000 arthrometer , pre-operatively and on four post-operative occasions ; 6 months , 1 year , 2 years and 7 years after the reconstruction . The BPTB group consisted of 22 patients , while there were 25 patients in the HS group . There were no significant differences in the mean side-to-side knee laxity between the BPTB and the HS group pre-operatively or at the follow-up examinations . There was a tendency towards a reduction in side-to-side knee laxity over time in both groups , measured with the KT-1000 arthrometer . The decrease was significant when analysing the injured and uninjured knee separately ( injured side p < 0. Output:	Medial meniscal injury/meniscectomy showed moderate evidence for influencing OA development ( tibiofemoral OA and compartment unspecified ) . Lateral meniscal injury/meniscectomy showed moderate evidence for no relationship ( compartment unspecified ) , as did time between injury and reconstruction ( tibiofemoral and patellofemoral OA ) . CONCLUSIONS Medial meniscal injury/meniscectomy after ACL rupture increased the risk of OA development . In contrast , it seems that lateral meniscal injury/meniscectomy has no relationship with OA development . Our results suggest that time between injury and reconstruction does not influence patellofemoral and tibiofemoral OA development . Many determinants showed conflicting and limited evidence and no determinant showed strong evidence
MS22042	*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: & NA ; Forty‐nine patients suffering from lateral humeral epicondylalgia were enrolled in a double‐blind study to observe the effects of Ga‐As laser applied to acupuncture points . The Mid 1500 IRRADIA laser machine was used , wavelength : 904 nm , mean power output : 12 mW , peak value : 8.3 W ; frequency : 70 Hz ( pulse train ) . Localization of points : LI 10 , 11 , 12 , Lu 5 and SJ 5 . Each point was treated for 30 sec result ing in a dose of treatment of 0.36 J/point . The patients were treated 2–3 times weekly with 10 treatments in all . Follow‐ups were done after 3 months and 1 year . No significant differences were observed between the laser and the placebo group in relation to the subjective or objective outcome after 10 treatments or at the follow‐ups Abstract Objective : To assess the association between competing interests and authors ' conclusions in r and omised clinical trials . Design : Epidemiological study of r and omised clinical trials published in the BMJ from January 1997 to June 2001 . Financial competing interests were defined as funding by for profit organisations and other competing interests as personal , academic , or political . Studies : 159 trials from 12 medical specialties . Main outcome measures : Authors ' conclusions defined as interpretation of extent to which overall results favoured experimental intervention . Conclusions appraised on 6 point scale ; higher scores favour experimental intervention . Results : Authors ' conclusions were significantly more positive towards the experimental intervention in trials funded by for profit organisations alone compared with trials without competing interests ( mean difference 0.48 ( SE 0.13 ) , P=0.014 ) , trials funded by both for profit and non-profit organisations ( 0.30 ( SE 0.10 ) , P=0.003 ) , and trials with other competing interests ( 0.45 ( SE 0.13 ) , P=0.006 ) . Other competing interests and funding from both for profit and non-profit organisations were not significantly associated with authors ' conclusions . The association between financial competing interests and authors ' conclusions was not explained by method ological quality , statistical power , type of experimental intervention ( pharmacological or non-pharmacological ) , type of control intervention ( for example , placebo or active drug ) , or medical specialty . Conclusions : Authors ' conclusions in r and omised clinical trials significantly favoured experimental interventions if financial competing interests were declared . Other competing interests were not significantly associated with authors ' conclusions The treatment of lateral epicondylalgia , a widely-used model of musculoskeletal pain in the evaluation of many physical therapy treatments , remains somewhat of an enigma . The protagonists of a new treatment technique for lateral epicondylalgia report that it produces substantial and rapid pain relief , despite a lack of experimental evidence . A r and omized , double blind , placebo-controlled repeated- measures study evaluated the initial effect of this new treatment in 24 patients with unilateral , chronic lateral epicondylalgia . Pain-free grip strength was assessed as an outcome measure before , during and after the application of the treatment , placebo and control conditions . Pressure-pain thresholds were also measured before and after the application of treatment , placebo and control conditions . The results demonstrated a significant and substantial increase in pain-free grip strength of 58 % ( of the order of 60 N ) during treatment but not during placebo and control . In contrast , the 10 % change in pressure-pain threshold after treatment , although significantly greater than placebo and control , was substantially smaller than the change demonstrated for pain-free grip strength . This effect was only present in the affected limb . The selective and specific effect of this treatment technique provides a valuable insight into the physical modulation of musculoskeletal pain and requires further investigation BACKGROUND AND PURPOSE Lateral epicondylitis ( " tennis elbow " ) is a common entity . Several nonoperative interventions , with varying success rates , have been described . The aim of this study was to compare the effectiveness of 2 protocol s for the management of lateral epicondylitis : ( 1 ) manipulation of the wrist and ( 2 ) ultrasound , friction massage , and muscle stretching and strengthening exercises . SUBJECTS AND METHODS Thirty-one subjects with a history and examination results consistent with lateral epicondylitis participated in the study . The subjects were r and omly assigned to either a group that received manipulation of the wrist ( group 1 ) or a group that received ultrasound , friction massage , and muscle stretching and strengthening exercises ( group 2 ) . Three subjects were lost to follow-up , leaving 28 subjects for analysis . Follow-up was at 3 and 6 weeks . The primary outcome measure was a global measure of improvement , as assessed on a 6-point scale . Analysis was performed using independent t tests , Mann-Whitney U tests , and Fisher exact tests . RESULTS Differences were found for 2 outcome measures : success rate at 3 weeks and decrease in pain at 6 weeks . Both findings indicated manipulation was more effective than the other protocol . After 3 weeks of intervention , the success rate in group 1 was 62 % , as compared with 20 % in group 2 . After 6 weeks of intervention , improvement in pain as measured on an 11-point numeric scale was 5.2 ( SD=2.4 ) in group 1 , as compared with 3.2 ( SD=2.1 ) in group 2 . DISCUSSION AND CONCLUSION Manipulation of the wrist appeared to be more effective than ultrasound , friction massage , and muscle stretching and strengthening exercises for the management of lateral epicondylitis when there was a short-term follow-up . However , replication of our results is needed in a large-scale r and omized clinical trial with a control group and a longer-term follow-up Abstract Objective To investigate the efficacy of physiotherapy compared with a wait and see approach or corticosteroid injections over 52 weeks in tennis elbow . Design Single blind r and omised controlled trial . Setting Community setting , Brisbane , Australia . Participants 198 participants aged 18 to 65 years with a clinical diagnosis of tennis elbow of a minimum six weeks ' duration , who had not received any other active treatment by a health practitioner in the previous six months . Interventions Eight sessions of physiotherapy ; corticosteroid injections ; or wait and see . Main outcome measures Global improvement , grip force , and assessor 's rating of severity measured at baseline , six weeks , and 52 weeks . Results Corticosteroid injection showed significantly better effects at six weeks but with high recurrence rates thereafter ( 47/65 of successes subsequently regressed ) and significantly poorer outcomes in the long term compared with physiotherapy . Physiotherapy was superior to wait and see in the short term ; no difference was seen at 52 weeks , when most participants in both groups reported a successful outcome . Participants who had physiotherapy sought less additional treatment , such as non-steroidal anti-inflammatory drugs , than did participants who had wait and see or injections . Conclusion Physiotherapy combining elbow manipulation and exercise has a superior benefit to wait and see in the first six weeks and to corticosteroid injections after six weeks , providing a reasonable alternative to injections in the mid to long term . The significant short term benefits of corticosteroid injection are paradoxically reversed after six weeks , with high recurrence rates , implying that this treatment should be used with caution in the management of tennis elbow OBJECTIVE The aim of this study was to evaluate the effectiveness of 904-nm low-level laser therapy ( LLLT ) in the management of lateral epicondylitis . BACKGROUND DATA Lateral epicondylitis is characterized by pain and tenderness over the lateral elbow , which may also result in reduction in grip strength and impairment in physical function . LLLT has been shown effective in its therapeutic effects in tissue healing and pain control . METHODS Thirty-nine patients with lateral epicondylitis were r and omly assigned to receive either active laser with an energy dose of 0.275 J per tender point ( laser group ) or sham irradiation ( placebo group ) for a total of nine sessions . The outcome measures were mechanical pain threshold , maximum grip strength , level of pain at maximum grip strength as measured by the Visual Analogue Scale ( VAS ) and the subjective rating of physical function with Disabilities of the Arm , Shoulder and H and ( DASH ) question naire . RESULTS Significantly greater improvements were shown in all outcome measures with the laser group than with the placebo group ( p < 0.0125 ) , except in the two subsections of DASH . CONCLUSION This study revealed that LLLT in addition to exercise is effective in relieving pain , and in improving the grip strength and subjective rating of physical function of patients with lateral epicondylitis OBJECTIVE This study was undertaken to compare the effectiveness of a protocol of combination of laser with plyometric exercises and a protocol of placebo laser with the same program , in the treatment of tennis elbow . BACKGROUND DATA The use of low-level laser has been recommended for the management of tennis elbow with contradictory results . Also , plyometric exercises was recommended for the treatment of the tendinopathy . METHODS Fifty patients who had tennis elbow participated in the study and were r and omised into two groups . Group A ( n = 25 ) was treated with a 904 Ga-As laser CW , frequency 50 Hz , intensity 40 mW and energy density 2.4 J/cm(2 ) , plus plyometric exercises and group B ( n = 25 ) that received placebo laser plus the same plyometric exercises . During eight weeks of treatment , the patients of the two groups received 12 sessions of laser or placebo , two sessions per week ( weeks 1 - 4 ) and one session per week ( weeks 5 - 8 ) . Pain at rest , at palpation on the lateral epicondyle , during resisted wrist extension , middle finger test , and strength testing was evaluated using Visual Analogue Scales . Also it was evaluated the grip strength , the range of motion and weight test . Parameters were determined before the treatment , at the end of the eighth week course of treatment ( week 8) , and eighth ( week 8) after the end of treatment . RESULTS Relative to the group B , the group A had ( 1 ) a significant decrease of pain at rest at the end of 8 weeks of the treatment ( p < 0.005 ) and at the end of following up period ( p < 0.05 ) , ( 2 ) a significant decrease in pain at palpation and pain on isometric testing at 8 weeks of treatment ( p < 0.05 ) , and at 8 weeks follow-up ( p < 0.001 ) , ( 3 ) a significant decrease in pain during middle finger test at the end of 8 weeks of treatment ( p < 0.01 ) , and at the end of the follow-up period ( p < 0.05 ) , ( 4 ) a significant decrease of pain during grip strength testing at 8 weeks of treatment ( p < 0.05 ) , and at 8 weeks follow-up ( p < 0.001 ) , ( 5 ) a significant increase in the wrist range of motion at 8 weeks follow-up ( p < 0.01 ) , ( 6 ) an increase in grip strength at 8 weeks of treatment ( p < 0.05 ) and at 8 weeks follow-up ( p < 0.01 ) , and ( 7 ) a significant increase in weight-test at 8 weeks of treatment ( p < 0.05 ) and at 8 weeks follow-up ( p < 0.005 ) . CONCLUSION The results suggested that the combination of laser with plyometric exercises was more effective treatment than placebo laser with the same plyometric exercises at the end of the treatment as well as at the follow-up . Future studies are needed to establish the relative and absolute effectiveness of the above protocol OBJECTIVE To investigate the course of lateral epicondylitis and identify prognostic indicators associated with short- and longterm outcome of pain intensity . METHODS We prospect ively followed patients ( n = 349 ) from 2 r and omized controlled trials investigating conservative interventions for lateral epicondylitis in primary care . Uni- and multivariate linear regression analyses were used to investigate the association between potential prognostic indicators and pain intensity ( 0 - 100 point scale ) measured at 1 , 6 , and 12 months after r and omization . Potential prognostic factors were duration of elbow complaints , concomitant neck pain , concomitant shoulder pain , previous elbow complaints , baseline pain scores , age , gender , involvement of dominant side , social class , and work status . The variables " study " and " treatment " were included as covariates in all models . RESULTS Pain scores at 1 month followup were higher in patients with severe pain , a long duration of elbow complaints , and concomitant shoulder pain . At 12 month followup , the only different prognostic indicator for poor outcome was concomitant neck pain , in place of shoulder pain . Patients from higher social classes reported lower pain scores at 12 month followup than patients from lower social classes . CONCLUSIONS Lateral epicondylitis seems to be a self-limiting condition in most patients . Long duration of elbow complaints , concomitant neck pain , and severe pain at presentation are associated with poor outcome at 12 months . Our results will help care providers give patients accurate information regarding their prognosis and assist in medical decision-making OBJECTIVES Pulsed low-intensity ultrasound therapy ( LIUS ) has been found to be beneficial in accelerating fracture healing and has produced positive results in animal tendon repair . In the light of this we undertook a r and omized , double-blind , placebo controlled trial to assess the effectiveness of LIUS vs placebo therapy daily for 12 weeks in patients with chronic lateral epicondylitis ( LE ) . METHODS Patients with LE of at least Output:	No serious side-effects were reported . Conclusion LLLT administered with optimal doses of 904 nm and possibly 632 nm wavelengths directly to the lateral elbow tendon insertions , seem to offer short-term pain relief and less disability in LET , both alone and in conjunction with an exercise regimen .
MS22043	*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 Increasing evidence suggests an important role of carbohydrate quality in the development of type 2 diabetes . OBJECTIVE Our objective was to prospect ively examine the association between glycemic index , glycemic load , and dietary fiber and the risk of type 2 diabetes in a large cohort of young women . DESIGN In 1991 , 91249 women completed a semiquantitative food-frequency question naire that assessed dietary intake . The women were followed for 8 y for the development of incident type 2 diabetes , and dietary information was up date d in 1995 . RESULTS We identified 741 incident cases of confirmed type 2 diabetes during 8 y ( 716 300 person-years ) of follow-up . After adjustment for age , body mass index , family history of diabetes , and other potential confounders , glycemic index was significantly associated with an increased risk of diabetes ( multivariate relative risks for quintiles 1 - 5 , respectively : 1 , 1.15 , 1.07 , 1.27 , and 1.59 ; 95 % CI : 1.21 , 2.10 ; P for trend = 0.001 ) . Conversely , cereal fiber intake was associated with a decreased risk of diabetes ( multivariate relative risks for quintiles 1 - 5 , respectively : 1 , 0.85 , 0.87 , 0.82 , and 0.64 ; 95 % CI : 0.48 , 0.86 ; P for trend = 0.004 ) . Glycemic load was not significantly associated with risk in the overall cohort ( multivariate relative risks for quintiles 1 - 5 , respectively : 1 , 1.31 , 1.20 , 1.14 , and 1.33 ; 95 % CI : 0.92 , 1.91 ; P for trend = 0.21 ) . CONCLUSIONS A diet high in rapidly absorbed carbohydrates and low in cereal fiber is associated with an increased risk of type 2 diabetes Previous studies suggest that a low-glycaemic index ( LGI ) diet may improve insulin sensitivity ( IS ) . As IS has been shown to decrease during refeeding , we hypothesised that an LGI- v. high-GI ( HGI ) diet might have favourable effects during this phase . In a controlled nutritional intervention study , sixteen healthy men ( aged 26·8 ( SD 4·1 ) years , BMI 23·0 ( SD 1·7 ) kg/m2 ) followed 1 week of overfeeding , 3 weeks of energy restriction and of 2 weeks refeeding at ^50 % energy requirement ( 50 % carbohydrates , 35 % fat and 15 % protein ) . During refeeding , subjects were divided into two matched groups receiving either high-fibre LGI or lower-fibre HGI foods ( GI 40 v. 74 , fibre intake 65 ( SD 6 ) v. 27 ( SD 4 ) g/d ) . Body weight was equally regained in both groups with refeeding ( mean regain 70·5 ( SD 28·0)% of loss ) . IS was improved by energy restriction and decreased with refeeding . The decreases in IS were greater in the HGI than in the LGIgroup ( group £ time interactions for insulin , homeostasis model assessment of insulin resistance ( HOMAIR ) , Matsuda IS index (MatsudaISI);all P,0·05 ) . Mean interstitial glucose profiles during the day were also higher in the HGI group ( DAUCHGI-LGI of continuous interstitial glucose monitoring : 6·6 mmol/l per 14 h , P¼0·04 ) . At the end of refeeding , parameters of IS did not differ from baseline values in either diet group ( adiponectin , insulin , HOMAIR , Matsuda ISI , M-value ; all P.0·05 ) . In conclusion , nutritional stress imposed by dietary restriction and refeeding reveals a GI/fibre effect in healthy non-obese subjects . LGI foods rich in fibre may improve glucose metabolism during the vulnerable refeeding phase of a weight cycle BACKGROUND Insulin sensitivity ( Si ) is improved by weight loss and exercise , but the effects of the replacement of saturated fatty acids ( SFAs ) with monounsaturated fatty acids ( MUFAs ) or carbohydrates of high glycemic index ( HGI ) or low glycemic index ( LGI ) are uncertain . OBJECTIVE We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome . DESIGN We conducted a 5-center , parallel design , r and omized controlled trial [ RISCK ( Reading , Imperial , Surrey , Cambridge , and Kings ) ] . The primary and secondary outcomes were changes in Si ( measured by using an intravenous glucose tolerance test ) and cardiovascular risk factors . Measurements were made after 4 wk of a high-SFA and HGI ( HS/HGI ) diet and after a 24-wk intervention with HS/HGI ( reference ) , high-MUFA and HGI ( HM/HGI ) , HM and LGI ( HM/LGI ) , low-fat and HGI ( LF/HGI ) , and LF and LGI ( LF/LGI ) diets . RESULTS We analyzed data for 548 of 720 participants who were r and omly assigned to treatment . The median Si was 2.7 × 10(-4 ) mL · μU(-1 ) · min(-1 ) ( interquartile range : 2.0 , 4.2 × 10(-4 ) mL · μU(-1 ) · min(-1 ) ) , and unadjusted mean percentage changes ( 95 % CIs ) after 24 wk treatment ( P = 0.13 ) were as follows : for the HS/HGI group , -4 % ( -12.7 % , 5.3 % ) ; for the HM/HGI group , 2.1 % ( -5.8 % , 10.7 % ) ; for the HM/LGI group , -3.5 % ( -10.6 % , 4.3 % ) ; for the LF/HGI group , -8.6 % ( -15.4 % , -1.1 % ) ; and for the LF/LGI group , 9.9 % ( 2.4 % , 18.0 % ) . Total cholesterol ( TC ) , LDL cholesterol , and apolipoprotein B concentrations decreased with SFA reduction . Decreases in TC and LDL-cholesterol concentrations were greater with LGI . Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations . CONCLUSIONS This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si . Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects , with tentative evidence of improvements in Si in the LF-treatment group . This trial was registered at clinical trials.gov as IS RCT N29111298 OBJECTIVE To examine the relation between weight change and weight fluctuation ( cycling ) and mortality in middle-aged men . METHODS A prospect i ve study of 5608 men aged 40 to 59 years at screening , drawn from one general practice in each of 24 British towns . Changes in weight observed during a 12- to 14-year period were related to mortality during the subsequent 8 years . RESULTS There were 943 deaths from all causes : 458 cardiovascular disease ( CVD ) and 485 non-CVD deaths . Those with stable weight or weight gain had the lowest total , CVD , and non-CVD mortality . Sustained weight loss or weight fluctuation ( loss-gain or gain-loss ) showed a significantly higher mortality risk than stable weight even after adjustment for lifestyle variables ( relative risk [ 95 % confidence interval ] , 1.60 [ 1.32 - 1.95 ] , 1.50 [ 1.17 - 1.91 ] , and 1.63 [ 1.24 - 2.14 ] , respectively ) . Adjustment or exclusion of men with preexisting disease markedly attenuated the increased risk of CVD and total mortality associated with sustained weight loss and weight gain-weight loss . In long-term nonsmokers , any weight loss since screening was associated with an increased risk of mortality , but this was markedly attenuated by adjustment for preexisting disease . Recent ex-smokers showed the most marked increase in mortality associated with sustained weight loss . CONCLUSIONS The increased mortality in middle-aged men with sustained weight loss and weight fluctuation ( cycling ) is determined to a major extent by disadvantageous lifestyle factors and preexisting disease . The evidence suggests that weight loss and weight fluctuation ( cycling ) in these men does not directly increase the risk of death OBJECTIVE Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM , whereas dietary fiber is suspected to reduce incidence . These hypotheses have not been evaluated prospect ively . RESEARCH DESIGN AND METHODS We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease , who were 40–75 years of age in 1986 . Diet was assessed at baseline by a vali date d semiquantitative food frequency question naire . During 6-years of follow-up , 523 incident cases of NIDDM were documented . RESULTS The dietary glycemic index ( an indicator of carbohydrate 's ability to raise blood glucose levels ) was positively associated with risk of NIDDM after adjustment for age , BMI , smoking , physical activity , family history of diabetes , alcohol consumption , cereal fiber , and total energy intake . Comparing the highest and lowest quintiles , the relative risk ( RR ) of NIDDM was 1.37 ( 95 % CI , 1.02–1.83 , P trend = 0.03 ) . Cereal fiber was inversely associated with risk of NIDDM ( RR = 0.70 ; 95 % CI , 0.51–0.96 , P trend = 0.007 ; for > 8.1 g/day vs. < 3.2 g/day ) . The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM ( RR = 2.17 , 95 % CI , 1.04–4.54 ) when compared with a low glycemic load and high cereal fiber intake . CONCLUSIONS These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men . Further , they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM The risk of coronary heart disease ( CHD ) is influenced by family history , insulin sensitivity ( IS ) , and diet . Adiposity affects CHD and IS . The cellular mechanism of IS is thought to involve the adipocyte cytokine tumor necrosis factor-alpha ( TNF-alpha ) . Insulin-stimulated glucose uptake in isolated subcutaneous and omental adipocytes obtained during elective surgery was measured in 61 premenopausal women , 24 with a parental history ( PH ) of CHD . In vivo IS was measured using the short insulin tolerance test ( SITT ) in 28 women , 16 with PH-CHD , before and 3 weeks after r and omization to a low glycemic index ( LGI ) or high glycemic index ( HGI ) diet . In vitro adipocyte IS and TNF-alpha production was measured following dietary modification . On the habitual diet , in vitro insulin-stimulated glucose uptake in adipocytes as a percentage increase over basal was less in women with PH-CHD than in those without it ( presented as the median with 95 % confidence limits : subcutaneous , 28 % ( 17 % to 39 % ) v 96 % ( 70 % to 120 % ) , P < .01 ) ; omental , 40 % ( 28 % to 52 % ) v 113 % ( 83 % to 143 % ) , P < .01 ) . In vivo IS in 16 PH-CHD subjects and 12 controls before dietary r and omization was similar , and increased in both groups consuming a LGI versus HGI diet ( PH-CHD , 0.31 ( 0.26 to 0.37 ) v 0.14 ( 0.10 to 0.24 ) mmol/L/min , P < .01 ; controls , 0.31 ( 0.1 to 0.53 ) v 0.15 ( 0.06 to 0.23 ) mmol/L/min , P < .05 ) . Adipocyte IS was greater in PH-CHD women on a LGI versus HGI diet ( subcutaneous , 50 % ( 20 % to 98 % ) v 13 % ( 1 % to 29 % ) ; omental , Output:	There is also a Cochrane systematic review which suggests that the GI may play a role in promoting weight loss . Therefore , the literature , as it currently st and s , presents a convincing case for the clinical application of the GI in the management of body weight and glucose homeostasis . In this issue of the British Journal of Nutrition , Lagerpusch et al. observed that in the dynamic phase of weight gain , a high-fibre , low-GI diet reduced daytime measurements of interstitial glucose when compared with an energy-matched lowfibre , high-GI diet . Furthermore , the deterioration in insulin sensitivity induced by refeeding was attenuated , though the effects of the two dietary interventions were resolved at the end of the refeeding phase . The authors do not offer any suggestions as to which specific dietary manipulation they believe may be driving their observed improvements in glucose metabolism and insulin sensitivity . In two large-scale epidemiological studies ( the Nurses ’ Health Study and Health Professionals Follow-up Study ) , it has been demonstrated that the risk of developing type 2 diabetes increases with a concomitant increase in dietary glycaemic load ( the GI multiplied by the amount of carbohydrate consumed ) and a reduction in fibre consumption . The uncoupling of these two aspects of the diet meant that the relationship disappeared or was significantly weaker . Furthermore , the Reading , Imperial , Surrey , Cambridge , and Kings ( RISCK ) study , a large multicentre dietary intervention in over 500 adults at risk of CVD , aim ed to eluci date how dietary changes may influence insulin sensitivity and other CVD risk factors . A surprising finding of the study was the absence of an improvement in insulin sensitivity following a lowv . high-GI diet . This raises the intriguing question of whether the dietary deconstruction seen in most nutritional interventions , in line with the current reductionist scientific approach , is actually detrimental . By controlling for every aspect of the diet , could we actually be missing important physiological effects that occur from dietary manipulations which often go h and -in-h and , like GI and dietary fibre ? In the gastrointestinal tract , low-GI diets with a high fibre content slow gastric emptying , reduce digesta transit rate and alter the luminal environment , all of which will ultimately delay glucose absorption and result in an ameliorated insulin response . For example , high-fibre , low-GI diets may promote insulin sensitivity by improving metabolic flexibility , i.e. the ability of an organism to modify fuel oxidation in response to changes in nutrient availability . Metabolic flexibility enables an efficient transition from lipid oxidation and high rates of fatty acid uptake during the fasted state , to suppression of lipid oxidation and increased glucose uptake and utilisation in response to insulin stimulation .
MS22044	*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 Intracranial hemorrhage in patients receiving oral anticoagulant ( OAC ) therapy is associated with poor neurological outcome . Prothrombin complex concentrate ( PCC ) is the gold – st and ard therapy to normalize hemostasis but remains underused . Ultra-rapid reversal of anticoagulation could reduce the time to biological and surgical hemostasis , and might improve outcome . We report the use of bolus infusions of PCC to immediately reverse anticoagulation and allow for urgent neurosurgical care . Design Prospect i ve , observational study . Setting Neurosurgical intensive care unit , university hospital . Patients and participants Eighteen patients with OAC-associated intracranial hemorrhage requiring urgent neurosurgical intervention . Interventions All patients received 20 UI/kg of PCC as an intravenous bolus infusion ( 3 min ) and 5 mg of enteral vitamin K. Surgery was started immediately , without waiting for blood sample results . Measurements and results Serial blood sample s were performed to assess prothrombin time . Coagulation was considered normal when the international normalized ratio was ≤ 1.5 . All patients , including nine who were over-anticoagulated , had complete reversal of anticoagulation immediately after the bolus of PCC . No hemorrhagic or thrombotic adverse effect was observed intra- or postoperatively . Conclusions A bolus infusion of PCC completely reverses anticoagulation within 3 min . Neurosurgery can be performed immediately in OAC-related intracranial hemorrhage . This study shows that OAC – treated patients can be managed as rapidly as non – anticoagulated patients Background Co-fact © , prothrombin complex concentrate , is used for restoring the international normalized ratio ( INR ) in patients on vitamin K antagonists ( VKA ) presenting with acute bleeding . In this prospect i ve cohort study , we evaluated whether adequate INR values were reached in ED patients using the Sanquin ( Federation of Dutch Thrombosis Services ) treatment protocol . Methods We evaluated this protocol for two target INR groups : group 1 , target INR ≤ 1.5 ( for life-threatening bleeding/immediate intervention ) ; group 2 , target INR 1.6 - 2.1 ( in cases of a minor urgent surgery or serious overdosing of anticoagulant ) . We specifically wanted to identify both under- and over-treated patients . Reversing VKA anticoagulation therapy to unnecessarily low INR values may involve thrombotic risks . Apart from this risk , the patient is also administered an excess amount of the drug . This means unnecessary costs and may present problems with restoring an anticoagulated state at a later time . Results In our cohort , the Sanquin dosing protocol was followed for 45/60 patients . It appeared that out of the 41 patients in group 1 ( target INR ≤ 1.5 ) , 35 ( 85 % ) achieved the goal INR . This occurred more often than for the 19 patients in group 2 ( target INR 1.6–2.1 ) , where only 6 ( 32 % ) achieved the goal INR . Using the protocol result ed in a positive trend toward better INR reversal in group 1.In group 2 , no relation between using the protocol and achieving the desired INR value was detected . Physicians ignoring the proposed dose of Co-fact © prescribed significantly less Co-fact © ( even when correcting for patient weight ) . It appeared that patients in group 1 had a significantly lower baseline INR than patients in group 2 . Group 2 patients , on the other h and , had a baseline INR > 7.5 in 53 % of the cases . Conclusion In our cohort , for most patients in INR group 2 treated with Co-fact © , the achieved INR value was outside the desired range of 1.6 - 2.1 . The supra-therapeutic range of baseline INR in group 2 may have contributed to the different kind of bleeding witnessed in this patient group . Our results support the idea that treatment of patients on vitamin K antagonists with Co-fact © could benefit from a slightly different approach , taking into account the INR value to which the patient needs to be reversed BACKGROUND Prothrombin complex concentrate ( PCC ) can substantially shorten the time needed to reverse antivitamin K oral anticoagulant therapy ( OAT ) . OBJECTIVES . To determine the effectiveness and safety of emergency OAT reversal by a balanced pasteurized nanofiltered PCC ( Beriplex P/N ) containing coagulation factors II , VII , IX , and X , and anticoagulant proteins C and S. PATIENTS AND METHODS Patients receiving OAT were eligible for this prospect i ve multinational study if their International Normalized Ratio ( INR ) exceeded 2 and they required either an emergency surgical or urgent invasive diagnostic intervention or INR normalization due to acute bleeding . Stratified 25 , 35 , or 50 IU kg(-1 ) PCC doses were infused based on initial INR . Study endpoints included INR normalization ( < /=1.3 ) by 30 min after PCC infusion and hemostatic efficacy . RESULTS Forty-three patients , 26 requiring interventional procedures and 17 experiencing acute bleeding , received PCC infusions at a median rate of 7.5 mL min(-1 ) ( 188 IU min(-1 ) ) . At 30 min thereafter , INR declined to < /=1.3 in 93 % of patients . At all postinfusion time points through 48 h , median INR remained between 1.2 and 1.3 . Clinical hemostatic efficacy was classified as very good or satisfactory in 42 patients ( 98 % ) . Prompt and sustained increases in circulating coagulation factors and anticoagulant proteins were observed . One fatal suspected pulmonary embolism in a patient with metastatic cancer was judged to be possibly PCC-related . CONCLUSIONS PCC treatment serves as an effective rapid hemorrhage control re source in the emergency anticoagulant reversal setting . More widespread availability of PCC is warranted to ensure its benefits in appropriate patients BACKGROUND Fresh frozen plasma ( FFP ) and prothrombin complex concentrates ( PCC ) reverse oral anticoagulants . We compared PCC and FFP intraoperative administration in patients undergoing heart surgery with cardiopulmonary bypass ( CPB ) . METHODS Forty patients [ with international normalized ratio (INR)≥ 2·1 ] assigned semi-urgent cardiac surgery were r and omized to receive either FFP ( n = 20 ) or PCC ( n = 20 ) . Prior to CPB , they received either 2 units of FFP or half of the PCC dose calculated according to body weight , initial INR and target INR ( ≤ 1·5 ) . After CPB and protamine administration , patients received either another 2 units of FFP or the other half PCC dose . Additional doses were administered if INR was still too high ( ≥ 1·5 ) . RESULTS Fifteen minutes after CPB , more patients reached INR target with PCC ( P = 0·007 ) : 7/16 patients vs. 0/15 patients with FFP ; there was no difference 1 h after CPB ( 6/15 patients with PCC vs. 4/15 patients with FFP reached target ) . Fifteen minutes after CPB , median INR ( range ) decreased to 1·6 ( 1·2 - 2·2 ) with PCC vs. 2·3 ( 1·5 - 3·5 ) with FFP ; 1 h after CPB both groups reached similar values [ 1·6 ( 1·3 - 2·2 ) with PCC and 1·7 ( 1·3 - 2·7 ) with FFP ] . With PCC , less patients needed additional dose ( 6/20 ) than with FFP ( 20/20 ) ( P < 0·001 ) . Both groups differed significantly on the course of factor II ( P = 0·0023 ) and factor X ( P = 0·008 ) over time . Dilution of coagulation factors was maximal at CPB onset . Safety was good for both groups , with only two related oozing cases with FFP . CONCLUSION PCC reverses anticoagulation safely , faster and with less bleeding than FFP Introduction Prothrombin complex concentrates ( PCC ) are haemostatic blood preparations indicated for urgent anticoagulation reversal , though the optimal dose for effective reversal is still under debate . The latest generation of PCCs include four coagulation factors , the so-called 4-factor PCC . The aim of this study was to compare the efficacy and safety of two doses , 25 and 40 IU/kg , of 4-factor PCC in vitamin K antagonist ( VKA ) associated intracranial haemorrhage . Methods We performed a phase III , prospect i ve , r and omised , open-label study including patients with objective ly diagnosed VKA-associated intracranial haemorrhage between November 2008 and April 2011 in 22 centres in France . Patients were r and omised to receive 25 or 40 IU/kg of 4-factor PCC . The primary endpoint was the international normalised ratio ( INR ) 10 minutes after the end of 4-factor PCC infusion . Secondary endpoints were changes in coagulation factors , global clinical outcomes and incidence of adverse events ( AEs ) . Results A total of 59 patients were r and omised : 29 in the 25 IU/kg and 30 in the 40 IU/kg group . Baseline demographics and clinical characteristics were comparable between the groups . The mean INR was significantly reduced to 1.2 - and ≤1.5 in all patients of both groups - 10 minutes after 4-factor PCC infusion . The INR in the 40 IU/kg group was significantly lower than in the 25 IU/kg group 10 minutes ( P = 0.001 ) , 1 hour ( P = 0.001 ) and 3 hours ( P = 0.02 ) after infusion . The 40 IU/kg dose was also effective in replacing coagulation factors such as PT ( P = 0.038 ) , FII ( P = 0.001 ) , FX ( P < 0.001 ) , protein C ( P = 0.002 ) and protein S ( 0.043 ) , 10 minutes after infusion . However , no differences were found in haematoma volume or global clinical outcomes between the groups . Incidence of death and thrombotic events was similar between the groups . Conclusions Rapid infusion of both doses of 4-factor PCC achieved an INR of 1.5 or less in all patients with a lower INR observed in the 40 IU/kg group . No safety concerns were raised by the 40 IU/kg dose . Further trials are needed to evaluate the impact of the high dose of 4-factor PCC on functional outcomes and mortality . Trial registration Eudra CT number 2007 - 000602 - 73 INTRODUCTION Prothrombin complex concentrates ( PCCs ) are used for the urgent reversal of oral vitamin K antagonists in patients with life-threatening bleeding or prior to urgent procedures /surgery . PCCs offer rapid and complete reversal without the disadvantages of volume overload and adverse reactions seen with fresh frozen plasma ( FFP ) . There is concern about the risk of thrombosis associated with the use PCCs ; data on this is limited at present . OBJECTIVES To determine the incidence of objective ly confirmed arterial or venous thromboembolism within 30 days following the administration of PROTHROMBINEX ® -VF ( PTX-VF ) to acutely reverse a prolonged INR . MATERIAL S/ METHODS A prospect i ve observational study was conducted at two teaching hospitals in Auckl and , NZ . All patients who received PTX-VF for the acute reversal of prolonged INR were eligible . Baseline patient demographics and reasons for PTX-VF administration were recorded . Patients were review ed at days 7 and 30 , to confirm/exclude thromboembolism or adverse events . RESULTS 173 patients were enrolled from August 2008 to March 2009 . The most frequent indication for reversal was acute bleeding . At 30 days 4.6 % ( 8/173 ) patients had a definite/probable thrombotic event , and 16.7 % had died either due to the presenting bleed ( intracranial haemorrhage ) or a complication of their presenting complaint ( e.g. sepsis , renal failure ) . CONCLUSIONS Acute reversal of anticoagulant therapy with PTX-VF is associated with a significant rate of thromboembolism ( 4.6 % ) within 30 days . These events can be explained by ongoing cessation of anticoagulant therapy in patients with ongoing risk factors for arterial or venous thrombosis , rather than directly attributable to PTX-VF therapy Introduction Prothrombin Complex Concentrate ( PCC ) is a key treatment in the management of bleeding related to Vitamin K antagonists ( VKA ) . This study aim ed to evaluate prospect ively PCC use in patients with VKA-related bleeding in view of the French guidelines published in 2008 . Methods All consecutive patients with VKA-related bleeding treated with a 4-factor PCC ( Octaplex ® ) were selected in 33 French hospitals . Collected data included demographics , site and severity of bleeding , modalities of PCC administration , International Normalized Ratio ( INR ) values before and after PCC administration , outcomes and survival rate 15 days after infusion . Results Of 825 patients who received PCC between August 2008 and December 2010 , 646 had severe bleeding . The main haemorrhage sites were intracranial ( 4 Output:	Relatively good clinical and INR outcomes were reported with the use of any treatment protocol while less good results were reported for INR outcome when a predefined protocol was missing ( doctor strategy ) . Lowest PCC dosages were infused in the fixed dose strategy . In emergency VKA reversal , a predefined PCC dosing protocol seems essential . We found no evidence that one dosing strategy is superior .
MS22045	*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 aim of this double-blind , placebo-controlled study was to determine whether a prolonged course of low-dose ganciclovir prevented the development of clinical cytomegalovirus disease after heart transplantation . METHODS Fifty-six consecutive patients were stratified into two groups : cytomegalovirus-positive recipients ( n = 40 ) and cytomegalovirus-negative recipients of organs from cytomegalovirus-positive donors ( n = 16 ) . All patients received equine antithymocyte globulin induction for 7 days and maintenance doses of cyclosporine , azathioprine , and prednisolone . Ganciclovir ( 5 mg/kg intravenously ) or matching placebo was given with the premedication , three times weekly for the first 6 weeks after transplantation and for another 2 weeks for each treated rejection episode between 6 and 12 weeks . RESULTS Ganciclovir prophylaxis reduced the actuarial incidence of cytomegalovirus disease from 71 % to 11 % in cytomegalovirus-mismatched patients ( p < 0.01 ) . Ganciclovir prophylaxis did not reduce the incidence of cytomegalovirus disease in cytomegalovirus-positive recipients ( 25 % in both placebo and ganciclovir groups ) but did delay its onset and reduce its morbidity . There were no adverse reactions during ganciclovir administration . Gastritis was the most common clinical manifestation of cytomegalovirus disease . Pneumonitis and myocarditis were seen only in placebo-treated cytomegalovirus-mismatched patients . All patients with clinical cytomegalovirus disease responded to ganciclovir , 10 mg/kg/day for 2 weeks . CONCLUSIONS Prolonged low-dose ganciclovir prophylaxis after heart transplantation reduces the incidence of cytomegalovirus disease in cytomegalovirus-mismatched patients and reduces the morbidity of cytomegalovirus disease in cytomegalovirus-positive recipients The use of postdetection antiviral treatment of cytomegalovirus ( CMV ) as a strategy to prevent infection and disease in solid-organ transplant patients has not been evaluated by placebo-controlled trials . We carried out such a study in 69 patients who had received liver transplants and had positive results of CMV polymerase chain reaction within 8 weeks after transplantation but did not have concomitant CMV infection or disease . These patients were r and omly assigned to receive placebo or oral ganciclovir for 8 weeks . CMV infection developed in 21 % and disease developed in 12 % of placebo recipients ( P = .022 ) , compared with 3 % and 0 % , respectively , among ganciclovir recipients ( P = .003 ) . Similarly , in the placebo arm , 55 % and 36 % of CMV-negative patients who received organs from CMV-positive donors developed CMV infection or disease , respectively ( P = .02 ) , compared with 11 % and 0 % of such patients in the ganciclovir arm ( P < .01 ) . Oral ganciclovir administered on CMV detection by PCR prevents CMV infection or disease after liver transplantation Cytomegalovirus is the most important infectious cause of complications and death in organ transplant recipients . The three major consequences of infection with this virus are cytomegalovirus disease ; superinfection with opportunistic pathogens result ing from host defects caused by the virus ; and allograft injury [ 1 , 2 ] . The interaction of the following three factors determines whether cytomegalovirus disease develops in a transplant recipient infected with cytomegalovirus : 1 ) whether the donor and donor organ or the recipient , or both , harbor latent virus that can be reactivated after transplant [ 1 ] ; 2 ) whether the transplant recipient can mount an immune response to the virus [ both cellular and humoral ] ; and 3 ) the type of immunosuppressive therapy administered after transplant [ 4 ] . Transplant recipients in whom primary infection develops at the time of transplant ( donor : cytomegalovirus antibody positive ; recipient : cytomegalovirus antibody negative ) or who test positive for cytomegalovirus antibody before transplantation and require antilymphocyte antibody therapy after transplantation have a greater than 50 % attack rate of cytomegalovirus disease [ 4 ] . Each risk group accounts for 10 % to 20 % of all transplant recipients . Preventing cytomegalovirus disease in these two patient population s is a priority for transplant physicians . Cytomegalovirus disease has been prevented by prolonged administration ( 3 to 4 months ) of antiviral therapies such as acyclovir [ 5 ] , anticytomegalovirus hyperimmune globulin [ 6 ] , or the combination of these two therapies [ 7 ] . These prophylactic strategies reduce the attack rate of cytomegalovirus disease , but this benefit is attenuated in patients who receive antilymphocyte antibody therapy [ 1 ] . Because the risk for developing cytomegalovirus disease depends on the type of immunosuppression administered after transplantation , we have proposed an alternative approach to preventing cytomegalovirus disease . This approach targets patients at greatest risk for cytomegalovirus disease for treatment with the most potent anticytomegalovirus therapy available . The antiviral therapy is administered when the risk is greatest ( for example , during treatment with antilymphocyte antibodies ) . To distinguish this approach from preventive strategies used in all patients ( nontargeted prophylaxis ) , we introduced the term preemptive therapy [ 8 ] . Preliminary studies suggested that ganciclovir administered as preemptive therapy to patients receiving antilymphocyte antibodies might reduce the attack rate of cytomegalovirus disease in transplant recipients who are positive for cytomegalovirus antibody . This multiinstitutional , r and omized clinical trial was design ed to assess the efficacy and safety of preemptive ganciclovir therapy in preventing cytomegalovirus disease in transplant recipients who are positive for cytomegalovirus antibody and who are receiving antilymphocyte antibodies . Methods Patients Consecutive renal transplant recipients who tested positive for cytomegalovirus antibody and who received a kidney from cytomegalovirus antibody-positive or antibody-negative donors at Albany Medical Center , Emory University Hospital , Massachusetts General Hospital , New Engl and Medical Center , University of Chicago Medical Center , and Yale-New Haven Hospital were eligible for enrollment in the study . Patients were r and omly assigned to receive either preemptive ganciclovir or no ganciclovir every day that antilymphocyte antibody therapy ( muromonab-CD3 [ OKT3 ] , antithymocyte globulin , or antilymphocyte globulin ) was administered . Separate r and omization lists were used in each transplantation center ; within each center , separate r and omization lists were used for cadaveric and living , related donors . The investigators at each site knew which patients received the study drug and which patients received no anticytomegalovirus therapy . The cytomegalovirus antibody status of donors and recipients was determined using enzyme immunoassay on recipient serum obtained before transplantation and on donor serum obtained before transfusion . Patients were excluded from the study if they were younger than 20 years of age , were pregnant , had received another organ in addition to a kidney , had received any anticytomegalovirus therapy ( defined as more than 1.2 g of acyclovir per day , unselected immune globulin , or cytomegalovirus hyperimmune globulin ) , or refused to give consent . The committees on human experimentation at each institution approved the study . All study participants were observed for the following outcomes during the 6 months after they received antilymphocyte antibodies : 1 ) cytomegalovirus disease ; 2 ) other infectious diseases ; 3 ) and noninfectious diagnoses . Allograft function 6 months after administration of antilymphocyte antibody was recorded as either present ( for those not requiring dialysis ) or absent ( for those receiving dialysis ) . Serum creatinine levels were recorded for all patients with functioning allografts 6 months after antilymphocyte antibody therapy . Patients were evaluated for cytomegalovirus viremia and disease in three ways . First , the virology laboratory at each program tried to isolate cytomegalovirus from buffy-coat specimens at least every month using either centrifugation culture [ 9 ] , conventional culture techniques [ 10 ] , or both . Second , buffy-coat specimens were cultured for cytomegalovirus when any of the following signs , symptoms , or laboratory abnormalities were present : temperature greater than 38 C , leukocyte count less than 3.0 109 cells/L , dyspnea , abdominal pain , or gastrointestinal bleeding . Third , a biopsy specimen was obtained from any abnormal site , and all biopsy specimens were examined histologically for the presence of characteristic cytomegalovirus inclusion bodies and uptake of immunofluorescent-labeled anticytomegalovirus antibodies . Patients with other signs or symptoms suggesting infection ( such as cough , headache , diarrhea , allograft discomfort , or dysuria ) were evaluated using st and ard diagnostic protocol s. At all study sites , the diagnostic protocol included at least a chest radiograph , leukocyte count , renal and liver function tests , two sets of blood cultures , urinalysis , urine culture , and cultures from other potential sites of infection . For patients who did not survive the 6-month observation period , data on the cause and date of death were collected . Definition of Cytomegalovirus Disease Cytomegalovirus disease was defined as either the cytomegalovirus syndrome or tissue-invasive disease developing within 6 months of antilymphocyte antibody therapy or within 1 month of discontinuing immunosuppression after allograft loss . The cytomegalovirus syndrome was diagnosed when both virologic and clinical criteria were met within a 7-day period . Virologic criteria were fulfilled when cytomegalovirus was isolated from a buffy-coat specimen or bronchoalveolar fluid . Clinical criteria were fulfilled when patients had a temperature higher than 38 C [ without antipyretic agents ] for 3 or more consecutive days and within 7 days of two or more of the following : 1 ) leukopenia [ leukocyte count < 3.0 109 cells/L on two consecutive measurements after stopping azathioprine therapy ] ; 2 ) hepatitis [ serum alanine aminotransferase > 1.5 times the upper limit of normal , without serologic evidence of active hepatitis B or hepatitis C virus ] ; 3 ) atypical lymphocytosis [ more than 20 % of leukocytes ] ; and 4 ) pneumonitis ( an abnormal result on chest radiograph and no alternative explanation [ including absence of Pneumocystis carinii in respiratory secretions ] ) . These criteria were modified slightly from those used by other research ers [ 6 ] because isolation of cytomegalovirus from buffy-coat specimens or bronchoalveolar fluid predicts presence of cytomegalovirus disease , whereas isolation of cytomegalovirus from urine and saliva may not [ 11 ] . Tissue-invasive cytomegalovirus disease was diagnosed histopathologically by showing the presence of inclusion bodies characteristic of cytomegalovirus or by an immunochemical stain positive for cytomegalovirus antigens in a biopsy specimen from a lesion or an abnormal site ( gastrointestinal tract , lung , or liver ) . The investigator at each study site made decisions about treating cytomegalovirus disease . Study Drug Administration The study drug was given daily ( or according to the schedule in Table 1 only when the patient already had intravenous access for administration of antilymphocyte antibodies . The study medication was started within 24 hours of the first dose of each course of antilymphocyte antibodies . Patients receiving the study drug were given ganciclovir infusions based on daily serum creatinine concentrations ( Table 1 ) . Table 1 . Ganciclovir Dosage Schedule according to Daily Serum Creatinine Concentration Leukocyte count , platelet count , and serum creatinine concentration were monitored daily during antilymphocyte antibody therapy in patients who received preemptive ganciclovir therapy and in controls . Sample Size and Statistical Analysis In the primary analysis , the proportion of patients with cytomegalovirus disease in the two study groups were compared . On the basis of our previous study [ 4 ] , we assumed that cytomegalovirus disease would develop in 60 % of controls . We wanted to enroll 48 patients who could be evaluated in each group ( for a total of 96 ) to detect a decrease in the proportion of patients with cytomegalovirus disease from 60 % ( in controls ) to 30 % or less ( in patients receiving preemptive ganciclovir therapy ) ; that is , we predicted that preemptive ganciclovir treatment would yield a 50 % lower attack rate ( using a two-sided test , = 0.05 and power = 0.8 ) . Initial analyses were done on an Output:	Antiviral prophylaxis is associated with a significant reduction in the risk of CMV infection and all-cause mortality in CMV-negative and CMV-positive renal transplant recipients from CMV-positive donors , regard-less of the immunosuppressive treatments used ( evidence from SR ) . Pre-emptive therapy has been found to be effective in preventing CMV disease but not all-cause mortality in these patients , even if evidence is less satisfactory compared to data on antiviral prophylaxis ( evidence from SR ) . There is insufficient evidence of conclusive recommendations on treatment of CMV-negative recipients of renal transplants from CMV-negative donors .
MS22046	*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 This study examined the extent to which being abused and /or neglected in childhood increases a person 's risk for promiscuity , prostitution , and teenage pregnancy . METHODS A prospect i ve cohorts design was used to match , on the basis of age , race , sex , and social class , cases of abused and /or neglected children from 1967 to 1971 with nonabused and nonneglected children ; subjects were followed into young adulthood . From 1989 to 1995 1196 subjects ( 676 abused and /or neglected and 520 control subjects were located and interviewed . RESULTS Early childhood abuse and /or neglect was a significant predictor of prostitution for females ( odds ratio [ OR ] = 2.96 ) . For females , sexual abuse ( OR = 2.54 ) and neglect ( OR = 2.58 ) were associated with prostitution , whereas physical abuse was only marginally associated . Childhood abuse and neglect were not associated with increased risk for promiscuity or teenage pregnancy . CONCLUSIONS These findings strongly support a relationship between childhood victimization and subsequent prostitution . The presumed causal sequence between childhood victimization and teenage pregnancy may need to be reevaluated The relationship between sexual and physical abuse history and negative health effects has been well-documented in medical facility sample s. Few studies have examined the role of abuse history and its relationship with chronic fatigue and psychiatric disorders in a diverse , r and omly selected community-based sample . The present study compared rates of different types of abuse events in individuals with chronic fatigue and non-symptomatic controls . Relationships between specific types of abuse and psychiatric disorders commonly associated with chronic fatigue were also explored . A stratified r and om sample of 18,675 adults residing in ethnically and socioeconomically diverse neighborhoods in Chicago first completed a telephone screening question naire . A control group and a group of individuals with chronic fatigue symptomatology were identified and administered a semi-structured psychiatric interview assessing DSM-IV Axis I psychiatric disorders and a sexual and physical abuse history question naire . Controlling for sociodemographic differences , fatigue outcome was significantly predicted by childhood sexual abuse and the total number of different childhood abuse events . Within the chronic fatigue group , diagnosis of posttraumatic stress disorder ( PTSD ) was significantly predicted by childhood sexual abuse , childhood death threat , the total number of childhood abuse events , and lifetime abuse events . Sexual abuse during adolescence or adulthood significantly predicted other anxiety disorders among individuals with chronic fatigue . These findings suggest that a history of abuse , particularly during childhood , may play a role in the development and perpetuation of a wide range of disorders involving chronic fatigue . Among individuals with chronic fatigue , PTSD and other anxiety disorders appear to demonstrate the strongest association with abuse history . The implication s of these findings are discussed Using a r and omly selected community-based sample , this investigation examined whether histories of childhood sexual , physical , and death threat abuse predicted adulthood outcomes of specific medical and psychiatric conditions involving chronic fatigue . This study also tested prior suggestions that most individuals with chronic fatigue syndrome report a past history of interpersonal abuse . Multinomial logistic regression was used to examine the relationship between abuse history and chronic fatigue group outcomes while controlling for the effects of sociodemographics . Compared with healthy controls , childhood sexual abuse was significantly more likely to be associated with outcomes of idiopathic chronic fatigue , chronic fatigue explained by a psychiatric condition , and chronic fatigue explained by a medical condition . None of the abuse history types were significant predictors of chronic fatigue syndrome . A closer examination of individuals in the chronic fatigue syndrome group revealed that significantly fewer individuals with CFS reported abuse as compared with those who did not . The implication s of these findings are discussed Patterns of physical comorbidity among women with posttraumatic stress disorder ( PTSD ) were explored using Michigan Medicaid cl aims data . PTSD-diagnosed women ( n = 2,133 ) were compared with 14,948 r and omly selected women in three health outcome areas : ICD-9 categories of disease , chronic conditions associated with sexual assault history in previous research , and reproductive health conditions . PTSD was associated with increased risk of all categories of diseases ( OR range = 1.3 - 4.8 ) , endometriosis ( OR = 2.7 ) , and dyspareunia ( OR = 3.4 ) . When PTSD was not complicated by other mental health conditions , odds ratios for chronic conditions ranged from 1.9 for fibromyalgia to 4.3 for irritable bowel . Comorbidity with depression or a dissociative or borderline personality disorder raised risk in a dose-response pattern OBJECTIVE Clinic based studies suggest that adverse events in childhood may predispose to chronic pain in adult life . These have been conducted on highly selected groups , and it is unknown whether these relationships hold in the general population and to what extent the increased rate of adverse childhood events in persons with pain is an artefact of differential reporting . We examined the hypothesis that chronic widespread pain was associated with reports of adverse experiences in childhood and whether any observed relationships could be explained by differential recall . METHODS A cross sectional population based screening survey was conducted . Subjects completed a question naire that included assessment s of pain and psychological state . In total , 296 subjects who had demonstrated psychological distress were r and omly selected and had a detailed interview , which included an assessment of 14 adverse childhood experiences . Medical records relating to childhood were also examined for those subjects . RESULTS The prevalence of self-reported adverse childhood experiences was greatest in adult subjects with current chronic widespread pain . Exposure to illness in family members , parental loss , operations , and abuse were all associated with increased , but nonsignificant , odds of having chronic widespread pain versus those without such exposures . However the only statistically significant association was with childhood hospitalizations . From medical record information the associations of hospitalizations ( OR 5.1 , 95 % CI 2.0 - 13.0 ) and operations ( OR 3.0 , 95 % CI 1.2 - 7.2 ) with pain previously noted were partly explained by differential recall between subjects with and without pain : hospitalizations , OR 2.2 , 95 % CI 0.9 - 5.5 ; operations , OR 1.2 , 95 % CI 0.5 - 3.4 . CONCLUSION Although several reported adverse events in childhood were observed to be associated with chronic widespread pain in adulthood , only reports of hospitalizations were significantly associated . Validation of self-reported exposures suggests that there was differential recall of past events among those with and without pain , and this differential recall explained the association between hospitalizations and current chronic pain . Such differential recall may explain other observations of an association between reports of adverse childhood events and chronic pain in adulthood To profile differences in current physical symptoms and medical conditions among women users of Veterans Administration ( VA ) health services with and without a self-reported history of sexual assault sustained during military service , we conducted a cross-sectional analysis of a nationally representative , r and om sample of women veterans using VA outpatient services ( n = 3632 ) . A self-administered , mailed survey asked whether women had sustained sexual assault while in the military and requested information about a spectrum of physical symptoms and medical conditions . A history of sexual assault while in the military was reported by 23 % of women VA users and was associated with current physical symptoms and medical conditions in every domain assessed . For example , women who reported sexual assault were more likely to indicate that they had a " heart attack " within the past year , even after adjusting for age , hypertension , diabetes , and smoking history ( OR 2.3 , 95 % CI 1.3 - 4.0 ) . Among women reporting a history of sexual assault while in the military , 26 % endorsed > or = 12 of 24 symptoms/conditions , compared with 11 % of women with no reported sexual assault while in the military ( p < 0.001 ) . Clinicians need to be attuned to the high frequency of sexual assault occurring while in the military reported by women VA users and its associated array of current physical symptoms and medical conditions . Clinicians should consider screening both younger and older patients for a sexual violence history , especially patients with multiple physical symptoms BACKGROUND Little is known about the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis ( CFS/ME ) ; prospect i ve studies suggest a role for premorbid mood disorder . AIMS To examine childhood and early adult adversity , ill health and physical activity as premorbid risk markers for CFS/ME by 42 years , taking psychopathology into account . METHOD Data were from the 1958 British birth cohort , a prospect i ve study from birth to 42 years ( n = 11 419 ) . The outcomes were self-reported CFS/ME ( n = 127 ) and operationally defined CFS-like illness ( n = 241 ) at 42 years . RESULTS Adjusting for psychopathology , parental physical abuse ( odds ratio ( OR ) = 2.10 , 95 % CI 1.16 - 3.81 ) , childhood gastrointestinal symptoms ( OR = 1.58 , 95 % CI 1.00 - 2.50 ) and parental reports of many colds ( OR = 1.65 , 95 % CI 1.09 - 2.50 ) were independently associated with self-reported CFS/ME . Female gender and premorbid psychopathology were the only risk markers for CFS-like illness , independent of comorbid psychopathology . CONCLUSIONS This confirms the importance of premorbid psychopathology in the aetiological pathways of CFS/ME , and replicates retrospective findings that childhood adversity may play a role in a minority Abstract Prior studies of careseeking fibromyalgia ( FM ) patients often report that they have an elevated risk of psychiatric disorders , but biased sampling may distort true risk . The current investigation utilizes state‐of‐the‐art diagnostic procedures for both FM and psychiatric disorders to estimate prevalence rates of FM and the comorbidity of FM and specific psychiatric disorders in a diverse community sample of women . Participants were screened by telephone for FM and MDD , by r and omly selecting telephone numbers from a list of households with women in the NY/NJ metropolitan area . Eligible women were invited to complete physical examinations for FM and clinician‐administered psychiatric interviews . Data were weighted to adjust for sampling procedures and population demographics . The estimated overall prevalence of FM among women in the NY/NJ metropolitan area was 3.7 % ( 95 % CI = 3.2 , 4.4 ) , with higher rates among racial minorities . Although risk of current MDD was nearly 3‐fold higher in community women with than without FM , the groups had similar risk of lifetime MDD . Risk of lifetime anxiety disorders , particularly obsessive compulsive disorder and post‐traumatic stress disorder , was approximately 5‐fold higher among women with FM . Overall , this study found a community prevalence for FM among women that replicates prior North American studies , and revealed that FM may be even more prevalent among racial minority women . These community‐based data also indicate that the relationship between MDD and FM may be more complicated than previously thought , and call for an increased focus on anxiety disorders in FM Abstract Previous studies of the association between posttraumatic stress disorder ( PTSD ) and chronic widespread pain ( CWP ) or fibromyalgia have not examined the role of familial or genetic factors . The goals of this study were to determine if symptoms of PTSD are related to CWP in a genetically informative community‐based sample of twin pairs , and if so , to ascertain if the association is due to familial or genetic factors . Data were obtained from the University of Washington Twin Registry , which contains 1042 monozygotic and 828 dizygotic twin pairs . To assess the symptoms of PTSD , we used questions from the Impact of Events Scale ( IES ) . IES scores were partitioned into terciles . CWP was defined as pain located in 3 body regions lasting at least 1 week during the past 3 months . R and om‐effects regression models , adjusted for demographic features and depression , examined the relationship between IES and CWP . IES scores were strongly associated with CWP ( P < 0.0001 ) . Compared to those in the lowest IES tercile , twins in the highest tercile were 3.5 times more likely to report CWP . Although IES scores were associated with CWP more strongly among dizygotic than among monozygotic twins , this difference was not significant . Our findings suggest that PTSD symptoms , as measured by IES , are strongly linked to CWP , but this association is not explained by a common familial or genetic vulnerability to both conditions . Future research is needed to underst and the temporal association of PTSD and CWP , as well as the physiological underpinnings of this relationship Background —In out patients and the community , an association between abuse ( particularly sexual abuse ) and irritable bowel syndrome ( IBS ) has been observed , but whether there is a causal link continues to be disputed . Aims —To test the hypothesis that psychological factors explain the apparent association between abuse and IBS . Methods —A sample of residents of Penrith ( a Sydney suburb sociodemographically similar to the Australian population ) selected r and omly from the electoral rolls ( that by law include the entire population of age 18 years and above ) was mailed a vali date d self report question naire . Measured were gastrointestinal ( GI ) symptoms including the Rome criteria for IBS , abuse ( including the st and ardised Drossman questions ) , neuroticism ( Eysenck Personality Question naire ) , and psychological morbidity ( General Health Question naire ) . Results —The response rate was 64 % ( n=730 Output:	This association was robust against both publication bias and the generally low quality of the literature . The magnitude of the association with PTSD was significantly larger than that with sexual or physical abuse . The association of reported trauma with chronic fatigue syndrome was larger than the association with either irritable bowel syndrome or fibromyalgia . Studies using nonvali date d question naires or self-report of trauma reported larger associations than did those using vali date d question naires . Findings are consistent with the hypothesis that traumatic events are associated with an increased prevalence of functional somatic syndromes .
MS22047	*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 the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) , interferential currents ( IFCs ) , and shortwave diathermy ( SWD ) against each other and sham intervention with exercise training and education as a multimodal package . DESIGN A double-blind , r and omized , controlled , multicenter trial . SETTING Departments of physical medicine and rehabilitation in 4 centers . PARTICIPANTS Patients ( N=203 ) with knee osteoarthritis ( OA ) . INTERVENTIONS The patients were r and omized by the principal center into the following 6 treatment groups : TENS sham , TENS , IFCs sham , IFCs , SWD sham , and SWD . All interventions were applied 5 times a week for 3 weeks . In addition , exercises and an education program were given . The exercises were carried out as part of a home-based training program after 3 weeks ' supervised group exercise . MAIN OUTCOME MEASURES Primary outcome was a visual analog scale ( 0 - 100 mm ) to assess knee pain . Other outcome measures were time to walk a distance of 15 m , range of motion , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , Nottingham Health Profile , and paracetamol intake ( in grams ) . RESULTS We found a significant decrease in all assessment parameters ( P<.05 ) , without a significant difference among the groups except WOMAC stiffness score and range of motion . However , the intake of paracetamol was significantly lower in each treatment group when compared with the sham groups at 3 months ( P<.05 ) . Also , the patients in the IFCs group used a lower amount of paracetamol at 6 months ( P<.05 ) in comparison with the IFCs sham group . CONCLUSIONS Although all groups showed significant improvements , we can suggest that the use of physical therapy agents in knee OA provided additional benefits in improving pain because paracetamol intake was significantly higher in the patients who were treated with 3 sham interventions in addition to exercise and education The purpose of this study was to compare the effectiveness of transcutaneous nerve stimulation ( TENS ) , electroacupuncture ( EA ) , and ice massage with placebo treatment for the treatment of pain . Subjects ( n = 100 ) diagnosed with osteoarthritis ( OA ) of the knee were treated with these modalities . The parameters for evaluating the effectiveness of treatment include pain at rest , stiffness , 50 foot walking time , quadriceps muscle strength , and knee flexion degree . The results showed ( a ) that all three methods could be effective in decreasing not only pain but also the objective parameters in a short period of time ; and ( b ) that the treatment results in TENS , EA and ice massage were superior to placebo Background The present study tests whether a combined treatment of acupuncture and transcutaneous electrical nerve stimulation ( TENS ) is more effective than acupuncture or TENS alone for treating knee osteoarthritis ( OA ) . Methods Thirty-two patients with knee OA were r and omly allocated to four groups . The acupuncture group ( ACP ) received only acupuncture treatment at selected acupoints for knee pain ; the TENS group ( TENS ) received only TENS treatment at pain areas ; the acupuncture and TENS group ( A&T ) received both acupuncture and TENS treatments ; the control group ( CT ) received topical poultice ( only when necessary ) . Each group received specific weekly treatment five times during the study . Outcome measures were pain intensity in a visual analogue scale ( VAS ) and knee function in terms of the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Results The ACP , TENS and A&T groups reported lower VAS and WOMAC scores than the control group . Significant reduction in pain intensity ( P = 0.039 ) and significant improvement in knee function ( P = 0.008 ) were shown in the A&T group . Conclusion Combined acupuncture and TENS treatment was effective in pain relief and knee function improvement for the sample d patients suffering from knee OA In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVE This study examined the optimal stimulation duration of transcutaneous electrical nerve stimulation ( TENS ) for relieving osteoarthritic knee pain and the duration ( as measured by half-life ) of post-stimulation analgesia . SUBJECTS Thirty-eight patients received either : ( i ) 20 minutes ( TENS20 ) ; ( ii ) 40 minutes ( TENS40 ) ; ( iii ) 60 minutes ( TENS60 ) of TENS ; or ( iv ) 60 minutes of placebo TENS ( TENS(PL ) ) 5 days a week for 2 weeks . METHODS A visual analogue scale recorded the magnitude and pain relief period for up to 10 hours after stimulation . RESULTS By Day10 , a significantly greater cumulative reduction in the visual analogue scale scores was found in the TENS40 ( 83.40 % ) and TENS60 ( 68.37 % ) groups than in the TENS20 ( 54.59 % ) and TENS(PL ) ( 6.14 % ) groups ( p < 0.000 ) , such a group difference was maintained in the 2-week follow-up session ( p < 0.000 ) . In terms of the duration of post-stimulation analgesia period , the duration for the TENS40 ( 256 minutes ) and TENS60 ( 258 minutes ) groups was more prolonged than in the other 2 groups ( TENS20 = 168 minutes , TENS(PL ) = 35 minutes ) by Day10 ( p < 0.000 ) . However , the TENS40 group produced the longest pain relief period by the follow-up session . CONCLUSION 40 minutes is the optimal treatment duration of TENS , in terms of both the magnitude ( VAS scores ) of pain reduction and the duration of post-stimulation analgesia for knee osetoarthritis Abstract Objective : To study the effects of transcutaneous electrical nerve stimulation ( TENS ) on joint position sense ( JPS ) in knee osteoarthritis ( OA ) subjects . Methods : Thirty subjects with knee OA ( 40–60 years old ) using non-r and om sampling participated in this study . In order to evaluate the absolute error of repositioning of the knee joint , Qualysis Track Manager system was used and sensory electrical stimulation was applied through the TENS device . Results : The mean errors in repositioning of the joint , in two position of the knee joint with 20 and 60 degree angle , after applying the TENS was significantly decreased ( p < 0.05 ) . Conclusion : Application of TENS in subjects with knee OA could improve JPS in these subjects Cetin N , Aytar A , Atalay A , Akman MN : Comparing hot pack , short-wave diathermy , ultrasound , and TENS on isokinetic strength , pain , and functional status of women with osteoarthritic knees : a single-blind , r and omized , controlled trial . Am J Phys Med Rehabil 2008;87:443–451 . Objective : To investigate the therapeutic effects of physical agents administered before isokinetic exercise in women with knee osteoarthritis . Design : One hundred patients with bilateral knee osteoarthritis were r and omized into five groups of 20 patients each : group 1 received short-wave diathermy + hot packs and isokinetic exercise ; group 2 received transcutaneous electrical nerve stimulation + hot packs and isokinetic exercise ; group 3 received ultrasound + hot packs and isokinetic exercise ; group 4 received hot packs and isokinetic exercise ; and group 5 served as controls and received only isokinetic exercise . Results : Pain and disability index scores were significantly reduced in each group . Patients in the study groups had significantly greater reductions in their visual analog scale scores and scores on the Lequesne index than did patients in the control group ( group 5 ) . They also showed greater increases than did controls in muscular strength at all angular velocities . In most parameters , improvements were greatest in groups 1 and 2 compared with groups 3 and 4 . Conclusions : Using physical agents before isokinetic exercises in women with knee osteoarthritis leads to augmented exercise performance , reduced pain , and improved function . Hot pack with a transcutaneous electrical nerve stimulator or short-wave diathermy has the best outcome It is not clear whether segmental innocuous stimulation has a stronger analgesic effect than segmental noxious stimulation for chronic pain and whether the fading of current sensation during treatment interferes with the analgesic effect , as suggested by the gate control theory . Electrical stimulation ( by way of Interferential Current ) applied at the pain area ( segmental ) was administered to 4 groups of patients with osteoarthritis ( OA ) knee pain . Two groups were administered with noxious stimulation ( 30 % above pain threshold ) and two with innocuous stimulation ( 30 % below pain threshold ) . In each group half of the patients received a fixed current intensity while the other half raised the intensity continuously during treatment whenever fading of sensation was perceived . Group 5 and 6 received sham stimulation and no treatment , respectively . The outcome measures were : chronic pain intensity , morning stiffness , range of motion ( ROM ) , pain threshold and % pain reduction . Both noxious and innocuous stimulation significantly decreased chronic pain ( P<0.001 ) and morning stiffness ( P<0.01 ) and significantly increased pain threshold ( P<0.001 ) and ROM ( P<0.001 ) compared with the control groups . Nevertheless , noxious stimulation decreased pain intensity ( P<0.05 ) and increased pain threshold ( P<0.001 ) significantly more than innocuous stimulation . No differences in treatment outcomes were found between adjusted and unadjusted stimulation . ( a ) Interferential current is very effective for chronic OA knee pain , ( b ) segmental noxious stimulation produces a stronger analgesic effect than segmental innocuous stimulation , ( c ) the fading of sensation during treatment , does not decrease the analgesic effect . Possible mechanisms explaining the findings are discussed Background : According to a recent meta analysis study , there is strong evidence to support the view that transcutaneous electrical nerve stimulation ( TENS ) is an effective treatment for managing osteoarthritis ( OA ) knee pain . However , there is limited evidence showing its effectiveness in improving physical function . This study examined whether TENS alone can improve physical function in terms of range of knee motion and the Timed-Up- and -Go Test . Methods : Subjects were r and omly allocated into 2 groups receiving TENS at 100 Hz or a placebo TENS . Outcome measures included : 1 ) visual analog scale for measuring the intensity of the present pain , 2 ) Timed-Up- and -Go Test , and 3 ) range of knee motion ( ROM ) . Repeated- measures analysis of variance and Pearson correlation were used for data analyses . Results : By day 10 , TENS produced a significantly greater increase in maximum knee ROM than the placebo group ( P = 0.033 ) . TENS also significantly increased the pain-limited knee ROM across sessions , but the between-group difference was short of significance ( P = 0.067 ) . The decrease in time in performing the Timed-Up- and -Go Test was also not significantly different between the 2 groups . A moderate correlation was observed between the reduction in pain scores and the improvement in the Timed-Up- and -Go Test . Conclusions : Our findings suggested that TENS did improve some of the physical parameters but over 10 days was unable to produce significant improvement in functional performance among people with knee OA . A larger-scale study with the assessment of other functional outcomes may be required to clarify if TENS could improve function in people with knee OA . Also , exercise can be considered to be an important adjunct treatment to TENS to improve function significantly OBJECTIVE This is a double blind study that examined the optimal stimulation frequency of transcutaneous electrical nerve stimulation in reducing pain due to knee osteoarthritis . SUBJECTS Thirty-four subjects were r and omly allocated into 4 groups receiving transcutaneous electrical nerve stimulation at either : ( i ) 2 Hz ; ( ii ) 100 Hz ; ( iii ) an alternating frequency of 2 Hz and 100 Hz ( 2/100 Hz ) ; or ( iv ) a placebo transcutaneous electrical nerve stimulation . METHODS Treatment was administered 5 days a week for 2 weeks . The outcome measures included : ( i ) a visual analogue scale ; ( ii ) a timed up- and -go test ; and ( iii ) a range of knee motion . RESULTS The 3 active transcutaneous electrical nerve stimulation groups ( 2 Hz , Output:	DISCUSSION TENS might relieve pain due to knee osteoarthritis .
MS22048	*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: Emerging health problems require rapid advice . We describe the development and pilot testing of a systematic , transparent approach used by the World Health Organization ( WHO ) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A ( H5N1 ) virus infection . We first search ed for systematic review s of r and omized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection , including case reports and animal and in vitro studies . A panel of clinical experts , clinicians with experience in treating patients with H5N1 , influenza research ers , and method ologists was convened for a two-day meeting . Panel members review ed the evidence prior to the meeting and agreed on the process . It took one month to put together a team to prepare the evidence profiles ( i.e. , summaries of the evidence on important clinical and policy questions ) , and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting . A draft manuscript for publication was prepared within 10 days following the panel meeting . Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines . The process could be improved by shortening the time required to commission evidence profiles . Further development is needed to facilitate stakeholder involvement , and evaluate and ensure the guideline 's usefulness STUDY OBJECTIVE We report on the incremental costs associated with improvements in health-related quality of life ( HRQL ) following 6 months of respiratory rehabilitation compared with conventional community care . DESIGN Prospect i ve r and omized controlled trial of rehabilitation . SETTING A respiratory rehabilitation unit . PARTICIPANTS Eighty-four subjects who completed the rehabilitation trial . INTERVENTION Two months of inpatient rehabilitation followed by 4 months of outpatient supervision . MEASUREMENTS AND RESULTS All costs ( hospitalization , medical care , medications , home care , assistive devices , transportation ) were included . Simultaneous allocation was used to determine capital and direct and indirect hospitalization costs . The incremental cost of achieving improvements beyond the minimal clinical ly important difference in dyspnea , emotional function , and mastery was $ 11,597 ( Canadian ) . More than 90 % of this cost was attributable to the inpatient phase of the program . Of the nonphysician health-care professionals , nursing was identified as the largest cost center , followed by physical therapy and occupational therapy . The number of subjects needed to be treated ( NNT ) to improve one subject was 4.1 for dyspnea , 4.4 for fatigue , 3.3 for emotion , and 2.5 for mastery . CONCLUSION Cost estimates of various approaches to rehabilitation should be combined with valid , reliable , and responsive measures of outcome to enable cost-effectiveness measures to be reported . Comparison studies with the same method are necessary to determine whether the improvements in HRQL that follow inpatient rehabilitation are cheap or expensive . Such information will be important in identifying the extent to which alternative approaches to rehabilitation can influence re source allocation . A consideration of cost-effectiveness from the perspective of NNT may be useful in the evaluation of health-care programs The aim of this paper is to assess the health economic consequences of substituting ipratropium with the new , once-daily bronchodilator tiotropium in patients with a diagnosis of chronic obstructive pulmonary disease ( COPD ) . This prospect i ve cost-effectiveness analysis was performed alongside two 1‐yr r and omised , double-blind clinical trials in the Netherl and s and Belgium . Patients had a diagnosis of COPD and a forced expiratory volume in one second ( FEV1 ) ≤65 % predicted normal . Patients were r and omised to tiotropium ( 18 µg once daily ) or ipratropium ( 2 puffs of 20 µg administered four times daily ) in a ratio of 2:1 . The mean number of exacerbations was reduced from 1.01 in the ipratropium group ( n=175 ) to 0.74 in the tiotropium group ( n=344 ) . The percentages of patients with a relevant improvement on the St. George 's Respiratory Question naire ( SGRQ ) were 34.6 % and 51.2 % respectively . Compared to ipratropium , the number of hospital admissions , hospital days and unscheduled visits to healthcare providers was reduced by 46 % , 42 % and 36 % respectively . Mean annual healthcare costs including the acquisition cost of the study drugs were 1721 ( sem 160 ) in the tiotropium group and 1,541 ( SEM 163 ) in the ipratropium group ( difference 180 ) . Incremental cost-effectiveness ratios were 667 per exacerbation avoided and 1084 per patient with a relevant improvement on the SGRQ . Substituting tiotropium for ipratropium in chronic obstructive pulmonary disease patients offers improved health outcomes and is associated with increased costs of 180 per patient per year BACKGROUND Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures , and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify . Lamotrigine and topiramate are also thought to possess broad spectrum activity . The SANAD study aim ed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify . METHODS SANAD was an unblinded r and omised controlled trial in hospital-based outpatient clinics in the UK . Arm B of the study recruited 716 patients for whom valproate was considered to be st and ard treatment . Patients were r and omly assigned to valproate , lamotrigine , or topiramate between Jan 12 , 1999 , and Aug 31 , 2004 , and follow-up data were obtained up to Jan 13 , 2006 . Primary outcomes were time to treatment failure , and time to 1-year remission , and analysis was by both intention to treat and per protocol . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N38354748 . FINDINGS For time to treatment failure , valproate was significantly better than topiramate ( hazard ratio 1.57 [ 95 % CI 1.19 - 2.08 ] ) , but there was no significant difference between valproate and lamotrigine ( 1.25 [ 0.94 - 1.68 ] ) . For patients with an idiopathic generalised epilepsy , valproate was significantly better than both lamotrigine ( 1.55 [ 1.07 - 2.24 ] and topiramate ( 1.89 [ 1.32 - 2.70 ] ) . For time to 12-month remission valproate was significantly better than lamotrigine overall ( 0.76 [ 0.62 - 0.94 ] ) , and for the subgroup with an idiopathic generalised epilepsy 0.68 ( 0.53 - 0.89 ) . But there was no significant difference between valproate and topiramate in either the analysis overall or for the subgroup with an idiopathic generalised epilepsy . INTERPRETATION Valproate is better tolerated than topiramate and more efficacious than lamotrigine , and should remain the drug of first choice for many patients with generalised and unclassified epilepsies . However , because of known potential adverse effects of valproate during pregnancy , the benefits for seizure control in women of childbearing years should be considered Output:	At present , disaggregated re source utilization accompanied by some cost information seems to be the most promising approach . The method for assigning values to costs , including external or indirect cost ( such as time off work ) , can have a significant impact on the outcome of any economic evaluation .
MS22049	*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 —Statins primarily metabolized by cytochrome P450 3A4 ( CYP3A4 ) reportedly reduce clopidogrel ’s metabolism to active metabolite , thus attenuating its inhibition of platelet aggregation ex vivo . However , the clinical impact of this interaction has not been evaluated . Methods and Results —Clopidogrel for the Reduction of Events During Observation ( CREDO ) was a double-blind , placebo-controlled , r and omized trial comparing pretreatment ( 300 mg ) and 1-year ( 75 mg/d ) clopidogrel therapy ( clopidogrel ) with no pretreatment and 1-month clopidogrel therapy ( 75 mg/d ) ( control ) after a planned percutaneous coronary intervention . All patients received aspirin . The 1-year primary end point was a composite of death , myocardial infa rct ion , and stroke . We performed a post hoc analysis to evaluate the clinical efficacy of concomitant clopidogrel and statin administration , categorizing baseline statin use to those predominantly CYP3A4-metabolized ( atorvastatin , lovastatin , simvastatin , and cerivastatin ) ( CYP3A4-MET ) or others ( pravastatin and fluvastatin ) ( non-CYP3A4-MET ) . Of the 2116 patients enrolled , 1001 received a CYP3A4-MET and 158 a non-CYP3A4-MET statin . For the overall study population , the primary end point was significantly reduced in the clopidogrel group ( 8.5 % versus 11.5 % , RRR 26.9 % ; P = 0.025 ) . This clopidogrel benefit was similar with statin use , irrespective of treatment with a CYP3A4-MET ( 7.6 % clopidogrel , 11.8 % control , RRR 36.4 % , 95 % CI 3.9 to 57.9 ; P = 0.03 ) or non-CYP3A4-MET statin ( 5.4 % clopidogrel , 13.6 % control , RRR 60.6 % , 95 % CI −23.9 to 87.4 ; P = 0.11 ) . Patients given atorvastatin or pravastatin had similar 1-year event rates . Additionally , concomitant therapy with statins had no impact on major or minor bleeding rates . Conclusions —Although ex vivo testing has suggested a potential negative interaction when coadministering a CYP3A4-metabolized statin with clopidogrel , this was not clinical ly observed statistically in a post hoc analysis of a placebo-controlled study BACKGROUND Despite current treatments , patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events . We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients . METHODS We r and omly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel ( 300 mg immediately , followed by 75 mg once daily ) ( 6259 patients ) or placebo ( 6303 patients ) in addition to aspirin for 3 to 12 months . RESULTS The first primary outcome --a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group ( relative risk with clopidogrel as compared with placebo , 0.80 ; 95 percent confidence interval , 0.72 to 0.90 ; P<0.001 ) . The second primary outcome --the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group ( relative risk , 0.86 ; 95 percent confidence interval , 0.79 to 0.94 ; P<0.001 ) . The percentages of patients with in-hospital refractory or severe ischemia , heart failure , and revascularization procedures were also significantly lower with clopidogrel . There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group ( 3.7 percent vs. 2.7 percent ; relative risk , 1.38 ; P=0.001 ) , but there were not significantly more patients with episodes of life-threatening bleeding ( 2.2 percent [ corrected ] vs. 1.8 percent ; P=0.13 ) or hemorrhagic strokes ( 0.1 percent vs. 0.1 percent ) . CONCLUSIONS The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation . However , the risk of major bleeding is increased among patients treated with clopidogrel Background —We observed that the prodrug clopidogrel was less effective in inhibiting platelet aggregation with coadministration of atorvastatin during point-of-care platelet function testing . Because atorvastatin is metabolized by cytochrome P450 ( CYP ) 3A4 , we hypothesized that clopidogrel might be activated by CYP3A4 . Methods and Results —Platelet aggregation was measured in 44 patients undergoing coronary artery stent implantation treated with clopidogrel or clopidogrel plus pravastatin or atorvastatin , and in 27 volunteers treated with clopidogrel and either erythromycin or trole and omycin , CYP3A4 inhibitors , or rifampin , a CYP3A4 inducer . Atorvastatin , but not pravastatin , attenuated the antiplatelet activity of clopidogrel in a dose-dependent manner . Percent platelet aggregation was 34±23 , 58±15 ( P = 0.027 ) , 74±10 ( P = 0.002 ) , and 89±7 ( P = 0.001 ) in the presence of clopidogrel and 0 , 10 , 20 , and 40 mg of atorvastatin , respectively . Erythromycin attenuated platelet aggregation inhibition ( 55±12 versus 42±12 % platelet aggregation;P = 0.002 ) , as did trole and omycin ( 78±18 versus 45±18 % platelet aggregation;P < 0.0003 ) , whereas rifampin enhanced platelet aggregation inhibition ( 33±18 versus 56±20 % platelet aggregation , P = 0.001 ) . Conclusions —CYP3A4 activates clopidogrel . Atorvastatin , another CYP3A4 substrate , competitively inhibits this activation . Use of a statin not metabolized by CYP3A4 and point-of-care platelet function testing may be warranted in patients treated with clopidogrel Output:	They report no evidence for a specific drug interaction and find that PPIs were associated with an increased risk for adverse cardiovascular outcomes independent of clopidogrel use . In other words , the adverse effects attributed to this suspected drug interaction are not only 4- to 9-fold larger than clopidogrel 's benefits , as established by RCT data , but also occur in an etiologically implausible time window during which clopidogrel has not been shown to be therapeutically active . The previous efficacy evidence suggests that the adverse events attributed to concomitant administration of clopidogrel and PPIs are more likely related to residual confounding from unmeasured adverse prognostic variables among patients who receive PPIs . An abstract publication from a post hoc analysis of the CREDO ( Clopidogrel for the Reduction of Events During Observation ) study ( 2 ) has also reported an increased risk for adverse events with PPIs , independent of clopidogrel exposure . Although PPIs have been inappropriately prescribed , with a lack of objective benefit , in young patients with dyspepsia , previous works from the same Danish data base ( 13 ) and other data bases ( 14 ) have clearly demonstrated that elderly patients with ACS who receive combination antiplatelet regimens have a 4- to 5-fold increase in their risk for serious gastrointestinal bleeding , which can be reduced with PPIs ( 15 , 16 ) . Many studies ( 17 , 18 ) have also suggested that periprocedural bleeding during percutaneous coronary intervention , including gastrointestinal bleeding , is associated with increased long-term mortality .
MS22050	*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 effect of pharmaceutical care on the prevention , detection , and resolution of medication-related problems in high-risk patients in a rural community was studied . Adult patients who received care at clinics in a medically underserved area of Alabama and who were identified as being at high risk of medication-related adverse events were r and omly assigned to a control group or an intervention group . The control group received st and ard medical care , and the intervention group received pharmaceutical care , including a medical record review , a medication history review , pharmacotherapeutic evaluation , and patient medication education and monitoring over a one-year period . A total of 69 patients completed the study ( 33 in the intervention group and 36 in the control group ) . The percentage of patients responding to hypertension , diabetes , dyslipidemia , and anticoagulation therapy increased significantly in the intervention group and declined in the control group . Ratings for inappropriate prescribing improved in all 10 domains evaluated in the intervention group but worsened in 5 domains in the control group . There were no significant differences between the groups at 12 months in health-related quality of life or medication misadventures . Medication compliance scores improved in the intervention group but not in the control group . Medication knowledge increased in the intervention group and decreased in the control group . Pharmaceutical care in a rural , community-based setting appeared to reduce inappropriate prescribing , enhance disease management , and improve medication compliance and knowledge without adversely affecting health-related quality of life Background Older people are at increased risk of drug-related problems ( DRPs ) caused by inappropriate use or underuse of medications which may be increased during care transitions . Objective To examine the effects of applying a vali date d prescribing appropriateness criteria -set during medication review in a cohort of older ( ≥65 years ) Australians at the time of discharge from hospital . Setting Private hospital and homes of older patients in Sydney , Australia . Methods Cognitively well English speaking patients aged 65 years or over taking five or more medications were recruited . A prescribing appropriateness criteria -set and SF-36 health-related quality of life health ( HRQoL ) survey were applied to all patients at discharge . Patients were then r and omly assigned to receive either usual care ( control , n = 91 ) or discharge medication counselling and a medication review by a clinical pharmacist ( intervention , n = 92 ) . Medication review recommendations were sent to the general practitioners of intervention group patients . All patients were followed up at 3 months post discharge , where the prescribing appropriateness criteria -set was reapplied and HRQoL survey repeated . Main outcome measures change in the number of prescribing appropriateness criteria met ; change in HRQoL ; number and causes of DRPS identified by medication review ; intervention patient medication recommendation implementation rates . Results There was no significant difference in the number of criteria applicable and met in intervention patients , compared to control patients , between follow-up and discharge ( 0.09 ≤ p ≤ 0.97 ) . While the difference between groups was positive at follow-up for SF-36 scores , the only domain that reached statistical significance was that for vitality ( p = 0.04 ) . Eighty-eight intervention patient medication review s identified 750 causes of DRPs ( 8.5 ± 2.7 per patient ) . No causes of DRPs were identified in four patients . Of these causes , 76.4 % ( 573/750 ) were identified by application of the prescribing appropriateness criteria -set . GPs implemented a relatively low number ( 42.4 % , 318/750 ) of recommendations . Conclusion Application of a prescribing appropriateness criteria -set during medication review in intervention patients did not increase the number of criteria met , nor result in a significant improvement in HRQoL. Higher recommendation implementation rates may require additional facilitators , including a higher quality of collaboration Objective To undertake a process evaluation of pharmacists ' recommendations arising in the context of a complex IT-enabled pharmacist-delivered r and omised controlled trial ( PINCER trial ) to reduce the risk of hazardous medicines management in general practice s. Methods PINCER pharmacists manually recorded patients ' demographics , details of interventions recommended , actions undertaken by practice staff and time taken to manage individual cases of hazardous medicines management . Data were coded , double-entered into SPSS version 15 and then summarised using percentages for categorical data ( with 95 % confidence interval ( CI ) ) and , as appropriate , means ( ± st and ard deviation ) or medians ( interquartile range ) for continuous data . Key findings Pharmacists spent a median of 20 min ( interquartile range 10 , 30 ) review ing medical records , recommending interventions and completing actions in each case of hazardous medicines management . Pharmacists judged 72 % ( 95 % CI 70 , 74 ; 1463/2026 ) of cases of hazardous medicines management to be clinical ly relevant . Pharmacists recommended 2105 interventions in 74 % ( 95 % CI 73 , 76 ; 1516/2038 ) of cases and 1685 actions were taken in 61 % ( 95 % CI 59 , 63 ; 1246/2038 ) of cases ; 66 % ( 95 % CI 64 , 68 ; 1383/2105 ) of interventions recommended by pharmacists were completed and 5 % ( 95 % CI 4 , 6 ; 104/2105 ) of recommendations were accepted by general practitioners ( GPs ) , but not completed at the end of the pharmacists ' placement ; the remaining recommendations were rejected or considered not relevant by GPs . Conclusions The outcome measures were used to target pharmacist activity in general practice towards patients at risk from hazardous medicines management . Recommendations from trained PINCER pharmacists were found to be broadly acceptable to GPs and led to ameliorative action in the majority of cases . It seems likely that the approach used by the PINCER pharmacists could be employed by other practice pharmacists following appropriate training OBJECTIVE To measure the effect of nurse practitioner and pharmacist consultations on the appropriate use of medications by patients . DESIGN We studied patients in the intervention arm of a r and omized controlled trial . The main trial intervention was provision of multidisciplinary team care and the main outcome was quality and processes of care for chronic disease management . SETTING Patients were recruited from a single publicly funded family health network practice of 8 family physicians and associated staff serving 10 000 patients in a rural area near Ottawa , Ont . PARTICIPANTS A total of 120 patients 50 years of age or older who were on the practice roster and who were considered by their family physicians to be at risk of experiencing adverse health outcomes . INTERVENTION A pharmacist and 1 of 3 nurse practitioners visited each patient at his or her home , conducted a comprehensive medication review , and developed a tailored plan to optimize medication use . The plan was developed in consultation with the patient and the patient 's doctor . We assessed medication appropriateness at the study baseline and again 12 to 18 months later . MAIN OUTCOME MEASURES We used the medication appropriateness index to assess medication use . We examined associations between personal characteristics and inappropriate use at baseline and with improvements in medication use at the follow-up assessment . We recorded all drug problems encountered during the trial . RESULTS At baseline , 27.2 % of medications were inappropriate in some way and 77.7 % of patients were receiving at least 1 medication that was inappropriate in some way . At the follow-up assessment s these percentages had dropped to 8.9 % and 38.6 % , respectively ( P < .001 ) . Patient characteristics that were associated with receiving inappropriate medication at baseline were being older than 80 years of age ( odds ratio [ OR ] = 5.00 , 95 % CI 1.19 to 20.50 ) , receiving more than 4 medications ( OR = 6.64 , 95 % CI 2.54 to 17.4 ) , and not having a university-level education ( OR = 4.55 , 95 % CI 1.69 to 12.50 ) . CONCLUSION We observed large improvements in the appropriate use of medications during this trial . This might provide a mechanism to explain some of the reductions in mortality and morbidity observed in other trials of counseling and advice provided by pharmacists and nurses . TRIAL REGISTRATION NUMBER NCT00238836 ( Clinical Trials.gov ) OBJECTIVES To determine whether a computerized tool that alerted pharmacists when patients aged 65 and older were newly prescribed potentially inappropriate medications was effective in decreasing the proportion of patients dispensed these medications . DESIGN Prospect i ve , r and omized trial . SETTING U.S. health maintenance organization . PARTICIPANTS All 59,680 health plan members aged 65 and older were r and omized to intervention ( n=29,840 ) or usual care ( n=29,840 ) . Pharmacists received alerts on all patients r and omized to intervention who were newly prescribed a targeted medication . INTERVENTION Prescription and age information were linked to alert pharmacists when a patient aged 65 and older was newly prescribed one of 11 medications that are potentially inappropriate in older people . MEASUREMENTS Physicians and pharmacists collaborated to develop the targeted medication list , indications for medication use for which an intervention should occur , intervention guidelines and scripts , and to implement the intervention . RESULTS Over the 1-year study , 543 ( 1.8 % ) intervention group patients aged 65 and older were newly dispensed prescriptions for targeted medications , compared with 644 ( 2.2 % ) usual care group patients ( P=.002 ) . For medication use indications in which an intervention should occur , dispensings of amitriptyline ( P<.001 ) and diazepam ( P=.02 ) were reduced . CONCLUSIONS This study demonstrated the effectiveness of a computerized pharmacy alert system plus collaboration between healthcare professionals in decreasing potentially inappropriate medication dispensings in elderly patients . Coupling data available from information systems with the knowledge and skills of physicians and pharmacists can improve prescribing safety in patients aged 65 and older BACKGROUND The pharmaceutical care approach serves as a model for medication review , involving collaboration between GPs , pharmacists , patients , and carers . Its use is advocated with older patients who are typically prescribed several drugs . However , it has yet to be thoroughly evaluated . AIM To estimate the effectiveness of pharmaceutical care for older people , shared between GPs and community pharmacists in the UK , relative to usual care . DESIGN OF STUDY Multiple interrupted time-series design in five primary care trusts which implemented pharmaceutical care at 2-month intervals in r and om order . Patients acted as their own controls , and were followed over 3 years including their 12 months ' participation in pharmaceutical care . SETTING In 2002 , 760 patients , aged > or = 75 years , were recruited from 24 general practice s in East and North Yorkshire . Sixty-two community pharmacies also took part . A total of 551 participants completed the study . METHOD Pharmaceutical care was undertaken by community pharmacists who interviewed patients , developed and implemented pharmaceutical care plans together with patients ' GPs , and thereafter undertook monthly medication review s. Pharmacists and GPs attended training before the intervention . Outcome measures were the UK Medication Appropriateness Index , the Short Form-36 Health Survey ( SF-36 ) , and serious adverse events . RESULTS The intervention did not lead to any statistically significant change in the appropriateness of prescribing or health outcomes . Although the mental component of the SF-36 decreased as study participants become older , this trend was not affected by pharmaceutical care . CONCLUSION The RESPECT model of pharmaceutical care ( R and omised Evaluation of Shared Prescribing for Elderly people in the Community over Time ) shared between community pharmacists and GPs did not significantly change the appropriateness of prescribing or quality of life in older patients Background Small trials with short term follow up suggest pharmacists ’ interventions targeted at healthcare professionals can improve prescribing . In comparison with clinical guidance , contemporary statin prescribing is sub-optimal and achievement of cholesterol targets falls short of accepted st and ards , for patients with atherosclerotic vascular disease who are at highest absolute risk and who st and to obtain greatest benefit . We hypothesised that a pharmacist-led complex intervention delivered to doctors and nurses in primary care , would improve statin prescribing and achievement of cholesterol targets for incident and prevalent patients with vascular disease , beyond one year . Methods We allocated general practice s to a 12-month Statin Outreach Support ( SOS ) intervention or usual care . SOS was delivered by one of 11 pharmacists who had received additional training . SOS comprised academic detailing and practical support to identify patients with vascular disease who were not prescribed a statin at optimal dose or did not have cholesterol at target , followed by individualised recommendations for changes to management . The primary outcome was the proportion of patients achieving cholesterol targets . Secondary outcomes were : the proportion of patients prescribed simvastatin 40 mg with target cholesterol achieved ; cholesterol levels ; prescribing of simvastatin 40 mg ; prescribing of any statin and the proportion of patients with cholesterol tested . Outcomes were assessed after an average of 1.7 years ( range 1.4–2.2 years ) , and practice level simvastatin 40 Output:	Conclusion : Overall , this review demonstrates that pharmacist-led interventions may improve prescribing appropriateness in community-dwelling older adults .
MS22051	*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 efficacy of bendamustine versus chlorambucil in a phase III trial of previously untreated patients with Binet stage B/C chronic lymphocytic leukaemia ( CLL ) was re‐evaluated after a median observation time of 54 months in May 2010 . Overall survival ( OS ) was analysed for the first time . At follow‐up , investigator‐assessed complete response ( CR ) rate ( 21·0 % vs 10·8 % ) , median progression‐free survival ( 21·2 vs 8·8 months ; P < 0·0001 ; hazard ratio 2·83 ) and time to next treatment ( 31·7 vs 10·1 months ; P < 0·0001 ) were improved for bendamustine over chlorambucil . OS was not different between groups for all patients or those ≤65 years , > 65 years , responders and non‐responders . However , patients with objective response or a CR experienced a significantly longer OS than non‐responders or those without a CR . Significantly more patients on chlorambucil progressed to second/further lines of treatment compared with those on bendamustine ( 78·3 % vs 63·6 % ; P = 0·004 ) . The benefits of bendamustine over chlorambucil were achieved without reducing quality of life . In conclusion , bendamustine is significantly more effective than chlorambucil in previously untreated CLL patients , with the achievement of a CR or objective response appearing to prolong OS . Bendamustine should be considered as a preferred first‐line option over chlorambucil for CLL patients ineligible for fludarabine , cyclophosphamide and rituximab Although chronic lymphocytic leukemia ( CLL ) is a disease of elderly patients , subjects older than 65 years are heavily underrepresented in clinical trials . The German CLL study group ( GCLLSG ) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil . A total of 193 patients with a median age of 70 years were r and omized to receive fludarabine ( 25 mg/m(2 ) for 5 days intravenously , every 28 days , for 6 courses ) or chlorambucil ( 0.4 mg/kg body weight [ BW ] with an increase to 0.8 mg/kg , every 15 days , for 12 months ) . Fludarabine result ed in a significantly higher overall and complete remission rate ( 72 % vs 51 % , P = .003 ; 7 % vs 0 % , P = .011 ) . Time to treatment failure was significantly shorter in the chlorambucil arm ( 11 vs 18 months ; P = .004 ) , but no difference in progression-free survival time was observed ( 19 months with fludarabine , 18 months with chlorambucil ; P = .7 ) . Moreover , fludarabine did not increase the overall survival time ( 46 months in the fludarabine vs 64 months in the chlorambucil arm ; P = .15 ) . Taken together , the results suggest that in elderly CLL patients the first-line therapy with fludarabine alone does not result in a major clinical benefit compared with chlorambucil . This trial is registered with www.is rct n.org under identifier IS RCT N 36294212 Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed BACKGROUND Chronic lymphocytic leukemia ( CLL ) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression . We conducted an international , open-label , r and omized phase 3 trial to compare two oral agents , ibrutinib and chlorambucil , in previously untreated older patients with CLL or small lymphocytic lymphoma . METHODS We r and omly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil . The primary end point was progression-free survival as assessed by an independent review committee . RESULTS The median age of the patients was 73 years . During a median follow-up period of 18.4 months , ibrutinib result ed in significantly longer progression-free survival than did chlorambucil ( median , not reached vs. 18.9 months ) , with a risk of progression or death that was 84 % lower with ibrutinib than that with chlorambucil ( hazard ratio , 0.16 ; P<0.001 ) . Ibrutinib significantly prolonged overall survival ; the estimated survival rate at 24 months was 98 % with ibrutinib versus 85 % with chlorambucil , with a relative risk of death that was 84 % lower in the ibrutinib group than in the chlorambucil group ( hazard ratio , 0.16 ; P=0.001 ) . The overall response rate was higher with ibrutinib than with chlorambucil ( 86 % vs. 35 % , P<0.001 ) . The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib . Adverse events of any grade that occurred in at least 20 % of the patients receiving ibrutinib included diarrhea , fatigue , cough , and nausea ; adverse events occurring in at least 20 % of those receiving chlorambucil included nausea , fatigue , neutropenia , anemia , and vomiting . In the ibrutinib group , four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage . A total of 87 % of the patients in the ibrutinib group are continuing to take ibrutinib . CONCLUSIONS Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma , as assessed by progression-free survival , overall survival , response rate , and improvement in hematologic variables . ( Funded by Pharmacyclics and others ; RESONATE-2 Clinical Trials.gov number , NCT01722487 . ) BACKGROUND The monoclonal anti-CD20 antibody rituximab , combined with chemotherapeutic agents , has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia ( CLL ) but not in those with coexisting conditions . We investigated the benefit of the type 2 , glycoengineered antibody obinutuzumab ( also known as GA101 ) as compared with that of rituximab , each combined with chlorambucil , in patients with previously untreated CLL and coexisting conditions . METHODS We r and omly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale ( CIRS ) ( range , 0 to 56 , with higher scores indicating worse health status ) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil , obinutuzumab plus chlorambucil , or rituximab plus chlorambucil . The primary end point was investigator-assessed progression-free survival . RESULTS The patients had a median age of 73 years , creatinine clearance of 62 ml per minute , and CIRS score of 8 at baseline . Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil , as compared with chlorambucil monotherapy , increased response rates and prolonged progression-free survival ( median progression-free survival , 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone ; hazard ratio for progression or death , 0.18 ; 95 % confidence interval [ CI ] , 0.13 to 0.24 ; P<0.001 ; and 16.3 months with rituximab-chlorambucil vs. 11.1 months with chlorambucil alone ; hazard ratio , 0.44 ; 95 % CI , 0.34 to 0.57 ; P<0.001 ) . Treatment with obinutuzumab-chlorambucil , as compared with chlorambucil alone , prolonged overall survival ( hazard ratio for death , 0.41 ; 95 % CI , 0.23 to 0.74 ; P=0.002 ) . Treatment with obinutuzumab-chlorambucil , as compared with rituximab-chlorambucil , result ed in prolongation of progression-free survival ( hazard ratio , 0.39 ; 95 % CI , 0.31 to 0.49 ; P<0.001 ) and higher rates of complete response ( 20.7 % vs. 7.0 % ) and molecular response . Infusion-related reactions and neutropenia were more common with obinutuzumab-chlorambucil than with rituximab-chlorambucil , but the risk of infection was not increased . CONCLUSIONS Combining an anti-CD20 antibody with chemotherapy improved outcomes in patients with CLL and coexisting conditions . In this patient population , obinutuzumab was superior to rituximab when each was combined with chlorambucil . ( Funded by F. Hoffmann-La Roche ; Clinical Trials.gov number , NCT01010061 . ) Early results of the fludarabine , cyclophosphamide , and rituximab ( FCR ) regimen in 224 patients showed that it was highly active as initial therapy of chronic lymphocytic leukemia . In this report , we present the final results of all 300 study patients at a median follow up of 6 years . The overall response rate was 95 % , with complete remission in 72 % , nodular partial remission in 10 % , partial remission due to cytopenia in 7 % , and partial remission due to residual disease in 6 % . Two patients ( < 1 % ) died within 3 months of starting therapy . Six-year overall and failure-free survival were 77 % and 51 % , respectively . Median time to progression was 80 months . Pretreatment characteristics independently associated with inferior response were age 70 years or older , beta2-microglobulin twice the upper limit of normal ( 2N ) or more , white cell count 150 x 10(9)/L or more , abnormal chromosome 17 , and lactate dehydrogenase 2N or more . No pretreatment characteristic was independently associated with decreased complete remission duration . The risk of late infection was 10 % and 4 % for the first and second years of remission , respectively , and less than 1.5 % per year for the third year onward . In a multivariate analysis of patients receiving fludarabine-based therapy at our center , FCR therapy emerged as the strongest independent determinant of survival BACKGROUND On the basis of promising results that were reported in several phase 2 trials , we investigated whether the addition of the monoclonal antibody rituximab to first-line chemotherapy with fludarabine and cyclophosphamide would improve the outcome of patients with chronic lymphocytic leukaemia . METHODS Treatment-naive , physically fit patients ( aged 30 - 81 years ) with CD20-positive chronic lymphocytic leukaemia were r and omly assigned in a one-to-one ratio to receive six courses of intravenous fludarabine ( 25 mg/m(2 ) per day ) and cyclophosphamide ( 250 mg/m(2 ) per day ) for the first 3 days of each 28-day treatment course with or without rituximab ( 375 mg/m(2 ) on day 0 of first course , and 500 mg/m(2 ) on day 1 of second to sixth courses ) in 190 centres in 11 countries . Investigators and patients were not masked to the computer-generated treatment assignment . The primary endpoint was progression-free survival ( PFS ) . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00281918 . FINDINGS 408 patients were assigned to fludarabine , cyclophosphamide , and rituximab ( chemoimmunotherapy group ) and 409 to fludarabine and cyclophosphamide ( chemotherapy group ) ; all patients were analysed . At 3 years after r and Output:	Treatment ranking reflected improved PFS and OS with G-Clb over other treatment strategies ( median rank of one for both endpoints ) . Conclusion G-Clb is likely to show superior efficacy to other treatment options selected in our NMA for unfit treatment-naïve patients with CLL .
MS22052	*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 aim of this research was to compare the accuracy outcomes of open- and closed-tray implant impressions for partially edentulous patients . Eleven partially edentulous spaces in seven patients with two existing implants for fixed partial dentures were included . Group I ( closed-tray ) and group II ( open-tray ) were compared using microcomputed tomography scanning . No statistically significant differences were found between the closed- and open-tray techniques ( P = .317 ) . The subjective evaluation of patient comfort showed no differences with either impression technique . There were no differences seen between open- and closed-tray impression techniques in partially edentulous patients when implants had less than 10 degrees of angulation Output:	The most accurate results were achieved with two configurations : ( 1 ) the optical intraoral system with powder and ( 2 ) the open technique with splinted squared transfer copings , using polyether as impression material
MS22053	*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: Disturbed sleep is a common problem , particularly among elderly people , and is usually treated with hypnotics . The side effects of longterm administration of hypnotic drugs are well known , but despite this there remains a substantial population of chronic users . These people can be helped to reduce their dependence on hypnotics through psychological techniques . A group of longterm users treated in this manner were shown to reduce their intake of hypnotics significantly more than a group of users who did not receive any psychological treatment . Furthermore , the treated patients did not experience any deterioration in their sleep patterns , and their subjective refreshment from sleep improved significantly . For the patient with sleep problems , psychological techniques are preferable to the longterm use of hypnotics both as a weaning-off agent and as an alternative to drugs We described characteristics of subjects with benzodiazepine dependence that was typically complicated by harmful and hazardous alcohol use or high benzodiazepine doses , and assessed predictors of successful discontinuation of benzodiazepines for this group . Seventy-six patients who participated in a r and omized clinical trial of two different gradual withdrawal treatment approaches were assessed . The trial was conducted between February 1995 and July 1999 . The mean age ±SD of subjects was 40.0±9.6 years , 55 % were male , 38 % were married or cohabiting , and 70 % had received more than nine years of education . The median benzodiazepine dose was 35 mg /day ( range 2.5–180 ) in diazepam equivalents . The median duration of benzodiazepine use was 84 ( range 8–360 ) months . Subjects with lower benzodiazepine doses and no previous withdrawal attempts were more successful at benzodiazepine discontinuation . Cluster B personality/borderline personality disorder was associated with an inability to stop benzodiazepine use and with “ dropping out ” of treatment . Alcohol use – related disorders or other psychiatric diagnoses were not associated with outcome . Further studies on predictors of successful benzodiazepine discontinuation in different population s are required . Patients manifesting cluster B personality/borderline personality disorder and benzodiazepine dependence may need concomitant treatment for their personality disorders to benefit from benzodiazepine discontinuation treatment Background The prevalence of substance use in people acutely admitted to in-patient psychiatric wards is high and the patients ` duration of stay is limited . Motivational interviewing is a method with evidence based effect in short interventions . The aims of the present study were to compare the effects of 2 sessions of motivational interviewing and treatment as usual ( intervention group ) with treatment as usual only ( control group ) on adult patients with comorbid substance use admitted to a psychiatric in-patient emergency unit . Methods This was an open r and omised controlled trial including 135 patients where substance use influenced the admittance . After admission and assessment s , the patients were allocated to the intervention group ( n = 67 ) or the control group ( n = 68 ) . The primary outcome was self-reported days per month of substance use during the last 3 months at 3 , 6 , 12 and 24 months after inclusion . Data was analysed with a multilevel linear repeated measures regression model . Results Both groups reduced substance use during the first 12 months with no substantial difference between the 2 groups . At 2 year follow-up , the control group had increased their substance use with 2.4 days ( 95 % confidence interval ( CI ) –1.5 to 6.3 ) , whereas the intervention group had reduced their monthly substance use with 4.9 days ( 95 % CI 1.2 to 8.6 ) compared to baseline . The 2 year net difference was 7.3 days of substance use per month ( 95 % CI 1.9 to 12.6 , p < 0.01 ) in favour of the intervention group . Conclusions The present study suggests that 2 sessions of motivational interviewing to patients with comorbid substance use admitted to a psychiatric emergency unit reduce substance use frequency substantially at 2 year follow-up . Trial registration Clinical Trials.gov Identifier : Eighty-six participants wishing to stop benzodiazepine and who met DSM-IV ( Diagnostic and Statistical Manual of Mental Disorders , 4th ed . American Psychological Association , 1994 ) criteria for anxiety disorder or insomnia were assessed pre- and post-taper on clinical , pharmacological and psychosocial measures . An initial cohort of 41 participants received treatment as usual ( taper only ) plus physician counselling in the same clinic setting . A second cohort of 45 participants were r and omly allocated to group cognitive-behavioural therapy ( CBT ) plus taper , or group support ( GS ) plus taper . At 3 months follow-up , the outcomes in both the CBT and the GS subgroups were equivalent . Intention to treat analysis revealed a slight advantage to the CBT over the GS group and the CBT group showed higher self-efficacy post-taper . Over all 86 participants , a high-baseline level of psychological distress , anxiety and dosage predicted a poor outcome , but increase in self-efficacy contributed to a successful outcome particularly in those with initially poor baseline predictors . Although there was a decrease in positive affect during preliminary stages of tapered discontinuation compared to baseline , there was no significant overall increase in negative affect Objective To evaluate the association between use of benzodiazepines and incident dementia . Design Prospect i ve , population based study . Setting PAQUID study , France . Participants 1063 men and women ( mean age 78.2 years ) who were free of dementia and did not start taking benzodiazepines until at least the third year of follow-up . Main outcome measures Incident dementia , confirmed by a neurologist . Results During a 15 year follow-up , 253 incident cases of dementia were confirmed . New use of benzodiazepines was associated with an increased risk of dementia ( multivariable adjusted hazard ratio 1.60 , 95 % confidence interval 1.08 to 2.38 ) . Sensitivity analysis considering the existence of depressive symptoms showed a similar association ( hazard ratio 1.62 , 1.08 to 2.43 ) . A secondary analysis pooled cohorts of participants who started benzodiazepines during follow-up and evaluated the association with incident dementia . The pooled hazard ratio across the five cohorts of new benzodiazepine users was 1.46 ( 1.10 to 1.94 ) . Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50 % increase in the risk of dementia ( adjusted odds ratio 1.55 , 1.24 to 1.95 ) compared with never users . The results were similar in past users ( odds ratio 1.56 , 1.23 to 1.98 ) and recent users ( 1.48 , 0.83 to 2.63 ) but reached significance only for past users . Conclusions In this prospect i ve population based study , new use of benzodiazepines was associated with increased risk of dementia . The result was robust in pooled analyses across cohorts of new users of benzodiazepines throughout the study and in a complementary case-control study . Considering the extent to which benzodiazepines are prescribed and the number of potential adverse effects of this drug class in the general population , indiscriminate widespread use should be caution ed against OBJECTIVE This study tested cognitive behavior therapy ( CBT ) in hypnotic-dependent , late middle-age and older adults with insomnia . METHOD Seventy volunteers age 50 and older were r and omized to CBT plus drug withdrawal , placebo biofeedback ( PL ) plus drug withdrawal , or drug withdrawal ( MED ) only . The CBT and PL groups received eight , 45 min weekly treatment sessions . The drug withdrawal protocol comprised slow tapering monitored with about six biweekly , 30 min sessions . Assessment including polysomnography ( PSG ) , sleep diaries , hypnotic consumption , daytime functioning question naires , and drug screens collected at baseline , posttreatment , and 1-year follow-up . RESULTS Only the CBT group showed significant sleep diary improvement , sleep onset latency significantly decreased at posttreatment . For all sleep diary measures for all groups , including MED , sleep trended to improvement from baseline to follow-up . Most PSG sleep variables did not significantly change . There were no significant between group differences in medication reduction . Compared to baseline , the three groups decreased hypnotic use at posttreatment , down 84 % , and follow-up , down 66 % . There was no evidence of withdrawal side-effects . Daytime functioning , including anxiety and depression , improved by posttreatment . Rigorous method ological features , including documentation of strong treatment implementation and the presence of a credible placebo , elevated the confidence due these findings . CONCLUSIONS Gradual drug withdrawal was associated with substantial hypnotic reduction at posttreatment and follow-up , and withdrawal side-effects were absent . When supplemented with CBT , participants accrued incremental self-reported , but not PSG , sleep benefits AIMS Chronic benzodiazepine use is highly prevalent and is associated with a variety of negative health consequences . The present study examined the long-term effectiveness of a tailored patient education intervention on benzodiazepine use . DESIGN A r and omized controlled trial was conducted comprising three arms , comparing ( i ) a single tailored intervention ; ( ii ) a multiple tailored intervention and ( iii ) a general practitioner letter . The post-test took place after 12 months . PARTICIPANTS Five hundred and eight patients using benzodiazepines were recruited by their general practitioners and assigned r and omly to one of the three groups . INTERVENTION Two tailored interventions , the single tailored intervention ( patients received one tailored letter ) and the multiple tailored intervention ( patients received three sequential tailored letters at intervals of 1 month ) , were compared to a short general practitioner letter that modelled usual care . The tailored interventions not only provided different and more information than the general practitioner letter ; they were also personalized and adapted to individual baseline characteristics . The information in both tailored interventions was the same , but in the multiple tailored intervention the information was provided to the participants spread over three occasions . In the multiple tailored intervention , the second and the third tailored letters were based on short and st and ardized telephone interviews . MEASUREMENTS Benzodiazepine cessation at post-test was the outcome measure . FINDINGS The results showed that participants receiving the tailored interventions were twice as likely to have quit benzodiazepine use compared to the general practitioner letter . Particularly among participants with the intention to discontinue usage at baseline , both tailored interventions led to high percentages of those who actually discontinued usage ( single tailored intervention 51.7 % ; multiple tailored intervention 35.6 % ; general practitioner letter 14.5 % ) . CONCLUSIONS It was concluded that tailored patient education can be an effective tool for reducing benzodiazepine use , and can be implemented easily This study examined contingent methadone take-home privileges for effectiveness in reducing on-going supplemental drug use of methadone maintenance patients . Fifty-three new intakes were r and omly assigned to begin receiving take-home privileges after 2 consecutive weeks of drug-free urines or to a noncontingent procedure in which take-homes were delivered independently of urine test results . The contingent procedure produced more individuals with at least 4 consecutive weeks of abstinence ( 32 % vs. 8 % ) ; 28 % of noncontingent subjects also achieved abstinence after shifting to the contingent procedure . Lower baseline rate of drug-free urines was strongly associated with successful outcome , whereas the type of drug abused ( cocaine vs. benzodiazepines ) did not influence outcomes . Findings support a recommendation for using contingent take-home incentives to motivate abstinence during methadone maintenance treatment This study evaluated the specific effectiveness of cognitive-behavior therapy ( CBT ) combined with medication tapering for benzodiazepine discontinuation among generalized anxiety disorder ( GAD ) patients by using a nonspecific therapy control group . Sixty-one patients who had used benzodiazepines for more than 12 months were r and omly assigned to the experimental conditions . Nearly 75 % of patients in the CBT condition completely ceased benzodiazepine intake , as compared with 37 % in the control condition . Results of the 3- , 6- , and 12-month follow-ups confirmed the maintenance of complete cessation . Discontinuation rates remained twice as high in the CBT condition . The number of patients who no longer met GAD criteria was also greater in the CBT condition . The addition of specific CBT components thus seemed to facilitate benzodiazepine tapering among patients with GAD BACKGROUND Benzodiazepine withdrawal programmes have never been experimentally compared with a nonintervention control condition . AIMS To evaluate the efficacy and feasibility of tapering off long-term benzodiazepine use in general practice , and to evaluate the value of additional group cognitive-behavioural therapy ( CBT ) . METHOD A 3-month r and omised , 3-month controlled trial was conducted in which 180 people attempting to discontinue long-term benzodiazepine use were assigned to tapering off plus group CBT , tapering off alone or usual care . RESULTS Tapering off led to a significantly higher proportion of successful discontinuations than usual care ( 62 % nu . 21 % ) . Adding group CBT did not increase the success rate ( 58 % v. 62 % ) . Neither successful discontinuation nor intervention type affected psychological functioning . Both tapering strategies showed good feasibilityin general practice . CONCLUSIONS Tapering off is a feasible and effective way of discontinuing long-term benzodiazepine use in general practice . The addition of group CBT is of limited value Despite recent emphasis on integr Output:	AUTHORS ' CONCLUSIONS CBT plus taper is effective in the short term ( three month time period ) in reducing BZD use . However , this is not sustained at six months and subsequently . Currently there is insufficient evidence to support the use of MI to reduce BZD use . There is emerging evidence to suggest that a tailored GP letter versus a generic GP letter , a st and ardised interview versus TAU , and relaxation versus TAU could be effective for BZD reduction . There is currently insufficient evidence for other approaches to reduce BZD use
MS22054	*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 Mild traumatic brain injury ( mTBI ) secondary to blast exposure is the most common battlefield injury in Southwest Asia . There has been little prospect i ve work in the combat setting to test the efficacy of new counter measures . The goal of this study was to compare the efficacy of N-acetyl cysteine ( NAC ) versus placebo on the symptoms associated with blast exposure mTBI in a combat setting . Methods This study was a r and omized double blind , placebo-controlled study that was conducted on active duty service members at a forward deployed field hospital in Iraq . All symptomatic U.S. service members who were exposed to significant ordnance blast and who met the criteria for mTBI were offered participation in the study and 81 individuals agreed to participate . Individuals underwent a baseline evaluation and then were r and omly assigned to receive either N-acetyl cysteine ( NAC ) or placebo for seven days . Each subject was re-evaluated at 3 and 7 days . Outcome measures were the presence of the following sequelae of mTBI : dizziness , hearing loss , headache , memory loss , sleep disturbances , and neurocognitive dysfunction . The resolution of these symptoms seven days after the blast exposure was the main outcome measure in this study . Logistic regression on the outcome of ‘ no day 7 symptoms ’ indicated that NAC treatment was significantly better than placebo ( OR = 3.6 , p = 0.006 ) . Secondary analysis revealed subjects receiving NAC within 24 hours of blast had an 86 % chance of symptom resolution with no reported side effects versus 42 % for those seen early who received placebo . Conclusion This study , conducted in an active theatre of war , demonstrates that NAC , a safe pharmaceutical countermeasure , has beneficial effects on the severity and resolution of sequelae of blast induced mTBI . This is the first demonstration of an effective short term countermeasure for mTBI . Further work on long term outcomes and the potential use of NAC in civilian mTBI is warranted . Trial Registration Clinical Trials.gov BACKGROUND Traumatic brain injury is a major cause of death and disability . We sought to assess the safety and efficacy of dexanabinol , a synthetic cannabinoid analogue devoid of psychotropic activity , in severe traumatic brain injury . METHODS 861 patients with severe traumatic brain injury admitted to 86 specialist centres from 15 countries were included in a multi-centre , placebo-controlled , phase III trial . Patients were r and omised to receive a single intravenous 150 mg dose of dexanabinol or placebo within 6 h of injury . The primary outcome was the extended Glasgow outcome scale assessed at 6 months , with the point of dichotomisation into unfavourable versus favourable outcome differentiated by baseline prognostic risk . Prespecified subgroup analyses were defined by injury severity , recruitment rate , and time to dosing . Secondary analysis included control of intracranial pressure and quality of life . Analysis were prespecified in the protocol and the statistical analysis plan . This study is registered with Clinical Trials.gov , number NCT00129857 . FINDINGS 846 patients were included in the efficacy analysis . The extended Glasgow outcome scale at 6 months did not differ between groups ; 215 ( 50 % ) patients in the dexanabinol group and 214 ( 51 % ) patients in the placebo group had an unfavourable outcome ( odds ratio for a favourable response 1.04 ; 95 % CI 0.79 - 1.36 ) . Improvements in the control of intracranial pressure or quality of life were not recorded and subgroup analysis showed no indication of differential treatment effects . Dexanabinol was not associated with hepatic , renal , or cardiac toxic effects . INTERPRETATION Dexanabinol is safe , but is not efficacious in the treatment of traumatic brain injury OBJECTIVE To investigate whether supplementation with branched-chain amino acids ( BCAAs ) may improve recovery of patients with a posttraumatic vegetative or minimally conscious state . DESIGN Patients were r and omly assigned to 15 days of intravenous BCAA supplementation ( n=22 ; 19.6g/d ) or an isonitrogenous placebo ( n=19 ) . SETTING Tertiary care rehabilitation setting . PARTICIPANTS Patients ( N=41 ; 29 men , 12 women ; mean age , 49.5+/-21 y ) with a posttraumatic vegetative or minimally conscious state , 47+/-24 days after the index traumatic event . INTERVENTION Supplementation with BCAAs . MAIN OUTCOME MEASURE Disability Rating Scale ( DRS ) as log(10)DRS . RESULTS Fifteen days after admission to the rehabilitation department , the log(10)DRS score improved significantly only in patients who had received BCAAs ( log(10)DRS score , 1.365+/-0.08 to 1.294+/-0.05 ; P<.001 ) , while the log(10)DRS score in the placebo recipients remained virtually unchanged ( log(10)DRS score , 1.373+/-0.03 to 1.37+/-0.03 ; P not significant ) . The difference in improvement of log(10)DRS score between the 2 groups was highly significant ( P<.000 ) . Moreover , 68.2 % ( n=15 ) of treated patients achieved a log(10)DRS point score of .477 or higher ( 3 as geometric mean ) that allowed them to exit the vegetative or minimally conscious state . CONCLUSIONS Supplemented BCAAs may improve the recovery from a vegetative or minimally conscious state in patients with posttraumatic vegetative or minimally conscious state An accurate prognostic model is extremely important in severe traumatic brain injury ( TBI ) for both patient management and research . Clinical prediction models must be vali date d both internally and externally before they are considered widely applicable . Our aim is to independently externally vali date two prediction models , one developed by the Corticosteroid R and omization After Significant Head injury ( CRASH ) trial investigators , and the other from the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury ( IMPACT ) group . We used a cohort of 300 patients with severe TBI ( Glasgow Coma Score [ GCS ] ≤8 ) consecutively admitted to the National Neuroscience Institute ( NNI ) , Singapore , between February 2006 and December 2009 . The CRASH models ( base and CT ) predict 14 day mortality and 6 month unfavorable outcome . The IMPACT models ( core , extended , and laboratory ) estimate 6 month mortality and unfavorable outcome . Validation was based on measures of discrimination and calibration . Discrimination was assessed using the area under the receiving operating characteristic curve ( AUC ) , and calibration was assessed using the Hosmer-Lemeshow ( H-L ) goodness-of-fit test and Cox calibration regression analysis . In the NNI data base , the overall observed 14 day mortality was 47.7 % , and the observed 6 month unfavorable outcome was 71.0 % . The CRASH base model and all three IMPACT models gave an underestimate of the observed values in our cohort when used to predict outcome . Using the CRASH CT model , the predicted 14 day mortality of 46.6 % approximated the observed outcome , whereas the predicted 6 month unfavorable outcome was an overestimate at 74.8 % . Overall , both the CRASH and IMPACT models showed good discrimination , with AUCs ranging from 0.80 to 0.89 , and good overall calibration . We conclude that both the CRASH and IMPACT models satisfactorily predicted outcome in our patients with severe TBI BACKGROUND AND PURPOSE Enzogenol , a flavonoid-rich extract from Pinus radiata bark with antioxidant and anti-inflammatory properties has been shown to improve working memory in healthy adults . In traumatic brain injury ( TBI ) , oxidation and inflammation have been linked to poorer cognitive outcomes . Hence , this phase II , r and omized controlled trial investigated safety , compliance and efficacy of Enzogenol for improving cognitive functioning in people following mild TBI . METHODS Sixty adults , who sustained a mild TBI , 3 - 12 months prior to recruitment , and who were experiencing persistent cognitive difficulties [ Cognitive Failures Question naire ( CFQ ) score > 38 ] , were r and omized to receive Enzogenol ( 1000 mg/day ) or matching placebo for 6 weeks . Subsequently , all participants received Enzogenol for a further 6 weeks , followed by placebo for 4 weeks . Compliance , side-effects , cognitive failures , working and episodic memory , post-concussive symptoms and mood were assessed at baseline , 6 , 12 and 16 weeks . Simultaneous estimation of treatment effect and breakpoint was effected , with confidence intervals ( CIs ) obtained through a treatment-placebo balance-preserving bootstrap procedure . RESULTS Enzogenol was found to be safe and well tolerated . Trend and breakpoint analyses showed a significant reduction in cognitive failures after 6 weeks [ mean CFQ score , 95 % CI , Enzogenol versus placebo -6.9 ( -10.8 to -4.1 ) ] . Improvements in the frequency of self-reported cognitive failures were estimated to continue until week 11 before stabilizing . Other outcome measures showed some positive trends but no significant treatment effects . CONCLUSIONS Enzogenol supplementation is safe and well tolerated in people after mild TBI , and may improve cognitive functioning in this patient population . This study provides Class IIB evidence that Enzogenol is well tolerated and may reduce self-perceived cognitive failures in patients 3 - 12 months post-mild TBI Output:	FINDINGS Critical evaluation of the six studies that met inclusion criteria suggests that antioxidant therapies such as amino acids , vitamins C and E , progesterone , N-acetylcysteine , and enzogenol may be safe and effective adjunctive therapies in adult patients with TBI . Although certain limitations were found , the overall trend of using antioxidant therapies to improve the clinical outcomes of TBI was positive . LINKING EVIDENCE TO ACTION By incorporating antioxidant therapies into practice , clinicians can help attenuate the oxidative posttraumatic brain damage and optimize patients ' recovery
MS22055	*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 antiplatelet effect of clopidogrel may be attenuated by short-term coadministration of lipophilic statins . We investigated whether the coadministration of atorvastatin for 5 weeks in patients with acute coronary syndromes ( ACS ) could affect the antiplatelet potency of clopidogrel . Methods and Results —Forty-five hypercholesterolemic patients with the first episode of an ACS were included in the study . Patients were r and omized to receive daily either 10 mg of atorvastatin ( n=21 ) or 40 mg of pravastatin ( n=24 ) . Thirty patients who underwent percutaneous coronary intervention ( PCI ) received a loading dose of 375 mg of clopidogrel , followed by 75 mg/d for at least 3 months . In the remaining 15 patients who refused to undergo PCI , clopidogrel therapy was not administered . Eight normolipidemic patients with the first episode of an ACS were also included and received only clopidogrel . The serum levels of soluble CD40L and the adenosine 5′-diphosphate– or thrombin receptor activating peptide-14–induced platelet aggregation , as well as P-selectin and CD40L surface expression , were studied at baseline ( within 30 minutes after admission ) and 5 weeks later . Neither atorvastatin nor pravastatin significantly influenced the clopidogrel-induced inhibition of platelet activation , nor did clopidogrel influence the therapeutic efficacy of atorvastatin . Conclusions —Atorvastatin does not affect the antiplatelet potency of clopidogrel when coadministered for 5 weeks in ACS patients BACKGROUND Gastrointestinal complications are an important problem of antithrombotic therapy . Proton-pump inhibitors ( PPIs ) are believed to decrease the risk of such complications , though no r and omized trial has proved this in patients receiving dual antiplatelet therapy . Recently , concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel . METHODS We r and omly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo , in addition to aspirin . The primary gastrointestinal end point was a composite of overt or occult bleeding , symptomatic gastroduodenal ulcers or erosions , obstruction , or perforation . The primary cardiovascular end point was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , revascularization , or stroke . The trial was terminated prematurely when the sponsor lost financing . RESULTS We planned to enroll about 5000 patients ; a total of 3873 were r and omly assigned and 3761 were included in analyses . In all , 51 patients had a gastrointestinal event ; the event rate was 1.1 % with omeprazole and 2.9 % with placebo at 180 days ( hazard ratio with omeprazole , 0.34 , 95 % confidence interval [ CI ] , 0.18 to 0.63 ; P<0.001 ) . The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo ( hazard ratio , 0.13 ; 95 % CI , 0.03 to 0.56 ; P = 0.001 ) . A total of 109 patients had a cardiovascular event , with event rates of 4.9 % with omeprazole and 5.7 % with placebo ( hazard ratio with omeprazole , 0.99 ; 95 % CI , 0.68 to 1.44 ; P = 0.96 ) ; high-risk subgroups did not show significant heterogeneity . The two groups did not differ significantly in the rate of serious adverse events , though the risk of diarrhea was increased with omeprazole . CONCLUSIONS Among patients receiving aspirin and clopidogrel , prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding . There was no apparent cardiovascular interaction between clopidogrel and omeprazole , but our results do not rule out a clinical ly meaningful difference in cardiovascular events due to use of a PPI . ( Funded by Cogentus Pharmaceuticals ; Clinical Trials.gov number , NCT00557921 . ) BACKGROUND Recent pharmacodynamic and retrospective clinical analyses have suggested that proton pump inhibitors ( PPIs ) may modify the antiplatelet effects of clopidogrel bisulfate . METHODS We conducted a retrospective cohort study of persons enrolled in a multistate health insurance plan with commercial and Medicare clients to evaluate adverse clinical outcomes in patients using clopidogrel plus a PPI compared with clopidogrel alone . Patients who were discharged from the hospital after myocardial infa rct ion ( MI ) or coronary stent placement and treated with clopidogrel plus a PPI ( n = 1033 ) were matched 1:1 ( using propensity scoring ) with patients with similar cardiovascular risk factors treated with clopidogrel alone . Rehospitalizations for MI or coronary stent placement were evaluated for up to 360 days . A sub analysis was conducted to study the impact of pantoprazole sodium , the most used PPI . RESULTS Patients who received clopidogrel plus a PPI had a 93 % higher risk of rehospitalization for MI ( adjusted hazard ratio , 1.93 ; 95 % confidence interval , 1.05 - 3.54 ; P = .03 ) and a 64 % higher risk of rehospitalization for MI or coronary stent placement ( 1.64 ; 1.16 - 2.32 ; P = .005 ) than did patients receiving clopidogrel alone . Increased risk of rehospitalization for MI or coronary stent placement was also observed for the subgroup of patients receiving clopidogrel plus pantoprazole ( adjusted hazard ratio , 1.91 ; 95 % confidence interval , 1.19 - 3.06 ; P = .008 ) . CONCLUSIONS Patients who received clopidogrel plus a PPI had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone . Prospect i ve clinical trials and laboratory analyses of biochemical interactions are warranted to further evaluate the potential impact of PPIs on the efficacy of clopidogrel CONTEXT Following percutaneous coronary intervention ( PCI ) , short-term clopidogrel therapy in addition to aspirin leads to greater protection from thrombotic complications than aspirin alone . However , the optimal duration of combination oral antiplatelet therapy is unknown . Also , although current clinical data suggest a benefit for beginning therapy with a clopidogrel loading dose prior to PCI , the practical application of this therapy has not been prospect ively studied . OBJECTIVES To evaluate the benefit of long-term ( 12-month ) treatment with clopidogrel after PCI and to determine the benefit of initiating clopidogrel with a preprocedure loading dose , both in addition to aspirin therapy . DESIGN , SETTING , AND PARTICIPANTS The Clopidogrel for the Reduction of Events During Observation ( CREDO ) trial , a r and omized , double-blind , placebo-controlled trial conducted among 2116 patients who were to undergo elective PCI or were deemed at high likelihood of undergoing PCI , enrolled at 99 centers in North America from June 1999 through April 2001 . INTERVENTIONS Patients were r and omly assigned to receive a 300-mg clopidogrel loading dose ( n = 1053 ) or placebo ( n = 1063 ) 3 to 24 hours before PCI . Thereafter , all patients received clopidogrel , 75 mg/d , through day 28 . From day 29 through 12 months , patients in the loading-dose group received clopidogrel , 75 mg/d , and those in the control group received placebo . Both groups received aspirin throughout the study . MAIN OUTCOME MEASURES One-year incidence of the composite of death , myocardial infa rct ion ( MI ) , or stroke in the intent-to-treat population ; 28-day incidence of the composite of death , MI , or urgent target vessel revascularization in the per- protocol population . RESULTS At 1 year , long-term clopidogrel therapy was associated with a 26.9 % relative reduction in the combined risk of death , MI , or stroke ( 95 % confidence interval [ CI ] , 3.9%-44.4 % ; P = .02 ; absolute reduction , 3 % ) . Clopidogrel pretreatment did not significantly reduce the combined risk of death , MI , or urgent target vessel revascularization at 28 days ( reduction , 18.5 % ; 95 % CI , -14.2 % to 41.8 % ; P = .23 ) . However , in a prespecified subgroup analysis , patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6 % ( 95 % CI , -1.6 % to 62.9 % ; P = .051 ) for this end point compared with no reduction with treatment less than 6 hours before PCI . Risk of major bleeding at 1 year increased , but not significantly ( 8.8 % with clopidogrel vs 6.7 % with placebo ; P = .07 ) . CONCLUSIONS Following PCI , long-term ( 1-year ) clopidogrel therapy significantly reduced the risk of adverse ischemic events . A loading dose of clopidogrel given at least 3 hours before the procedure did not reduce events at 28 days , but subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events OBJECTIVES The goal of comparative effectiveness analysis is to examine the relationship between two variables , treatment , or exposure and effectiveness or outcome . Unlike data obtained through r and omized controlled trials , research ers face greater challenges with causal inference with observational studies . Recognizing these challenges , a task force was formed to develop a guidance document on method ological approaches to addresses these biases . METHODS The task force was commissioned and a Chair was selected by the International Society for Pharmacoeconomics and Outcomes Research Board of Directors in October 2007 . This report , the second of three reported in this issue of the Journal , discusses the inherent biases when using secondary data sources for comparative effectiveness analysis and provides method ological recommendations to help mitigate these biases . RESULTS The task force report provides recommendations and tools for research ers to mitigate threats to validity from bias and confounding in measurement of exposure and outcome . Recommendations on design of study included : the need for data analysis plan with causal diagrams ; detailed attention to classification bias in definition of exposure and clinical outcome ; careful and appropriate use of restriction ; extreme care to identify and control for confounding factors , including time-dependent confounding . CONCLUSIONS Design of nonr and omized studies of comparative effectiveness face several daunting issues , including measurement of exposure and outcome challenged by misclassification and confounding . Use of causal diagrams and restriction are two techniques that can improve the theoretical basis for analyzing treatment effects in study population s of more homogeneity , with reduced loss of generalizability OBJECTIVES This study sought to compare the effect of 2 proton pump inhibitors ( PPIs ) on platelet response to clopidogrel after coronary stenting for non-ST-segment elevation acute coronary syndrome ( NSTE ACS ) . BACKGROUND Use of omeprazole has been reported to significantly decrease the clopidogrel antiplatelet effect because of cytochrome P450 interaction . Because all PPIs are metabolized by CYP2C19 , but to a varying degree , we hypothesized that the reported negative omeprazole-clopidogrel drug interaction may not be caused by a class effect . METHODS A total of 104 patients undergoing coronary stenting for NSTE ACS were prospect ively included and r and omized to omeprazole or pantoprazole 20 mg . They received at discharge 75-mg aspirin and 150-mg clopidogrel . Platelet reactivity index ( PRI ) vasoactive stimulated phosphoprotein ( VASP ) was used to assess clopidogrel response and adenosine diphosphate (ADP)-induced aggregation for platelet reactivity ( ADP-Ag ) . RESULTS After 1 month , patients receiving pantoprazole had a significantly better platelet response to clopidogrel as assessed with the PRI VASP : 36 + /- 20 % versus 48 + /- 17 % ( p = 0.007 ) . We identified more clopidogrel nonresponders in the omeprazole group than in the pantoprazole group : 44 % versus 23 % ( p = 0.04 ) , odds ratio : 2.6 ( 95 % confidence interval : 1.2 to 6.2 ) . Conversely , we did not observe any significant difference in platelet reactivity with ADP-Ag between the omeprazole and pantoprazole groups : 52 + /- 15 % and 50 + /- 18 % , respectively ( p = 0.29 ) . CONCLUSIONS The present findings suggest the preferential use of pantoprazole compared with omeprazole in patients receiving clopidogrel to avoid any potential Output:	There was also no clinical evidence for a positive interaction according to specific PPIs . Conclusion The observed association between clopidogrel and PPIs is found uniquely in studies judged to be of low quality and with an increased risk of bias .
MS22056	*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 Neuromuscular training may reduce risk factors that contribute to ACL injury incidence in female athletes . Multi-component , ACL injury prevention training programs can be time and labor intensive , which may ultimately limit training program utilization or compliance . The purpose of this study was to determine the effect of neuromuscular training on those classified as " high-risk " compared to those classified as " low-risk . " The hypothesis was that high-risk athletes would decrease knee abduction moments while low-risk and control athletes would not show measurable changes . Methods Eighteen high school female athletes participated in neuromuscular training 3 × /week over a 7-week period . Knee kinematics and kinetics were measured during a drop vertical jump ( DVJ ) test at pre/post training . External knee abduction moments were calculated using inverse dynamics . Logistic regression indicated maximal sensitivity and specificity for prediction of ACL injury risk using external knee abduction ( 25.25 Nm cutoff ) during a DVJ . Based on these data , 12 study subjects ( and 4 controls ) were grouped into the high-risk ( knee abduction moment > 25.25 Nm ) and 6 subjects ( and 7 controls ) were grouped into the low-risk ( knee abduction < 25.25 Nm ) categories using mean right and left leg knee abduction moments . A mixed design repeated measures ANOVA was used to determine differences between athletes categorized as high or low-risk . Results Athletes classified as high-risk decreased their knee abduction moments by 13 % following training ( Dominant pre : 39.9 ± 15.8 Nm to 34.6 ± 9.6 Nm ; Non-dominant pre : 37.1 ± 9.2 to 32.4 ± 10.7 Nm ; p = 0.033 training X risk factor interaction ) . Athletes grouped into the low-risk category did not change their abduction moments following training ( p > 0.05 ) . Control subjects classified as either high or low-risk also did not significantly change from pre to post-testing . Conclusion These results indicate that " high-risk " female athletes decreased the magnitude of the previously identified risk factor to ACL injury following neuromuscular training . However , the mean values for the high-risk subjects were not reduced to levels similar to low-risk group following training . Targeting female athletes who demonstrate high-risk knee abduction loads during dynamic tasks may improve efficacy of neuromuscular training . Yet , increased training volume or more specific techniques may be necessary for high-risk athletes to substantially decrease ACL injury risk Background : Previous studies have found significant predictors for functional outcome after anterior cruciate ligament ( ACL ) reconstruction ; however , studies examining predictors for functional outcome in nonoperatively treated individuals are lacking . Hypothesis : Single-legged hop tests predict self-reported knee function ( International Knee Documentation Committee [ IKDC ] 2000 ) in nonoperatively treated ACL-injured individuals 1 year after baseline testing . Study Design : Cohort study ( prognosis ) ; Level of evidence , 2 . Methods : Ninety-one nonoperatively treated patients with an ACL injury were tested using 4 single-legged hop tests on average 74 ± 30 days after injury in a prospect i ve cohort study . Eighty-one patients ( 89 % ) completed the IKDC 2000 1 year later . Patients with an IKDC 2000 score equal to or higher than the age- and gender-specific 15th percentile score from previously published data on an uninjured population were classified as having self-reported function within normal ranges . Logistic regression analyses were performed to identify predictors of self-reported knee function . The area under the curve ( AUC ) from receiver operating characteristic curves was used as a measure of discriminative accuracy . Optimal limb symmetry index ( LSI ) cutoff for the best single-legged hop test was defined as the LSI with the highest product of sensitivity and specificity . Results : Single hop for distance symmetry indexes predicted self-reported knee function at the 1-year follow-up ( P = .036 ) . Combinations of any 2 hop tests ( AUC = 0.64 - 0.71 ) did not give a higher discriminative accuracy than the single hop alone ( AUC = 0.71 ) . A cutoff of 88 % ( LSI ) for the single hop revealed a sensitivity of 71.4 % and a specificity of 71.7 % . Conclusion : The single hop for distance ( LSI ) significantly predicted self-reported knee function after 1 year in nonoperatively treated ACL-injured patients . Combinations of 2 single-legged hop tests did not lead to higher discriminative accuracy than the single hop alone BACKGROUND Knee valgus load during sports movement is viewed as an important predictor of non-contact anterior cruciate ligament injury risk , particularly in females . Formulating movement strategies that can reduce valgus loading during these movements therefore appears pertinent to reducing anterior cruciate ligament injury rates . With this in mind , the current study examined the relationship between peak valgus moment and lower extremity postures at impact during a sidestep cutting task . METHODS Ten male and ten female NCAA athletes had initial contact three-dimensional hip , knee and ankle angles and subsequent knee valgus moment quantified during the execution of ( n=10 trials ) sidesteps . Peak valgus data were normalized to mass and height and tested for the main effect of gender ( ANOVA , P<0.05 ) . Intra-subject correlations between the eight initial joint angles and the normalized valgus moment were then conducted across the ten sidestepping trials . The ensuing slopes of regression were su bmi tted to a two- sample t-test to determine whether mean slope values were significantly different from zero and for the main effect of gender ( P<0.05 ) . FINDINGS Females had significantly larger normalized knee valgus moments than males . A greater peak valgus moment was associated with larger initial hip flexion and internal rotation , and with larger initial knee valgus angle . Peak knee valgus moment was more sensitive to initial hip internal rotation and knee valgus position in females . INTERPRETATION Training of neuromuscular control at the hip joint may reduce the likelihood of anterior cruciate ligament injury via a valgus loading mechanism during sidestepping , especially in females Background : The incidence of second anterior cruciate ligament ( ACL ) injuries in the first 12 months after ACL reconstruction ( ACLR ) and return to sport ( RTS ) in a young , active population has been reported to be 15 times greater than that in a previously uninjured cohort . There are no reported estimates of whether this high relative rate of injury continues beyond the first year after RTS and ACLR . Hypothesis : The incidence rate of a subsequent ACL injury in the 2 years after ACLR and RTS would be less than the incidence rate reported within the first 12 months after RTS but greater than the ACL injury incidence rate in an uninjured cohort of young athletes . Study Design : Cohort study ; Level of evidence , 2 . Methods : Seventy-eight patients ( mean age , 17.1 ± 3.1 years ) who underwent ACLR and were ready to return to a pivoting/cutting sport and 47 controls ( mean age , 17.2 ± 2.6 years ) who also participated in pivoting/cutting sports were prospect ively enrolled . Each participant was followed for injury and athlete exposure ( AE ) data for a 24-month period after RTS . Twenty-three ACLR and 4 control participants suffered an ACL injury during this time . Incidence rate ratios ( IRRs ) were calculated to compare the rates ( per 1000 AEs ) of ACL injury in athletes in the ACLR and control groups . For the ACLR group , similar comparisons were conducted for side of injury by sex . Results : The overall incidence rate of a second ACL injury within 24 months after ACLR and RTS ( 1.39/1000 AEs ) was nearly 6 times greater ( IRR , 5.71 ; 95 % CI , 2.0 - 22.7 ; P = .0003 ) than that in healthy control participants ( 0.24/1000 AEs ) . The rate of injury within 24 months of RTS for female athletes in the ACLR group was almost 5 times greater ( IRR , 4.51 ; 95 % CI , 1.5 - 18.2 ; P = .0004 ) than that for female controls . Although only a trend was observed , female patients within the ACLR group were twice as likely ( IRR , 2.43 ; 95 % CI , 0.8 - 8.6 ) to suffer a contralateral injury ( 1.13/1000 AEs ) than an ipsilateral injury ( 0.47/1000 AEs ) . Overall , 29.5 % of athletes suffered a second ACL injury within 24 months of RTS , with 20.5 % sustaining a contralateral injury and 9.0 % incurring a retear injury of the ipsilateral graft . There was a trend toward a higher proportion of female participants ( 23.7 % ) who suffered a contralateral injury compared with male participants ( 10.5 % ) ( P = .18 ) . Conversely , for ipsilateral injuries , the incidence proportion between female ( 8.5 % ) and male ( 10.5 % ) participants was similar . Conclusion : These data support the hypothesis that in the 24 months after ACLR and RTS , patients are at a greater risk to suffer a subsequent ACL injury compared with young athletes without a history of ACL injuries . In addition , the contralateral limb of female patients appears at greatest risk PURPOSE The aim of this study was to determine the rates of contralateral anterior cruciate ligament ( ACL ) rupture and of ACL graft rupture after ACL reconstruction using either patellar tendon or hamstring tendon autograft , and to identify any patient characteristics that may increase this risk . TYPE OF STUDY Case series . METHODS Over a 2-year period , 760 endoscopic ACL reconstructions were performed in 743 patients . Bone-patellar tendon-bone autograft was used in 316 patients and 4-str and hamstring tendon in 427 patients . Those patients with a previous contralateral ACL rupture or those who underwent a simultaneous bilateral ACL reconstruction were excluded , leaving 675 knees ( 675 patients ) for review . Persons not involved in the index operation or the care of the patient conducted follow-up assessment by telephone interview conducted 5 years after surgery . Patients were question ed about the incidence of ACL graft rupture , contralateral ACL rupture , symptoms of instability or significant injury , family history of ACL injury , and activity level according to the International Knee Documentation Committee scale . From our prospect i ve data base we obtained further information on graft source , meniscal or articular surface injury , and gender . Binary logistic regression was used to measure the relative association between the measured variables and the risk of graft rupture and contralateral ACL rupture . RESULTS Five years after primary ACL reconstruction , 612 of the 675 patients ( 90.7 % ) were assessed . ACL graft rupture occurred in 39 patients ( 6 % ) and contralateral ACL rupture occurred in 35 patients ( 6 % ) . Three patients suffered both a graft rupture and a contralateral ACL injury . The odds of ACL graft rupture were increased 3-fold by a contact mechanism of initial injury . Return to level 1 or 2 sports increased the risk of contralateral ACL injury by a factor of 10 . The risk of sustaining an ACL graft rupture was greatest in the first 12 months after reconstruction . No other studied variable increased the risk of repeat ACL injury . CONCLUSIONS After reconstruction , repeat ACL injury occurred in 12 % of patients over 5 years . Twelve months after reconstruction , the ACL graft is at no greater risk than the contralateral ACL , suggesting that adequate graft and muscular function for most activities is achieved by this time . Risk factors for repeat ACL injury identified included a return to competitive side-stepping , pivoting , or jumping sports , and the contact mechanism of the index injury . Female patients were at no greater risk of repeat ACL injury than male patients and graft choice did not affect the rate of repeat ACL injury . LEVEL OF EVIDENCE Level IV , case series Background : Tearing an anterior cruciate ligament ( ACL ) graft is a devastating occurrence after ACL reconstruction ( ACLR ) . Identifying and underst and ing the independent predictors of ACLR graft failure is important for surgical planning , patient counseling , and efforts to decrease the risk of graft failure . Hypothesis : Patient and surgical variables will predict graft failure after ACLR . Study Design : Prospect i ve cohort study . Methods : A multicenter group initiated a cohort study in 2002 to identify predictors of ACLR outcomes , including graft failure . First , to control for confounders , a single surgeon ’s data ( n = 281 ACLRs ) were used to develop a multivariable regression model for ACLR graft failure . Evaluated variables were graft type ( autograft vs allograft ) , sex , age , body mass index , activity at index injury , presence of a meniscus tear , and primary versus revision reconstruction . Second , the model was vali date d with the rest of the multicenter study ’s data ( n = 645 ACLRs ) to evaluate the generalizability of the model . Results : Patient age and ACL graft type were significant predictors of graft failure for all study surgeons . Patients in the age group of 10 to 19 years had the highest percentage of graft failures . The odds of graft rupture with an allograft reconstruction are 4 times higher than those of autograft reconstructions . For each 10-year Output:	Conclusion : This systematic review and meta- analysis demonstrates that younger age and a return to high level of activity are salient factors associated with secondary ACL injury . These data indicate that activity modification , improved rehabilitation and return-to-play guidelines , and the use of integrative neuromuscular training may help athletes more safely reintegrate into sport and reduce second injury in this at-risk population
MS22057	*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 A phase I dose escalation of hypofractionated stereotactic radiotherapy ( H-SRT ) in recurrent or persistent malignant gliomas as a means of increasing the biologically effective dose and decreasing the high rate of reoperation due to toxicity associated with single-fraction stereotactic radiosurgery ( SRS ) and brachytherapy . MATERIAL S AND METHODS From November 1994 to September 1996 , 25 lesions in 20 patients with clinical and /or imaging evidence of malignant glioma persistence or recurrence received salvage H-SRT . Nineteen patients at the time of initial diagnosis had glioblastoma multiforme ( GBM ) and one patient had an anaplastic astrocytoma . All of these patients with tumor persistence or recurrence had received initial fractionated radiation therapy ( RT ) with a mean and median dose of 60 Gy ( 44.0 - 72.0 Gy ) . The median time from completion of initial RT to H-SRT was 3.1 months ( 0.7 - 45.5 months ) . Salvage H-SRT was delivered using daily 3.0 - 3.5 Gy fractions ( fxs ) . Three different total dose levels were sequentially evaluated : 24.0 Gy/3.0 Gy fxs ( five lesions ) , 30.0 Gy/3.0 Gy fxs ( 10 lesions ) , and 35.0 Gy/3.5 Gy fxs ( nine lesions ) . Median treated tumor volume measured 12.66 cc ( 0.89 - 47.5 cc ) . The median ratio of prescription volume to tumor volume was 2.8 ( 1.4 - 5.0 ) . Toxicity was judged by RTOG criteria . Response was determined by clinical neurologic improvement , a decrease in steroid dose without clinical deterioration , and /or radiologic imaging . RESULTS No grade 3 toxicities were observed and no reoperation due to toxicity was required . At the time of analysis , 13 of 20 patients had died . The median survival time from the completion of H-SRT is 10.5 months with a 1-year survival rate of 20 % . Neurological improvement was found in 45 % of patients . Decreased steroid requirements occurred in 60 % of patients . Minor imaging response was noted in 22 % of patients . Using Fisher 's exact test , response of any kind correlated strongly to total dose ( p = 0.0056 ) . None of six lesions treated with 21 Gy or 24 Gy responded , whereas there was a 79 % response rate among the 19 lesions treated with 30 or 35 Gy . Tumor volumes < or = 20 cc were associated with a higher likelihood of response ( p = 0.053 ) . CONCLUSIONS H-SRT used in this cohort of previously irradiated patients with malignant glioma was not associated with the need for reoperation due to toxicity or grade 3 toxicity . This low toxicity profile and encouraging H-SRT dose-related response outcome justifies further evaluation and dose escalation The purpose of this study was to retrospectively evaluate the survival of patients with high- grade gliomas treated with external beam radiotherapy with or without radiosurgical boost . From July 1993 to April 1998 , 32 patients were selected , 15 of which received radiosurgery . Inclusion criteria were age > 18 years , histological confirmation of high- grade glioma , primary tumor treatment with curative intent , unifocal tumor and supratentorial location . All patients were found to be in classes III – VI , according to the recursive partitioning analysis proposed by the Radiation Therapy Oncology Group . The median interval between radiotherapy and radiosurgery was 5 weeks ( range 1–13 ) . Treatment volumes ranged from 2.9 to 70.3 cc ( median 15.0 cc ) . Prescribed radiosurgery doses varied from 8.0 to 12.5 Gy ( median 10.0 Gy ) . Radiosurgery and control groups were well balanced with respect to prognostic factor distributions . Median actuarial survival time in radiosurgery and control groups was 21.4 months and 11.6 months , respectively ( p=0.0254 ) . Among patients with KPS≥80 , median survival time was 11.0 months and 53.9 months in the control and radiosurgery groups , respectively ( p=0.0103 ) . Radiosurgery was the single factor correlated with survival on Cox model analysis ( p=0.0362 ) and was associated with a 2.76 relative reduction in the risk of cancer death ( 95 % confidence interval ( CI ) 1.07–7.13 ) . Our results suggest that radiosurgery may confer a survival advantage for patients in RPA classes III – VI , especially for those with Karnofsky performance status ≥80 . The definitive role of radiosurgical boost for patients with high- grade gliomas awaits the results of r and omized trials Background . The treatment of recurrent gliomas is palliative ; however , the local pattern of tumor recurrence permits retreatment with single fraction , high dose stereotactic radiotherapy or radiosurgery ( RS ) . Twenty-two patients with recurrent glioma have been treated on a dose escalation protocol with fractionated stereotactic external beam radiotherapy ( SRT ) . All had previously received radical radiotherapy ( median dose 55 Gy ) as part of the initial treatment . The dose of SRT was increased from 30 Gy in six fractions to 50 Gy in ten fractions . Median survival from the date of SRT was 9.8 months . There was no significant acute morbidity but five patients who received > or = 40 Gy developed steroid responsive neurological deterioration assumed to represent late radiation damage . The survival and toxicity in patients with recurrent glioma are comparable with interstitial therapy . Fractionated SRT is a noninvasive form of localised radiation which may be a suitable alternative to interstitial therapy in this group of patients In a non-r and omised study in six centres in the UK , 24 patients with previously untreated small-cell lung cancer of limited extent were treated with a regimen of alternating chemotherapy and radiotherapy to assess response , toxicity , and the feasibility of applying such a regimen on a multicentre basis in the UK . The intention was to give six courses of chemotherapy on five consecutive days at 4-week intervals : etoposide 75 mg m-2 on days 1 , 2 , and 3 ; doxorubicin 40 mg m-2 on day 1 ; cisplatin 100 mg m-2 on day 2 ; and cyclophosphamide 300 mg m-2 on days 2 , 3 , 4 and 5 . A dose of 20 Gy thoracic radiotherapy was to be given following the 2nd and the 3rd courses , and one of 15 Gy following the 4th course . After 12 patients had been admitted , the cisplatin dosage was reduced to 80 mg m-2 because of unacceptable toxicity . Two patients were withdrawn during treatment on review of their histology because their diagnosis was found to be incorrect . Only one patient of the 12 treated with cisplatin 100 mg m-2 was able to complete treatment , compared with five of the eligible ten given the lower dosage . Among the 22 patients with confirmed small-cell disease , a complete response was reported in 14 ( 64 % ) and a partial response in a further three ( total response rate 77 % ) . Myelosuppression was the commonest serious adverse effect . It occurred in 19 of the 24 patients and gave rise to septicaemia in five , four of whom were receiving the higher cisplatin dose . Sixteen patients required blood transfusion and ten platelet transfusion . Vomiting , oesophagitis , and peripheral neuropathy occurred in 12 , four and four patients , respectively , and radiation pneumonitis developed in two . Treatment was considered a contributory cause of death in four . The working party concluded that the alternating regimen was feasible in only a small proportion of centres in the UK , and decided not to embark on a multicentre r and omised trial comparing alternating with conventional scheduling Despite the progress in neurosurgery and radiotherapy , almost all patients treated with malignant gliomas develop recurrent tumors and die of their disease . Eighty-eight patients ( median age 56 years ) with recurrent glioblastoma ( median tumor volume 32.7 cm3 ) were treated with noninvasive fractionated stereotactic radiosurgery and concurrent paclitaxel used as a sensitizer . The median interval between diagnosis of primary glioblastoma and salvage radiosurgery was 7.8 months . Four weekly treatments ( median dose : 6.0 Gy ) were delivered after the 3-hour paclitaxel infusion ( median dose : 120 mg/m2 ) . Survival was calculated by the Kaplan-Meier method from radiosurgery treatment . Overall median survival was 7.0 months , and the 1-year and 2-year actuarial survival rates were 17 % and 3.4 % , respectively . When grouped by performance status , there was no difference in survival between the patients with low and high Karnofsky score . Patients with tumor volume less than 30 cm3 survived significantly longer than those with tumor greater than 30 cm3 ( 9.4 vs. 5.7 months , p = 0.0001 ) . Their 1-year survival rate was 40 % and 8 % , respectively . Eleven patients ( 11 % ) had reoperation because of exp and ing mass . Stable disease was seen in 40 % of patients ( n = 34 ) , and increase in radiographically detected mass was observed in 41 patients ( 48.8 % ) . Although the treatment of recurrent GBM is mostly palliative , the fractionated radiosurgery offers a chance for prolonged survival , especially in patients with a smaller tumor volume PURPOSE The purpose is twofold : ( 1 ) to identify the malignant glioma patients treated in a trial of hyperfractionated radiotherapy ( RT ) and carmustine ( BCNU ) who may have been eligible for a stereotactic radiosurgery ( SRS ) boost ; and ( 2 ) to compare survival of such patients with that of those considered SRS-ineligible . PATIENTS AND METHODS From January 1983 to July 1989 , 778 malignant glioma patients were enrolled on Radiation Therapy Oncology Group ( RTOG ) 83 - 02 , a r and omized phase I/II hyperfractionated RT dose-escalation trial with BCNU chemotherapy . The SRS criteria used in a single-institution trial were applied to these patients ; they are : Karnofsky performance status ( KPS ) of greater than 60 ; well-circumscribed tumor less than 4.0 cm ; no subependymal spread ; and a location not adjacent to brainstem or optic chiasm . RESULTS Eighty-nine patients ( 11.9 % ) were identified as potentially SRS-eligible . The median survival times ( MST ) and 18-month survival rates of the 89 eligible and 643 ineligible patients were 14.4 versus 11.7 months and 40 % versus 27 % , respectively ( P = .047 ) . The MST and 18-month survival rate of the 544 SRS-ineligible patients with KPS greater than 60 were 12.1 months and 29 % , respectively , and were not statistically inferior to the survival of the SRS-eligible group ( P = .21 ) . Multivariate analysis revealed age , KPS , and histopathology to be strongly predictive of survival , and SRS eligibility was also significantly predictive ( P = .047 ) . CONCLUSION SRS-eligible patients enrolled on RTOG 83 - 02 had survival superior to that of the SRS-ineligible group , and this advantage is mainly due to the selection of a subgroup with a high minimum KPS OBJECT After conventional doses of 55 to 65 Gy of fractionated irradiation , glioblastoma multiforme ( GBM ) usually recurs at its original location . This institutional phase II study was design ed to assess whether dose escalation to 90 cobalt gray equivalent ( CGE ) with conformal protons and photons in accelerated fractionation would improve local tumor control and patient survival . METHODS Twenty-three patients were enrolled in this study . Eligibility criteria included age between 18 and 70 years , Karnofsky Performance Scale score of greater than or equal to 70 , residual tumor volume of less than 60 ml , and a supratentorial , unilateral tumor . Actuarial survival rates at 2 and 3 years were 34 % and 18 % , respectively . The median survival time was 20 months , with four patients alive 22 to 60 months postdiagnosis . Analysis by Radiation Therapy Oncology Group prognostic criteria or Medical Research Council indices showed a 5- to 11-month increase in median survival time over those of comparable conventionally treated patients . All patients developed new areas of gadolinium enhancement during the follow-up period . Histological examination of tissues obtained at biopsy , resection , or autopsy was conducted in 15 of 23 patients . Radiation necrosis only was demonstrated in seven patients , and their survival was significantly longer than that of patients with recurrent tumor ( p = 0.01 ) . Tumor regrowth occurred most commonly in areas that received doses of 60 to 70 CGE or less ; recurrent tumor was found in only one case in the 90-CGE volume . CONCLUSIONS A dose of 90 CGE in accelerated fractionation prevented central recurrence in almost all cases . The Output:	There is a lack of evidence of survival advantages to use this treatment at the time of diagnosis or relapse . There is also insufficient evidence regarding the benefice/harms in the use of stereotactic fractionated radiation therapy for patients with glioma . Stereotactic irradiation as boost in primary diagnosed glioma or relapsed tumour is not associated with survival improvement .
MS22058	*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 effectiveness of cimetidine ( 30–40 mg/ kg/day ) was evaluated in 32 children with gastroesophageal reflux disease complicated by esophagitis who entered a r and om double-blind trial for 12 weeks . Esophagitis was diagnosed in all patients by endoscopy with biopsy . Seventeen patients ( age , mean ± SD : 21.7 ± 97.65 months ) received cimetidine ( c-pts ) , and 15 ( age , mean ± SD : 29.03 ± 39.73 months ) received a placebo ( p-pts ) . All patients received intensive postural therapy . Based on clinical and endoscopic ( and histologic ) data , 12 c-pts and three p-pts were healed ( p < 0.01 ) , the condition of four c-pts and three p-pts had improved ( not statistically significant ) , and the condition of one c-pt and nine p-pts had worsened ( p < 0.01 ) . Both clinical and esophagitis scores significantly decreased only in the c-pt group , as compared with p-pts . Improvement of esophagitis was seen in all ( 100 % ) of c-pts with mild or moderate esophagitis versus 57.14 % of p-pts ( p < 0.01 ) and in 87.5 % of c-pts with severe esophagitis as compared with 25 % of the p-pt group ( p < 0.01 ) . We conclude that cimetidine is an effective agent for treatment of reflux esophagitis in children . Although gastroesophageal reflux disease in infancy has a naturally self-limited course with conservative care ( thickened feedings and posture adjustment ) , extensive pharmacologic therapy is needed in the presence of esophagitis In order to evaluate the use of sucralfate in the treatment of children with reflux esophagitis , we studied 66 children aged from 4 months to 12 years ( mean 5.9 years , SD 3.5 ) diagnosed to have gastroesophageal reflux by means of esophageal isotopic examination and radiology . An endoscopic examination was carried out in all cases . None of the patients suffered from kidney disease or had taken antacids , cimetidine , sucralfate or antirheumatic drugs in the two weeks prior to the study . Patients were divided into three groups matched according to age , grade of esophagitis , sex , nutritional state and semiology and treated with sucralfate in tablets , cimetidine , or sucralfate in suspension ; no dietetic or postural measures were used . On days 14 , 28 , 42 and 56 , clinical control was carried out and endoscopy was done on day 28 , this being repeated on day 56 if the course was not satisfactory . From the statistical analysis of the results we deduce that there are no differences between the three groups . Therefore sucralfate appears to be a useful drug for the treatment of children with esophagitis due to GER Background : Epidemiological studies have shown an association between gastro-oesophageal reflux disease ( GORD ) and asthma , and oesophageal acid perfusion may cause bronchial constriction . However , no causative relation has been proven . Aim : To assess whether acid suppression would lead to reduced asthma symptoms in children with concomitant asthma and GORD . Methods : Thirty eight children ( mean age 10.8 years , range 7.2–16.8 ; 29 males ) with asthma and a reflux index ⩾5.0 assessed by 24 hour oesophageal pH monitoring were r and omised to 12 weeks of treatment with omeprazole 20 mg daily or placebo . The groups were similar in age , gender , mean reflux index , and asthma severity . Primary endpoints were asthma symptoms ( daytime wheeze , symptoms at night , in the morning , and during exercise ) and quality of life ( PAQLQ ) . Secondary endpoints were changes in lung function and the use of short acting bronchodilators . At the end of the study a repeated pH study was performed to confirm the efficacy of acid suppression . Results : The change in total symptom score did not differ significantly between the omeprazole and the placebo group , and decreased by 1.28 ( 95 % CI −0.1 to 2.65 ) and 1.28 ( 95 % CI −0.72 to 3.27 ) respectively . The PAQLQ score increased by 0.62 ( 95 % CI 0.29 to 0.95 ) in the omeprazole group compared to 0.50 ( 95 % CI 0.29 to 0.70 ) in the placebo group . Change in lung function and use of short acting bronchodilators were similar in the groups . The acid suppression was adequate ( reflux index < 5.0 ) under omeprazole treatment . Conclusion : Omeprazole treatment did not improve asthma symptoms or lung function in children with asthma and GORD The effect of antisecretory treatment on extraesophageal symptoms of gastroesophageal reflux disease was evaluated . Seventy-eight children presenting with typical and extraesophageal symptoms of gastroesophageal reflux disease underwent a multichannel intraluminal impedance and pH monitoring ( MII/pH ) . Children with a positive MII/pH were r and omly treated with proton pump inhibitors ( PPIs ) or histamine H(2 ) -receptor antagonists ( H(2 ) RAs ) during 3 months . At the end of the treatment period , all patients were recalled . A second treatment period of 3 months was given to those patients who were not symptom-free after 3 months . Thirty-five of the forty-one ( 85.4 % ) children with a pathologic MII/pH presented with extraesophageal symptoms and were treated with PPIs ( omeprazole ; n:19 ) or H(2 ) RAs ( ranitidine ; n:16 ) for 12 weeks . After 3 months , 11/19 ( 57.9 % ) PPI-treated patients had a complete resolution of symptoms ; 6/8 nonresponders were treated with PPI for another 3 months and became all symptom-free . The other two underwent a Nissen fundoplication . Only 5/16 ( 31.2 % ) patients treated with H(2 ) RAs had a complete resolution of symptoms after 3 months ; 1/11 was treated again with H(2 ) RAs during 3 months , and 10/11 were changed to PPIs . In 3/10 , a partial resolution of symptoms was achieved , while in 7/10 , a complete remission was obtained ( P < 0.05 ) . Antisecretory reflux treatment improves extraesophageal reflux symptoms . The efficacy of PPIs is superior to that of H(2 ) RAs in these children Thirty two consecutive patients ( age range 6 months-13.4 years ) with severe reflux oesophagitis were r and omised to a therapeutic trial for eight weeks during which they received either st and ard doses of omeprazole ( 40 mg/day/1.73 m2 surface area ) or high doses of ranitidine ( 20 mg/kg/day ) . Twenty five patients completed the trial ( 12 on omeprazole , 13 on ranitidine ) . At entry and at the end of the trial patients underwent symptomatic score assessment , endoscopic and histological evaluation of the oesophagus , and simultaneous oesophageal and gastric pH measurement ; results are given as median ( range ) . Both therapeutic regimens were effective in decreasing clinical score ( omeprazole before 24.0 ( 15 - 33 ) , after 9.0 ( 0 - 18 ) ; ranitidine before 19.5 ( 12 - 33 ) , after 9.0 ( 6 - 12 ) ) , in improving the histological degree of oesophagitis ( omeprazole before 8.0 ( 6 - 10 ) , after 2.0 ( 0 - 60 ) ; ranitidine before 8.0 ( 8 - 10 ) , after 2.0 ( 2 - 6 ) , and in reducing oesophageal acid exposure , measured as minutes of reflux at 24 hour pH monitoring ( omeprazole before 129.4 ( 84 - 217 ) , after 44.6 ( 0.16 - 128 ) ; ranitidine before 207.3 ( 66 - 306 ) , after 58.4 ( 32 - 128 ) ) as well as intragastric acidity , measured as median intragastric pH ( omeprazole before 2.1 ( 1.0 - 3.0 ) , after 5.1 ( 2.2 - 7.4 ) ; ranitidine before 1.9 ( 1.6 - 4 ) , after 3.4 ( 2.3 - 5.3 ) ) . Serum gastrin concentration was > 150 ng/l in four patients on omeprazole and in three patients on ranitidine . It is concluded that in children with refractory reflux oesophagitis high doses of ranitidine are comparable with omeprazole for the healing of oesophagitis and relief of symptoms ; both drugs result ed in efficacious reduction of intragastric acidity and intra-oesophageal acid exposure In order to study the importance of gastro-oesophageal reflux ( GOR ) as a trigger of asthma the effect of inhibition of gastric acid secretion on asthma was assessed in a double-blind , cross-over , placebo-controlled trial over four weeks in 37 children and adolescents ( mean age 14 yrs ) with bronchial asthma . Ranitidine 300 mg , ( 150 mg if B.W. was less than 40 kg ) was given as a single evening dose during four weeks . In previous investigations 18 of the 37 patients had been shown to have pathological GOR by 24 h pH monitoring in the oesophagus . The remaining 19 patients with normal GOR served as controls for possible effects of ranitidine on asthma , not related to reduction of GOR . A modest ( 30 % ) but statistically significant reduction of nocturnal asthma symptoms was produced by ranitidine in the patients with pathological GOR when compared to those with normal GOR . There was a significant correlation between the improvement in asthma symptoms and the degree of acid reflux . Side-effects of ranitidine were negligible . Acid reflux appears to be only a weak stimulus for bronchoconstriction in children and adolescents with bronchial asthma and pathological GOR . Further confirmative trials with more potent inhibitors of gastric acid secretion are , however , warranted Purpose Gastroesophageal reflux disease ( GERD ) occurs in pediatric patients when reflux of gastric contents presents with troublesome symptoms . The present study compared the effects of omeprazole and ranitidine for the treatment of symptomatic GERD in infants of 2 - 12 months . Methods This study was a clinical r and omized double-blind trial and parallel-group comparison of omeprazole and ranitidine performed at Children Training Hospital in Tabriz , Iran . Patients received a st and ard treatment for 2 weeks . After 2 weeks , the patients with persistent symptoms were enrolled in this r and omized study . Results We enrolled 76 patients in the present study and excluded 16 patients . Thirty patients each were included in group A ( ranitidine ) and in group B ( omeprazole ) . GERD symptom score for groups A and B was 47.17±5.62 and 51.93±5.42 , respectively , with a P value of 0.54 , before the treatment and 2.47±0.58 and 2.43±1.15 , respectively , after the treatment ( P=0.98 ) . No statistically significant differences were found between ranitidine and omeprazole in their efficacy for the treatment of GERD . Conclusion The safety and efficacy of ranitidine and omeprazole have been demonstrated in infants . Both groups of infants showed a statistically significant decrease in the score of clinical variables after the treatment OBJECTIVES : To evaluate the efficacy of acid-suppressive maintenance therapy for gastroesophageal reflux disease ( GERD ) in children , after the healing of reflux esophagitis . METHODS : Forty-eight children ( median age 105 months , range 32–170 ) with erosive reflux esophagitis were initially treated with omeprazole 1.4 mg/kg/day for 3 months . Patients in endoscopic remission were assigned in a r and omized , blinded manner by means of a computer-generated list to three groups of 6-month maintenance treatment : group A ( omeprazole at half the starting dose , once daily before breakfast ) , group B ( ranitidine 10 mg/kg/day , divided in two doses ) , and group C ( no treatment ) . Endoscopic , histological , and symptomatic scores were evaluated at : T0 , enrollment ; T1 , assessment for remission at 3 months after enrollment ( healing phase ) ; T2 , assessment for effective maintenance at 12 months after T0 ( 3 months after the completion of the maintenance phase ) . Relapse was defined as the recurrence of macroscopic esophageal lesions . After the completion of the maintenance phase , patients without macroscopic esophagitis relapse were followed up for GERD symptoms Output:	CONCLUSION Proton pump inhibitors or histamine H2 receptor antagonists may be used to treat children with gastroesophageal reflux disease , but not to treat asthma or unspecific symptoms
MS22059	*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 study aim ed at evaluating the activity and toxicity of gemcitabine monochemotherapy in a unselected series of elderly patients with advanced bladder cancer . The secondary objectives were to establish whether there is a correlation between treatment and Comprehensive Geriatric Assessment ( CGA ) and , in addition , to determine overall patient survival . Methods : Treatment consisted of six courses of chemotherapy with gemcitabine at a dosage of 1,200 mg/m2 on days 1 and 8 , every 21 days . CGA , as described by Gruppo Italiano di Oncologia Geriatrica , was assessed for evaluating the functional status of patients before , during , and after treatment . Results : Twenty-five patients were enrolled ( M/F 22/3 ) , 22 of these were evaluable for response and 23 for toxicity . Characteristics of patients : median age 76 years ( range 71–87 ) ; ECOG performance status ( PS ) 1 in 12 patients and 2 in 13 patients ; clinical stage III in 6 patients and IV in 19 patients . At the end of the therapy the parameters of CGA improved in 4 cases ( 17 % ) , remained unchanged in 17 cases ( 74 % ) and worsened only in 2 cases ( 9 % ) . Two patients were not evaluable . Response evaluation showed 3 ( 13.5 % ) complete responses ( CRs ) and 7 ( 32 % ) partial responses ( PRs ) , for an overall response rate of 45.5 % [ 95 % confidence interval ( CI ) , 24.3–65.7 % ] . Three ( 13.5 % ) patients had stable disease ( SD ) and 9 ( 41 % ) disease progression ( DP ) . Median overall survival was 8 months and median time to progression was 5 months . Treatment was generally well tolerated , with 1 patient having grade 3 gastrointestinal toxicity and 3 having grade 4 neutropenia . Conclusions : We conclude that gemcitabine can be safely administered in monochemotherapy , is effective and does not worsen the functional status of elderly patients with advanced bladder cancer PURPOSE To evaluate the efficacy and toxicity of weekly paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma ( TCC ) of the urothelial tract . PATIENTS AND METHODS Patients with advanced unresectable TCC were enrolled onto this multicenter , community-based , phase II trial . Initially , patients were treated with paclitaxel 110 mg/m(2 ) and gemcitabine 1,000 mg/m(2 ) by intravenous infusion on days 1 , 8 , and 15 every 28 days . Patients who had an objective response or stable disease continued treatment for a maximum of six courses . Paclitaxel was decreased to 90 mg/m(2 ) and gemcitabine was decreased to 800 mg/m(2 ) for the last 12 patients because of a concerning incidence of pulmonary toxicity in the first 24 patients . RESULTS Thirty-six patients were enrolled between September 1998 and March 2003 . Twenty-four patients received the higher doses of paclitaxel and gemcitabine , and 12 patients received the lower doses . Twenty-five ( 69.4 % ) of 36 patients had major responses to treatment , including 15 patients ( 41.7 % ) with complete responses . With a median follow-up time of 38.7 months , the median survival time was 15.8 months . Grade 3 and 4 toxicities included granulocytopenia ( 36.1 % ) , thrombocytopenia ( 8.3 % ) , and neuropathy ( 16.7 % ) . Five patients ( 13.9 % ) had grade s 3 to 5 pulmonary toxicity , and one patient had grade 2 pulmonary toxicity . CONCLUSION Weekly paclitaxel and gemcitabine is an active regimen in the treatment of patients with advanced TCC . However , because of the high incidence of pulmonary toxicity associated with this schedule of paclitaxel and gemcitabine , we recommend against the use of this regimen in this patient population BACKGROUND To investigate a novel schedule of gemcitabine ( G ) , paclitaxel ( P ) , and carboplatin ( C ) , based on pre clinical studies demonstrating greater activity and decreased toxicity of administering P prior to C. MATERIAL / METHODS The effect of the P and C drug sequence on tumor cell viability was assessed with a tetrazolium assay on T24 bladder and DU145 prostate cancer cells . Patients with transitional cell cancer ( TCC ) and other advanced malignancies were treated with G and P on days 1 , 8 , and 15 of each 28 day cycle . C was administered on day 2 at an AUC of 5 . Doses of G and P were varied among cohorts of three patients . RESULTS Pre clinical studies demonstrated that the sequence of P followed by C induced greater cytotoxicity than the reverse sequence . The recommended phase II dose ( RPTD ) was defined as 70 mg/m2 P , 300 mg/m2 G , and C with AUC of 5 . Therapy was well tolerated ; fever and neutropenia occurred in only one patient at the RPTD . Grade 3 thrombocytopenia occurred in 5 of 21 patients treated at the RPTD . Out of all 37 patients treated on study , 9 achieved a partial tumor response ( PR ) and two patients achieved a complete response ( CR ) . Out of the 15 patients with TCC , six had a PR and two had a CR . CONCLUSIONS Pre clinical studies demonstrated that the sequence of paclitaxel followed by carboplatin was more effective than the opposite sequence . Administration of gemcitabine and paclitaxel followed by carboplatin was well tolerated and clinical ly active . GCP should be compared to other combination regimens under investigation for the treatment of TCC Our objective was to determine the response to gemcitabine plus docetaxel in advanced urothelial transitional cell carcinoma in a phase II trial , and gemcitabine distribution between plasma and erythrocytes , following docetaxel administration . Patients with locally advanced or metastatic transitional cell carcinoma , following a maximum of one prior chemotherapy regimen , were given gemcitabine 800 mg/m2 on days 1 and 8 plus docetaxel 85 mg/m2 on day 8 , every 21 days . Gemcitabine was measured in the plasma and erythrocytes of nine patients before and after docetaxel administration . Thirty-four patients ( median 63 years ; range 49–79 years ) , of whom seven had prior chemotherapy and 27 were chemotherapy-naive , received a median of six cycles ( range 1–6 ) . Complete and partial remissions were observed in two and 16 ( including three pretreated ) patients , respectively , for an overall response rate of 53 % . Median response duration was 5 months ( range 1–39 + ) . Haematoxicity was manageable , despite grade 3 infections in 24 % of patients , but other toxicities were mostly mild . An apparent shift of gemcitabine from plasma to erythrocytes occurred after docetaxel in five of six patients evaluable for this analysis . We conclude gemcitabine plus docetaxel is tolerable and highly active in treated and untreated patients with advanced transitional cell carcinoma BACKGROUND Despite the fact that new drugs have emerged from clinical research in urothelial cancer during the last decade , the prognosis of patients with advanced disease remains poor with a median survival of 12 to 14 months . We design ed a feasibility study of gemcitabine and oxaliplatin ( GO ) in patients with advanced urothelial cancer . PATIENTS AND METHODS Twenty patients received bimonthly cycles of gemcitabine 1500 mg/m2 and oxaliplatin 85 mg/m2 . The cycles were given at 2-week intervals without G-CSF support . Thirteen patients were treated with the GO combination as first-line chemotherapy because of a poor performance status or a creatinine clearance < 1 ml/s . RESULTS The median number of cycles of GO was 5 ( 1 - 7 ) . The median number of days between cycles was 14 throughout the treatment . Seven ( 8 % ) out of 87 cycles had to be delayed because of neutropenia or asthenia . A 25 % dose reduction in the doses of cytotoxic drugs was necessary in 2 patients . Chemotherapy was stopped before the sixth cycle because of an early death related to a myocardial infa rct ion in 1 patient , a grade 3 neuropathy in 1 patient and a progressive disease in 9 patients . CONCLUSION Using these doses and schedules , the GO regimen appears a safe therapy for patients with advanced urothelial cancer . Phase II studies are required to assess the possible role of this combination in advanced urothelial cancer AIM Chemotherapeutic agents are active in transitional cell cancer of the urothelium , and combinations have shown promising results . The objective of this study was to evaluate the palliative chemotherapy with gemcitabine , paclitaxel , and cisplatin for transitional cell carcinoma . METHODS Thirty-four patients with advanced transitional cell carcinoma of the urothelium were treated between 2000 and 2007 . All patients received chemotherapy with intravenous gemcitabine at a dose of 1000 mg/m2 on days I and VIII , intravenous paclitaxel at a dose of 80 mg/m2 on days I and VIII , and intravenous cisplatin at a dose of 50 mg/m2 on day II . Treatment courses were repeated every 21 days . After completion of four to six courses in this regimen an application of intravenous gemcitabine at a dose of 1000 mg/m2 followed repeating every 28 days . RESULTS Twelve patients ( 35.3 % ) had 1 visceral sites of metastases . Twenty two patients ( 64.7 % ) had achieved objective responses to treatment ( 29.4 % complete responses ) . The median actuarial survival was 18.5 months , and the actuarial one-year and two-year survival rates were 56 % and 26 % respectively . After a median follow-up of 16.3 months , 18 patients remained alive . The median progression-free survival was 7 months . Median survival time for patients with ECOG status 0 , 1 , and 2 was 45 , 12 , and 10.5 months respectively . Grade 3 - 4 neutropenia occurred in 41.2 % of patients . CONCLUSIONS The combination of gemcitabine , paclitaxel , and cisplatin is a highly effective and tolerable regimen for patients with advanced transitional cell carcinoma of the urothelium . This treatment should be considered as a suitable option that deserves further prospect i ve evaluation . ECOG performance status and visceral metastases are important predictive factors for survival Clinical trials in urothelial cancer exclude a large population of patients . An observational study evaluated the behavior of frail patients not eligible for cisplatin- or carboplatin-based regimens . Urothelial cancer patients requiring chemotherapy with either chronic renal failure ( creatinine clearance < 60 ml/min ) , and /or performance status ( PS ) ≥2 and /or cardiac dysfunction were prospect ively observed . The treatment associated gemcitabine 1200 mg/m2 and oxaliplatin 85 mg/m2 , bimonthly ( GO ) . Over 2 years , 31 of 45 ( 69 % ) patients with urothelial cancer requiring chemotherapy were not eligible for cisplatin- or carboplatin-based chemotherapy . Sixteen ( 52 % ) had a PS ≥2 , 23 ( 74 % ) had creatinine clearance < 60 ml/min , and 20 ( 65 % ) had an underlying cardiopathy . A total of 178 cycles of GO were administered ( median 6 per patient , range 2–12 ) . No aggravation of renal or cardiac status was noted . Acute grade 3 and 4 neutropenia and thrombocytopenia were observed in 16 and 13 % of patients , respectively , with one febrile neutropenia . The median progression-free and overall survival values were 4.2 and 9.5 months , respectively . The majority of urothelial cancer patients have severe renal or cardiac comorbidities , and we conclude that in this subset of patients the combination of gemcitabine and oxaliplatin is well tolerated , and its clinical activity warrants further evaluation PURPOSE To determine the efficacy of gemcitabine and cisplatin combination therapy in patients with advanced and /or metastatic transitional cell urothelial carcinoma . PATIENTS AND METHODS Forty-two chemonaïve patients with Karnofsky performance status ( KPS ) > or = 70 were treated with cisplatin 35 mg/m2 followed by gemcitabine 1000 mg/m2 ( 30 min i.v . infusion ) on days 1 , 8 , and 15 every twenty-eight days . RESULTS Thirty-eight patients were evaluable for efficacy . Half had visceral disease . There were seven complete ( 18 % ) and nine partial responses ( 24 % ) , for a response rate of 42 % ( 95 % confidence interval ( 95 % CI ) : 26%-59 % ) . Responses were independently review ed . Median response duration was 13.5 months ( 95 % CI : 8.5 - 18.1 months ) Output:	• Gemcitabine combined chemotherapy is active in the management of metastatic bladder cancer . • GCis may be considered an alternative regime to MVAC . •
MS22060	*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 aim of this study was to evaluate the efficacy , safety and acceptability of two monthly transcervical applications of quinacrine 252 mg and ibuprofen 55.5 mg as pellets for non-surgical female sterilization . From August 1992 through October 1996 , a prospect i ve clinical study was conducted on 200 normal women seeking surgical sterilization voluntarily in the Family Planning Clinic of the Department of Obstetrics and Gynecology , Regency Hospital , Wonosobo , Central Java , Indonesia . Quinacrine 252 mg and ibuprofen 55.5 mg were inserted transcervically , as pellets , using a Copper T IUD insertor in the proliferative phase of two consecutive menstrual cycles . The women were followed up 6 , 12 , 24 and 48 months after insertion . There were no major complications during the insertion procedures , and side-effects which occurred during the us e of the methods were transient . Cumulative life-table continuation rate per 100 women at four years was 0.91±0.02 ( SE ) . The pregnancy fail ure rate was 0.04 or 4.3 % . The results of this study indicate that intrauterine insertion of quinacrine pellets is a safe , acceptable and effective method of non-surgical female sterilization Objective To compare patient satisfaction , discomfort , procedure time , success rate and adverse events of hysteroscopic ( ESSURE , Conceptus Inc , San Carlos , USA ) versus laparoscopic sterilisation Approximately 200 women of American Society of Anesthesiologists class I and II physical status electing outpatient laparoscopic tubal sterilization with Yoon rings were involved in a double-blind study to evaluate postoperative pain relief after intraoperative suprapubic infiltration of the fallopian mesosalpinx . The postoperative pain levels were lower after bilateral infiltration of 0.5 % bupivacaine beneath the site of ring application . Postoperative , suprapubic infiltration provided safe , prolonged and effective pain relief , allowed prompt ambulation and early discharge , and reduced the need for narcotic analgesics and postoperative analgesia OBJECTIVE To assess the safety , effectiveness , and reliability of a tubal occlusion microinsert for permanent contraception , as well as to document patient recovery from the placement procedure and overall patient satisfaction . METHODS A cohort of 518 previously fertile women seeking sterilization participated in this prospect i ve , phase III , international , multicenter trial . Microinsert placement was attempted in 507 women . Microinserts were placed bilaterally into the proximal fallopian tube lumens under hysteroscopic visualization in outpatient procedures . RESULTS Bilateral placement of the microinsert was achieved in 464 ( 92 % ) of 507 women . The most common reasons for failure to achieve satisfactory placement were tubal obstruction and stenosis or difficult access to the proximal tubal lumen . More than half of the women rated the average pain during the procedure as either mild or none , and 88 % rated tolerance of device placement procedure as good to excellent . Average time to discharge was 80 minutes . Sixty percent of women returned to normal function within 1 day or less , and 92 % missed 1 day or less of work . Three months after placement , correct microinsert placement and tubal occlusion were confirmed in 96 % and 92 % of cases , respectively . Comfort was rated as good to excellent by 99 % of women at all follow-up visits . Ultimately , 449 of 518 women ( 87 % ) could rely on the microinsert for permanent contraception . After 9620 woman-months of exposure to intercourse , no pregnancies have been recorded . CONCLUSION This study demonstrates that hysteroscopic interval tubal sterilization with microinserts is well tolerated and results in rapid recovery , high patient satisfaction , and effective permanent contraception OBJECTIVE To evaluate the reliability of pelvic X-ray and transvaginal ultrasound to localize Essure microinserts ( Conceptus , San Carlos , California ) after successful placement in both fallopian tubes 3 months after placement . DESIGN Prospect i ve , observational study . SETTING Gynecology departments at two teaching hospitals . PATIENT(S ) One hundred eighty-two patients who underwent hysteroscopic sterilization by placement of Essure microinserts between August 2002 and August 2004 . INTERVENTION(S ) Transvaginal ultrasound , pelvic X-ray , and hysterosalpingography ( HSG ) 3 months after sterilization with Essure . MAIN OUTCOME MEASURE(S ) Transvaginal ultrasound confirmation of correct localization of microinserts after a 3-month follow-up . RESULT ( S ) In 150 of 182 patients , confirmation of successful bilateral placement of two microinserts ( 300 devices ) was possible . In 9 patients it was not possible to identify both devices with ultrasound , or there was doubt about the extension of the device through the uterotubal junction . The other 291 devices were identified as being in a good position . CONCLUSION ( S ) Hysterosalpingography at the 3-month follow-up after successful placement of Essure microinserts can be replaced by transvaginal ultrasonography . A 3-month follow-up with HSG after the Essure procedure is only required after unsatisfactory placements . In those patients in whom transvaginal ultrasonography can not confirm satisfactory localization , a complementary pelvic X-ray should be performed OBJECTIVE To evaluate women 's satisfaction and tolerance of hysteroscopic sterilization . DESIGN Prospect i ve analysis of case series . SETTING Gynecology department in a teaching hospital . PATIENT(S ) A total of 1,630 women who underwent hysteroscopic sterilization by placement of Essure microinserts ( Conceptus , Inc. , Mountain View , CA ) from January 2003 to June 2006 . INTERVENTION(S ) Transvaginal ultrasound examination , pelvic x-ray examination , and hysterosalpingography 3 months after sterilization with Essure microinserts . Satisfaction was assessed by a visual analog scale . Adverse effects and tolerance also were recorded . MAIN OUTCOME MEASURE(S ) Transvaginal ultrasound and pelvic x-ray confirmation of correct localization of microinserts and patient 's satisfaction and tolerance after a 3-month follow-up . RESULT ( S ) The rate of successful insertion was 99 % . Most of women returned to their daily activities on the same day of insertion , and 86.5 % considered the procedure painless or scarcely painful . All the patients were highly satisfied after hysteroscopic sterilization : 91 % of subjects by visual analog scale ( on a 0 to 10 scale ) rated the method at 10 ( high satisfaction degree ) , and none of the subjects rated it under 8 . For patients , the most valuable aspects of the procedure were absence of surgery room ( 52.7 % ) , method 's quickness and comfort ( 19.9 % ) , and permanent sterilization ( 18.2 % ) . More than 97 % of the patients said that they would recommend the procedure to others . CONCLUSION ( S ) This study provides evidence that Essure microinserts can be placed in a usual gynecologic consultation room in st and ard conditions without any type of anesthesia or sedation and are associated with great overall patient satisfaction . Women also have high tolerance for the procedure and describe minor postoperative pain OBJECTIVE The present study examines the safety , effectiveness , and local tissue response for a new transcervical fallopian tube permanent contraceptive device , the STOP device ( Conceptus , Inc. , San Carlos , CA ) . DESIGN Nonr and omized prospect i ve evaluation of tubal occlusion and histologic response . SETTING Inpatient , university and university-affiliated medical centers in the United States and Mexico . PATIENT(S ) Premenopausal and perimenopausal women with benign indications for hysterectomy who were able to defer their hysterectomy for 1 to 13 weeks . INTERVENTION(S ) A transcervically placed microcoil ( STOP device ) was inserted into the fallopian tubes of women who were scheduled for hysterectomy , and the device was worn for 1 to 12 weeks . At hysterectomy , hysterosalpingography was done to determine tubal occlusion ; subsequently , the tubes containing the STOP devices were processed , sectioned , and evaluated to determine the histologic response . MAIN OUTCOME MEASURE(S ) Ability to place a device and evaluate tubal occlusion and tissue response . RESULT ( S ) Devices were placed in 33 women , representing 57 tubes ; the women wore the devices from 1 day to 30 weeks . Histology on 27 women ( 47 tubes ) showed an acute inflammatory and fibrotic response in the short term that , over time , became a chronic inflammatory response with extensive fibrosis . CONCLUSION ( S ) The localized tissue response and notable absence of any normal tubal architecture in the segment of the fallopian tube containing the STOP device supports the postulated mechanisms of action of the device . Prehysterectomy study findings suggest the usefulness of the STOP device for pregnancy prevention , this is being evaluated in long-term safety and effectiveness studies OBJECTIVE To determine the feasibility and patient satisfaction of female sterilisation using the Essure system in an outpatient hysteroscopy clinic without conscious sedation or general anaesthesia . DESIGN Prospect i ve cohort study . SETTING Outpatient hysteroscopy clinic in a large teaching hospital . POPULATION Women undergoing outpatient hysteroscopic sterilisation using the Essure system for permanent fertility control . METHODS Demographic and procedural data were prospect ively collected from 112 consecutive women undergoing outpatient hysteroscopic sterilisation without sedation or general anaesthesia . A hysterosalpingogram ( HSG ) was performed routinely in all women 3 months after the procedure to confirm bilateral tubal occlusion . Postal question naires were sent at this time enquiring about patient satisfaction and experience with the outpatient procedure . Multivariable logistic regression was used to identify factors independently predictive of successful completion of the procedure . MAIN OUTCOME MEASURES Technical feasibility , predictive factors for technical success ( operator , body mass index , uterine size , axis , menstrual phase and cervical stenosis ) , complications , tubal occlusion on HSG , patient satisfaction and procedure-related experience . RESULTS Successful bilateral tubal placement of the Essure microinserts was achieved in 103/112 ( 92 % , 95 % CI 85 - 96 % ) women . Nonsecretory phase of the menstrual cycle ( P = 0.04 ) and a clinical ly normal-sized uterus ( P = 0.003 ) were independently predictive for successful completion of the outpatient procedure on multivariable modelling . There were no major procedure-related complications recorded , but transient vasovagal reactions occurred in 5/112 ( 5 % ) women . Of the original cohort of 112 women with successful procedures , 84 women were 3 months postprocedure and had undergone a HSG . Bilateral tubal occlusion was confirmed in 83/84 ( 99 % , 95 % CI 94 - 100 % ) women at 3 months and in 100 % at 6 months . Seventy-six of 84 ( 91 % ) had returned the question naires , and 70/73 ( 96 % , 95 % CI 88 - 99 % ) were satisfied with their overall experience of the procedure including radiological follow up , with most reporting being ' very satisfied ' ( 64/73 , 88 % , 95 % CI 78 - 94 % ) . CONCLUSIONS Outpatient hysteroscopic sterilisation using the Essure system without sedation or general anaesthesia is a successful and safe procedure associated with high rates of patient satisfaction . If practical , women should be scheduled to have their procedures in the proliferative phase of the menstrual cycle to optimise successful placement of Essure devices , especially if the uterus is clinical ly enlarged Self-reported postoperative pain was reduced significantly ( P less than .05 ) for up to six hours in a group of ambulatory surgical patients with the application of 5 mL of 1 % etidocaine to the b and ed portion of each fallopian tube after laparoscopic tubal ligation with Falope Rings in comparison to a control group receiving normal saline . The etidocaine group had less nausea and vomiting and smaller antiemetic and analgesic requirements than did the control group , though those results were not statistically significant Objective To compare objective ly the pain associated with tubal occlusion by Silastic rings versus electrocoagulation during laparoscopic tubal ligation under local anesthesia . Methods Consecutive patients scheduled for laparoscopic tubal ligation under local anesthesia were r and omized to Silastic rings ( N = 50 ) or electrocoagulation { N = 52 ) as the method of tubal occlusion . Sterilization was performed under local anesthesia in a st and ard fashion . Bupivacaine 0.5 % was used as the local anesthetic agent . Operative pain was measured based on intraoperative anesthesia requirements and a modified McGill pain question naire . This question naire was used to assess pain at 15 minutes , 1 hour , and 24 hours postoperatively . Results Demographics were similar for the two groups . Operative time was shorter in the Silastic – ring group ( 16.7 versus 21.8 minutes ; P = .001 ) , and this group also required less intra Output:	Electrocoagulation was associated with less morbidity including post-operative pain when compared with the modified Pomeroy and tubal ring methods , despite the risk of burns to the small bowel . The small sample size and the relative short period of follow-up in these studies limited the power to show clinical or statistical differences for rare outcomes such as failure rates .
MS22061	*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 research was to evaluate the anticaries effectiveness of a low-dose ( 500 ppm F , low-NaF ) sodium fluoride dentifrice , a high-dose ( 2,800 ppm F , high-NaF ) sodium fluoride dentifrice and an experimental 0.454 % stabilized stannous fluoride ( 1,100 ppm F ) with sodium hexametaphosphate ( SnF2-HMP ) dentifrice , each relative to a st and ard 1,100 ppm F sodium fluoride positive control dentifrice . Subjects ( n = 955 , with ∼239 per group ) with a mean age of 10.6 ( ∼9–12 years ) were r and omly assigned to one of four dentifrice treatments . Two calibrated examiners independently measured visual-tactile caries as DMFS that was supplemented with a radiographic examination at baseline , 12 months and 24 months for each subject . Generally similar results were independently observed by both examiners at the conclusion of the 2-year study period . Considering all subjects that attended at least 60 % of the supervised brushing sessions , statistically significantly less caries was observed in the high-NaF group compared to the control group . Similarly , statistically significantly less caries was observed in the SnF2-HMP group as compared to the control group . Differences in caries increments between the low-NaF and control groups were not statistically significant . One of the examiners observed these same statistically significant differences after 1 year . In conclusion , the results of this clinical trial indicated that while no difference in caries increments was observed between the low-NaF and control groups , both the high-NaF and the SnF2-HMP groups experienced significantly fewer lesions than the control group OBJECTIVE To compare the effectiveness of annual topical application of silver diamine fluoride ( SDF ) solution , semi-annual topical application of SDF solution , and annual application of a flowable high fluoride-releasing glass ionomer in arresting active dentine caries in primary teeth . METHODS A total of 212 children , aged 3 - 4 years , were r and omly allocated to one of three groups for treatment of carious dentine cavities in their primary teeth : Gp1-annual application of SDF , Gp2-semi-annual application of SDF , and Gp3-annual application of glass ionomer . Follow-up examinations were carried out every six months to assess whether the treated caries lesions had become arrested . RESULTS After 24 months , 181 ( 85 % ) children remained in the study . The caries arrest rates were 79 % , 91 % and 82 % for Gp1 , Gp2 and Gp3 , respectively ( p=0.007 ) . In the logistic regression model using GEE to adjust for clustering effect , higher caries arrest rates were found in lesions treated in Gp2 ( OR=2.98 , p=0.007 ) , those in anterior teeth ( OR=5.55 , p<0.001 ) , and those in buccal/lingual smooth surfaces ( OR=15.6 , p=0.004 ) . CONCLUSION Annual application of either SDF solution or high fluoride-releasing glass ionomer can arrest active dentine caries . Increasing the frequency of application to every 6 months can increase the caries arrest rate of SDF application . CLINICAL SIGNIFICANCE Arrest of active dentine caries in primary teeth by topical application of SDF solution can be enhanced by increasing the frequency of application from annually to every 6 months , whereas annual paint-on of a flowable glass ionomer can also arrest active dentine caries and may provide a more aesthetic outcome Root caries is common in institutionalized elders , and effective prevention methods are needed . This clinical trial compared the effectiveness of four methods in preventing new root caries . From 21 residential homes , 306 generally healthy elders having at least 5 teeth with exposed sound root surfaces were r and omly allocated into one of four groups : ( 1 ) individualized oral hygiene instruction ( OHI ) ; ( 2 ) OHI and applications of 1 % chlorhexidine varnish every 3 months ; ( 3 ) OHI and applications of 5 % sodium fluoride varnish every 3 months ; and ( 4 ) OHI and annual applications of 38 % silver diamine fluoride ( SDF ) solution . Two-thirds ( 203/306 ) of the elders were followed for 3 years . Mean numbers of new root caries surfaces in the four groups were 2.5 , 1.1 , 0.9 , and 0.7 , respectively ( ANOVA , p < 0.001 ) . SDF solution , sodium fluoride varnish , and chlorhexidine varnish were more effective in preventing new root caries than giving OHI alone OBJECTIVES Little is known about the effect of Cervitec , a chlorhexidine-thymol varnish , on root caries . Our objective was to determine whether a 3-monthly application of Cervitec over 1 year would limit the progress of existing root caries lesions and reduce the incidence of dental root caries in a group of dentate institutionalized elderly , as a complement to their usual oral hygiene practice s. METHODS A double-blind r and omized clinical trial was conducted in 68 subjects ( 34 per group ) in two residences in Almería ( Spain ) . Twenty-one subjects with 60 root caries lesions and 25 with 65 lesions , in the Cervitec and placebo groups , respectively , completed the study . Varnishes were applied twice in the first week , 1 month later , and every 3 months until the end of the study . Clinical parameters associated with established lesions were determined at baseline and after 6 and 12 months , as was the incidence of root caries lesions . RESULTS The clinical evolution of lesions was significantly better in the Cervitec group as opposed to the placebo group in terms of width , height , color , and texture . The increase in root caries was significantly lower ( p=0.039 ) in the Cervitec group . CONCLUSION According to these results , Cervitec may help to control established root lesions and reduce the incidence of root caries lesion among institutionalized elderly A clinical trial was conducted to compare the effect of different caries – preventive strategies on caries progression in lower – income , ethnically diverse persons 60 years of age and older . Two hundred and ninety – seven subjects were r and omized into one of five experimental groups . Group 1 received usual care from a public health department or a private practitioner . Group 2 received an educational program of 2 h duration implemented twice a year . Group 3 received the educational program plus a 0.12 % chlorhexidine rinse weekly . Group 4 received the education and chlorhexidine interventions and a fluoride varnish application twice a year . Group 5 received all the above interventions as well as scaling and root planing every 6 months throughout the 3–year study . A carious event was defined as the onset of a carious lesion , a filling , or an extraction on a surface which was sound at baseline . Two hundred and one subjects remained in the study for the 3–year period . Groups that received usual intraoral procedures ( groups 3 , 4 , and 5 ) had a 27 % reduction for coronal caries events ( p = 0.09 ) and 23 % for root caries events ( p = 0.15 ) , when compared to the groups that received no intraoral procedures ( groups 1 and 2 ) . Routine preventive treatments may have had only a small – to – moderate effect upon caries development Background / Aims : Root caries among elderly communities is of growing public health concern globally . This controlled clinical trial investigated the effectiveness of silver diamine fluoride and oral health education in preventing and arresting root caries . Methods : Two hundred sixty-six elderly subjects who had at least 5 teeth with exposed root surfaces and did not have serious life-threatening medical diseases were allocated to 3 groups according to a computer-generated r and om list : group 1 ( the control group ) received oral hygiene instructions ( OHI ) annually ; group 2 received OHI and silver diamine fluoride ( SDF ) application annually , and group 3 was given OHI and SDF application annually , plus an oral health education ( OHE ) programme every 6 months . Results : Two hundred twenty-seven elderly subjects were followed for 24 months . The mean numbers of new root caries surfaces in groups 1 , 2 and 3 were 1.33 , 1.00 and 0.70 , respectively ( ANOVA , p < 0.05 ) . Group 3 had fewer root surfaces with new caries than group 1 ( Scheffé multiple-comparison test , p < 0.05 ) . The mean numbers of arrested root caries surfaces in groups 1 , 2 and 3 were 0.04 , 0.28 and 0.33 , respectively ( ANOVA , p < 0.01 ) . Group 3 and group 2 had a greater number of active root caries surfaces which became arrested than group 1 ( Scheffé multiple-comparison test , p < 0.05 ) . Conclusion : Annual application of SDF together with biannual OHE was effective in preventing new root caries and arresting root caries among community-dwelling elderly subjects The purpose of this study was to determine the effect of a 48-month preventive dental program on the incidence of root caries in an urban , geriatric , noninstitutionalized population residing in an optimally fluori date d area . The 466 participants were r and omly assigned to one of three groups at baseline . Group A ( control ) : 171 subjects using a placebo mouthrinse daily ; group B : 147 subjects receiving semiannual applications of a topical APF gel ( 1.2 % F- ) with the daily use of a placebo mouthrinse ; group C : 148 subjects using a fluori date d mouthrinse daily , ACT ( 0.05 % F- ) . At baseline , the numbers of surfaces at risk , and decayed and filled surfaces were recorded . After 48 months , in addition , the number of reversed and new lesions were determined , and the incremental DMFS calculated . The data were analyzed by ANCOVA . The incremental DMFS were : A = 0.91 , B = 0.27 , C = 0.26 . The incremental DMFS in groups B and C were significantly lower than in group A ( P < .05 ) . The number of reversed lesions in group C ( 1.53 + /- 2.03 ) was significantly greater than in group A ( 1.11 + /- 1.74 ) and group B ( 1.01 + /- 1.86 ) ( P < .05 ) . The number of new lesions in group B ( 1.36 + /- 2.00 ) was significantly less than in group A ( 1.99 + /- 2.65 ) ( P < .05 ) . The daily use of the fluoride mouthrinse significantly increased the number of reversed lesions Arresting Caries Treatment ( ACT ) has been proposed to manage untreated dental caries in children . This prospect i ve r and omized clinical trial investigated the caries-arresting effectiveness of a single spot application of : ( 1 ) 38 % silver diamine fluoride ( SDF ) with tannic acid as a reducing agent ; ( 2 ) 38 % SDF alone ; ( 3 ) 12 % SDF alone ; and ( 4 ) no SDF application in primary teeth of 976 Nepalese schoolchildren . The a priori null hypothesis was that the different treatments have no effect in arresting active cavitated caries . Only the single application of 38 % SDF with or without tannic acid was effective in arresting caries after 6 months ( 4.5 and 4.2 mean number of arrested surfaces ; p < 0.001 ) , after 1 year ( 4.1 and 3.4 ; p < 0.001 ) , and after 2 years ( 2.2 and 2.1 ; p < 0.01 ) . Tannic acid conferred no additional benefit . ACT with 38 % SDF provides an alternative when restorative treatment for primary teeth is not an option Objective The aim of this single – blind , multicenter , parallel , r and omized controlled trial was to evaluate the effectiveness of the application of a high-fluoride toothpaste on root caries in adults . Methods Adult patients ( n = 130 , ♂ = 74 , ♀ = 56 ; mean age ± SD : 56.9 ± 12.9 ) from three participating centers , diagnosed with root caries , were r and omly allocated into two groups : Test ( n = 64 , ♂ = 37 , ♀ = 27 ; lesions = 144 ; mean age : 59.0 ± 12.1 ; intervention : high-fluoride toothpaste with 5000 ppm F ) , and Control ( n = 66 , ♂ = 37 , ♀ = 29 ; lesions = 160 ; mean age : 54.8 ± 13.5 ; intervention : regular-fluoride toothpaste with 1350 ppm F ) groups . Clinical examinations and surface hardness scoring of the carious lesions were performed for each subject at specified time intervals ( T0 – at baseline before intervention , T1 – at 3 months and T2 – at 6 months after intervention ) . Mean surface hardness scores ( HS ) were calculated for each patient . Statistical analyses comprised of two-way analysis of variance and post hoc comparisons using the Bonferroni – Dunn correction . Results At T0 , there was no statistical difference between the two groups with regard to gender ( P = 0.0682 , unpaired t-test ) , or age ( P = 0.9786 , chi-squared test ) , and for the overall HS ( Test group : HS = 3.4 Output:	Regular use of dentifrices containing 5,000 ppm F- and quarterly professionally applied CHX or SDF varnishes seem to be efficacious to decrease progression and initiation of root caries , respectively .
MS22062	*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 Geriatric evaluation and management has become st and ard care for community dwelling older adults following an acute admission to hospital . It is unclear whether this approach is beneficial for the frailest older adults living in permanent residential care . This study was undertaken to evaluate ( 1 ) the feasibility and consumer satisfaction with a geriatrician-led supported discharge service for older adults living in residential care facilities ( RCF ) and ( 2 ) its impact on the uptake of Advanced Care Planning ( ACP ) and acute health care service utilisation . Methods In 2002–4 a r and omised controlled trial was conducted in Melbourne , Australia comparing the geriatrician – led outreach service to usual care for RCF residents . Patients were recruited during their acute hospital stay and followed up at the RCF for six months . The intervention group received a post-discharge home visit within 96 hours , at which a comprehensive geriatric assessment was performed and a care plan developed . Participants and their families were also offered further meetings to discuss ACPs and document Advanced Directives ( AD ) . Additional review s were made available for assessment and management of intercurrent illness within the RCF . Consumer satisfaction was surveyed using a postal question naire . Results The study included 116 participants ( 57 intervention and 59 controls ) with comparable baseline characteristics . The service was well received by consumers demonstrated by higher satisfaction with care in the intervention group compared to controls ( 95 % versus 58 % , p = 0.006).AD were completed by 67 % of participants /proxy decision makers in the intervention group compared to 13 % of RCF residents prior to service commencement . At six months there was a significant reduction in outpatient visits ( intervention 21 ( 37 % ) versus controls 45 ( 76 % ) , ( p < 0.001 ) , but no difference in readmissions rates ( 39 % intervention versus 34 % control , p = 0.6 ) . There was a trend towards reduced hospital bed-day utilisation ( intervention 271 versus controls 372 days ) . Conclusion It is feasible to provide a supported discharge service that includes geriatrician assessment and care planning within a RCF . By exp and ing the service there is the potential for acute health care cost savings by decreasing the dem and for outpatient consultation and further reducing acute care bed-days OBJECTIVES This study describes the outcomes of an intervention program in Nursing Homes and their effects on emergency room attendance , hospital admissions , and pharmaceutical expenditure . MATERIAL AND METHODS This involved non-r and omised community intervention in Nursing Homes with a control group . The program was implemented gradually from 2007 to 2009 in 10 Nursing Homes ( 857 beds ) which participated voluntarily . The control group consisted of 14 Nursing homes ( 1,200 beds ) , which refused to participate or were not assigned to our Primary Care centres . Intervention consisted of comprehensive geriatric assessment and follow-up visits by trained personnel , review and adjustment of drug treatment , case management and staff training . RESULTS In the Nursing Homes where the program was carried out , emergency room attendance decreased from 1165‰ ( 95%CI 1100 - 1240 ] ) in 2006 to 674‰ ( 95%CI 620 - 730 ) in 2009 , while in the control group it increased from 1071 ( 95%CI 1020 - 1130 ) to 1246‰ ( 95%CI 1190 - 1310 ) . The hospital admissions also decreased from 48.4 % ( 95%CI 45 - 52 ) in 2006 to 32.1 % ( 95%CI 29 - 35 ) in 2009 , while in the control group increased from 43.5 % ( 95%CI 41 - 46 ) to 55.8 % ( 95%CI 53 - 59 ) . There was also a 9 % reduction in pharmacy cost compared with an increase of 11.9 % in the control group . CONCLUSIONS The intervention has proved effective at reducing hospital admissions and emergency room attendance in institutionalised patients , thereby streamlining pharmacy costs OBJECTIVES To examine the frequency and reasons for potentially avoidable hospitalizations of nursing home ( NH ) residents . DESIGN Medical records were review ed as a component of a project design ed to develop and pilot test clinical practice tools for reducing potentially avoidable hospitalization . SETTING NHs in Georgia . PARTICIPANTS In 10 NHs with high and 10 with low hospitalization rates , 10 hospitalizations were r and omly selected , including long- and short-stay residents . MEASUREMENTS Ratings using a structured review by expert NH clinicians . RESULTS Of the 200 hospitalizations , 134 ( 67.0 % ) were rated as potentially avoidable . Panel members cited lack of on-site availability of primary care clinicians , inability to obtain timely laboratory tests and intravenous fluids , problems with quality of care in assessing acute changes , and uncertain benefits of hospitalization as causes of these potentially avoidable hospitalizations . CONCLUSION In this sample of NH residents , experienced long-term care clinicians commonly rated hospitalizations as potentially avoidable . Support for NH infrastructure , clinical practice and communication tools for health professionals , increased attention to reducing the frequency of medically futile care , and financial and other incentives for NHs and their affiliated hospitals are needed to improve care , reduce avoidable hospitalizations , and avoid unnecessary healthcare expenditures in this population Residents of long-term care facilities have highly complex care needs and quality of care is of international concern . Maintaining resident wellness through proactive assessment and early intervention is key to decreasing the need for acute hospitalization . The Residential Aged Care Integration Program ( RACIP ) is a quality improvement intervention to support residential aged care staff and includes on-site support , education , clinical coaching , and care coordination provided by gerontology nurse specialists ( GNSs ) employed by a large district health board . The effect of the outreach program was evaluated through a r and omized comparison of hospitalization 1 year before and after program implementation . The sample included 29 intervention facilities ( 1,425 residents ) and 25 comparison facilities ( 1,128 residents ) receiving usual care . Acute hospitalization rate unexpectedly increased for both groups after program implementation , although the rate of increase was significantly less for the intervention facilities . The hospitalization rate after the intervention increased 59 % for the comparison group and 16 % for the intervention group ( rate ratio ( RR ) = 0.73 , 95 % confidence interval ( CI ) = 0.61 - 0.86 , P < .001 ) . Subgroup analysis showed a significantly lower rate change for those admitted for medical reasons for the intervention group ( 13 % increase ) than the comparison group ( 69 % increase ) ( RR = 0.67 , 95 % CI = 0.56 - 0.82 , P < .001 ) . Conversely , there was no significant difference in the RR for surgical admissions between the intervention and comparison groups ( RR = 1.0 , 95 % CI = 0.68 - 1.46 , P = .99 ) . The integration of GNS expertise through the RACIP intervention may be one approach to support staff to provide optimal care and potentially improve resident health 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 To assess the effect of a Screening Tool of Older Persons potentially inappropriate Prescriptions/Screening Tool to Alert doctors to Right Treatment ( STOPP/START ) medication intervention on clinical and economic outcomes . DESIGN Parallel-group r and omized trial . SETTING Chronic care geriatric facility . PARTICIPANTS Residents aged 65 and older prescribed with at least one medication ( N = 359 ) were r and omized to receive usual pharmaceutical care or undergo medication intervention . INTERVENTION Screening medications with STOPP/START criteria followed up with recommendations to the chief physician . MEASUREMENTS The outcome measures assessed at the initiation of the intervention and 1 year later were number of hospitalizations and falls , Functional Independence Measure ( FIM ) , quality of life ( measured using the Medical Outcomes Study 12-item Short-Form Health Survey ) , and costs of medications . RESULTS The average number of drugs prescribed was significantly lower in the intervention than in the control group after 1 year ( P < .001 ) . The average drug costs in the intervention group decreased by 103 shekels ( US$ 29 ) per participant per month ( P < .001 ) . The average number of falls in the intervention group dropped significantly ( P = .006 ) . Rates of hospitalization , FIM scores , and quality of life measurements were similar for both groups . CONCLUSION Implementation of STOPP/START criteria reduced the number of medications , falls , and costs in a geriatric facility . Their incorporation in those and similar setting s is recommended OBJECTIVE To describe the process and outcomes of nursing home ( NH ) residents transferred to hospital EDs . METHODS This was a prospect i ve , observational study conducted at 2 Midwestern community teaching hospitals during a 12-month period . All elder patients ( > 64 years of age ) transferred to hospital EDs from regional NHs were eligible for the study . Hospital records were used to abstract relevant descriptive and clinical data . Need for ambulance use was grade d prospect ively using 3 categories of urgency developed in other studies . Transfers were considered " appropriate " based on outcome measures or if the problem necessitated diagnostic and /or therapeutic procedures not available in the NH . Transfer documentation was evaluated using a st and ardized 18-item checklist . RESULTS A total of 709 consecutive NH patients made 1,012 ED visits . Their mean age was 83.4 years ( range 65 - 100 ) ; 76 % were female . The majority of patients ( 94 % ) were transferred by ambulance . Ambulance transfer was classified as emergent ( 16 % of patients ) , urgent ( 45 % ) , or routine ( 39 % ) . There were 319 ( 45 % ) patients subsequently admitted to the hospital . Approximately 77 % ( 546/709 ) of the NH transfers were considered appropriate by the emergency physician ( EP ) . Sixty-seven patients ( 10 % ) were transferred without any documentation . For those patients with transfer documentation , 6 common discrepancies were identified . CONCLUSION Although the majority of NH transfers in this population were appropriate , many patients were transferred without adequate documentation for the EP The dem and s of long-term care facilities ( LTCFs ) residents are complex which usually require a range of professionals and caregivers to provide treatment and care . To reduce this fragmentation of care , integrated care models are developed in modern health care system , and a gradual change from traditional LTCF care to integrated care has occurred in many countries . Although integrated care is assumed to improve the quality of care , evidence s supporting these effects are insufficient . We recruited 7 private LTCF ( 74 residents ) in northern Taipei and r and omized them into integrated care model ( N=42 , mean age=82.8+/-8.0 years , 54.8 % males ) and traditional model ( N=32 , 81.7+/-8.8 years , 43.8 % males ) . Integrated care model group was provided an actively working interdisciplinary team in addition to traditional nursing and personal care in traditional model group . Physical function , nutritional status and several quality indicators ( unplanned feeding tube replacement , unplanned urinary catheter replacement , pneumonia , urinary tract infection and so on ) were compared with both groups . Overall , LTCF residents in the integrated care model group showed significant improvement in serum levels of albumin ( 3.78+/-0.32 vs. 3.60+/-0.45 , p=0.004 ) and hemoglobin ( 12.62+/-1.58 vs. 12.03+/-1.24 , p=0.004 ) during the study period . Among selected quality indicators , subjects in integrated care model group were similar to traditional model group except that integrated care model group had a significantly reduced unplanned feeding tube replacement rate . In conclusion , the clinical effectiveness of integrated care model among severly disabled LTCF residents is minimal and a further cost-effectiveness study is needed to promote optimal quality of care in this setting OBJECTIVE To assess effect of a complex , multidisciplinary intervention aim ed at reducing avoidable acute hospitalization of residents of residential aged care ( RAC ) facilities . DESIGN Cluster r and omized controlled trial . SETTING RAC facilities with higher than expected hospitalizations in Auckl and , New Zeal and , were recruited and r and omized to intervention or control . PARTICIPANTS A total of 1998 residents of 18 intervention facilities and 18 control facilities . INTERVENTION A facility-based complex intervention of 9 months ' duration . The intervention comprised gerontology nurse specialist (GNS)-led staff education , facility bench-marking , GNS resident review , and multidisciplinary ( geriatrician , primary -care physician , pharmacist , GNS , and facility nurse ) discussion of residents selected using st and ard criteria . MAIN OUTCOME MEASURES Primary end point was avoidable hospitalizations . Secondary end points were all acute admissions , mortality , and acute bed-days . Follow-up was for a total of 14 months . RESULTS The intervention did not affect main study end points : number of acute avoidable hospital admissions ( RR 1.07 ; 95 % CI 0.85 - Output:	Despite the heterogeneity of studies , there is limited evidence that interventions delivered by geriatrics-trained staff reduce hospitalisations in nursing home residents .
MS22063	*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 Given the long term benefits observed with metformin use in diabetes patients , a role in modulating oxidative stress is imputable . Effects of metformin on markers of oxidative stress , antioxidant reserve , and HDL-c associated antioxidant enzymes were investigated . METHODS In a clinical trial setting ( Registered under Clinical Trials.gov Identifier no. NCT01521624 ) 99 medication-naïve , newly diagnosed type 2 diabetes patients were r and omly assigned to either metformin or lifestyle modification . AOPP , AGE , FRAP , activities of LCAT , and PON were measured at baseline and after 12-weeks . RESULTS Baseline values of the oxidative stress markers did not differ significantly between the two groups . In cases , after three months treatment , there was a significant reduction in AOPP ( 137.52 ± 25.59 , 118.45 ± 38.42 , p < 0.001 ) , and AGE ( 69.28 ± 4.58 , 64.31 ± 8.64 , p = 0.002 ) . FRAP and PON increased significantly ( 1060.67 ± 226.69 , 1347.80 ± 251.40 , p < 0.001 and 29.85 ± 23.18 , 37.86 ± 27.60 , p = 0.012 respectively ) . LCAT levels remained unchanged ( 45.23 ± 4.95 , 46.15 ± 6.28 , p = 0.439 ) . Comparing the two groups in a final multivariate model , AOPP , FRAP , and AGE levels changed more significantly in metformin compared with lifestyle modification alone ( p = 0.007 , p < 0.001 and p < 0.001 respectively ) . Escalation in LCAT or PON activities did not differ between the two groups ( p = 0.199 and 0.843 respectively ) . CONCLUSIONS Use of metformin is more effective in reducing oxidative stress compared with lifestyle modification alone Epidemiological studies have identified a robust association between type II diabetes mellitus and Alzheimer disease ( AD ) , and neurobiological studies have suggested the presence of central nervous system insulin resistance in individuals with AD . Given this association , we hypothesized that the central nervous system – penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and /or symptomatic therapy for AD , and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid ( CSF ) , neuroimaging , and cognitive biomarkers . Twenty nondiabetic subjects with mild cognitive impairment or mild dementia due to AD were r and omized to receive metformin then placebo for 8 weeks each or vice versa . CSF and neuroimaging ( Arterial Spin Label MRI ) data were collected for biomarker analyses , and cognitive testing was performed . Metformin was found to be safe , well-tolerated , and measureable in CSF at an average steady-state concentration of 95.6 ng/mL. Metformin was associated with improved executive functioning , and trends suggested improvement in learning/memory and attention . No significant changes in cerebral blood flow were observed , though post hoc completer analyses suggested an increase in orbitofrontal cerebral blood flow with metformin exposure . Further study of these findings is warranted RationalE pidemiological evidence suggests that individuals with diabetes mellitus are at greater risk of developing Alzheimer ’s disease , and controversy overwhelms the usefulness of the widely prescribed insulin-sensitizing drug , metformin , on cognition . Objectives Through the scopolamine-induced memory deficit model , we investigated metformin influence on cognitive dysfunction and explored underlying mechanisms . Methods Sixty adult male Wistar rats were r and omly assigned into 5 groups ( 12 rats each ) to receive either normal saline , scopolamine 1 mg/kg intraperitoneally once daily , scopolamine + oral metformin ( 100 mg/kg/day ) , scopolamine + oral metformin ( 300 mg/kg/day ) or scopolamine + oral rivastigmine ( 0.75 mg/kg/day ) for 14 days . Cognitive behaviours were tested using Morris water maze and passive avoidance tasks . Biochemically , brain oxidative ( malondialdehyde ) and inflammatory ( TNF-α ) markers , nitric oxide , Akt , phospho-Akt , phospho-tau and acetyl cholinesterase activity in hippocampal and cortical tissues were assessed . Results The lower dose of metformin ( 100 mg/kg ) ameliorated scopolamine-induced impaired performance in both Morris water maze and passive avoidance tasks , and was associated with significant reduction of inflammation and to a lesser extent oxidative stress versus rivastigmine . Given the role of total Akt in regulation of abnormal tau accumulation and degradation , our finding that metformin 100 decreased the elevated total Akt while increasing its phosphorylated form explains its beneficial modulatory effect on phosphorylated tau in both tissues , and could further clarify its protection against memory impairment . Conclusion Metformin , only in the average human antidiabetic dose , offers a protective effect against scopolamine-induced cognitive impairment , while no deleterious effect was observed with the higher dose , which may support a bonus effect of metformin in type 2 diabetic patients AIM Advanced research has radically changed both diagnosis and treatment of diabetes during last three decades ; a number of classes of oral antidiabetic agents are currently available for better glycemic control . Present study aims to evaluate the effect of metformin on different stress and inflammatory parameters in diabetic subjects . METHODS 208 type 2 diabetes patients were r and omly assigned for metformin and placebo . RESULTS Reactive oxygen species generation , advanced oxidation protein products ( 179.65±13.6 , 120.65±10.5 μmol/l ) and pentosidine ( 107±10.4 , 78±7.6 pmol/ml ) were found to be reduced by metformin treatment compared to placebo . On the other h and metformin administration enhanced total thiol and nitric oxide level ( p<0.05 ) . But nutrient level ( Mg(+2 ) , Ca(+2 ) ) in plasma was not altered by the treatment . Significant restoration of C reactive protein ( p<0.05 ) was noticed after metformin therapy . Metformin administration also improved Na(+)K(+)ATPase activity ( 0.28±0.08 , 0.41±0.07 μmol Pi/mg/h ) in erythrocyte membrane . CONCLUSIONS This study explores that metformin treatment restores the antioxidant status , enzymatic activity and inflammatory parameters in type 2 diabetic patients . Metformin therapy improves the status of oxidative and nitrosative stress altered in type 2 diabetes . This study unfolds the cardio protective role of metformin as an oral hypoglycemic agent Metformin ( Met ) is used to treat neurodegenerative disorders such as Alzheimer 's disease ( AD ) . Conversely , high-fat diets ( HFD ) have been shown to increase AD risk . In this study , we investigated the neuroprotective effects of Met on β-amyloid (Aβ)-induced impairments in hippocampal synaptic plasticity in AD model rats that were fed a HFD . In this study , 32 adult male Wistar rats were r and omly assigned to four groups : group I ( control group , regular diet ) ; group II ( HFD+vehicle ) ; group III ( HFD+Aβ ) ; or group IV ( Met+HFD+Aβ ) . Rats fed a HFD were injected with Aβ to induce AD , allowed to recover , and treated with Met for 8 weeks . The rats were then anesthetized with intraperitoneal injections of urethane and placed in a stereotaxic apparatus for surgery , electrode implantation , and field potential recording . In vivo electrophysiological recordings were then performed to measure population spike ( PS ) amplitude and excitatory postsynaptic potential ( EPSP ) slope in the hippocampal dentate gyrus . Long-term potentiation ( LTP ) was induced by high-frequency stimulation of the perforant pathway . Blood sample s were then collected to measure plasma levels of triglycerides , low-density lipoproteins , very low-density lipoprotein , and cholesterol . After induction of LTP , PS amplitude and EPSP slope were significantly decreased in Aβ-injected rats fed a HFD compared to vehicle-injected animals or untreated animals that were fed a normal diet . Met treatment of Aβ-injected rats significantly attenuated these decreases , suggesting that Met decreased the effects of Aβ on LTP . These findings suggest that Met treatment is neuroprotective against the detrimental effects of Aβ and HFDs on hippocampal synaptic plasticity Epilepsy is known as one of the most frequent neurological diseases , characterized by an enduring predisposition to generate epileptic seizures . Oxidative stress is believed to directly participate in pathways leading to neurodegeneration , which serves as the most important propagating factor , leading to the epileptic condition and cognitive decline . Moreover , there is also a growing body of evidence showing the disturbance of antioxidant system balance and consequently increased production of reactive species in patients with epilepsy . A meta- analysis , conducted in the present review confirms an association between epilepsy and increased lipid peroxidation . Furthermore , it was also shown that some of the antiepileptic drugs could potentially be responsible for additionally increased lipid peroxidation . Therefore , it is reasonable to propose that during the epileptic process neuroprotective treatment with antioxidants could lead to less sever structural damages , reduced epileptogenesis and milder cognitive deterioration . To evaluate this hypothesis studies investigating the neuroprotective therapeutic potential of various antioxidants in cells , animal seizure models and patients with epilepsy have been review ed . Numerous beneficial effects of antioxidants on oxidative stress markers and in some cases also neuroprotective effects were observed in animal seizure models . However , despite these encouraging results , till now only a few antioxidants have been further applied to patients with epilepsy as an add-on therapy . Based on the several positive findings in animal models , a strong need for more carefully planned , r and omized , double-blind , cross-over , placebo-controlled clinical trials for the evaluation of antioxidants efficacy in patients with epilepsy is warranted Background . In a recent r and omized controlled trial ( RCT ) in obese adolescents , 18 month-treatment with metformin versus placebo was reported to lead to stabilisation of the BMI . This study aim ed to compare the effect of metformin on BMI in obese adolescents in daily practice versus results obtained in an RCT . Methods . Obese adolescents treated off label with metformin in daily practice in an outpatient clinic with a follow-up of ≥18 months were identified . Anthropometric and biochemical data were collected at baseline and at 18 months . Patients treated with metformin for 18 months in an RCT were used for comparison . BMI was compared between the two groups . Results . Nineteen patients ( median age 14.3 ( interquartile range 11.7–15.7 ) years , BMI 31.3 ( 28.8–33.8 ) kg/m2 ) treated in daily practice were compared to 23 patients receiving metformin in the RCT ( age 13.6 ( 12.6–15.3 ) years , BMI 29.8 ( 28.1–34.5 ) kg/m2 ) . BMI change after 18 months was −0.36 ( −2.10–1.58 ) versus + 0.22 ( −2.87–1.27 ) kg/m2 for the two groups , respectively . In the multivariable model , BMI change was not statistically significantly different between the two groups ( p = 0.61 ) . Conclusion . Treatment with metformin in obese adolescents in daily practice result ed in a comparable change in BMI as observed in an RCT . This trial is registered with Clinical Trials.gov number : NCT01487993 Output:	In these studies , metformin showed to control seizure attacks by attenuating seizure generation , delaying the onset of epilepsy , reducing hippocampal neuronal loss , and averting cognitive impairments in both acute and chronic models of an epileptic seizure . The possible mechanisms for its antiseizure or antiepileptic action might be due to activation of AMPK , antiapoptotic , antineuroinflammatory , and antioxidant properties , which possibly modify disease progression through affecting epileptogenesis . Conclusion This review revealed the benefits of metformin in alleviating symptoms of epileptic seizure and modifying different cellular and molecular changes that affect the natural history of the disease in addition to its good safety profile
MS22064	*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 aim was to assess the effects of a Tai Chi – based program on health-related quality of life ( HR-QOL ) in people with elevated blood glucose or diabetes who were not on medication for glucose control . Method 41 participants were r and omly allocated to either a Tai Chi intervention group ( N = 20 ) or a usual medical-care control group ( N = 21 ) . The Tai Chi group involved 3 × 1.5 h supervised and group-based training sessions per week for 12 weeks . Indicators of HR-QOL were assessed by self-report survey immediately prior to and after the intervention . Results There were significant improvements in favor of the Tai Chi group for the SF36 subscales of physical functioning ( mean difference = 5.46 , 95 % CI = 1.35–9.57 , P < 0.05 ) , role physical ( mean difference = 18.60 , 95 % CI = 2.16–35.05 , P < 0.05 ) , bodily pain ( mean difference = 9.88 , 95 % CI = 2.06–17.69 , P < 0.05 ) and vitality ( mean difference = 9.96 , 95 % CI = 0.77–19.15 , P < 0.05 ) . Conclusions The findings show that this Tai Chi program improved indicators of HR-QOL including physical functioning , role physical , bodily pain and vitality in people with elevated blood glucose or diabetes who were not on diabetes medication OBJECTIVE This study aim ed to vali date the effects of a simplified , gentle form of t'ai chi chuan in patients with type 2 diabetes and who are also obese . DESIGN The study was design ed to be a r and omized controlled trial . SETTING This study was conducted in the department of metabolism and endocrinology at Cheng Ching Hospital , in Taichung , Taiwan . SUBJECTS The study subjects were hospital-based patients with type 2 diabetes and who were also obese ( ages 40 - 70 , with a body-mass index [ BMI ] range of 30 - 35 ) . The patients were r and omly selected and grouped into t'ai chi exercise ( TCE ) and conventional exercise ( CE ) groups . INTERVENTIONS After receiving instruction in t'ai chi , the TCE group and the CE group practice d three times per week , including one practice session lasting up to 1 hour , for 12 weeks . OUTCOME MEASURES Hemoglobin A1C , serum lipid profile , serum malondialdehyde , and C-reactive protein were measured . Physical parameters of body weight and BMI were also measured . Diet and medications of participants were monitored carefully while biochemical and physical conditions were analyzed . RESULTS After 12 weeks , hemoglobin A1C values of the TCE group did not decrease ( 8.9 ± 2.7 % : 8.3 ± 2.2 % ; p = 0.064 ) . BMI ( 33.5 ± 4.8 : 31.3 ± 4.2 ; p = 0.038 ) and serum lipids , including triglyceride ( 214 ± 47 mg/dL : 171 ± 34 mg/dL ; p = 0.012 ) and high density lipoprotein cholesterol ( 38 ± 16 mg/dL : 45 ± 18 mg/dL ; p = 0.023 ) had significant improvements . Serum malondialdehyde tended to decrease from baseline ( 2.66 ± 0.78 μmol/L : 2.31 ± 0.55 μmol/L ; p = 0.035 ) , and C-reactive protein also decreased ( 0.39 ± 0.19 mg/dL : 0.22 ± 0.15 mg/dL ; p = 0.014 ) . No improvements occurred in BMI , lipids , and oxidative stress profiles in the CE group . CONCLUSIONS T'ai chi exercise practice d by patients who are obese and have type 2 diabetes is efficient and safe when supervised by professionals and helps improve parameters , such as BMI , lipid profile , C-reactive protein , and malondialdehyde . Periodic monitoring of blood glucose , blood pressure , heart rate , breathing , physical fitness , and symptoms of discomfort of patients who exercise helps prevent injury . Simple , gentle TCE can be applied as regular daily exercise for patients with type 2 diabetes even when such patients are obese Older adults with type 2 diabetes have mobility impairment and reduced fitness . This study aim ed to test the efficacy of the “ Tai Chi for Diabetes ” form , developed to address health-related problems in diabetes , including mobility and physical function . Thirty-eight older adults with stable type 2 diabetes were r and omized to Tai Chi or sham exercise , twice a week for 16 weeks . Outcomes included gait , balance , musculoskeletal and cardiovascular fitness , self-reported activity and quality of life . Static and dynamic balance index ( −5.8 ± 14.2 ; p = 0.03 ) and maximal gait speed ( 6.2 ± 11.6 % ; p = 0.005 ) improved over time , with no significant group effects . There were no changes in other measures . Non-specific effects of exercise testing and /or study participation such as outcome expectation , socialization , the Hawthorne effect , or unmeasured changes in health status or compliance with medical treatment may underlie the modest improvements in gait and balance observed in this sham-exercise-controlled trial . This Tai Chi form , although developed specifically for diabetes , may not have been of sufficient intensity , frequency , or duration to effect positive changes in many aspects of physiology or health status relevant to older people with diabetes BACKGROUND Previous research has suggested that tai chi offers a therapeutic benefit in patients with fibromyalgia . METHODS We conducted a single-blind , r and omized trial of classic Yang-style tai chi as compared with a control intervention consisting of wellness education and stretching for the treatment of fibromyalgia ( defined by American College of Rheumatology 1990 criteria ) . Sessions lasted 60 minutes each and took place twice a week for 12 weeks for each of the study groups . The primary end point was a change in the Fibromyalgia Impact Question naire ( FIQ ) score ( ranging from 0 to 100 , with higher scores indicating more severe symptoms ) at the end of 12 weeks . Secondary end points included summary scores on the physical and mental components of the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) . All assessment s were repeated at 24 weeks to test the durability of the response . RESULTS Of the 66 r and omly assigned patients , the 33 in the tai chi group had clinical ly important improvements in the FIQ total score and quality of life . Mean ( + /-SD ) baseline and 12-week FIQ scores for the tai chi group were 62.9+/-15.5 and 35.1+/-18.8 , respectively , versus 68.0+/-11 and 58.6+/-17.6 , respectively , for the control group ( change from baseline in the tai chi group vs. change from baseline in the control group , -18.4 points ; P<0.001 ) . The corresponding SF-36 physical-component scores were 28.5+/-8.4 and 37.0+/-10.5 for the tai chi group versus 28.0+/-7.8 and 29.4+/-7.4 for the control group ( between-group difference , 7.1 points ; P=0.001 ) , and the mental-component scores were 42.6+/-12.2 and 50.3+/-10.2 for the tai chi group versus 37.8+/-10.5 and 39.4+/-11.9 for the control group ( between-group difference , 6.1 points ; P=0.03 ) . Improvements were maintained at 24 weeks ( between-group difference in the FIQ score , -18.3 points ; P<0.001 ) . No adverse events were observed . CONCLUSIONS Tai chi may be a useful treatment for fibromyalgia and merits long-term study in larger study population s. ( Funded by the National Center for Complementary and Alternative Medicine and others ; Clinical Trials.gov number , NCT00515008 . This study examined the effects of a 24-week Tai Chi intervention on physical function in individuals with peripheral neuropathy . Twenty-five women and men with peripheral neuropathy were recruited . Plantar pressure detection threshold was assessed with a 5.07 gauge monofilament . Functional gait was assessed by the 6-min walk and timed up- and -go tests . Isokinetic leg strength and st and ing balance was also assessed . Twenty-four consecutive weeks of modified , group-based Tai Chi practice was completed , with testing repeated every six weeks throughout . No adverse events were observed and attendance was 17 + /- 4 sessions per 6 weeks . After 6 weeks of Tai Chi , participants increased 6-min walk ( P < 0.0001 ) , timed up- and -go ( P < 0.0001 ) , and leg strength ( P < 0.01 ) performance . Continued improvement was observed in the timed up- and -go . Plantar sensation improved ( P = 0.003 ) following the Tai Chi intervention . Group-based Tai Chi is a safe , plausible , and effective intervention for those with PN BACKGROUND a large proportion of adults with type 2 diabetes remain sedentary despite evidence of benefits from exercise for type 2 diabetes . Simplified Yang Tai Chi has been shown in one study to have no effect on insulin sensitivity in older adults . However , a modified Tai Chi form , Tai Chi for Diabetes ( TCD ) has recently been composed , cl aim ing to improve diabetes control . METHODS subjects were r and omised to Tai Chi or sham exercise , twice a week for 16 weeks . Primary outcomes were insulin resistance 72 h post-exercise ( HOMA2-IR ) , and long-term glucose control ( HbA(1c ) ) . RESULTS thirty-eight subjects ( 65 + /- 7.8 years , 79 % women ) were enrolled . Baseline BMI was 32.2 + /- 6.3 kg/m(2 ) , 84 % had osteoarthritis , 76 % hypertension , and 34 % cardiac disease . There was one dropout , no adverse events , and median compliance was 100 (0 - 100)% . There were no effects of time or group assignment on insulin resistance or HbA(1c ) ( -0.07 + /- 0.4 % Tai Chi versus 0.12 + /- 0.3 % Sham ; P = 0.13 ) at 16 weeks . Improvement in HbA(1c ) was related to decreased body fat ( r = 0.484 , P = 0.004 ) and improvement in insulin resistance was related to decreased body fat ( r = 0.37 , P = 0.03 ) and central adiposity ( r = 0.38 , P = 0.02 ) , as well as increased fat-free mass ( r = -0.46 , P = 0.005 ) . CONCLUSIONS TCD did not improve glucose homeostasis or insulin sensitivity measured 72 h after the last bout of exercise . More intense forms of Tai Chi may be required to produce the body composition changes associated with metabolic benefits in type 2 diabetes OBJECTIVE To examine the effect of high-intensity progressive resistance training combined with moderate weight loss on glycemic control and body composition in older patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Sedentary , overweight men and women with type 2 diabetes , aged 60 - 80 years ( n = 36 ) , were r and omized to high-intensity progressive resistance training plus moderate weight loss ( RT & WL group ) or moderate weight loss plus a control program ( WL group ) . Clinical and laboratory measurements were assessed at 0 , 3 , and 6 months . RESULTS HbA(1c ) fell significantly more in RT & WL than WL at 3 months ( 0.6 + /- 0.7 vs. 0.07 + /- 0.8 % , P < 0.05 ) and 6 months ( 1.2 + /- 1.0 vs. 0.4 + /- 0.8 % , P < 0.05 ) . Similar reductions in body weight ( RT & WL 2.5 + /- 2.9 vs. WL 3.1 + /- 2.1 kg ) and fat mass ( RT & WL 2.4 + /- 2.7 vs. WL 2.7 + /- 2.5 kg ) were observed after 6 months . In contrast , lean body mass ( LBM ) increased in the RT & WL group ( 0.5 + /- 1.1 kg ) and decreased in the WL group ( 0.4 + /- 1.0 ) after 6 months ( P < 0.05 ) . There were no between-group differences for fasting glucose , insulin , serum lipids and lipoproteins , or resting blood pressure . CONCLUSIONS High-intensity progressive resistance training , in combination with moderate weight loss , was effective in improving glycemic control in older patients with type 2 diabetes . Additional benefits of improved muscular strength and LBM identify high-intensity resistance training as a feasible and effective component in the management program for older patients with type 2 diabetes OBJECT Output:	Conclusions Tai Chi seems to be effective in treating type 2 diabetes . Different training duration s and styles result in variable effectiveness . The evidence was insufficient to support whether long-term Tai Chi training was more effective
MS22065	*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: Ten patients with acute and 60 with chronic renal failure ( both groups having hyperkalaemia ) , were managed at Kenyatta National Hospital in the medical wards and Renal Unit between August , 1995 and January , 1996 . They were divided into seven different treatment groups , each consisting of ten patients . Treatment A glucose 25 g i.v . with insulin 10 units i.v . , treatment B 50 mmol of 8.4 % sodium bicarbonate infusion , treatment C 0.5 mg of salbutamol i.v . in 50mls 5 % dextrose , treatment D was a combination of treatments A and B , treatment E was a combination of treatment B and C , treatment F was a combination of treatments A and C while treatment G was a combination of treatments A and B and C. Serum potassium was measured , 30 minutes , 1 hour , 2 hours , 4 hours and 8 hours after treatment . Plasma glucose concentration was measured before treatment was given and 1 hour after in all patients . Electrocardiography was done before treatment on all patients and repeated 30 minutes and 1 hour after treatment for the patients with hyperkalaemic changes on the initial recording . All treatment modalities had satisfactory potassium lowering effects . Of the single therapeutic approaches , treatment A and C were equieffective , but better than treatment B ( P < 0.001 ) . Amongst the two regimen combinations , treatment D and F were more efficacious than treatment E and all the single therapeutic approaches ( P < 0.001 ) . Treatment G was the most efficacious in lowering serum potassium in this study . All treatment modalities had maximum serum potassium lowering effect at 1 - 2 hours . A fall in plasma glucose concentration was a notable feature of treatments A and D , but significant hypoglycaemia occurred in 20 % of patients receiving treatment A and in none on treatment D. The ECG changes of hyperkalaemia did not correlate with serum potassium levels . The normalisation of hyperkalaemic ECG alteration occurred within the first 30 minutes after treatment . In conclusion , combination therapies for hyperkalaemia appear to be more efficacious than single therapeutic approaches . Inclusion of salbutamol seems to protect against insulin induced hypoglycaemia . The maximum potassium lowering effect is observed 1 - 2 hours of administration of either agents . The potassium reducing effect remains significant compared to baseline values even after 8 hours . If dialysis can not be instituted early enough it seems reasonable to repeat treatment every 4 - 6 hours to sustain the effect . Repeated administration of glucose with insulin may not be safe because of the hypoglycaemic effect . Other single and combination therapies can theoretically be repeated regularly until dialysis is initiated although this requires further clinical evaluation Three groups of patients with acute or chronic renal failure ( GFR less than 5 ml/min ) and hyperkalaemia ( K+ greater than or equal to 6 mEq/l ) , similar in age , serum creatinine and pretreatment K+ . Group A ( n = 24 ) received salbutamol 0.5 mg i.v . in 15 min , group B ( n = 10 ) received glucose 40 g i.v . plus 10 units insulin i.v . in 15 min , and group C ( n = 10 ) received salbutamol 0.5 mg i.v . , glucose 40 g i.v . and insulin 10 units i.v . over a 15-min period . Serum potassium was measured at 30 , 60 , 180 and 360 min after administration of treatment . All treatments reduced serum potassium , maximal at 30 or 60 min , and ranging from -0.5 + /- 0.1 to -1.5 + /- 0.2 mEq/l ; patients in group C exhibited a significantly greater decrement in serum potassium , when compared to group B at 60 ( -1.5 + /- 0.2 vs -1 + /- 0.1 mEq/l , respectively ; P less than 0.01 ) and 180 min ( -1.2 + /- 0.2 vs -0.7 + /- 0.1 mEq/l , respectively ; P less than 0.05 ) . There were no significant differences between groups A and C. Patients from group C had moderate tachycardia and more prolonged hyperglycaemia than those from group B , but all treatments were well tolerated Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Hyperkalemia contributes to significant mortality and limits the use of cardioprotective and renoprotective renin – angiotensin – aldosterone blockers . Current therapies are poorly tolerated and not always effective . Here we conducted a phase 2 r and omized , double-blind , placebo-controlled dose-escalation study to assess safety and efficacy of ZS-9 . This oral selective cation exchanger that preferentially entraps potassium in the gastrointestinal tract was given to patients with stable Stage 3 chronic kidney disease and hyperkalemia ( 5.0 to 6.0 mEq/l ) during a 2-day period . Of 90 eligible patients with mean baseline serum potassium of 5.1 mEq/l , 30 were r and omized to placebo , 12–0.3 g , 24–3 g , or 24 to 10 g of ZS-9 three times daily for 2 days with regular meals . None withdrew and ZS-9 dose-dependently reduced serum potassium . The primary efficacy end point ( rate of serum potassium decline in the first 48 h ) was met with significance in the 3- and 10-g cohorts . From baseline , mean serum potassium was significantly decreased by 0.92±0.52 mEq/l at 38 h. Urinary potassium excretion significantly decreased with 10-g ZS-9 as compared to placebo at day 2 ( + 15.8 + /− 21.8 vs. + 8.9 + /− 22.9 mEq per 24h ) from placebo at day 2 . In this short-term study , no serious adverse events were reported ; only mild constipation in the 3-g dose group was possibly related to treatment . Thus , ZS-9 was well-tolerated in patients with stable chronic kidney disease and hyperkalemia leading to a rapid , sustained reduction in serum potassium Chronic kidney disease ( CKD ) in heart failure ( HF ) increases the risk of hyperkalaemia ( HK ) , limiting angiotensin‐converting enzyme inhibitor ( ACE‐I ) or angiotensin receptor blocker ( ARB ) use . Patiromer is a sodium‐free , non‐absorbed potassium binder approved for HK treatment . We retrospectively evaluated patiromer 's long‐term safety and efficacy in HF patients from AMETHYST‐DN BACKGROUND Hyperkalaemia is a commonly encountered problem in dialysis patients with end-stage renal disease ( ESRD ) . The aim of the present study was to assess the effect of fludrocortisone acetate ( FCA ) on reducing serum potassium levels in haemodialysis ( HD ) patients with hyperkalaemia . METHODS Prospect ively , 21 HD patients with hyperkalaemia were enrolled in this study . Patients were divided into two groups , including FCA ( 0.1 mg/d , n = 13 ) administration or no treatment ( control , n = 8) for 10 months . No changes in dialysis or drug regimens were made during this period . Result . There were no significant differences in the baseline characteristics and biochemical parameters between the two groups ( FCA therapy and control ) . At 10-months after FCA therapy , serum potassium levels were not significantly different between the treatment and control groups [ median value ( range ) : 5.2 ( 4.4 - 6.0 ) vs 5.8 ( 4.8 - 6.3 ) mEq/l , P = 0.121 ] . However , using the Wilcoxon signed ranks test , serum potassium levels were significantly lower at the end of the 10 month time period after FCA therapy compared with serum potassium levels of the pre-treatment period [ 5.2 ( 4.4 - 6.0 ) vs 6.1 ( 5.3 - 6.8 ) , P = 0.01 ] . The biochemical values , including sodium , chloride , protein , albumin , blood nitrogen , creatinine , interdialytic weight change and blood pressure , did not show significant difference in comparisons between the two groups and pre- and post-FCA therapy period . CONCLUSIONS FCA therapy appears to slightly decrease serum potassium value in hyperkalaemic HD patients . However , these results are insufficient to explain the effectiveness of FCA . Therefore , potentially large-scale studies with increased dose concentrations are needed to minimize the positive potassium balance in hyperkalaemic HD patients BACKGROUND AND OBJECTIVES Hyperkalemia affects up to 10 % of patients with CKD . Sodium polystyrene sulfonate has long been prescribed for this condition , although evidence is lacking on its efficacy for the treatment of mild hyperkalemia over several days . This study aim ed to evaluate the efficacy of sodium polystyrene sulfonate in the treatment of mild hyperkalemia . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In total , 33 out patients with CKD and mild hyperkalemia ( 5.0 - 5.9 mEq/L ) in a single teaching hospital were included in this double-blind r and omized clinical trial . We r and omly assigned these patients to receive either placebo or sodium polystyrene sulfonate of 30 g orally one time per day for 7 days . The primary outcome was the comparison between study groups of the mean difference of serum potassium levels between the day after the last dose of treatment and baseline . RESULTS The mean duration of treatment was 6.9 days . Sodium polystyrene sulfonate was superior to placebo in the reduction of serum potassium levels ( mean difference between groups , -1.04 mEq/L ; 95 % confidence interval , -1.37 to -0.71 ) . A higher proportion of patients in the sodium polystyrene sulfonate group attained normokalemia at the end of their treatment compared with those in the placebo group , but the difference did not reach statistical significance ( 73 % versus 38 % ; P=0.07 ) . There was a trend toward higher rates of electrolytic disturbances and an increase in gastrointestinal side effects in the group receiving sodium polystyrene sulfonate . CONCLUSIONS Sodium polystyrene sulfonate was superior to placebo in reducing serum potassium over 7 days in patients with mild hyperkalemia and CKD BACKGROUND Previous small uncontrolled studies suggested that fludrocortisone may significantly decrease serum potassium concentrations in hemodialysis patients , possibly through enhancement of colonic potassium secretion . The aim of this study is to evaluate the effect of oral fludrocortisone on serum potassium concentrations in hyperkalemic hemodialysis patients in an open-label r and omized controlled trial . METHODS Thirty-seven hemodialysis patients with predialysis hyperkalemia were r and omly allocated to administration of either oral fludrocortisone ( 0.1 mg/d ; n = 18 ) or no treatment ( control ; n = 19 ) for 3 months . The primary outcome measure was midweek predialysis serum potassium concentration , which was measured monthly during the trial . Prospect i ve power calculations indicated that the study had an 80 % probability of detecting a decrease in serum potassium levels of 0.7 mEq/L ( 0.7 mmol/L ) . RESULTS Baseline patient characteristics were similar , except for slightly longer total weekly dialysis hours in the fludrocortisone group ( 13.0 + /- 1.3 versus 12.1 + /- 1.0 ; P = 0.02 ) . At the end of the study period , no significant changes in serum potassium concentrations were observed between the fludrocortisone and control groups ( 4.8 + /- 0.5 versus 5.2 + /- 0.7 mEq/L [ mmol/L ] , respectively ; P = 0.10 ) . Similar results were obtained when changes in serum potassium levels over time were examined between the 2 arms by using repeated- measures analysis of variance , with or without adjustment for total weekly dialysis hours . Secondary outcomes , including predialysis mean arterial pressure , interdialytic weight gain , serum sodium level , and hospitalization for hyperkalemia , were not significantly different between groups . There were no observed adverse events . CONCLUSION Administering fludrocortisone to hyperkalemic hemodialysis patients is safe and well tolerated , but does not achieve clinical ly important decreases in serum potassium levels Background : Hyperkalemia is a common medical emergency that may result in serious cardiac arrhythmias . St and ard therapy with insulin plus glucose reliably lowers the serum potassium concentration ( [ K+ ] ) but carries the risk of hypoglycemia Output:	Sodium or calcium polystyrene sulfonate ( moderate confidence ) , sodium zirconium cyclosilicate ( moderate confidence ) , and insulin plus dextrose ( moderate confidence ) showed superior efficacy to , respectively , placebo , no treatment , placebo , and dextrose . Other therapies ( low confidence ) showed similar efficacy compared to active or inactive alternatives .
MS22066	*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 this report is to present the results of a double-blind drug trial in which an oral corticosteroid , methylprednisolone ( Medrol ) , was compared to oral cyanocobalamin ( vitamin B12 ) in patients with multiple sclerosis . This pair of drugs was chosen for comparison for several reasons . If multiple sclerosis is a peculiar auto-immune disease related to the myelin of the brain , then it might be reasonable to expect that corticosteroids may favorably alter the course of the disease.1A number of reports in the recent literature have dealt with clinical trials of corticosteroids and corticotropin ( ACTH ) in the treatment of patients with multiple sclerosis . Studies by Alex and er et al on corticotropin,2,3which did not include modern statistical design s such as r and omization of administration of placebo and corticotropin and a double-blind technique , have indicated a favorable response . Miller et al,4utilizing a modern statistical design , also concluded that The immunological effects of high‐dose methylprednisolone in attacks of multiple sclerosis and acute optic neuritis have only been examined in a few r and omized , controlled trials . We studied immunological changes in 50 patients with optic neuritis or multiple sclerosis who underwent lumbar puncture before and 1 week after completing a 15‐day course of oral high‐dose methylprednisolone treatment . Treatment result ed in a decrease in the concentration of myelin basic protein , a decrease in the serum concentration of immunoglobulin G ( IgG ) and intrathecal IgG synthesis , an increase in the cerebrospinal fluid concentration of transforming growth factor‐β1 , and changes in the expression of CD25 , CD26 , and human leukocyte antigen‐DR ( HLA‐DR ) on CD4 T‐cells . No effect was seen on the cerebrospinal fluid leucocyte count or the cerebrospinal fluid activity of matrix metalloproteinase‐9 ( MMP‐9 ) . The lack of a persistent effect on cerebrospinal fluid leucocyte recruitment and MMP‐9 activity , despite changes in IgG synthesis , T‐cell activation , and cytokine production , suggests that modulation of the function of inflammatory cells may contribute to the clinical efficacy of oral high‐dose methylprednisolone treatment in optic neuritis and multiple sclerosis 30 patients with acute exacerbations of multiple sclerosis were treated by ACTH , dexamethasone or methylprednisolone in a double-blind r and omized study . Clinical parameters were assessed ; cerebrospinal fluid and neurophysiological parameters ( visual- and brainstem-evoked potentials ) were evaluated at the beginning and at the end of treatment . Dexamethasone was more effective than ACTH and 6-methylprednisolone in shortening bout duration . Neither CSF nor neurophysiological parameters were significantly affected by therapy The efficacy of dexamethasone ( DX ) and methylprednisolone ( MP ) at high ( HD ) and low ( LD ) dose in acute multiple sclerosis ( MS ) relapses was evaluated by a double-blind trial in 31 patients followed for 1 year . DX and HDMP were similarly efficacious in promoting recovery , while LDMP was ineffective in the short-term outcome and was followed by an early clinical reactivation . The different outcomes seem to be related to different immunomodulating effects , mainly on cerebrospinal fluid ( CSF ) IgG synthesis and on peripheral blood and CSF CD4 + lymphocyte subsets We investigated the effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in patients with multiple sclerosis . Following a double blind trial design ed to compare the effect of oral and intravenous methylprednisolone treatment on promoting recovery from acute relapses of multiple sclerosis , 80 patients were followed for two years with six-monthly assessment s during which all subsequent relapses were recorded . The annual relapse rate was slightly higher in the oral compared with the intravenous methylprednisolone-treated patients ( 1.06 vs. 0.78 ) , but the adjusted difference between the two groups was not statistically significant ( 0.18 ; 95 % CI -0.19 to 0.55 , P=0.3 ) . The time to onset and the severity of the first relapse after treatment , the number of relapse free patients at the end of the follow-up period , and the severity of the relapses during the follow-up period were similar in the two groups . This trial did not show a statistically significant difference in relapse rate during the first two years following oral compared with intravenous methylprednisolone treatment Objective : To assess the efficacy of oral high-dose methylprednisolone in acute optic neuritis ( ON ) . Background : It has been determined that oral high-dose methylprednisolone is efficacious in attacks of MS . Methods : A total of 60 patients with symptoms and signs of ON with a duration of less than 4 weeks and a visual acuity of 0.7 or less were r and omized to treatment with placebo ( n = 30 ) or oral methylprednisolone ( n = 30 ; 500 mg daily for 5 days , with a 10-day tapering period ) . Visual function was measured and symptoms were scored on a visual analog scale ( VAS ) before treatment and after 1 , 3 , and 8 weeks . Primary efficacy measures were spatial vision and VAS scores the first 3 weeks ( analysis of variance with baseline values as the covariate ) , and changes in spatial vision and VAS scores after 8 weeks . A significance level of p < 0.0125 was employed . Results : The VAS score ( p = 0.008 ) but not the spatial visual function ( p = 0.03 ) differed in methylprednisolone- and placebo-treated patients during the first 3 weeks . After 8 weeks the improvement in VAS scores ( p = 0.8 ) and spatial visual function ( p = 0.5 ) was comparable with methylprednisolone- and placebo-treated patients . A post hoc subgroup analysis suggested that patients with more severe baseline visual deficit and patients treated early after onset of symptoms had a more pronounced response to treatment . The risk of a new demyelinating attack within 1 year was unaffected by treatment . No serious adverse events were seen . Conclusion : Oral high-dose methylprednisolone treatment improves recovery from ON at 1 and 3 weeks , but no effect could be demonstrated at 8 weeks or on subsequent attack frequency Objective : There is only limited evidence from adequately controlled clinical trials to support high-dose methylprednisolone therapy for attacks of multiple sclerosis ( MS ) and none supporting oral administration . We assessed the effect of oral high-dose methylprednisolone therapy in attacks of MS . Methods : Twenty-five patients with an attack of MS lasting less than 4 weeks were r and omized to placebo treatment . Twenty-six patients received oral methylprednisolone ( 500 mg once a day for 5 days with a 10-day tapering period ) . The patients received scores on the Scripps Neurological Rating Scale ( NRS ) and Kurtzke Exp and ed Disability Status Scale . The symptoms were scored on a visual analog scale ( VAS ) before treatment and after 1 , 3 , and 8 weeks of treatment . Primary efficacy measures were NRS and VAS scores in the first 3 weeks and changes in NRS score and answers to an efficacy question naire administered after 8 weeks of treatment . Results : Changes in NRS scores among methylprednisolone- and placebo-treated patients differed significantly in the first 3 weeks and after 8 weeks(p = 0.005 and p = 0.0007 ) . VAS scores the first 3 weeks and treatment efficacy after 8 weeks also favored a beneficial effect of methylprednisolone treatment ( p = 0.02 and p = 0.05 ) . After 1 , 3 , and 8 weeks , 4 % , 24 % , and 32 % in the placebo group and 31 % , 54 % , and 65 % in the methylprednisolone group had improved one point on the Exp and ed Disability Status Scale score ( all p < 0.05 ) . No serious adverse events were seen . Conclusion : Oral high-dose methylprednisolone is recommended for managing attacks of MS To compare the efficacy of high-dose intravenous methylprednisolone with intramuscular ACTH in the treatment of acute relapse in multiple sclerosis , we undertook a double-blind , r and omized , controlled study involving 61 patients . There was a marked improvement in both groups in the course of the study , but no difference between them in either the rate of recovery or the final outcome . High-dose IV methylprednisolone is a safe alternative to ACTH in the management of acute relapse in MS Oral prednisone 1might be a convenient , inexpensive alternative to IV methylprednisolone ( IVMP ) if the bioequivalent dose was known . We compared the total amount of steroid absorbed after 1250 mg oral prednisone vs 1 gram IVMP in 16 patients with multiple sclerosis ( MS ) . At 24 hours , the mean area under the concentration-time curve ( AUC ) , the main component of bioavailability , did not differ between groups ( p = 0.122 ) . This suggests that the amount of absorbed corticosteroid is similar after either steroid at these doses BACKGROUND An intravenous rather than oral course of methylprednisolone is often prescribed for treating acute relapses in multiple sclerosis ( MS ) despite the lack of evidence to support this route of administration . Our double-blind placebo-controlled r and omised trial was design ed to compare the efficacy of commonly used intravenous and oral steroid regimens in promoting recovery from acute relapses in MS . METHODS 42 patients with clinical ly definite relapse in MS received oral , and 38 intravenous , methylprednisolone . Clinical measurements at entry and at 1 week , 4 weeks , 12 weeks , and 24 weeks included Kurtzke 's exp and ed disability status scale ( EDSS ) , Hauser 's Ambulatory Index , and an arm-function index . The primary outcome criterion was a difference between the two treatment groups of one or more EDSS grade s at 4 weeks . FINDINGS There were no significant differences between the two groups at any stage of the study in any measurement taken : the mean difference in EDSS at 4 weeks ( adjusted for baseline level ) was 0.07 grade s more in those taking oral steroids ( 95 % CI -0.46 to 0.60 ) . The most optimistic outcome for intravenous therapy is an average benefit of less than half a grade improvement on EDSS over oral treatment . INTERPRETATION Since our study did not show any clear advantage of the intravenous regime we conclude that it is preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for reasons of patient convenience , safety , and cost Many patients with multiple sclerosis ( MS ) are currently receiving treatment with interferon (IFN)–β . Early identification of nonresponder patients is crucial to try different therapeutic approaches . We investigated various criteria of treatment response to assess which criterion better identifies patients with a poor response We investigated in multiple sclerosis the difference between two commonly used oral and intravenous steroid regimens on the level of adhesion molecule expression on blood T lymphocytes , the distribution of circulating T cell subsets , and the concentration of serum tumour necrosis factor alpha . Venous blood sample s were collected from a cohort of 22 patients with acute relapses who were participating in a r and omised trial comparing intravenous methylprednisolone 1000 mg daily for 3 days with oral methylprednisolone 48 mg daily for one week , 24 mg daily for one week , and finally 12 mg daily for one week . There was a similar significant reduction of T cell LFA-1 surface expression and serum TNF alpha concentrations after 4 days of treatment with each regimen . There was no change in other lymphocyte adhesion molecules expression ( ICAM-1 , LFA-3 or CD2 ) at day 4 , although LFA-3 and CD2 expression was moderately decreased at day 28 and day 90 respectively ; nor was there any change in the distribution of lymphocyte subsets ( CD4 , CD8 , and CD45RA , CD45RO ) , although a small decrease in CD45RO circulatory T cells was noted at day 28 . This study suggests that some of the beneficial effects of glucocorticosteroids may be related to the inhibition of lymphocyte adhesion as well as the modulation of proinflammatory cytokines The objective of this study was to investigate the feasibility of treating relapses of multiple sclerosis ( MS ) at home with oral dexamethasone . Twenty-five out of 28 consecutive patients with MS who presented with a relapse of less than 2 weeks ' duration were treated on an open basis with oral dexamethasone 16 mg per day ( four divided doses ) for 5 consecutive days . After one week , the exp and ed disability status scale ( EDSS ) had improved by one or more grade s in 88 % ( 22 patients ) and after 4 weeks in 92 % ( 23 patients ) . Treatment was well tolerated . We conclude that a course of oral dexamethasone 16 mg per day shortens the duration of an exacerbation in MS in a similar way as seen after high dose i.v . methylprednisolone . Although a r and omized study is needed to test this treatment regimen against i.v . high do Output:	The analysis of the five included trials comparing intravenous versus oral steroid therapy for MS relapses do not demonstrate any significant differences in clinical ( benefits and adverse events ) , radiological or pharmacological outcomes . Based on the evidence , oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy in the treatment of MS relapses
MS22067	*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 : As a result of recent publications , we hypothesized that period of 8 weeks after initiation of treatment is a useful l and mark point for cytotoxic agents for advanced non-small cell lung cancer ( NSCLC ) . To test this hypothesis , we conducted l and mark analyses with clinical trials employing cytotoxic agents . Our goal was to assess the proper design of clinical trials with cytotoxic agents for NSCLC for maximizing patients ’ benefit . Methods : We conducted l and mark analyses of a phase II study of pemetrexed in locally advanced or metastatic NSCLC and a phase III study of Four-Arm Cooperative Study for advanced NSCLC . A total of 806 patients who received chemotherapy ( pemetrexed , cisplatin and irinotecan , paclitaxel and carboplatin , cisplatin and gemcitabine , cisplatin and vinorelbine ) were included in this assessment . Results : Tumor-shrinkage rate at 8 weeks was significantly associated with longer survival in the study with pemetrexed ( p = 0.043 ) , whereas tumor-shrinkage rate at 4 weeks did not correlated with survival ( p = 0.139 ) . Similarly , using the Four-Arm Cooperative Study data , the optimal l and mark point was 8 weeks ( p = 0.002 ) , not 4 weeks ( p = 0.190 ) . Conclusion : The l and mark point for NSCLC was 8 weeks with all cytotoxic agents in our analysis when the therapy was given as a frontline or subsequent therapy . Our result suggests the concept of a disease-specific l and mark point , which may lead to a change of phase II/III clinical study design to evaluate cytotoxic agents and clinical investigators , and their sponsors may consider an early look to assess the efficacy of cytotoxic agents for NSCLC Background : Bevacizumab , the anti-vascular endothelial growth factor agent , provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer . We report the final overall survival ( OS ) analysis from the phase III AVAiL trial . Patients and methods : Patients ( n = 1043 ) received cisplatin 80 mg/m2 and gemcitabine 1250 mg/m2 for up to six cycles plus bevacizumab 7.5 mg/kg ( n = 345 ) , bevacizumab 15 mg/kg ( n = 351 ) or placebo ( n = 347 ) every 3 weeks until progression . Primary end point was progression-free survival ( PFS ) ; OS was a secondary end point . Results : Significant PFS prolongation with bevacizumab compared with placebo was maintained with longer follow-up { hazard ratio ( HR ) [ 95 % confidence interval ( CI ) ] 0.75 ( 0.64–0.87 ) , P = 0.0003 and 0.85 ( 0.73–1.00 ) , P = 0.0456 } for the 7.5 and 15 mg/kg groups , respectively . Median OS was > 13 months in all treatment groups ; nevertheless , OS was not significantly increased with bevacizumab [ HR ( 95 % CI ) 0.93 ( 0.78–1.11 ) , P = 0.420 and 1.03 ( 0.86–1.23 ) , P = 0.761 ] for the 7.5 and 15 mg/kg groups , respectively , versus placebo . Most patients ( ∼62 % ) received multiple lines of post study treatment . Up date d safety results are consistent with those previously reported . Conclusions : Final analysis of AVAiL confirms the efficacy of bevacizumab when combined with cisplatin – gemcitabine . The PFS benefit did not translate into a significant OS benefit , possibly due to high use of efficacious second-line therapies Categorizations of best response observed at week 8 ( between week 3 and 14 ) of first-line treatment in two studies of bevacizumab plus chemotherapy in Western ( 878 patients ) and Chinese ( 198 patients ) patients with non-small cell lung cancer were assessed together with baseline prognostic factors in multivariate parametric models to predict overall survival ( OS ) and progression free survival ( PFS ) . Predictive performances of the models were assessed by simulating multiple replicates of the studies . Disease control rate ( DCR ) was the best response categorization to predict OS and PFS . In the OS model , DCR fully captured bevacizumab effect . For PFS , DCR did not fully capture bevacizumab treatment effect . The models adequately predicted OS and PFS distributions in each arm as well as bevacizumab hazard ratio ( HR ) for OS and PFS , for example , in Western patients ( model prediction [ 95 % prediction interval ] : 0.84 [ 0.71 - 0.98 ] vs. observed : 0.77 for OS and 0.59 [ 0.49 - 0.72 ] vs. observed : 0.58 for PFS ) . Covariates in the models captured endpoint differences seen in Chinese patients . There was no impact of Chinese ethnicity on the DCR relationship to OS or PFS . DCR predicted OS benefit with bevacizumab in first-line NSCLC patients . Western data can be used to inform design of studies in Chinese patients PURPOSE A traditional end point for colon adjuvant clinical trials is overall survival ( OS ) , with 5 years demonstrating adequate follow-up . A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice . METHODS Individual patient data were pooled from 18 r and omized phase III colon cancer adjuvant clinical trials . Trials included 43 arms , with a pooled sample size of 20,898 patients . The primary hypothesis was that disease-free survival ( DFS ) , with 3 years of follow-up , is an appropriate primary end point to replace OS with 5 years of follow-up . RESULTS The recurrence rates for years 1 through 5 were 12 % , 14 % , 8 % , 5 % , and 3 % , respectively . Median time from recurrence to death was 12 months . Eighty percent of recurrences were in the first 3 years ; 91 % of patients with recurrence by 3 years died before 5 years . Correlation between 3-year DFS and 5-year OS was 0.89 . Comparing control versus experimental arms within each trial , the correlation between hazard ratios for DFS and OS was 0.92 . Within-trial log-rank testing using both DFS and OS provided the same conclusion in 23 ( 92 % ) of 25 cases . Formal measures of surrogacy were satisfied . CONCLUSION In patients treated on phase III adjuvant colon clinical trials , DFS and OS are highly correlated , both within patients and across trials . These results suggest that DFS after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens , although marginally significant DFS improvements may not translate into significant OS benefits Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions BACKGROUND Whether progression-free survival ( PFS ) or overall survival ( OS ) is the more appropriate endpoint in clinical trials of metastatic cancer is controversial . In some disease and treatment setting s , an improvement in PFS does not result in an improved OS . METHODS We partitioned OS into two parts and expressed it as the sum of PFS and survival postprogression ( SPP ) . We simulated r and omized clinical trials with two arms that had respective medians for PFS of 6 and 9 months . We assumed no treatment difference in median SPP . We found the probability of a statistically significant benefit in OS for various median SPP and observed P values for PFS . We compared the sample sizes required for PFS vs OS for various median SPP . We compare our results with the literature regarding surrogacy of PFS for OS by use of the correlation between hazard ratios for PFS and OS . All statistical tests were two-sided . RESULTS For a trial with observed P value for improvement in PFS of .001 , there was a greater than 90 % probability for statistical significance in OS if median SPP was 2 months but less than 20 % if median SPP was 24 months . For a trial requiring 280 patients to detect a 3-month difference in PFS , 350 and 2440 patients , respectively , were required to have the same power for detecting a real difference in OS that is carried over from the 3-month benefit in PFS when the median SPP was 2 and 24 months . CONCLUSIONS Addressing SPP is important in underst and ing treatment effects . For clinical trials with a PFS benefit , lack of statistical significance in OS does not imply lack of improvement in OS , especially for diseases with long median SPP . Although there may be no treatment effect on SPP , its variability so dilutes the OS comparison that statistical significance is likely lost . OS is a reasonable primary endpoint when median SPP is short but is too high a bar when median SPP is long , such as longer than 12 months BACKGROUND Many more phase II studies have favorable outcomes than the subsequent phase III trials . We used historical data from phase II and phase III studies for patients with extensive-stage small-cell lung cancer ( SCLC ) to generate a statistical model to provide assistance in selecting chemotherapy regimens from phase II studies for subsequent use in phase III r and omized studies . METHODS Information from 21 phase III trials for patients with extensive-stage SCLC initiated during the period from 1972 through 1990 was review ed to identify those that were preceded by phase II studies of the same regimen . We used data from all the trial pairs to develop a statistical model in which the number of patients , the median survival of patients , and the number of deaths observed in the phase II trial are used to estimate the statistical power of the subsequent phase III trial . All statistical tests were two-sided . RESULTS Nine phase II studies were identified that preceded phase III trials of the same regimen . The regimens from two phase II studies with the greatest expected power in the phase III trial ( 0 . 62 and 0.58 ) both demonstrated significantly prolonged survival when compared with st and ard treatment in subsequent phase III trials ( P<. 001 and P = .002 , respectively ) . The regimens from six of the other phase II studies , for which the median power expected in the phase III trial was 0.28 ( range , 0.19 - 0.52 ) , showed no difference when compared with st and ard treatment in a phase III trial . CONCLUSIONS Phase II studies for particular regimens that have an expected power of greater than 0.55 provide a reasonable basis for proceeding with a phase III trial This paper is an overview of the new response evaluation criteria in solid tumours : revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents Several challenging and often controversial issues arise in oncology trials with the use of the end point progression-free survival ( PFS ) , defined to be the time to detection of progressive disease or death . While this end point does not directly measure how a patient feels , functions , or survives , it does provide insights about whether an intervention affects the tumor burden process , the intended mechanism through which it is hoped that most anticancer agents will provide benefit . However , simply achieving statistically significant effects on PFS is insufficient to obtaining reliable evidence of important clinical benefit , and even is insufficient to justifying the conclusion that the experimental intervention is " reasonably likely to provide clinical benefit . " The magnitude of the effect on PFS in addition to the statistical strength of evidence is of great importance in interpreting the reliability of the evidence regarding clinical efficacy . PFS has several important properties , including being a direct measure of the effect of treatment on the tumor burden process , being sensitive to cytostatic as well as cytotoxic mechanisms of interventions , and incorporating the clinical ly relevant event of death , increasing its sensitivity to influential harmful mechanisms and avoiding substantial bias that arises when deaths are censored . To obtain reliable evidence about the effect of an intervention on PFS and patient survival , Output:	ORrr , followed by HRpfs , had the strongest association with HRos at the trial level . However , these measures were not strong enough to replace OS
MS22068	*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 : Severe traumatic brain injury ( TBI ) in children is associated with substantial long-term morbidity and mortality . Currently , there are no successful neuroprotective/neuroreparative treatments for TBI . Numerous pre clinical studies suggest that bone marrow-derived mononuclear cells ( BMMNCs ) , their derivative cells ( marrow stromal cells ) , or similar cells ( umbilical cord blood cells ) offer neuroprotection . OBJECTIVE : To determine whether autologous BMMNCs are a safe treatment for severe TBI in children . METHODS : Ten children aged 5 to 14 years with a postresuscitation Glasgow Coma Scale of 5 to 8 were treated with 6 × 106 autologous BMMNCs/kg body weight delivered intravenously within 48 hours after TBI . To determine the safety of the procedure , systemic and cerebral hemodynamics were monitored during bone marrow harvest ; infusion-related toxicity was determined by pediatric logistic organ dysfunction ( PELOD ) scores , hepatic enzymes , Murray lung injury scores , and renal function . Conventional magnetic resonance imaging ( cMRI ) data were obtained at 1 and 6 months postinjury , as were neuropsychological and functional outcome measures . RESULTS : All patients survived . There were no episodes of harvest-related depression of systemic or cerebral hemodynamics . There was no detectable infusion-related toxicity as determined by PELOD score , hepatic enzymes , Murray lung injury scores , or renal function . cMRI imaging comparing gray matter , white matter , and CSF volumes showed no reduction from 1 to 6 months postinjury . Dichotomized Glasgow Outcome Score at 6 months showed 70 % with good outcomes and 30 % with moderate to severe disability . CONCLUSION : Bone marrow harvest and intravenous mononuclear cell infusion as treatment for severe TBI in children is logistically feasible and safe OBJECTIVE We sought to assess the safety and therapeutic efficacy of autologous human bone marrow derived mononuclear cell transplantation on spinal cord injury in a phase I/II , nonr and omized , open-label study , conducted on 297 patients . MATERIAL S AND METHODS We transplanted unmanipulated bone marrow mononuclear cells through a lumbar puncture , and assessed the outcome using st and ard neurologic investigations and American Spinal Injury Association ( ASIA ) protocol , and with respect to safety , therapeutic time window , CD34-/+ cell count , and influence on sex and age . RESULTS No serious complications or adverse events were reported , except for minor reversible complaints . Sensory and motor improvements occurred in 32.6 % of patients , and the time elapsed between the injury and the treatment considerably influenced the outcome of the therapy . The CD34-/+ cell count determined the state of improvement , or no improvement , but not the degree of improvement . No correlation was found between level of injury and improvement , and age and sex had no role in the outcome of the cellular therapy . CONCLUSION Transplant of autologous human bone marrow derived mononuclear cells through a lumbar puncture is safe , and one-third of spinal cord injury patients show perceptible improvements in the neurologic status . The time elapsed between injury and therapy and the number of CD34-/+ cells injected influenced the outcome of the therapy To assess the safety and therapeutic efficacy of autologous human bone marrow cell ( BMC ) transplantation and the administration of granulocyte macrophage-colony stimulating factor ( GM-CSF ) , a phase I/II open-label and nonr and omized study was conducted on 35 complete spinal cord injury patients . The BMC s were transplanted by injection into the surrounding area of the spinal cord injury site within 14 injury days ( n = 17 ) , between 14 days and 8 weeks ( n = 6 ) , and at more than 8 weeks ( n = 12 ) after injury . In the control group , all patients ( n = 13 ) were treated only with conventional decompression and fusion surgery without BMC transplantation . The patients underwent preoperative and follow-up neurological assessment using the American Spinal Injury Association Impairment Scale ( AIS ) , electrophysiological monitoring , and magnetic resonance imaging ( MRI ) . The mean follow-up period was 10.4 months after injury . At 4 months , the MRI analysis showed the enlargement of spinal cords and the small enhancement of the cell implantation sites , which were not any adverse lesions such as malignant transformation , hemorrhage , new cysts , or infections . Furthermore , the BMC transplantation and GM-CSF administration were not associated with any serious adverse clinical events increasing morbidities . The AIS grade increased in 30.4 % of the acute and subacute treated patients ( AIS A to B or C ) , whereas no significant improvement was observed in the chronic treatment group . Increasing neuropathic pain during the treatment and tumor formation at the site of transplantation are still remaining to be investigated . Long-term and large scale multicenter clinical study is required to determine its precise therapeutic effect . Disclosure of potential conflicts of interest is found at the end of this article BACKGROUND AIMS Spinal cord injury is common among young subjects involved in motor vehicle accidents . Mechanisms and attempts to reverse post-traumatic pathophysiologic consequences are still being investigated . Unfortunately no effective and well-established treatment modality has been developed so far . The regeneration capability of the human nervous system following an injury is highly limited . METHODS The study involved four patients ( two male , two female ) who had suffered spinal cord injury as a result of various types of trauma . On neurologic examination , all the patients were determined to be in American Spinal Injury Association ( ASIA ) grade A. All patients were treated with decompression , stabilization and fusion for vertebral trauma anteriorly , as well as intralesional implantation of cellular bone marrow concentrates using a posterior approach 1 month after the first operation . The patients were then treated and followed-up in the physical rehabilitation clinic . RESULTS At the end of the post-operative 1-year follow-up , two of the patients were classified as ASIA C while one was classified as ASIA B. One patient showed no neurologic change ; none of the patients suffered from any complications or adverse effects as a result of intralesional application of bone marrow cells . CONCLUSIONS The results of this experimental study show the potential contribution of intralesional implantation of bone marrow to neuronal regeneration in the injured spinal cord , with neuronal changes . In light of the results of this experimental study , the potential for regenerative treatment in injuries of the human spinal cord is no longer a speculation but an observation Output:	Data from published trials revealed that encouraging results were achieved by autologous BMMNCs for the treatment of spinal cord injury .
MS22069	*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 relative efficacy of streptokinase and tissue plasminogen activator and the roles of intravenous as compared with subcutaneous heparin as adjunctive therapy in acute myocardial infa rct ion are unresolved questions . The current trial was design ed to compare new , aggressive thrombolytic strategies with st and ard thrombolytic regimens in the treatment of acute myocardial infa rct ion . Our hypothesis was that newer thrombolytic strategies that produce earlier and sustained reperfusion would improve survival . METHODS In 15 countries and 1081 hospitals , 41,021 patients with evolving myocardial infa rct ion were r and omly assigned to four different thrombolytic strategies , consisting of the use of streptokinase and subcutaneous heparin , streptokinase and intravenous heparin , accelerated tissue plasminogen activator ( t-PA ) and intravenous heparin , or a combination of streptokinase plus t-PA with intravenous heparin . ( " Accelerated " refers to the administration of t-PA over a period of 1 1/2 hours -- with two thirds of the dose given in the first 30 minutes -- rather than the conventional period of 3 hours . ) The primary end point was 30-day mortality . RESULTS The mortality rates in the four treatment groups were as follows : streptokinase and subcutaneous heparin , 7.2 percent ; streptokinase and intravenous heparin , 7.4 percent ; accelerated t-PA and intravenous heparin , 6.3 percent , and the combination of both thrombolytic agents with intravenous heparin , 7.0 percent . This represented a 14 percent reduction ( 95 percent confidence interval , 5.9 to 21.3 percent ) in mortality for accelerated t-PA as compared with the two streptokinase-only strategies ( P = 0.001 ) . The rates of hemorrhagic stroke were 0.49 percent , 0.54 percent , 0.72 percent , and 0.94 percent in the four groups , respectively , which represented a significant excess of hemorrhagic strokes for accelerated t-PA ( P = 0.03 ) and for the combination strategy ( P < 0.001 ) , as compared with streptokinase only . A combined end point of death or disabling stroke was significantly lower in the accelerated-tPA group than in the streptokinase-only groups ( 6.9 percent vs. 7.8 percent , P = 0.006 ) . CONCLUSIONS The findings of this large-scale trial indicate that accelerated t-PA given with intravenous heparin provides a survival benefit over previous st and ard thrombolytic regimens IMPORTANCE Data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of patients with minor stroke or transient ischemic attack treated with clopidogrel . OBJECTIVE To estimate the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack . DESIGN , SETTING , AND PARTICIPANTS Three CYP2C19 major alleles ( * 2 , * 3 , * 17 ) were genotyped among 2933 Chinese patients from 73 sites who were enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events ( CHANCE ) r and omized trial conducted from January 2 , 2010 , to March 20 , 2012 . INTERVENTIONS Patients with acute minor ischemic stroke or transient ischemic attack in the trial were r and omized to treatment with clopidogrel combined with aspirin or to aspirin alone . MAIN OUTCOMES AND MEASURES The primary efficacy outcome was new stroke . The secondary efficacy outcome was a composite of new composite vascular events ( ischemic stroke , hemorrhagic stroke , myocardial infa rct ion , or vascular death ) . Bleeding was the safety outcome . RESULTS Among 2933 patients , 1948 ( 66.4 % ) were men , with a mean age of 62.4 years . Overall , 1207 patients ( 41.2 % ) were noncarriers and 1726 patients ( 58.8 % ) were carriers of loss-of-function alleles ( * 2 , * 3 ) . After day 90 follow-up , clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles ( P = .02 for interaction ; events among noncarriers , 41 [ 6.7 % ] with clopidogrel-aspirin vs 74 [ 12.4 % ] with aspirin ; hazard ratio [ HR ] , 0.51 [ 95 % CI , 0.35 - 0.75 ] ; events among carriers , 80 [ 9.4 % ] with clopidogrel-aspirin vs 94 [ 10.8 % ] with aspirin ; HR , 0.93 [ 95 % CI , 0.69 to 1.26 ] ) . Similar results were observed for the secondary composite efficacy outcome ( noncarriers : 41 [ 6.7 % ] with clopidogrel-aspirin vs 75 [ 12.5 % ] with aspirin ; HR , 0.50 [ 95 % CI , 0.34 - 0.74 ] ; carriers : 80 [ 9.4 % ] with clopidogrel-aspirin vs 95 [ 10.9 % ] with aspirin ; HR , 0.92 [ 95 % CI , 0.68 - 1.24 ] ; P = .02 for interaction ) . The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles ( 2.3 % for carriers and 2.5 % for noncarriers in the clopidogrel-aspirin group vs 1.4 % for carriers and 1.7 % for noncarriers in the aspirin only group ; P = .78 for interaction ) . CONCLUSIONS AND RELEVANCE Among patients with minor ischemic stroke or transient ischemic attack , the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles . These findings support a role of CYP2C19 genotype in the efficacy of this treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00979589 OBJECT Symptomatic intracranial atherosclerotic disease ( ICAD ) has a high risk of recurrent stroke . Genetic polymorphisms in CYP2C19 and CES1 are associated with adverse outcomes in cardiovascular patients , but have not been studied in ICAD . The authors studied CYP2C19 and CES1 single-nucleotide polymorphisms ( SNPs ) in symptomatic ICAD patients . METHODS Genotype testing for CYP2C19 * 2 , ()3 , ()8 , ()17 and CES1 G143E was performed on 188 adult symptomatic ICAD patients from 3 medical centers who were medically managed with clopidogrel and aspirin . Testing was performed prospect ively at 1 center , and retrospectively from a DNA sample biorepository at 2 centers . Multiple logistic regression and Cox regression analysis were performed to assess the association of these SNPs with the primary endpoint , which was a composite of transient ischemic attack ( TIA ) , stroke , myocardial infa rct ion , or death within 12 months . RESULTS The primary endpoint occurred in 14.9 % of the 188 cases . In multiple logistic regression analysis , the presence of the CYP2C19 loss of function ( LOF ) alleles 2 , * 3 , and * 8 in the medically managed patients was associated with lower odds of primary endpoint compared with wild-type homozygotes ( odds ratio [ OR ] 0.13 , 95 % CI 0.03 - 0.62 , p = 0.0101 ) . Cox regression analysis demonstrated the CYP2C19 LOF carriers had a lower risk for the primary endpoint , with hazard ratio ( HR ) of 0.27 ( 95 % CI 0.08 - 0.95 ) , p = 0.041 . A sensitivity analysis of a secondary composite endpoint of TIA , stroke , or death demonstrated a significant trend in multiple logistic regression analysis of CYP2C19 variants , with lower odds of secondary endpoint in patients carrying at least 1 LOF allele ( * 2 , * 3 , * 8) than in wild-type homozygotes ( OR 0.27 , 95 % CI 0.06 - 1.16 , p = 0.078 ) . Cox regression analysis demonstrated that the carriers of CYP2C19 LOF alleles had a lower risk forthe secondary composite endpoint ( HR 0.22 , 95 % CI 0.05 - 1.04 , p = 0.056 ) . CONCLUSIONS This is the first study examining genetic variants and their effects in symptomatic ICAD . Variant alleles of CYP2C19 ( * 2 , * 3 , * 8) were associated with lower odds of the primary and secondary composite endpoints . However , the direction of the association was opposite of what is expected based on this SNP . This may reflect an incomplete underst and ing of this genetic variation and its effect in symptomatic ICAD and warrants further investigations BACKGROUND Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events . Aspirin and ticlopidine have been shown to be effective , but both have potentially serious adverse effects . Clopidogrel , a new thienopyridine derivative similar to ticlopidine , is an inhibitor of platelet aggregation induced by adenosine diphosphate . METHODS CAPRIE was a r and omised , blinded , international trial design ed to assess the relative efficacy of clopidogrel ( 75 mg once daily ) and aspirin ( 325 mg once daily ) in reducing the risk of a composite outcome cluster of ischaemic stroke , myocardial infa rct ion , or vascular death ; their relative safety was also assessed . The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke , recent myocardial infa rct ion , or symptomatic peripheral arterial disease . Patients were followed for 1 to 3 years . FINDINGS 19,185 patients , with more than 6300 in each of the clinical subgroups , were recruited over 3 years , with a mean follow-up of 1.91 years . There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32 % risk of ischaemic stroke , myocardial infa rct ion , or vascular death compared with 5.83 % with aspirin . These rates reflect a statistically significant ( p = 0.043 ) relative-risk reduction of 8.7 % in favour of clopidogrel ( 95 % Cl 0.3 - 16.5 ) . Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4 % . There were no major differences in terms of safety . Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash ( 0.26 % vs 0.10 % ) , diarrhoea ( 0.23 % vs 0.11 % ) , upper gastrointestinal discomfort ( 0.97 % vs 1.22 % ) , intracranial haemorrhage ( 0.33 % vs 0.47 % ) , and gastrointestinal haemorrhage ( 0.52 % vs 0.72 % ) , respectively . There were ten ( 0.10 % ) patients in the clopidogrel group with significant reductions in neutrophils ( < 1.2 x 10(9)/L ) and 16 ( 0.17 % ) in the aspirin group . INTERPRETATION Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke , myocardial infa rct ion , or vascular death . The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin BACKGROUND Stroke is common during the first few weeks after a transient ischemic attack ( TIA ) or minor ischemic stroke . Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone . METHODS In a r and omized , double-blind , placebo-controlled trial conducted at 114 centers in China , we r and omly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin ( clopidogrel at an initial dose of 300 mg , followed by 75 mg per day for 90 days , plus aspirin at a dose of 75 mg per day for the first 21 days ) or to placebo plus aspirin ( 75 mg per day for 90 days ) . All participants received open Output:	Conclusions : Carriers of CYP2C19 loss-of-function alleles are at greater risk of stroke and composite vascular events than noncarriers among patients with ischemic stroke or TIA treated with clopidogrel
MS22070	*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: Summary Vitamin D status was assessed in 142 elderly Dutchmen participating in a prospect i ve population -based study of environmental factors in the aetiology of non-insulin-dependent diabetes mellitus . Of the men aged 70–88 years examined between March and May 1990 , 39 % were vitamin D depleted . After adjustment for confounding by age , BMI , physical activity , month of sampling , cigarette smoking and alcohol intake the 1-h glucose and area under the glucose curve during a st and ard 75-g oral glucose tolerance test ( OGTT ) were inversely associated with the serum concentration of 25-OH vitamin D ( r = −0.23 , p < 0.01 ; r = −0.26 , p < 0.01 , respectively ) . After excluding newly diagnosed diabetic patients total insulin concentrations during OGTT were also inversely associated with the concentration of 25-OH vitamin D ( r = −0.18 to −0.23 , p < 0.05 ) . Hypovitaminosis D may be a significant risk factor for glucose intolerance . [ Diabetologia ( 1997 ) 40 : 344–347 More than 25 % of the U.S. population aged ≥65 years has diabetes ( 1 ) , and the aging of the overall population is a significant driver of the diabetes epidemic . Although the burden of diabetes is often described in terms of its impact on working-age adults , diabetes in older adults is linked to higher mortality , reduced functional status , and increased risk of institutionalization ( 2 ) . Older adults with diabetes are at substantial risk for both acute and chronic microvascular and cardiovascular complications of the disease . Despite having the highest prevalence of diabetes of any age-group , older persons and /or those with multiple comorbidities have often been excluded from r and omized controlled trials of treatments— and treatment targets — for diabetes and its associated conditions . Heterogeneity of health status of older adults ( even within an age range ) and the dearth of evidence from clinical trials present challenges to determining st and ard intervention strategies that fit all older adults . To address these issues , the American Diabetes Association ( ADA ) convened a Consensus Development Conference on Diabetes and Older Adults ( defined as those aged ≥65 years ) in February 2012 . Following a series of scientific presentations by experts in the field , the writing group independently developed this consensus report to address the following questions : 1 . What is the epidemiology and pathogenesis of diabetes in older adults ? 2 . What is the evidence for preventing and treating diabetes and its common comorbidities in older adults ? 3 . What current guidelines exist for treating diabetes in older adults ? 4 . What issues need to be considered in individualizing treatment recommendations for older adults ? 5 . What are consensus recommendations for treating older adults with or at risk for diabetes ? 6 . How can gaps in the evidence best be filled ? According to the most recent surveillance data , the prevalence of diabetes among U.S. adults aged ≥65 years varies from 22 to 33 % , depending on the diagnostic criteria OBJECTIVE To examine whether lower serum levels of serum 25-hydroxyvitamin ( OH ) D [ 25(OH)D ] are associated with increased risk of developing type 2 diabetes . RESEARCH DESIGN AND METHODS A post hoc analysis of three nested case-control studies of fractures , colon cancer , and breast cancer that measured serum 25(OH)D levels in women participating in the Women ’s Health Initiative ( WHI ) Clinical Trials and Observational Study who were free of prevalent diabetes at baseline . Diabetes was defined as self-report of physician diagnosis or receiving insulin or oral hypoglycemic medication . We used inverse probability weighting to make the study population representative of the WHI population as a whole . Weighted logistic regression models compared 25(OH)D levels ( divided into quartiles , clinical cut points [ < 50 , 50–<75 , ≥75 nmol/L ] , or as a continuous variable ) using the distribution of control subjects and adjusted for multiple confounding factors . RESULTS Of 5,140 women ( mean age 66 years ) followed for an average of 7.3 years , 317 ( 6.2 % ) developed diabetes . Regardless of the cut points used or as a continuous variable , 25(OH)D levels were not associated with diabetes incidence in either age or fully adjusted models . Nor was any relationship found between 25(OH)D and incident diabetes when evaluated by strata of BMI , race/ethnicity , or r and omization status in the Calcium Vitamin D trial . CONCLUSIONS Lower serum 25(OH)D levels were not associated with increased risk of developing type 2 diabetes in this racially and ethnically diverse population of postmenopausal women OBJECTIVE Institutionalised elderly people at northern latitudes may be at elevated risk for vitamin D deficiency . In addition to osteoporosis-related disorders , vitamin D deficiency may influence several medical conditions conferring an increased mortality risk . The aim of this study was to explore the prevalence of vitamin D deficiency and its association with mortality . DESIGN The Study of Health and Drugs in the Elderly ( SHADES ) is a prospect i ve cohort study among elderly people ( > 65 years ) in 11 nursing homes in Sweden . METHODS We analysed the levels of 25-hydroxyvitamin D₃ ( 25(OH)D₃ ) at baseline . Vital status of the subjects was ascertained and hazard ratios ( HRs ) for mortality according to 25(OH)D₃ quartiles were calculated . RESULTS We examined 333 study participants with a mean follow-up of 3 years . A total of 147 ( 44 % ) patients died within this period . Compared with the subjects in Q4 ( 25(OH)D₃ > 48 nmol/l ) , HR ( with 95 % CI ) for mortality was 2.02 ( 1.31 - 3.12 ) in Q1 ( 25(OH)D₃ < 29 nmol/l ) ( P<0.05 ) ; 2.03 ( 1.32 - 3.14 ) in Q2 ( 25(OH)D₃ 30 - 37 nmol/l ) ( P<0.05 ) and 1.6 ( 1.03 - 2.48 ) in Q3 ( 25(OH)D₃ 38 - 47 nmol/l ) ( P<0.05 ) . The mean 25(OH)D₃ concentration was 40.2 nmol/l ( S.D. 16.0 ) and 80 % had 25(OH)D₃ below 50 nmol/l . The vitamin D levels decreased from baseline to the second and third measurements . CONCLUSIONS Vitamin D deficiency was highly prevalent and associated with increased mortality among the elderly in Swedish nursing homes . Strategies are needed to prevent , and maybe treat , vitamin D deficiency in the elderly in nursing homes and the benefit of vitamin D supplementation should be evaluated in r and omised clinical trials BACKGROUND The combined impact of lifestyle factors on incidence of diabetes mellitus later in life is not well established . The objective of this study was to determine how lifestyle factors , assessed in combination , relate to new-onset diabetes in a broad and relatively unselected population of older adults . METHODS We prospect ively examined associations of lifestyle factors , measured using repeated assessment s later in life , with incident diabetes mellitus during a 10-year period ( 1989 - 1998 ) among 4883 men and women 65 years or older ( mean [ SD ] age at baseline , 73 [ 6 ] years ) enrolled in the Cardiovascular Health Study . Low-risk lifestyle groups were defined by physical activity level ( leisure-time activity and walking pace ) above the median ; dietary score ( higher fiber intake and polyunsaturated to saturated fat ratio , lower trans-fat intake and lower mean glycemic index ) in the top 2 quintiles ; never smoked or former smoker more than 20 years ago or for fewer than 5 pack-years ; alcohol use ( predominantly light or moderate ) ; body mass index less than 25 ( calculated as weight in kilograms divided by height in meters squared ) ; and waist circumference of 88 cm for women or 92 cm for men . The main outcome measure was incident diabetes defined annually by new use of insulin or oral hypoglycemic medications . We also evaluated fasting and 2-hour postchallenge glucose levels . RESULTS During 34,539 person-years , 337 new cases of drug-treated diabetes mellitus occurred ( 9.8 per 1000 person-years ) . After adjustment for age , sex , race , educational level , and annual income , each lifestyle factor was independently associated with incident diabetes . Overall , the rate of incident diabetes was 35 % lower ( relative risk , 0.65 ; 95 % confidence interval , 0.59 - 0.71 ) for each 1 additional lifestyle factor in the low-risk group . Participants whose physical activity level and dietary , smoking , and alcohol habits were all in the low-risk group had an 82 % lower incidence of diabetes ( relative risk , 0.18 ; 95 % confidence interval , 0.06 - 0.56 ) compared with all other participants . When absence of adiposity ( either body mass index < 25 or waist circumference < or = 88/92 cm for women/men ) was added to the other 4 low-risk lifestyle factors , incidence of diabetes was 89 % lower ( relative risk , 0.11 ; 95 % confidence interval , 0.01 - 0.76 ) . Overall , 9 of 10 new cases of diabetes appeared to be attributable to these 5 lifestyle factors . Associations were slightly attenuated , but still highly significant , for incident diabetes defined by medication use or glucose level . CONCLUSION Even later in life , combined lifestyle factors are associated with a markedly lower incidence of new-onset diabetes mellitus BACKGROUND Vitamin D insufficiency was shown to be associated with adverse musculoskeletal and nonskeletal outcomes in numerous observational studies . However , some studies did not control for confounding factors such as age or seasonal variation of 25-hydroxyvitamin D [ 25(OH)D ] . OBJECTIVE We sought to determine the effect of vitamin D status on health outcomes . DESIGN Healthy community-dwelling women ( n = 1471 ) with a mean age of 74 y were followed in a 5-y trial of calcium supplementation . 25(OH)D was measured at baseline in all women . Skeletal and nonskeletal outcomes were evaluated according to seasonally adjusted vitamin D status at baseline . RESULTS Fifty percent of women had a seasonally adjusted 25(OH)D concentration < 50 nmol/L. These women were significantly older , heavier , and less physically active and had more comorbidities than women with a seasonally adjusted 25(OH)D concentration > or = 50 nmol/L. Women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L had an increased incidence of stroke and cardiovascular events that did not persist after adjustment for between-group differences in age or comorbidities . Women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L were not at increased risk of adverse consequences for any musculoskeletal outcome , including fracture , falls , bone density , or grip strength or any nonskeletal outcomes , including death , myocardial infa rct ion , cancer , heart failure , diabetes , or adverse changes in blood pressure , weight , body composition , cholesterol , or glucose . CONCLUSIONS Vitamin D insufficiency is more common in older , frailer women . Community-dwelling older women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L were not at risk of adverse outcomes over 5 y after control for comorbidities . R and omized placebo-controlled trials are needed to determine whether vitamin D supplementation in individuals with vitamin D insufficiency influences health outcomes . This trial was registered at www.anzctr.org.au as ACTRN 012605000242628 Output:	In conclusion , our data suggest that hypovitaminosis D is associated with an elevated risk of future diabetes in older people .
MS22071	*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: Secondary hypogonadism is not an infrequent abnormality in older patients presenting with the primary complaint of erectile dysfunction . Because of the role of testosterone in mediating sexual desire and erectile function in men , these patients are usually treated with exogenous testosterone , which , while elevating the circulating and rogens , suppresses gonadotropins from the hypothalamic-pituitary axis . The response of this form of therapy , although extolled in the lay literature , has usually not been effective in restoring or even improving sexual function . This failure of response could be the result of suppression of gonadotropins or the lack of a cause and effect relationship between sexual function and circulating and rogens in this group of patients . Further , because exogenous testosterone can potentially increase the risk of prostate disease , it is important to be sure of the benefit sought , i.e. an increase in sexual function . In an attempt to answer this question , we measured the hormone levels and studied the sexual function in 17 patients with erectile dysfunction who were found to have secondary hypogonadism . This double blind , placebo-controlled , cross-over study consisted of treatment with clomiphene citrate and a placebo for 2 months each . Similar to our previous observations , LH , FSH , and total and free testosterone levels showed a significant elevation in response to clomiphene citrate over the response to placebo . However , sexual function , as monitored by question naires and nocturnal penile tumescence and rigidity testing , did not improve except for some limited parameters in younger and healthier men . The results confirmed that there can be a functional secondary hypogonadism in men on an out-patient basis , but correlation of the hormonal status does not universally reverse the associated erectile dysfunction to normal , thus requiring closer scrutiny of cl aims of cause and effect relationships between hypogonadism and erectile dysfunction OBJECTIVE To evaluate the effect of clomiphene in men with hypogonadism and conventionally treated nonfunctioning pituitary adenomas ( NFPA ) . PATIENTS AND METHODS Open label , single-arm , prospect i ve trial . Nine hypogonadal men ( testosterone < 300 ng/dL and low/normal LH ) with previously treated NFPA . Clomiphene ( 50 mg/day orally ) for 12 weeks . Testosterone , estradiol , LH , FSH , prolactin and erectile function were evaluated before and after 10 days , 4 , 8 and 12 weeks of clomiphene treatment . RESULTS After clomiphene treatment , testosterone and erectile function improved in only one patient . In the remaining eight patients , testosterone levels decreased whereas LH , FSH , and estradiol remained unchanged . Insulin sensitivity increased in unresponsive patients . CONCLUSIONS Compared with hypogonadal men with prolactinomas under dopaminergic therapy , clomiphene treatment failed to restore normal testosterone levels in most patients with conventionally treated NFPA The objective of this study was to assess the effects of oral testosterone supplementation therapy on glucose homeostasis , obesity and sexual function in middle-aged men with type 2 diabetes and mild and rogen deficiency . Forty-eight middle-aged men , with type 2 diabetes , ( visceral ) obesity and symptoms of and rogen deficiency , were included in this open-label study . Twenty-four subjects received testosterone undecanoate ( TU ; 120 mg daily , for 3 months ) ; 24 subjects received no treatment . Body composition was analyzed by bio-impedance . Parameters of metabolic control were determined . Symptoms of and rogen deficiency and erectile dysfunction were scored by self-administered question naires . TU had a positive effect on ( visceral ) obesity : statistically significant reduction in body weight ( 2.66 % ) , waist-hip ratio ( -3.96 % ) and body fat ( -5.65 % ) ; negligible changes were found in the control group . TU significantly improved metabolic control : decrease in blood glucose values and mean glycated hemoglobin ( HbA1c ) ( from 10.4 to 8.6 % ) . TU treatment significantly improved symptoms of and rogen deficiency ( including erectile dysfunction ) , with virtually no change in the control group . There were no adverse effects on blood pressure or hematological , biochemical and lipid parameters , and no adverse events . Oral TU treatment of type 2 diabetic men with and rogen deficiency improves glucose homeostasis and body composition ( decrease in visceral obesity ) , and improves symptoms of and rogen deficiency ( including erectile dysfunction ) . In these men , the benefit of testosterone supplementation therapy exceeds the correction of symptoms of and rogen deficiency and also includes glucose homeostasis and metabolic control Although weight loss associated with human immunodeficiency virus ( HIV ) infection is multifactorial in its pathogenesis , it has been speculated that hypogonadism , a common occurrence in HIV disease , contributes to depletion of lean tissue and muscle dysfunction . We , therefore , examined the effects of testosterone replacement by means of And roderm , a permeation-enhanced , nongenital transdermal system , on lean body mass , body weight , muscle strength , health-related quality of life , and HIV-disease markers . We r and omly assigned 41 HIV-infected , ambulatory men , 18 - 60 yr of age , with serum testosterone levels below 400 ng/dL , to 1 of 2 treatment groups : group I , two placebo patches ( n = 21 ) ; or group II , two testosterone patches design ed to release 5 mg testosterone over 24 h. Eighteen men in the placebo group and 14 men in the testosterone group completed the 12-week treatment . Serum total and free testosterone and dihydrotestosterone levels increased , and LH and FSH levels decreased in the testosterone-treated , but not in the placebo-treated , men . Lean body mass and fat-free mass , measured by dual energy x-ray absorptiometry , increased significantly in men receiving testosterone patches [ change in lean body mass , + 1.345 + /- 0.533 kg ( P = 0.02 compared to no change ) ; change in fat-free mass , + 1.364 + /- 0.525 kg ( P = 0.02 compared to no change ) ] , but did not change in the placebo group [ change in lean body mass , 0.189 + /- 0.470 kg ( P = NS compared to no change ) ; change in fat-free mass , 0.186 + /- 0.470 kg ( P = NS compared to no change ) ] . However , there was no significant difference between the 2 treatment groups in the change in lean body mass . The change in lean body mass during treatment was moderately correlated with the increment in serum testosterone levels ( r = 0.41 ; P = 0.02 ) . The testosterone-treated men experienced a greater decrease in fat mass than those receiving placebo patches ( P = 0.04 ) . There was no significant change in body weight in either treatment group . Changes in overall quality of life scores did not correlate with testosterone treatment ; however , in the subcategory of role limitation due to emotional problems , the men in the testosterone group improved an average of 43 points of a 0 - 100 possible score , whereas those in the placebo group did not change . Red cell count increased in the testosterone group ( change in red cell count , + 0.1 + /- 0.1 10(12)/L ) but decreased in the placebo group ( change in red cell count , -0.2 + /- 0.1 10(12)/L ) . CD4 + and CD8 + T cell counts and plasma HIV copy number did not significantly change during treatment . Serum prostate-specific antigen and plasma lipid levels did not change in either treatment group . Testosterone replacement in HIV-infected men with low testosterone levels is safe and is associated with a 1.35-kg gain in lean body mass , a significantly greater reduction in fat mass than that achieved with placebo treatment , an increased red cell count , and an improvement in role limitation due to emotional problems . Further studies are needed to assess whether testosterone supplementation can produce clinical ly meaningful changes in muscle function and disease outcome in HIV-infected men Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p < 0.001 ) . Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p < 0.001 ) . Interventions were well tolerated with no abnormalities in safety measures . Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels BACKGROUND Whole body and abdominal obesity are associated with increased risk of diabetes mellitus and heart disease . The effects of testosterone therapy on whole body and visceral fat mass in HIV-infected men with abdominal obesity are unknown . OBJECTIVE The objective of this study was to determine the effects of testosterone therapy on intraabdominal fat mass and whole body fat distribution in HIV-infected men with abdominal obesity . METHODS IN this multicenter , r and omized , placebo-controlled , double-blind trial , 88 HIV-positive men with abdominal obesity ( waist-to-hip ratio > 0.95 or mid-waist circumference > 100 cm ) and total testosterone 125 - 400 ng/dl , or bioavailable testosterone less than 115 ng/dl , or free testosterone less than 50 pg/ml on stable antiretroviral regimen , and HIV RNA less than 10,000 copies per milliliter were r and omized to receive 10 g testosterone gel or placebo daily for 24 wk . Fat mass and distribution were determined by abdominal computerized tomography and dual energy x-ray absorptiometry during wk 0 , 12 , and 24 . We used an intention-to-treat approach and nonparametric statistical methods . RESULTS Baseline characteristics were balanced between groups . In 75 subjects evaluated , median percent change from baseline to wk 24 in visceral fat did not differ significantly between groups ( testosterone 0.3 % , placebo 3.1 % , P = 0.75 ) . Total ( testosterone -1.5 % , placebo 4.3 % , P = 0.04 ) and sc ( testosterone-7.2 % , placebo 8.1 % , P < 0.001 ) abdominal fat mass decreased in testosterone-treated men , but increased in placebo group . Testosterone therapy was associated with significant decrease in whole body , trunk , and appendicular fat mass by dual energy x-ray absorptiometry ( all P < 0.001 ) , whereas whole body and trunk fat increased significantly in the placebo group . The percent of individuals reporting a decrease in abdomen ( P = 0.01 ) , neck ( P = 0.08 ) , and breast size ( P = 0.01 ) at wk 24 was significantly greater in testosterone-treated than placebo-treated men . Testosterone-treated men had greater increase in lean body mass than placebo ( testosterone 1.3 % , placebo -0.3 , P = 0.02 ) . Plasma insulin , fasting glucose , and total high-density lipoprotein and low-density lipoprotein cholesterol levels did not change significantly . Testosterone therapy was well tolerated . CONCLUSIONS Testosterone therapy in HIV-positive men with abdominal obesity and low testosterone was associated with greater decrease in whole body , total , and sc abdominal fat mass and a greater increase in lean mass compared to placebo . However , changes in visceral fat mass were not significantly different between groups . Further studies are needed to determine testosterone effects on insulin sensitivity and cardiovascular risk BACKGROUND The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept . We sought evidence -based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level . METHODS We surveyed a r and om population sample of 3369 men between the ages of 40 and 79 years at eight European centers . Using question naires , we collected data with regard to the subjects ' general , sexual , physical , and psychological health . Levels of total testosterone Output:	Available evidence seems to suggest that testosterone replacement therapy is able to improve central obesity ( subjects with MetS ) and glycometabolic control ( patients with MetS and T2DM ) , as well as to increase lean body mass ( HIV , chronic obstructive pulmonary disease ) , along with insulin resistance ( MetS ) and peripheral oxygenation ( chronic kidney diseases ) .
MS22072	*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: Partner notification ( PN ) is an important method for controlling the AIDS epidemic worldwide . Here , we looked into the differences between two PN counseling modes for HIV ( + ) men who have sex with men in Taiwan . Using r and om assignment , we placed 42 of the 84 subjects into the experimental group where they received two sessions of PN counseling , while the control group ( 42 ) received only one session . All 84 subjects were single males with an average age of 28.06 . The mean number of successful notified partner was 5.38 ( SD = 3.44 ) in the experimental which was statistically significantly higher than 2.81 ( SD = 1.62 ) in the control group ( β = 0.650 , p = 0.000 ) . The notification success rate was 77.13 % in the experimental and 74.21 % in the control group ( IRR 1.039 , 95 % CI 0.83–1.30 ) . In the experimental and control group , the average number of the partners accepted an HIV test was 1.86 ( SD = 1.58 ) and 0.79 ( SD = 0.66 ) ( β = 0.601 , p = 0.000 ) , and 39.74 and 27.27 % of the tested partners were HIV positive ( IRR 1.457 , 95 % CI 0.69–3.06 ) . The study results may be used to improve the policies and practice s for PN and contact follow-up Background Partner services ( PSs ) are a long-st and ing component of HIV control programs in the United States and some parts of Europe . Small r and omized trials suggest that HIV PS can be effective in identifying persons with undiagnosed HIV infection . However , the scalability and effectiveness of HIV PS in low-income countries are unknown . Methods We used data collected from 2009 to 2010 through a large HIV PS program in Cameroon to evaluate HIV PS in a developing country . HIV-positive index cases diagnosed in antenatal care , voluntary counseling and testing , and inpatient facilities were interviewed to collect information on their sexual partners . Partners were contacted via telephone or home visit to notify , test , and enroll those found to be HIV positive in medical care . Results Health advisors interviewed 1462 persons with HIV infection during the evaluation period ; these persons provided information about 1607 sexual partners . Health advisors notified 1347 ( 83.8 % ) of these partners , of whom 900 ( 66.8 % ) were HIV tested . Of partners tested , 451 ( 50.1 % ) were HIV positive , of whom 386 ( 85.6 % ) enrolled into HIV medical care . An average 3.2 index cases needed to be interviewed to identify 1 HIV case . Conclusions HIV PS can be successfully implemented in a developing country and is highly effective in identifying persons with HIV infection and linking them to care BACKGROUND We sought to compare two methods of notifying sex partners of subjects infected with the human immunodeficiency virus ( HIV ) or persons who had shared needles with them ( needle-sharing partners ) : " patient referral , " in which the responsibility for notifying partners was left to the patient , and " provider referral , " in which providers attempted to notify partners . METHODS Names of sex partners and needle-sharing partners and information on how to locate them were obtained from consenting HIV-infected subjects identified in the HIV-testing programs at three public health departments in North Carolina . The subjects were r and omly assigned to a patient-referral group ( in which patients had the initial responsibility for notifying their partners ) or a provider-referral group ( in which the study counselor notified the partners ) . The success of attempts to notify partners was monitored by means of interviews with counselors conducted both in the field and at the health department . RESULTS Of 534 HIV-positive persons identified at the health departments , 247 ( 46 percent ) did not return for counseling after the test , 8 were counseled outside the study , and 117 ( 22 percent ) were ineligible . Of the 162 invited to participate , 88 ( 54 percent ) declined and 74 ( 46 percent ) agreed . The subjects were mostly male ( 69 percent ) , black ( 87 percent ) , homosexual or bisexual ( 76 percent of the men ) , and had a median age of 30 years . Thirty-nine were assigned to the provider-referral group and 35 to the patient-referral group . In the provider-referral group 78 of 157 partners ( 50 percent ) were successfully notified , whereas in the patient-referral group only 10 of 153 ( 7 percent ) were notified . Of the partners notified by the counselors , 94 percent were not aware that they had been exposed to HIV . Overall , 23 percent of the partners notified and tested were HIV-positive . CONCLUSIONS In this trial , leaving the notification of partners up to the subjects ( patient referral ) was quite ineffective , despite the North Carolina law requiring that partners be notified . Partner notification by public health counselors ( provider referral ) was significantly more effective . Although the effectiveness of notification procedures is constrained by the accuracy of the information provided by HIV-infected patients , counselors who notify the partners of an infected patient can refer them to educational , medical , and support services targeted to persons at high risk for HIV infection and may encourage the adoption of less risky behavior BACKGROUND Assisted partner services for index patients with HIV infections involves elicitation of information about sex partners and contacting them to ensure that they test for HIV and link to care . Assisted partner services are not widely available in Africa . We aim ed to establish whether or not assisted partner services increase HIV testing , diagnoses , and linkage to care among sex partners of people with HIV infections in Kenya . METHODS In this cluster r and omised controlled trial , we recruited non-pregnant adults aged at least 18 years with newly or recently diagnosed HIV without a recent history of intimate partner violence who had not yet or had only recently linked to HIV care from 18 HIV testing services clinics in Kenya . Consenting sites in Kenya were r and omly assigned ( 1:1 ) by the study statistician ( restricted r and omisation ; balanced distribution in terms of county and proximity to a city ) to immediate versus delayed assisted partner services . Primary outcomes were the number of partners tested for HIV , the number who tested HIV positive , and the number enrolled in HIV care , in those who were interviewed at 6 week follow-up . Participants within each cluster were masked to treatment allocation because participants within each cluster received the same intervention . This trial is registered with Clinical Trials.gov , number NCT01616420 . FINDINGS Between Aug 12 , 2013 , and Aug 31 , 2015 , we r and omly allocated 18 clusters to immediate and delayed HIV assisted partner services ( nine in each group ) , enrolling 1305 participants : 625 ( 48 % ) in the immediate group and 680 ( 52 % ) in the delayed group . 6 weeks after enrolment of index patients , 392 ( 67 % ) of 586 partners had tested for HIV in the immediate group and 85 ( 13 % ) of 680 had tested in the delayed group ( incidence rate ratio 4·8 , 95 % CI 3·7 - 6·4 ) . 136 ( 23 % ) partners had new HIV diagnoses in the immediate group compared with 28 ( 4 % ) in the delayed group ( 5·0 , 3·2 - 7·9 ) and 88 ( 15 % ) versus 19 ( 3 % ) were newly enrolled in care ( 4·4 , 2·6 - 7·4 ) . Assisted partner services did not increase intimate partner violence ( one intimate partner violence event related to partner notification or study procedures occurred in each group ) . INTERPRETATION Assisted partner services are safe and increase HIV testing and case-finding ; implementation at the population level could enhance linkage to care and antiretroviral therapy initiation and substantially decrease HIV transmission . FUNDING National Institutes of Health OBJECTIVE This analysis describes the Outreach-Assisted Model of Partner Notification , an innovative strategy for encouraging seropositive injecting drug users ( IDUs ) to inform their partners of shared human immunodeficiency virus ( HIV ) exposure . The analysis focuses on two core components of the notification process : the identification of at-risk partners and preferences for self-tell vs. outreach assistance in informing partners of possible exposure to the virus . METHODS Using community outreach techniques , 386 IDUs were recruited for HIV pretest counseling , testing , and partner notification over a 12-month period . Of these , 63 tested HIV seropositive , and all but three returned for their test results . The 60 who were informed of their serostatus were r and omly assigned to either a minimal or an enhanced intervention condition . Participants assigned to the minimal ( self-tell ) group were strongly encouraged to inform their partners of possible exposure . Those assigned to the enhanced ( outreach-assisted ) group had the option of either informing one or more of their partner(s ) themselves or choosing to have the project 's outreach team do so . RESULTS Together , the 60 index persons who received their results provided names or at least one piece of locating information for a total of 142 partners with whom they perceived having shared possible exposure to the virus within the past five years . By itself , drug use accounted for half of all partners named . Sexual behavior alone accounted for 25 % of named partners . Eighty-two percent of the enhanced group preferred to have the outreach team tell at least one partner ; the team was requested to notify 71 % of the total number of partners whom this group named . CONCLUSIONS Findings suggest that IDUs want to notify their partners of shared HIV exposure . Outreach assistance was the preferred mode in the majority of cases . Exp and ing traditional community-based HIV outreach activities to include delivering street-based counseling , test , a partner notification appears to be a positive and workable prevention strategy Background : Sexual partners of persons with newly diagnosed HIV infection require HIV counseling , testing and , if necessary , evaluation for therapy . However , many African countries do not have a st and ardized protocol for partner notification , and the effectiveness of partner notification has not been evaluated in developing countries . Methods : Individuals with newly diagnosed HIV infection presenting to sexually transmitted infection clinics in Lilongwe , Malawi , were r and omized to 1 of 3 methods of partner notification : passive referral , contract referral , or provider referral . The passive referral group was responsible for notifying their partners themselves . The contract referral group was given seven days to notify their partners , after which a health care provider contacted partners who had not reported for counseling and testing . In the provider referral group , a health care provider notified partners directly . Results : Two hundred forty-five index patients named 302 sexual partners and provided locator information for 252 . Among locatable partners , 107 returned for HIV counseling and testing ; 20 of 82 [ 24 % ; 95 % confidence interval ( CI ) : 15 % to 34 % ] partners returned in the passive referral arm , 45 of 88 ( 51 % ; 95 % CI : 41 % to 62 % ) in the contract referral arm , and 42 of 82 ( 51 % ; 95 % CI : 40 % to 62 % ) in the provider referral arm ( P < 0.001 ) . Among returning partners ( n = 107 ) , 67 ( 64 % ) of were HIV infected with 54 ( 81 % ) newly diagnosed . Discussion : This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa . Active partner notification was feasible , acceptable , and effective among sexually transmitted infections clinic patients . Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners Objective : Determine the cost and effectiveness of partner notification for human immunodeficiency virus ( HIV ) infection . Methods : Persons testing HIV positive in three areas were r and omly assigned one of four approaches to partner notification . Analysis plans changed because disease intervention specialists notified many partners from the patient referral group . We dropped the patient referral group and combined the others to assess the cost and effectiveness of provider referral . Results : The 1,070 patients reported 8,633 partners . Of those , 1,035 were located via record search or in person . A previous positive test was reported by 248 partners . Of the 787 others , 560 were tested : 438 were HIV negative and 122 were newly identified as HIV positive . The intervention specialist 's time totaled 197 minutes per index patient . The cost of the intervention specialist 's time , travel , and overhead was $ 268,425 : $ 251 per index patient , $ 427 per partner notified , or $ 2,200 per new HIV infection identified . No demographic characteristic of the index patient strongly predicted the likelihood of finding an infected partner . Conclusion : We could not compare the effectiveness of different partner notification approaches because of frequent crossover between r and omized groups . The cost of partner notification can be compared with other approaches to acquired immunodeficiency syndrome prevention , but the benefits are not easily measured . We do not know the number of HIV cases prevented or the value of fulfilling the ethical obligation to warn partners of a potential threat to their health The incidence of human immunodeficiency virus ( HIV ) infection has significantly increased among black men who have sex with men ( MSM ) in the United States , and young black MSM have been disproportionately affected . HIVinfected black MSM are also less likely to engage in HIV care and achieve viral suppression than MSM of other races/ethnicities . Eng Output:	Conclusion : Assisted partner notification improved partner testing and diagnosis of HIV-positive partners , with few reports of harm .
MS22073	*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: Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should PURPOSE To compare the efficacy of immediate functionally loaded implants placed with a flapless procedure ( test group ) versus implants placed after flap elevation and conventional load-free healing ( control group ) in partially edentulous patients . MATERIAL S AND METHODS Forty patients were r and omized : 20 to the flapless immediately loaded group and 20 to the conventional group . To be immediately loaded , implants had to be inserted with a minimum torque > 45 Ncm . Implants in the immediately loaded group were provided with full acrylic resin temporary restorations the same day . Implants in the conventional group were submerged ( anterior region ) or left unsubmerged ( posterior region ) and were left load-free for 3 months ( m and ibles ) or 4 months ( maxillae ) . Provisional restorations were replaced with definitive single metal-ceramic crowns 1 month postloading . Outcome measures were prosthesis and implant failures , biological and prosthetic complications , postoperative edema , pain , and use of analgesics . Independent sample chi2 tests , Mann-Whitney tests , t tests , and paired t tests were used with a significance level of .05 . RESULTS Fifty-two implants were placed in the flapless group and 56 in the conventionally loaded group . In the flapless group , 1 flap had to be raised to control the direction of the bur and 1 implant did not reach the planned primary stability and was treated as belonging to the conventional group . After 3 years no dropouts or failures occurred . There was no statistically significant difference for complications ; however , patients in the conventional group had significantly more postoperative edema and pain and consumed more analgesics than those in the flapless group . Osstell values were significantly higher at baseline in the flapless group ( P = .033 ) . When comparing baseline data with years 1 , 2 , and 3 within each group , mean Osstell values of the flapless group did not increase , whereas there were statistically significant increases in the Periotest values . CONCLUSIONS Implants can be successfully placed flapless and loaded immediately without compromising success rates ; the procedure decreases treatment time and patient discomfort The objective of this clinical study was to compare the survival rates of early loaded implants placed using flapless and flapped surgical techniques and to determine the bone density in the implant recipient sites using computerized tomography ( CT ) . The study population consisted of 12 patients who were referred implant placement . One group consisted of five patients referred for the placement of 14 implants and treated with a flapless procedure . The other group consisted of seven patients referred for the placement of 45 implants with a conventional flapped procedure . Patients were selected r and omly . CT machine was used for pre-operative evaluation of the jaw bone and the mean bone density value of each implant recipient site was recorded in Hounsfield units ( HU ) . All implants were placed using CT-guided surgical stents . The early loading protocol s included 2 months of healing in the m and ible and 3 months of healing in the maxilla . Single-implant crowns , implant-supported fixed partial dentures , and implant-retained over dentures were delivered to the patients . Of 59 implants placed , one was lost in the conventional flapped group within the first month of healing , meaning overall implant survival rate of 98.3 % average 9 months later . The highest average bone density value ( 801 + /- 239 HU ) was found in the anterior m and ible , followed by 673 + /- 449 HU for the posterior maxilla , 669 + /-346 HU for the anterior maxilla and 538 + /- 271 HU for the posterior m and ible . The results of this study show that the early loading of implants placed utilizing flapless surgical technique with CT-guided surgical stents may be possible BACKGROUND Regarding the Brånemark implant system , nonresorbable sutures have been advocated for reapproximation of the flaps . Fast-absorbable sutures are frequently used in oral surgery , which is convenient for both the patient and the surgeon . It would be advantageous if fast-absorbable sutures are suitable in implant surgery as well . PURPOSE The purpose of this study was to compare irradiated polyglactin 910 ( Vicryl Rapide , Ethicon GmbH , Norderstedt , Germany ) suture with a nonresorbable polyfilament suture ( Supramid , Schwarz , Resorba GmbH , Nürnberg , Germany ) used in oral implant surgery . MATERIAL S AND METHODS The study comprised 101 edentulous patients ( 52 females , 49 males ) who were provided with 350 Brånemark implants . They were r and omized to receive either Vicryl Rapide suture ( n = 61 ) or 3 - 0 Supramid suture ( n = 40 ) . The patients were evaluated after 10 days and at the time of abutment surgery . Any wound complications and implant losses were recorded . RESULTS The implant failure rate at abutment surgery was low ( 1.2 % ) , and no difference was seen between the two suture groups . A higher incidence of complications ( mainly wound dehiscence ) was found in the absorbable suture group , especially when a continuous suture was used . CONCLUSIONS The results of this study indicate that it is possible to use irradiated polyglactin 910 sutures in oral implant surgery without affecting the rate of early implant failure . However , it is recommended to add interrupted " security sutures " if a continuous suture technique is used in combination with fast-absorption suture material AIM The aim of this controlled r and omized clinical trial was to evaluate the efficacy of a xenogeneic collagen matrix ( CM ) to augment the keratinized tissue around implants supporting prosthetic restorations at 6 months when compared with the st and ard treatment , the connective tissue autograft , CTG ) . MATERIAL S AND METHODS This r and omized longitudinal parallel controlled clinical trial studied 24 patients with at least one location with minimal keratinized tissue ( ≤1 mm ) . MAIN OUTCOME MEASURE The 6-month width of keratinized tissue . As secondary outcomes the esthetic outlook , the maintenance of peri-implant mucosal health and the patient morbidity were assessed pre-operatively and 1 , 3 , and 6 months post-operatively . RESULTS At 6 months , Group CTG attained a mean width of keratinized tissue of 2.75 ( 1.5 ) mm , while the corresponding figure in Group CM was 2.8 ( 0.4 ) mm , the inter-group differences not being statistically significant . The surgical procedure in both groups did not alter significantly the mucosal health in the affected abutments . There was a similar esthetic result and significant increase in the vestibular depth in both groups as a result of the surgery . In the CM group it changed from 2.2 ( 3.3 ) to 5.1 ( 2.5 ) mm at 6 months . The patients treated with the CM referred less pain , needed less pain medication , and the surgical time was shorter , although these differences were not statistically significant when compared with the CTG group . CONCLUSIONS These results prove that this new CM was as effective and predictable as the CTG for attaining a b and of keratinized tissue PURPOSE The aim of this study was to compare the pain experienced after implant placement with 2 different surgical procedures : a flapless surgical procedure using an image-guided system based on a template and an open-flap procedure . MATERIAL S AND METHODS The study population consisted of 60 patients who were referred for implant placement . One group consisted of 30 patients who were referred for the placement of 80 implants and treated with a flapless procedure . The other group consisted of 30 patients who were referred for the placement of 72 implants with a conventional procedure . Patients were selected r and omly . They were requested to fill out a question naire using a visual analog scale ( VAS ) to assess the pain experienced and to indicate the number of analgesic tablets taken every postoperative day from the day of the surgery ( DO ) to 6 days after surgery ( D6 ) . RESULTS The results showed a significant difference in pain measurements , with higher scores on the VAS with open-flap surgery ( P < .01 ) . Pain decreased faster with the flapless procedure ( P = .05 ) . The number of patients who felt no pain ( VAS = 0 ) was higher with the flapless procedure ( 43 % at DO versus 20 % ) . With the flapless procedure , patients took fewer pain tablets ( P = .03 ) and the number of tablets taken decreased faster ( P = .04 ) . DISCUSSION Minimally invasive procedures may be requested by patients to reduce their anxiety and the pain experienced and thus increase the treatment acceptance rate . CONCLUSION With the flapless procedure , patients experienced pain less intensely and for shorter periods of time PURPOSE To evaluate the efficacy of flapless versus open flap implant placement in partially edentulous patients . MATERIAL S AND METHODS Forty patients with two separate edentulous areas characterised by residual bone at least 5 mm thick and 10 mm in height had these sites r and omised following a split-mouth design to receive at least one implant to each side after flap elevation or not . Implants were first placed in one site , and after 2 weeks in the other site freeh and . Implants inserted with a torque > 48 Ncm were immediately loaded with full occluding acrylic temporary restorations . Definitive single cemented crowns or screw-retained metal ceramic fixed dental prostheses were delivered after 2 months . Outcome measures were prosthesis and implant failures , complications , postoperative swelling and pain , consumption of analgesics , patient preference , surgical time , marginal bone level changes , and implant stability quotient ( ISQ ) values . RESULTS Seventy-six implants were placed flapless and 67 after flap elevation . In the flapless group , four flaps had to be raised to control the direction of the bur , whereas one haemorrhage and one fracture of the buccal bone occurred in two patients of the flap elevation group . Four implants did not reach the planned stability ( three belonging to the flapless group ) and they were all immediately replaced by larger diameter ones . After 1 year , no drop-outs occurred . Two definitive bridges could not be placed when planned ( one in each group ) and two crowns had to be remade ( one in each group ) . Two implants failed in each group , all in different patients . There were no statistically significant differences for prosthetic and implant failures , complications , ISQ values and marginal bone levels between groups . However , flapless implant placement required significantly less operation time ( 17 minutes less , saving almost two-thirds of the time for implant placement ) , induced less postoperative pain , swelling , analgesic consumption and was preferred by patients . Mean ISQ values of both groups significantly decreased over time . CONCLUSIONS Implants can be successfully placed flapless and loaded immediately , reducing treatment time and patient discomfort AIM The aim of this study was to test a new collagen matrix ( CM ) aim ed to increase keratinized gingiva/mucosa when compared with the free connective tissue graft ( CTG ) . MATERIAL AND METHODS This r and omized longitudinal parallel controlled clinical trial studied 20 patients with at least one location with minimal keratinized tissue ( < or=1 mm ) . MAIN OUTCOME MEASURE The 6-month width of keratinized tissue . As secondary outcomes , the aesthetic outlook , the maintenance of periodontal health and the patient morbidity were assessed pre-operatively at 1 , 3 and 6 months . RESULTS At 6 months , the CTG attained a mean width of keratinized tissue of 2.6 ( 0.9 ) mm , while the CM was 2.5 ( 0.9 ) mm , these differences being insignificant . In both groups , there was a marked contraction ( 60 % and 67 % , respectively ) although the periodontal parameters were not affected . The CM group had a significantly lower patient morbidity ( pain and medication intake ) as well as reduced surgery time . CONCLUSIONS These results prove that this new CM was as effective and predictable as the CTG for attaining a b and of keratinized tissue , but its use was associated with a significantly lower patient morbidity OBJECTIVES To evaluate and compare the outcome of dental implants placed using a flapless protocol and immediate loading with a conventional protocol and loading after 6 weeks . MATERIAL S AND METHODS Fourteen patients with bilateral maxillary edentulous areas were treated using Straumann SLA-implants . Using a r and omized split-mouth design , implants were placed in one side of the maxilla using a stereolithographic surgical guide for flapless surgery and immediately loaded on temporary abutments with a bridge ( test ) . Implants in the other side were placed using the conventional protocol and loaded after 6 weeks of healing ( control ) . Clinical and radiographic evaluation of peri-implant tissues was performed at time of implant surgery , and after 1 week , 6 weeks , 3 , 6 , 12 and 18 months . RESULTS A total of 70 implants were placed ( 3 Output:	On a patient , rather than per implant basis , implants placed with a flapless technique and implant exposures performed with laser induced statistically significantly less postoperative pain than flap elevation . Sites augmented with soft tissues connective grafts showed a better aesthetic and thicker tissues . Both palatal autografts or the use of a porcine-derived collagen matrix are effective in increasing the height of keratinised mucosa at the price of a 0.5 mm recession of peri-implant soft tissues . There is limited weak evidence suggesting that flapless implant placement is feasible and has been shown to reduce patient postoperative discomfort in adequately selected patients , that augmentation at implant sites with soft tissue grafts is effective in increasing soft tissue thickness improving aesthetics and that one technique to increase the height of keratinised mucosa using autografts or an animal-derived collagen matrix was able to achieve its goal but at the price of a worsened aesthetic outcome ( 0.5 mm of recession ) .
MS22074	*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: Few studies have evaluated efficacy of psychotherapies for pathological gambling . Pathological gamblers ( N = 231 ) were r and omly assigned to ( a ) referral to Gamblers Anonymous ( GA ) , ( b ) GA referral plus a cognitive- behavioral ( CB ) workbook , or ( c ) GA referral plus 8 sessions of individual CB therapy . Gambling and related problems were assessed at baseline , 1 month later , posttreatment , and at 6- and 12-month follow-ups . CB treatment reduced gambling relative to GA referral alone during the treatment period and result ed in clinical ly significant improvements , with some effects maintained throughout follow-up ( ps = .05 ) . Individual CB therapy improved some outcomes compared with the CB workbook . Attendance at GA and number of CB therapy sessions or workbook exercises completed were associated with gambling abstinence . These data suggest the efficacy of this CB therapy approach OBJECTIVE To examine the influence of co-occurring conditions on gambling treatment outcomes . DESIGN , SETTING AND PARTICIPANTS Prospect i ve cohort study of problem gamblers . Participants were recruited from consecutive referrals to a gambling therapy service in 2008 . Inclusion criteria were : ( i ) assessed as a problem gambler based on a screening interview including DSM-IV criteria for pathological gambling , and ( ii ) suitable for admission to a treatment program . Cognitive-behavioural therapy was based on grade d exposure-to-gambling urge . One-to-one treatment was conducted with 1-hour sessions weekly for up to 12 weeks . MAIN OUTCOME MEASURES Problem gambling screening and co-occurring conditions including depression , anxiety and alcohol use . RESULTS Of 127 problem gamblers , 69 were males ( 54 % ) , mean age was 43.09 years , and 65 ( 51 % ) reported a duration of problem gambling greater than 5 years . Median time for participants ' enrolment in the study was 8.9 months . Results from mixed effects logistic regression analysis indicated that individuals with higher depression levels had a greater likelihood ( 13 % increase in odds [ 95 % CI , 1%-25 % ] ) of problem gambling during treatment and at follow-up . CONCLUSION Addressing depression may be associated with improved treatment outcomes in problem gambling ; conversely , treatment of problem gambling improves affective instability . We therefore recommend a dual approach that treats both depression and problem gambling Sixty-eight individuals were r and omised to either six sessions of imaginal desensitisation plus motivational interviewing ( IDMI ) or Gamblers Anonymous . Individuals assigned to IDMI had significantly greater reductions in Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling total scores , gambling urges and gambling behaviour . People who failed to respond to Gamblers Anonymous reported significantly greater reduction in pathological gambling symptoms following later assignment to IDMI . Abstinence was achieved by 63.6 % during the acute IDMI treatment period Two brief treatments for problem gambling were compared with a waiting-list control in a r and omized trial . Eighty-four percent of participants ( N = 102 ) reported a significant reduction in gambling over a 12-month follow-up period . Participants who received a motivational enhancement telephone intervention and a self-help workbook in the mail , but not those who received the workbook only , had better outcomes than participants in a 1-month waiting-list control . Participants who received the motivational interview and workbook showed better outcomes than those receiving the workbook only at 3- and 6-month follow-ups . At the 12-month follow-up , the advantage of the motivational interview and workbook condition was found only for participants with less severe gambling problems . Overall , these results support the effectiveness of a brief telephone and mail-based treatment for problem gambling BACKGROUND Pathological gambling ( PG ) , a disabling disorder experienced by approximately 1 % of adults , has few empirically vali date d treatments . A recent study demonstrated that 6 sessions of imaginal desensitization plus motivational interviewing ( IDMI ) was effective in achieving abstinence for a majority of individuals with PG . This study sought to examine whether those benefits were maintained 6 months post-treatment . METHODS Sixty-eight individuals who met DSM-IV criteria for PG were r and omly assigned to 6 sessions of IDMI or Gamblers Anonymous ( GA ) referral over an 8-week period . Participants who failed to respond to GA were offered IDMI after the 8-week acute treatment period . All individuals who responded to IDMI were contacted after 6 months and assessed with measures of gambling severity and psychosocial functioning . RESULTS Forty-four participants completed 6 sessions of IDMI ( 25 initially assigned to IDMI and 19 to GA ) . Thirty-five of the 44 ( 79.5 % ) responded during acute treatment , and all 35 were available for a 6-month evaluation . All gambling severity scales maintained statistically significant gains from baseline , although some measures showed significant worsening compared with post-IDMI treatment . CONCLUSIONS Six sessions of IDMI result ed in statistically significant reductions in PG urges and behavior , which were largely maintained for 6 months AIMS College students experience high rates of problem and pathological gambling , yet little research has investigated methods for reducing gambling in this population . This study sought to examine the efficacy of brief intervention strategies . DESIGN R and omized trial . SETTING College campuses . PARTICIPANTS A total of 117 college student problem and pathological gamblers . INTERVENTIONS Students were assigned r and omly to : an assessment -only control , 10 minutes of brief advice , one session of motivational enhancement therapy ( MET ) or one session of MET , plus three sessions of cognitive-behavioral therapy ( CBT ) . The three interventions were design ed to reduce gambling . MEASUREMENTS Gambling was assessed at baseline , week 6 and month 9 using the Addiction Severity Index-gambling ( ASI-G ) module , which also assesses days and dollars wagered . FINDINGS Compared to the assessment -only condition , those receiving any intervention had significant decreases in ASI-G scores and days and dollars wagered over time . The MET condition decreased significantly ASI-G scores and dollars wagered over time , and increased the odds of a clinical ly significant reduction in gambling at the 9-month follow-up relative to the assessment -only condition , even after controlling for baseline indices that could impact outcomes . The Brief Advice and MET+CBT conditions had benefits on some , but not all , indices of gambling . None of the interventions differed significantly from one another . Conclusions These results suggest the efficacy of brief interventions for reducing gambling problems in college students A substantial proportion of pathological gamblers engage in gambling-related illegal behavior . We examined differences in baseline characteristics and treatment outcomes in two groups : pathological gamblers who did and did not commit gambling-related illegal acts in the year before treatment . Participants were 231 pathological gamblers enrolled in a r and omized study of treatment that included cognitive behavior therapy and referral to Gamblers Anonymous ( GA ) . Participants reporting recent illegal behavior ( n = 63 ) endorsed more severe lifetime and recent ( past-year ) gambling disorder symptoms and higher gambling-related debt than did gamblers who denied illegal behavior ( n = 168 ) . Those who reported illegal behavior also maintained a significantly higher severity of gambling disorder throughout treatment , although both groups experienced similar improvements in gambling symptoms over time . While pathological gamblers with or without gambling-related illegal behavior appeared to improve at a similar rate regardless of the treatment provided , more intensive treatment may be warranted for individuals with gambling-related illegal behavior , as they demonstrated greater gambling severity throughout treatment and follow-up Effective therapies for pathological gambling exist , but their use is limited to about 10 % of the target population . In an attempt to lower the barriers for help , Internet-based cognitive behavioural therapy ( ICBT ) has been shown to be effective when delivered to a non-depressed sample with pathological gambling . This study sought to extend this finding to a larger , more representative population , and also test a model to predict responder status . Following advertisement , a total of 284 participants started an 8-week ICBT programme with minimal therapist contact via e-mail and weekly telephone calls of less than 15 min . The average time spent on each participant , including telephone conversations , e-mail , and administration , was 4 h. In addition to a mixed effects model to evaluate the effectiveness of the treatment , two logistic regression analyses were performed with the following eight pre-defined response predictor variables : work-life satisfaction , primary gambling activity , debts due to gambling , social support , personal yearly salary , alcohol consumption , stage of change , and dissociative gambling . ICBT result ed in statistically significant reductions in the scores of pathological gambling , anxiety , and depression as well as an increase in quality of life compared to pre-treatment levels . Follow-ups carried out in the treatment group at 6 , 18 , and 36 months indicated that treatment effects were sustained . Using the eight predictor variable model rendered an acceptable predictive ability to identify responders both at post-test ( AUC = .72 , p < .01 ) and at 36-month follow-up ( AUC = .70 , p < .01 ) . We conclude that ICBT for pathological gamblers , even if depressed , can be effective and that outcome can partly be predicted by pre-treatment characteristics This exploratory study investigated the effect of interventions design ed to improve compliance and reduce dropout rates during the outpatient treatment of pathological gambling at a University-based gambling treatment clinic . Forty subjects ( 29 males , 11 females , mean age = 37.6 ) meeting DSM-IV criteria ( APA , 1994 ) for pathological gambling were r and omly assigned to either a cognitive-behavioural treatment or a cognitive-behavioural treatment combined with interventions design ed to improve treatment compliance . Compliance was indicated by the completion of all treatment sessions . Outcome measures were DSM-IV criteria assessed by structured clinical interview , South Oaks Gambling Screen scores , and percentage of income gambled . Logistic regression analyses identified pretreatment characteristics predicting compliance and outcome . Compliance-improving interventions significantly reduced dropout rates , result ing in superior outcomes at posttreatment compared to the cognitive behavioural treatment alone . At 9-month follow-up , there was no difference in outcome between treatments , although both produced clinical ly significant change . Comorbid problem drinking , drug use , and problem gambling duration predicted poor compliance . Poor outcome was predicted by comorbid problem drinking . The clinical implication s of these results are discussed in light of the exploratory nature of the study and the need for future research to address compliance , outcome , and comorbidity issues This study examined the efficacy of two group treatments for pathological gambling , a node-link mapping-enhanced cognitive-behavioral group therapy ( CBGT-mapping ) and twelve-step facilitated ( TSF ) group treatment . Forty-nine participants meeting criteria for pathological gambling were recruited from local newspaper advertisements . These participants were r and omly assigned to one of three conditions : TSF ( n = 11 ) , CBGT-mapping ( n = 18 ) , and Wait-List control ( n = 9 ) ; 11 refused treatment prior to r and omization . Outcome measures included number of DSM-IV criteria met , perception of control/self-efficacy , desire to gamble , and frequency of gambling episodes . Analyses revealed a significant treatment group × time interaction ( η²partial = .39 ) . Specifically , the group treatments result ed in significant improvements in the dependent measures , while the Wait-List group remained relatively stable . Overall , CBGT-mapping and TSF had no significant differences on any outcome measure at follow-up assessment s. Analysis of post-treatment and 6-month follow-up reveal a significant improvement in gambling outcomes ( i.e. , fewer DSM-IV criteria met , greater self-efficacy , and fewer gambling episodes ( η²partial = .35 ) , with treatment gains maintained at 6 months . These results are consistent with previous research for group treatment for pathological gambling and provide support for the utility of TSF and a mapping-based CBT therapy as viable intervention for pathological gambling The transtheoretical model has been applied to many addictive disorders . In this study , psychometrics properties of the University of Rhode Isl and Change Assessment ( URICA ) scale were evaluated in 234 pathological gamblers initiating treatment . Four components were identified -- reflective of precontemplation , contemplation , action , and maintenance stages -- with internal consistency from .74 to .88 . Cluster analyses identified 4 patterns of responding , ranging from ambivalent to active change . The 4 clusters differed with respect to baseline gambling variables and treatment engagement and outcomes assessed 2 months later . A continuous measure of readiness to change was also correlated with gambling severity and predictive of reductions in gambling . This study provides initial support for reliability and validity of the URICA in treatment-seeking gamblers , and it suggests that stage of change may have an impact on outcomes INTRODUCTION Cognitive-behavioural therapy ( CBT ) seems to offer effective treatment for pathological gambling ( PG ) . However , it has not yet been established which techniques yield the best results , or whether exposure and response prevention ( ERP ) techniques are of additional use . OBJECTIVES To evaluate clinical and socio-demographic characteristics of a PG sample at baseline , comparing cognitive-behavioural group intervention , with and without exposure , with response prevention ( CBT + ERP vs. CBT ) , to compare the results of ther Output:	Male gender and low depression levels were the most consistent predictors of successful treatment outcomes across multiple time-points . Likely predictors of successful treatment outcomes also included older age , lower gambling symptom severity , lower levels of gambling behaviours and alcohol use , and higher treatment session attendance . Mixed results were identified for treatment goal , while education , income , preferred gambling activity , problem gambling duration , anxiety , any psychiatric comorbidity , psychological distress , substance use , prior gambling treatment and medication use were not significantly associated with treatment outcomes at any time-point .
MS22075	*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 study was design ed to assess the effect of performance feedback on stress reactivity after recovery from maximal exercise . Forty competitive athletes were recruited to complete a maximal exercise test . Performance feedback was manipulated after the exercise test to give four groups : ( 1 ) high performance , ( 2 ) low performance , ( 3 ) accurate feedback and ( 4 ) no exercise control . Cardiovascular reactivity was assessed during psychological stress . The results indicate that accurate feedback participants experienced lower relative reactivity to stress ( lower mean arterial pressure ) than their no-exercise counterparts . These results demonstrate that the stressbuffering effect of exercise extends to maximal exercise . In addition , high-performance participants experienced lower relative reactivity than low-performance participants . Thus , low-performance feedback was sufficient to remove the buffering effect of exercise . There were no differences between the high-performance and accurate feedback conditions , or between the low-performance and control conditions Endogenous opiate peptides can regulate neuroendocrine and circulatory responses to behavioral stress and may be important in the pathogenic effects of sympathoadrenal reactivity . We tested this hypothesis by examining the effect of the opiate antagonist naloxone on blood pressure responses to behavioral stress in young adults with high , medium , or low casual blood pressures . Naloxone increased mean arterial pressure responses to stress in subjects with low casual pressure , but had no significant effect on responses in subjects with high casual pressure . These results suggest opioidergic inhibition of sympathetic nervous system responses may be deficient in persons at risk for essential hypertension Thirty-six competitive sportsmen and 36 inactive men participated in a two-session experiment . Session 1 involved exercise to exhaustion so as to assess maximal oxygen consumption ( VO2 max ) . In Session 2 , both groups were r and omized into three experimental conditions : 20 min of exercise at high intensity ( 70 % VO2max ) or moderate intensity ( 50 % VO2max ) or a light exercise control . Following 30 min of recovery , all subjects performed mental arithmetic and public speech tasks in a counterbalanced order . Cardiovascular , electrodermal , respiratory , and subjective variables were recorded . Sportsmen had higher VO2max , lower body fat , and lower resting heart rate ( HR ) than inactive men . A postexercise hypotensive response was observed among subjects in the 70 % and 50 % VO2max conditions , accompanied by baroreceptor reflex inhibition in the 70 % condition . Systolic pressure was lower during mental arithmetic and during recovery from the speech task in the high-intensity than in the control group . Diastolic pressure was lower following mental arithmetic in the high-intensity group . No differences in HR reactivity , electrodermal , or respiratory parameters were observed , but baroreceptor reflex sensitivity was inhibited during mental arithmetic . The results are discussed in relation to previous reports of suppressed cardiovascular reactivity to mental stress tests following vigorous exercise and the role of stress-related processes in the antihypertensive response to physical training The effects of exercise on subsequent psychophysiological responses to mental stress were assessed in a study of 30 normotensive male volunteers . Participants were r and omly allocated to three experimental conditions--20-min exercise at 100 Watts ( high exercise ) , 20-min exercise at 25 Watts ( low exercise ) , or 20-min no exercise ( control ) . After a recovery period of 20 min , all subjects performed a mental arithmetic task for four 5-min trials . Blood pressure and heart rate were monitored continuously using a Finapres , and respiration and electrodermal activity were also recorded . Baroreceptor reflex control of heart rate was assessed using power spectrum analysis . Exercise produced consistent increases in systolic blood pressure , heart rate , and subjective tension , together with reductions in systemic resistance and baroreflex sensitivity . The systolic and diastolic blood pressure and heart rate reactions to mental arithmetic were significantly blunted in the high exercise compared with control conditions , with the low exercise group showing an intermediate pattern . Subjective responses to mental stress were unaffected by prior exercise . The pattern of hemodynamic response was not a result of changes in baroreflex sensitivity . The mechanisms underlying this result are discussed in relation to the discrepancies between subjective and physiological responses to mental stress , and the implication s for the use of exercise in stress management This investigation compared patterns of regional cerebral blood flow ( rCBF ) during exercise recovery both with and without postexercise hypotension ( PEH ) . Eight subjects were studied on 3 days with r and omly assigned conditions : 1 ) after 30 min of rest ; 2 ) after 30 min of moderate exercise ( M-Ex ) at 60 - 70 % heart rate ( HR ) reserve during PEH ; and 3 ) after 30 min of light exercise ( L-Ex ) at 20 % HR reserve with no PEH . Data were collected for HR , mean blood pressure ( MBP ) , and ratings of perceived exertion and relaxation , and rCBF was assessed by use of single-photon-emission computed tomography . With the use of ANOVA across conditions , there were differences ( P < 0.05 ; mean + /- SD ) from rest during exercise recovery from M-Ex ( HR = + 12 + /- 3 beats/min ; MBP = -9 + /- 2 mmHg ) , but not from L-Ex ( HR = + 2 + /- 2 beats/min ; MBP = -2 + /- 2 mmHg ) . After M-Ex , there were decreases ( P < 0.05 ) for the anterior cingulate ( -6.7 + /- 2 % ) , right and left inferior thalamus ( -10 + /- 3 % ) , right inferior insula ( -13 + /- 3 % ) , and left inferior anterior insula (-8 + /- 3 % ) , not observed after L-Ex . There were rCBF decreases for leg sensorimotor regions after both M-Ex ( -15 + /- 4 % ) and L-Ex ( -12 + /- 3 % ) and for the left superior anterior insula ( -7 + /- 3 % and -6 + /- 3 % ) , respectively . Data show that there are rCBF reductions within specific regions of the insular cortex and anterior cingulate cortex coupled with a postexercise hypotensive response after M-Ex . Findings suggest that these cerebral cortical regions , previously implicated in cardiovascular regulation during exercise , may also be involved in PEH The role of endogenous opioids in aerobic fitness-induced decrements in cardiovascular stress reactivity was examined by comparing the effects of opioid antagonism with naltrexone on responses to stress in young adults with high versus low levels of aerobic fitness . Two hundred forty subjects were given an activity question naire and males with the highest ( Fit ) and lowest ( Nonfit ) aerobic activity profiles were recruited for maximal oxygen consumption ( VO2max ) treadmill testing and psychological stress testing ( final sample N = 28 ) . Heart rate and blood pressures were measured during performance on a computer-controlled arithmetic task after pretreatment with either naltrexone ( Trexan , DuPont ) or a placebo . During placebo challenges , Fit subjects , compared with Nonfit , showed lower heart rate reactivity during stress and lower mean arterial blood pressures immediately before and during recovery from stress . Naltrexone eliminated these reactivity differences by increasing heart rate reactivity and raising mean arterial blood pressure in Fit subjects . These data suggest that aerobic fitness is associated with enhanced opioidergic inhibition of circulatory stress reactivity . Opioidergic modulatory effects on stress reactivity may comprise an important mechanism in fitness-associated risk reduction for cardiovascular disease We evaluated the experimental hypothesis that an acute bout of aerobic exercise ( AE ) serves as a buffer to psychosocial stress responses in low to moderate physically fit women . Forty-eight ( 24 White , 24 Black ) 25- to 40-year-old women participated in two counterbalanced experimental conditions : an attention control and a 40-min bout of AE at 70 % heart rate ( HR ) reserve . The attention control and AE treatments were followed by ( a ) 30 min of quiet rest , ( b ) exposure to mental and interpersonal threat , and ( c ) 5 min of recovery . Blood pressure ( BP ) and HR were monitored at baseline , during the stressors , and throughout recovery . Self-reported distress was assessed before each stressor and upon completion of the recovery period . The results provided clear evidence that exercise dampens BP reactivity to psychosocial stress . Additionally , compared with the attention placebo control , AE reduced both the frequency and intensity of anxiety-related thoughts that occur in anticipation of interpersonal threat and challenge We examined the correspondence between laboratory measures of cardiovascular reactivity ( CVR ) and within-person changes in cardiovascular activity during the challenges of daily life , after adjustment for posture , activity , and other effects . Healthy adults ( n = 335 ) were administered laboratory measures of CVR along with 6 days of ambulatory blood pressure monitoring and electronic diary reports . Compared with low reactors , high laboratory systolic blood pressure ( SBP ) reactors showed larger increases in SBP during periods of high task dem and or low decisional control in daily life . High diastolic blood pressure ( DBP ) reactors showed larger increases in ambulatory DBP during situations rated as both low control and high dem and . This multilevel modeling approach may enhance our ability to detect the correspondence between laboratory and ambulatory measures of CVR , and to identify the circumstances under which it may be most clearly observed BACKGROUND The study objective was to determine the health and quality -of-life effects of moderate-intensity exercise among older women family caregivers . METHODS This 12-month r and omized controlled trial involved a volunteer sample of 100 women aged 49 to 82 years who were sedentary , free of cardiovascular disease , and caring for a relative with dementia . Participants were r and omized to 12 months of home-based , telephone-supervised , moderate-intensity exercise training or to an attention-control ( nutrition education ) program . Exercise consisted of four 30- to 40-minute endurance exercise sessions ( brisk walking ) prescribed per week at 60 % to 75 % of heart rate reserve based on peak treadmill exercise heart rate . Main outcomes were stress-induced cardiovascular reactivity levels , rated sleep quality , and reported psychological distress . RESULTS Compared with nutrition participants ( NU ) , exercise participants ( EX ) showed significant improvements in the following : total energy expenditure ( baseline and post-test means [ SD ] for EX = 1.4 [ 1.9 ] and 2.2 [ 2.2 ] kcal/kg/day ; for NU = 1.2 [ 1.7 ] and 1.2 [ 1.6 ] kcal/kg/day ; p < .02 ) ; stress-induced blood pressure reactivity ( baseline and post-test systolic blood pressure reactivity values for EX = 21.6 [ 12.3 ] and 12.4 [ 11.2 ] mm Hg ; for NU = 17.9 [ 10.2 ] and 17.7 [ 13.8 ] mm Hg ; p < .024 ) ; and sleep quality ( p < .05 ) . NU showed significant improvements in percentages of total calories from fats and saturated fats relative to EX ( p values < .01 ) . Both groups reported improvements in psychological distress . Conclusions . Family caregivers can benefit from initiating a regular moderate-intensity exercise program in terms of reductions in stress-induced cardiovascular reactivity and improvements in rated sleep quality Objectives : Mild to moderate acute , endurance exercise has generally been shown to reduce blood pressure ( BP ) in hypertensive ( HT ) individuals . Whether a slightly more strenuous bout of exercise can elicit a greater and more prolonged BP reduction is unknown . Therefore , the purpose of this study was to examine the effects of two , 30-min exercise bouts , conducted at 50 % and 75 % of maximal oxygen uptake ( VO2max ) , on the quantity and quality of BP reduction over a 24-h period . Methods : Sixteen , Stage 1 and 2 non-medicated , HT ( 8 men/8 women ) subjects were matched with normotensive ( NT ) men and women ( n = 16 ) . All subjects were evaluated for VO2max with a symptom-limited treadmill test and then completed a 30-min exercise bout at 50 % and 75 % of VO2max as well as a control ( no exercise ) session in r and om fashion on separate days . Twenty-four hour ambulatory BPs were measured after both the exercise and control setting s. Data was assessed at 1 , 3 , 6 , 12 , and 24 h post-exercise and control session . Results : A repeated- measures ANOVA showed non-significant differences between HT men and women and that both exercise intensities , relative to the control session , significantly ( P < 0.05 ) reduced systolic ( s ) and diastolic ( d ) bps . nt subjects showed non-significant reductions following both intensities . the reductions in the ht men and women averaged 4 and 9 mm hg (sbp)/5 and 7 mm hg ( dbp ) for 50 % and 75 % , respectively . on average , the ht subjects ( men and women combined ) maintained significant sbp reductions for 13 h after the 75 % bout compared to 4 h after the 50 % intensity . likewise , dbp was reduced for an average of 11 h following the 75 % bout compared to 4 h after the 50 % intensity . Conclusions : These results suggest that an exercise bout conducted between 50–75 % VO2max significantly decreases SBP and DBP in HT subjects and that a greater and longer-lasting absolute reduction is evident following a 75 % of maximum bout of exercise The effect of 30 min of cycling exercise at 60 % VO2max on hemodynamic responses to the Stroop and cold pressor tests in 12 norm Output:	In conclusion , an acute bout of aerobic exercise appears to have a significant impact on the BP response to a psychosocial stressor
MS22076	*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 study the pharmacodynamic properties of the subcutaneously injected long-acting insulin analog HOE901 ( 30 microg/ml zinc ) in comparison with those of NPH insulin and placebo . RESEARCH DESIGN AND METHODS In this single-center double-blind euglycemic glucose clamp study , 15 healthy male volunteers ( aged 27 + /- 4 years , BMI 22.2 + /- 1.8 kg/m2 ) received single subcutaneous injections of 0.4 U/kg body wt of HOE901 , NPH insulin , or placebo on 3 study days in a r and omized order . The necessary glucose infusion rates ( GIRs ) to keep blood glucose concentrations constant at 5.0 mmol/l were determined over a 30-h period after administration . RESULTS The injection of HOE901 did not induce the pronounced peak in metabolic activity observed with NPH insulin ( GIRmax 5.3 + /- 1.1 vs. 7.7 + /- 1.3 mg x kg(-1 ) x min(-1 ) ) ( P < 0.05 ) ; after an initial rise , metabolic activity was rather constant over the study period . This lack of peak was confirmed by a lower glucose consumption in the first 4 h after injection ( area under the curve from 0 to 4 h [ AUC(0 - 4 h ) ] 1.02 + /- 0.34 vs. 1.48 + /- 0.34 g/kg ) ( P < 0.001 ) with HOE901 , as compared with NPH insulin . In this single-dose study , the metabolic effect measured over a period of 30 h was lower with HOE901 than with NPH insulin ( AUC(0 - 30 h ) 7.93 + /- 1.82 vs. 9.24 + /- 1.29 g/kg ) ( P < 0.05 ) . CONCLUSIONS This study shows that the soluble long-acting insulin analog HOE901 induces a smoother metabolic effect than NPH insulin , from which a better substitution of basal insulin requirements may follow Objective Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn ( NPH ) insulin in r and omized controlled trials . Evidence of severe hypoglycemic risk with insulin detemir , insulin glargine , or NPH insulin is presented from a nationwide retrospective data base study . Research design and methods Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin , insulin glargine , or insulin detemir in Finl and between 2000 and 2009 were analyzed . Incidence rates with 95 % confidence intervals ( CIs ) were calculated using Poisson regression . Hazard ratios were estimated using Cox 's regression with adjustments for relevant background variables . Results The adjusted risk of hospital/ secondary healthcare visits due to the first severe hypoglycemic event was 21.7 % ( 95 % CI 9.6–32.1 % , p < 0.001 ) lower for insulin detemir and 9.9 % ( 95 % CI 1.5–17.6 % , p = 0.022 ) lower for insulin glargine versus NPH insulin . Risk of hypoglycemic coma recurrence was 36.3 % ( 95 % CI 8.9–55.5 % , p = 0.014 ) lower for detemir and 9.5 % but not significantly ( 95 % CI −10.2 to 25.7 % , p = 0.318 ) lower for glargine versus NPH insulin . Risk of all hypoglycemic coma events was 30.8 % ( 95 % CI 16.2–42.8 % , p-value < 0.001 ) lower for detemir and 15.6 % ( 95 % CI 5.1–25.0 % , p-value 0.005 ) lower for glargine versus NPH . Insulin detemir had a significantly lower risk for first ( 13.1 % lower [ p = 0.034 ] ) , recurrent ( 29.6 % lower [ p = 0.021 ] ) , and all ( 17.9 % lower [ p = 0.016 ] ) severe hypoglycemic events than insulin glargine . Conclusions There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice In this open study of clinical practice , 142 paediatric patients with type 1 diabetes mellitus ( > 1 year duration ) , stratified by age , received pr and ial insulin ( regular or lispro ) and either once daily insulin glargine ( GLAR ; n=74 ) , titrated to target fasting blood glucose ( FBG ) levels 4.4 - 7.8 mmol/l , or NPH/semilente insulin ( NPH insulin , administered once , twice or three times daily ; n=68 ) , titrated to target FBG 4.4 - 8.9 mmol/l . Both groups were treated for 20 + /- 10 months . HbA(1c ) significantly increased in GLAR ( 7.3 + /- 1.0 % to 7.6 + /- 1.1 % ; p = 0.003 ) and NPH/semilente insulin ( 7.7 + /- 1.6 % to 8.3 + /- 1.5 % ; p = 0.0001 ) treated patients . The incidence of symptomatic hypoglycaemia was comparable between GLAR versus NPH/semilente insulin at endpoint ( 2.19 vs. 1.94 episodes/week ) ; however , the overall incidence of severe hypoglycaemia was significantly lower with GLAR versus NPH/semilente insulin ( 0.14 vs. 0.73 events/patient-year ; p = 0.002 ) . The daily insulin dose was similar between the treatment groups ; however , perceived quality of life ( QoL ) was better with GLAR . GLAR is associated with equivalent glycaemic control , less severe hypoglycaemia and improved QoL compared with NPH/semilente insulin OBJECTIVE To define the relationship between HbA(1c ) and plasma glucose ( PG ) levels in patients with type 1 diabetes using data from the Diabetes Control and Complications Trial ( DCCT ) . RESEARCH DESIGN AND METHODS The DCCT was a multicenter , r and omized clinical trial design ed to compare intensive and conventional therapies and their relative effects on the development and progression of diabetic complications in patients with type 1 diabetes . Quarterly HbA(1c ) and corresponding seven-point capillary blood glucose profiles ( premeal , postmeal , and bedtime ) obtained in the DCCT were analyzed to define the relationship between HbA(1c ) and PG . Only data from complete profiles with corresponding HbA(1c ) were used ( n = 26,056 ) . Of the 1,441 subjects who participated in the study , 2 were excluded due to missing data . Mean plasma glucose ( MPG ) was estimated by multiplying capillary blood glucose by 1.11 . Linear regression analysis weighted by the number of observations per subject was used to correlate MPG and HbA(1c ) . RESULTS Linear regression analysis , using MPG and HbA(1c ) summarized by patient ( n = 1,439 ) , produced a relationship of MPG ( mmol/l ) = ( 1.98 . HbA(1c ) ) - 4.29 or MPG ( mg/dl ) = ( 35.6 . HbA(1c ) ) - 77.3 , r = 0.82 ) . Among individual time points , afternoon and evening PG ( postlunch , predinner , postdinner , and bedtime ) showed higher correlations with HbA(1c ) than the morning time points ( prebreakfast , postbreakfast , and prelunch ) . CONCLUSIONS We have defined the relationship between HbA(1c ) and PG as assessed in the DCCT . Knowing this relationship can help patients with diabetes and their healthcare providers set day-to-day targets for PG to achieve specific HbA(1c ) goals OBJECTIVE To determine the efficacy and safety of insulin glargine ( IG ) in children and adolescents with type 1 diabetes . In a prospect i ve , 6-month study , 80 patients , aged 2 - 19 years , received IG once daily plus insulin regular or rapid analogue before meals . The data of body mass index , frequency of severe hypoglycaemia , daily mean blood glucose , fasting blood glucose , haemoglobin A1c and total daily insulin dosage before and after institution of glargine therapy were collected . RESULTS After 6 months , the average HbA1c level in the entire cohort dropped from 7.63+/-0.81 to 7.14+/-0.70 % ( p<0.001 ) . Fasting blood glucose decreased from 161+/-37 to 150+/-35 mg/dl ( p<0.05 ) in the total group . Severe hypoglycaemic episodes were reduced from 0.18 events per patient in the 6 months before IG therapy to 0.11 events per patient in the 6 months after IG therapy . The total daily insulin dose was reduced in the entire group from 0.90+/-0.32 to 0.83+/-0.29 u/kg/day ( p<0.05 ) . Body mass index ( BMI ) remained unchanged . In the 14 preschooler children , the HbA1c dropped from 7.54+/-0.60 to 6.96+/-0.57 % ( p<0.05 ) . CONCLUSIONS Insulin glargine is an efficacious treatment to improve metabolic control in children and adolescents with type 1 diabetes . It also improved the metabolic control in preschool-age children , without increasing the number of hypoglycaemic events BACKGROUND The goal of new therapies introduced for type 1 diabetes should be to decrease hypoglycemic episodes while improving glycemic control . METHODS A data base was used to computer match the baseline A1C values in 196 subjects with type 1 diabetes receiving multiple daily injections ( MDI ) consisting of four or more injections per day . There were 98 patients transferred from NPH to insulin glargine ( Lantus , Aventis Pharmaceuticals , Bridgewater , NJ ) , and 98 patients remained on NPH throughout the study . The gender distribution and mean age ( approximately 32 years ) , duration of diabetes ( approximately 16 years ) , and duration of treatment ( approximately 13 months ) were not significantly different between the groups . The majority of patients were well controlled ( > 50 % in both groups had an A1C < 7 % ) . RESULTS The mean A1c values were not significantly different in the groups at baseline or at follow-up . Severe hypoglycemic episodes per patient per year were significantly lower in the glargine group compared with the NPH group ( 0.5 vs. 1.2 , respectively ; P = 0.04 ) . The mean end-of- study total ( P = 0.03 ) and long-acting ( P = 0.0001 ) doses were significantly reduced from baseline in the group that switched to glargine , but not in the group that remained on NPH , with no change in the short-acting dose in either group . The weight gain was significantly higher in the NPH group at the end of the study ( P = 0.004 ) with no significant change in the glargine group . CONCLUSIONS Transfer to glargine treatment from NPH in MDI regimens significantly reduces severe hypoglycemic episodes despite a decline in long-acting basal insulin without significant weight gain OBJECTIVE Insulin glargine offers sustained insulin delivery for 24 h. Change to glargine treatment consistently results in lower fasting glucose and fewer hypoglycemic episodes in children with type 1 diabetes compared to continuation of NPH , although glargine has not been shown to improve HbA1c in r and omized trials . Studies comparing glargine and NPH in multiple injection therapy in children treated from diagnosis of type 1 diabetes are lacking . METHODS HbA1c and insulin requirement were compared in a retrospective study of children ( 7 - 17 yr of age ) with type 1 diabetes treated from diagnosis with basal insulin glargine ( n = 49 ) or NPH ( n = 49 ) in a multiple injection therapy ( MIT ) regimen with a rapid-acting insulin analogue . Patients were followed every third month for 1 yr . HbA1c , insulin dose , and weight data were retrieved . RESULTS HbA1c ( mean ± SD ) was lower at 3 - 5 months ( 5.5 ± 0.89 vs. 6.2 ± 0.89 % , p < 0.05 ) and 6 - 9 months ( 5.6 ± 1.14 vs. 6.6 ± 0.99 % ; p < 0.001 ) in glargine treated . After Output:	Conclusion Given the high heterogeneity of the studies , the discrete value presented by the estimated effect on effectiveness and safety , potential conflicts of interest of the studies , and the appreciable higher cost of insulin glargine , there is still no support for recommending first-line therapy with analogs .
MS22077	*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: Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design Eighteen children with hemiplegia , mean age 8 years 5 months , underwent gait analysis and musculoskeletal modelling using specially design ed software . The maximum lengths of the hamstrings were determined for each child walking in and out of an ankle-foot orthosis ( AFO ) . The muscles were deemed to be short if shorter than the normal average -1SD . In bare feet 8 participants had short medial hamstrings with a higher proportion of these in the less involved individuals . All participants showed an increase in maximum hamstring length when wearing an AFO . In all but one child this was sufficient to restore hamstring length to within normal limits . These finding suggest that hamstring pathology in hemiplegic gait is usually secondary to more distal lower limb pathology This study compared the functional efficacy of three commonly prescribed ankle-foot orthosis ( AFO ) configurations ( solid [ SAFO ] , hinged [ HAFO ] , and posterior leaf spring [ PLS ] ) . Sixteen independently ambulatory children ( 10 males , six females ; mean age 8 years 4 months , SD 2 years 4 months ; range 4 years 4 months to 11 years 6 months ) with spastic diplegia participated in this study . Four children were classified at level I of the Gross Motor Function Classification System ( GMFCS ; Palisano et al. 1997 ) ; the remaining 12 were at level II . Children were assessed barefoot ( BF ) at baseline ( baseline assessment of energy consumption was performed with shoes on , no AFO ) and in each orthotic configuration after three months of use , using gait analysis , oxygen consumption , and functional outcome measures . AFO use did not markedly alter joint kinematics or kinetics at the pelvis , hip , or knee . All AFO configurations normalized ankle kinematics in stance , increased step/stride length , decreased cadence , and decreased energy cost of walking . Functionally , all AFO configurations improved the execution of walking/running/jumping skills , upper extremity coordination , and fine motor speed/dexterity . However , the quality of gross motor skill performance and independence in mobility were unchanged . These results suggest that most children with spastic diplegia benefit functionally from AFO use . However , some children at GMFCS level II demonstrated a subtle but detrimental effect on function with HAFO use , shown by an increase in peak knee extensor moment in early stance , excessive ankle dorsiflexion , decreased walking velocity , and greater energy cost . Therefore , constraining ankle motion by using a PLS or SAFO should be considered for most , but not all , children with spastic diplegia Twenty-one subjects with spastic diplegic cerebral palsy were studied to quantify the effects of fixed and articulated ankle-foot orthoses ( AFOs ) on gait and delineate criteria for their use . Children underwent gait analysis under three conditions , fixed AFOs ( FAFOs ) , articulated AFOs ( AAFOs ) , and shoes alone . Greater dorsiflexion occurred at initial contact with both FAFOs and AAFOs than shoes alone . Dorsiflexion at terminal stance was greatest in AAFOs . Plantarflexor power generation at preswing was preserved in AAFOs . No differences were found in knee position during stance . Knee-extensor strength was positively related to knee extension during stance . No relationships were found between dorsiflexion range of motion , calf spasticity and strength , and peak dorsiflexion during stance . AAFOs are appropriate for subjects with varying degrees of calf spasticity , as long as adequate passive range of motion is available . These findings can be applied primarily to children who do not have a preexisting tendency to crouch Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field The purpose of this study was to examine the effectiveness of the hinged ankle-foot orthosis ( HAFO ) , posterior leaf spring ( PLS ) , and solid ankle-foot orthosis ( SAFO ) , in preventing contracture , improving efficiency of gait , and enhancing performance of functional motor skills in 30 children ( 21 male , 9 female ; mean age 9 years 4 months ; age range 4 to 18 years , ) with spastic hemiplegia . Following a 3-month baseline period of no ankle-foot orthosis ( AFO ) use , each AFO was worn for 3 months after which ankle range of motion , gait analysis , energy consumption , and functional motor skills were assessed . The HAFO and PLS increased passive ankle dorsiflexion and normalization of ankle rocker function during gait . Normalization of knee motion in stance was dependent upon the knee abnormality present and AFO configuration . The HAFO was the most effective in controlling knee hyperextension in stance , while PLS was the most effective in promoting knee extension in children with > 10 degree knee flexion in stance . Energy efficiency was improved in 21 of the children , with 13 of these children demonstrating the greatest improvement in HAFO and PLS . Improvements in functional mobility were greatest in the HAFO and PLS The effectiveness of ankle-foot orthoses ( AFOs ) on walking pattern was studied in 12 children with cerebral palsy between the ages of 3 and 7 years . Over a 2-year period two trials of fortnightly periods without AFOs were carried out . The range of ankle dorsiflexion , video analysis looking specifically at footfall , and rank scoring of the mediolateral shear force obtained using an oscilloscope printout from a Kistler force platform were compared with measurements obtained during periods when the child was wearing AFOs . The results using different outcomes were consistent , and indicated that the range of movement and gait deteriorated during the two trial periods during which the splints were not worn compared with periods during which the splints were worn . This finding needs to be confirmed in a large r and omised controlled trial BACKGROUND AND PURPOSE This study compared the effects of dynamic ankle-foot orthoses ( DAFOs ) with a plantar-flexion stop , polypropylene solid ankle-foot orthoses ( AFOs ) , and no AFOs on the gait of children with cerebral palsy ( CP ) . These orthoses were used to reduce the excessive ankle plantar flexion during the stance phase of gait . SUBJECTS AND METHODS Ten children with spastic CP ( 6 with diplegia and 4 with hemiplegia ) were tested after wearing no AFOs for an initial 2-week period , solid AFOs for 1 month , no AFOs for an additional 2 weeks , and DAFOs for 1 month . The effects of the two orthoses and no AFOs on lower-extremity muscle timing , joint motions , and temporal-distance characteristics were compared . RESULTS Both orthoses increased stride length , decreased cadence , and reduced excessive ankle plantar flexion when compared with no orthoses . No differences were found for the gait variables when comparing the two orthoses . CONCLUSION AND DISCUSSION Based on the data , the authors believe that although both orthoses would be recommended for children with spastic CP and excessive ankle plantar flexion during stance , additional individual factors should be considered when selecting either orthosis OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity OBJECTIVE To investigate the effectiveness of the hinged ankle-foot orthosis ( AFO ) on sit-to-st and ( STS ) transfers in children with spastic cerebral palsy . DESIGN Before-after trial . SETTING University-affiliated hospital . PARTICIPANTS Nineteen spastic diplegic children ( age range , 2 - 6 y ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES The transitional movement of STS was tested in r and om order with children while wearing the barefoot and hinged AFOs . The temporal , kinematic , and kinetic data during the task were collected by using a motion analyzer ( with 6 infrared cameras ) . Statistical comparison between barefoot and hinged AFO was done with the Wilcoxon signed-rank test . RESULTS Total duration of STS transfer was significantly shortened with the hinged AFO ( P < .05 ) . The initial knee flexion , the initial angle , and the final angle of ankle dorsiflexion were increased with the AFO , compared with when barefoot ( P < .05 ) . However , the increased pelvic tilt and hip flexion while barefoot was not reduced with the AFO . The maximal moment and power of hip and knee joints were significantly increased with the AFO ( P < .05 ) , whereas the maximal moment and power of the ankle joint were not significantly changed when wearing the AFO . CONCLUSIONS Although proximal compensatory strategy of increased pelvic tilt and hip flexion did not change with the hinged AFO , some improvements of temporal , kinematic , and kinetic parameters were identified during the task . These findings suggest that a hinged AFO is beneficial for STS transfer activity for children with spastic diplegia Several studies indicated that walking with an ankle foot orthosis ( AFO ) impaired third rocker . The purpose of this study was to evaluate the effects of two types of orthoses , with similar goal setting s , on gait , in a homogeneous group of children , using both barefoot and shoe walking as control conditions . Fifteen children with hemiplegia , aged between 4 and 10 years , received two types of individually tuned AFOs : common posterior leaf-spring ( PLS ) and Dual Carbon Fiber Spring AFO ( CFO ) ( with carbon fibre at the dorsal part of the orthosis ) . Both orthoses were expected to prevent plantar flexion , thus improving first rocker , allowing dorsiflexion to improve second rocker , absorbing energy during second rocker , and returning it during the third rocker . The effect of the AFOs was studied using objective gait analysis , including 3D kinematics , and kinetics in four conditions : barefoot , shoes without AFO , and PLS and CFO combined with shoes . Several gait parameters significantly changed in shoe walking compared Output:	The findings of this review have been used to generate guidelines for best practice of reporting for AFO intervention studies .
MS22078	*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 this study was to compare changes in velocity-specific adaptations in moderately resistance-trained athletes who trained with either low or high resistances . The study used tests of sport-specific skills across an intermediate-to high-velocity spectrum . Thirty NCAA Division I baseball players were r and omly assigned to either a low-resistance ( 40–60 % 1 repetition maximum [ 1RM ] ) training group or a high-resistance ( 70–90 % 1RM ) training group . Both of the training groups intended to maximally accelerate each repetition during the concentric phase ( IMCA ) . The 10 weeks of training consisted of 4 training sessions a week using basic core exercises . Peak force , velocity and power were evaluated during set angle and depth jumps as well as weighted jumps using 30 and 50 % 1RM . Squat 1RMs were also tested . Although no interactions for any of the jump tests were found , trends supported the hypothesis of velocity-specific training . Percentage gains suggest that the combined use of heavier training loads ( 70–90 % 1RM ) and IMCA tend to increase peak force in the lower-body leg and hip extensors . Trends also show that the combined use of lighter training loads ( 40–60 % 1RM ) and IMCA tend to increase peak power and peak velocity in the lower-body leg and hip extensors . The high-resistance group improved squats more than the low-resistance group ( p < 0.05 ; + 22.7 vs. + 16.1 kg ) . The results of this study support the use of a combination of heavier training loads and IMCA to increase 1RM strength in the lower bodies of resistance-trained athletes The purpose of the present study was to examine the influence of direct supervision on muscular strength , power , and running speed during 12 weeks of resistance training in young rugby league players . Two matched groups of young ( 16.7 ± 1.1 years [ mean ± SD ] ) , talented rugby league players completed the same periodized resistance-training program in either a supervised ( SUP ) ( N = 21 ) or an unsupervised ( UNSUP ) ( N = 21 ) environment . Measures of 3 repetition maximum ( 3RM ) bench press , 3RM squat , maximal chin-ups , vertical jump , 10– and 20-m sprints , and body mass were completed pretest ( week 0 ) , midtest ( week 6 ) , and posttest ( week 12 ) training program . Results show that 12 weeks of periodized resistance training result ed in an increased body mass , 3RM bench press , 3RM squat , maximum number of chin-ups , vertical jump height , and 10– and 20-m sprint performance in both groups ( p < 0.05 ) . The SUP group completed significantly more training sessions , which were significantly correlated to strength increases for 3RM bench press and squat ( p < 0.05 ) . Furthermore , the SUP group significantly increased 3RM squat strength ( at 6 and 12 weeks ) and 3RM bench press strength ( 12 weeks ) when compared to the UNSUP group ( p < 0.05 ) . Finally , the percent increase in the 3RM bench press , 3RM squat , and chin-upmax was also significantly greater in the SUP group than in the UNSUP group ( p < 0.05 ) . These findings show that the direct supervision of resistance training in young athletes results in greater training adherence and increased strength gains than does unsupervised training For many sporting activities , initial speed rather than maximal speed would be considered of greater importance to successful performance . The purpose of this study was to identify the relationship between strength and power and measures of first-step quickness ( 5-m time ) , acceleration ( 10-m time ) , and maximal speed ( 30-m time ) . The maximal strength ( 3 repetition maximum [ 3RM ] ) , power ( 30-kg jump squat , countermovement , and drop jumps ) , isokinetic strength measures ( hamstring and quadriceps peak torques and ratios at 608·s-1 and 3008·s-1 ) and 5-m , 10-m , and 30-m sprint times of 26 part-time and full-time professional rugby league players ( age 23.2 ± 3.3 years ) were measured . To examine the importance of the strength and power measures on sprint performance , a correlational approach and a comparison between means of the fastest and slowest players was used . The correlations between the 3RM , drop jump , isokinetic strength measures , and the 3 measures of sport speed were nonsignificant . Correlations between the jump squat ( height and relative power output ) and countermovement jump height and the 3 speed measures were significant ( r = −0.43 to −0.66 , p < 0.05 ) . The squat and countermovement jump heights as well as squat jump relative power output were the only variables found to be significantly greater in the fast players . It was suggested that improving the power to weight ratio as well as plyometric training involving countermovement and loaded jump-squat training may be more effective for enhancing sport speed in elite players Six men and six women trained the elbow flexors of both arms 3 d.wk-1 for 20 wk . In each training session , one arm did 3 - 5 sets of 10 maximal concentric actions on an accommodating resistance device ( ARD ) , the other arm 3 - 5 sets of 8 - 12 coupled eccentric/concentric actions ( repetitions ) to volitional failure ( 8 - 12 RM ) on a weight resistance device ( WRD ) . The average " intensity " ( force of concentric actions ) was approximately 1.25 times greater in ARD training , the average " volume " ( number of actions x force of actions ) 1.6 times greater in WRD training , and the time required to complete a training session the same for each . Both types of training produced significant increases in a single maximum weight lift ( 1 RM on the WRD ) , in the peak force of a single maximal concentric action measured on the ARD and an isovelocity dynamometer , and in biceps , brachialis , and total elbow flexor cross-sectional area ( CSA ) . Biceps Type I and II fiber area did not change significantly . WRD training produced greater increases than ARD training in the 1 RM test on the WRD and in brachialis CSA . The data indicate that both of these common training regimens effectively increase strength and muscle mass , but the weight training regimen may be more effective for increasing muscle mass The purpose of this study was to determine if three training loads equated by volume differed in terms of the temporal , kinematic and kinetic characteristics of each set . Twelve experienced weightlifters ( 30.2+/-10.6 years old and 75.8+/-13.0 kg ) performed three sets ( 6 x 30 % 1RM , 3 x 60 % 1RM and 2 x 90 % 1RM ) of ballistic squats on an instrumented supine squat machine . Repeated measures ANOVA and Tukey HSD post hoc comparisons were used to distinguish significant differences between the three training loads on a variety of temporal , kinematic and kinetic variables . Significantly ( p < 0.05 ) greater total time under tension during the eccentric ( 41 - 53 % ) and concentric phases ( 27 - 31 % ) was observed for the 30 % 1RM condition compared to the other two conditions . Similarly , the lighter loading intensity result ed in significantly greater total eccentric ( 9 - 19 % ) and concentric ( 14 - 24 % ) force output compared to the other two conditions . Greater total power output was associated with the 30 % 1RM condition for both the eccentric ( 25 - 48 % ) and concentric ( 40 - 69 % ) phases . Greater total work ( 9 - 24 % ) was also associated with the 30 % 1RM condition . The 60 % 1RM condition produced significantly greater total work , force and power compared to the 90 % 1RM condition . However , greater concentric impulse ( 29 - 42 % ) was associated with the 90 % 1RM condition . It is suggested that strength and power research needs to adopt a set kinematic and kinetic analysis approach within the research design s so that a better underst and ing of the nature of the neuromuscular adaptations elicited by different loading parameters is achieved The purpose of this investigation was to examine the effect of an 8-week training program with heavy- vs. light-load jump squats on various physical performance measures and electromyography ( EMG ) . Twenty-six athletic men with varying levels of resistance training experience performed sessions of jump squats with either 30 % ( JS30 , n = 9 ) or 80 % ( JS80 , n = 10 ) of their one repetition maximum in the squat ( 1RM ) or served as a control ( C , n = 7 ) . An agility test , 20-m sprint , and jump squats with 30 % ( 30J ) , 55 % ( 55J ) , and 80 % ( 80J ) of their 1RM were performed before and after training . Peak force , peak velocity ( PV ) , peak power ( PP ) , jump height , and average EMG ( concentric phase ) were calculated for the jumps . There were significant increases in PP and PV in the 30J , 55J , and 80J for the JS30 group ( p < 0.05 ) . The JS30 group also significantly increased in the 1RM with a trend towards improved 20-m sprint times . In contrast , the JS80 group significantly increased both PF and PP in the 55J and 80J and significantly increased in the 1RM but ran significantly slower in the 20-m sprint . In the 30J the JS30 group 's percentage increase in EMG activity was significantly different from the C group . In the 80J the JS80 group 's percentage increase in EMG activity was significantly different from the C group . This investigation indicates that training with light-load jump squats results in increased movement velocity capabilities and that velocity-specific changes in muscle activity may play a key role in this adaptation Abstract Seventeen subjects performed resistance training of the leg extensor and flexor muscle groups two ( 2/wk ) or three ( 3/wk ) times per week . Changes in the relative myosin heavy chain ( MHC ) isoform contents ( I , IIa and IIx ) of the vastus lateralis and isometric , isokinetic and squat-lift one-repetition maximum ( 1RM ) strength were compared between conditions after both a common training period ( 6 weeks ) and number of training sessions ( 18 ) . After 6 weeks and 18 sessions ( 9 weeks for the 2/wk group ) , increments in 1RM strength for the 3/wk and 2/wk groups were similar [ effect size ( ES ) differences ≈0.3 , 3/wk > 2/wk ] , whereas the 2/wk group presented greater isokinetic ( ES differences = 0.3–1.2 ) and isometric ( ES differences ≈0.7 ) strength increases than the 3/wk condition . A significant ( P < 0.05 ) increase in MHC IIa percentage was evident for the 2/wk group after 18 sessions . Both training groups exhibited a trend towards a reduction in the relative MHC IIx and an increase in MHC IIa contents ( ES range = 0.5–1.24 ) . However , correlations between changes in the strength and MHC profiles were weak ( r2 : 0.0–0.5 ) . Thus , isometric and isokinetic strength responses to variations in training frequency differed from 1RM strength responses , and changes in strength were not strongly related to alterations in relative MHC content This study was performed to determine which of three theoretically optimal resistance training modalities result ed in the greatest enhancement in the performance of a series of dynamic athletic activities . The three training modalities included 1 ) traditional weight training , 2 ) plyometric training , and 3 ) explosive weight training at the load that maximized mechanical power output . Sixty-four previously trained subjects were r and omly allocated to four groups that included the above three training modalities and a control group . The experimental groups trained for 10 wk performing either heavy squat lifts , depth jumps , or weighted squat jumps . All subjects were tested prior to training , after 5 wk of training and at the completion of the training period . The test items included 1 ) 30-m sprint , 2 ) vertical jumps performed with and without a countermovement , 3 ) maximal cycle test , 4 ) isokinetic leg extension test , and 5 ) a maximal isometric test . The experimental group which trained with the load that maximized mechanical power achieved the best overall results in enhancing dynamic athletic performance recording statistically significant ( P < 0.05 ) improvements on most test items and producing statistically superior results to the two other training modalities on the jumping and isokinetic tests The purpose of this study was to explore the effects of 5 weeks of eccentrically loaded and unloaded jump squat training in experienced resistance-trained athletes during the strength/ power phase of a 15-week periodized off-season resistance training program . Forty-seven male college football players were r and omly assigned to 1 of 3 groups . One group performed the jump squat exercise using both concentric and eccentric phases of contraction ( CE ; n = 15 ) . A second group performed the jump squat exercise using the concentric phase only ( n = 16 ) , and a third group did not perform the jump squat exercise and served as control ( CT ; n = 16 ) . No significant differences between the groups were seen in power , vertical jump height , 40-yd sprint speed and agility performance . In addition , no differences between the groups were seen in integrated electromyography activity during the jump squat exercise . Significant differences between the CE and CT groups were seen in D 1RM squat ( 65.8 and 27.5 kg , respectively ) and D 1RM power clean ( 25.9 and 3.8 kg , respectively ) . No other between-group differences were observed . Results of this study provide evidence of the benefits Output:	Conclusion Based on current findings , training frequencies of two to four resistance training sessions per muscle group/week can be prescribed to develop upper and lower body strength and power . Strength levels can be maintained for up to 3 weeks of detraining , but decay rates will increase thereafter ( i.e. 5–16 weeks ) . The effect of explosive-ballistic training and detraining on pure power development and decay in elite rugby and American football players remain inconclusive . The long-term effects of periodized resistance training programmes on strength and power seem to follow the law of diminishing returns , as training exposure increases beyond 12–24 months , adaptation rates are reduced
MS22079	*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 spite of ongoing prevention developments , anterior cruciate ligament injury rates and the associated sex-disparity have remained , suggesting an incomplete underst and ing of the injury mechanism . While both fatigue and decision making are known in isolation to directly impact anterior cruciate ligament injury risk , their combined manifestations remain unknown . We thus examined the combined effects of fatigue and decision making on lower limb kinematics during sports relevant l and ings . METHODS Twenty five female National College Athletic Association athletes had initial contact and peak stance phase 3D lower limb joint kinematics quantified during anticipated and unanticipated single ( left and right ) leg l and ings , both before and during the accumulation of fatigue . Jump direction was governed by light stimuli activated prior to and during the pre-l and phase of respective anticipated and unanticipated trials . To induce fatigue , subjects performed repetitive squat ( n=5 ) and r and omly ordered jump sequences , until squats were no longer possible . Subject-based measures of each dependent factor were then calculated across pre-fatigue trials , and for those denoting 100 % and 50 % fatigue , and su bmi tted to a 3-way mixed design analysis of covariance to test for the main effects of fatigue time , decision and leg . FINDINGS Fatigue caused significant increases in initial contact hip extension and internal rotation , and in peak stance knee abduction and internal rotation and ankle supination angles . Fatigue-induced increases in initial contact hip rotations and in peak knee abduction angle were also significantly more pronounced during unanticipated compared to anticipated l and ings . INTERPRETATION The integrative effects of fatigue and decision making may represent a worst case scenario in terms of anterior cruciate ligament injury risk during dynamic single leg l and ings , by perpetuating substantial degradation and overload of central control mechanisms UNLABELLED Fatigue has been shown to alter the biomechanics of lower extremity during l and ing tasks . To date , no study has examined the effects of two types of fatigue on kinetics and kinematics . OBJECTIVES This study was conducted to assess biomechanical differences between two fatigue protocol s [ Slow Linear Oxidative Fatigue Protocol ( SLO-FP ) and Functional Agility Short-Term Fatigue Protocol ( FAST-FP ) ] . DESIGN Single-group repeated measures design . METHODS Fifteen female collegiate soccer players had to perform five successful trials of unanticipated sidestep cutting ( SS ) pre- and post-fatigue protocol s. The SLO-FP consisted of an initial VO(2peak ) test followed by 5-min rest , and a 30-min interval run . The FAST-FP consisted of 4 sets of a functional circuit . Biomechanical measures of the hip and knee were obtained at different instants while performing SS pre- and post-fatigue . Repeated 2 × 2 ANOVAs were conducted to examine task and fatigue differences . Alpha level set a priori at 0.05 . RESULTS During the FAST-FP , participants had increased knee internal rotation at initial contact ( IC ) ( 12.5 ± 5.9 ° ) when compared to the SLO-FP ( 7.9 ± 5.4 ° , p<0.001 ) . For hip flexion at IC , pre-fatigue had increased angles ( 36.4 ± 8.4 ° ) compared to post-fatigue ( 30.4 ± 9.3 ° , p=0.003 ) , also greater knee flexion during pre-fatigue ( 25.6 ± 6.8 ° ) than post-fatigue ( 22.4 ± 8.4 ° , p=0.022 ) . CONCLUSION The results of this study showed that hip and knee mechanics were substantially altered during both fatigue conditions OBJECTIVE : To compare the effects of an isokinetic fatigue protocol and a functional fatigue protocol on time to stabilization ( TTS ) , ground reaction force ( GRF ) , and joint kinematics during a jump l and ing . DESIGN AND SETTING : Subjects were assessed on 2 occasions for TTS , GRF , and joint kinematics immediately before and after completing a fatigue protocol . One week separated the 2 sessions , and the order of fatigue protocol s was r and omly assigned and counterbalanced . SUBJECTS : Twenty healthy male ( n = 8 , age = 21.8 + /- 1.4 years , height = 180.6 + /- 7.6 cm , and mass = 74.1 + /- 13.0 kg ) and female ( n = 12 , age = 22.2 + /- 2.1 years , height = 169.3 + /- 9.8 cm , and mass = 62.5 + /- 10.1 kg ) subjects volunteered to participate . MEASUREMENTS : Subjects performed 2-legged jumps equivalent to 50 % of maximum jump height , followed by a single-leg l and ing onto the center of a forceplate 70 cm from the starting position . Peak vertical GRF and vertical , medial-lateral , and anterior-posterior TTS were obtained from forceplate recordings . Maximum ankle dorsiflexion , knee-flexion , and knee-valgum angles were determined using 3-dimensional motion analysis . RESULTS : A 2-way analysis of variance with repeated measures revealed no significant differences when comparing TTS , GRF , and joint kinematics after isokinetic and functional fatigue protocol s. CONCLUSIONS : No difference was noted between isokinetic and functional fatigue protocol s relative to dynamic stability when l and ing from a jump Background Altered motor control strategies in l and ing and jumping maneuvers are a potential mechanism of noncontact anterior cruciate ligament injury . There are biomechanical differences between male and female athletes in the l and ing phase of stop-jump tasks . Fatigue is a risk factor in musculoskeletal injuries . Hypothesis Lower extremity muscle fatigue alters the knee kinetics and kinematics during the l and ing phase of 3 stop-jump tasks and increases an athlete 's risk of anterior cruciate ligament injury . Study Design Controlled laboratory study . Methods Three-dimensional videography and force plate data were collected for 20 recreational athletes ( 10 male and 10 female athletes ) performing 3 stop-jump tasks before and after completing a fatigue exercise . Knee joint angles and result ant forces and moments were calculated . Results Both male and female subjects had significantly increased peak proximal tibial anterior shear forces ( P = . 01 ) , increased valgus moments ( P = . 03 ) , and decreased knee flexion angles ( P = . 03 ) during l and ings of all 3 stop-jump tasks when fatigued . Fatigue did not significantly affect the peak knee extension moment for male or female athletes . Conclusion Fatigued recreational athletes demonstrate altered motor control strategies , which may increase anterior tibial shear force , strain on the anterior cruciate ligament , and risk of injury for both female and male subjects . Clinic Relevance Fatigued athletes may have an increased risk of noncontact anterior cruciate ligament injury PURPOSE Anterior cruciate ligament injuries and patellofemoral pain syndrome are both common and significant injuries to the knee that have been associated with hip weakness . Prospect i ve studies have linked the risk of experiencing either injury to alterations in the frontal plane knee angle and moment during activity . These components of knee mechanics are theorized to be affected by hip abductor weakness . The purpose of this study was to identify the effects of isolated hip abductor fatigue-induced weakness on lower extremity kinematics and kinetics in recreationally active women . METHODS Twenty participants performed cut , jump , and run tasks off a raised platform while three-dimensional motion analysis data were collected . Participants then performed an isolated hip abductor fatigue protocol in side lying against isokinetic resistance , followed immediately by repeated biomechanical data collection . Separate repeated- measures ANOVA ( P G 0.05 ) were used for each dependent variable . RESULTS After the hip fatigue protocol , regardless of task , the knee angle at initial ground contact was more adducted ( pre = 0.7 degrees + /- 3.4 degrees , post = 1.2 degrees + /- 3.9 degrees , F(1,19 ) = 5.3 , P = 0.032 ) , the knee underwent greater range of motion into abduction ( pre = 0.7 degrees + /- 1.5 degrees , post = 2.1 degrees + /- 1.6 degrees , F(1,19 ) = 73.2 , P < 0.001 ) , and there was a greater internal knee adductor moment ( pre = -2.6 + /- 13.3 N x m , post = 4.7 + /- 14.1 N x m , F(1,19 ) = 41.0 , P < 0.001 ) during the weight acceptance phase of stance . CONCLUSIONS This study demonstrates that simulated hip abductor weakness causes small alterations of frontal plane knee mechanics . Although some of these alterations occurred in directions associated with increased risk of knee injury , changes were small in magnitude , and the effect of these small changes on knee injury risk is unknown PURPOSE Fatigue contributes directly to anterior cruciate ligament ( ACL ) injury via promotion of high risk biomechanics . The potential for central fatigue to dominate this process , however , remains unclear . With central ly mediated movement behaviors being trainable , establishing this link seems critical for improved injury prevention . We thus determined whether fatigue-induced l and ing biomechanics were governed by a central ly fatiguing mechanism . METHODS Twenty female NCAA athletes had initial contact ( IC ) and peak stance ( PS ) three-dimensional hip and knee biomechanics quantified during anticipated and unanticipated single-leg l and ings , before and during unilateral fatigue accumulation . To induce fatigue , subjects performed repetitive ( n = 3 ) single-leg squats and r and omly ordered l and ings , until squats were no longer possible . Subject-based dependent factors were calculated across prefatigue trials and for those denoting 100 % , 75 % , 50 % , and 25 % fatigue and were su bmi tted to three-way mixed- design analyses of covariance to test for decision , fatigue time , and limb effects . RESULTS Fatigue produced significant ( P < 0.01 ) decreases in IC knee flexion angle and PS knee flexion moment and increases in PS hip internal rotation and knee abduction angles and moments , with differences maintained from 50 % fatigue through to maximum . Fatigue-induced increases in PS hip internal rotation angles and PS knee abduction angles and loads were also significantly ( P < 0.01 ) greater during unanticipated l and ings . Apart from PS hip moments , significant limb differences in fatigued l and ing biomechanics were not observed . CONCLUSIONS Unilateral fatigue induces a fatigue crossover to the contralateral limb during single-leg l and ings . Central fatigue thus seems to be a critical component of fatigue-induced sports l and ing strategies . Hence , targeted training of central control processes may be necessary to counter successfully the debilitative impact of fatigue on ACL injury risk BACKGROUND Lower extremity kinematics may change as a result of impaired hip muscle function , thereby placing athletes at increased risk of injury . The purpose of this study was to examine whether experimentally-induced hip extensor fatigue alters lower extremity kinematics during a jump-l and ing task in women . METHODS Forty healthy women were r and omly assigned to an experimental group in which participants performed modified Biering-Sørenson tests to fatigue the hip extensors or to a sham control group in which participants performed repeated push-ups to exhaustion . Three-dimensional hip and knee kinematics and gluteus maximus electromyography ( EMG ) signals were measured during jump-l and ing tests to examine the effects of hip extensor fatigue . FINDINGS Hip extension strength decreased in the experimental group by 25 % following the intervention , thereby confirming effects of the fatigue intervention . No group × time interactions in hip and knee motions were statistically significant , indicating that hip and knee kinematics did not change following the fatigue-inducing intervention . Gluteus maximus recruitment during the post-fatigue test , however , increased by 55 % in the experimental group . INTERPRETATION A 25 % reduction in hip extensor strength did not lead to changes in hip or knee kinematics . Rather , participants accommo date d for the loss of strength by recruiting more Gmax activation to complete the task . Gmax recruitment may compensate when hip extensor strength is impaired , suggesting that improved neuromuscular control can influence motor performance when strength is diminished Abstract The main aim of this study was to assess neuromuscular fatigue during a typical high-load , low-repetition loading protocol . Muscle stimulations were used to assess maximum voluntary contraction , resting single- and double-pulse twitch characteristics , and superimposed double-pulse twitch force ( used to calculate voluntary activation ) before and after an acute knee extension loading protocol . In our participants , who had previous resistance training experience , the mean voluntary activation level was 96.2 % in an unfatigued state . Maximum voluntary contraction ( −11.8 % ) , resting double-pulse twitch force ( −10.6 % ) , and voluntary activation ( −2.1 % ) were markedly decreased as a consequence of loading ( P < 0.05 ) . In addition , although potentiated twitch characteristics were observed during the loading protocol , this was short-lived , as fatigue surpassed the potentiation mechanisms . Our results show that both central and peripheral mechanisms contributed to neuromuscular fatigue during the present loading protocol Output:	There was no consistency among investigations regarding the effects of fatigue on hip , knee , or ankle joint angles and moments or surface electromyography muscle activation patterns . The fatigue protocol s typically did not produce statistically significant changes in ground-reaction forces . Conclusion : Published fatigue protocol s did not uniformly produce alterations in lower limb neuromuscular factors that heighten the risk of noncontact ACL injuries . Therefore , justification does not currently exist for major changes in ACL injury prevention training programs to account for potential fatigue effects .
MS22080	*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 Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely Background Previous analysis of a single data set in acute pain following third molar extraction demonstrated a strong relationship between the speed of reduction of pain intensity and overall pain relief , as well as need for additional analgesia . Methods Individual patient data analysis of a single r and omized , double-blind trial of placebo , paracetamol 1000 mg , ibuprofen sodium 400 mg and ibuprofen-poloxamer 400 mg following third molar extraction . Visual analogue scale pain intensity ( VASPI ) and other measurements were made at baseline , every 5–45 min , and at 60 , 90 , 120 , 180 , 240 , 300 and 360 min . Results Most patients produced consistent VASPI results over time . For placebo and paracetamol , few patients achieved low VASPI scores and maintained them . For both ibuprofen formulations , VASPI scores fell rapidly during the first hour and were then typically maintained until later re-medication . Analysis of all patients showed that rapid VASPI reduction in the first hour was strongly correlated with good overall pain relief ( high total pain relief over 0–6 h ) , and with lesser need for additional analgesia within 6 h. Results for this analysis were in very good agreement with a previous analysis , validating the relationship between fast initial pain intensity reduction and overall good pain relief in this setting . Conclusions In acute pain following third molar extraction , faster acting analgesic formulations provide earlier onset of pain relief , better overall pain relief and a less frequent need for additional analgesia , indicating longer lasting pain relief Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data OBJECTIVES To survey the frequency of use of indirect comparisons in systematic review s and evaluate the methods used in their analysis and interpretation . Also to identify alternative statistical approaches for the analysis of indirect comparisons , to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within review s. DATA SOURCES Electronic data bases . REVIEW METHODS The Data base of Abstract s of Review s of Effects ( DARE ) was search ed for systematic review s involving meta- analysis of r and omised controlled trials ( RCTs ) that reported both direct and indirect comparisons , or indirect comparisons alone . A systematic review of MEDLINE and other data bases was carried out to identify published methods for analysing indirect comparisons . Study design s were created using data from the International Stroke Trial . R and om sample s of patients receiving aspirin , heparin or placebo in 16 centres were used to create meta-analyses , with half of the trials comparing aspirin and placebo and half heparin and placebo . Methods for indirect comparisons were used to estimate the contrast between aspirin and heparin . The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results . Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken . RESULTS Of the review s identified through DARE , 31/327 ( 9.5 % ) included indirect comparisons . A further five review s including indirect comparisons were identified through electronic search ing . Few review s carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest . Few method ological papers were identified . Some valid approaches for aggregate data that could be applied using st and ard software were found : the adjusted indirect comparison , meta-regression and , for binary data only , multiple logistic regression ( fixed effect models only ) . Simulation studies showed that the naive method is liable to bias and also produces over-precise answers . Several methods provide correct answers if strong but unverifiable assumptions are fulfilled . Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly r and omised comparisons . Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies , but the direction of such discrepancy is unpredictable . CONCLUSIONS Direct evidence from good- quality RCTs should be used wherever possible . Without this evidence , it may be necessary to look for indirect comparisons from RCTs . However , the results may be susceptible to bias . When making indirect comparisons within a systematic review , an adjusted indirect comparison method should ideally be used employing the r and om effects model . If both direct and indirect comparisons are possible within a review , it is recommended that these be done separately before considering whether to pool data . There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect . Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons . Research into how evidence from indirect comparisons compares to that from non-r and omised studies may also be warranted . Investigations using individual patient data from a meta- analysis of several RCTs using different protocol s and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records Output:	There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics . Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses .
MS22081	*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 benefit of CT coronary angiography ( CTCA ) in patients presenting with stable chest pain has not been systematic ally studied . We aim ed to assess the effect of CTCA on the diagnosis , management , and outcome of patients referred to the cardiology clinic with suspected angina due to coronary heart disease . METHODS In this prospect i ve open-label , parallel-group , multicentre trial , we recruited patients aged 18 - 75 years referred for the assessment of suspected angina due to coronary heart disease from 12 cardiology chest pain clinics across Scotl and . We r and omly assigned ( 1:1 ) participants to st and ard care plus CTCA or st and ard care alone . R and omisation was done with a web-based service to ensure allocation concealment . The primary endpoint was certainty of the diagnosis of angina secondary to coronary heart disease at 6 weeks . All analyses were intention to treat , and patients were analysed in the group they were allocated to , irrespective of compliance with scanning . This study is registered with Clinical Trials.gov , number NCT01149590 . FINDINGS Between Nov 18 , 2010 , and Sept 24 , 2014 , we r and omly assigned 4146 ( 42 % ) of 9849 patients who had been referred for assessment of suspected angina due to coronary heart disease . 47 % of participants had a baseline clinic diagnosis of coronary heart disease and 36 % had angina due to coronary heart disease . At 6 weeks , CTCA reclassified the diagnosis of coronary heart disease in 558 ( 27 % ) patients and the diagnosis of angina due to coronary heart disease in 481 ( 23 % ) patients ( st and ard care 22 [ 1 % ] and 23 [ 1 % ] ; p<0·0001 ) . Although both the certainty ( relative risk [ RR ] 2·56 , 95 % CI 2·33 - 2·79 ; p<0·0001 ) and frequency of coronary heart disease increased ( 1·09 , 1·02 - 1·17 ; p=0·0172 ) , the certainty increased ( 1·79 , 1·62 - 1·96 ; p<0·0001 ) and frequency seemed to decrease ( 0·93 , 0·85 - 1·02 ; p=0·1289 ) for the diagnosis of angina due to coronary heart disease . This changed planned investigations ( 15 % vs 1 % ; p<0·0001 ) and treatments ( 23 % vs 5 % ; p<0·0001 ) but did not affect 6-week symptom severity or subsequent admittances to hospital for chest pain . After 1·7 years , CTCA was associated with a 38 % reduction in fatal and non-fatal myocardial infa rct ion ( 26 vs 42 , HR 0·62 , 95 % CI 0·38 - 1·01 ; p=0·0527 ) , but this was not significant . INTERPRETATION In patients with suspected angina due to coronary heart disease , CTCA clarifies the diagnosis , enables targeting of interventions , and might reduce the future risk of myocardial infa rct ion . FUNDING The Chief Scientist Office of the Scottish Government Health and Social Care Directorates funded the trial with supplementary awards from Edinburgh and Lothian 's Health Foundation Trust and the Heart Diseases Research Fund BACKGROUND Many patients have symptoms suggestive of coronary artery disease ( CAD ) and are often evaluated with the use of diagnostic testing , although there are limited data from r and omized trials to guide care . METHODS We r and omly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography ( CTA ) or to functional testing ( exercise electrocardiography , nuclear stress testing , or stress echocardiography ) . The composite primary end point was death , myocardial infa rct ion , hospitalization for unstable angina , or major procedural complication . Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure . RESULTS The mean age of the patients was 60.8±8.3 years , 52.7 % were women , and 87.7 % had chest pain or dyspnea on exertion . The mean pretest likelihood of obstructive CAD was 53.3±21.4 % . Over a median follow-up period of 25 months , a primary end-point event occurred in 164 of 4996 patients in the CTA group ( 3.3 % ) and in 151 of 5007 ( 3.0 % ) in the functional-testing group ( adjusted hazard ratio , 1.04 ; 95 % confidence interval , 0.83 to 1.29 ; P=0.75 ) . CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing ( 3.4 % vs. 4.3 % , P=0.02 ) , although more patients in the CTA group underwent catheterization within 90 days after r and omization ( 12.2 % vs. 8.1 % ) . The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group ( 10.0 mSv vs. 11.3 mSv ) , but 32.6 % of the patients in the functional-testing group had no exposure , so the overall exposure was higher in the CTA group ( mean , 12.0 mSv vs. 10.1 mSv ; P<0.001 ) . CONCLUSIONS In symptomatic patients with suspected CAD who required noninvasive testing , a strategy of initial CTA , as compared with functional testing , did not improve clinical outcomes over a median follow-up of 2 years . ( Funded by the National Heart , Lung , and Blood Institute ; PROMISE Clinical Trials.gov number , NCT01174550 . ) OBJECTIVES The study aim was to determine observational differences in costs of care by the coronary disease diagnostic test modality . BACKGROUND A number of diagnostic strategies are available with few data to compare the cost implication s of the initial test choice . METHODS We prospect ively enrolled 11,372 consecutive stable angina patients who were referred for stress myocardial perfusion tomography or cardiac catheterization . Stress imaging patients were matched by their pretest clinical risk of coronary disease to a series of patients referred to cardiac catheterization . Composite 3-year costs of care were compared for two patients management strategies : 1 ) direct cardiac catheterization ( aggressive ) and 2 ) initial stress myocardial perfusion tomography and selective catheterization of high risk patients ( conservative ) . Analysis of variance techniques were used to compare costs , adjusting for treatment propensity and pretest risk . RESULTS Observational comparisons of aggressive as compared with conservative testing strategies reveal that costs of care were higher for direct cardiac catheterization in all clinical risk subsets ( range : $ 2,878 to $ 4,579 ) , as compared with stress myocardial perfusion imaging plus selective catheterization ( range : $ 2,387 to $ 3,010 , p < 0.0001 ) . Coronary revascularization rates were higher for low , intermediate and high risk direct catheterization patients as compared with the initial stress perfusion imaging cohort ( 13 % to 50 % , p < 0.0001 ) ; cardiac death or myocardial infa rct ion rates were similar ( p > 0.20 ) . CONCLUSIONS Observational assessment s reveal that stable chest pain patients who undergo a more aggressive diagnostic strategy have higher diagnostic costs and greater rates of intervention and follow-up costs . Cost differences may reflect a diminished necessity for re source consumption for patients with normal test results In patients with stable ischemic heart disease ( SIHD ) , myocardial revascularization should be performed to either improve survival or improve symptoms and functional status among patients who are not well controlled with optimal medical therapy ( OMT ) . A general consensus exists on the core elements of OMT , which include both lifestyle intervention and intensive secondary prevention with proven pharmacotherapies . By contrast , however , there is less general agreement as to what constitutes the optimal approach to revascularization in SIHD patients . The COURAGE and FAME 2 r and omized trials form the foundation of the current clinical evidence base and raise the important question : “ What is the impact of myocardial ischemia on myocardial revascularization in stable ischemic heart disease?”ZusammenfassungBei Patienten mit stabiler ischämischer Herzkrankheit ( SIHD ) sollte eine myokardiale Revaskularisierung erfolgen , um entweder das Überleben oder die Symptome und den Funktionszust and bei Patienten zu verbessern , bei denen die Erkrankung trotz optimaler medikamentöser Therapie ( OMT ) nicht gut unter Kontrolle ist . Es besteht ein allgemeiner Konsens bei den Kernelementen der OMT , zu denen sowohl eine Änderung der Lebensweise als auch eine intensive Sekundärprävention mit bewährter Pharmakotherapie gehören . Dagegen besteht jedoch eine geringere Übereinstimmung hinsichtlich des optimalen Ansatzes für die Revaskularisierung bei SIHD-Patienten . Die r and omisierten Studien COURAGE und FAME 2 bilden die Grundlage der aktuellen klinischen Evidenzbasierung und werfen die wichtige Frage auf : „ Wie beeinflusst die Myokardischämie eine myokardiale Revaskularisierung bei stabiler ischämischer Herzkrankheit ? OBJECTIVES To assess the acceptability and feasibility of functional tests as a gateway to angiography for management of coronary artery disease ( CAD ) , the ability of diagnostic strategies to identify patients who should undergo revascularisation , patient outcomes in each diagnostic strategy , and the most cost-effective diagnostic strategy for patients with suspected or known CAD . DESIGN A rapid systematic review of economic evaluations of alternative diagnostic strategies for CAD was carried out . A pragmatic and generalisable r and omised controlled trial was undertaken to assess the use of the functional cardiac tests : angiography ( controls ) ; single photon emission computed tomography ( SPECT ) ; magnetic resonance imaging ( MRI ) ; stress echocardiography . SETTING The setting was Papworth Hospital NHS Foundation Trust , a tertiary cardiothoracic referral centre . PARTICIPANTS Patients with suspected or known CAD and an exercise test result that required non-urgent angiography . INTERVENTIONS Patients were r and omised to one of the four initial diagnostic tests . MAIN OUTCOME MEASURES Eighteen months post-r and omisation : exercise time ( modified Bruce protocol ) ; cost-effectiveness compared with angiography ( diagnosis , treatment and follow-up costs ) . The aim was to demonstrate equivalence in exercise time between those r and omised to functional tests and those r and omised to angiography [ defined as the confidence interval ( CI ) for mean difference from angiography within 1 minute ] . RESULTS The 898 patients were r and omised to angiography ( n = 222 ) , SPECT ( n = 224 ) , MRI ( n = 226 ) or stress echo ( n = 226 ) . Initial diagnostic tests were completed successfully with unequivocal results for 98 % of angiography , 94 % of SPECT ( p = 0.05 ) , 78 % of MRI ( p < 0.001 ) and 90 % of stress echocardiography patients ( p < 0.001 ) . Some 22 % of SPECT patients , 20 % of MRI patients and 25 % of stress echo patients were not subsequently referred for an angiogram . Positive functional tests were confirmed by positive angiography in 83 % of SPECT patients , 89 % of MRI patients and 84 % of stress echo patients . Negative functional tests were followed by positive angiograms in 31 % of SPECT patients , 52 % of MRI patients and 48 % of stress echo patients tested . The proportions that had coronary artery bypass graft surgery were 10 % ( angiography ) , 11 % ( MRI ) and 13 % ( SPECT and stress echo ) and percutaneous coronary intervention 25 % ( angiography ) , 18 % ( SPECT ) and 23 % ( MRI and stress echo ) . At 18 months , comparing SPECT and stress echo with angiography , a clinical ly significant difference in total exercise time can be ruled out . The MRI group had significantly shorter mean total exercise time of 35 seconds and the upper limit of the CI was 1.14 minutes less than in the angiography group , so a difference of at least 1 minute can not be ruled out . At 6 months post-treatment , SPECT and angiography had equivalent mean exercise time . Compared with angiography , the MRI and stress echo groups had significantly shorter mean total exercise time of 37 and 38 seconds , respectively , and the upper limit of both CIs was 1.16 minutes , so a difference of at least 1 minute can not be ruled out . The differences were mainly attributable to revascularised patients . There were significantly more non-fatal adverse events in the stress echo group , mostly admissions for chest pain , but no significant difference in the number of patients reporting events . Mean ( 95 % CI ) total additional costs over 18 months , compared with angiography , were 415 pounds ( -310 pounds to 1084 pounds ) for SPECT , 426 pounds ( -247 pounds to 1088 pounds ) for MRI and 821 pounds ( 10 pounds to 1715 pounds ) for stress echocardiography , with very little difference in quality -adjust Output:	Nonetheless , the findings from this systematic review suggest that for patients with a low to intermediate prior probability of having obstructive CAD , computed tomography coronary angiography ( CTCA ) may be cost-effective as an initial diagnostic imaging test in comparison with CAG or other non-invasive diagnostic tests . If functional testing is required , stress echocardiography ( SE ) or single-photon emission computed tomography ( SPECT ) are suggested to be cost-effective initial strategies in patients with intermediate prior probability of CAD . Immediate CAG is suggested to be a cost-effective strategy for patients at a high prior probability of having obstructive CAD whom may benefit from revascularization . The study emphasizes the inextricable link between clinical effectiveness and economic efficiency . Evidence suggests that the optimal diagnostic imaging strategy for individuals suspected of having CAD is CTCA for low and intermediate disease probability , followed by SE or SPECT as necessary , and invasive CAG for high disease probability .
MS22082	*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 Joint hypermobility ( JH ) or " ligamentous laxity " is felt to be an underlying risk factor for many types of musculoskeletal presentation in paediatrics , and joint hypermobility syndrome ( JHS ) describes such disorders where symptoms become chronic , often more generalized and associated with functional impairment . Clinical features are felt to have much in common with more severe disorders , including Ehlers-Danlos syndrome ( EDS ) , osteogenesis imperfecta and Marfan syndrome , although this has not been formally studied in children . We defined the clinical characteristics of all patients with joint hypermobility-related presentations seen from 1999 to 2002 in a tertiary referral paediatric rheumatology unit . METHODS Patients were identified and recruited from paediatric rheumatology clinic and ward , and a dedicated paediatric rheumatology hypermobility clinic at Great Ormond Street Hospital . Data were collected retrospectively on the patients from the paediatric rheumatology clinics ( 1999 - 2002 ) and prospect ively on patients seen in the hypermobility clinic ( 2000 - 2002 ) . Specifically , historical details of developmental milestones , musculoskeletal or soft tissue diagnoses and symptoms , and significant past medical history were recorded . Examination features sought included measurements of joint and soft tissue laxity , and associated conditions such as scoliosis , dysmorphic features , cardiac murmurs and eye problems . RESULTS One hundred and twenty-five children ( 64 females ) were included on whom sufficient clinical data could be identified and who had clinical problems ascribed to JH present for longer than 3 months . Sixty-four were from the paediatric rheumatology clinic and 61 from the hypermobility clinic . No differences were found in any of the measures between the two population s and results are presented in a combined fashion . Three-quarters of referrals came from paediatricians and general practitioners but in only 10 % was hypermobility recognized as a possible cause of joint complaint . The average age at onset of symptoms was 6.2 yr and age at diagnosis 9.0 yr , indicating a 2- to 3-yr delay in diagnosis . The major presenting complaint was arthralgia in 74 % , abnormal gait in 10 % , apparent joint deformity in 10 % and back pain in 6 % . Mean age at first walking was 15.0 months ; 48 % were considered " clumsy " and 36 % as having poor coordination in early childhood . Twelve per cent had " clicky " hips at birth and 4 % actual congenital dislocatable hip . Urinary tract infections were present in 13 and 6 % of the female and male cases , respectively . Thirteen and 14 % , respectively , had speech and learning difficulties diagnosed . A history of recurrent joint sprains was seen in 20 % and actual subluxation/dislocation of joints in 10 % . Forty per cent had experienced problems with h and writing tasks , 48 % had major limitations of school-based physical education activities , 67 % other physical activities and 41 % had missed significant periods of schooling because of symptoms . Forty-three per cent described a history of easy bruising . Examination revealed that 94 % scored > or = 4/9 on the Beighton scale for generalized hypermobility , with knees ( 92 % ) , elbows ( 87 % ) , wrists ( 82 % ) , h and metacarpophalangeal joints ( 79 % ) , and ankles ( 75 % ) being most frequently involved . CONCLUSIONS JHS is poorly recognized in children with a long delay in the time to diagnosis . Although there is a referral bias towards joint symptoms , a surprisingly large proportion is associated with significant neuromuscular and motor development problems . Our patients with JHS also show many overlap features with genetic disorders such as EDS and Marfan syndrome . The delay in diagnosis results in poor control of pain and disruption of normal home life , schooling and physical activities . Knowledge of the diagnosis and simple interventions are likely to be highly effective in reducing the morbidity and cost to the health and social services In 30 healthy volunteers with clinical ly inconspicuous knee joints and nine patients with posttraumatic recurrent patella dislocation , the proprioceptive abilities of the knee joint were evaluated by an angle reproduction test . The results of the control goup showed no gender-or dominant-specific difference . The patient group showed a significant deterioration of proprioceptive capability in the injured knee joint . Even in the contralateral , uninjured knee joint , the angle reproduction test result was significantly reduced compared with the control group . After applying an elastic knee b and age , the control group and the patients with patella dislocation showed a significant improvement of the proprioceptive capability The objective of the present study is to compare and quantify the postural differences and joint pain distribution between subjects with benign joint hypermobility syndrome ( BJHS ) and the normal population . This observational , non-r and omized , and controlled study was conducted at Rheumatology and Physical Medicine and Rehabilitation Medicine Departments of a tertiary care teaching hospital . Subjects comprise 35 persons with diagnosis of BJHS , and the control group was matched for age and sex . Reedco ’s Posture score ( RPS ) and visual analogue scale ( VAS ) were the outcome measures . The subjects were assessed for pain in ten major joints and rated on a VAS . A st and ard posture assessment was conducted using the Reedco ’s Posture score . The same procedure was executed for an age- and sex-matched control group . Mean RPS for the BJHS group was 55.29 ± 8.15 and for the normal group it was 67 ± 11.94 . The most common postural deviances in subjects with BJHS were identified in the following areas of head , hip ( Sagittal plane ) , upper back , trunk , and lower back ( Coronal plane ) . Intensity of pain was found to be more in BJHS persons than that of the normal persons , and the knee joints were the most affected . The present study compared and quantified the postural abnormalities and the pain in BJHS persons . The need for postural re-education and specific assessment and training for the most affected joints are discussed . There is a significant difference in posture between subjects with BJHS and the normal population . BJHS persons need special attention to their posture re-education during physiotherapy sessions to reduce long-term detrimental effects on the musculoskeletal system We carried out a prospect i ve study to determine the validity of different sets of criteria to define the hypermobility syndrome ( HMS ) , as well as the frequency , reliability and clinical features of HMS items . All consecutive cases of HMS attending the rheumatological outpatient clinic of Hospital del Mar ( Barcelona , Spain ) constituted the index group ( n = 114 ) . A control group of non-HMS rheumatological patients ( n = 59 ) was r and omly selected to assess suitable cutoff points and particular HMS item prevalences . Beighton 's , Carter 's and Rotés ' HMS scores correlated very highly among them . Both the correlation coefficients obtained between each pair of sets of HMS criteria and the predictive efficiencies were uniformly high , suggesting high concurrent and predictive validity . All but 2 of the major items were more frequent among women . A basic set of criteria to define HMS is proposed . In relation to previous criteria the new scale shows better internal reliability and homogeneity . Results suggest that it may be suitable for screening studies and in clinical rheumatological setting OBJECTIVE To determine differences between hypermobile subjects and controls in terms of maximum strength , rate of force development , and balance . METHODS We recruited 13 subjects with hypermobility and 18 controls . Rate of force development and maximal voluntary contraction ( MVC ) during single leg knee extension of the right knee were measured isometrically for each subject . Balance was tested twice on a force plate with 15-second single-leg st and s on the right leg . Rate of force development ( N/second ) and MVC ( N ) were extracted from the force-time curve as maximal rate of force development (= limit Deltaforce/Deltatime ) and the absolute maximal value , respectively . RESULTS The hypermobile subjects showed a significantly higher value for rate of force development ( 15.2 % higher ; P = 0.038 , P = 0.453 , epsilon = 0.693 ) and rate of force development related to body weight ( 16.4 % higher ; P = 0.018 , P = 0.601 , epsilon = 0.834 ) than the controls . The groups did not differ significantly in MVC ( P = 0.767 , P = 0.136 , epsilon = 0.065 ) , and MVC related to body weight varied r and omly between the groups ( P = 0.921 , P = 0.050 , epsilon = 0.000 ) . In balance testing , the mediolateral sway of the hypermobile subjects showed significantly higher values ( 11.6 % higher ; P = 0.034 , P = 0.050 , epsilon = 0.000 ) than that of controls , but there was no significant difference ( 4.9 % difference ; P = 0.953 , P = 0.050 , epsilon = 0.000 ) in anteroposterior sway between the 2 groups . CONCLUSION Hypermobile women without acute symptoms or limitations in activities of daily life have a higher rate of force development in the knee extensors and a higher mediolateral sway than controls with normal joint mobility Quantification of dynamic balance is often necessary to assess a patient 's level of injury or ability to function in order to initiate an appropriate plan of care . Some therapists use the star-excursion test in an attempt to quantify dynamic balance . This test requires the patient to balance on one leg while reaching with the other leg . For the purpose of this study , the reach was performed in four directions . No previous research ers have attempted to evaluate the reliability of this test . Twenty healthy subjects between the ages of 18 and 35 years participated in this study . During two testing sessions , each subject was required to perform five reaching trials in four directions . Reliability estimates , calculated using the intraclass correlation coefficient ( 2 , 1 ) , ranged from 0.67 to 0.87 . Six duplicate practice sessions were suggested to increase this range above 0.86 . Task complexity may account for the moderate reliability estimates . Subjects should engage in a learning period before being evaluated on the star-excursion test Output:	To conclude , lower limb joint proprioception is reduced in those with BJHS compared to non-BJHS cohorts , whilst unclear in the upper limb
MS22083	*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 Observational studies report a relationship between anticholinergic drug scale ( ADS ) score and cognitive function . This study investigated whether a reduced ADS score improved cognitive function in a frail elderly population . METHODS This r and omized , controlled , single-blinded trial , recruited long-term residents with an ADS score of greater than or equal to 3 from 22 nursing homes in Norway . The participants were r and omly allocated ( 1:1 ) to intervention or control . The intervention was a pharmacist-initiated reduction of ADS score after multidisciplinary drug review s. Primary end point was Consortium to Establish a Registry for Alzheimer 's Disease 10-wordlist test for immediate recall . Secondary end points were Mini-Mental Sate Examination , delayed recall and recognition of words , saliva flow , and serum anticholinergic activity (SAA).The participants were retested after 4 and 8 weeks , and the study groups were compared after adjusting for baseline differences . RESULTS Eighty-seven patients were included . The median ADS score was reduced by 2 units ( p < .0001 ) in the intervention group and remained unchanged in the control group . After 8 weeks , the adjusted mean difference in immediate recall was 0.54 words between the intervention and control group ( 95 % confidence interval [ CI ] : -0.91 , 2.05 ; p = .48 ) . The study groups did not differ significantly in any of the other cognitive end points , salvia flow , or SAA at either follow-up ( p > .18 ) . CONCLUSION Pharmacist-initiated drug changes significantly reduced ADS score but did not improve cognitive function in nursing home residents . Moreover , the drug changes did not reduce SAA or mouth dryness significantly , which might indicate limited applicability of the ADS score to prevent prescription risks in this population The use of prescription drugs in older people is high and many commonly prescribed drugs have anticholinergic effects . We examined the relationship between ACB on mortality and in-patient length of stay in the oldest old hospitalised population . This was a retrospective analysis of prospect i ve audit using hospital audit data from acute medical admissions in three hospitals in Engl and and Scotl and . Baseline use of possible or definite anticholinergics was determined according to the Anticholinergic Cognitive Burden Scale . The main outcome measures were decline in-hospital mortality , early in-hospital mortality at 3- and 7-days and in-patient length of stay . A total of 419 patients ( including 65 patients with known dementia ) were included [ median age=92.9 , inter-quartile range ( IQR ) 91.4 - 95.1 years ] . 256 ( 61.1 % ) were taking anticholinergic medications . Younger age , greater number of pre-morbid conditions , ischemic heart disease , number of medications , higher urea and creatinine levels were significantly associated with higher total ACB burden on univariate regression analysis . There were no significant differences observed in terms of in-patient mortality , in-patient hospital mortality within 3- and 7-days and likelihood of prolonged length of hospital stay between ACB categories . Compared to those without cardiovascular disease , patients with cardiovascular disease showed similar outcome regardless of ACB load ( either = 0 or > 0 ACB ) . We found no association between ACB and early ( within 3- and 7-days ) and in-patient mortality and hospital length of stay outcomes in this cohort of oldest old in the acute medical admission setting Background Delirium prevalence in the intensive care unit ( ICU ) is high . Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms . Methods / Design This is a r and omized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis . Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium ( PMD ) and those assigned to the control group will receive no change in their usual ICU care . The primary outcomes of the trial are ( 1 ) delirium severity as measured by the Delirium Rating Scale revised-98 ( DRS-R-98 ) and ( 2 ) delirium duration as determined by the Confusion Assessment Method for the ICU ( CAM-ICU ) . The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients : dopamine , acetylcholine , and gamma-aminobutyric acid . The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines , and introduce a low-dose of haloperidol at 0.5 - 1 mg for 7 days . The protocol will be delivered by a combination of computer ( artificial intelligence ) and pharmacist ( human intelligence ) decision support system to increase adherence to the PMD protocol . Discussion The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU.Trial Registration Clinical Trials.gov : BACKGROUND Adverse effects of anticholinergic medications may contribute to events such as falls , delirium , and cognitive impairment in older patients . To further assess this risk , we developed the Anticholinergic Risk Scale ( ARS ) , a ranked categorical list of commonly prescribed medications with anticholinergic potential . The objective of this study was to determine if the ARS score could be used to predict the risk of anticholinergic adverse effects in a geriatric evaluation and management ( GEM ) cohort and in a primary care cohort . METHODS Medical records of 132 GEM patients were review ed retrospectively for medications included on the ARS and their result ant possible anticholinergic adverse effects . Prospect ively , we enrolled 117 patients , 65 years or older , in primary care clinics ; performed medication reconciliation ; and asked about anticholinergic adverse effects . The relationship between the ARS score and the risk of anticholinergic adverse effects was assessed using Poisson regression analysis . RESULTS Higher ARS scores were associated with increased risk of anticholinergic adverse effects in the GEM cohort ( crude relative risk [ RR ] , 1.5 ; 95 % confidence interval [ CI ] , 1.3 - 1.8 ) and in the primary care cohort ( crude RR , 1.9 ; 95 % CI , 1.5 - 2.4 ) . After adjustment for age and the number of medications , higher ARS scores increased the risk of anticholinergic adverse effects in the GEM cohort ( adjusted RR , 1.3 ; 95 % CI , 1.1 - 1.6 ; c statistic , 0.74 ) and in the primary care cohort ( adjusted RR , 1.9 ; 95 % CI , 1.5 - 2.5 ; c statistic , 0.77 ) . CONCLUSION Higher ARS scores are associated with statistically significantly increased risk of anticholinergic adverse effects in older patients Abstract Objective To assess the potential of anticholinergic drugs as a cause of non-degenerative mild cognitive impairment in elderly people . Design Longitudinal cohort study . Setting 63 r and omly selected general practice s in the Montpellier region of southern France . Participants 372 people aged > 60 years without dementia at recruitment . Main outcome measures Anticholinergic burden from drug use , cognitive examination , and neurological assessment . Results 9.2 % of subjects continuously used anticholinergic drugs during the year before cognitive assessment . Compared with non-users , they had poorer performance on reaction time , attention , delayed non-verbal memory , narrative recall , visuospatial construction , and language tasks but not on tasks of reasoning , immediate and delayed recall of wordlists , and implicit memory . Eighty per cent of the continuous users were classified as having mild cognitive impairment compared with 35 % of non-users , and anticholinergic drug use was a strong predictor of mild cognitive impairment ( odds ratio 5.12 , P = 0.001 ) . No difference was found between users and non-users in risk of developing dementia at follow-up after eight years . Conclusions Elderly people taking anticholinergic drugs had significant deficits in cognitive functioning and were highly likely to be classified as mildly cognitively impaired , although not at increased risk for dementia . Doctors should assess current use of anticholinergic drugs in elderly people with mild cognitive impairment before considering administration of acetylcholinesterase inhibitors OBJECTIVES To examine the longitudinal relationship between cumulative exposure to anticholinergic medications and memory and executive function in older men . DESIGN Prospect i ve cohort study . SETTING A Department of Veterans Affairs primary care clinic . PARTICIPANTS Five hundred forty-four community-dwelling men aged 65 and older with diagnosed hypertension . MEASUREMENTS The outcomes were measured using the Hopkins Verbal Recall Test ( HVRT ) for short-term memory and the instrumental activity of daily living ( IADL ) scale for executive function at baseline and during follow-up . Anticholinergic medication use was ascertained using participants ' primary care visit records and quantified as total anticholinergic burden using a clinician-rated anticholinergic score . RESULTS Cumulative exposure to anticholinergic medications over the preceding 12 months was associated with poorer performance on the HVRT and IADLs . On average , a 1-unit increase in the total anticholinergic burden per 3 months was associated with a 0.32-point ( 95 % confidence interval (CI)= 0.05 - 0.58 ) and 0.10-point ( 95 % CI=0.04 - 0.17 ) decrease in the HVRT and IADLs , respectively , independent of other potential risk factors for cognitive impairment , including age , education , cognitive and physical function , comorbidities , and severity of hypertension . The association was attenuated but remained statistically significant with memory ( 0.29 , 95 % CI=0.01 - 0.56 ) and executive function ( 0.08 , 95 % CI=0.02 - 0.15 ) after further adjustment for concomitant non-anticholinergic medications . CONCLUSION Cumulative anticholinergic exposure across multiple medications over 1 year may negatively affect verbal memory and executive function in older men . Prescription of drugs with anticholinergic effects in older persons deserves continued attention to avoid deleterious adverse effects Although there is an underst and able emphasis on the side effects of individual medications , the cumulative effects of medications have received little attention in palliative care prescribing . Anticholinergic load reflects a cumulative effect of medications that may account for several symptoms and adverse health outcomes frequently encountered in palliative care . A secondary analysis of 304 participants in a r and omised controlled trial had their cholinergic load calculated using the Clinician-Rated Anticholinergic Scale ( modified version ) longitudinally as death approached from medication data collected prospect ively by study nurses on each visit . Mean time from referral to death was 107 days , and mean 4.8 visits were conducted in which data were collected . Relationships to key factors were explored . Data showed that anticholinergic load rose as death approached because of increasing use of medications for symptom control . Symptoms significantly associated with increasing anticholinergic load included dry mouth and difficulty concentrating ( P < 0.05 ) . There were also significant associations with increasing anticholinergic load and decreasing functional status ( Australia-modified Karnofsky Performance Scale ; and quality of life ( P < 0.05 ) . This study has documented in detail the longitudinal anticholinergic load associated with medications used in a palliative care population between referral and death , demonstrating the biggest contributor to anticholinergic load in a palliative care population is from symptom-specific medications , which increased as death approached AIM Increasing evidence from experimental studies and clinical observations suggests that drugs with anticholinergic properties can cause physical and mental impairment . The aim of the present study was to evaluate the relationship between the use of drugs with anticholinergic activity and negative outcomes in older nursing home residents . METHODS We used data from the data base of the U.L.I.S.S.E project ( Un Link Informatico sui Servizi Sanitari Esistenti per l'Anziani ) , a prospect i ve multicenter observational study . Patients from 31 facilities in Italy were assessed at baseline and at 6 and 12 months by trained personnel , using the Minimum Data Set for Nursing Home ( MDS-NH ) . The only exclusion criterion was age younger than 65 years . The Anticholinergic Risk Scale ( ARS ) , a list of commonly prescribed drugs with potential anticholinergic effects , was used to calculate the anticholinergic load . RESULTS A total population of 1490 patients was analyzed ; almost half of the sample ( 48 % ) was using drugs with anticholinergic properties . The population of patients with ARS 1 or higher had a higher comorbidity index ( P < .003 ) and greater cognitive impairment ( CPS 5 - 6 ) ( P < .007 ) . They were more likely to suffer from heart failure , Parkinson disease , depression , anxiety , and schizophrenia . In multivariate analysis , a higher score in the ARS scale was associated with a greater likelihood of functional decline ( described as the loss of ≥1 ADL point ) ( odds ratio [ OR ] 1.13 ; confidence interval [ CI ] 1.03 - Output:	The Drug Burden Index was the most commonly used scale or tool in community and data base studies , while the Anticholinergic Risk Scale was used more frequently in care homes and hospital setting s. The association between anticholinergic burden and clinical outcomes varied by index and study . Falls and hospitalisation were consistently found to be associated with anticholinergic burden . Mortality , delirium , physical function and cognition were not consistently associated . Conclusions Anticholinergic burden scales vary in their rationale , use and association with outcomes .
MS22084	*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 have evaluated the perioperative effects of melatonin with those of midazolam in 75 women in a prospect i ve , r and omized , double-blind , placebo-controlled study . Patients were given sublingual midazolam 15 mg , melatonin 5 mg or placebo , approximately 100 min before a st and ard anaesthetic . Sedation , anxiety and orientation were quantified before , and 10 , 30 , 60 and 90 min after premedication , and 15 , 30 , 60 and 90 min after admission to the recovery room . Psychomotor performance was evaluated at these times also , using the digit-symbol substitution test ( DSST ) and the Trieger dot test ( TDT ) . Patients who received premedication with either midazolam or melatonin had a significant decrease in anxiety levels and increase in levels of sedation before operation compared with controls . Midazolam produced the highest scores for sedation at 30 and 60 min after administration and significant psychomotor impairment in the preoperative period compared with melatonin or placebo . After operation , patients who received midazolam or melatonin premedication had increased levels of sedation at 30 min and impairment in performance on the DSST at 15 , 30 and 90 min compared with controls . There were no significant differences between the three groups for anxiety levels or TDT performance after operation . Amnesia was notable only in the midazolam group for one preoperative event ( entry into the operating room ) . Patient satisfaction was noted in the midazolam and melatonin groups only . We have demonstrated that melatonin can be used effectively for premedication of adult patients Background Studies have shown that there is a high prevalence of depression in cancer patients . Women with breast cancer may have an even higher risk of depression particularly in a postmenopausal or estrogen deficiency state . A small number of r and omized controlled trials have examined the efficacy of antidepressants compared to that of a placebo in cancer patients , but some results have been difficult to interpret due to a heterogeneous patient group . In the current investigation , we screened newly diagnosed early stage breast cancer patients for depressive symptoms prior to the initiation of adjuvant therapy and investigated whether the oral antidepressant fluoxetine affected depressive symptoms , completion of adjuvant treatment , and quality of life . Methods Patients with newly diagnosed early stage breast cancer were screened for depressive symptoms prior to the initiation of adjuvant therapy . Patients with depressive symptoms were r and omized to a daily oral fluoxetine or a placebo . Patients were then followed for 6 months and evaluated for quality of life , completion of adjuvant treatment , and depressive symptoms . Results A high percentage of patients with newly diagnosed early stage breast cancer were found to have depressive symptoms prior to the initiation of adjuvant therapy . The use of fluoxetine for 6 months result ed in an improvement in quality of life , a higher completion of adjuvant treatment ( chemotherapy , hormonal therapy , chemotherapy plus hormonal therapy ) , and a reduction in depressive symptoms compared to patients who received placebo . Conclusions An antidepressant should be considered for early stage breast cancer patients with depressive symptoms who are receiving adjuvant treatment Introduction Breast cancer represents about one-third of all cancer diagnoses and accounts for about 15 % of cancer deaths in women . Many of these patients experience depression , anxiety , sleep disturbances and cognitive dysfunction . This may adversely affect quality of life and also contribute to morbidity and mortality . Melatonin is a regulatory circadian hormone having , among others , a hypnotic and an antidepressive effect . It has very low toxicity and very few adverse effects compared with the more commonly used antidepressants and hypnotics . Methods and analysis The objective of this double-blind , r and omised , placebo-controlled trial is to investigate whether treatment with oral melatonin has a prophylactic or ameliorating effect on depressive symptoms , anxiety , sleep disturbances and cognitive dysfunction in women with breast cancer . Furthermore , the authors will examine whether a specific clock-gene , PER3 , is correlated with an increased risk of depressive symptoms , sleep disturbances or cognitive dysfunction . The MELODY trial is a prospect i ve double-blinded , r and omised , placebo-controlled trial in which the authors intend to include 260 patients . The primary outcome is depressive symptoms measured by the Major Depression Inventory . The secondary outcomes are anxiety measured by a Visual Analogue Scale , total sleep time , sleep efficiency , sleep latency and periods awake measured by actigraphy and changes in cognitive function measured by a neuropsychological test battery . Tertiary outcomes are fatigue , pain , well-being and sleep quality /quantity measured by Visual Analogue Scale and sleep diary and sleepiness measured by the Karolinska Sleepiness Scale . The PER3 genotype is also to be determined in blood sample Summary Background . Fatigue can significantly interfere with a cancer patient ’s ability to fulfill daily responsibilities and enjoy life . It commonly co-exists with depression in patients undergoing chemotherapy , suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue . Methods . We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy r and omly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor ( SSRI ) paroxetine ( Paxil ® , SmithKline Beecham Pharmaceuticals ) or an identical-appearing placebo . Patients began their study medication seven days following their first on- study treatment and continued until seven days following their fourth on- study treatment . Seven days after each treatment , participants completed question naires measuring fatigue ( Multidimensional Assessment of Fatigue , Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist ) and depression ( Profile of Mood States-Depression subscale [ POMS-DD ] and Center for Epidemiologic Studies -Depression [ CES-D ] ) . Results . Repeated- measures ANOVAs , after controlling for baseline measures , showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D ( p=0.006 ) and the POMS-DD ( p=0.07 ) but not in reducing fatigue ( all measures , ps > 0.27 ) . Conclusions . Although depression was significantly reduced in the 44 patients receiving paroxetine compared to the 50 patients receiving placebo , indicating that a biologically active dose was used , no significant differences between groups on any of the measures of fatigued were observed . Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment BACKGROUND Low urinary melatonin levels have been associated with an increased risk of breast cancer in premenopausal women . However , the association between melatonin levels and breast cancer risk in postmenopausal women remains unclear . METHODS We investigated the association between melatonin levels and breast cancer risk in postmenopausal women in a prospect i ve case-control study nested in the Hormones and Diet in the Etiology of Breast Cancer Risk cohort , which included 3966 eligible postmenopausal women . The concentration of melatonin 's major metabolite , 6-sulfatoxymelatonin , was measured in a baseline 12-hour overnight urine sample from 178 women who later developed incident breast cancer and from 710 matched control subjects . We used multivariable-adjusted conditional logistic regression models to investigate associations . Relative risks are reported as odds ratios ( ORs ) . All statistical tests were two-sided . RESULTS Increased melatonin levels were associated with a statistically significantly lower risk of invasive breast cancer in postmenopausal women ( for women in the highest quartile of total overnight 6-sulfatoxymelatonin output vs the lowest quartile , multivariable OR also adjusted for testosterone = 0.56 , 95 % confidence interval [ CI ] = 0.33 to 0.97 ; P(trend ) = .02 ) . This association was strongest among never and past smokers ( OR = 0.38 , 95 % CI = 0.20 to 0.74 ; P(trend ) = .001 ) and after excluding women who were diagnosed with invasive breast cancer within 4 years after urine collection ( OR = 0.34 , 95 % CI = 0.15 to 0.75 ; P(trend ) = .002 ) . We did not observe substantial variation in relative risks by hormone receptor status of breast tumors . Among the 3966 women in the cohort , 40 of the 992 women in the highest quartile of 6-sulfatoxymelatonin developed breast cancer during follow-up , compared with 56 of the 992 women in the lowest quartile of 6-sulfatoxymelatonin . CONCLUSION Results from this prospect i ve study provide evidence for a statistically significant inverse association between melatonin levels , as measured in overnight morning urine , and invasive breast cancer risk in postmenopausal women BACKGROUND Exposure to light at night may increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin by the pineal gl and , which , in turn , could increase the release of estrogen by the ovaries . This study investigated whether such exposure is associated with an increased risk of breast cancer in women . METHODS Case patients ( n = 813 ) , aged 20 - 74 years , were diagnosed from November 1992 through March 1995 ; control subjects ( n = 793 ) were identified by r and om-digit dialing and were frequency matched according to 5-year age groups . An in-person interview was used to gather information on sleep habits and bedroom lighting environment in the 10 years before diagnosis and lifetime occupational history . Odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) were estimated by use of conditional logistic regression , with adjustment for other potential risk factors . RESULTS Breast cancer risk was increased among subjects who frequently did not sleep during the period of the night when melatonin levels are typically at their highest ( OR = 1.14 for each night per week ; 95 % CI = 1.01 to 1.28 ) . Risk did not increase with interrupted sleep accompanied by turning on a light . There was an indication of increased risk among subjects with the brightest bedrooms . Graveyard shiftwork was associated with increased breast cancer risk ( OR = 1.6 ; 95 % CI = 1.0 to 2.5 ) , with a trend of increased risk with increasing years and with more hours per week of graveyard shiftwork ( P = .02 , Wald chi-squared test ) . CONCLUSION The results of this study provide evidence that indicators of exposure to light at night may be associated with the risk of developing breast cancer BACKGROUND AND PURPOSE To estimate the prevalence of insomnia symptoms and syndrome in the general population , describe the types of self-help treatments and consultations initiated for insomnia , and examine help-seeking determinants . PATIENTS AND METHODS A r and omly selected sample of 2001 French-speaking adults from the province of Quebec ( Canada ) responded to a telephone survey about sleep , insomnia , and its treatments . RESULTS Of the total sample , 25.3 % were dissatisfied with their sleep , 29.9 % reported insomnia symptoms , and 9.5 % met criteria for an insomnia syndrome . Thirteen percent of the respondents had consulted a healthcare provider specifically for insomnia in their lifetime , with general practitioners being the most frequently consulted . Daytime fatigue ( 48 % ) , psychological distress ( 40 % ) , and physical discomfort ( 22 % ) were the main determinants prompting individuals with insomnia to seek treatment . Of the total sample , 15 % had used at least once herbal/dietary products to facilitate sleep and 11 % had used prescribed sleep medications in the year preceding the survey . Other self-help strategies employed to facilitate sleep included reading , listening to music , and relaxation . CONCLUSIONS These findings confirm the high prevalence of insomnia in the general population . While few insomnia sufferers seek professional consultations , many individuals initiate self-help treatments , particularly when daytime impairments such as fatigue become more noticeable . Improved knowledge of the determinants of help-seeking behaviors could guide the development of effective public health prevention and intervention programs to promote healthy sleep Mounting evidence suggests habitual sleep duration is associated with various health outcomes ; both short and long sleep duration have been implicated in increased risk of cardiovascular disease , diabetes , and all-cause mortality . However , data on the relation between sleep duration and cancer risk are sparse and inconclusive . A link between low levels of melatonin , a hormone closely related to sleep , and increased risk of breast cancer has recently been suggested but it is unclear whether duration of sleep may affect breast cancer risk . We explored the association between habitual sleep duration reported in 1986 and subsequent risk of breast cancer in the Nurses ' Health Study using Cox proportional hazards models . During 16 years of follow-up , 4,223 incident cases of breast cancer occurred among 77,418 women in this cohort . Compared with women sleeping 7 hours , covariate-adjusted hazard ratios and 95 % confidence intervals for those sleeping < or = 5 , 6 , 8 , and > or = 9 hours were 0.93 ( 0.79 - 1.09 ) , 0.98 ( 0.91 - 1.06 ) , 1.05 ( 0.97 - 1.13 ) , and 0.95 ( 0.82 - 1.11 ) , respectively . A moderate trend in risk increase towards longer sleep duration was observed when analyses were restricted to participants who reported same sleep duration in 1 Output:	The data presented in this review encourage the performance of new clinical trials to investigate the possible use of melatonin in cancer patients suffering from sleep-wake and mood disturbances , also considering that melatonin registered a low toxicity in cancer patients
MS22085	*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 present study aim ed : ( 1 ) to assess and improve the level of women 's involvement in a strategy to control onchocerciasis by community-directed treatment with ivermectin ( CDTI ) in three parishes of Rukungiri District , Ug and a ; ( 2 ) to measure the performance of female community-directed health workers ( CDHWs ) in comparison with males ; and ( 3 ) to identify culturally acceptable means of enhancing women 's involvement in community-directed healthcare . Health education sessions were used to instruct community members to select female CDHWs in Masya Parish and to stress their potential importance in Karangara Parish ; this subject was not raised in Mukono Parish . In all , 403 mature women who were r and omly selected from the three parishes were interviewed as to their : ( 1 ) knowledge of the classes of people not eligible to take ivermectin ; ( 2 ) knowledge and beliefs about the benefits of ivermectin ; ( 3 ) participation in decision-making ; and ( 4 ) attitudes on the performance of female CDHWs . For analysis , the respondees were divided into : ( 1 ) those who had or had not taken ivermectin treatment during the previous year ; and ( 2 ) those who had or had not attended health education sessions . During the period when face-to-face interviews with women in r and omly selected households were being carried out , participatory evaluation meetings ( PEMs ) were conducted in selected communities from the same parishes in order to reach a consensus on issues which could not easily be included in individual face-to-face interviews . Participant observations were also made regarding : how communities selected their CDHWs ; how the CDHWs organised the distribution exercise and treated community members ; and how the CDHWs kept records in order to underst and issues which were deliberately hidden from the research ers during face-to-face interviews and PEMs . Significantly , the women who had been treated or health educated in Masya Parish were : ( 1 ) more knowledgeable on the groups which were not supposed to be treated ; ( 2 ) aware of women 's involvement in mobilisation of other community members ; ( 3 ) involved in CDTI decision-making ; and ( 4 ) had a better attitude towards female CDHWs ' performance compared with males when compared with those from Karangara and Mukono parishes . There were no differences between the attitude of women in Karangara and Mukono parishes towards performance of female CDHWs . Face-to-face interviews and records from all parishes indicated that female CDHWs achieved as good a coverage as their male counterparts , and sometimes better , in about the same time . Health education increased the number of female CDHWs from nine to 52 in Masya Parish , from 7 to 22 in Karangara Parish and from 6 to 20 in Mukono Parish . Health education improved the attitude of women towards female CDHWs , but the actual experience of having and observing female CDHWs in action in Masya Parish had a more significant positive impact on the womenfolk , as well as on the rest of the community members , and created an impetus for more of them to become actively involved in actual ivermectin distribution . The present authors conclude that recruiting more female CDHWs and supervisors would reduce the current male domination of the health delivery services , greatly strengthening the activities of CDTI programmes Background Few large and rigorous evaluations of participatory interventions systematic ally describe their context and implementation , or attempt to explain the mechanisms behind their impact . This study reports process evaluation data from the Ekjut cluster-r and omised controlled trial of a participatory learning and action cycle with women 's groups to improve maternal and newborn health outcomes in Jharkh and and Orissa , eastern India ( 2005 - 2008 ) . The study demonstrated a 45 % reduction in neonatal mortality in the last two years of the intervention , largely driven by improvements in safe practice s for home deliveries . Methods A participatory learning and action cycle with 244 women 's groups was implemented in 18 intervention clusters covering an estimated population of 114 141 . We describe the context , content , and implementation of this intervention , identify potential mechanisms behind its impact , and report challenges experienced in the field . Methods included a review of intervention documents , qualitative structured discussion s with group members and non-group members , meeting observations , as well as descriptive statistical analysis of data on meeting attendance , activities , and characteristics of group attendees . Results Six broad , interrelated factors influenced the intervention 's impact : ( 1 ) acceptability ; ( 2 ) a participatory approach to the development of knowledge , skills and ' critical consciousness ' ; ( 3 ) community involvement beyond the groups ; ( 4 ) a focus on marginalized communities ; ( 5 ) the active recruitment of newly pregnant women into groups ; ( 6 ) high population coverage . We hypothesize that these factors were responsible for the increase in safe delivery and care practice s that led to the reduction in neonatal mortality demonstrated in the Ekjut trial . Conclusions Participatory interventions with community groups can influence maternal and child health outcomes if key intervention characteristics are preserved and tailored to local context s. Scaling-up such interventions requires ( 1 ) a detailed underst and ing of the way in which context affects the acceptability and delivery of the intervention ; ( 2 ) planned but flexible replication of key content and implementation features ; ( 3 ) strong support for participatory methods from implementing agencies This article presents a detailed description of a community mobilization intervention involving women 's groups in Mchinji District , Malawi . The intervention was implemented between 2005 and 2010 . The intervention aims to build the capacities of communities to take control of the mother and child health issues that affect them . To achieve this it comprises trained local female facilitators establishing groups and using a manual , participatory rural appraisal tools and picture cards to guide them through a community action cycle to identify and implement solutions to mother and child health problems . Significant re source inputs include salaries for facilitators and supervisors , and training , equipment and material s to support their work with groups . It is hypothesized that the groups will catalyse community collective action to address mother and child health issues and improve the health and reduce the mortality of mothers and children . Their impact , implementation and cost-effectiveness have been rigorously evaluated through a r and omized controlled trial design . The results of these evaluations will be reported in 2011 OBJECTIVE To determine the extent to which the community-directed approach used in onchocerciasis control in Africa could effectively and efficiently provide integrated delivery of other health interventions . METHODS A three-year experimental study was undertaken in 35 health districts from 2005 to 2007 in seven research sites in Cameroon , Nigeria and Ug and a. Four trial districts and one comparison district were r and omly selected in each site . All districts had established ivermectin treatment programmes , and in the trial districts four other established interventions - vitamin A supplementation , use of insecticide-treated nets , home management of malaria and short-course , directly-observed treatment for tuberculosis patients - were progressively incorporated into a community-directed intervention ( CDI ) process . At the end of each of the three study years , we performed quantitative evaluations of intervention coverage and provider costs , as well as qualitative assessment s of the CDI process . FINDINGS With the CDI strategy , significantly higher coverage was achieved than with other delivery approaches for all interventions except for short-course , directly-observed treatment . The coverage of malaria interventions more than doubled . The district-level costs of delivering all five interventions were lower in the CDI districts , but no cost difference was found at the first-line health facility level . Process evaluation showed that : ( i ) participatory processes were important ; ( ii ) recurrent problems with the supply of intervention material s were a major constraint to implementation ; ( iii ) the communities and community implementers were deeply committed to the CDI process ; ( iv ) community implementers were more motivated by intangible incentives than by external financial incentives . CONCLUSION The CDI strategy , which builds upon the core principles of primary health care , is an effective and efficient model for integrated delivery of appropriate health interventions at the community level in Africa A study of knowledge , attitudes and practice was carried out in the Rukungiri district of Ug and a , in order to investigate the involvement of women in community-directed treatment with ivermectin ( CDTI ) , for the control of onchocerciasis . The data analysed came from interviews with 260 adult women ( one from each of 260 r and omly-selected households in 20 onchocerciasis-endemic communities ) , community informants , and participatory evaluation meetings ( PEM ) in eight communities . The women who had been treated with ivermectin in 1999 generally had more knowledge of the benefits of taking ivermectin , were more likely to have attended the relevant health-education sessions and were more involved in community decisions on the method of ivermectin distribution than the women who had not received ivermectin in that year . There were fewer female community-directed health workers ( CDHW ) than male CDHW in the communities investigated . The reasons for not attending health-education sessions , not participating in community meetings concerning the CDTI , and the reluctance of some women to serve as CDHW were investigated . The most common reasons given were domestic chores , a reluctance to express their views in meetings outside their own kinship group , suspicions that other women might take advantage of them , and a lack of interest . Most of the women interviewed ( as well as other community members ) felt that there were relatively few women CDHW . The women attributed this to a lack of interaction and trust amongst themselves , which result ed in more men than women being selected as CDHW . The rest of the community members were not against women working as CDHW . It is recommended that communities be encouraged to select women to serve as CDHW in the CDTI , and that the performances of male and female CDHW be compared Background Neonatal mortality rates are high in rural Nepal where more than 90 % of deliveries are in the home . Evidence suggests that death rates can be reduced by interventions at community level . We describe an intervention which aim ed to harness the power of community planning and decision making to improve maternal and newborn care in rural Nepal . Methods The development of 111 women 's groups in a population of 86 704 in Makwanpur district , Nepal is described . The groups , facilitated by local women , were the intervention component of a r and omized controlled trial to reduce perinatal and neonatal mortality rates . Through participant observation and analysis of reports , we describe the implementation of this intervention : the community entry process , the facilitation of monthly meetings through a participatory action cycle of problem identification , community planning , and implementation and evaluation of strategies to tackle the identified problems . Results In response to the needs of the group , participatory health education was added to the intervention and the women 's groups developed varied strategies to tackle problems of maternal and newborn care : establishing mother and child health funds , producing clean home delivery kits and operating stretcher schemes . Close linkages with community leaders and community health workers improved strategy implementation . There were also indications of positive effects on group members and health services , and most groups remained active after 30 months . Conclusion A large scale and potentially sustainable participatory intervention with women 's groups , which focused on pregnancy , childbirth and the newborn period , result ed in innovative strategies identified by local communities to tackle perinatal care problems The challenges of community-directed treatment with ivermectin ( CDTI ) for onchocerciasis control in Africa have been : maintaining a desired treatment coverage , dem and for monetary incentives , high attrition of community distributors and low involvement of women . This study assessed how challenges could be minimised and performance improved using existing traditional kinship structures . In classic CDTI areas , community members decide upon selection criteria for community distributors , centers for health education and training , and methods of distributing ivermectin . In kinship enhanced CDTI , similar procedures were followed at the kinship level . We compared 14 r and omly selected kinship enhanced CDTI communities with 25 classic CDTI communities through interviews of 447 and 750 household members and 127 and 64 community distributors respectively . Household respondents from kinship enhanced CDTI reported better performance ( P<0.001 ) than classic CDTI on the following measures of program effectiveness : ( a ) treatment coverage ( b ) decision on treatment location and ( c ) mobilization for CDTI activities . There were more female distributors in kinship enhanced CDTI than in classic CDTI . Attrition was not a problem . Kinship enhanced CDTI had a higher number of community distributors per population working among relatives , and were more likely to be involved in additional health care activities . The results suggest that kinship enhanced CDTI was more effective than classic CDTI In Ug and a , human onchocerciasis is controlled by annual , mass , community-directed , ivermectin-treatment programmes ( CDITP ) in all endemic communities where the prevalence of the disease is > or = 30 % . This is a practical , long-term and cost-effective strategy . In some communities , this system succeeds in providing treatment at the desired level of coverage ( i.e. 90 % of the annual treatment objective , which is itself equivalent to all those individuals eligible to take ivermectin ) . Other communities , however , fail to reach this target . The aim of the present study was to determine the factors that were significantly associated with success or failure in achieving this target . The data analysed were answers to a question naire completed by 10 household heads r and omly selected from each of 64 r and omly selected endemic communities ( of which 36 succeeded and 28 failed to reach their coverage target ) in the four districts of Kabale , Moyo , Nebbi and Rukungiri . Among the programme-related factors investigated , success was associated , at a statistical level of significance ( P < or = 0.05 ) , with involvement of community members in : ( 1 ) decisions about the execution of the programme ; ( 2 ) attendance at health-education sessions ; ( 3 ) selection of the community-based distributors ( CDB ) ; and ( 4 ) rewarding CBD in kind . In general , the involvement of community members in the planning and execution of a CDITP ( and the result ant sense of pride in community ownership ) was more likely to produce successful results than when external health workers or even community leaders or local councils took responsibility OBJECTIVES To assess and compare the effectiveness of Output:	Results When considering what communities have , articles reported external linkages as the most frequently gained re source , especially when partnerships result ed in more community power over the intervention . In contrast , financial assets were the least mentioned , despite their importance for sustainability . With how communities act , articles discussed challenges of ensuring inclusive participation and detailed strategies to improve inclusiveness . Very little was reported about strengthening community cohesiveness and collective efficacy despite their importance in community initiatives . When review ing for whom communities act , the importance of strong local leadership was mentioned frequently , while conflict resolution strategies and skills were rarely discussed . Synergies were found across these elements of community capability , with tangible success in one area leading to positive changes in another . Access to information and opportunities to develop skills were crucial to community participation , critical thinking , problem solving and ownership . Conclusions Strengthening community capability is critical to ensuring that community participation leads to genuine empowerment .
MS22086	*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 Combination of erlotinib and bevacizumab is a promising regimen in advanced non-squamous non-small-cell lung cancer ( NSCLC ) . We are conducting a single arm phase II trial which aims to evaluate the efficacy and safety of this regime as a second- or third-line chemotherapy . Methods Key eligibility criteria were histologically or cytologically confirmed non-squamous NSCLC , stage III/IV or recurrent NSCLC not indicated radical chemoradiation , prior one or two regimen of chemotherapy , age 20 years or more , and performance status of two or less . The primary endpoint is objective response rate . The secondary endpoints include overall survival , progression-free survival , disease control rate and incidence of adverse events . This trial plans to accrue 80 patients based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate of 35 % and a null hypothesis threshold response rate of 20 % . A subset analysis according to EGFR mutation status is planned . Discussion We have presented the design of a single arm phase II trial to evaluate the efficacy and safety of combination of bevacizumab and erlotinib in advanced non-squamous NSCLC patients . In particular we are interested in determining the merit of further development of this regimen and whether prospect i ve patient selection using EGFR gene is necessary in future trials . Trial registration This trial was registered at the UMIN Clinical Trials Registry as UMIN000004255 ( http://www.umin.ac.jp/ctr/index.htm ) PURPOSE Bevacizumab ( Avastin ; Genentech , South San Francisco , CA ) is a recombinant , humanized anti-vascular endothelial growth factor monoclonal antibody . Erlotinib HCl ( Tarceva , OSI-774 ; OSI Pharmaceuticals , New York , NY ) is a potent , reversible , highly selective and orally available HER-1/epidermal growth factor receptor tyrosine kinase inhibitor . Pre clinical data in various xenograft models produced greater growth inhibition than with either agent alone . Additionally , both agents have demonstrated benefit in patients with previously treated non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A phase I/II study in two centers examined erlotinib and bevacizumab ( A+T ) in patients with nonsquamous stage IIIB/IV NSCLC with > or = one prior chemotherapy . In phase I , erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days was established as the phase II dose , although no dose-limiting toxicities were observed . Phase II assessed the efficacy and tolerability of A+T at this dose . Pharmacokinetic parameters were evaluated . Results Forty patients were enrolled and treated in this study ( 34 patients at phase II dose ) ; the median age was 59 years ( range , 36 to 72 years ) , 21 were female , 30 had adenocarcinoma histology , nine were never-smokers , and 22 had > or = two prior regimens ( three patients had > or = four prior regimens ) . The most common adverse events were mild to moderate rash , diarrhea , and proteinuria . Preliminary data showed no pharmacokinetic interaction between A + T. Eight patients ( 20.0 % ; 95 % CI , 7.6 % to 32.4 % ) had partial responses and 26 ( 65.0 % ; 95 % CI , 50.2 % to 79.8 % ) had stable disease as their best response . The median overall survival for the 34 patients treated at the phase II dose was 12.6 months , with progression-free survival of 6.2 months . CONCLUSION Encouraging antitumor activity and safety of A + T support further development of this combination for patients with advanced NSCLC and other solid tumors BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens . The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy . The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy PURPOSE The phase III , r and omized , placebo-controlled Sequential Tarceva in Unresectable NSCLC ( SATURN ; BO18192 ) study found that erlotinib maintenance therapy extended progression-free survival ( PFS ) and overall survival in patients with advanced non-small-cell lung cancer ( NSCLC ) who had nonprogressive disease following first-line platinum-doublet chemotherapy . This study included prospect i ve analysis of the prognostic and predictive value of several biomarkers . PATIENTS AND METHODS M and atory diagnostic tumor specimens were collected before initiating first-line chemotherapy and were tested for epidermal growth factor receptor ( EGFR ) protein expression by using immunohistochemistry ( IHC ) , EGFR gene copy number by using fluorescent in situ hybridization ( FISH ) , and EGFR and KRAS mutations by using DNA sequencing . An EGFR CA simple sequence repeat in intron 1 ( CA-SSR1 ) polymorphism was evaluated in blood . RESULTS All 889 r and omly assigned patients provided tumor sample s. EGFR IHC , EGFR FISH , KRAS mutation , and EGFR CA-SSR1 repeat length status were not predictive for erlotinib efficacy . A profound predictive effect on PFS of erlotinib relative to placebo was observed in the EGFR mutation-positive subgroup ( hazard ratio [ HR ] , 0.10 ; P < .001 ) . Significant PFS benefits were also observed with erlotinib in the wild-type EGFR subgroup ( HR , 0.78 ; P = .0185 ) . KRAS mutation status was a significant negative prognostic factor for PFS . CONCLUSION This large prospect i ve biomarker study found that patients with activating EGFR mutations derive the greatest PFS benefit from erlotinib maintenance therapy . No other biomarkers were predictive for outcomes with erlotinib , although the study was not powered for clinical outcomes in biomarker subgroups other than EGFR IHC-positive [ corrected ] . KRAS mutations were prognostic for reduced PFS . The study demonstrated the feasibility of prospect i ve tissue collection for biomarker analyses in NSCLC BACKGROUND Poor PS is a negative prognostic factor for survival and a risk factor for treatment-related toxicity with st and ard platinum-doublet chemotherapy for advanced NSCLC . A phase II study combining erlotinib and bevacizumab for treatment of recurrent NSCLC showed encouraging efficacy and acceptable toxicity . PATIENTS AND METHODS This single-arm phase II study evaluated erlotinib and bevacizumab as first-line therapy for newly diagnosed nonsquamous advanced NSCLC patients with Eastern Cooperative Oncology Group PS ≥ 2 or age 70 or older . Only patients eligible for bevacizumab per label were enrolled . Patients received erlotinib 150 mg orally daily and bevacizumab 15 mg/kg intravenously on day 1 every 21 days for up to 6 cycles . The primary end point was the rate of nonprogressive disease at 4 months ( alternative hypothesis > 60 % ) . RESULTS Twenty-five patients were enrolled , with median age 77 years ( range , 52 - 90 years ) , 44 % female , 20 % never- or remote-smokers . Ninety-two percent of patients enrolled had PS of 2 per investigator assessment . The rate of nonprogressive disease at 4 months was 28 % . There were no complete responses , 1 patient achieved a partial response , and 11 patients ( 44 % ) experienced stable disease as best response . Rash , fatigue , and diarrhea were the most common toxicities . CONCLUSION The combination of erlotinib and bevacizumab had insufficient activity in the absence of known activating epidermal growth factor receptor gene mutations to warrant study in newly diagnosed elderly or poor PS patients with nonsquamous NSCLC BACKGROUND Bevacizumab and erlotinib target different tumour growth pathways with little overlap in their toxic-effect profiles . On the basis of promising results from a phase 1/2 trial assessing safety and activity of erlotinib plus bevacizumab for recurrent or refractory non-small-cell lung cancer ( NSCLC ) , we aim ed to assess efficacy and safety of this combination in a phase 3 trial . METHODS In our double-blind , placebo-controlled , r and omised phase 3 trial ( BeTa ) , we enrolled patients with recurrent or refractory NSCLC who presented to 177 study sites in 12 countries after failure of first-line treatment . Patients were r and omly allocated in a one-to-one ratio to receive erlotinib plus bevacizumab ( bevacizumab group ) or erlotinib plus placebo ( control group ) according to a computer-generated r and omisation sequence by use of an interactive voice response system . The primary endpoint was overall survival in all enrolled patients . Patients , study staff , and investigators were masked to treatment assignment . We assessed safety by calculation of incidence of adverse events and tissue was collected for biomarker analyses . This trial is registered with Clinical Trials.gov , number NCT00130728 . FINDINGS Overall survival did not differ between 317 controls and 319 patients in the bevacizumab group ( hazard ratio [ HR ] 0·97 , 95 % CI 0·80 - 1·18 , p=0·7583 ) . Median overall survival was 9·3 months ( IQR 4·1 - 21·6 ) for patients in the bevacizumab group compared with 9·2 months ( 3·8 - 20·2 ) for controls . Progression-free survival seemed to be longer in the bevacizumab group ( 3·4 months [ 1·4 - 8·4 ] ) than in the control group ( 1·7 months [ 1·3 - 4·1 ] ; HR 0·62 , 95 % CI 0·52 - 0·75 ) and objective response rate suggested some clinical activity of bevacizumab and erlotinib . However , these secondary endpoint differences could not be defined as significant because the study prespecified that the primary endpoint had to be significant before testing of secondary endpoints could be done , to control type I error rate . In the bevacizumab group , 130 ( 42 % ) of 313 patients with safety data had a serious adverse event , compared with 114 ( 36 % ) controls . There were 20 ( 6 % ) grade 5 adverse events , including two arterial thromboembolic events , in the bevacizumab group , and 14 ( 4 % ) in the control group . INTERPRETATION Addition of bevacizumab to erlotinib does not improve survival in patients with recurrent or refractory NSCLC . FUNDING Genentech BACKGROUND With use of EGFR tyrosine-kinase inhibitor monotherapy for patients with activating EGFR mutation-positive non-small-cell lung cancer ( NSCLC ) , median progression-free survival has been extended to about 12 months . Nevertheless , new strategies are needed to further extend progression-free survival and overall survival with acceptable toxicity and tolerability for this population . We aim ed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non-squamous NSCLC with activating EGFR mutation-positive disease . METHODS In this open-label , r and omised , multicentre , phase 2 study , patients from 30 centres across Japan with stage IIIB/IV or recurrent non-squamous NSCLC with activating EGFR mutations , Eastern Cooperative Oncology Group performance status 0 or 1 , and no previous chemotherapy for advanced disease received erlotinib 150 mg/day plus bevacizumab 15 mg/kg every 3 weeks or erlotinib 150 mg/day monotherapy as Output:	The addition of bevacizumab to erlotinib can significantly improve PFS and the ORR in the second-line treatment of NSCLC with an acceptable and manageable risk of rash and diarrhoea .
MS22087	*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 reported incidence of acute pelvic inflammatory disease ( PID ) has decreased but rates of tubal infertility have not , suggesting that a large proportion of PID leading to infertility may be undetected . Sub clinical PID is common in women with uncomplicated chlamydial or gonococcal cervicitis or with bacterial vaginosis . We assessed whether women with sub clinical PID are at an increased risk for infertility . METHODS : A prospect i ve observational cohort of 418 women with or at risk for gonorrhea or chlamydia or with bacterial vaginosis was recruited . Women with acute PID were excluded . An endometrial biopsy was performed to identify endometritis ( sub clinical PID ) . After provision of therapy for gonorrhea , chlamydia and bacterial vaginosis participants were followed-up for fertility outcomes . RESULTS : There were 146 incident pregnancies during follow-up , 50 pregnancies in 120 ( 42 % ) women with sub clinical PID and 96 in 187 ( 51 % ) women without sub clinical PID . Women with sub clinical PID diagnosed at enrollment had a 40 % reduced incidence of pregnancy compared with women without sub clinical PID ( hazard ratio 0.6 , 95 % confidence interval 0.4–0.8 ) . Women with Neisseria gonorrhoeae or Chlamydia trachomatis , in the absence of sub clinical PID , were not at increased risk for infertility . CONCLUSION : Sub clinical PID decreases subsequent fertility despite provision of treatment for sexually transmitted diseases . These findings suggest that a proportion of female infertility is attributable to sub clinical PID and indicate that current therapies for sexually transmitted diseases are inadequate for prevention of infertility . LEVEL OF EVIDENCE : Objective : The aim of this study was investigate the impact of vaginal flora and vaginal inflammation on conception and early pregnancy loss following in-vitro fertilization ( IVF ) . Methods : We enrolled 91 women who were undergoing IVF . At embryo transfer ( ET ) , all of the women had quantitative vaginal culture , ET catheter-tip culture , and vaginal Gram stain scored for bacterial vaginosis and quantitated for polymorphonuclear leukocytes ( PMNs ) . Conception and early pregnancy loss were compared with culture and Gram stain results . Statistical analyses included the Chi-square test , Fisher 's exact test and the Mann – Whitney U-test . Results : The overall live birth rate ( LBR ) was 30 % ( 27/91 ) , and the rate of early pregnancy loss was 34 % ( 14/41 ) . In women with bacterial vaginosis , intermediate flora and normal flora , the conception rates were 30 % ( 3/10 ) , 39 % ( 12/31 ) and 52 % ( 26/50 ) , respectively ( p = 0.06 for trend ) . Early pregnancy loss occurred in 33 % ( 1/3 ) , 42 % ( 5/12 ) and 31 % ( 8/26 ) of women , respectively ( p = 0.06 , comparing intermediate and normal flora ) . The vaginal log concentration of hydrogen peroxide-producing lactobacilli was 7.3 ± 1.7 in women with a live birth ( n = 27 ) and 4.9 ± 2.5 in those with early pregnancy loss ( n = 14 ) ( p = 0.1 ) . Conclusions : IVF patients with bacterial vaginosis and with a decreased vaginal log concentration of hydrogen peroxide-producing lactobacilli may have decreased conception rates and increased rates of early pregnancy loss . A larger prospect i ve treatment trial design ed to evaluate the impact on IVF outcomes of optimizing the vaginal flora prior to IVF may be warranted Objectives : To vali date a simplified grading scheme for Gram stained smears of vaginal fluid for the diagnosis of bacterial vaginosis ( BV ) against the accepted “ gold ” st and ard of Amsel ’s composite criteria . Methods : Women attending genitourinary medicine ( GUM ) clinics , as part of a multicentre study , were diagnosed as having BV if three or more of the following criteria were present ; homogeneous discharge , elevated vaginal pH , production of amines , and presence of “ clue ” cells . Women with less than three of the criteria were considered as normal . Simultaneously , smears were made of vaginal fluid and Gram stained and then assessed qualitatively as normal ( grade I ) , intermediate ( grade II ) , or consistent with BV ( grade III ) . Two new grade s were used , grade 0 , epithelial cells only with no bacteria , and grade IV , Gram positive cocci only . Results : BV was diagnosed in 83/162 patient visits using the composite criteria , the remainder being regarded as normal . The majority of patients with BV had a smear assessed as grade III ( 80/83 , 96 % ) and the majority of normal women had a smear assessed as grade I ( normal , 48/79 , 61 % ) , giving a high sensitivity ( 97.5 % ) , specificity ( 96 % ) , and predictive value for a positive ( 94.1 % ) and negative ( 96 % ) test , kappa index = 0.91 . Smears assessed as grade II were found predominantly ( 12/13 ) among patients diagnosed as normal , with less than three of the composite criteria . Grade s 0 and IV were both only found among normal women . Conclusion : This simplified assessment of Gram stained smears can be used as an alternative to Amsel ’s criteria and is more applicable for use in busy GUM clinics Objective To assess whether the rate of bacterial vaginosis ( BV ) is higher in women with tubal factor infertility compared with those with other causes of infertility Purpose The aim of this study was to investigate the impact of bacterial vaginal flora on life-birth rate during ICSI and influence of metronidazole as antibiotic treatment course before ICSI . Method We enrolled 71 women who were undergoing ICSI . At embryo transfer ( ET ) , all of the women had quantitative vaginal culture , ET catheter-tip culture , and vaginal Gram stain scored for bacterial vaginosis . Results The overall live birth rate ( LBR ) was 36.6 % ( 26/71 ) , and the rate of early pregnancy loss was 13 % ( 4/30 ) . In women with bacterial vaginosis , intermediate flora and normal flora , the conception rates were 35 % ( 9/26 ) , 42 % ( 14/33 ) and 58 % ( 7/12 ) , respectively ( p = 0.06 for trend ) . Metronidazole effect to bacterial flora in vaginal . The predominant species isolated from the tip of the embryo transfer catheter in negative pregnancy was Staphylococcus epidermidis ( 7 vs. 15.2 % ) , and Streptococcus viridians ( 11 vs. 24 % ) . Conclusions Woman with bacterial vaginosis and with a decreased vaginal concentration of hydrogen peroxide-producing lactobacilli may have decreased conception rates and increased rates of failed pregnancy . A larger prospect i ve treatment trial design ed to evaluate the impact on ICSI outcomes of optimizing the vaginal flora prior to ICSI may be warranted The objective of this prospect i ve cohort study was to eluci date whether bacterial vaginosis ( BV ) is associated with a pro-inflammatory endometrial secretion cytokine profile and whether there is a relationship between BV and the concentrations of a number of key regulatory cytokines , chemokines and growth factors . A total of 198 women undergoing IVF treatment were included . Prior to embryo transfer , participants underwent screening for BV according to Nugent criteria by a Gram-stained cervical smear . The concentrations of 17 soluble mediators of human implantation were measured by multiplex immunoassay in endometrial secretions aspirated prior to embryo transfer . Seventeen ( 8.6 % ) women had BV ( Nugent score > 6 ) . Multivariable logistic regression showed a significant positive association between interleukin-beta and the presence of BV ( P=0.011 ; Nugent score > 6 versus 6 ) and a significant negative association between eotaxin and BV ( P=0.003 ) . No significant differences were found in the ratios of distinct pro- and anti-inflammatory cytokines in endometrial secretions from women with or without BV . In conclusion , BV is associated with higher concentrations of interleukin-beta in endometrial secretions compared with women without BV . However , no distinct difference in pro- and anti-inflammatory profiles is present . An effect on endometrial receptivity is unlikely Output:	SUMMARY ANSWER The incidence of BV is significantly higher among patients with tubal infertility when compared with patients with non-tubal infertility . BV does not impinge on conception rates but is significantly associated with pre clinical pregnancy loss , though not with first trimester abortion . Still , there is strong circumstantial evidence that supports a causal link between BV and tubal infertility . Studies with a longitudinal design , on the other h and , strongly support a relation between BV and early pregnancy loss . Unfortunately , no study looked beyond first trimester fetal loss , although it is plausible that the high preterm birth rates with IVF are , at least , in part attributable to BV
MS22088	*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: Thirteen tetraplegic patients were included in the study of the effects of respiratory muscle training and of electrical stimulation of the abdominal muscles on their respiratory capabilities . Each patient was subjected for three 1 month lasting periods of the study : for inspiratory muscle training , expiratory muscle training and for a period without training . The sequence of these three periods was r and om for each patient . Respiratory tests ( RT ) measuring forced vital capacity ( FVC ) and forced expiratory volume in one second ( FEV1 ) were conducted before and following each monthly period . Measurements were taken under four sets of conditions : the patients ' unassisted efforts , their efforts combined with pressure manually applied by a therapist to the upper part of their abdomen , and their efforts accompanied by electrical stimulation ( ES ) of the abdominal muscles during the early phase of expirium , once triggered by the therapist and once by the patients themselves . RT values were increased following respiratory muscle training and inspiratory training apparently had a slightly greater effect than its expiratory counterpart . The increments of values of RT were statistically significant ( P<0.05 ) after the inspiratory muscle training . RT measurements were greater when the patient 's voluntary effort was combined with ES of abdominal muscles than when it was not . This study concludes that respiratory muscle training is a potentially effective approach and that ES of the abdominal muscles has potentials to improve coughing in tetraplegic patients Study design : This was a prospect i ve observational study . Objectives : To review airway management of patients with acute cervical spinal cord injury ( CSCI ) who are admitted to the intensive care unit ( ICU ) and to develop a classification and regression tree ( CART ) to direct clinical decision making in airway management . Setting : This study was carried out in Australia . Methods : All patients with CSCI who required intubation and mechanical ventilation and who were admitted to ICU in three tertiary hospitals in Melbourne between October 2004 and May 2009 and two other interstate hospitals between December 2004 and December 2005 were included . Airway management was recorded . Results : A total of 114 patients were included . Tracheostomy insertion occurred in 68 patients ( 59.7 % ) . Using CART analysis , it was found that the variables forced vital capacity , the volume of pulmonary secretion and gas exchange were predictive of airway management on 82.3 % occasions with an 8.7 % extubation failure rate . Conclusion : A CART can be useful in clinical decision making regarding airway management in CSCI OBJECTIVE To evaluate if resistive inspiratory muscle training ( RIMT ) can improve lung function in patients with complete tetraplegia within half a year after trauma . DESIGN A prospect i ve study . The experimental patients received training with a Diemolding Healthcare Division inspiratory muscle trainer for 15 to 20 minutes per session , twice per day , 7 days a week for 6 weeks . SETTING Hospital-based rehabilitation units . PATIENTS Twenty patients who were in their first 6 months of complete cervical cord injury were r and omly enrolled into RIMT ( 10 patients ) and control ( 10 patients ) groups . MAIN OUTCOME MEASURE Spirometry , lung volume test , maximal inspiratory pressure , maximal expiratory pressure , and modified Borg scale measurements at rest were performed before training and at the end of 6 weeks of training . RESULTS Most of the pulmonary parameters showed statistically significant improvements within the RIMT and control groups , but the improvements were greater in the RIMT group . In addition , the improvements in total lung capacity , total lung capacity predicted percentage , vital capacity , minute ventilation , forced expiratory volume in 1 second predicted percentage , and the resting Borg scale in the RIMT group showed significantly greater improvement . CONCLUSION RIMT can improve ventilatory function , respiratory endurance , and the perceived difficulty of breathing in patients with complete cervical spinal cord injury within half a year after trauma Study design : Prospect i ve single centre study . Objectives : Pulmonary rehabilitation focuses on improving the expiratory muscle function in order to increase the reduced cough capacity in patients with cervical spinal cord injuries ( SCI ) . However , an improvement in the inspiratory function is also important for coughing effectively . Therefore , this study was to examine the significance of the inspiratory muscle strength on the cough capacity in the patients with a cervical SCI . Setting : SCI unit , Yonsei Rehabilitation Hospital , Seoul , Korea . Methods : The vital capacity ( VC ) , maximum inspiratory pressure ( MIP ) , and maximum expiratory pressure ( MEP ) were measured . Moreover , the unassisted peak cough flow ( PCF ) and assisted PCF under three conditions were evaluated . Results : All three assisted cough methods showed a significantly higher value than the unassisted method ( P<0.001 ) . The VC correlated with the voluntary cough capacity and the MIP ( R=0.749 ) correlated more significantly with the VC than the MEP ( R=0.438 ) ( P<0.01 ) . The MIP showed a higher correlation with both the unassisted PCF and all three assisted PCFs than the MEP ( P<0.001 ) . Conclusions : The management of the inspiratory muscle strength should be considered in the pulmonary rehabilitation at cervical SCI patients We examined the effects of ventilatory muscle endurance training on resting breathing pattern in 12 C6-C7 traumatic quadriplegics at least 1 year post-injury . All subjects had complete motor loss below the lesion level . Subjects were r and omly assigned to a training ( N = 6 ) , or a control group ( N = 6 ) . Baseline tests included measurement of resting ventilation and breathing pattern using mercury in rubber strain gauges for 20 minutes in a seated position ; maximum inspiratory mouth pressure ( MIP ) at FRC , and sustainable inspiratory mouth pressure for 10 minutes ( SIP ) ; lung volumes , and arterial blood gases ( ABG 's ) . The training protocol consisted of breathing through an inspiratory resistor equivalent to 85 % SIP for 15 minutes twice daily , 5 days a week for 8 weeks . Both trainers and controls attended the lab every 2 weeks for re assessment of MIP and SIP and the inspiratory resistance was increased in the training group as SIP increased . At the end of 8 weeks , baseline tests were repeated . All subjects had normal ABG 's . There was a significant increase in mean MIP and SIP in both the control group ( 30 % ± 19 % and 31 % ± 18 % respectively ) , and in the training group ( 42 % ± 24 % and 78 % ± 49 % respectively ) . Although the absolute values for both MIP and SIP were greater in the training group than in the control group , the differences were not significant . The alterations in resting breathing pattern were also the same in both groups . Mean frequency decreased significantly in the control group ( 20.2/minute to 16.9/minute ) and , while insignificant , the change in frequency in the training group was the same , 19.4/minute to 16.4/minute . Mean tidal volume ( Vt ) increased 18.2 % of baseline Vt in the control group and 17.0 % baseline in the trainers , result ing in no change in minute ventilation . As MIP and SIP increased similarly in both groups , the data from the control and trainers was pooled and timing changes re-evaluated pre- and post- study . A significant decrease in mean Ti/Ttot was observed , while no change in Vt/ Ti was found . We concluded that the testing procedure itself provided the stimulus result ing in a significant increase in MIP and SIP . The addition of training did not increase MIP and SIP further . The increased MIP and SIP result ed in a slower and deeper breathing pattern and a significantly shorter Ti/Ttot in both trainers and control subjects OBJECTIVE To compare the effects of inspiratory resistance training and isocapnic hyperpnoea vs incentive spirometry ( placebo ) on respiratory function , voice , thorax mobility and quality of life in individuals with tetraplegia . DESIGN R and omized controlled trial . PATIENTS / METHODS A total of 24 individuals with traumatic , complete tetraplegia ( C5-C8 , American Spinal Injury Association ( ASIA ) Impairment Scale ; AIS A ) were r and omly assigned to 1 of 3 groups . They completed 32 supervised training sessions over a period of 8 weeks . Before and after the training period , the following tests were performed : body plethysmography , inspiratory and expiratory muscle strength , subjective breathing parameters using a visual analogue scale , voice measurements , thorax mobility and quality of life . Cohen 's effect sizes and Kruskal-Wallis tests for differences between pre- and post-training values were calculated . RESULTS Compared with placebo training , inspiratory resistance training showed high effect sizes for inspiratory muscle strength ( d = 1.13 ) , the subjective ability " to blow one 's nose " ( d = 0.97 ) and the physical component of quality of life ( d = 0.82 ) . Isocapnic hyperpnoea compared with placebo showed a high effect size for breathlessness during exercise ( d = 0.81 ) . We found a significant effect of inspiratory resistance training vs placebo ( p = 0.016 ) and vs isocapnic hyperpnoea ( p = 0.012 ) for inspiratory muscle strength . CONCLUSION In individuals with motor and sensory complete tetraplegia during the first year post-injury , inspiratory resistance training is more advantageous than isocapnic hyperpnoea , performed 4 times a week for 10 min Adults and children with neuromuscular disease exhibit weak cough and are susceptible to recurrent chest infections , a major cause of morbidity and mortality . Mechanical insufflation/exsufflation may improve cough efficacy by increasing peak cough flow . It was hypothesised that mechanical insufflation/exsufflation would produce a greater increase in peak cough flow than other modes of cough augmentation . The acceptability of these interventions was also compared . Twenty-two patients aged 10–56 yrs ( median 21 yrs ) with neuromuscular disease and 19 age-matched controls were studied . Spirometry was performed and respiratory muscle strength measured . Peak cough flow was recorded during maximal unassisted coughs , followed in r and om order by coughs assisted by physiotherapy , noninvasive ventilation , insufflation and exsufflation , and exsufflation alone . Subjects rated strength of cough , distress and comfort on a visual analogue scale . In the neuromuscular disease group , mean±sd forced expiratory volume in one second was 0.8±0.6 L·s−1 , forced vital capacity 0.9±0.8 L , maximum inspiratory pressure 25±16 cmH2O , maximum expiratory pressure 26±22 cmH2O and unassisted peak cough flow 169±90 L·min−1 . The greatest increase in peak cough flow was observed with mechanical insufflation/exsufflation at 235±111 L·min−1 ( p<0.01 ) . All techniques showed similar patient acceptability . Mechanical insufflation/exsufflation produces a greater increase in peak cough flow than other st and ard cough augmentation techniques in adults and children with neuromuscular disease Stolzmann KL , Gagnon DR , Brown R , Tun CG , Garshick E : Risk factors for chest illness in chronic spinal cord injury : A prospect i ve study . Objective : Chest illnesses commonly cause morbidity in persons with chronic spinal cord injury . Risk factors remain poorly characterized because previous studies have not accounted for factors other than spinal cord injury . Design : Between 1994 and 2005 , 403 participants completed a respiratory question naire and underwent spirometry . Participants were contacted at a median of 1.7 yrs [ interquartile range : 1.3–2.5 yrs ] apart over a mean ( SD ) of 5.1 ± 3.0 yrs and asked to report chest illnesses that had result ed in time off work , spent indoors , or in bed since prior contact . Results : In 97 participants , there were 247 chest illnesses ( 0.12/person-year ) with 54 hospitalizations ( 22 % ) . Spinal cord injury level , completeness of injury , and duration of injury were not associated with illness risk . Adjusting for age and smoking history , any wheeze ( relative risk = 1.92 ; 95 % confidence interval : 1.19 , 3.08 ) , pneumonia or bronchitis since spinal cord injury ( relative risk = 2.29 ; 95 % confidence interval : 1.40 , 3.75 ) , and physician-diagnosed chronic obstructive pulmonary disease ( relative risk = 2.17 ; 95 % confidence interval : 1.08 , 4.37 ) were associated with a greater risk of chest illness . Each percent-predicted decrease in forced expiratory volume in 1 sec was associated with a 1.2 % increase in risk of chest illness ( P = 0.030 ) . Conclusions : In chronic spinal cord injury , chest illness result ing in time spent away from usual activities was not related to the level or completeness of spinal cord injury but was related to reduced pulmonary function , wheeze , chronic obstructive pulmonary disease , a history of pneumonia and bronchitis , and smoking OBJECTIVE To assess the effectiveness of expiratory muscle training on the pulmonary function of spinal cord injured patients . DESIGN R and omized controlled trial . SETTING Acute inpatient rehabilitation hospital . PARTICIPANTS Patients ( N=29 , 22 men and 7 women ) with recent traumatic , motor complete , spinal cord injury ( SCI ) at or above level T1 consecutively admitted to an SCI rehabilitation service . Subjects were r and omized to either resistance training ( n=16 ) or sham Output:	A significant benefit of RMT was revealed for five outcomes : vital capacity ( mean difference ( 95 % confidence interval))=0.41(0.17–0.64 ) l , maximal inspiratory pressure=10.66(3.59 , 17.72 ) cmH2O , maximal expiratory pressure=10.31(2.80–17.82 ) cmH2O , maximum voluntary ventilation=17.51(5.20 , 29.81 ) l min−1 and inspiratory capacity=0.35(0.05 , 0.65 ) l. No effect was found for total lung capacity , peak expiratory flow rate , functional residual capacity , residual volume , expiratory reserve volume or forced expiratory volume in 1 second . Conclusion : RMT increases respiratory strength , function and endurance during the period of training .
MS22089	*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 The need for zinc in the optimal healing of wounds was demonstrated by the acceleration of healing of granulating wounds caused by excision of pilonidal-sinus tracts in young , healthy airmen who were given zinc sulphate U.S.P. , 220 mg . t.i.d . by mouth during the period of repair . The rate of healing was determined by measurements of the wound volumes and the number of days for complete repair . Ten r and omly selected controls ( mean age 25·0 years and wound volume 32·3 ml . ) were matched against ten who were given the drug ( mean age 24·6 years and wound volume 54·5 ml . ) . The days ±S.E. for healing averaged 80·1±13·7 in the controls and 45·8±2·6 ( Output:	Overall , there was no evidence of a beneficial effect of treatment with zinc sulphate on the number of ulcers healed .
MS22090	*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 primary purpose of this r and omized controlled trial ( RCT ) was to compare knee-specific outcomes ( stiffness , pain , function ) between patellar retention and resurfacing up to 10 years after primary total knee arthroplasty ( TKA ) . Secondarily , we compared re-operation rates . Methods 38 subjects with non-inflammatory arthritis were r and omized at primary TKA surgery to receive patellar resurfacing ( n = 21 ; Resurfaced group ) or to retain their native patella ( n = 17 ; Non-resurfaced group ) . Evaluations were performed preoperatively , one , five and 10 years postoperatively by an evaluator who was blinded to group allocation . Self-reported knee-specific stiffness , pain and function , the primary outcomes , were measured by the Western Ontario McMaster Osteoarthritis Index ( WOMAC ) . Revision rate was determined at each evaluation and through hospital record review . Results 30 ( 88 % ) and 23 ( 72 % ) of available subjects completed the five and 10-year review respectively . Knee-specific scores continued to improve for both groups over the 10-years , despite diminishing overall health with no significant group differences seen . All revisions occurred within five years of surgery ( three Non-resurfaced subjects ; one Resurfaced subject ) ( p = 0.31 ) . Two revisions in the Non-resurfaced group were due to persistent anterior knee pain . Conclusions We found no differences in knee-specific results between groups at 5–10 years postoperatively . The Non-resurfaced group had two revisions due to anterior knee pain similar to rates reported in other studies . Knee-specific results provide useful postoperative information and should be used in future studies comparing patellar management strategies . Clinical Trials.gov BACKGROUND The need for patella resurfacing remains an area of considerable controversy in total knee replacement surgery . There would appear to be no reported evidence on the effect of patella resurfacing on knee function , as measured by functional range of movement used in a series of tasks , in patients undergoing knee replacement . The object of this study was to measure knee joint motion during functional activities both prior to and following total knee replacement in a r and omised group of patients with and without patella resurfacing and to compare these patient groups with a group of normal age-matched subjects . METHODS The study design was a double blinded , r and omised , prospect i ve , controlled trial . The knee joint functional ranges of movement of a group of patients ( n=50 , mean age=70 years ) with knee osteoarthritis were investigated prior to and following total knee arthroplasty ( 4 months and 18 - 24 months ) along with a group of normal subjects ( n=20 , mean age=67 ) . Patients were r and omly allocated into two groups , those who received patella resurfacing ( n=25 ) and those who did not ( n=25 ) . Flexible electrogoniometry was used to measure the flexion-extension angle of the knees with respect to time in eleven functional activities . FINDINGS No statistically significant differences ( alpha level 0.05 ) in joint excursion of the affected knee were found between patients who received patella resurfacing and those who did not . INTERPRETATION Routine patella resurfacing in a typical knee arthroplasty population does not result in an increase in the functional range of movement used after knee replacement BACKGROUND In total knee arthroplasty ( TKA ) , h and ling of the patella surface is still quite controversial . We carried out a prospect i ve r and omized study to compare circumpatellar electrocautery plus patella resurfacing vs circumpatellar electrocautery only in the single-staged bilateral TKA in Chinese population . METHODS One hundred five patients diagnosed with late-staged osteoarthritis who received single-staged bilateral TKA were screened and 53 patients were included . All patients received the same posterior cruciate-stabilizing total knee prostheses . Patients were r and omized to receive circumpatellar electrocautery plus patellar resurfacing or circumpatellar electrocautery only for the first TKA , and the second knee received the opposite treatment . All patients were followed for a minimum of 2 years . RESULTS No differences were found with regard to Knee Society Score , Feller score , anterior knee pain , and revision rates . Fifty-two percent of patients had no preference with regard to pain and function , 27 % of patients preferred the resurfacing plus circumpatellar electrocautery knee while 21 % of the patients preferred the circumpatellar electrocautery only knee . The Insall-Salvati index and the patella tilt were a little smaller in the resurfacing group . One patient ( 2.1 % ) in the circumpatellar electrocautery group underwent a patella resurfacing revision for severe anterior knee pain and patella subluxation . CONCLUSION Equivalent clinical results for circumpatellar electrocautery plus resurfacing and circumpatellar electrocautery alone of the patella in TKA were demonstrated in selective Chinese population with thick enough patella Background There is no difference in the functional outcomes 6 months after total knee arthroplasty ( TKA ) for knee osteoarthritis between patellar resurfacing and non-resurfacing . Thus , we have performed this study to compare the short-term clinical outcomes of TKA performed with and without the patella resurfacing . Methods A total of 50 patients with osteoarthritis of the knee ( OAK ) were r and omized to receive patellar resurfacing ( n=24 ; resurfaced group ) or to retain their native patella ( n=26 ; non-resurfaced group ) based on envelope selection and provided informed consent . Disease specific outcomes including Knee Society Score ( KSS ) , Knee Society Function Score ( KSKS-F ) , Kujala Anterior Knee Pain Scale ( AKPS ) , Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , Short Form 36 ( SF-36 ) , and functional patella-related activities were measured within six months of follow-up . Results There was no significant difference between the resurfaced and non-resurfaced groups in pre and post-operative improvement of range of motion ( ROM ) ( P=0.421 ) , KSS ( P=0.782 , P=0.553 ) , KSKS-F ( P=0.241 , P=0.293 ) , AKPS ( P=0.128 , P=0.443 ) , WOMAC ( P=0.700 , P=0.282 ) , and pain scores ( P=0.120 , P=0.508 ) . There was no difference in ROM between resurfaced and non-resurfaced group pre ( 15.24 ° and 15.45 ° ) and post-operative ( 18.48 ° and 18.74 ) . No side effects related to patella was observed in any of the groups . Revision was required in none of the participants . Conclusion The results showed no significant difference between patellar resurfacing and non-resurfacing in TKA for all outcome measures in a short term . Level of evidence : Introduction : Anterior knee pain following total knee arthroplasty is estimated to occur in 4 - 49 % of patients . Some orthopedic surgeons use circumpatellar electrocautery ( diathermy ) to reduce the prevalence of postsurgical anterior knee pain ; however , the extent of its use is unknown . Material s and Methodology : In April 2009 , a postal question naire was sent to all 98 departments of orthopedic surgery in The Netherl and s. The questions focused on the frequency of total knee arthroplasties , patellar resurfacing , and the use of circumpatellar electrocautery . Results : The response rate was 92 % . A total of 18,876 TKAs , 2,096 unicompartmental knee arthroplasties , and 215 patellofemoral arthroplasties are performed yearly in The Netherl and s by the responding orthopedic surgeons . Of the orthopedic surgeons performing TKA , 13 % always use patellar resurfacing in total knee arthroplasty for osteoarthritis , 49 % use selective patellar resurfacing , and 38 % never use it . Fifty-six percent of orthopedic surgeons use circumpatellar electrocautery when not resurfacing the patella , and 32 % use electrocautery when resurfacing the patella . Conclusion : There is no consensus among Dutch orthopedic surgeons on the use of patellar resurfacing or circumpatellar electrocautery in total knee replacement performed for osteoarthritis . A prospect i ve clinical trial is currently underway to fully evaluate the effect of circumpatellar electrocautery on the prevalence of anterior knee pain following total knee arthroplasty Complications of patellar resurfacing in total knee arthroplasty have rekindled the interest of many surgeons in patellar retention . In a prospect i ve study 20 r and omly selected patients of 40 underwent patellar resurfacing in combination with their total knee arthroplasty . The other 20 patients were left with an unresurfaced patella . Within 24 months of follow-up , the advantages of patellar resurfacing could be seen according to the Knee Society Score . Especially in advanced osteoarthritis of the knee joint , the patients achieved better scores in climbing stairs and in function . The superior functional results are arguments for patellar resurfacing , at least in knees with advanced osteoarthritis Background : Whether to resurface the patella during a primary total knee arthroplasty performed for the treatment of degenerative osteoarthritis remains a controversial issue . Parameters that have been suggested as being useful in guiding this decision include patient height and weight , the presence of anterior knee pain preoperatively , and the grade of chondromalacia encountered intraoperatively . The purpose of this study was to determine whether these parameters were predictive of the clinical result following total knee arthroplasty with or without patellar resurfacing . Methods : Eighty-six patients ( 118 knees ) undergoing primary total knee arthroplasty for the treatment of osteoarthritis were enrolled in a prospect i ve , r and omized , double-blind study . All patients received the same posterior-cruciate-sparing total knee prosthetic components . Patients were r and omized to treatment with or without resurfacing of the patella . Evaluations consisted of the determination of a Knee Society clinical score , the completion of a patient satisfaction question naire , specific questions relating to patellofemoral symptoms , and radiographs . Sixty-seven patients ( ninety-three knees ) were followed for a minimum of five years ( range , sixty to eighty-four months ; average , 70.5 months ) . Results : With the numbers available , there was no significant difference between the groups treated with and without resurfacing with regard to the overall Knee Society score or the pain and function subscores . Obesity , the degree of patellar chondromalacia , and the presence of preoperative anterior knee pain did not predict postoperative clinical scores or the presence of postoperative anterior knee pain . Conclusions : The occurrence of anterior knee pain could not be predicted with any clinical or radiographic parameter studied . On the basis of these results , it seems likely that postoperative anterior knee pain is related either to the component design or to the details of the surgical technique , such as component rotation , rather than to whether or not the patella is resurfaced 350 knees were evaluated in a prospect i ve , r and omized , double-blinded study of selective patellar resurfacing in primary total knee arthroplasty . Knees with exposed bone on the patellar articular surface were excluded . 327 knees were evaluated at a mean follow-up of 7.8years . 114 knees followed for greater than 10 years were analyzed separately . Satisfaction was higher in patients with a resurfaced patella . In patients followed for at least 10 years , no significant difference was found . No difference was found in KSS scores or survivorship . No complications of patellar resurfacing were identified . The vast majority of patients with remaining patellar articular cartilage do very well with total knee arthroplasty regardless of patellar resurfacing . Patient satisfaction may be slightly higher with patellar resurfacing The aim of this study was to assess medium term results of patellar resurfacing in total knee arthroplasty , specifically looking at anterior knee pain , patellofemoral function and need for reoperation . A prospect i ve cohort study was conducted with patients undergoing staged bilateral knee arthroplasty with the patella being resurfaced only on one side . This was due to change in the clinical practice of the senior author . Sixty patients were review ed clinical ly and radiologically on a regular basis . The surgery was either performed or supervised by the senior author in all cases . All patients received the cemented press-fit condylar © prosthesis . The Knee Society clinical rating system was used . Scores were recorded pre-operatively and post-operatively at three months , one year , two years and three yearly thereafter . The mean age of patients in the study group was 75 years ( range : 62–89 years ) . There were 42 women and 18 men in the study . The mean duration of follow-up was 4.5 years ( range : 2–12 years ) . There was no significant difference in the pre-operative scores in both groups . There Output:	Based on the main findings of this meta- analysis , patellar resurfaced TKA was demonstrated to have performed superior overall . Patellar resurfacing detected a lower rate of postoperative anterior knee pain and reoperation . Moreover , the resurfacing group showed greater value of the HSS , KSS and related subscales .
MS22091	*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 Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain , PGP , in pregnant women . However , the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition . The aim of the present work was to assess adverse effects of acupuncture on the pregnancy , mother , delivery and the fetus/neonate in comparison with women that received stabilising exercises as adjunct to st and ard treatment or st and ard treatment alone . Methods In all , 386 women with PGP entered this controlled , single-blind trial . They were r and omly assigned to st and ard treatment plus acupuncture ( n = 125 ) , st and ard treatment plus specific stabilising exercises ( n = 131 ) or to st and ard treatment alone ( n = 130 ) for 6 weeks . Acupuncture that may be considered strong was used and treatment was started as early as in the second trimester of pregnancy . Adverse effects were recorded during treatment and throughout the pregnancy . Influence on the fetus was measured with cardiotocography ( CTG ) before-during and after 43 acupuncture sessions in 43 women . A st and ardised computerized method to analyze the CTG reading numerically ( Oxford 8000 , Oxford , Engl and ) was used . After treatment , the women rated their overall experience of the treatment and listed adverse events if any in a question naire . Data of analgesia and oxytocin augmentation during labour , duration of labour , frequency of preterm birth , operative delivery , Apgar score , cord-blood gas/acid base balance and birth weight were also recorded . Results There were no serious adverse events after any of the treatments . Minor adverse events were common in the acupuncture group but women rated acupuncture favourably even despite this . The computerized or visually assessed CTG analyses of antenatal recordings in connection with acupuncture were all normal . Conclusion This study shows that acupuncture administered with a stimulation that may be considered strong led to minor adverse complaints from the mothers but had no observable severe adverse influences on the pregnancy , mother , delivery or the fetus/neonate Background . Low back and pelvic pain is common in pregnancy and postpartum , but there is no well documented effect of treatment in pregnancy . The aim of the study was to assess whether a group intervention program for pregnant women with pelvic girdle pain has any effect on pain and daily function postpartum . Methods . Pregnant women with pelvic pain between the 18th and 32nd week of gestation were invited to participate in a r and omized clinical study . Among 958 examined women , 569 ( 59 % ) fulfilled the inclusion criteria . Women r and omized to the intervention group ( n = 275 ) participated in an education program that consisted of information , ergonomics , exercises , pain management , advice for daily life movement , pelvic belt/crutches , and information about delivery . Women r and omized to the control group ( n = 285 ) were not offered any treatment , but were free to seek advice or other treatment . Clinical measures and self‐evaluated utility of the intervention were measured by a visual analogue scale 0–10 . Results . Mean debut of pelvic girdle pain in pregnancy was at week 15 . Altogether 42 % of the women reported problems with low back pain earlier , and 34 % reported a family history of pelvic girdle pain in pregnancy . Median visual analogue scale score for all activities at inclusion was 6 both in the control group and the intervention group . At 6 and 12 months postpartum the score was reduced to 1.7/1.6 and 1.1/0.9 . In the intervention group , 75 % marked a self‐evaluated utility visual analogue scale score > 7 . In the control group , 60 % had search ed for alternative treatment . Conclusions . Postpartum pelvic girdle pain improved with time both in the intervention group and the control group , but there were no statistically significant differences between the groups . Self‐evaluated utility of the intervention was , however , high in the intervention group This study was undertaken to investigate the effects of acupuncture in low back and pelvic pain during pregnancy under real life conditions , as compared with patients undergoing conventional treatment alone . A total of 61 conventionally treated pregnant women were allocated r and omly into two groups to be treated or not by acupuncture . Twenty-seven patients formed the study group and 34 the control group . They reported the severity of pain using a Numerical Rating Scale from 0 to 10 , and their capacity to perform general activities , to work , and to walk . We also assessed the use of analgesic drugs . Women were followed up for eight weeks and interviewed five times , at two-week intervals . All women completed the study . In the study group the average pain during the study period showed a larger reduction ( 4.8 points ) than the control group ( −0.3 points ) ( P<0.0001 ) . Average pain scores decreased by at least 50 % over time in 21 ( 78 % ) patients in the acupuncture group and in five ( 15 % ) patients in the control group ( P<0.0001 ) . Maximum pain and pain at the moment of interview were also less in the acupuncture group compared with the control group . The capacity to perform general activities , to work and to walk was improved significantly more in the study group than in the control group ( P<0.05 ) . The use of paracetamol was lower in the acupuncture group ( P<0.01 ) . These results indicate that acupuncture seems to alleviate low back and pelvic pain during pregnancy , as well as to increase the capacity for some physical activities and to diminish the need for drugs , which is a great advantage during this period OBJECTIVE To investigate if water-gymnastics during pregnancy may reduce the intensity of back/low back pain and the number of days on sick-leave . METHODS A prospect i ve , r and omized study . One hundred and twenty-nine women were r and omized to participate in water-gymnastics once a week during the second half of pregnancy and 129 were r and omized to a control group . The women in both groups filled in question naires in gestational weeks 18 , 34 and within the first postpartum week . Every day from week 18 to labor they assessed the intensity of back/low back pain . RESULTS Back pain intensity increased during pregnancy . No excess risk for the pregnancy associated with water-gymnastics was observed . The women participating in water-gymnastics recorded a lower intensity of back/low back pain . The total number of days on sick-leave because of back/low back pain was 982 in the water-gymnastics group ( 124 women ) compared with 1484 in the control group ( 120 women ) . After weeks 32 33 , seven women in the water-gymnastics group compared with 17 in the control group were on sickleave because of back/ low back pain ( p=0.031 ) . CONCLUSIONS Intensity of back/low back pain increased with advancing pregnancy . There was no excess risk for urinary or vaginal infections associated with water-gymnastics . Water-gymnastics during the second half of pregnancy significantly reduced the intensity of back/ low back pain . Water-gymnastics decreased the number of women on sick-leave because of back/low back pain . Water-gymnastics during pregnancy can be recommended as a method to relieve back pain and may reduce the need for sick-leave Abstract Objectives To compare the efficacy of st and ard treatment , st and ard treatment plus acupuncture , and st and ard treatment plus stabilising exercises for pelvic girdle pain during pregnancy . Design R and omised single blind controlled trial . Setting s East Hospital , Gothenburg , and 27 maternity care centres in Sweden . Participants 386 pregnant women with pelvic girdle pain . Interventions Treatment for six weeks with st and ard treatment ( n = 130 ) , st and ard treatment plus acupuncture ( n = 125 ) , or st and ard treatment plus stabilising exercises ( n = 131 ) . Main outcome measures Primary outcome measure was pain ( visual analogue scale ) ; secondary outcome measure was assessment of severity of pelvic girdle pain by an independent examiner before and after treatment . Results After treatment the stabilising exercise group had less pain than the st and ard group in the morning ( median difference = 9 , 95 % confidence interval 1.7 to 12.8 ; P = 0.0312 ) and in the evening ( 13 , 2.7 to 17.5 ; P = 0.0245 ) . The acupuncture group , in turn , had less pain in the evening than the stabilising exercise group ( −14 , −18.1 to −3.3 ; P = 0.0130 ) . Furthermore , the acupuncture group had less pain than the st and ard treatment group in the morning ( 12 , 5.9 to 17.3 ; P < 0.001 ) and in the evening ( 27 , 13.3 to 29.5 ; P < 0.001 ) . Attenuation of pelvic girdle pain as assessed by the independent examiner was greatest in the acupuncture group . Conclusion Acupuncture and stabilising exercises constitute efficient complements to st and ard treatment for the management of pelvic girdle pain during pregnancy . Acupuncture was superior to stabilising exercises in this study Background . The study was design ed to evaluate the analgesic effect and possible adverse effects of acupuncture for pelvic and low‐back pain during the last trimester of pregnancy A single center , prospect i ve , r and omized , single blinded , controlled study comparing the effects and safety of " sitting pelvic tilt exercise " in relieving back pain during the third trimester in primigravida was carried out . The sample s were composed of 67 primigravidas who attended the prenatal clinic at King Chulalongkorn Memorial Hospital . All subjects were selected by the r and om sampling technique and allocated into two groups for the experimental group and the control group ; for 32 and 35 pregnants , respectively . The experimental group received the pelvic tilt exercise program for 8 weeks during the third trimester . Pain intensity was measured by visual analogue scale ( VAS ) at day 0 and day 56 in both groups . The result of the study revealed 1 ) The mean VAS of back pain in the experimental group was significantly lower at day 56 than at day 0 and lower than the control group at day 56 ( p < 0.05 ) by unpaired t-test 2 ) There was no incidence of preterm labor , low birth weight or neonatal complication in the experimental group . In conclusion , the " sitting pelvic tilt exercise " during the third trimester in primigravidas could decrease back pain intensity without incidence of preterm labor , low birth weight or neonatal complication BACKGROUND AND PURPOSE Symphysis pubis pain is a significant problem for some pregnant women . The purpose of this study was to investigate the effects of exercise , advice , and pelvic support belts on the management of symphysis pubis dysfunction during pregnancy . SUBJECTS Ninety pregnant women with symphysis pubis dysfunction were r and omly assigned to 3 treatment groups . METHODS A r and omized masked prospect i ve experimental clinical trial was conducted . Specific muscle strengthening exercises and advice concerning appropriate methods for performing activities of daily living were given to the 3 groups , and 2 of the groups were given either a rigid pelvic support belt or a nonrigid pelvic support belt . The dependent variables , which were measured before and after the intervention , were a Rol and -Morris Question naire score , a Patient-Specific Functional Scale score , and a pain score ( 101-point numerical rating score ) . RESULTS After the intervention , there was a significant reduction in the Rol and -Morris Question naire score , the Patient-Specific Functional Scale score , and the average and worst pain scores in all groups . With the exception of average pain , there were no significant differences between groups for the other measures . DISCUSSION AND CONCLUSION The findings indicate that the use of either a rigid or a nonrigid pelvic support belt did not add to the effects provided by exercise and advice Background . Prevention of lumbopelvic pain in pregnancy has been sparsely studied . One aim of this study was to assess if a 12‐week training program during pregnancy can prevent and /or treat lumbopelvic pain . A r and omized controlled trial was conducted at Trondheim University Hospital and three outpatient physiotherapy clinics . Three hundred and one healthy nulliparous women were included at 20 weeks of pregnancy and r and omly allocated to a training group ( 148 ) or a control group ( 153 ) . Methods . The outcome measures were self‐reported symptoms of lumbopelvic pain ( once per week or more ) , sick leave , and functional status . Pain drawing was used to document the painful area of the body . The intervention included daily pelvic floor muscle training at home , and weekly group training over 12 weeks including aerobic exercises , pelvic floor muscle and additional exercises , and information related to pregnancy . Results . At 36 weeks of gestation women in the training group were significantly less likely to report lumbopelvic pain : 65/148 ( 44 % ) versus 86/153 ( 56 % ) ( p = 0.03 ) . Three months after delivery the difference was 39/148 ( 26 % ) in the training group versus 56/153 ( 37 % ) in the control group ( p = 0.06 ) . There was no difference in sick leave during pregnancy , but women in the training group had significantly ( p = 0.01 ) higher scores on functional status . Conclusions . A 12‐week specially design ed training program during pregnancy was effective in preventing lumbopelvic pain in pregnancy Study Design This study analyzed an education and training program concerning back and pelvic problems among pregnant women . Objective Output:	Low- quality evidence from single trials suggested no significant difference in pain or function between two types of pelvic support belt , between osteopathic manipulation ( OMT ) and usual care or sham ultrasound ( sham US ) . Very low- quality evidence suggested that a specially- design ed pillow may relieve night pain better than a regular pillow . For pelvic pain , there was moderate- quality evidence that acupuncture significantly reduced evening pain better than exercise ; both were better than usual care . Low- quality evidence from single trials suggested that adding a rigid belt to exercise improved average pain but not function ; acupuncture was significantly better than sham acupuncture for improving evening pain and function , but not average pain ; and evening pain relief was the same following either deep or superficial acupuncture . Low- quality evidence from single trials suggested that OMT significantly reduced pain and improved function ; either a multi-modal intervention that included manual therapy , exercise and education ( MOM ) or usual care significantly reduced disability , but only MOM improved pain and physical function ; acupuncture improved pain and function more than usual care or physiotherapy ; pain and function improved more when acupuncture was started at 26- rather than 20- weeks ' gestation ; and auricular ( ear ) acupuncture significantly improved these outcomes more than sham acupuncture . Moderate- quality evidence suggested that acupuncture or exercise , tailored to the stage of pregnancy , significantly reduced evening pelvic pain or lumbo-pelvic pain more than usual care alone , acupuncture was significantly more effective than exercise for reducing evening pelvic pain , and a 16- to 20-week training program was no more successful than usual prenatal care at preventing pelvic or LBP . Physiotherapy , OMT , acupuncture , a multi-modal intervention , or the addition of a rigid pelvic belt to exercise seemed to relieve pelvic or back pain more than usual care alone . Acupuncture was more effective than physiotherapy at relieving evening lumbo-pelvic pain and disability and improving pain and function when it was started at 26- rather than 20-weeks ' gestation , although the effects were small . There was no significant difference in LBP and function for different support belts , exercise , neuro emotional technique or spinal manipulation ( SMT ) , or in evening pelvic pain between deep and superficial acupuncture .
MS22092	*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 As part of a continuous quality control effort to measure the interrater reliability of urodynamic studies performed at multiple centers , we compared agreement levels for urodynamic studies between central and local physician review ers . We report interrater reliability findings for the filling cystometrogram . MATERIAL S AND METHODS Following a satisfactory interrater reliability study among 4 central physician review ers in 33 tracings 36 urodynamic study tracings from 9 Urinary Incontinence Treatment Network continence treatment centers and 13 Urinary Incontinence Treatment Network certified urodynamic study testers were r and omly selected for review . These tracings were originally interpreted by 11 local physician review ers using st and ardized Urinary Incontinence Treatment Network interpretation guidelines . Each of the 4 central physician review ers review ed 9 r and omly assigned tracings and none review ed tracings from his or her center . Local and central physician review ers were instructed to categorize values as invalid if specified technical quality assurance st and ards were not met or the signal pattern suggested implausible values because of technical deficiencies . An intraclass correlation coefficient was calculated for continuous ( numerical ) variables and a kappa statistic was calculated for qualitative values with acceptable agreement defined a priori as an intraclass correlation coefficient of greater than 0.6 . RESULTS Filling cystometrogram baseline pressure , Valsalva leak point pressure , and volume and pressure measurements at maximum cystometric capacity had excellent intraclass correlation coefficients of 0.74 to 0.99 . There were no significant differences between local and central physician review er means , indicating excellent agreement . CONCLUSIONS With proper quality control measures in place and a set of st and ardized interpretive guidelines excellent interrater reliability between local and central physician review er can be achieved for numerical cystometrogram variables OBJECTIVES The aim of this study was to compare the long-term success rates , complication rates and patient satisfaction rates for Pelvicol pubovaginal sling ( Bard ) versus TVT ( Gynecare ) in surgical treatment of urodynamic stress incontinence ( USI ) in women . DESIGN Prospect i ve r and omized cohort trial . SETTING District General Hospital , South West of Engl and . METHODS One hundred and forty-two women with urodynamic stress incontinence were r and omized to either surgical procedure ( Pelvicol = 74 , TVT = 68 ) with median follow-up of 36 month . A postal question naire was sent to all women and the response rate was excellent at approximately 90 % in both groups . RESULTS Cure of incontinence , as identified by a quality of life improvement > 90 % , and /or patient-determined continent status as dry , were comparable in both groups . When the cure rates were adjusted assuming the non-respondents as failures the figures were almost identical ( p > 0.05 ) . Preoperative continence pad usage was similar for both groups . Overall , a postoperative significant decrease in pad score was noted in both groups ( p = 0.01 ) but there was no significant difference between the groups ( p > 0.05 ) . Statistical analysis failed to detect significant differences between both groups as regards complication rates such as frequency , nocturia , de-novo urgency or dyspareunia . CONCLUSION Pelvicol sling is a safe procedure in the surgical management of USI with similar success rate and patient satisfaction rate to TVT up to three years of follow-up Purpose : To compare short-term results of autologous pubovaginal sling and synthetic transobturator ( TOT ) SAFYRE sling in the treatment of female stress urinary incontinence ( SUI ) . Methods : Twenty women referred for surgical treatment of SUI were assigned r and omly to autologous pubovaginal sling or synthetic TOT sling . Inclusion criteria were primary treatment of SUI and urodynamic study showing SUI without detrusor overactivity . Pre- and postoperative quantification of the severity of incontinence was done by pad test and a vali date d question naire ( King ’s Health Question naire ) . Results : There were no differences in patients ’ mean age , parity , body mass index , rate of postmenopausal state , pelvic floor defects and mean Valsalva leak point pressure in the preoperative urodynamic study . Mean operating time ( 21.1 ± 3.8 vs. 69.5 ± 23.7 min ; P<0.001 ) and hospital stay ( 28.8 ± 8.4 vs. 44.4 ± 5.8 h ; P<0.001 ) was shorter in the TOT than the autologous group . The postoperative pad test ( 39.4 ± 12.5 vs. 8.4 ± 5.2 g ; P=0.01 ) and the absent in the improvement in the quality of life were significantly higher in the TOT group . Conclusion : Our initial results suggest that the synthetic TOT technique had worse effectiveness for treating female SUI compared to autologous pubovaginal sling OBJECTIVE Objective of the study was to compare the efficacy and the complications of tension-free vaginal tape ( TVT ) and Burch colposuspension in the treatment of female genuine stress incontinence ( GSI ) . METHODS In this controlled , prospect i ve , r and omized study , participated 35 patients who underwent Burch colposuspension and 36 patients that underwent TVT procedure . Patients with prolapse more than first degree , previous surgical treatment of stress urinary incontinence ( SUI ) and detrusor instability were excluded from the study . RESULTS The operative time for TVT was significantly shorter compared to BC . The severity and duration of postoperative pain for TVT was significantly less compared to BC . The necessary time for return to normal activity was 10 days for TVT and 21 days for BC . The cure rate after 24 months of follow-up was as follows : TVT : 84 % and BC : 86 % , while the improvement was 7 % for TVT and 6 % for BC . CONCLUSIONS TVT and Burch colposuspension are equally effective in the management of female GSI at two years follow-up . TVT procedure requires much less operative time , has much shorter hospitalization time , with significantly less postoperative pain and faster return to normal daily activities than Burch colposuspension AIM The efficacy , safety and hospital costs of the tension-free vaginal tape procedure were compared with the pubovaginal sling operation . METHODS A total of 60 women urodynamically diagnosed as having stress or mixed urinary incontinence were operated on using either the tension-free vaginal tape or pubovaginal sling operation in a prospect i ve manner . Preoperative characteristics of the women were not significantly different for the groups . The women were followed for up to 24 months . RESULTS In the tension-free vaginal tape group , the operation time was shorter , numbers of analgesics postoperatively required were less and hospital charges were less expensive compared to those in the pubovaginal sling operation ( P < 0.01 ) . Kaplan-Meier survival analysis showed a marginal significant difference ( P = 0.059 ) in the objective cumulative cure rates at 24 months between the groups receiving the former ( 70.3 % ) and latter ( 48.3 % ) procedures . Subjective cure rates were not significantly different ( P = 0.101 ) . In both groups , an improvement in quality of life was significant and surgical complications were identical . De novo urge incontinence developed in 6 % and 10 % in the former and latter , respectively . CONCLUSIONS The tension-free tape was significantly superior to the pubovaginal sling in terms of operation time , postoperative pain , and hospital charges , but not in cure rates . A longer follow up with a larger sample size is necessary to draw definite conclusions OBJECTIVES To describe the methods and rationale for the first r and omized controlled trial conducted by the Urinary Incontinence Treatment Network . METHODS The primary objective of this clinical trial is to compare two commonly performed surgical procedures for stress urinary incontinence-the Burch colposuspension and the autologous rectus fascial sling-for overall treatment success for urinary incontinence and stress-type symptoms of incontinence at 24 months after surgery . Secondary aims include a comparison of complications , quality of life , sexual function , patient satisfaction , costs , and the need for additional treatments or surgery ; and an evaluation of the prognostic value of preoperative urodynamic studies . The Stress Incontinence Surgical Treatment Efficacy Trial is being conducted on 655 women with predominant stress urinary incontinence , as determined by history and physical examination , urinary stress test with witnessed leakage , and voiding diary . Administration of all question naires and performance of examinations , tests , and both surgical procedures are st and ardized within and across the clinical centers . Assessment s occur preoperatively and at 6 weeks and 3 , 6 , 12 , 18 , and 24 months postoperatively . A sample of 655 women ensures 80 % power to detect a 12 % difference ( 60 % versus 72 % ) at the 5 % significance level . The intent-to-treat analysis will use Fisher 's exact test and time-to-failure analyses . RESULTS Enrollment was completed in June 2004 with 24 months of follow-up to end in June 2006 . CONCLUSIONS This is the first large , multicenter r and omized clinical trial comparing these two st and ard-of-care procedures for stress incontinence Various authors have reported that a pubovaginal sling is efficacious for correction of all types of female stress incontinence.7 Autologous , cadaver , and synthetic allografts have been utilized as supporting material s. Leach et al16 have suggested that autologous slings decay over time , result ing in recurrent stress incontinence . Badlani et al10 have reported that synthetic material s are more durable in maintaining stable cure rates than autologous slings . Infectious and erosive complications of synthetic material s are well known . Urethral erosion is the most feared complication of synthetic sling surgery , causing many urologie surgeons to shy away from using synthetic bio material s. However , not all synthetic material s result in equally unfavorable reaction to human host tissues . Various synthetic material s have differing inherent biochemical and surface characteristics that result in different biological outcomes . This chapter will review these characteristics Abstract We compared morbidity and success rate of pubovaginal sling with Burch colposuspension operations in Type I/type II genuine stress urinary incontinence ( GSI ) . The study included patients who had no preoperative detrusor instability ( DI ) , no recurrent GSI , no severe pelvic prolapsus and whose Valsalva leak point pressure ( VLPP ) values were higher than 90 cm water . Twenty three of free-rectus fascial sling and 23 of Burch colposuspension operations were performed r and omly on the patients by a single surgeon . There was no statistical difference between patients in terms of age , BMI , parity , number of daily pads used and preoperative bladder neck mobility . Operation time , change in hematocrit , spontaneous voiding time , length of hospitalization and urinary infection were not different in 2 procedures . 17 patients from both groups could be compared after one year . The bladder neck mobility of both groups were similar . One surgical failure , 1 DI , 1 severe cystocele and 1 enterocele were found in the Burch group while only 1 DI was found in the pubovaginal sling group . When pubovaginal sling operation was performed as the primary surgery on the patients with type I/II GSI , the morbidity , complications and 1 year success rate are the same as Burch procedure OBJECTIVES To compare short-term functional outcomes , urodynamic parameters , and quality of life of transobturator and retropubic routes in the cure of urinary stress incontinence . POPULATION AND METHODS This prospect i ve , multicentre study involved 88 women undergoing suburethral sling procedure for stress urinary incontinence ( SUI ) . The retropubic route ( RPR ) and the transobturator route ( TOR ) were used in 42 and 46 women , respectively . No difference in epidemiologic and preoperative urinary functional status ( SUI stage , and pollakiuria , nocturia , and urgency rates ) was found between the groups . Functional results and quality of life were evaluated before surgery and at 1 , 3 , 6 , and 12 mo postoperatively . Urodynamic examinations were performed before and 3 mo after surgery . RESULTS The mean follow-up was 10 mo . No difference in the rate of de novo urge incontinence and immediate and late voiding dysfunction was noted between the groups . No difference in the cure rate was observed between the groups ( 89.3 % in the RPR group and 88.6 % in the TOR group ) . RPR was associated with a significant decrease in maximum urinary flow and an increase in residual urine volume . Quality of life was significantly improved after surgery without difference between the groups . CONCLUSIONS Retropubic and transobturator routes for treatment of female SUI have similar high cure rates and quality of life improvement . Because of advantages in the rate of complications and postoperative pain previously demonstrated on the same population , the transobturator route appears to be the best option for the treatment of urinary incontinence Objective To compare the pubovaginal sling and transurethral Macroplastique in the treatment of female stress urinary incontinence ( SUI ) and intrinsic sphincter deficiency ( ISD ) Objective To assess the effectiveness and late postoperative morbidity of the Burch procedure and the sling procedure for the treatment of recurrent urinary stress incontinence after vaginal hysterectomy and anterior repair . Methods Clinical , urodynamic , and sonographic examinations were done on 77 women suffering with recurrent urinary stress incontinence . The women were Output:	The data on sub urethral sling operations remain too few to address the effects of this type of surgical treatment .
MS22093	*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 study aim ed to evaluate the effectiveness of the Norton score in predicting the likely occurrence of pressure sores compared to the Waterlow scale in Hong Kong . Two elderly care wards ( one male and one female ) were chosen , the sample size was 185 and the mean age of subjects was 80.4 . Each newly admitted patient was assessed using both the Norton calculation and the Waterlow calculation . At the end of the research , there were eight patients who had sore formation . The results indicated that the Norton score identified six out of the eight patients while the Waterlow identified seven of them . The Waterlow calculation , however , seems to have misidentified 72 patients as being in the ' at risk group ' . In view of a fear of the misdirection of re sources the Norton score was found to be the better of the two and its use in the elderly care units in this study should be continued until a better scoring system is found It is now well known that st and ard statistical procedures become invali date d when applied to cluster r and omized trials in which the unit of inference is the individual . A result ing consequence is that research ers conducting such trials are faced with a multitude of design choices , including selection of the primary unit of inference , the degree to which clusters should be matched or stratified by prognostic factors at baseline , and decisions related to cluster subsampling . Moreover , application of ethical principles developed for individually r and omized trials may also require modification . We discuss several topics related to these issues , with emphasis on the choices that must be made in the planning stages of a trial and on some potential pitfalls to be avoided This study investigated the influence on the number of pressure sores developing in patients nursed in a hospice when three levels of pressure support were used in association with a risk assessment tool . The study was design ed as phase one of an epidemiological study examining the use of a modified Norton scoring system . This was followed by a second phase of the study , when patients were allocated to pressure sore support systems according to their risk assessment score . A total of 327 patients entered , 223 in phase one and 104 in phase two . A significant reduction in the development of pressure sores was observed in the second phase of the study The presence of pressure ulcers imposes a huge burden on the older person 's quality of life and significantly increases their risk of dying . The objective of this study was to determine patient characteristics associated with the presence of pressure ulcers and to evaluate the risk factors associated with mortality among older patients with pressure ulcers . A prospect i ve observational study was performed between Oct 2012 and May 2013 . Patients with preexisting pressure ulcers on admission and those with hospital acquired pressure ulcers were recruited into the study . Information on patient demographics , functional status , nutritional level , stages of pressure ulcer and their complications were obtained . Cox proportional hazard analysis was used to assess the risk of death in all patients . 76/684 ( 11.1 % ) patients had pre-existing pressure ulcers on admission and 30/684 ( 4.4 % ) developed pressure ulcers in hospital . There were 68 ( 66 % ) deaths by the end of the median follow-up period of 12 ( IQR 2.5 - 14 ) weeks . Our Cox regression model revealed that nursing home residence ( Hazard Ratio , HR=2.33 , 95 % confidence interval , CI=1.30 , 4.17 ; p=0.005 ) , infected deep pressure ulcers ( HR=2.21 , 95 % CI=1.26 , 3.87 ; p=0.006 ) and neutrophilia ( HR=1.76 ; 95 % CI 1.05 , 2.94 ; p=0.031 ) were independent predictors of mortality in our elderly patients with pressure ulcers . The prevalence of pressure ulcers in our setting is comparable to previously reported figures in Europe and North America . Mortality in patients with pressure ulcer was high , and was predicted by institutionalization , concurrent infection and high neutrophil counts Objectives : To study the components of two risk assessment scales for decubitus ulcer risk , Waterlow and Braden , and of the Chailey score for the same purpose . Design : Experimental study of patients at risk of developing decubitus ulcers . Setting : The West Midl and s and Yorkshire . Subjects : One hundred and fifty wheelchair users from the West Midl and s and 9022 patients from a District General Hospital in York , the latter consisting of all admissions to the hospital in a four-month period . Interventions : Braden , Chailey scores ( wheelchair users ) and Waterlow scores ( all subjects ) measured . Main outcome measures : Development of a pressure sore , receiver operating characteristic ( ROC ) curves . Results : Waterlow outperformed Braden for classification of wheelchair patients with respect to decubitus ulcer . The Chailey score performed r and omly in this group . The sensitivity and specificity as seen in ROC curves was different for Waterlow scores for wheelchair users and general patients , the latter being much better classified . Only three items out of 11 in the Waterlow score appeared to have any classification ability in the wheelchair group . Conclusions : Risk indicators used for general patients are probably poorly suited for wheelchair users . There is a need for large-scale predictive studies of wheelchair users and other groups to allow regression analysis of the subscales of risk indicators . From the provisional data of this study it appears that splitting patients by gender and into full and part-time wheelchair users classifies almost as well the much more complicated risk assessment tools currently available A report of a r and omized , controlled trial ( RCT ) should convey to the reader , in a transparent manner , why the study was undertaken and how it was conducted and analyzed . For example , a lack of adequately reported r and omization has been associated with bias in estimating the effectiveness of interventions ( 1 , 2 ) . To assess the strengths and limitations of an RCT , readers need and deserve to know the quality of its methods . Despite several decades of educational efforts , RCTs still are not being reported adequately ( 3 - 6 ) . For example , a review of 122 recently published RCTs that evaluated the effectiveness of selective serotonin-reuptake inhibitors as first-line management strategy for depression found that only 1 ( 0.8 % ) paper described r and omization adequately ( 5 ) . Inadequate reporting makes the interpretation of RCT results difficult if not impossible . Moreover , inadequate reporting borders on unethical practice when biased results receive false credibility . History of CONSORT In the mid-1990s , two independent initiatives to improve the quality of reports of RCTs led to the publication of the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement ( 7 ) , which was developed by an international group of clinical trialists , statisticians , epidemiologists , and biomedical editors . CONSORT has been supported by a growing number of medical and health care journals ( 8 - 11 ) and editorial groups , including the International Committee of Medical Journal Editors ( ICMJE , also known as the Vancouver Group ) ( 12 ) , the Council of Science Editors ( CSE ) , and the World Association of Medical Editors ( WAME ) . CONSORT is also published in Dutch , English , French , German , Japanese , and Spanish . It can be accessed on the Internet , along with other information about the CONSORT group ( 13 ) . The CONSORT statement comprises a checklist and flow diagram for reporting an RCT . For convenience , the checklist and diagram together are called simply CONSORT . They are primarily intended for use in writing , review ing , or evaluating reports of simple two-group , parallel RCTs . Preliminary data indicate that the use of CONSORT does indeed help to improve the quality of reports of RCTs ( 14 , 15 ) . In an evaluation ( 14 ) of 71 RCTs published in three journals in 1994 , allocation concealment was not clearly reported in 43 ( 61 % ) of the RCTs . Four years later , after these three journals required that authors reporting an RCT use CONSORT , the proportion of papers in which allocation concealment was not clearly reported had dropped to 39 % ( 30 of 77 ; mean difference , 22 % [ 95 % CI of the difference , 38 % to 6 % ] ) . The usefulness of CONSORT is enhanced by continuous monitoring of the biomedical literature ; this monitoring allows CONSORT to be modified depending on the merits of maintaining or dropping current items and including new items . For example , when Meinert ( 16 ) observed that the flow diagram did not provide important information about the number of participants who entered each phase of an RCT ( enrollment , treatment allocation , follow-up , and data analysis ) , the diagram could be modified to accommo date the information . The checklist is similarly flexible . This iterative process makes the CONSORT statement a continually evolving instrument . While participants in the CONSORT group and their degree of involvement vary over time , members meet regularly to review the need to refine CONSORT . At the 1999 meeting , the participants decided to revise the original statement . This report reflects changes determined by consensus of the CONSORT group , partly in response to emerging evidence on the importance of various elements of RCTs . Revision of the CONSORT Statement Thirteen members of the CONSORT group met in May 1999 with the primary objective of revising the original CONSORT checklist and flow diagram , as needed . The group discussed the merits of including each item in the light of current evidence . As in developing the original CONSORT statement , our intention was to keep only those items deemed fundamental to reporting st and ards for an RCT . Some items not considered essential may well be highly desirable and should still be included in an RCT report even though they are not included in CONSORT . Such items include approval of an institutional ethical review board , sources of funding for the trial , and a trial registry number ( as , for example , the International St and ard R and omized Controlled Trial Number [ IS RCT N ] used to register an RCT at its inception [ 17 ] ) . Shortly after the meeting , a revised version of the checklist was circulated to the group for additional comments and feedback . Revisions to the flow diagram were similarly made . All these changes were discussed when CONSORT participants met in May 2000 , and the revised statement was finalized shortly afterward . The revised CONSORT statement includes a 22-item checklist ( Table ) and a flow diagram ( Figure ) . Its primary aim is to help authors improve the quality of reports of simple two-group , parallel RCTs . However , the basic philosophy underlying the development of the statement can be applied to any design . In this regard , additional statements for other design s will be forthcoming from the group ( 13 ) . CONSORT can also be used by peer review ers and editors to identify reports with inadequate description of trials and those with potentially biased results ( 1 , 2 ) . Table . Checklist of Items To Include When Reporting a R and omized Trial Figure . Flow diagram of the progress through the phases of a r and omized trial ( enrollment , intervention allocation , follow-up , and data analysis ) . During the 1999 meeting , the group also discussed the benefits of developing an explanatory document to enhance the use and dissemination of CONSORT . The document is patterned on reporting of statistical aspects of clinical research ( 18 ) , which was developed to help facilitate the recommendations of the ICMJE 's Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals . Three members of the CONSORT group , with assistance from members on some checklist items , drafted an explanation and elaboration document . That document ( 19 ) was circulated to the group for additions and revisions and was last revised after review at the latest CONSORT group meeting . Changes to CONSORT 1 . In the revised checklist , a new column for Paper Section and Topic integrates information from the Subheading column that was contained in the original statement . 2 . The Was It Reported ? column has been integrated into a Reported on Page Number column , as requested by some journals . 3 . Each item of the checklist is now numbered , and the syntax and order have been revised to improve the flow of information . 4 . Title and Abstract are now combined in the first item . 5 . While the content of the revised checklist is similar to that of the original one , some items that previously were combined are now separate . For example , authors had been asked to describe primary and secondary outcome ( s ) measure(s ) and the minimum important difference(s ) , and indicate how the target sample size was projected . In the new version , issues pertaining to outcomes ( item 6 ) and sample size ( item 7 ) are separate , enabling authors to be more explicit about each . Moreover , some items request additional information . For example , for outcomes ( item 6 ) authors are asked to report any methods used to enhance the quality of measurements , such as multiple observations . 6 . The item asking for the unit of r and omization ( for example , cluster ) has been dropped because specific checklists have been developed for reporting cluster RCTs ( 20 ) and other design types ( 13 ) since publication of the original checklist . 7 . Whenever possible , new evidence is incorporated into the revised checklist . For example , authors are asked to be explicit about whether the analysis reported is by intention to treat ( item 16 ) . This request is based in part on the observations ( 21 ) that authors do not adequately describe and apply intention-to-treat analysis and that reports not providing this information are less likely to provide other relevant information , such as losses to follow-up ( 22 ) . 8 . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow-up , and analysis ) . The revised diagram explicitly includes the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers lets the reader know whether the authors have performed an intention-to-treat analysis ( 21 - 23 ) . Because some of the information may not always be known and to accommo date other information , the structure of the flow diagram may need to be modified for a particular trial . Inclusion of the participant flow diagram in the report is strongly recommended but may be unnecessary for simple trials , such as those without any participant withdrawals or dropouts . Discussion Specifically developed to guide authors about how to improve the quality of reporting of simple two-group , parallel RCTs , CONSORT encourages transparency with reporting of the methods and results so that reports of RCTs can be interpreted both readily Output:	There is no reliable evidence to suggest that the use of structured , systematic pressure ulcer risk assessment tools reduces the incidence of pressure ulcers
MS22094	*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 Skin and mucosal herpes simplex virus type 2 ( HSV-2 ) shedding predominantly occurs in short sub clinical episodes . We assessed whether st and ard-dose or high-dose antiviral therapy reduces the frequency of such shedding . METHODS HSV-2-seropositive , HIV-seronegative people were enrolled at the University of Washington Virology Research Clinic ( WA , USA ) . We did three separate but complementary open-label cross-over studies comparing no medication with aciclovir 400 mg twice daily ( st and ard-dose aciclovir ) , valaciclovir 500 mg daily ( st and ard-dose valaciclovir ) with aciclovir 800 mg three times daily ( high-dose aciclovir ) , and st and ard-dose valaciclovir with valaciclovir 1 g three times daily ( high-dose valaciclovir ) . The allocation sequence was generated by a r and om number generator . Study drugs were supplied in identical , numbered , sealed boxes . Study periods lasted 4 - 7 weeks , separated by 1 week wash-out . Participants collected genital swabs four times daily for quantitative HSV DNA PCR . Clinical data were masked from laboratory personnel . The primary endpoint was within-person comparison of shedding rate in each study group . Analysis was per protocol . The trials are registered at Clinical Trials.gov ( NCT00362297 , NCT00723229 , NCT01346475 ) . RESULTS Of 113 participants r and omised , 90 were eligible for analysis of the primary endpoint . Participants collected 23 605 swabs ; 1272 ( 5·4 % ) were HSV-positive . The frequency of HSV shedding was significantly higher in the no medication group ( n=384 , 18·1 % of swabs ) than in the st and ard-dose aciclovir group ( 25 , 1·2 % ; incidence rate ratio [ IRR ] 0·05 , 95 % CI 0·03 - 0·08 ) . High-dose aciclovir was associated with less shedding than st and ard-dose valaciclovir ( 198 [ 4·2 % ] vs 209 [ 4·5 % ] ; IRR 0·79 , 95 % CI 0·63 - 1·00 ) . Shedding was less frequent in the high-dose valaciclovir group than in the st and ard-dose valaciclovir group ( 164 [ 3·3 % ] vs 292 [ 5·8 % ] ; 0·54 , 0·44 - 0·66 ) . The number of episodes per person-year did not differ significantly for st and ard-dose valaciclovir ( 22·6 ) versus high-dose aciclovir ( 20·2 ; p=0·54 ) , and st and ard-dose valaciclovir ( 14·9 ) versus high-dose valaciclovir ( 16·5 ; p=0·34 ) , but did for no medication ( 28·7 ) and st and ard-dose aciclovir ( 10·0 ; p=0·001 ) . Median episode duration was longer for no medication than for st and ard-dose aciclovir ( 13 h vs 7 h ; p=0·01 ) and for st and ard-dose valaciclovir than for high-dose valaciclovir ( 10 h vs 7 h ; p=0·03 ) , but did not differ significantly between st and ard-dose valaciclovir and high-dose aciclovir ( 8 h vs 8 h ; p=0·23 ) . Likewise , maximum log(10 ) copies of HSV detected per mL was higher for no medication than for st and ard dose aciclovir ( 3·3 vs 2·9 ; p=0·02 ) , and for st and ard-dose valaciclovir than for high-dose valaciclovir ( 2·5 vs 3·0 ; p=0·001 ) , but no significant difference was recorded for st and ard-dose valaciclovir versus high-dose aciclovir ( 2·7 vs 2·8 ; p=0·66 ) . 80 % of episodes were sub clinical in all study groups . Except for a higher frequency of headaches with high-dose valaciclovir ( n=13 , 30 % ) than with other regimens , all regimens were well tolerated . INTERPRETATION Short bursts of sub clinical genital HSV reactivation are frequent , even during high-dose antiherpes therapy , and probably account for continued transmission of HSV during suppressive antiviral therapy . More potent antiviral therapy is needed to eliminate HSV transmission . FUNDING NIH . Valaciclovir was provided for trial 3 for free by GlaxoSmithKline Summary Herpes simplex virus type 2 ( HSV-2 ) is considered as a major co-factor of both sexual transmission and acquisition of the human immunodeficiency virus ( HIV ) . The HIV epidemic in Senegal is characterized by a remarkable and stable low prevalence . Whether HSV-2 may also constitute a possible co-factor favouring the spreading of HIV epidemic in Senegal is yet unknown . This prompted us to evaluate the HSV-2 seroprevalence in the sentinel population of pregnant women in Senegal . Two hundred and sixty pregnant women attending Roi Baudouin maternity in the capital city Dakar ( n = 135 ) and the antenatal clinic in Kaolack ( n = 125 ) , the third city of Senegal , were prospect ively recruited between March and August 2003 . Fifty-six women ( 22 % ) were positive for HSV-2 serology . The prevalence of HSV-2 seropositivity was higher in women living in Dakar ( 26 % ) than in those living in Kaolack ( 16 % ) ( P < 0.01 ) . Only two women from Dakar and two other from Kaolack were found to be HIV-1-infected . Our observations suggest a seemingly low seroprevalence of HSV-2 infection in adult women Senegal , comparable with those usually reported in Western countries . Further , epidemiological surveys are needed to confirm these results in the general population Background : The epidemiologic utility of STARHS hinges not only on producing accurate estimates of HIV incidence , but also on identifying risk factors for recent HIV infection . Methods : As part of an HIV seroincidence study , 800 Rw and an female sex workers ( FSW ) were HIV tested , with those testing positive further tested by BED-CEIA ( BED ) and AxSYM Avidity Index ( Ax-AI ) assays . A sample of HIV-negative ( N=397 ) FSW were followed prospect ively for HIV seroconversion . We compared estimates of risk factors for : 1 ) prevalent HIV infection ; 2 ) recently acquired HIV infection ( RI ) based on three different STARHS classifications ( BED alone , Ax-AI alone , BED/Ax-AI combined ) ; and 3 ) prospect ively observed seroconversion . Results : There was mixed agreement in risk factors between methods . HSV-2 coinfection and recent STI treatment were associated with both prevalent HIV infection and all three measures of recent infection . A number of risk factors were associated only with prevalent infection , including widowhood , history of forced sex , regular alcohol consumption , prior imprisonment , and current breastfeeding . Number of sex partners in the last 3 months was associated with recent infection based on BED/Ax-AI combined , but not other STARHS-based recent infection outcomes or prevalent infection . Risk factor estimates for prospect ively observed seroconversion differed in magnitude and direction from those for recent infection via STARHS . Conclusions : Differences in risk factor estimates by each method could reflect true differences in risk factors between the prevalent , recently , or newly infected population s , the effect of study interventions ( among those followed prospect ively ) , or assay misclassification . Similar investigations in other population s/ setting s are needed to further establish the epidemiologic utility of STARHS for identifying risk factors , in addition to incidence rate estimation To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition , we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy . CD4 + and CD8 + T cells and a mixed population of plasmacytoid and myeloid dendritic cells ( DCs ) , including cells expressing the C-type lectin receptor DC-SIGN , persisted at sites of HSV-2 reactivation for months after healing , even with daily antiviral therapy . The CD4 + T cells that persisted reacted to HSV-2 antigen , were enriched for expression of the chemokine receptor CCR5 , and were contiguous to DCs expressing the interleukin-3 receptor CD123 or DC-SIGN . Ex vivo infection with a CCR5-tropic strain of HIV-1 revealed greater concentrations of integrated HIV-1 DNA in cells derived from healed genital lesion biopsies than in cells from control skin biopsies . The persistence and enrichment of HIV receptor – positive inflammatory cells in the genitalia help explain the inability of anti – HSV-2 therapy to reduce HIV acquisition Genital herpes continues to be epidemic throughout most sexually active population s [ 1 - 4 ] . A recent serosurvey indicated that 21.7 % of the U.S. population have HSV-2 antibodies , which represents a 31 % increase in prevalence in the last decade [ 5 , 6 ] . The seroprevalence of HSV-2 averages 30 % in most family practice and obstetrics clinics and 30 % to 50 % among sexually transmitted disease clinic attendees . Seroprevalence is consistently higher in women than in men [ 7 , 8 ] . The natural history of HSV infection includes acute or sub clinical first-episode mucocutaneous infection , establishment of neuronal latency , and intermittent virus reactivation with or without associated recurrent symptoms [ 9 , 10 ] . Although this sequence of events has been recognized for more than five decades , little is known about the long-term natural history of genital herpes . In the late 1970s , supported by the National Institutes of Health , we began a prospect i ve study of a large cohort of persons with recently acquired symptomatic genital HSV infection in order to define more precisely the natural history of genital herpes . Clinical , demographic , and recurrence data were collected for 457 patients who presented with virologically , serologically , and clinical ly confirmed first-episode genital infection . More than half of these patients did not receive antiviral therapy during their primary episode , providing a population not likely to be replicated in the future . We summarize the natural history of symptomatic recurrences in the complete population and in the subset of untreated patients . Methods In 1974 , a research clinic dedicated to the study of genital herpes infection was established at Harborview Medical Center , a King Countyfunded hospital affiliated with the University of Washington . Patients were referred by their private physicians or by the sexually transmitted disease clinic at Harborview , or responded to advertisements for participation in clinical studies of HSV infection . Only patients willing to participate in prospect i ve studies with long-term follow-up or in therapeutic trials were enrolled . Between 1974 and 1988 , we registered 457 patients with serologically and virologically proven first-episode infection who were followed for at least 60 days from the onset of infection . At the initial clinic visit , genital lesions were cultured and described by anatomic site , stage , and area . Patients were then generally followed at 2- to 3-day intervals until their lesions had healed . The median number of visits and genital examinations during the initial disease episode was 5 ( range , 3 to 14 visits ) . After resolution of the first clinical episode , patients were instructed to return to the clinic during each recurrence or for routine visits at least every 2 to 3 months . Patients who were unable to return for each recurrence were instructed to maintain a diary of onset and resolution date s for each recurrence . These data were collected at the following clinic visit . In general , we insisted that patients return for recurrences until they were able to recognize the signs and symptoms of genital herpes reactivation and to fill out patient diaries about onset and healing of reactivations . We defined a recurrence of genital herpes as the presence of genital ulcerations . We defined duration of a recurrence as the number of days from the first appearance of genital lesions to the reepithelialization of all lesions . If new lesions appeared before complete healing of other lesions , all were considered part of the same episode . We report only recognized symptomatic ( lesional ) recurrences and do not address sub clinical shedding of HSV in the genital tract . Serum specimens from both the acute and convalescent phases were obtained from all patients and tested for HSV-specific antibodies by Western blot ; all patients showed seroconversion to HSV-1 or HSV-2 [ 11 , 12 ] . Some had antibodies to HSV-1 in their acute-phase specimen and antibodies to both HSV-1 and HSV-2 in their convalescent-phase specimens . Patients were categorized as having primary first-episode disease if their acute-phase serum specimen showed absence of antibodies to HSV by Western blot . Based on Western blot profiles of convalescent-phase specimens and the subtype of the Output:	Interpretation A large burden of HIV is likely to be attributable to HSV-2 infection , even if the effect of HSV-2 infection on HIV had been imperfectly measured in studies providing adjusted RR estimates , potentially because of residual confounding . The contribution is likely to be greatest in areas where HSV-2 is highly prevalent , particularly Africa . New preventive interventions against HSV-2 infection could not only improve the quality of life of millions of people by reducing the prevalence of herpetic genital ulcer disease , but could also have an additional , indirect effect on HIV transmission .
MS22095	*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 effect of television viewing ( TVV ) and pubertal status of 9- to 14-y-old girls on mealtime food intake ( FI ) after a premeal glucose drink was determined . On four separate mornings , girls r and omly received equally sweetened drinks containing Sucralose ( control ) or glucose ( 1.0 g/kg body weight ) in 250 mL of water 2 h after a st and ardized breakfast . FI from an ad libitum pizza meal was measured 30 min later with or without TVV . Appetite was measured at 15 min intervals to lunch and postmeal . TVV at mealtime had no effect on FI , however , glucose suppressed FI more with no TVV compared with TVV ( 24 versus 10 % , p < 0.001 ) , primarily because of its effect in peripubertal girls ( p < 0.028 ) . In postpubertal girls ( n = 8) , glucose reduced FI by ∼27 % in both the no TVV and TVV conditions , but in peripubertal girls ( n = 17 ) , reduction in FI was 22 % without TVV and only 1 % while TVV . Appetite correlated with FI at 30 min only in postpubertal girls . TVV at mealtime reduced caloric compensation after consumption of the glucose drink in peripubertal , but not postpubertal , girls , with no effect on mealtime FI . ( Clinical trial number NCT01025687 . The long-term physiological effects of refined carbohydrates on appetite and mood remain unclear . Reported effects when subjects are not blind may be due to expectations and have rarely been studied for more than 24 h. The present study compared the effects of supplementary soft drinks added to the diet over 4 weeks on dietary intake , mood and BMI in normal-weight women ( n 133 ) . Subjects were categorised as ' watchers ' or ' non-watchers ' of what they ate then received sucrose or artificially sweetened drinks ( 4 x 250 ml per d ) . Expectancies were varied by labelling drinks ' sugar ' or ' diet ' in a counter-balanced design . Sucrose supplements provided 1800 kJ per d and sweetener supplements provided 67 kJ per d. Food intake was measured with a 7 d diary and mood with ten single Likert scales . By 4 weeks , sucrose supplements significantly reduced total carbohydrate intake ( F(1,129 ) = 53.81 ; P<0.001 ) , fat ( F(2,250 ) = 33.33 ; P<0.001 ) and protein intake ( F(2,250 ) = 28.04 ; P<0 - 001 ) compared with sweetener supplements . Mean daily energy intake increased by just under 1000 kJ compared with baseline ( t ( 67 df ) = 3.82 ; P < 0.001 ) and was associated with a non-significant trend for those receiving sucrose to gain weight . There were no effects on appetite or mood . Neither dietary restraint status as measured by the Dutch Eating Behaviour Question naire nor the expectancy procedure had effects . Expectancies influenced mood only during baseline week . It is concluded that sucrose satiates , rather than stimulates , appetite or negative mood in normal-weight subjects The objective was to compare the effects of ad libitum consumption of commonly consumed meal-time beverages on energy and fluid intakes and post-meal average subjective appetite and blood glucose in healthy adults . In a r and omized controlled design , 29 males and females consumed to satiation an ad libitum pizza meal with one of five beverages in unlimited amount including water ( 0 kcal ) , 1 % milk ( 44 kcal/100 ml ) , regular cola ( 44 kcal/100 ml ) , orange juice ( 44 kcal/100 ml ) and diet cola ( 0 kcal ) . Food and fluid intakes were measured at the meal . Average subjective appetite and blood glucose were measured before and for 2h after the meal . Although energy intake from pizza was similar among all beverage treatments , the amount of fluid consumed ( g ) varied among the beverages with intake of orange juice higher than regular and diet cola , but not different from water or milk . Meal-time ingestion of caloric beverages , milk , orange juice and regular cola , led to higher total meal-time energy intakes compared to either water or diet cola . Post-meal blood glucose area under the curve ( AUC ) was lower after milk than after meals with water , orange juice and regular cola and post-meal average subjective appetite AUC was lower after milk than after meals with water . Meal intakes of nutrients including protein , calcium , phosphorus , zinc , vitamins B12 , A and D were higher at the meal with milk compared to the other beverages . Thus , caloric beverages consumed ad libitum during a meal add to total meal-time energy intake , but 1 % milk favors a lower post-meal blood glucose and average subjective appetite score and adds to nutrient intake BACKGROUND The consumption of beverages that contain sugar is associated with overweight , possibly because liquid sugars do not lead to a sense of satiety , so the consumption of other foods is not reduced . However , data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain . METHODS We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age . Participants were r and omly assigned to receive 250 ml ( 8 oz ) per day of a sugar-free , artificially sweetened beverage ( sugar-free group ) or a similar sugar-containing beverage that provided 104 kcal ( sugar group ) . Beverages were distributed through schools . At 18 months , 26 % of the children had stopped consuming the beverages ; the data from children who did not complete the study were imputed . RESULTS The z score for the body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group ; the 95 % confidence interval ( CI ) of the difference was -0.21 to -0.05 . Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group ( 95 % CI for the difference , -1.54 to -0.48 ) . The skinfold-thickness measurements , waist-to-height ratio , and fat mass also increased significantly less in the sugar-free group . Adverse events were minor . When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study , the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group ( P=0.06 ) . CONCLUSIONS Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children . ( Funded by the Netherl and s Organization for Health Research and Development and others ; DRINK Clinical Trials.gov number , NCT00893529 . ) To examine whether artificial sweeteners aid in the control of long-term food intake and body weight , we gave free-living , normal-weight subjects 1150 g soda sweetened with aspartame ( APM ) or high-fructose corn syrup ( HFCS ) per day . Relative to when no soda was given , drinking APM-sweetened soda for 3 wk significantly reduced calorie intake of both females ( n = 9 ) and males ( n = 21 ) and decreased the body weight of males but not of females . However , drinking HFCS-sweetened soda for 3 wk significantly increased the calorie intake and body weight of both sexes . Ingesting either type of soda reduced intake of sugar from the diet without affecting intake of other nutrients . Drinking large volumes of APM-sweetened soda , in contrast to drinking HFCS-sweetened soda , reduces sugar intake and thus may facilitate the control of calorie intake and body weight This study investigated whether the addition of the high-intensity sweetener aspartame to a multidisciplinary weight-control program would improve weight loss and long-term control of body weight . One hundred sixty-three obese women were r and omly assigned to consume or to abstain from aspartame-sweetened foods and beverages during 16 wk of a 19-wk weight-reduction program ( active weight loss ) , a 1-y maintenance program , and a 2-y follow-up period . Women in both treatment groups lost approximately 10 % of initial body weight ( 10 kg ) during active weight loss . Among women assigned to the aspartame-treatment group , aspartame intake was positively correlated with percentage weight loss during active weight loss ( r = 0.32 , P < 0.01 ) . During maintenance and follow-up , participants in the aspartame group experienced a 2.6 % ( 2.6 kg ) and 4.6 % ( 4.6 kg ) regain of initial body weight after 71 and 175 wk , respectively , whereas those in the no-aspartame group gained an average of 5.4 % ( 5.4 kg ) and 9.4 % ( 9.4 kg ) , respectively . The aspartame group lost significantly more weight overall ( P = 0.028 ) and regained significantly less weight during maintenance and follow-up ( P = 0.046 ) than did the no-aspartame group . Percentage weight losses at 71 and 175 wk were also positively correlated with exercise ( r = 0.32 , P < 0.001 ; and r = 0.34 , P < 0.01 , respectively ) and self-reported eating control ( r = 0.37 , P < 0.001 ; and r = 0.33 , P < 0.01 , respectively ) . These data suggest that participation in a multidisciplinary weight-control program that includes aspartame may facilitate the long-term maintenance of reduced body weight Using a within-subjects design , we gave over-weight and normal-weight subjects a 500-mL drink of fructose , glucose , or aspartame diluted in lemon-flavored water or plain water in a r and omized fashion at about weekly intervals . Food intake was assessed at a buffet lunch that began 38 min after the preload was completed . Blood was drawn throughout and assayed for concentrations of glucose , insulin , glucagon , and free fatty acid . When subjects drank the fructose preload , they subsequently ate fewer overall calories and fewer grams of fat than when they drank any of the other preloads . The aspartame load did not stimulate intake beyond the plain-water control . The effects of the oxidation of fructose as a possible mechanism for the reduction in food intake is discussed . The effects of insulin in stimulating intake are also discussed The extent and time course of caloric compensation for surreptitious dilutions and supplements to the energy value of the diet were examined in free-living normal-weight adults . Ten subjects were provided lunches containing approximately 66 % more or less calories than their customary midday meal for 2-wk periods which were interposed between 1-wk baseline or recovery periods . Diet records were kept throughout the study . Total energy intakes did not differ among the three control periods ( weeks 1 , 4 , and 7 ) or between any of these periods and when subjects were provided the low-calorie meal . Total energy intake was significantly higher relative to all other periods when subjects ingested the high-calorie meal . To the extent that compensation occurred , it was apparent immediately and did not appear to change over the 2-wk study periods . The results suggest that humans compensate more readily for decreases than for increases in caloric intake BACKGROUND Sensory-specific satiety has been found to play an important role in food choice and meal termination , and it might be a factor contributing to obesity . OBJECTIVE We hypothesized that obese and normal-weight people have different sensitivities to sensory-specific satiety for high-fat foods . DESIGN Sensory-specific satiety was measured in 21 obese [ x body mass index ( BMI ; in kg/m(2 ) ) : 33.1 ] and 23 normal-weight ( BMI : 22.8 ) women who were matched for restrained eating behavior , physical activity , age , and smoking behavior . Food intake , appetite ratings , and liking scores before and after an ad libitum lunch were measured . Products differed in fat content and taste ( ie , low-fat sweet , low-fat savory , high-fat sweet , and high-fat savory ) , and the subjects tested all 4 products . In the first study , s and wiches were tested ; in the second study , snacks were tested . RESULTS Sensory-specific satiety for all products was observed in both subject groups . No significant differences were observed between the obese and normal-weight subjects in either sensory-specific satiety or food intake for any of the products or product categories tested . Taste ( sweet or savory ) had a significantly ( P < 0.05 ) stronger effect on sensory-specific satiety than did fat content . Appetite ratings strongly decreased after lunch , and appetite for a meal or snack after lunch was significantly higher in obese than in normal-weight subjects , whereas scores before lunch did not differ significantly . CONCLUSIONS Obese and normal-weight people do not differ in Output:	The preponderance of evidence from all human r and omized controlled trials indicates that LES do not increase EI or BW , whether compared with caloric or non-caloric ( for example , water ) control conditions . Overall , the balance of evidence indicates that use of LES in place of sugar , in children and adults , leads to reduced EI and BW , and possibly also when compared with water
MS22096	*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 aim of this study was to determine if a teledermatology consult system , using store- and -forward digital imaging technology , results in patients achieving a shorter time from referral date to date of initial definitive intervention when compared to a traditional referral process . Patients being referred to the dermatology consult service from the primary care clinics at the Durham VA Medical Center were r and omized to either a teledermatology consultation or usual care . A usual care consultation consisted of a text-based electronic consult request . A teledermatology consultation included digital images and a st and ardized history , in addition to the text-based electronic consult . Time to initial definitive intervention was defined as the time between referral date and the date the patient was scheduled for a clinic visit for those patients that the consultant requested a clinic-based evaluation , or the time between referral date and the date the consult was answered by the consultant if a clinic visit was not required . Patients in the teledermatology arm of the study reached a time to initial definitive intervention significantly sooner than did those patients r and omized to usual care ( median 41 days versus 127 days , p = 0.0001 , log-rank test ) . Additionally , 18.5 % of patients in the teledermatology arm avoided the need for a dermatology clinic-based visit compared to zero patients avoiding a dermatology clinic visit in the usual care arm of the study ( p < 0.001 , z-test ) . Teledermatology consult systems can result in significantly shorter times to initial definitive intervention for patients compared to traditional consult modalities , and , in some cases , the need for a clinic-based visit can be avoided The diagnostic accuracy of realtime teledermatology was measured using two different video cameras . One camera was a relatively low-cost , single-chip device camera 1 , while the other was a more expensive , three-chip camera camera 2 . The diagnosis obtained via the videolink was compared with the diagnosis made in person . Sixty-five new patients referred to a dermatology clinic were examined using camera 1 followed by a st and ard face-to-face consultation on the same day . A further 65 patients were examined using camera 2 and the same procedure implemented . Seventy-six per cent of conditions were correctly diagnosed by telemedicine using camera 2 compared with 62 using camera 1 . A working differential diagnosis was obtained in 12 of cases using camera 2 compared with 14 using camera 1 . The percentage of ` no diagnosis ` , wrong and missed diagnoses was halved using camera 2 compared with camera 1 . These results suggest that the performance of the more expensive camera was superior for realtime teledermatology OBJECTIVES To determine the reliability of videoconferencing technology in evaluating skin tumors , the impact of the technology on the clinicians ' degree of suspicion that a skin tumor is malignant , and the recommendation to do a biopsy . MATERIAL S AND METHODS Four skin cancer screenings were conducted at rural health care facilities in eastern North Carolina that were connected to East Carolina University School of Medicine . A dermatologist saw the patients in person at the local facility , and the same patient was seen by a dermatologist via a T-1 connection to Greenville , North Carolina . RESULTS The two physicians were in absolute agreement on 59 % of the 107 skin tumors evaluated . There were five lesions identified by the on-site dermatologist as a probable or definite malignancy . The degree of concern about a lesion being malignant and the decision whether to do a biopsy were not significantly different , as shown by kappa analysis . CONCLUSION The concern about the malignancy of a particular skin lesion and the recommendation whether to do a biopsy were not significantly affected by telemedicine technology BACKGROUND The Israel Defense Forces implemented a pilot teledermatology service in primary clinics . OBJECTIVES To assess user satisfaction and clinical short-term effectiveness of a computerized store and forward teledermatology service in urban and rural units . METHODS A multi-center prospect i ve uncontrolled cohort pilot trial was conducted for a period of 6 months . Primary care physicians referred patients to a board-certified dermatologist using text email accompanied by digital photographs . Diagnosis , therapy and management were sent back to the referring PCP . Patients were asked to evaluate the level of the CSAFTD service , effect of the service on accessibility to dermatologists , respect for privacy , availability of drugs , health improvement and overall satisfaction . PCPs assessed the quality of the teledermatology consultations they received , the contribution to their knowledge , and their overall satisfaction . RESULTS Tele-diagnosis alone was possible for 95 % ( n=413 ) of 435 CSAFTD referrals ; 22 % ( n=95 ) of referrals also required face-to-face consultation , Satisfaction with CSAFTD was high among patients in both rural and urban clinics , with significantly higher scores in rural units . Rural patients rated the level of service , accessibility and overall satisfaction higher than did urban patients . PCPs were satisfied with the quality of the service and its contribution to their knowledge . Rural physicians rated level of service and overall satisfaction higher than did urban physicians . Tele-referrals were completed more efficiently than referral for face-to-face appointments . CONCLUSIONS CSAFTD provided efficient , high quality medical service to rural and urban military clinics in the IDF OBJECTIVE To determine the effect of de grade d digital image resolution ( as viewed on a monitor ) on the accuracy and confidence of dermatologic interpretation . MATERIAL S AND METHODS Eight dermatologists interpreted 180 clinical cases divided into three Logical Competitor Sets ( LCS ) ( pigmented lesions , non-pigmented lesions , and inflammatory dermatoses ) . Each case was digitized at three different resolutions . The images were r and omized and divided into ( 9 ) 60-image sessions . The physicians were completely blinded concerning the image resolution . After 60 seconds per image , the viewer recorded a diagnosis and level of confidence . The result ant ROC curves compared the effect of LCS , level of clinical difficulty , and resolution of the digital image . One-way analysis of variance ( ANOVA ) compared the curves . RESULTS The areas beneath the ROC curves did not demonstrate any consistently significant difference between the digital image resolutions for all LCS and levels of difficulty . The only significant effect observed was amongst pigmented lesions ( LCS-A ) where the ROC curve area was significantly smaller in the easy images at high resolution compared to low and medium resolutions . For all other ROC curve comparisons within LCS-A , at all other levels of difficulty , as well as within the other LCS at all levels of difficulty , none of the differences was significant . CONCLUSION A 720 x 500 pixel image can be considered equivalent to a 1490 x 1000 pixel image for most store- and -forward teledermatology consultations Background Increasing use of teledermatology should be based on demonstration of favourable accuracy and cost – benefit analysis for the different methods of use of this technique Teledermatology consultations were organized between two health centres and two hospitals in Northern Irel and using low-cost videoconferencing equipment . A prospect i ve study of patient satisfaction was carried out . Following each teleconsultation , patients were asked to complete a question naire assessing their satisfaction with the service . Over 22 months , 334 patients were seen by a dermatologist over the video-link , and 292 patients 87 completed the 16-item question naire . Patients reported universal satisfaction with the technical aspects of teledermatology . The quality of both the audio and the display was highly acceptable to patients . Personal experiences of the teledermatology consultation were also favourable : 85 felt comfortable using the video-link . The benefits of teledermatology were generally recognized : 88 of patients thought that a teleconsultation could save time . Patients found the teledermatology consultation to be as acceptable as the conventional dermatology consultation . These findings suggest overall patient satisfaction with realtime teledermatology We studied the perceptions of general practitioners ( GPs ) towards teledermatology , before and after its introduction into eight general practice s for the purpose s of a r and omized controlled trial . A postal question naire was distributed before the trial and again one year later . Thirty-six of the 42 GPs responded on each occasion ( a response rate of 86 % ) . In the second survey , only 21 % of respondents indicated that they were satisfied with teledermatology in their practice , while 47 % said that they were dissatisfied . Thirty-one per cent said that they felt confident about diagnosis and management of care through teledermatology , and 28 % reported that they were unconfident . Only 23 % of respondents said that they would consider using a telemedicine system in the future , while 34 % said they would not ( 43 % were unsure ) . There were no significant findings to suggest that the GPs ' perceptions changed over time . Less favourable responses to telemedicine were found than has been observed in previous studies , which suggests that the model of telemedicine described in this study would not be widely acceptable to GPs We carried out a pilot study on the feasibility and accuracy of store- and -forward teledermatology based on patient-provided images and history as a triage tool for outpatient consultation . Patients referred by their general practitioner provided a history and images via the Internet . The information was review ed by one of 12 teledermatologists and the patient then visited a different dermatologist in person within two days . Three independent dermatologists compared the remote and in-person diagnoses in r and om order to determine diagnostic agreement . Broader agreement was also measured , by comparing the main disease groups into which the two diagnoses fell . The teledermatologists indicated whether an in-person consultation or further investigations were necessary . There were 105 eligible patients , aged four months to 72 years , who were willing to participate . For the 96 cases included in the analysis , complete diagnostic agreement was found in 41 % ( n= 39 ) , partial diagnostic agreement in 10 % ( n= 10 ) and no agreement in 49 % ( n= 47 ) . There was disease group agreement in 66 % of cases ( n= 63 ) . Nearly a quarter ( 23 % ) of participating patients could have safely been managed without an in-person visit to a dermatologist OBJECTIVE This report describes the design , development , and technical evaluation of a teledermatology system utilizing digital images and electronic forms captured through , stored on , and viewed through a common web server in an urban capitated delivery system . MATERIAL S AND METHODS The authors design ed a system whereby a primary care physician was able to seek a dermatologic consultation electronically , provide the specialist with digital images acquired according to a st and ardized protocol , and review the specialist response within 2 business days of the request . The setting s were two primary care practice s in eastern Massachusetts that were affiliated with a large integrated delivery system . Technical evaluation of the effectiveness of the system involved 18 patients . Main outcome measures included physician and patient satisfaction and comfort and efficiency of care delivery . RESULTS In 15 cases , the consultant dermatologist was comfortable in providing definitive diagnosis and treatment recommendations . In 3 cases , additional information ( laboratory studies or more history ) was requested . There were no instances where the dermatologist felt that a face-to-face visit was necessary . CONCLUSIONS This novel approach shows promise for the delivery of specialist expertise via the internet . Cost-effectiveness studies may be necessary for more widespread implementation OBJECTIVE To determine the relative efficacy of store- and -forward teledermatology vs face-to-face dermatology consultations in triage decisions about the need for a biopsy of neoplastic skin changes . DESIGN Prospect i ve study of consecutive patients judged by an internist to require dermatologic consultation for a skin growth . SETTING Private primary care and dermatology practice s and an academic dermatology practice . PATIENTS Patients requiring dermatology consultation for evaluation of skin growths . Patients were seen by a single primary care physician between July 10 , 1998 , and August 4 , 2000 . INTERVENTION Digital photographs of skin growths were obtained by the primary care physician and evaluated by a teledermatologist . The patient was then seen face-to-face by a dermatologist . A biopsy was performed if either dermatologist favored biopsy . MAIN OUTCOME MEASURES Decisions to perform a biopsy . Agreement between the dermatologists was assessed . RESULTS Of the 49 patients with evaluable photographs , the face-to-face dermatologist and teledermatologist recommended a biopsy for the same 26 patients , yielding a sensitivity of the teledermatologist of 1.00 ( 95 % confidence interval [ CI ] , 0.87 - 1.00 ) and a specificity of 1.00 ( 95 % CI , 0.85 - 1.00 ) . The agreement between the dermatologists ( kappa ) was 1.00 ( 95 % CI , 0.72 - 1.00 ) . CONCLUSION Store- and -forward teledermatology may provide an accurate and cost-effective method of determining whether skin growths in patients presenting to primary care physicians should undergo biopsy A r and omized controlled trial was carried out to measure the cost-effectiveness of realtime teledermatology compared with conventional outpatient dermatology care for patients from urban and rural areas . One urban and one rural health centre were linked to a regional hospital in Northern Irel and by ISDN at 128 kbit/s . Over two years , 274 patients required a hospital outpatient dermatology referral - 126 patients ( 46 % ) were r and omized to a telemedicine consultation and 148 ( 54 % ) to a conventional hospital outpatient consultation . Of those seen by telemedicine , 61 % were registered with an urban practice , compared with 71 % of those seen conventionally . The clinical outcomes of the two types of consultation were similar - almost half the patients were managed after a single consultation with the dermatologist . The observed marginal cost per patient of the initial realtime teledermatology consultation was 52.85 for those in urban areas and 59.93 per patient for those from rural areas . The observed marginal cost of the initial conventional consultation was 47.13 for urban patients and 48. Output:	Diagnostic accuracy was the most often used outcome measure and was found in phase I , II and IV . Compared with other specialties in telemedicine ( i.e. telesurgery , telepaediatrics ) , teledermatology seems to be a mature application . However , more evaluation studies with a focus on clinical outcomes such as preventable referrals or time to recovery are needed to prove that teledermatology indeed is a promising and cost-saving technology
MS22097	*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 This large , prospect i ve cohort study of private applicators , commercial applicators , and spouses of farmer applicators was undertaken to ascertain the etiology of cancers elevated in agriculture . METHODS The participants were matched to cancer registry files in Iowa and North Carolina . Incident cases were identified from enrollment through 31 December 2002 . St and ardized incidence ratios ( SIR ) were used to compare the cancer incidence of the participants with that of the total population in the two states . RESULTS The overall cancer incidence among farmers [ SIR 0.88 , 95 % confidence interval ( 95 % CI ) 0.84 - 0.91 ] and their spouses ( SIR 0.84 , 95 % CI 0.80 - 0.90 ) were significantly lower than expected , particularly for respiratory and urinary cancers . Commercial pesticide applicators had an overall cancer incidence comparable with the expected ( SIR 1.01 , 95 % CI 0.84 - 1.20 ) . Smoking prevalence was significantly lower than the national average . Prostate cancer was elevated among private applicators ( SIR 1.24 , 95 % CI 1.18 - 1.33 ) and commercial applicators ( SIR 1.37 , 0.98 - 1.86 ) . Excess ovarian cancer was observed for female applicators ( SIR 2.97 , 95 % CI 1.28 - 5.85 ) , but not for female spouses ( SIR 0.55 , 95 % CI 0.38 - 0.78 ) . Female spouses had a significant excess of melanoma ( SIR 1.64 , 95 % CI 1.24 - 2.09 ) , which was not observed among pesticide applicators . CONCLUSIONS Low overall cancer incidence rates seem to be a result of low overall smoking prevalence and other lifestyle factors , while excess cancer of the prostate and ovaries among applicators may be occupationally related . The excess risk of melanoma observed among spouses was unexpected We report the immunological and clinical results of a phase II trial with intravenously administered highly purified endotoxin ( Salmonella abortus equi ) in patients with advanced cancer . 15 patients with non-small cell lung cancer and 27 with colorectal cancer were entered into the study . 37 evaluable patients received at least four injections of endotoxin ( 4 ng/kg body weight ) and 1600 mg ibuprofen orally in 2-week intervals . Transient renal ( WHO grade 0 - 1 ) and hepatic ( WHO grade 0 - 4 ) toxicities occurred in several patients . Constitutional side-effects such as fever , chills and hypotension could not be prevented completely by pretreatment with ibuprofen . 3 patients in the colorectal cancer group demonstrated objective responses ( 1 complete remission ( CR ) , 2 partial remission ( PR ) ) . The complete remission has been maintained for more than 3 years , while the partial remissions were stable for 7 and 8 months , respectively . Only marginal antitumour effects were seen in the lung cancer group . Tolerance of the macrophage system to the stimulatory effect of endotoxin , as measured by human necrosis factor alpha ( TNF-alpha ) release into serum , built up after the first administration and remained at a steady-state level after each subsequent injection . In constrast , rising CD4:CD8 ratio and release of tumour necrosis factor beta ( TNF-beta ) indicated the continuing activation of the lymphocyte system by repetitive injections of endotoxin Objective : A prospect i ve study of newly exposed cotton workers was performed to investigate the natural history of respiratory symptoms and lung function changes . Methods : A total of 157 workers naive to cotton dust exposure were investigated by question naire , spirometry , and skin tests . They were examined before employment ( baseline ) and at the end of the first week , and the first , third , sixth , and 12th month after starting work . Acute airway response was defined as either a cross-first-shift or a cross-week fall in forced expiratory volume in one second ( FEV1 ) . The longitudinal change of lung function over the year was also calculated . Five hundred seventy-two personal dust sampling and 191 endotoxin measurements were performed to assess the exposure . Results : Forty percent of workers reported work-related symptoms in the first week of the study . Smoking , endotoxin , and dust concentrations were risk factors for all work-related symptoms . Acute airway responses were witnessed after immediate exposure . Female status was the only factor found to be predictive of acute airway response . The mean longitudinal fall in FEV1 at 1 year was 65.5 mL ( st and ard error = 37.2 ) . Age , early respiratory symptoms , and early fall in cross-week FEV1 were found to predict the 12-month fall in FEV1 . Cross-first-shift and cross-week falls in FEV1 reduced in magnitude during the course of the study . Conclusions : This study of workers naive to cotton dust exposure has demonstrated that respiratory symptoms and acute airway responses develop early following first exposure , and a tolerance effect develops in those workers with the continued exposure . Current smoking and increasing exposure predicts the development of work-related lower respiratory tract symptoms , while early symptoms and acute airway changes across the working week predict the longitudinal loss of lung function at 1 year Objectives Preventive workplace regulations are so far not based on an ubiquitously accepted threshold for airborne endotoxin in the bioaerosol . Methods In a cross-sectional study , 150 employees of a cotton spinning mill underwent lung function testing . Furthermore , in a r and om subset of 75 textile workers cross-shift lung function test and methacholine challenges were performed . Airborne current endotoxin exposure was classified as “ low ” , “ medium ” , and “ high ” ( ≤100 , > 100–≤450 , and > 450 Endotoxin Units (EU)/m3 , respectively ) based on endotoxin activity . Results The exposure – response relationship between current endotoxin exposure and prevalence of an obstructive ventilation pattern was significant ( test for linear trend : P = 0.019 ) ; the adjusted odds ratio for high endotoxin exposure was 11.22 ( 95 % confidence interval 1.03–121.17 ) . Within individuals , FEV1/FVC% was significantly reduced after the shift ( paired t test : P = 0.009 ) but not related to current endotoxin exposure . Twelve workers showed bronchial hyperresponsiveness ( 8.1 % before and 12.2 % after the work shift ; Fisher ’s exact test : P = 0.021 ) . Conclusion The study among German cotton textile workers suggests an exposure-dependent effect of current endotoxin exposure on lung function impairment with significant effects above 450 EU/m3 In order to evaluate chronic effects of long-term exposure to cotton dust on respiratory health , and the role of dust and endotoxin , longitudinal changes in lung function and respiratory symptoms were observed prospect ively from 1981 to 2001 in 447 cotton textile workers , along with 472 silk textile controls . The results from five surveys conducted over the 20-yr period are reported , including st and ardised question naires , pre- and post-shift spirometric measurements , work-area inhalable dust sample collection s and airborne Gram-bacterial endotoxin analysis . Cotton workers had more persistent respiratory symptoms and greater annual declines in forced expiratory volume in one second ( FEV1 ) and forced vital capacity as compared with silk workers . After exposure cessation , in the final 5-yr period , the rate of FEV1 decline tended to slow in nonsmoking males , but not in nonsmoking females . Workers who reported byssinotic symptoms more persistently suffered greater declines in FEV1 . Chronic loss in lung function was more strongly associated with exposure to endotoxin than to dust . In conclusion , the current study suggests that long-term exposure to cotton dust , in which airborne endotoxin appears to play an important role , results in substantial adverse chronic respiratory effects This case-referent study evaluated cancer risks among farmers in central Italy . Cancer cases ( N = 1674 , 17 sites ) were selected from all deceased men aged 35 - 80 years ; a r and om sample of 480 decedents formed the reference series . Farmers had a decreased risk of lung and bladder cancer and melanoma and nonsignificant excess risks for stomach , rectal , kidney , and nonmelanoma skin cancer . Stomach and kidney cancer were significantly increased among the farmers with > 10 years ' experience , and stomach , rectal , and pancreatic cancer were increased among licensed pesticide users with > 10 years ' experience . Possible relationships emerged between specific crops and cancer : fruit and colon and bladder cancer , wheat and prostate cancer , olives and kidney cancer , and potato and kidney cancer . The results regarding stomach , pancreatic , lung , bladder , and prostate cancer and melanoma congrue with earlier results . The kidney cancer excess , the association of colon and bladder cancer with orchard farming , and the excess of rectal cancer among licensed farmers are new and unexpected findings BACKGROUND Cancer incidence in women textile workers has not been adequately studied . The aim of this study was to examine site-specific cancer incidence patterns in a cohort of 267,400 women textile workers in Shanghai , China . METHODS Women employed by the Shanghai Textile Industry Bureau ( STIB ) were followed for cancer incidence from 1989 to 1998 . Age-adjusted st and ardized incidence ratios ( SIRs ) and 95 % confidence intervals ( CI ) were computed based on Shanghai Cancer Registry ( SCR ) rates . RESULTS There was a decrease in cancer incidence for the cohort compared with urban Shanghai women ( SIR = 0.91 , 95 % CI = 0.89 - 0.93 ) . There were small increased risks of other endocrine tumors ( SIR = 1.31 , 95 % CI = 1.02 - 1.65 ) . There were decreased risks for esophageal ( SIR = 0.54 , 95 % CI = 0.44 - 0.66 ) , stomach ( SIR = 0.79 , 95 % CI = 0.73 - 0.85 ) , rectal ( SIR = 0.88 , 95 % CI = 0.78 - 0.98 ) , lung ( SIR = 0.80 , 95 % CI = 0.74 - 0.86 ) , cervical ( SIR = 0.37 , 95 % CI = 0.28 - 0.50 ) , ovarian ( SIR = 0.85 , 95 % CI = 0.75 - 0.96 ) , and bladder cancers ( SIR = 0.63 , 95 % CI = 0.46 - 0.85 ) . CONCLUSIONS Women employed in the textile industry had a lower than expected cancer experience compared with urban Shanghai women . Further research on this cohort will examine associations between site-specific cancers and occupational exposures to dusts and chemicals Output:	Conclusion Despite several limitations , this meta- analysis based on high- quality studies adds weight to the hypothesis that occupational exposure to endotoxin in cotton textile production and agriculture is protective against lung cancer
MS22098	*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: Of 824 women screened , 410 were enrolled at midpregnancy in a prospect i ve , r and omized , controlled nutrition intervention study . Of these , 226 were predicted as likely to have small or large babies , 184 to have average-sized babies . Two hundred thirty eight mothers received USDA Women , Infants and Children ( WIC ) Food Supplementation vouchers from midpregnancy , 172 did not . Leukocyte protein synthesis ( as a cell model ) was significantly higher ( p = 0.009 ) by 36 weeks gestation in supplemented mothers . Mean birth weight of their babies was greater , 3254 vs 3163 g , ( + 91 g ) p = 0.039 , adjusted for sex , gestational age , prenatal visits , pregnancy interval , smoking , and previous low birth weight infants . Controlling for entry weight obviated the significance of the difference , except for WIC supplemented smokers ( greater than 10 cigarettes/day ) whose babies were significantly heavier by + 168 g ( p = 0.017 ) than those of unsupplemented smokers . WIC partially protects fetal growth in smokers Interpregnancy WIC supplementation was evaluated by comparing maternal nutritional status indicators and subsequent birth outcomes of 703 WIC participants divided into two groups . Study group women received postpartum benefits for 5 - 7 mo while control group women received postpartum benefits for only 0 - 2 mo . Both groups received prenatal benefits during each of two study pregnancies . Infants born to study group women had a higher mean birthweight ( 131 g ) and birthlength ( 0.3 cm ) and a lower risk of being less than or equal to 2500 g. Additionally , at the onset of the second pregnancy study group women had higher mean hemoglobin levels and lower risk of maternal obesity . These results suggest that postpartum WIC supplementation has positive benefits for both the mother and her subsequent infants BACKGROUND Studies of fruit and vegetable consumption in relation to overall health are limited . We evaluated the relationship between fruit and vegetable intake and the incidence of cardiovascular disease and cancer and of deaths from other causes in two prospect i ve cohorts . METHODS A total of 71 910 female participants in the Nurses ' Health study and 37,725 male participants in the Health Professionals ' Follow-up Study who were free of major chronic disease completed baseline semiquantitative food-frequency question naires in 1984 and 1986 , respectively . Dietary information was up date d in 1986 , 1990 , and 1994 for women and in 1990 and 1994 for men . Participants were followed up for incidence of cardiovascular disease , cancer , or death through May 1998 ( women ) and January 1998 ( men ) . Multivariable-adjusted relative risks were calculated with Cox proportional hazards analysis . RESULTS We ascertained 9329 events ( 1964 cardiovascular , 6584 cancer , and 781 other deaths ) in women and 4957 events ( 1670 cardiovascular diseases , 2500 cancers , and 787 other deaths ) in men during follow-up . For men and women combined , participants in the highest quintile of total fruit and vegetable intake had a relative risk for major chronic disease of 0.95 ( 95 % confidence interval [ CI ] = 0.89 to 1.01 ) times that of those in the lowest . Total fruit and vegetable intake was inversely associated with risk of cardiovascular disease but not with overall cancer incidence , with relative risk for an increment of five servings daily of 0.88 ( 95 % CI = 0.81 to 0.95 ) for cardiovascular disease and 1.00 ( 95 % CI = 0.95 to 1.05 ) for cancer . Of the food groups analyzed , green leafy vegetable intake showed the strongest inverse association with major chronic disease and cardiovascular disease . For an increment of one serving per day of green leafy vegetables , relative risks were 0.95 ( 95 % CI = 0.92 to 0.99 ) for major chronic disease and 0.89 ( 95 % CI = 0.83 to 0.96 ) for cardiovascular disease . CONCLUSIONS Increased fruit and vegetable consumption was associated with a modest although not statistically significant reduction in the development of major chronic disease . The benefits appeared to be primarily for cardiovascular disease and not for cancer The longitudinal study of pregnant women enrolled a national probability sample of 5,205 women first certified for WIC and 1,358 comparable low-income pregnant women in 174 WIC clinics located in 58 areas in the contiguous 48 states and in 55 prenatal clinics without WIC programs in counties with low program coverage . The women completed 24-h dietary recalls , histories of food expenditures , health care utilization , health and sociodemographic status , and anthropometric assessment . At late-pregnancy follow-up 3,967 WIC and 1043 control women were interviewed and 853 WIC and 762 control women completed 1-wk food expenditure diaries . Birth outcome was abstract ed ( from hospital records ) for 3,863 WIC and 1058 control women . Anthropometry , dietary intake , health , and use of health services were related to WIC among 2,619 r and om low-income preschoolers . Psychological development was assessed in 526 children aged 4 and 5 y. Control women had higher income , education , and employment status ; therefore , WIC program benefits probably were underestimated OBJECTIVE To examine the effectiveness of two methods of increasing fruit and fruit juice intake in pregnancy : midwives ' advice and vouchers exchangeable for juice . DESIGN Pregnant women were r and omly allocated to three groups : a control group , who received usual care ; an advice group , given advice and leaflets promoting fruit and fruit juice consumption ; and a voucher group , given vouchers exchangeable for fruit juice from a milk delivery firm . Dietary question naires were administered at ~16 , 20 and 32 weeks of pregnancy . Serum beta-carotene was measured at 16 and 32 weeks . SETTING An antenatal clinic in a deprived area . SUBJECTS Pregnant women aged 17 years and over . RESULTS The study comprised 190 women . Frequency of fruit consumption declined during pregnancy in all groups , but that of fruit juice increased substantially in the voucher group . Serum beta-carotene concentration increased in the voucher group , from 106.2 to 141.8 micromol l(-1 ) in women with measurements on both occasions ( P = 0.003 ) , decreased from 120.0 to 99.8 micromol l(-1 ) in the control group ( P = 0.005 ) , and was unchanged in the advice group . CONCLUSIONS Pregnant women drink more fruit juice if they receive vouchers exchangeable for juice supplied by the milk delivery service . Midwives ' advice to eat more fruit has no great effect . Providing vouchers for fruit juice is a simple method of increasing its intake in a deprived population and may be useful for other sections of the community Background There is overwhelming evidence that behavioural factors influence health , but their combined impact on the general population is less well documented . We aim ed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community . Methods and Findings We examined the prospect i ve relationship between lifestyle and mortality in a prospect i ve population study of 20,244 men and women aged 45–79 y with no known cardiovascular disease or cancer at baseline survey in 1993–1997 , living in the general community in the United Kingdom , and followed up to 2006 . Participants scored one point for each health behaviour : current non-smoking , not physically inactive , moderate alcohol intake ( 1–14 units a week ) and plasma vitamin C > 50 mmol/l indicating fruit and vegetable intake of at least five servings a day , for a total score ranging from zero to four . After an average 11 y follow-up , the age- , sex- , body mass– , and social class – adjusted relative risks ( 95 % confidence intervals ) for all-cause mortality(1,987 deaths ) for men and women who had three , two , one , and zero compared to four health behaviours were respectively , 1.39 ( 1.21–1.60 ) , 1.95 ( 1.70–-2.25 ) , 2.52 ( 2.13–3.00 ) , and 4.04 ( 2.95–5.54 ) p < 0.001 trend . The relationships were consistent in subgroups stratified by sex , age , body mass index , and social class , and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes . The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age . Conclusions Four health behaviours combined predict a 4-fold difference in total mortality in men and women , with an estimated impact equivalent to 14 y in chronological age In several studies , many nutrients in fruits and vegetables , such as dietary fiber , potassium , and antioxidants , have been associated with reduced risk for cardiovascular disease ( 1 - 5 ) . However , as review ed elsewhere ( 6 ) , most prospect i ve studies that have specifically examined intake of fruits and vegetables in relation to risk for cardiovascular disease have been small , and their results have been inconsistent . Dietary assessment s were often crude and available only at baseline , and few studies have examined the effects of specific types of vegetables or fruits . In a recent report ( 7 ) , we evaluated the association between fruit and vegetable intake and risk for ischemic stroke . We found that persons in the highest quintile of fruit and vegetable intake had a relative risk of 0.69 ( 95 % CI , 0.52 to 0.92 ) compared with the lowest quintile of intake ; moreover , a 1-serving/d increase in fruit or vegetable intake was associated with a 6 % lower risk for ischemic stroke , after controlling for st and ard cardiovascular risk factors . In the current study , we sought to evaluate the association between intake of overall and specific fruits and vegetables and incidence of coronary heart disease . Methods Study Sample The sample s for this analysis consisted of participants in the Nurses ' Health Study ( 8) and Health Professionals ' Follow-Up Study ( 1 ) . The two studies have similar design s ; in both , participants complete mailed question naires about medical history , health behaviors , and occurrence of cardiovascular and other outcomes every 2 years . The Nurses ' Health Study began in 1976 , when 121 700 female registered nurses 30 to 55 years of age were recruited ; diet was first assessed in 1980 . Health Professionals ' Follow-up Study participants were recruited in 1986 and comprise 51 529 male health professionals , including dentists , veterinarians , pharmacists , optometrists , osteopaths , and podiatrists , 40 to 75 years of age . Sample for Analysis We excluded participants with incomplete dietary assessment s or with previously diagnosed cancer , diabetes or cardiovascular disease that was reported before the first dietary assessment . We followed 84 251 eligible women during 14 years of follow-up and 42 148 eligible men during 8 years follow-up for incidence of coronary heart disease . The rate of follow-up for nonfatal events was 97 % of the total potential person-years of follow-up in both cohorts . Assessment of Coronary Heart Disease End Points Our primary end point was nonfatal myocardial infa rct ion or fatal coronary disease occurring after return of the 1980 question naire but before 1 June 1994 in women and after return of the 1986 question naire but before 1 January 1994 in men . We sought to review medical records for all such reports . Records were review ed by physicians who were blinded to the participants ' risk factor status . Myocardial infa rct ion was confirmed by using World Health Organization criteria : symptoms plus either diagnostic electrocardiographic changes or elevated levels of cardiac enzymes ( 9 ) . Infa rct ions that required hospital admission and for which confirmatory information was obtained by interview or letter , but for which no medical records were available , were design ated as probable . We included all confirmed and probable cases in our analyses because results were the same after probable cases were excluded . Deaths were identified by using state vital records and the National Death Index or were reported by next of kin and the U.S. postal system . Follow-up for deaths was more than 98 % complete [ 10 ] . Death certificates along with medical records were used to ascertain cause of death . Fatal coronary disease was categorized as definite if 1 ) it was confirmed by hospital record or autopsy or 2 ) coronary disease was listed as the cause of death on the certificate , this was the underlying and most plausible cause , and evidence of previous coronary disease was available . We did not rely on the statement of the cause of death on the death certificate alone as providing sufficient confirmation of death due to coronary heart disease . If no medical records were available , we categorized persons in whom coronary heart disease was the underlying cause on the death certificate as presumed coronary heart disease . Analyses limited to confirmed cases yielded results very similar to those obtained when all cases were included , although with less precision . Output:	The improved intake of targeted nutrients and foods , such as fruit and vegetables , could potentially reduce the rate of non-communicable diseases in adults , if the changes in diet are sustained . Associated improvements in perinatal outcomes were limited and most evident in women who smoked during pregnancy .
MS22099	*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 efficacy of self-recording of blood pressure in the management of hypertension was assessed in a r and omized clinical trial involving 140 persons who had been receiving antihypertensive therapy for a year or more , but whose diastolic blood pressure had remained at 95 mm Hg or higher . To control for the increased attention implicit in self-recording , which might affect blood pressure , the patients were assigned at r and om to one of the four groups : self-recording and monthly home visits , self-recording only , monthly home visits only , and neither self-recording nor monthly home visits . This design also permitted assessment of the effect of home visits . During the 6-month experiment no significant differences were apparent between the groups in either compliance or diastolic blood pressure . However , both self-recording and monthly home visits produced a reduction in blood pressure among patients who admitted to difficulty remembering to take their pills ; a reduction was not seen among patients who said they had no such difficulty . This confirmed an earlier observation suggesting that this easily identified group of patients may be the most responsive to intervention programs Abstract . Objectives : To compare compliance with an antihypertensive treatment administered either twice daily or three times daily . The two formulations of the antihypertensive treatment used ( nicardipine ) “ regular tablets ” ( t.d . ) and “ slow release tablets ” ( b.d . ) are bioequivalent at the daily dosage used in the study . Study design : Open , controlled , parallel design ed study with central ised , r and omised allocation to the treatment groups : TID group : A nicardipine 20 mg tablet , three times daily for 3 months . BID group : A capsule of slow release ( SR ) nicardipine , 50 mg twice daily for 3 months . Patients : 7274 hypertensive patients were investigated by 2.651 general practitioners . Compliance with the nicardipine was assessed by means of st and ardised interviews with the patients and by a question naire for the investigators . Results : Compliance was slightly higher in the BID than in the TID group ; 71.2 % and 24.5 % of patients in the first group declared their compliance was 100 % and 80 % compared to 82.3 % and 15 % in the second group . A statistically significant relationship was shown between compliance with nicardipine and the decrease in blood pressure after three months of therapy . However , no significant difference was noticed between the two groups of patients in the absolute decrease in blood pressure after the treatment period : 25.7/14.7 mm Hg in the TID group compared with 25.9/15.0 mm Hg in the BID group . Conclusions : A difference in compliance between the bioequivalent BID and TID formulations of the same active agent was shown in hypertensive patients . However , the difference was not large enough to lead to a difference either in the number of controlled patients or in the decrease in blood pressure . Reducing the number of daily doses does not automatically lead to greater efficacy of treatment Predictors of dropping out of care were examined for 171 treated hypertensive patients enrolled in a r and omized trial of social support strategies design ed to improve compliance and blood pressure control . Control patients who continued to receive routine care were more than twice as likely to drop out as patients who received routine care and periodic home visits by nurses or pharmacists ( odds ratio [OR]= 2.7 ) . The combination of home visits and a second intervention , having family members monitor patients ' blood pressure and compliance behavior , was no more effective than home visits alone ( OR = 1.1 ) . The home visits intervention was one of six variables identified by a stepwise regression as significant predictors of dropping out . Patients with four or more high-risk characteristics constituted 15 % of the sample but contributed almost half ( 46 % ) of the dropouts . Targeting support strategies at high-risk patients may be a cost-effective means of reducing uncontrolled hypertension Address correspondence to : L.D. Saunders , Department of Health Services Administration and Community Medicine , 13 - 103 Clinical Sciences Building , University of Alberta , Edmonton , Alberta Canada T6 G 2G3 among patients attending a primary health care ( PHC ) clinic in Soweto for antihypertensive drug therapy . In a 1-year follow-up study of an inception cohort of newly treated hypertensives , only 27 % were compliant ( defined as attending frequently enough to receive 80 % or more of their required treatment ) , 42 % were not seen after the first 3 months ( early dropouts ) , and 22 % continued to attend until the last 3 The effects of metoprolol ( Betaloc tablets ) in a group of 193 hypertensives were compared with the effects of a slow-release formulation ( Betaloc Durules ) in a further group of 196 patients . Patients were selected at r and om for treatment . There were no differences between the groups in terms of age , weight , sex , blood pressure , concurrent illness or concomitant therapy . Blood pressure control and apparent adverse effects were similar for both groups ; the overall withdrawal rate from each group was similar . Compliance , assessed by tablet counts , was significantly improved in the group receiving once-daily therapy . Simplification of the dosage regimen to once-daily therapy appears to improve the patient 's willingness to comply with the physician 's instructions A multifactorial health-education program design ed to enhance compliance with a once-daily regimen of atenolol was evaluated among 453 patients enrolled in health maintenance organizations ( HMOs ) . The initiation of the 180-day study period was used to classify patients as either new or existing cases of hypertension . In turn , patients in these two categories were r and omly assigned to a control or an experimental group . Patients assigned to the experimental groups received an enrollment kit upon exercising their initial prescription ( new patients ) or their first refill request ( existing patients ) . The kit contained : a 30-day supply of atenolol ; an educational newsletter about hypertension ; information on nutrition and life-style changes ; and an explanation of the intent and content of the program . Before the next scheduled prescription-refill date , each patient was contacted by telephone to inquire about his or her experience with the therapy and to stress the importance of adherence to the regimen . Each month thereafter , the newsletter and an enclosed prescription-refill reminder were mailed to each patient . The medication possession ratio , defined as the number of days ' supply of atenolol obtained by a patient during the 180-day study period , was significantly ( P less than or equal to 0.001 ) enhanced for the new and existing experimental groups relative to the control groups . Multiple regression analyses revealed that enrollment in the health-education program increased the number of days ' supply of atenolol obtained by existing patients by 27 ( P less than or equal to 0.001 ) , and by new patients by 40 ( P less than or equal to 0.001 ) Low rates of adherence to hypertensive therapy limit patients ' securing the full benefits of treatment . While some factors related to adherence have been identified , research on the effectiveness of interventions to increase adherence levels is sparse . The present study was design ed to assess the impact of a series of different interventions on a group of some 400 patients , all under the care of private physicians in a small community . A factorial design was employed to deliver four , sequential educational interventions , about four months apart , to r and omly selected sub-groups . Interviews before and after each intervention provided information concerning self-reported adherence , health status , health beliefs , and personal characteristics . Pertinent medical records and pharmacy data were also obtained . The first intervention — printed material —did not significantly affect adherence . The second and fourth interventions —nurse telephone calls and social support — each increased medication taking and the third intervention — self-monitoring — led to better weight control . There was no cumulative impact of the interventions and different aspects of regimens were not signiticantly related to one another In this r and omized controlled trial , the value of using occupational health nurses ( OHNs ) to monitor the care of hypertensive employees at work was compared with regular care ( RC ) delivered in the community . One year after entry , the blood pressure level , medication history , compliance with treatment , and cost of hypertensive care of the participants were determined by independent evaluators . The reduction in diastolic blood pressure ( DBP ) , the measure of effectiveness , was 10.5 + /- 1.1 mm Hg ( mean + /- SEM ) in the OHN group and 7.7 + /- 1.1 mm Hg in the RC group , and the proportion under good blood pressure control was 41.8 % and 31.0 % respectively . These between-group differences were not statistically significant . Although the employees in the OHN group were more medicated and had a lower treatment dropout rate , neither difference was statistically significant . In addition , the proportion of employees who were compliant with prescribed medication was virtually identical in both groups . The cost of the care received by employees in the OHN group of $ 404.14 for the year was substantially higher than that of $ 250.15 in the RC group with the difference principally related to the cost of visiting the OHNs and a significant difference in drug cost ( p less than 0.006 ) . The incremental cost-effectiveness ( C/E ) ratio of $ 53.67 per mm Hg DBP reduction per year for onsite blood pressure monitoring was higher than the base C/E ratio of $ 32.65 per mm Hg for regular care . Our findings indicate that monitoring the blood pressure of hypertensive employees at work is neither clinical ly effective nor cost-effective . ( ABSTRACT TRUNCATED AT 250 WORDS A 1-year , r and omized study was conducted to test the possibility of improving compliance with therapeutic regimens in hypertensives by means of certain simple arrangements . Patients were given written treatment instructions concerning hypertension , a personal blood-pressure follow-up card , and , for those who failed to attend their blood-pressure check-up , an invitation for a new check-up . Using matched pairs , 202 Finnish hypertensives were r and omly allocated either to an ordinary or a reorganized treatment group . By means of the latter system , patient compliance could be significantly ( p < 0.01 ) improved : Only 4 % of the patients in this group dropped out of treatment , compared with 19 % in the ordinary treatment group . By the end of the year , blood pressure had been lowered by at least 10 % in 95 % of the patients in the reorganized group and in 78 % of those in the ordinary group ( p < 0.01 ) . This was achieved in approximately 60 % of cases using chlorthalidone alone Poor compliance is a principal cause of treatment failure in hypertensive patients . Once-daily dosing improves compliance , but 24-h antihypertensive activity should be provided . The compliance , efficacy , and safety of amlodipine and nifedipine slow-release ( SR ) were compared in patients with mild-to-moderate essential hypertension recruited among 24 centers in France . After a 2-week washout period , 103 patients were r and omized to 12 weeks of 5 to 10 amlodipine mg once daily ( n = 55 ) or 20 mg nifedipine SR twice daily ( n = 48 ) . Compliance was calculated by electronic drug monitoring . Efficacy was measured by ambulatory and casual BP recordings . Patients receiving amlodipine demonstrated better compliance than patients receiving nifedipine SR with respect to compliance index ( the total number of doses taken divided by the total number of doses prescribed , expressed as a percentage ; 98.3 % v 87 % ; P < .0001 ) , days on which the correct number of doses were taken ( 92.5 % v 74.8 % ; P < .0001 ) , and prescribed doses taken on schedule ( 88.7 % v 71.6 % ; P < .0001 ) . Absolute and relative therapeutic coverage were higher in patients receiving amlodipine than nifedipine SR ( P < .0001 ) . Mean SBP and DBP decreased equally in both groups , although amlodipine offered better BP control compared with nifedipine SR at specific times of day . Fewer patients had high nocturnal SBP with amlodipine ( 39.3 % ) than nifedipine SR ( 71.4 % ; P = .042 ) . Adverse events and treatment withdrawals occurred less frequently in amlodipine-treated patients than in nifedipine SR-treated patients . Amlodipine ( 5 to 10 mg ) once daily provides improved compliance , better 24-h BP control , and fewer adverse events than 20 mg nifedipine SR twice daily in patients with mild-to-moderate hypertension A controlled , r and omized study was conducted in two chain pharmacies to determine the clinical value of comprehensive pharmacy services for hypertensive patients in a chain pharmacy setting . Twenty-seven patients were enrolled as intervention participants with 26 control subjects . Monthly services for the intervention group included blood pressure and heart rate assessment s and counseling on lifestyle modifications and drug therapy . Control patients received initial and final blood pressure measurements and minimal counseling . Both study and control groups completed quality -of-life question naires upon entering and completing the study . Results showed that blood pressure control was significantly improved in the study group . Compliance rates as well as energy/fatigue scores ( a quality -of-life scale ) improved in the study group compared with the control population . Community pharmacists in chain stores could have a beneficial effect on the health care of large numbers of patients if pharmaceutical care programs were developed This article reports a r and omized controlled trial design ed to test the effects of special packaging of antihypertensive medication on compliance and blood pressure control . One hundred eighty subjects who had exhibited elevated blood pressure greater than 90 mmHg in the two years prior to the study were recruited from patients receiving care at a community hospital-based family medicine practice Output:	REVIEW ERS ' CONCLUSIONS Reducing the number of daily doses appears to be effective in increasing adherence to blood pressure lowering medication and should be tried as a first line strategy , although there is less evidence of an effect on blood pressure reduction .

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