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MS22200	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A single blind trial and a placebo controlled double blind trial of lithium were carried out in elderly patients with tardive dyskinesia . In the pilot study , neuroleptics were continued : in the controlled trial , neuroleptics were discontinued . The results of both studies were essentially negative . Thus , the suppression effect of neuroleptics is much more dramatic than anything seen in the two studies . Several reasons for this were discussed namely , the severity and chronicity of the symptoms Tardive dyskinesia ( TD ) is a serious , often disabling , movement disorder that is caused by medications that block dopamine receptors ( i.e. , neuroleptics , anti-emetics ) . There is currently no st and ard treatment approach for physicians confronted with such patients . This may be the result of notions that TD is disappearing because of the switch to second-generation antipsychotic agents and that it is largely reversible . In this article we demonstrate that second-generation antipsychotics do , indeed , cause TD and , in fact , the frequency is likely higher than expected because of growing off-label uses and a tripling of prescriptions written in the last 10 years . In addition , studies demonstrate that TD actually remits in only a minority of patients when these drugs are withdrawn . Furthermore , neuroleptic agents are often utilized to treat TD , despite prolonged exposure being a risk factor for irreversibility . The outcome of these trends is a growing population afflicted with TD . We review non-neuroleptic agents that have shown positive results in small , early-phase , blinded trials , including tetrabenazine , amantadine , levetiracetam , piracetam , clonazepam , propranolol , vitamin B6 , and Ginkgo biloba . Other options , such as botulinum toxin and deep brain stimulation , will also be discussed , and a suggested treatment algorithm is provided . While these agents are reasonable treatment options at this time there is a need , with a concerted effort between neurology and psychiatry , for full-scale drug development , including multicenter , r and omized , blinded trials to confirm the effectiveness of the agents that were positive in phase 2 trials and the development of newer ones Twenty patients with signs of tardive dyskinesia secondary to antipsychotic medication participated in a double blind , controlled , parallel group study comparing codergocrine mesylate 4.5 mg once daily with a placebo . After 6 weeks medication a reduction in dyskinetic scores occurred in both groups , but at the end of a further 6-week period the patients on active treatment maintained their improvement while those on placebo did not . This may be due to a slow onset of action and a hangover of activity associated with the drug Eleven patients with tardive dyskinesia were treated with lithium carbonate in a placebo-controlled double-blind crossover study . No significant effect of lithium on either tardive dyskinesia or blood prolactin concentrations was demonstrated , but 5 patients developed pseudo-Parkinsonian features OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate Psychiatric in patients with tardive dyskinesia ( TD ) were treated with either lithium alone ( n = 9 ) or with a combination of lithium and lecithin ( n = 9 ) for 5 weeks in a double-blind , placebo-controlled experiment . A statistically significant but clinical ly unimportant improvement of TD occurred during both treatments . The addition of lecithin to lithium had no effect Despite the plethora of clinical drug trials in tardive dyskinesia , few consistent findings have emerged . One possible reason for this is that there have been no serious attempts to define the role of major neurotransmitter systems ( dopamine , norepinephrine , acetylcholine , serotonin , GABA ) in one specific population of tardive dyskinesia patients . This study reports a series of five controlled drug trials in a population of patients with persistent tardive dyskinesia ; each drug probed one of four neurotransmitter systems . The intra- and interpatient responses are analyzed and the implication s of the pharmacologic response profiles for the clinical management of tardive dyskinesia are discussed The effectiveness of a once-weekly i.m . injection of ceruletide ( 0.8 microgram/kg ) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia ( TD ) was evaluated in a double-blind , placebo-controlled , matched-pairs study . Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with ceruletide as compared with placebo . Analysis of the therapeutic response to ceruletide over the course of treatment revealed a slow , but long-lasting improvement of TD symptoms . Side effects , which were mild and transient , consisted mainly of nausea and epigastric discomfort . The incidence of side effects did not differ between the ceruletide- and placebo-treated groups . Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia The beneficial effect of estrogens on L -dopa-induced dyskinesias and on tardive dyskinesia has recently been reported . In this open pilot study , conjugated estrogens ( CE ) were BACKGROUND Antipsychotics remain the mainstay of drug intervention in the management of schizophrenia . However , long-term treatment with antipsychotics is associated with a variety of movement disorders , the most disabling of which is tardive dyskinesia ( TD ) , which occurs in up to 50 % of patients hospitalized with chronic schizophrenia . The pathophysiology of TD is still unclear and no definite treatment exists . Both dopamine receptor supersensitivity and oxidative stress-induced neurotoxicity in the nigrostriatal system are apparently implicated . The pineal hormone melatonin is a potent antioxidant and attenuates dopaminergic activity in the striatum and dopamine release from the hypothalamus . Thus , it may have a beneficial effect for both the treatment and prevention of TD . METHODS Using a double-blind , placebo-controlled , crossover study , we evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with schizophrenia and TD . The primary outcome measure was the change from baseline in Abnormal Involuntary Movement Scale ( AIMS ) score . RESULTS The decrease ( mean + /- SD ) in AIMS score was 2.45 + /- 1.92 for the melatonin and 0.77 + /- 1.11 for the placebo treatment groups ( P<.001 ) . No adverse events or side effects were noted . CONCLUSION This is the first clinical evidence for efficacy of melatonin in the treatment of TD OBJECTIVE Worldwide , conventional antipsychotic medication continues to be used extensively , and tardive dyskinesia ( TD ) remains a serious complication . The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD . METHOD This was a 12-week , double-blinded , r and omized study of ethyl-EPA 2g/day versus placebo as supplemental medication , in patients with schizophrenia or schizoaffective disorder , with established TD . RESULTS Eighty-four subjects were r and omized , of whom 77 were included in the analysis . Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores , but there were no significant between-group differences ( p=0.4 ) . Response rates ( > or=30 % improvement in TD symptoms ) also did not differ significantly between EPA-treated subjects ( 45 % ) and placebo-treated subjects ( 32 % ) ( p=0.6 ) . However , a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD . The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially , although this was not sustained beyond 6 weeks . CONCLUSIONS This trial failed to demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure . However , a modest and transient benefit is suggested in patients with more recent onset of TD . The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low , the study being underpowered , TD being too chronic in the majority of cases , differences in dietary fatty acid intake , or that EPA lacks an anti-dyskinetic action Eight psychiatric patients with tardive dyskinesia ( TD ) were treated with single doses of the synthetic met-enkephalin analogue FK 33 - 824 ( 1 , 2 , and 3 mg IM ) morphine ( 10 mg SC ) and naloxone , an opiate receptor antagonist ( 0.8 mg IM ) . The drug effects were assessed by blind evaluation of r and omly sequenced videotapes made before and during treatment . FK 33 - 824 ( 1,2 , and 3 mg IM ) slightly reduced TD ( P<0.05 ) and increased preexisting bradykinesia . The effect on TD , however , was pronounced only in patients concurrently treated with neuroleptics in relatively high doses . Morphine had a similar although weaker antihyperkinetic effect , whereas naloxone had no effect . Side effects of FK 33 - 824 included dizziness , heaviness in the extremities , slurred speech , and dryness of mouth . Morphine caused drowsiness , dizziness , ataxia , and nausea , and naloxone had no side effects . The results do not point to a primary role of enkephalin in the pathophysiology of TD , but enkephalin may interact with dopamine functions and potentiate some of the effects of neuroleptic drugs The unique role of ganglioside GM1 in neuronal plasticity led two centers , New York University and McLean Hospital , to study the effect of GM1 or placebo in patients with tardive dyskinesia . Results from the NYU cohort have already been published . We now present data from the entire cohort , allowing us to evaluate the effects of GM1 in the elderly compared to young adults . Subjects with tardive dyskinesia were r and omly assigned to single-blind placebo injections for 1 week , followed by 1 month of double-blind intramuscular placebo or GM1100 mg . The final sample included 29 patients : 12 younger than 55 years of age and 17 older . There was no GM1-versus-placebo difference observed in either-age group , or in the total group . However , whether on placebo or GM1 , repeated measures analysis of variance ( RANOVA ) found a significant difference in response between Abnormal Involuntary Movement Scale scores , taken baseline and week 4 , in the elderly compared to young adults . Scores for the young adults show initial improvement then deterioration back to baseline , and those for the elderly show continuing improvement during the 4-week trial . The importance of the placebo effect in the elderly and its meaning for studies of GM1 in tardive dyskinesia are discussed OBJECTIVE The study investigated the efficacy and tolerability of ethyl-eicosapentaenoic acid ( E-EPA ) as add-on treatment in chronic , severe schizophrenia . METHOD A r and omized , parallel-group , double-blind , placebo-controlled , fixed-dose , add-on study was conducted over 12 weeks . Forty patients with persistent symptoms after at least 6 months of stable antipsychotic treatment received E-EPA or placebo , in addition to their existing treatment . RESULTS At 12 weeks , the E-EPA group had significantly greater reduction of Positive and Negative Syndrome Scale total scores and of dyskinesia scores than the placebo group . CONCLUSIONS EPA may be an effective and well-tolerated add-on treatment in schizophrenia The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 199 Output:	AUTHORS ' CONCLUSIONS This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia .
MS22201	*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 determine cervical cancer screening coverage and the knowledge , attitudes and barriers toward screening tests among women in rural and urban areas of Tanzania , as well as explore how they view the acceptability of the HPV vaccine and potential barriers to vaccination . Setting A cross-sectional study using interview-administered question naires was conducted using multistage r and om sampling within urban and rural areas in Kilimanjaro Region , Tanzania . Participants Women aged 18–55 were asked to participate in the survey . The overall response rate was 97.5 % , with a final sample of 303 rural and 272 urban dwelling women . Primary and secondary outcome measures Descriptive and simple test statistics were used to compare across rural and urban strata . Multivariate logistic regression models were used to estimate ORs and 95 % CIs . Results Most women ( 82 % ) reported they had heard of cervical cancer , while self-reported cervical cancer screening among women was very low ( 6 % ) . In urban areas , factors associated with screening were : older age ( OR=4.14 , 95 % CI 1.86 to 9.24 for ages 40–49 , and OR=8.38 , 95 % CI 2.10 to 33.4 for > 50 years ) , having health insurance ( OR=4.15 , 95 % CI 1.52 to 11.4 ) , and having knowledge about cervical cancer ( OR=5.81 , 95 % CI 1.58 to 21.4 ) . In contrast , among women residing in rural areas , only condom use ( OR=6.44 , 95 % CI 1.12 to 37.1 ) was associated with screening . Women from both rural and urban areas had low vaccine-related knowledge ; however , most indicated they would be highly accepting if it were readily available ( 93 % ) . Conclusions The current proportion of women screened for cervical cancer is very low in Kilimanjaro Region , and our study has identified several modifiable factors that could be addressed to increase screening rates . Although best implemented concurrently , the availability of prophylactic vaccination for girls may provide an effective means of prevention if they are unable to access screening in the future AIMS The aims of this study were ( 1 ) to estimate what proportion of rural females had received cervical screening , ( 2 ) to assess knowledge , beliefs , attitudes , and demographics that influence cervical screening , and ( 3 ) to predict cervical screening accessibility based on demographic factors , knowledge , beliefs , and attitudes that influence cervical screening . METHODS The study sample consisted of r and omly selected , sexually active , rural females between 12 and 84 years of age . Five hundred fourteen females responded to an individually administered question naire . RESULTS Of the 514 participants , 91 % had never had cervical screening and 81 % had no previous knowledge of cervical screening tests ; 80 % of the group expressed positive beliefs about cervical screening tests after an educational intervention . Females who were financially independent were 6.61 % more likely to access cervical screening compared with those who were dependent on their husb and s. Females in mining villages were 4.47 % more likely to access cervical screening than those in traditional rural reserve villages . Females in resettlement villages were 20 % less likely to access cervical screening than those in traditional rural reserve villages . CONCLUSIONS Accessibility of screening services could be improved through planning and implementation of screening programs involving community leaders and culturally appropriate messages . The government should incorporate the human papillomavirus ( HPV ) vaccine in its immunization program for adolescents , and health education should be intensified to encourage women and their partners to comply with diagnostic and treatment regimens Background The Family Medical Program is a health care system in the Rio de Janeiro state . Women ’s health services offered by the Family Medical Program include preventive exams and screening , family planning , and prenatal follow-up . Although cervical cancer screening is offered , barriers to care still hinder the full success of the program , and we are attempting to identify these barriers . Methods We undertook a cross-sectional and prospect i ve study involving 351 women who were referred to the Family Medical Program between March 2009 and November 2010 . Demographic data were obtained through a structured household question naire . The dependent variable was defined as the non-realization of the Pap smear test following the protocol of the Health Ministry . Cervical sample s for screening were collected after clinical examination . Results Women who had undergone Pap smear testing at least once every 3 years comprised 282 of the participants ( 80.3 % ) . Most of the women had normal or inflammatory cytology ( 96.3 % ) . Illiteracy and the absence of symptomatic episodes of sexually transmitted disease were independent barriers to having cancer screening at regular intervals . Illiterate women were more likely to be older , not to be using any contraceptive method , and on average had more than two children , more than four pregnancies , and more than two abortions . Embarrassment was the greatest barrier to seeking professional care reported by all women , regardless of level of educational attainment . Other important barriers to seeking care and /or screening included time constraints , due to work or childcare . Conclusion This study indicates that the Family Medical Program effectively provides cervical cancer screening coverage for its eligible population , at the level m and ated by the WHO and the Brazilian Health Ministry . Fully 96.3 % of the women in our study had normal or benign inflammation on cytology . Underst and ing of barriers to care-seeking behavior that limit program adherence is one way to facilitate communication between providers and patients regarding the benefits of cancer screening Objectives . Community based breast cancer screening has decreased breast cancer mortality in women . This study examined the predictors of nonattendence for invitational breast cancer screening in relation to socioeconomic status in the city of Manisa , in western Turkey . Study Design . For the evaluation of the reasons for refusing to participate in the study , two districts were selected . 446 women aged between 50 and 69 years were selected from the program data base by systematic r and om sampling . Methods . The question naire consisted of sociodemographic variables and the adapted version of Champion 's Health Belief Model Scale . Univariete and multivariete logistic regression analysis were performed throughout the data analysis . Results . Being from an urban district and being from the western region were the risk factors for not participating in the screening program ( P = 0.014 , P = 0.023 ) . A statistical significance was found between mammography-benefit , mammography-barrier and program participation ( P = 0.044 , P = 0.006 ) . Although there were many more barriers for not participating in the screening program for the women of the slum district , the attendence rate of the slum district was higher than that of the urban district . Conclusions . Increased attendance may be achieved through enhancement of breast cancer awareness and by reducing some of the modifiable barriers Background To date , because of limited budgets and lower incidence of breast cancer , the majority of Asian countries do not have population -based screening programmes , but instead offer opportunistic screening . However , there have been few studies which have assessed the motivators for women attending such programmes and the appropriateness of the programmes in terms of targeting women at risk . Methods We conducted a prospect i ve cross-sectional study of 1,619 women aged 40 to 74 years attending a subsidized opportunistic screening mammogram from October 2011 to October 2013 at a private hospital in Malaysia . Breast cancer risk was estimated using the Gail Model and two-step cluster analysis was used to examine the motivators of attending screening . Results Although Malaysia comprises 54.5 % Malay , 24.5 % Chinese and 7.3 % Indian , the majority of women in the MyMammo Study were Chinese ( 70.1 % ) and 99.2 % had a < 2 % ten-year risk of breast cancer . The most commonly cited barriers were the perception of not being at risk and fear of painful mammography . We found that highly educated women , cited doctors , family and friends as their main motivators . Of those with only secondary school education , their main motivators were doctors . Conclusions Taken together , our results suggest the women attending opportunistic mammography screening in Asia are at low risk of breast cancer and this poses challenges to cost-effective and equitable strategies for cancer control . We propose that to improve uptake of screening mammography , awareness programmes should target both doctors and members of the public The purpose was to examine breast cancer screening behavior in Turkish women , the reasons for not doing screening and the relationship between health beliefs and levels of self-esteem , body perception , and hopelessness . This research was conducted as a descriptive , correlational study in an area covered by three neighborhood primary health care clinics in Bornova , Izmir . The data were collected between April and November 2006 from 382 women over 40 years of age who were selected using a stratified r and om sampling method and a descriptive information form , Champion 's Health Belief Model Scale ( CHBMS ) , the Rosenberg Self-Esteem Scale ( RSES ) , the Body Cathexis Scale ( BCS ) and the Beck Hopelessness Scale ( BHS ) . The breast cancer screening methods used by women participating in the research were , respectively , mammography ( 34 % ) , clinical breast examination ( 14.1 % ) , breast self-examination ( BSE ) ( 59.4 % ) . The reasons why women did not do breast cancer screening methods were determined to be : not having any symptoms , neglect , not sensing the need , and not knowing how BSE is done . In the examination of the women 's CHBMS subscale score means and RSES , BCS and BHS score mean a statistically significant relationships were determined between Benefits -BSE , Barriers-BSE , Confidence , Health motivation , Benefits -mammography and barriers-mammography subscale score means and RSES , BCS and BHS mean scores ( p<0.01 ) . It was found out that women with high level of self-esteem , high level of hope for the future and with a positive body perception have more positive health beliefs on breast cancer screening INTRODUCTION Cervical cancer is the third most common cancer among Malaysian women . However , the uptake of cervical cancer screening -- Pap smear -- by women in Malaysia has been low and remains a challenge . This study was conducted to assess the cervical screening practice s of rural women in Malaysia and to examine the factors associated with such practice s. METHODS A cross-sectional survey was conducted in five rural districts in Perak , Malaysia . 1,000 households were selected through multistage r and om sampling . Women aged 20 - 64 years were interviewed by trained enumerators using structured question naires . Binomial logistic regression was used to identify predictors of cervical screening through univariate and multivariate analyses . RESULTS Among the 959 respondents , only 48.9 % had undergone Pap smear at least once in the past three years . Women in the age group 40 - 49 years ( odds ratio 3.027 , 95 % confidence interval 1.546 - 5.925 ; p < 0.005 ) were found to be significantly more likely to attend cervical cancer screening as compared to those in the age group 20 - 29 years . Other significant predictors were being married with children , having knowledge of cervical cancer symptoms , receiving relevant information regarding cervical cancer from health personnel or campaigns , being engaged in family planning and receiving encouragement from husb and s. CONCLUSION Efforts to boost the uptake of Pap smear screening among the rural population should be targeted toward the predictors of positive uptake BACKGROUND Success of cervical screening initiatives depends on high participation of the target population , which in turn is determined by the women 's perceptions , health orientation and other socio-cultural issues . The present study identifies the immediate social and cultural barriers that prevent women to attend cervical screening facilities . METHODS Women non-compliant to a community-based cervical screening program were identified . From them 500 were r and omly selected for interview using a structured question naire that was design ed on the basis of feedbacks received from several focused group discussion s. Question naire listed 24 possible reasons for non-compliance . The women were asked to select the most pertinent reason(s ) for her non-attendance or to reveal if they had any reason other than the listed ones . RESULTS A total of 469 non-compliant women were interviewed . They had significantly lower literacy rate compared to the compliant women ( OR=2.25 ; 95 % CI : 1.23 - 4.13 ) . Nearly half of the interviewed women responded that they themselves opted to stay away from the program . Most common reasons cited for non-attendance in this group were reluctance to go for medical test in the absence of any symptoms and apprehension to have a test that detects cancer . Second major group of responders comprised of women who were willing , yet could not attend due to various hurdles . Most common hurdles were inability to leave household chores , pre-occupation with family problems and lack of approval from husb and s. CONCLUSIONS Modification of health behavior through education and social empowerment of women are essential for a population based cervical screening program to succeed in India BACKGROUND In India , breast cancer is the leading malignancy among women in a majority of the cancer registries . Therefore it is important to underst and screening practice s and its predictors , including in rural areas with high female literacy and good health indices . MATERIAL S AND METHODS A cross-sectional study with multistage sampling was conducted in Vypin Block , Ernakulam district , Kerala , India . Four Panchayats ( self administration units ) were r and omly chosen and a woman in every second household was invited to participate from the tenth ward of each . Thus a total of 809 women were interviewed . RESULTS The majority of the repondents ( 82.1 % ) were Output:	Lack of knowledge about CCa and BCa , and underst and ing of the role of screening were the key barriers to CCa and BCa screening in LMICs . Conclusions : Improvements to CCa and BCa screening uptake in LMICs must be accompanied by educational interventions which aim to improve knowledge and underst and ing of CCa and BCa and screening to asymptomatic women .
MS22202	*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: Praziquantel , a new antischistosomal compound , was tested for tolerance and efficacy against placebo in two double-blind clinical trials in Philippine patients infected with Schistosoma japonicum . The compound was given orally at a dose of 3 x 20 mg/kg at intervals of 4 hours to a total of 82 patients -some without advanced disease and some with hepatosplenic involvement . A total of 43 patients received placebo . In a single-blind trial , 42 patients were given a single oral dose of 50 mg/kg . Monitoring of vital organ functions included comprehensive laboratory tests and serial electrocardiograms . In 38 patients with hepatosplenic involvement due to advanced stages of infection , serial electroencephalograms were additionally recorded . No toxic effects were observed in any of these examinations . Undesirable side effects occurred in 53 % of the patients given 3 x 20 mg/kg and in 70 % after a dose of 1 x 50 mg/kg . They consisted mainly of abdominal discomfort , fever , sweating , and occasionally giddiness , but in general were transient and mild . At 6 months post-treatment , 60 of 75 patients treated with 3 x 20 mg/kg and 29 of 41 treated with 1 x 50 mg/kg were completely negative for eggs . At 12 months post-treatment , 25 of 33 and 14 of 26 patients in the two treatment groups were cured . Thus the divided dosage gave a superior therapeutic result . Praziquantel proved to be free of major toxicity , and was well tolerated , highly effective , and easy to administer . Confirmation of results in extended trials may soon permit large-scale treatment The first clinical trials of praziquantel against Schistosoma japonicum infections in Japan were planned to assess tolerance only . Three double-blind studies against placebo involving a total of 51 patients were conducted with dosages of praziquantel of 1 x 20 mg/kg body weight , 2 x 20 mg/kg , 3 x 20 mg/kg given on one day . The frequency of unwanted side effects was higher in the group of patients given praziquantel at a dose of 3 x 20 mg/kg than in all other drug- or placebo-treated patients . In general , the side effects , which included drowsiness , headache , lumbago , abdominal fullness , or epigastric discomfort , lasted for several hours but disappeared spontaneously . The results of laboratory tests showed no significant changes caused by treatment . The overall assessment showed excellent or good tolerance in all patients treated with praziquantel at the lower dose levels . In those given 3 x 20 mg/kg , tolerance was excellent in 1 of 12 patients , good in 9 , and fair in 2 , whereas the respective placebo-treated group showed excellent tolerance in 3 of 12 , good in 7 , and fair in 2 The combined effects of praziquantel and artesunate in the treatment of urinary schistosomiasis were assessed among 312 r and omly selected schoolchildren aged 4 - 20 years in Adim community , Nigeria . In the preliminary screening , infection was confirmed in 327 ( 38.5 % ) of the 850 subjects screened . Infected subjects who reported for treatment were then divided into six treatment groups of 52 subjects each ; 44 subjects in each group completed their treatment regimens and su bmi tted their urine for post-treatment assessment . Praziquantel and artesunate were administered orally at 40 mg/kg and 4 mg/kg body weight , respectively . Adverse effects due to drug reactions were assessed 72 h after medication and all perceived episodes of illness were treated . Morbidity indicators were assessed 56 days after the final dose of the drug regimens . All treatment regimens were well tolerated . The cure rates were 72.7 % in the praziquantel plus placebo-treated group and 70.5 % in the artesunate plus placebo group , while the artesunate plus praziquantel group had the highest cure rate ( 88.6 % ) . Haematuria and proteinuria were extensively reduced after treatment with the three drug regimens . This study confirmed that the treatment of urinary schistosomiasis with the combination of praziquantel and artesunate is safe and more effective than treatment with either drug alone Output:	According to the results , there is no statistically significant difference in different doses of PZQ for treating S. japonicum
MS22203	*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 St and ardized conditions to distinguish sub population s of colorectal cancer ( CRC ) patients more and less sensitive to cetuximab therapy remain undefined . MATERIAL S AND METHODS We retrospectively analyzed epidermal growth factor receptor ( EGFR ) copy number by fluorescence in situ hybridization ( FISH ) in paraffin-embedded tumor blocks from 85 chemorefractory CRC patients treated with cetuximab . Results were analyzed according to different score systems previously reported in colorectal and lung cancers . The primary end point of the study was identification of the EGFR FISH score that best associates with response rate ( RR ) . RESULTS Using receiver operating characteristic ( ROC ) analysis , the cut-off that best discriminated responders versus nonresponders to cetuximab was a mean of 2.92 EGFR gene copies per cell . This model showed sensitivity of 58.6 % [ 95 % confidence interval ( CI ) = 47.1 - 70.1 ) and specificity of 93.3 % ( 95 % CI = 80.6 - 100 ) . EGFR FISH-positive patients ( N = 43 , 50.6 % ) had significantly higher RR ( P = 0.0001 ) and significantly longer time to disease progression ( P = 0.02 ) than EGFR FISH negative ( N = 42 , 49.4 % ) . Other scoring systems result ed less accurate in discriminating patients with the highest likelihood of response to cetuximab therapy . CONCLUSIONS CRC patients with high EGFR gene copy number have an increased likelihood to respond to cetuximab therapy . Prospect i ve clinical trials with a careful st and ardization of assay conditions and pattern interpretation are urgently needed BACKGROUND The antiepidermal growth factor receptor ( antiEGFR ) monoclonal antibodies cetuximab and panitumumab have good clinical activity in about 10 % of patients with metastatic colorectal cancer that is resistant to chemotherapy . The molecular mechanisms underlying clinical response or resistance to these agents are unknown . METHODS Tumours from 31 patients with metastatic colorectal cancer who had either an objective response ( n=10 ) or stable disease or progressive disease ( n=21 ) after treatment with cetuximab or panitumumab were screened for genetic changes in EGFR or its immediate intracellular effectors . Specifically , we assessed the EGFR copy number and the mutation profile of the EGFR catalytic domain and of selected exons in KRAS , BRAF , and PIK3CA . RESULTS Eight of nine of patients with objective responses who were assessable by fluorescence in-situ hybridisation ( FISH ) had an increased EGFR copy number . By contrast , one of 21 non-responders assessable by FISH had an increased EGFR copy number ( p<0.0001 for responders vs non-responders , Fisher 's exact test ) . The mutation status of the EGFR catalytic domain and its immediate downstream effectors PIK3CA , KRAS , and BRAF did not correlate with disease response . In colorectal-cancer cell lines , the concentration of cetuximab that completely inhibited proliferation of cells with amplified EGFR copy number did not affect proliferation of cells with unamplified EGFR . INTERPRETATION We propose that the response to antiEGFR treatment has a genetic basis and suggest that patients might be selected for treatment on the basis of EGFR copy number BACKGROUND A large proportion of colorectal cancer patients does not benefit from the use of anti-epidermal growth factor receptor ( EGFR ) treatment although in the absence of a mutation of the K-RAS gene . Preliminary observations suggested that HER-3 , insulin-like growth factor-1 ( IGF-1 ) , nuclear factor-kB ( NF-kB ) and EGFR gene copy number ( GCN ) might identify patients not likely to benefit from anti-EGFR therapy . We tested the interaction between HER-3 , IGF-1 , NF-kB , EGFR GCN and K-RAS mutational analysis to verify the relative ability of these variables to identify a subgroup of patients more likely to benefit from EGFR-targeted treatment among those harbouring a K-RAS wild-type status . PATIENTS AND METHODS We retrospectively collected tumours from 168 patients with metastatic colorectal cancer treated with irinotecan-cetuximab . K-RAS was assessed with direct sequencing , EGFR amplification was assessed by chromogenic in situ hybridisation ( CISH ) and HER-3 , IGF-1 and NF-kB were assessed by immunohistochemistry . RESULTS In patients with K-RAS wild-type tumours , the following molecular factors result ed independently associated with response rate : HER-3 [ odds ratio (OR)=4.6 , 95 % confidence interval ( CI ) 1.8 - 13.6 , P=0.02 ] , IGF-1 ( OR=4.2 , 95 % CI 2 - 10.2 , P=0.003 ) and EGFR GCN ( OR=4.1 , 95 % CI 1.9 - 26.2 , P=0.04 ) . These factors also independently correlated with overall survival as follows : HER-3 [ hazard ratio (HR)=0.4 , 95 % CI 0.28 - 0.85 , P=0.008 ] , IGF-1 ( HR=0.47 , 95 % CI 0.24 - 0.76 , P<0.0001 ) and EGFR GCN ( HR=0.59 , 95 % CI 0.22 - 0.89 , P=0.04 ) . DISCUSSION We believe that our data may help further composing the molecular mosaic of EGFR-resistant tumours . The role of HER-3 , IGF-1 and CISH EGFR GCN should be prospect ively vali date d in clinical trials investigating anti-EGFR treatment strategies in colorectal cancer patients Output:	It was also shown that EGFR GCN is independent of other factors such as KRAS status . Among the anti-EGFR-treated patients , increased EGFR GCN appears to be associated with improved survival outcomes . The effect on survival appears to be related to patients receiving the line of treatment
MS22204	*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 Angiotensin receptor blockers ( ARBs ) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance . This study compared the effects of combined treatment using the ARB c and esartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospect i ve , r and omized controlled trial . Methods Between January 2008 and July 2009 , 53 cirrhotic patients with clinical ly significant portal hypertension were r and omized to receive either c and esartan and propranolol combination therapy ( 26 patients ) or propranolol monotherapy ( 27 patients ) . Before and 3 months after the administration of the planned medication , the hepatic venous pressure gradient ( HVPG ) was assessed in both groups . The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached , and the c and esartan dose was fixed at 8 mg qd . The primary endpoint was the HVPG response rate ; patients with an HVPG reduction of > 20 % of the baseline value or to < 12 mmHg were defined as responders . Results The mean portal pressure declined significantly in both groups , from 16 mmHg ( range , 12 - 28 mmHg ) to 13.5 mmHg ( range , 6 - 20 mmHg ) in the combination group ( P<0.05 ) , and from 17 mmHg ( range , 12 - 27 mmHg ) to 14 mmHg ( range , 7 - 25 mmHg ) in the propranolol monotherapy group ( P<0.05 ) . However , the medication-induced pressure reduction did not differ significantly between the two groups [ 3.5 mmHg ( range , -3 - 11 mmHg ) vs. 3 mmHg ( range , -8 - 10 mmHg ) , P=0.674 ] . The response rate ( 55.6 % vs. 61.5 % , P=0.435 ) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups . Conclusions The addition of c and esartan ( an ARB ) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension , and is thus not recommended Background Therapies that can slow the progression of liver fibrosis in chronic liver disease are needed . Evidence suggests that the renin-angiotensin system ( RAS ) contributes to inflammation and fibrosis in chronic liver disease . Both animal and limited human studies have shown that RAS inhibition with angiotensin-converting enzyme inhibitors ( ACEi ) and angiotensin receptor-1 [ AT-1 ] blockers ( ARBs ) has antifibrogenic properties . Aims In this study , we evaluated the effects of continuous ACEi/ARB use for 3.5 years on histological liver fibrosis progression in the HALT-C Trial cohort . Methods In the HALT-C Trial , subjects with chronic hepatitis C and advanced hepatic fibrosis ( Ishak stage ≥3 ) underwent serial liver biopsies at baseline , 1.5 years , and 3.5 years after r and omization . The primary outcome was a ≥2-point increase in Ishak fibrosis score in at least one of the two serial biopsies . Sixty-six subjects were continuously taking ACEi/ARBs over the observation period , 126 were taking other antihypertensive medications , and 343 subjects took no antihypertensive medications . Results The three groups were similar in baseline fibrosis scores , and the two groups being treated with antihypertensives were taking a similar number of antihypertensive medications . Fibrosis progression occurred in 33.3 % of the ACEi/ARB group , 32.5 % of the other antihypertensive medications group , and in 25.7 % of subjects taking no antihypertensive medications . No significant associations between ≥2-point increases in fibrosis scores and continuous ACEi/ARB use were apparent at either 1.5 or 3.5 years in diabetes-adjusted and unadjusted odds ratios . Conclusions ACEi/ARB therapy did not retard the progression of hepatic fibrosis BACKGROUND Recent studies have shown that the renin-angiotensin system is implicated in hepatic fibrogenesis in vitro and in vivo . However , no study was done in humans with alcoholic liver disease . AIM To investigate the antifibrotic effect of angiotensin II type 1 receptor ( AT1-R ) blocking agents ( ARB ) in patients with alcoholic liver disease . METHODS The primary outcome was improvement in patients ' histological features . Eighty-five patients with compensated alcoholic liver fibrosis ( ≥ F2 ) which was confirmed by baseline liver biopsy were r and omized ( intention-to-treat ( ITT ) ) to receive either ARB , c and esartan ( 8 mg/day ) with ursodeoxycholic acid ( UDCA ) ( 600 mg/day ) ( n = 42 ) or UDCA alone ( n = 43 ) as control for 6 months and follow-up liver biopsies were conducted . RESULTS According to the Laennec fibrosis system , c and esartan showed significantly higher rates of histological improvements ( ITT , 33.3 % vs. 11.6 % , P = 0.020 ) . In addition , the fibrosis score was significantly reduced from 3.4 ± 1.4 to 3.1 ± 1.5 ( P = 0.005 ) in the c and esartan group . C and esartan also reduced the area of fibrosis and α-smooth muscle actin positive from 11.3 ± 6.0 to 8.3 ± 4.7 and 28.7 ± 10.5 to 23.9 ± 10.3 ( % ) , and the hydroxyproline levels ( μg/g liver tissue ) from 7.8 ± 2.4 to 6.3 ± 1.7 respectively ( P < 0.05 ) . In addition , the relative expression of transforming growth factor-β1(TGF-β1 ) , collagen-1 , AT1-R , tissue inhibitor of metalloproteinase 1 ( TIMP-1 ) , metalloproteinases2 ( MMP2 ) , Rac1 and p22phox by real-time RT-PCR decreased in the c and esartan group ( P < 0.05 ) . Mean arterial blood pressure in the c and esartan group decreased mildly but significantly ( P < 0.001 ) . No significant complications and side effects were observed during the present study . CONCLUSIONS Administration of ARB in compensated alcoholic liver disease induces improvement of fibrosis in histological and quantitative measurements Output:	Serum fibrosis markers such as TGF-β1 , collagen I , IV , TIMP-1 , and MMP2 were significantly reduced in the intervention group . No significant difference was found in serum creatinine levels between the intervention and control groups , and significant renal dysfunction was not observed after administration of RAS inhibitors . Conclusions RAS inhibitors are potential therapeutic agents for hepatic fibrosis , which can be safely used in patients with chronic liver disease
MS22205	*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 subset of head and neck cancers is associated with the human papillomavirus ( HPV ) . Viral infection is closely correlated with expression of p16(INK4A ) in these tumors . We evaluated p16(INK4A ) as a prognostic marker of treatment response and survival in a well-defined and prospect ively collected cohort of patients treated solely with conventional radiotherapy in the Danish Head and Neck Cancer Group ( DAHANCA ) 5 trial . PATIENTS AND METHODS Immunohistochemical expression of p16(INK4A ) was analyzed in pretreatment paraffin-embedded tumor blocks from 156 patients treated with conventional primary radiotherapy alone . The influence of p16(INK4A ) status on locoregional tumor control , disease-specific survival , and overall survival after radiotherapy was evaluated . RESULTS p16(INK4A ) positivity was found in 35 tumors ( 22 % ) . Tumor-positivity for p16(INK4A ) was significantly correlated with improved locoregional tumor control ( 5-year actuarial values 58 % v 28 % ; P = .0005 ) , improved disease-specific survival ( 72 % v 34 % ; P = .0006 ) , and improved overall survival ( 62 % v 26 % ; P = .0003 ) . In multivariate analysis , p16(INK4A ) remained a strong independent prognostic factor for locoregional failure ( hazard ratio [ HR ] , 0.35 ; 95 % CI , 0.19 to 0.64 ) , disease-specific death ( HR , 0.36 ; 95 % CI , 0.20 to 0.64 ) , and overall death ( HR , 0.44 ; 95 % CI , 0.28 to 0.68 ) . CONCLUSION Expression of p16(INK4A ) has a major impact on treatment response and survival in patients with head and neck cancer treated with conventional radiotherapy PURPOSE To investigate the safety and clinical utility of the sentinel node procedure in early-stage vulvar cancer patients . PATIENTS AND METHODS A multicenter observational study on sentinel node detection using radioactive tracer and blue dye was performed in patients with T1/2 ( < 4 cm ) squamous cell cancer of the vulva . When the sentinel node was found to be negative at pathologic ultrastaging , inguinofemoral lymphadenectomy was omitted , and the patient was observed with follow-up for 2 years at intervals of every 2 months . Stopping rules were defined for the occurrence of groin recurrences . RESULTS From March 2000 until June 2006 , a sentinel node procedure was performed in 623 groins of 403 assessable patients . In 259 patients with unifocal vulvar disease and a negative sentinel node ( median follow-up time , 35 months ) , six groin recurrences were diagnosed ( 2.3 % ; 95 % CI , 0.6 % to 5 % ) , and 3-year survival rate was 97 % ( 95 % CI , 91 % to 99 % ) . Short-term morbidity was decreased in patients after sentinel node dissection only when compared with patients with a positive sentinel node who underwent inguinofemoral lymphadenectomy ( wound breakdown in groin : 11.7 % v 34.0 % , respectively ; P < .0001 ; and cellulitis : 4.5 % v 21.3 % , respectively ; P < .0001 ) . Long-term morbidity also was less frequently observed after removal of only the sentinel node compared with sentinel node removal and inguinofemoral lymphadenectomy ( recurrent erysipelas : 0.4 % v 16.2 % , respectively ; P < .0001 ; and lymphedema of the legs : 1.9 % v 25.2 % , respectively ; P < .0001 ) . CONCLUSION In early-stage vulvar cancer patients with a negative sentinel node , the groin recurrence rate is low , survival is excellent , and treatment-related morbidity is minimal . We suggest that sentinel node dissection , performed by a quality -controlled multidisciplinary team , should be part of the st and ard treatment in selected patients with early-stage vulvar cancer BACKGROUND The improved prognosis for patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma ( HNSCC ) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospect i ve clinical trial . METHODS We prospect ively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group ( ECOG ) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and st and ard fractionation radiation therapy . The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction ( PCR ) and in situ hybridization . Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan-Meier analysis . The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age , ECOG performance status , stage , and other covariables was estimated by use of a multivariable Cox proportional hazards model . All statistical tests were two-sided . RESULTS Genomic DNA of oncogenic HPV types 16 , 33 , or 35 was located within tumor cell nuclei of 40 % ( 95 % confidence interval [ CI ] = 30 % to 50 % ) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR . Compared with patients with HPV-negative tumors , patients with HPV-positive tumors had higher response rates after induction chemotherapy ( 82 % vs 55 % , difference = 27 % , 95 % CI = 9.3 % to 44.7 % , P = .01 ) and after chemoradiation treatment ( 84 % vs 57 % , difference = 27 % , 95 % CI = 9.7 % to 44.3 % , P = .007 ) . After a median follow-up of 39.1 months , patients with HPV-positive tumors had improved overall survival ( 2-year overall survival = 95 % [ 95 % CI = 87 % to 100 % ] vs 62 % [ 95 % CI = 49 % to 74 % ] , difference = 33 % , 95 % CI = 18.6 % to 47.4 % , P = .005 , log-rank test ) and , after adjustment for age , tumor stage , and ECOG performance status , lower risks of progression ( hazard ratio [ HR ] = 0.27 , 95 % CI = 0.10 to 0.75 ) , and death from any cause ( HR = 0.36 , 95 % CI = 0.15 to 0.85 ) than those with HPV-negative tumors . CONCLUSION For patients with HNSCC of the oropharynx , tumor HPV status is strongly associated with therapeutic response and survival PURPOSE To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer . PATIENTS AND METHODS Eligible women had squamous cell carcinoma , at least 1-mm invasion , and tumor size ≥ 2 cm and ≤ 6 cm . The primary tumor was limited to the vulva , and there were no groin lymph nodes that were clinical ly suggestive of cancer . All women underwent intraoperative lymphatic mapping , sentinel lymph node biopsy , and inguinal femoral lymphadenectomy . Histologic ultra staging of the sentinel lymph node was prescribed . RESULTS In all , 452 women underwent the planned procedures , and 418 had at least one sentinel lymph node identified . There were 132 node-positive women , including 11 ( 8.3 % ) with false-negative nodes . Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node . The sensitivity was 91.7 % ( 90 % lower confidence bound , 86.7 % ) and the false-negative predictive value ( 1-negative predictive value ) was 3.7 % ( 90 % upper confidence bound , 6.1 % ) . In women with tumor less than 4 cm , the false-negative predictive value was 2.0 % ( 90 % upper confidence bound , 4.5 % ) . CONCLUSION Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva Output:	Implementation of sentinel lymph node biopsy in patients with tumours not exceeding 4 cm is safe and efficiently eliminates redundant groin dissections .
MS22206	*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: Leg ulcers are a chronic manifestation of sickle-cell disease ( SCD ) and are often painful , disabling , and difficult to treat . RGD peptide matrix treatment is a novel therapy design ed to provide a topical synthetic extracellular matrix that can act as a temporary substitute for the damaged natural matrix at the ulcer site . In this r and omized , placebo-controlled , double-blind , prospect i ve , multicenter investigation , SCD patients with full-thickness leg ulcers were treated with st and ard therapy plus RGD peptide matrix or saline placebo once weekly for up to 10 weeks . Healing in patients with chronic ulcers ( 2 months or greater in duration ) was significantly accelerated ( P = .0085 ) in RGD peptide matrix recipients compared with the placebo group . In these chronic ulcer cases , the average percent ulcer closure ( decrease in ulcer surface area ) in the RGD peptide matrix group ( 54.4 % + /- 8.9 % ) exceeded that in the placebo group ( 19.0 % + /- 24.3 % ) nearly threefold by study endpoint . Furthermore , RGD peptide matrix was equally effective in promoting healing of long persistent ulcers and ulcers of shorter duration . In contrast , st and ard therapy plus placebo was significantly less effective ( P = .001 ) in promoting healing for ulcers of progressively greater duration . The results of this study provide preliminary evidence that RGD peptide matrix treatment may significantly accelerate healing of chronic sickle-cell leg ulcers A new dressing for chronic wounds , BioFilm hydrogel dressing , was compared to a hydrocolloid dressing ( HCD ) control in a clinical trial involving 90 patients and 129 Stage I and II wounds ( defined by Enis and Sarmienti ) . The testing sites included both acute care and extended care facilities . A comparison of healing response and functional characteristics of both dressings was part of this assessment . Biofilm dressings demonstrated a healing advantage over the HCD . In addition , clinicians judged that the hydrogel dressings were easier to use and had superior fluid management capability and product integrity with minimal disruption to the healing wounds The author reports an open controlled trial on 72 patients affected by different types of skin ulcers , in which a heterologous lyophilized collagen sponge was compared with Dextranomer as healing adjuvant . The rationale of use and pharmacological properties of this collagen are outlined and explain its outst and ing results 1 . Topical irrigation with normal saline is known to produce rapid healing in chronic leg ulcers . This study was design ed to determine if the rate of healing could be improved by the addition of topical nutrition to the irrigating solution . 2 . Forty-eight patients with chronic leg ulcers were admitted to hospital for a minimum of 6 weeks bed-rest . During this time the ulcers were continuously irrigated by one of four test solutions . The solutions were : normal saline ; a dilute amino acid solution isotonic with the normal saline ; a hyperosmolar saline solution ; a hyperosmolar amino acid solution . There were 12 ulcers in each group . 3 . The amino acid solutions produced significantly faster healing than the saline solutions ( P less than 0.01 ) . Concentration had no significant effect on healing ( P greater than 0.15 ) . 4 . The application of amino acids does appear to enhance healing in this model of delayed wound healing . This effect does not depend only on the osmolarity of the solution used Applications of Condress ( patented sheets of pure bovine collagen ) on open skin surfaces ( 30 cases of " ulcus cruris " , 5 cases of decubitus , and malum perforans ; 10 cases of full-thickness burns ) were examined in a controlled trial . Quantification of regeneration speed , macrophotographic survey of granulation tissue and epithelial border , thermographic and chromometric evaluation of the skin microcirculation , and histological observation of regenerating tissues , were the parameters used . The following results were obtained : marked reduction of healing time , different aspects of the granulation-tissue responses , different times of topical collagenolysis , increased vascular perfusion , histological activation of angiogenesis , fibrogenesis , histiomacrophage function and superficial absorption . The employment of Condress in burn areas seems to be highly promising In a prospect i ve , r and omised , controlled trial of 92 patients with full-thickness pressure ulcers , the efficacy of an alginate wound dressing was compared to that of an established local treatment with dextranomer paste . During treatment , a minimal 40 % reduction in wound area was obtained in 74 % of the patients in the alginate group and in 42 % of those in the dextranomer group . The median time taken to achieve this goal was four weeks with alginate and more than eight weeks in the control group . Mean surface area reduction per week was 2.39cm2 ( sd 3.54 ) and 0.27cm2 ( sd 3.21 ) in the alginate and dextranomer groups respectively ( p=0.0001 ) . This difference was still highly significant when the sub-groups of almost completely healed subjects at the end of the study were considered . This striking healing efficacy of an alginate dressing suggests it possesses pharmacological properties which require further investigation Cultured epidermal allografts have been successfully used to treat a wide variety of skin defects ranging from burns to leg ulcers . Their postulated mechanism of action is through release of multiple cytokines that stimulate epithelialization from the wound periphery as well as from remnant epidermal appendages . A r and omized , controlled clinical trial was undertaken to compare the efficacy of cryopreserved cultured allograft dressings ( CCAD ) with tulle-gras dressings in the treatment of split-skin graft donor sites . Five patients were enrolled in the study and in each patient , half of the donor site was allografted and the other half was treated with tulle-gras control . The mean time to complete healing was 6.2 days for CCAD compared with 9.6 days ( p = 0.035 ) for the tulle-gras controls . Patient assessment of pain with dressing changes was also significantly lower at the CCAD-treated sites than at the control sites ( p = 0.001 ) . The results indicate that cultured allografts offer greater patient comfort and earlier maturation of regenerated skin The first r and omized , blinded , placebo-controlled human trials of recombinant basic fibroblast growth factor ( bFGF ) for pressure sore treatment were performed . Three different concentrations of bFGF in five dosing schedules were tested for safety using hematology , serum chemistries , urinalysis , absorption , antibody formation , and signs of toxicity . Efficacy was evaluated by wound volumes , histology , and photography . No toxicity , significant serum absorption , or antibody formation occurred . In six of eight subgroups , there was a trend toward efficacy with bFGF treatment . When all subgroups were combined , comparison of the slopes of the regression curves of volume decrease over initial pressure sore volume demonstrated a greater healing effect for the bFGF-treated patients ( p < 0.05 ) . Histologically , bFGF-treated wound sections demonstrated increased fibroblasts and capillaries . More patients treated with bFGF achieved > 70 % wound closure ( p < 0.05 ) . Blinded observers were able to distinguish differences in visual wound improvement between bFGF and placebo groups . These data suggest that bFGF may be effective in the treatment of chronic wounds A total of 67 patients with pressure ulcers were r and omized into one of three treatment modalities : hydrogel sheet dressing , hydrocolloid , or wet-to-moist gauze . Safety , efficacy , and physical attributes of the three dressings were evaluated . No statistical significance was found in wound healing rate among the three treatments . Hydrogel sheets were advantageous in allowing wound visualization without dressing or wound disruption Interleukin-1beta is produced by numerous cell types including monocytes and fibroblasts . It has been shown to stimulate multiple cell types including fibroblasts , keratinocytes , endothelial cells , neutrophils , macrophages , and lymphocytes . Previously , interleukin-1beta was shown to accelerate healing in partial-thickness and full-thickness wounds in animals and was also shown to be safe when applied topically in Phase I human trials . Therefore a prospect ively r and omized , blind , placebo-controlled trial was performed with patients with chronic pressure ulcers . Doses of interleukin-1beta of .01 microg , .10 microg , and 1.0 microg per square centimeter did not show acceleration of healing of the pressure ulcers . Therefore use of recombinant human interleukin-1beta in this study was safe but , at the dose levels tested , did not result in improvement in the healing ratio OBJECTIVE To assess the effect of different dressings on venous ulcer healing . DESIGN A r and omised clinical trial . MATERIAL S Patients were r and omised to treatment with one of three dressings : a zinc oxide impregnated b and age , a zinc oxide impregnated stockingette , or an alginate dressing . All patients were treated as out patients and had compression b and aging with two minimal stretch b and ages ( Elastocrepe ) and a stockingette ( Tubigrip ) to keep the b and ages in place . METHODS One hundred and thirteen patients ( 133 ulcerated limbs ) with chronic ulceration of the leg due to venous disease alone , and attending Fremantle Hospital Leg Ulcer Clinic , Western Australia were entered into the study . Healing was measured as complete healing of the ulcerated limb or failure of the limb to heal within 9 months . RESULTS There was no significant difference between the three groups in ulcer size , duration , and other parameters compared . Healing was affected significantly by ulcer size and which leg was ulcerated . There was significantly faster healing with the paste b and age . CONCLUSION The use of a paste b and age significantly improved the healing of chronic venous ulcers when used in combination with compression b and aging , and compared to an alginate dressing and a zinc oxide impregnated stockingette OBJECTIVE To determine the efficacy of the daily topical application of recombinant platelet-derived growth factor-BB ( rPDGF-BB ) , a recognized vulnerary agent , in the treatment of deep pressure ulcers . DESIGN Prospect i ve , r and omized , double-blind trial . SETTING Patients were treated in a nursing home or a hospital setting before transfer to a nursing home . PATIENTS Eligibility criteria included a clean pressure ulcer that had been adequately debrided and the absence of severe cardiac , pulmonary , or renal conditions . The causes of the ulcers were not related to a venous or arterial vascular disorder . The patients were elderly ( mean age , 68 to 74 years ) . INTERVENTIONS After r and omization , patients were given daily topical aqueous rPDGF-BB ( dosage , 100 or 300 micrograms/mL ) or placebo and saline gauze dressings were applied daily in addition to frequent turning . MAIN OUTCOME MEASURE Serial volume measurements of the healing wounds were taken using alginate molds . RESULTS The ulcers of 41 patients were analyzed . At the end of 28 days , median ulcer volumes had decreased to 83 % , 29 % , and 40 % of the initial size in the groups receiving placebo , rPDGF-BB , 100 micrograms/dL , and rPDGF-BB , 300 micrograms/mL , respectively . When adjusted for initial volume , ulcer volume after 28 days of treatment was smaller in the rPDGF-BB-treated groups compared with the placebo group ( analysis of covariance , P = .056 ) . Ulcers in the two rPDGF-BB-treated groups were significantly smaller in volume compared with those in the placebo group , using a linear contrast procedure . CONCLUSIONS Data from this small trial suggest that local application of rPDGF-BB may be of therapeutic benefit in accelerating the healing of chronic pressure ulcers We performed a r and omized , double‐blind study of the efficacy of locally applied zinc oxide on the healing of leg ulcers . Thirty‐seven geriatric patients , nineteen with arterial and eighteen with venous leg ulcers , were treated either with a gauze compress medicated with zinc oxide ( 400 μg ZnO/cm2 ) or with an identical compress without zinc oxide . The treatment was assessed from ulcer size measurements and the presence or abscncc of granulation and ulcer debridement over a period of 8 weeks . The zinc‐treated patients ( 83 % success rate ) responded significantly better ( P < 0·05 ) than the placebo‐treated patients ( 42 % success rate ) . The results suggest that healing of leg ulcers is improved after the addition of zinc oxide to the local regimen To determine the effect of bacterial colonization on venous ulcer healing , 82 patients with 100 venous ulcerated limbs were each studied prospect ively for six months . Despite bacteriological swab results , topical or systemic antibiotics were not administered unless cellulitis supervened . Initial ulcer size , length of ulcer history and time to complete healing of colonized and uncolonized ulcers were determined and compared OBJECTIVE To compare the clinical effectiveness and wound management properties of a copolymer membrane , Inerpan ( Synthélabo ) , and a hydrocolloid dressing , Comfeel ( Coloplast ) , in the treatment of decubitus ulcers in the elderly . DESIGN Open , r and omized , multicentric French study , with two parallel groups of patients . PATIENTS 168 in- patients aged more 65 years ( mean age : 82 years ) suffering from grade II to grade IV ( in the Shea classification ) pressure sores . TRIAL PERIOD : Either 8 weeks or Output:	A meta- analysis of five reports comparing a hydrocolloid dressing with a traditional treatment suggested that treatment with the hydrocolloid result ed in a statistically significant improvement in the rate of pressure sore healing . There was no difference in the proportion of ulcers healed between patients treated with cryopreserved cultured allografts or a hydrocolloid , though the former-treated ulcers had a higher rate of epithelialisation . A collagen dressing was more effective than treatment with daily antiseptic . However , publication bias was indicated in a comparison of traditional and hydrocolloid dressings . Implication for practice : There is little evidence to indicate which dressings or topical agents are the most effective in the treatment of chronic wounds . However , there is evidence that hydrocolloid dressings are better than wet-to-dry dressings for the treatment of pressure sores . In the treatment of venous ulcers , low adherent dressings are as effective as hydrocolloid dressings beneath compression b and aging .
MS22207	*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 conflicting evidence concerning the influence of high-dose steroids on intracranial pressure ( ICP ) and outcome following severe head injury has led to the institution of the prospect i ve double-blind controlled trial reported here . Severely head-injured patients admitted to intensive care during a 3-year period were r and omly allocated to a dexamethasone- or placebo-treated group . Adults in the steroid group received dexamethasone , 50 mg intravenously , as a bolus on admission to the neurosurgical unit , then 100 mg on Days 1 , 2 , and 3 , 50 mg on Day 4 , and 25 mg on Day 5 on continuous intravenous infusion . Children received proportionate intravenous dosages calculated on a weight basis . Severity of head injury was assessed from admission Glasgow Coma Scale ( GCS ) scores and the appearance of the admission computerized tomography scan . Intracranial pressure ( ICP ) was monitored in all patients from the surface subarachnoid space . Outcome at 6 months was assessed using the Glasgow Outcome Scale . Steroid and placebo groups were similar in terms of admission GCS score , intracranial pathology , incidence of associated injuries , and time interval from injury to admission to intensive care . The ICP generally increased during the first 48 hours of intensive therapy ; there was no difference in this trend between the steroid and placebo groups . A poorer outcome was observed in patients with elevated ICP who received steroids . No increase in the incidence of pulmonary , gastrointestinal , or other extracranial complications was seen in the steroid group . The 6-month outcome did not differ between the steroid and placebo groups . No advantage of high-dose dexamethasone on ICP trends or clinical outcome in the treatment of severe head injury has emerged from this study In a prospect i ve r and omized double-blind multicenter trial , the efficacy and safety of a 51-hour ultra-high intravenous dexamethasone dosing regimen was investigated in patients with moderate and severe head injury . 300 patients between 15 and 55 years of age were r and omized to receive either placebo or dexamethasone : 500 mg intravenous infusion within 3 h after trauma initially , followed by 200 mg after 3 h , thereafter 8 times 200 mg at 6 hourly intervals , result ing in a total administered dose of 2,3 g in 51 hours . Primary end points for assessment of efficacy were : Modified Glasgow Coma Scale ( grading 3 - 16 ) on Day 5 , modified Glasgow Outcome Scale ( grading 1 - 6 ) 10 - 14 months after injury , and the time interval until consciousness improved above a level of modified GCS > or = 8 . Secondary endpoints were CT results and neurological and laboratory data . The two groups were well matched with respect to important prognostic variables , such as age , severity of trauma , and interval between trauma and application of the drug . 269 patients ( 89.7 % ) were available for final examination after 10 - 14 months . Results were surprisingly favourable in both groups : Lethality in the dexamethasone and placebo group was 14.3 and 15.4 % , respectively , and 61.7 and 57.4 % , respectively , achieved social and professional rehabilitation after 10 - 14 months ( outcome scale 6 ) . No statistical difference was seen between the dexamethasone and the placebo group in any of the primary end points of efficacy and safety ( incidence of upper gastrointestinal bleeding , infection , and thrombosis ) . ( ABSTRACT TRUNCATED AT 250 WORDS Summary Out of a total of 157 hospitalized head-injured children , twelve years of age and under , fifteen were considered to be severe , three of whom died within 72 hours of admission . Nine children with closed head injuries who were in coma for at least 24 hours ( did not open eyes , speak , or follow comm and s ) , with absent or impaired oculocephalic reflex , impaired pupil reactivity to light , and who were decerebrating for at least twelve hours , were studied . Five were given high dose dexamethasone therapy ( 1 mg/kg ) within six hours of injury , repeated at six hours , and then maintained at 1 mg/kg/day for eight days , and four either received none or were treated with a low dose regimen ( 0.25 mg/kg/day ) . In those receiving high dose therapy , intracranial pressure waves were noticeably less , peak intracranial pressure was lower , and intensive care and hospital stay were shorter . It was also noted that in the high dose therapy group spontaneous eye opening and speech returned sooner , and all were considered to have returned to their premorbid status by six months following injury . Of the no steroid or low dose group , one died , and of the remainder at six months one was aphasic and still decerebrating , another was aphasic and severely h and icapped , and the third returned to school seven months after injury The present studies were conducted to test whether the outcome of severe head injury is improved by early administration of the synthetic corticosteroid triamcinolone . In a prospect i ve , double-blind , multicenter clinical trial , 396 patients with severe head injury were r and omized to a steroid group ( n=187 ) receiving 200 mg triamcinolone acetonide ( Volon A soluble ) i.v . within 4 h after trauma , followed by 3 × 40 mg/day i.v . for 4 days , and 3 × 20 mg/day i.v . for a further 4 days , and a placebo group ( n=209 ) receiving injections which did not contain any active drug . The placebo group was subjected to the same st and ard treatment procedures . Clinical features were not different between the groups upon admission to hospital . Subdural hematoma , epidural hematoma , and focal supratentorial contusion were among the most frequent diagnoses . The result of treatment with triamcinolone was assessed at discharge from the hospital and at 1 year after trauma . using the Glasgow Outcome Scale . Differences in favor of steroid treatment could be detected with regard to the patients ' condition at discharge ( P=0.0634 ) . More patients with steroids had a good recovery ( 49.2 % vs 40.7 % ) , and fewer died ( 16.0 % vs 21.5 % ) . Differences in outcome were even more pronounced ( P<0.0145 ) in patients with a focal lesion and a Glasgow Coma Score on admission of < 8 ( n=93 ) . In this group , 34.8 % of the patients made a good recovery , as against 21.3 % of the placebo group ; mortality was also lower in the verum group ( 19.6 % vs 38.3 % ) . The results indicate that a major subgroup of patients with severe head injury benefits from early administration of triamcinolone . Efficacy of the treatment can be expected , in particular , in patients with a focal cerebral lesion and a Glasgow Coma Score of < 8 on admission . Administration of steroids beginning at the scene of an accident would therefore be beneficial in these cases A prospect i ve r and omised study was performed on 25 children aged 1.4 to 15.8 years with severe head injury ( Glasgow Coma Scale⪕7 ) to determine the clinical effectiveness and the impact on endogenous cortisol production of high-dose steroid therapy . Thirteen patients ( group 1 ) received dexamethasone 1 mg/kg/day during the first 3 days and 12 ( group 2 ) not . All patients were treated with a st and ardized regimen . Urinary free cortisol was measured by radioimmunoassay , and the clinical data were recorded at hourly intervals . Outcome was assessed 6 months later using the Glasgow Outcome Scale . We found a higher frequency of bacterial pneumonias in the dexamethasone-treated patients ( 7/13 versus 2/12 ) . Group 1 showed a suppression of endogenous cortisol production from day 1 to day 6 . In group 2 , menu free cortisol was up to 5-fold higher than under basal conditions . The results in group 2 showed taht the endogenous steroid production reacts adequately to the stress of severe head injury . It probably is sufficient to elicit maximum glucocorticoid effects . There was no other statistically significant difference in the clinical and laboratory data between the two groups . We conclude that dexamethasone in high doses suppresses endogenous cortisol production up to 6 days and may increase the risk of bacterial infection without affecting the outcome or the clinical and laboratory data In 1990 , the Second National Acute Spinal Cord Injury Study reported that high-dosage methylprednisolone improves neurologic recovery in spinal-injured humans . The study showed that patients who received the drug within 8 hr after injury improved , whereas those who received the drug later did not . The drug significantly increased recovery even in severely injured patients who were admitted with no motor or sensory function below the lesion , contradicting a long-held dogma that such patients would not recover . Some research ers , however , have question ed the stratification of the patient population , the use of summed neurologic change scores , and the absence of functional assessment s. The stratification by injury severity and treatment time was planned a priori and based on objective criteria . Detailed analyses revealed no differences between groups attributable to stratification or r and omization . While multivariate analyses of the summed neurologic scores were used , the conclusions were corroborated by other analytical approaches that did not rely on summed scores . For example , treatment with methylprednisolone more than doubled the probability that patients would convert from quadriplegia or paraplegia to quadriparesis or paraparesis , analgesia to hypalgesia , and anesthesia to hypesthesia . The treatment also significantly improved neurologic scores in lumbosacral segments , indicating that beneficial effects were not limited to segments close to the lesion site . The treatment did not significantly affect mortality or morbidity . The study strongly suggests that methylprednisolone has significant beneficial effects in human spinal cord injury , that these effects occur only when the drug is given within 8 hr , and that it helps even in patients with severe spinal cord injuries . These conclusions have important implication s for spinal cord injury care and research A prospect i ve double-blind study of the effects of dexamethasone administration on the outcome of patients with severe head injuries was performed . Patients were stratified for severity of neurological injury and were treated with placebo , low-dose dexamethasone ( 16 mg/day ) , or high-dose dexamethasone ( 96 mg/day ) for a period of 6 days . Outcome was evaluated at 6 months following injury . Of the 76 patients available for analysis , a good outcome was achieved in 37 % of placebo-treated patients , 44 % of low-dose-treated patients , and 29 % of high-dose-treated patients . These differences are not statistically significant . Similarly dexamethasone administration had no statistically significant effect on intracranial pressure patterns or serial neurological examinations during hospitalization . Gastrointestinal bleeding occurred in only one patient . Good outcome was associated with age under 10 years , lighter depth of coma on admission , and the preservation of brain-stem reflexes upon admission . A recalculation of data in previous clinical series purporting to show an improvement in outcome as a result of corticosteroid therapy shows no significant difference in outcome when steroid- and placebo-treated patients are compared . In our series , 90 % of all deaths were caused by recurrent intracranial hematomas , medical complications , or diffuse brain injuries with parenchymal hemorrhage and tissue disruption -- causes of death which can not be affected by corticosteroid therapy . The study suggests that dexamethasone in either high or low dosages has no significant effect on morbidity and mortality following severe head injury This is a prospect i ve r and omized study of the efficacy of steroid therapy in patients with severe head injury . One hundred patients were r and omized into two equal groups : the steroid group received 5 mg/kg/day of methylprednisolone , and the nonsteroid group received no drug . The groups were similar in their clinical features . All patients received a st and ardized therapeutic regimen . The patients were also classified as early responders or nonresponders to the overall treatment protocol without regard to steroid administration , on the basis of change in Glasgow Coma Scale score during the first 3 days of admission . There was no statistically significant difference in the outcome of the steroid and nonsteroid group at 6 months . Of the responders who were on steroids , 74 % had good outcomes or were disabled , compared with 56 % of the responders who did not receive steroids . In the nonresponder group , the patients on steroids were actually associated with a worse outcome than those who did not receive steroids : 75 % of the nonresponders who received steroids were dead or vegetative , compared to 56 % of those who were not receiving steroids . The data suggest that : 1 ) the effect of steroids may be different for different patient groups ; 2 ) in order to identify these patients , a sensitive coma scale is needed ; and 3 ) a rational approach to steroid therapy in head-injured patients may be to start all patients on steroids , but to discontinue their use in patients identified as not benefiting from steroid therapy MRC CRASH is a r and omised controlled trial ( IS RCT N74459797 ) of the effect of corticosteroids on death and disability after head injury . We r and omly allocated 10,008 adults with head injury and a Glasgow Coma Scale score of 14 or less , within 8 h of injury , to a 4 Output:	The increase in mortality with steroids in this trial suggest that steroids should no longer be routinely used in people with traumatic head injury
MS22208	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS Dapagliflozin , a highly selective inhibitor of sodium-glucose cotransporter 2 ( SGLT2 ) , reduces hyperglycaemia and weight in patients with type 2 diabetes mellitus ( T2DM ) by increasing urinary glucose excretion . Long-term glycaemic control , body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment . METHODS This r and omized , double-blind , placebo-controlled study ( NCT00855166 ) enrolled patients with T2DM [ mean : age 60.7 years ; HbA1c 7.2 % ; body mass index ( BMI ) 31.9 kg/m(2 ) ; body weight 91.5 kg ] inadequately controlled on metformin . Patients ( N = 182 ) were r and omly assigned 1 : 1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period . At week 102 , changes from baseline in HbA1c , weight , waist circumference , total body fat mass as measured by dual-energy X-ray absorptiometry ( DXA ) , serum markers of bone turnover , bone mineral density ( BMD ) as measured by DXA , and adverse events were evaluated . RESULTS A total of 140 patients ( 76.9 % ) completed the study . Over 102 weeks , dapagliflozin-treated patients showed reductions in HbA1c by -0.3 % , weight by -4.54 kg , waist circumference by -5.0 cm and fat mass by -2.80 kg without increase in rate of hypoglycaemia . Compared with placebo , no meaningful changes from baseline in markers of bone turnover or BMD were identified over 102 weeks . One fracture occurred in each treatment group . The frequency of urinary tract infection ( UTI ) and genital infection was similar in both treatment groups . CONCLUSIONS Over 102 weeks , dapagliflozin improved glycaemic control , and reduced weight and fat mass , without affecting markers of bone turnover or BMD in patients with T2DM inadequately controlled on metformin OBJECTIVE To determine whether dapagliflozin , which selectively inhibits renal glucose reabsorption , lowers hyperglycemia in patients with type 2 diabetes that is poorly controlled with high insulin doses plus oral antidiabetic agents ( OADs ) . RESEARCH DESIGN AND METHODS This was a r and omized , double-blind , three-arm parallel-group , placebo-controlled , 26-center trial ( U.S. and Canada ) . Based on data from an insulin dose-adjustment setting cohort ( n = 4 ) , patients in the treatment cohort ( n = 71 ) were r and omly assigned 1:1:1 to placebo , 10 mg dapagliflozin , or 20 mg dapagliflozin , plus OAD(s ) and 50 % of their daily insulin dose . The primary outcome was change from baseline in A1C at week 12 ( dapagliflozin vs. placebo , last observation carried forward [ LOCF ] ) . RESULTS At week 12 ( LOCF ) , the 10- and 20-mg dapagliflozin groups demonstrated −0.70 and −0.78 % mean differences in A1C change from baseline versus placebo . In both dapagliflozin groups , 65.2 % of patients achieved a decrease from baseline in A1C ≥0.5 % versus 15.8 % in the placebo group . Mean changes from baseline in fasting plasma glucose ( FPG ) were + 17.8 , + 2.4 , and −9.6 mg/dl ( placebo , 10 mg dapagliflozin , and 20 mg dapagliflozin , respectively ) . Postpr and ial glucose ( PPG ) reductions with dapagliflozin also showed dose dependence . Mean changes in total body weight were −1.9 , −4.5 , and −4.3 kg ( placebo , 10 mg dapagliflozin , and 20 mg dapagliflozin ) . Overall , adverse events were balanced across all groups , although more genital infections occurred in the 20-mg dapagliflozin group than in the placebo group . CONCLUSIONS In patients receiving high insulin doses plus insulin sensitizers who had their baseline insulin reduced by 50 % , dapagliflozin decreased A1C , produced better FPG and PPG levels , and lowered weight more than placebo Sodium – glucose cotransporter 2 ( SGLT2 ) inhibitors are a newly approved class of glucose-lowering medications with a novel mechanism of action . These agents increase glycosuria , which leads to improved glucose control . They also produce an osmotic diuresis that , in part , contributes to blood pressure reduction and calorie loss secondary to glycosuria leading to weight loss ( 1,2 ) . A recent review of SGLT2 inhibitors focuses on the blood pressure – lowering effects of the two approved glucose-lowering agents , dapagliflozin and canagliflozin ( 3 ) . While not approved as antihypertensive agents , they may potentially aid in lowering blood pressure in patients with diabetes . A review of studies in both hypertensive and normotensive patients with type 2 diabetes demonstrates a 4–10 mmHg reduction of systolic blood pressure ( 3 ) . In this issue of Diabetes Care , Tikkanen et al. ( 4 ) investigate the effectiveness and safety of the newest agent in this class , empagliflozin , on blood pressure using 24-h ambulatory blood pressure monitoring . This study r and omized over 800 subjects with type 2 diabetes , mean age of 60 years , and good kidney function ( i.e. , a mean estimated glomerular filtration rate [ eGFR ] of 84 mL/min/1.73 m2 ) . These subjects either were normotensive ( < 140/90 mmHg ) or had stage 1 hypertension ( ≥140/90 < 160/99 mmHg ) . They were r and omized to either empagliflozin 10 mg daily , empagliflozin 25 mg Uric acid is associated with cardiovascular disease and cardiovascular disease risk factors in adults , including chronic kidney disease , coronary artery disease , stroke , diabetes mellitus , preeclampsia , and hypertension . We examined the association between uric acid and elevated blood pressure in a large , nationally representative cohort of US adolescents , a population with a relatively low prevalence of cardiovascular disease and cardiovascular disease risk factors . Among 6036 adolescents 12 to 17 years of age examined in the 1999–2006 National Health and Nutrition Examination Survey , the mean age was 14.5 years , 17 % were obese ( body mass index : ≥95th percentile ) , and 3.3 % had elevated blood pressure . Mean serum uric acid level was 5.0 mg/dL , and 34 % had a uric acid level ≥5.5 mg/dL. In analyses adjusted for age , sex , race/ethnicity , and body mass index percentile , the odds ratio of elevated blood pressure , defined as a systolic or diastolic blood pressure ≥95th percentile for age , sex , and height , for each 0.1-mg/dL increase in uric acid level was 1.38 ( 95 % CI : 1.16–1.65 ) . Compared with < 5.5 mg/dL , participants with a uric acid level ≥5.5 mg/dL had a 2.03 times higher odds of having elevated blood pressure ( 95 % CI : 1.38–3.00 ) . In conclusion , increasing levels of serum uric acid are associated with elevated blood pressure in healthy US adolescents . Additional prospect i ve studies and clinical trials are needed to determine whether uric acid is merely a marker in a complex metabolic pathway or causal of hypertension and , thus , a potential screening and therapeutic target Output:	The drug class effect of SUA reduction suggesting SGLT2 inhibitors might be beneficial for diabetic patients with hyperuricemia
MS22209	*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 Many women discontinue their use of hormonal contraception , and even those who continue so may have difficulty using oral contraceptive pills consistently . New delivery systems , including the vaginal ring , may be easier to use , but user acceptability and satisfaction with these new methods may be affected by women 's experience with their bodies . MATERIAL S AND METHODS Data for this study were collected as part of a r and omized clinical trial on 201 women comparing immediate start of vaginal ring use with immediate start of low-dose oral contraceptive use . We assessed user satisfaction and method continuation 3 months after ring or pill initiation . RESULTS At 3 months , 174 of 201 subjects ( 87 % ) had follow-up interviews . Among the 174 study participants with follow-up data , 61 % of ring subjects and 34 % of pill subjects were very satisfied with their methods ( p=.003 ) . For posttrial contraception , 79 % of ring subjects chose to continue with the ring whereas 59 % of pill subjects chose to continue with the pill ( p<.001 ) . Women who reported greater comfort in touching their genitals , greater frequency of masturbation , more comfort with intercourse and past use of vaginal contraceptives and products were not more likely than others to be satisfied with the ring or to continue using it for birth control . CONCLUSION Women who were allocated to vaginal ring use , regardless of their baseline characteristics or behavior , were likely to be highly satisfied with the method and to continue its use This was an open-label multicenter study to compare the cycle control and effect on well-being of two oral contraceptives containing gestodene and one containing desogestrel . A total of 2419 healthy women ≤ 41 years of age were r and omized to receive oral contraceptives containing monophasic gestodene ( Minulet ® ; n = 806 , mean age 24.5 years ) , triphasic gestodene ( Tri-Minulet ® ; n = 808 , mean age 24.6 years ) or monophasic desogestrel ( Mercilon ® ; n = 805 , mean age 24.6 years ) . Subjects were to participate in the study for up to 13 treatment cycles . A modified Moos Menstrual Distress Question naire was used to evaluate menstrual symptoms and to assess overall well-being . A total of 698 women were withdrawn from the study , 154 due to adverse events . Cycle control with gestodene was superior to that with desogestrel at almost all time points , particularly for breakthrough bleeding and /or spotting , which occurred significantly less frequently with gestodene than with desogestrel at cycles 1–1 and 9–11 ( p < 0.05 ) . Generally , the proportion of subjects with breakthrough bleeding and /or spotting was almost twice as great with desogestrel as with gestodene . The duration of bleeding was not consistently different between the gestodene and desogestrel groups ; however , the intensity of bleeding was greater with gestodene at all time points ( p < 0.05 ) . The latent period before withdrawal bleeding was significantly longer for monophasic gestodene at cycles 1–5 and 8–10 ( p < 0.05 ) . Treatment significantly improved overall well-being at cycles 6 and 9 with triphasic gestodene and at cycle 13 with desogestrel ; however , no statistically significant differences among treatment groups in overall well-being scores or individual factors of well-being could be identified . All three treatments were well tolerated . The most common drug-related adverse events were headache ( 14.2 % ) , breast pain ( 6.2 % ) , nausea ( 4.1 % ) , metrorrhagia ( 5.9 % ) and abdominal pain ( 3.5 % ) . The incidence of adverse events in all treatment groups was similar , with the exception of metrorrhagia , which occurred in more patients in the desogestrel group than in the gestodene treatment groups ( p < 0.05 ) The early days of oral contraceptives showed some evidence that these medications may have caused undesirable side effects on the voice , mainly in terms of virilization . In a r and om study carried out at the university hospitals of Jena and Berlin ( Charité ) , two more recent drugs were tested in this regard , one containing cyproterone acetate ( Diane-35 ) and the other one levonorgestrel ( Microgynon ) , both from Schering . Ninety-one patients took part in extensive clinical and instrumental phoniatric investigations of voice function over a period of one year . No significant side effects on the voice could be proven for the two preparations . Gynecological and clinical effects of both Diane-35 and Microgynon were similar during the one-year study period . Women taking Diane-35 had less intracyclic bleedings and amenorrhea . Also , acne was more favorably influenced by Diane-35 The aim of this study was to compare contraceptive reliability , cycle control , and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol ( EE2 ) and 75 micrograms gestodene ( GSD ) , with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol . A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive . For the 20 micrograms EE2 preparation , 47.4 % of all women reported spotting at least once over a period of 12 treatment cycles , whereas this figure was 35.5 % for the 30 micrograms EE2 pill ( p < 0.05 ) . However , the incidence was within a range that corresponds to that of other OCs . The cumulative breakthrough bleeding rates ( at least once during the one year of treatment ) of 14.5 % ( 20 micrograms EE2 ) and 11.8 % ( 30 micrograms EE2 ) of women were not significantly different . In relation to all cycles , the intermenstrual bleeding rates were remarkably lower , indicating that the majority of the volunteers experienced such events only in few cycles under treatment : the spotting rate was 11.5 % ( 20 micrograms EE2 ) and 7.2 % ( 30 micrograms EE2 ) of all cycles , and the breakthrough bleeding rate was 2.6 % and 1.6 % of all cycles , respectively . Three pregnancies were recorded during the study ( one in the 20 micrograms EE2 + 75 micrograms GSD group , two in the 30 micrograms EE2 + 75 micrograms GSD group ) . All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect . The influence of both treatments on the blood pressure and body weight proved to be extremely slight . Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent . The discontinuation rate due to adverse events , including intermenstrual bleeding , was low ( 9.8 % for 20 micrograms EE2 + 75 micrograms GSD , and 7.2 % for 30 micrograms EE2 + 75 micrograms GSD ) and was in the lower range known for other oral contraceptives . Both preparations were well accepted by the volunteers . The data obtained demonstrate clinical ly acceptable cycle control , good tolerance , and a high st and ard of contraceptive reliability for both drugs . Prescription of the 20 micrograms EE2 preparation could be the first-line therapy in order to provide the lowest amount of EE2 possible . In case of persistent cycle control problems , a switch to the 30 micrograms EE2 drug should be considered BACKGROUND The aim of this prospect i ve study was to evaluate the changes in olfactory sensitivity of oral contraceptive ( pill ) users . METHODS Sixty women underwent rhinomanometric and olfactometric determinations during the follicular , periovular and luteal phases of the menstrual cycle , and at day 7 , 14 and 21 of contraceptive intake . Thirty-one women used 30 microg ethinyl oestradiol plus 75 microg gestodene and 29 women used 20 microg ethinyl oestradiol plus 150 microg desogestrel . RESULTS Rhinomanometry showed higher but not statistically significant values during the periovular phase than in the follicular and luteal phases . Olfactometry showed a higher sensitivity during the follicular and periovular phases than during the luteal phase of the menstrual cycle . The rhinomanometric surveys in pill users were statistically different from those of the luteal phase ( P < 0.02 ) and the follicular and periovular phases ( P < 0.001 ) . The olfactometric thresholds during the period of contraceptive use were statistically different from those of the follicular phase for a few odorous substances , and from those of the periovular phase for each odorous substance , but similar to those of the luteal phase ( P = NS ) . CONCLUSIONS Unlike the rhinomanometric airflow and trans-nasal pressure , the olfactory threshold to odours seems to depend on the variations of the ovarian steroids during the menstrual cycle and on the iatrogenic effects of oral contraceptives OBJECTIVE -- To describe the technique of hysterosalpingography with endocervical placement of the balloon of the catheter rather than endometrial placement . PATIENTS -- 48 consecutive patients undergoing hysterosalpingography in the course of infertility work-up at a university hospital . METHOD -- With the patient in the lithotomy position , the cervix is visualized and cleansed . The catheter and balloon are inserted in the cervical canal and inflated with the contrast agent . The contrast agent is injected slowly at low pressure , and three to six spot films are obtained . Only gentle traction can be applied by this method , so oblique views are obtained early in the examination . RESULTS -- Balloon placement was atraumatic . Although good views were obtained more frequently than with traditional techniques , about one-quarter of the studies were unsatisfactory . CONCLUSION -- This method is easy , atraumatic , and allows excellent visualization of the entire endometrial cavity and upper intracervical canal A r and omised cross-over trial was performed to compare the pharmacodynamic actions of three low-dose oral contraceptives ( OCs ) : Marvelon ( 150 micrograms desogestrel (DSG)+ 30 micrograms ethinyloestradiol ( EE ) ) , Mercilon ( 150 micrograms DSG + 20 micrograms EE ) and Microgynon ( 150 micrograms levonorgestrel ( LNG ) + 30 micrograms EE ) . None of the OCs produced any significant changes in serum cholesterol , LDL-C and apoprotein B. Triglycerides were increased by the desogestrel OCs but not by Microgynon . The latter however increased the glucose and insulin responses to a glucose tolerance test whereas Marvelon and Mercilon had no effect . HDL-C increased with Marvelon , was unchanged with Mercilon and was decreased with Microgynon . Apoprotein AII was increased by all three OCs but only the DSG OCs increased apoprotein AI . All OCs produced similar increases in caeruloplasmin but the increase in SHBG was much greater with Marvelon and Mercilon than with Microgynon . Testosterone was reduced more with Microgynon than with the DSG OCs . Many of the changes reflect the strong anti-oestrogenic action of LNG on metabolic parameters compared to DSG . Except for the effect on HDL-C , there was little difference between Marvelon and Mercilon on metabolic parameters and this complements the findings from large-scale clinical trials of the two OCs . Mercilon , therefore provides a very satisfactory alternative to Marvelon OBJECTIVES Our purpose was to define the frequency and reasons for oral contraceptive discontinuation and subsequent contraceptive behavior . STUDY DESIGN A nationwide prospect i ve study of 1657 women initiating or switching to the use of a new contraceptive from private practice s , clinics , and a health maintenance organization was performed . RESULTS Six months after a new oral contraceptive prescription , 68 % of new starts and 84 % of switchers still used oral contraceptives . Of women who discontinued , 46 % did so because of side effects , whereas 23 % had no continuing need . More than four fifths of women who discontinued oral contraceptives but remained at risk of unintended pregnancy either failed to adopt another method or adopted a less effective method . Fifteen percent of women who discontinued oral contraceptives resumed their use within the 7-month follow-up period . CONCLUSIONS Counseling should emphasize the possibility of side effects , stressing the fact that most will be transient , and the need to identify a backup method . Follow-up visits should be scheduled for 1 to 2 months after a prescription is written In a double-blind , controlled , r and omized , four-arm , bicentric clinical study , the effect of four oral contraceptives ( OCs ) on thyroid hormone parameters , cortisol , aldosterone , endothelin-1 and angiotensin II was investigated . Four groups composed of 25 volunteers each ( ages between 18 and 35 years ) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol ( EE ) + 2 mg dienogest ( DNG ) ( 30EE/DNG ) , 20 microg EE + 2 mg DNG ( 20EE/DNG ) , 10 microg EE + 2 mg estradiol valerate ( EV ) + 2 mg DNG ( EE/EV/DNG ) or 20 microg EE + 100 microg levonorgestrel ( LNG ) ( EE/L Output:	MAIN RESULTS No differences were found in contraceptive effectiveness for the 13 COC pairs for which this outcome was reported . Compared to the higher-estrogen pills , several COCs containing 20 μg EE result ed in higher rates of early trial discontinuation ( overall and due to adverse events such as irregular bleeding ) as well as increased risk of bleeding disturbances ( both amenorrhea or infrequent bleeding and irregular , prolonged , frequent bleeding , or breakthrough bleeding or spotting ) . Low-dose estrogen COCs result ed in higher rates of bleeding pattern disruptions .
MS22210	*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 — Prior small to modest-sized studies suggest a benefit of intravascular ultrasound ( IVUS ) guidance in noncomplex lesions . Whether IVUS guidance is associated with improved clinical outcomes after drug-eluting stent ( DES ) implantation in an unrestricted patient population is unknown . Methods and Results — Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents ( ADAPT-DES ) was a prospect i ve , multicenter , nonr and omized “ all-comers ” study of 8583 consecutive patients at 11 international centers design ed to determine the frequency , timing , and correlates of stent thrombosis and adverse clinical events after DES . Propensity-adjusted multivariable analysis was performed to examine the relationship between IVUS guidance and 1-year outcomes . IVUS was utilized in 3349 patients ( 39 % ) , and larger-diameter devices , longer stents , and /or higher inflation pressures were used in 74 % of IVUS-guided cases . IVUS guidance compared with angiography guidance was associated with reduced 1-year rates of definite/probable stent thrombosis ( 0.6 % [ 18 events ] versus 1.0 % [ 53 events ] ; adjusted hazard radio , 0.40 ; 95 % confidence interval , 0.21–0.73 ; P=0.003 ) , myocardial infa rct ion ( 2.5 % versus 3.7 % ; adjusted hazard radio , 0.66 ; 95 % confidence interval , 0.49–0.88 ; P=0.004 ) , and composite adjudicated major adverse cardiac events ( ie , cardiac death , myocardial infa rct ion , or stent thrombosis ) ( 3.1 % versus 4.7 % ; adjusted hazard radio , 0.70 ; 95 % confidence interval , 0.55–0.88 ; P=0.002 ) . The benefits of IVUS were especially evident in patients with acute coronary syndromes and complex lesions , although significant reductions in major adverse cardiac events were present in all patient subgroups those with including stable angina and single-vessel disease . Conclusions — In ADAPT-DES , the largest study of IVUS use to date , IVUS guidance was associated with a reduction in stent thrombosis , myocardial infa rct ion , and major adverse cardiac events within 1 year after DES implantation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00638794 OBJECTIVES This study sought to assess the impact of intravascular ultrasound ( IVUS ) guidance on clinical outcomes following drug-eluting stent implantation when treating long lesions . BACKGROUND The role of IVUS guidance when treating long lesions has been tested during bare-metal stent , but not during drug-eluting stent , implantation . METHODS A total of 543 patients treated with stents ≥ 28 mm in length were r and omly assigned to IVUS guidance ( n = 269 ) versus angiography guidance ( n = 274 ) . The primary endpoint was a composite of major adverse cardiac events ( MACE ) , including cardiovascular death , myocardial infa rct ion , target vessel revascularization , or stent thrombosis at 1 year following intervention . RESULTS In the intention-to-treat analysis , total stent length was 32.4 mm in the IVUS-guided arm versus 32.3 mm in angiography-guided arm ( p = 0.84 ) . Adjunct post-dilation was more frequently performed in the IVUS-guided arm ( 54.6 % vs. 44.5 % , p = 0.03 ) ; post-intervention minimal lumen diameters were similar ( 2.55 vs. 2.55 mm , respectively , p = 0.50 ) ; and MACE occurred in 12 ( 4.5 % ) patients in IVUS-guided arm and in 20 ( 7.3 % ) patients in the angiography-guided arm ( p = 0.16 ) . However , among the 269 patients assigned to IVUS guidance , IVUS was not used in 13 patients ( 4.8 % ) ; conversely , in 274 patients assigned to angiography alone , 41 patients ( 15.0 % ) were treated with IVUS guidance . Therefore , in a per- protocol analysis according to actual IVUS usage , minimum lumen diameter was larger ( 2.58 vs. 2.51 mm , p = 0.04 ) , and MACE rates were lower : 4.0 % in the IVUS-guided arm versus 8.1 % in the angiography-guided arm ( p = 0.048 ) . CONCLUSIONS A strategy of routine IVUS for drug-eluting stent implantation in long lesions did not improve the 1-year MACE rates . The IVUS use per operator decision was associated with improved results . ( A New Strategy Regarding Discontinuation of Dual Antiplatelet ; NCT01145079 ) BACKGROUND No r and omized studies have thus far evaluated intravascular ultrasound ( IVUS ) guidance in the drug-eluting stent ( DES ) era . The aim was to evaluate if IVUS optimized DES implantation was superior to angiographic guidance alone in complex lesions . METHODS R and omized , multicentre , international , open label , investigator-driven study evaluating IVUS vs angiographically guided DES implantation in patients with complex lesions ( defined as bifurcations , long lesions , chronic total occlusions or small vessels ) . Primary study endpoint was post-procedure in lesion minimal lumen diameter . Secondary end points were combined major adverse cardiac events ( MACE ) , target lesion revascularization , target vessel revascularization , myocardial infa rct ion ( MI ) , and stent thrombosis at 1 , 6 , 9 , 12 , and 24 months . RESULTS The study included 284 patients . No significant differences were observed in baseline characteristics . The primary study end point showed a statistically significant difference in favor of the IVUS group ( 2.70 mm ± 0.46 mm vs. 2.51 ± 0.46 mm ; P = .0002 ) . During hospitalization , no patient died , had repeated revascularization , or a Q-wave MI . No difference was observed in the occurrence of non-Q wave MI ( 6.3 % in IVUS vs. 7.0 % in angio-guided group ) . At 24-months clinical follow-up , no differences were still observed in cumulative MACE ( 16.9%vs . 23.2 % ) , cardiac death ( 0%vs . 1.4 % ) , MI ( 7.0%vs . 8.5 % ) , target lesion revascularization ( 9.2 % vs. 11.9 % ) or target vessel revascularization ( 9.8 % vs. 15.5 % ) , respectively in the IVUS vs. angio-guided groups . In total , only one definite subacute stent thrombosis occurred in the IVUS group . CONCLUSIONS A benefit of IVUS optimized DES implantation was observed in complex lesions in the post-procedure minimal lumen diameter . No statistically significant difference was found in MACE up to 24 months Background The importance of intravascular ultrasound (IVUS)-guided stenting of the unprotected left main coronary artery ( ULMCA ) remains controversial and has not been fully studied in the subset of patients with ULMCA . This study evaluated the clinical outcome of IVUS-guided stenting using a drug-eluting stent for ULMCA . Methods A total of 1,016 consecutive patients with ULMCA stenosis who underwent drug-eluting stent implantation from January 2006 to December 2011 were prospect ively registered . The primary endpoint of this nonr and omized registry was the rate of one-year major adverse cardiac events ( MACE , including cardiac death , myocardial infa rct ion , and target vessel revascularization ) . Stent thrombosis served as the safety endpoint . Propensity score matching was used to calculate the adjusted event rate . Results The unadjusted one-year MACE rate was 14.8 % in the IVUS-guided group ( n=337 , 33.2 % ) , significantly different from the 27.7 % ( P<0.001 ) in the angiography-guided group ( n=679 , 66.8 % ) . After propensity score matching , 291 paired patients were matched between the two groups , and the difference in one-year MACE between IVUS-guided ( 16.2 % ) versus angiography-guided ( 24.4 % ) groups was still significant ( P=0.014 ) , mainly driven by decreased rates of cardiac death ( 1.7 % ) and target vessel revascularization ( 3.4 % ) in the IVUS-guided group when compared with 5.2 % ( P=0.023 ) and 10.0 % ( P=0.002 ) in the angiography-guided group , respectively . Although it did not reach significance ( P=0.075 ) , the adjusted one-year rate of stent thrombosis in the angiography-guided group was higher than in the IVUS-guided group . Conclusion Compared with angiography guidance , IVUS-guided treatment of ULMCA using a drug-eluting stent was associated with a significant reduction of one-year cardiac death and target vessel revascularization , result ing in less frequent one-year MACE after propensity score matching OBJECTIVES This study sought to report the final 5 years follow-up of the l and mark LEADERS ( Limus Eluted From A Durable Versus ERodable Stent Coating ) trial . BACKGROUND The LEADERS trial is the first r and omized study to evaluate biodegradable polymer-based drug-eluting stents ( DES ) against durable polymer DES . METHODS The LEADERS trial was a 10-center , assessor-blind , noninferiority , " all-comers " trial ( N = 1,707 ) . All patients were central ly r and omized to treatment with either biodegradable polymer biolimus-eluting stents ( BES ) ( n = 857 ) or durable polymer sirolimus-eluting stents ( SES ) ( n = 850 ) . The primary endpoint was a composite of cardiac death , myocardial infa rct ion ( MI ) , or clinical ly indicated target vessel revascularization within 9 months . Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis ( ST ) ( Academic Research Consortium definition ) . Analysis was by intention to treat . RESULTS At 5 years , the BES was noninferior to SES for the primary endpoint ( 186 [ 22.3 % ] vs. 216 [ 26.1 % ] , rate ratio [ RR ] : 0.83 [ 95 % confidence interval ( CI ) : 0.68 to 1.02 ] , p for noninferiority < 0.0001 , p for superiority = 0.069 ) . The BES was associated with a significant reduction in the more comprehensive patient-orientated composite endpoint of all-cause death , any MI , and all-cause revascularization ( 297 [ 35.1 % ] vs. 339 [ 40.4 % ] , RR : 0.84 [ 95 % CI : 0.71 to 0.98 ] , p for superiority = 0.023 ) . A significant reduction in very late definite ST from 1 to 5 years was evident with the BES ( n = 5 [ 0.7 % ] vs. n = 19 [ 2.5 % ] , RR : 0.26 [ 95 % CI : 0.10 to 0.68 ] , p = 0.003 ) , corresponding to a significant reduction in ST-associated clinical events ( primary endpoint ) over the same time period ( n = 3 of 749 vs. n = 14 of 738 , RR : 0.20 [ 95 % CI : 0.06 to 0.71 ] , p = 0.005 ) . CONCLUSIONS The safety benefit of the biodegradable polymer BES , compared with the durable polymer SES , was related to a significant reduction in very late ST ( > 1 year ) and associated composite clinical outcomes . ( Limus Eluted From A Durable Versus ERodable Stent Coating [ LEADERS ] trial ; NCT00389220 ) Objective : To assess the role of the intravascular ultrasound ( IVUS ) during implantation of Drug‐eluting stents ( DES ) on long‐term outcome in patients with complex coronary artery disease and high clinical risk profile with special attention to the development of late stent thrombosis ( LST ) . Methods : Two hunderd and ten patients were r and omly assigned to receive DES either with ( N = 105 ) or without ( N = 105 ) the IVUS guidance . Dual antiplatelet treatment was administered for 6 months in all patients . At 18‐month follow‐up , the rates of Major adverse cardiac events ( MACEs ) ( death , myocardial infa rct ion , and reintervention ) were assessed in both groups with special attention to possible LST . Stent thrombosis was classified according to Academic Research Consortium ( ARC ) . Results : At the 18‐month follow‐up , there was no significant difference between both groups regarding MACE ( 11 % vs. 12 % ; P = NS ) . Stent thrombosis has occurred in four patients ( 3.8 % ) in the group with and in 6 patients ( 5.7 % ; P = NS ) in the group without the IVUS guidance . Conclus Output:	Conclusions IVUS guidance was associated with improved clinical outcomes , especially in patients with complex lesions admitted with ACS .
MS22211	*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: Generalized anxiety disorder ( GAD ) is a chronic anxiety disorder , associated with comorbidity and impairment in quality of life , for which improved psychosocial treatments are needed . GAD is also associated with reactivity to and avoidance of internal experiences . The current study examined the efficacy of an acceptance-based behavioral therapy aim ed at increasing acceptance of internal experiences and encouraging action in valued domains for GAD . Clients were r and omly assigned to immediate ( n = 15 ) or delayed ( n = 16 ) treatment . Acceptance-based behavior therapy led to statistically significant reductions in clinician-rated and self-reported GAD symptoms that were maintained at 3- and 9-month follow-up assessment s ; significant reductions in depressive symptoms were also observed . At posttreatment assessment 78 % of treated participants no longer met criteria for GAD and 77 % achieved high end-state functioning ; these proportions stayed constant or increased over time . As predicted , treatment was associated with decreases in experiential avoidance and increases in mindfulness Background : Mindfulness-based stress reduction ( MBSR ) proposes a systematic program for reduction of suffering associated with a wide range of medical conditions . Studies suggest improvements in general aspects of well-being , including quality of life ( QoL ) , coping and positive affect , as well as decreased anxiety and depression . Methods : A quasi-experimental study examined effects of an 8-week MBSR intervention among 58 female patients with fibromyalgia ( mean , 52 ± 8 years ) who underwent MBSR or an active social support procedure . Participants were assigned to groups by date of entry , and 6 subjects dropped out during the study . Self-report measures were vali date d German inventories and included the following scales : visual analog pain , pain perception , coping with pain , a symptom checklist and QoL. Pre- and postintervention measurements were made . Additionally , a 3-year follow-up was carried out on a subgroup of 26 participants . Results : Pre- to postintervention analyses indicated MBSR to provide significantly greater benefits than the control intervention on most dimensions , including visual analog pain , QoL subscales , coping with pain , anxiety , depression and somatic complaints ( Cohen d effect size , 0.40–1.10 ) . Three-year follow-up analyses of MBSR participants indicated sustained benefits for these same measures ( effect size , 0.50–0.65 ) . Conclusions : Based upon a quasi-r and omized trial and long-term observational follow-up , results indicate mindfulness intervention to be of potential long-term benefit for female fibromyalgia patients The purpose of this study was to gather data on the efficacy of a newly developed psychosocial group intervention for cancer patients , called mindfulness-based art therapy ( MBAT ) . One hundred and eleven women with a variety of cancer diagnoses were paired by age and r and omized to either an eight-week MBAT intervention group or a wait-list control group . Ninety-three participants ( 84 % ) completed both the pre- and post- study measurements . As compared to the control group , the MBAT group demonstrated a significant decrease in symptoms of distress ( as measured by the Symptoms Checklist-90-Revised ) and significant improvements in key aspects of health-related quality of life ( as measured by the Medical Outcomes Study Short-Form Health Survey ) . This investigation of MBAT provides initial encouraging data that support a possible future role for the intervention as a psychosocial treatment option for cancer patients Recovered recurrently depressed patients were r and omized to treatment as usual ( TAU ) or TAU plus mindfulness-based cognitive therapy ( MBCT ) . Replicating previous findings , MBCT reduced relapse from 78 % to 36 % in 55 patients with 3 or more previous episodes ; but in 18 patients with only 2 ( recent ) episodes corresponding figures were 20 % and 50 % . MBCT was most effective in preventing relapses not preceded by life events . Relapses were more often associated with significant life events in the 2-episode group . This group also reported less childhood adversity and later first depression onset than the 3-or-more-episode group , suggesting that these groups represented distinct population s. MBCT is an effective and efficient way to prevent relapse/recurrence in recovered depressed patients with 3 or more previous episodes This study evaluated mindfulness-based cognitive therapy ( MBCT ) , a group intervention design ed to train recovered recurrently depressed patients to disengage from dysphoria-activated depressogenic thinking that may mediate relapse/recurrence . Recovered recurrently depressed patients ( n = 145 ) were r and omized to continue with treatment as usual or , in addition , to receive MBCT . Relapse/recurrence to major depression was assessed over a 60-week study period . For patients with 3 or more previous episodes of depression ( 77 % of the sample ) , MBCT significantly reduced risk of relapse/recurrence . For patients with only 2 previous episodes , MBCT did not reduce relapse/recurrence . MBCT offers a promising cost-efficient psychological approach to preventing relapse/recurrence in recovered recurrently depressed patients OBJECTIVE To assess the effect of a meditation training program , Mindfulness-Based Stress Reduction ( MBSR ) , on depressive symptoms , psychological status , and disease activity in patients with rheumatoid arthritis ( RA ) through a r and omized , waitlist-controlled pilot study . METHODS Participants were r and omized to either an MBSR group , where they attended an 8-week course and 4-month maintenance program , or to a waitlist control group , where they attended all assessment visits and received MBSR free of charge after study end . Participants received usual care from their rheumatologists throughout the trial . Self-report question naires were used to evaluate depressive symptoms , psychological distress , well-being , and mindfulness . Evaluation of RA disease activity ( by Disease Activity Score in 28 joints ) included examination by a physician masked to treatment status . Adjusted means and mean changes in outcomes were estimated in mixed model repeated measures analyses . RESULTS Sixty-three participants were r and omized : 31 to MBSR and 32 to control . At 2 months , there were no statistically significant differences between groups in any outcomes . At 6 months , there was significant improvement in psychological distress and well-being ( P = 0.04 and P = 0.03 , respectively ) , and marginally significant improvement in depressive symptoms and mindfulness ( P = 0.08 and P = 0.09 , respectively ) . There was a 35 % reduction in psychological distress among those treated . The intervention had no impact on RA disease activity . CONCLUSION An 8-week MBSR class was not associated with change in depressive symptoms or other outcomes at 2-month followup . Significant improvements in psychological distress and well-being were observed following MBSR plus a 4-month program of continued reinforcement . Mindfulness meditation may complement medical disease management by improving psychological distress and strengthening well-being in patients with RA OBJECTIVE To test the short and longterm benefits of an 8 week mind-body intervention that combined training in mindfulness meditation with Qigong movement therapy for individuals with fibromyalgia syndrome ( FM ) . METHODS A total of 128 individuals with FM were r and omly assigned to the mind-body training program or an education support group that served as the control . Outcome measures were pain , disability ( Fibromyalgia Impact Question naire ) , depression , myalgic score ( number and severity of tender points ) , 6 minute walk time , and coping strategies , which were assessed at baseline and at 8 , 16 , and 24 weeks . RESULTS Both groups registered statistically significant improvements across time for the Fibromyalgia Impact Question naire , Total Myalgic Score , Pain , and Depression , and no improvement in the number of feet traversed in the 6 minute walk . However , there was no difference in either the rate or magnitude of these changes between the mind-body training group and the education control group . Salutary changes occurring by the eighth week ( which corresponded to the end of the mind-body and education control group sessions ) were largely maintained by both groups throughout the 6 month followup period . CONCLUSION While both groups showed improvement on a number of outcome variables , there was no evidence that the multimodal mind-body intervention for FM was superior to education and support as a treatment option . Additional r and omized controlled trials are needed before interventions of this kind can be recommended for treatment of FM & NA ; The objectives of this pilot study were to assess the feasibility of recruitment and adherence to an eight‐session mindfulness meditation program for community‐dwelling older adults with chronic low back pain ( CLBP ) and to develop initial estimates of treatment effects . It was design ed as a r and omized , controlled clinical trial . Participants were 37 community‐dwelling older adults aged 65 years and older with CLBP of moderate intensity occurring daily or almost every day . Participants were r and omized to an 8‐week mindfulness‐based meditation program or to a wait‐list control group . Baseline , 8‐week and 3‐month follow‐up measures of pain , physical function , and quality of life were assessed . Eighty‐nine older adults were screened and 37 found to be eligible and r and omized within a 6‐month period . The mean age of the sample was 74.9 years , 21/37 ( 57 % ) of participants were female and 33/37 ( 89 % ) were white . At the end of the intervention 30/37 ( 81 % ) participants completed 8‐week assessment s. Average class attendance of the intervention arm was 6.7 out of 8 . They meditated an average of 4.3 days a week and the average minutes per day was 31.6 . Compared to the control group , the intervention group displayed significant improvement in the Chronic Pain Acceptance Question naire Total Score and Activities Engagement subscale ( P = .008 , P = .004 ) and SF‐36 Physical Function ( P = .03 ) . An 8‐week mindfulness‐based meditation program is feasible for older adults with CLBP . The program may lead to improvement in pain acceptance and physical function Objective The objective of this study was to assess the effects of participation in a mindfulness meditation – based stress reduction program on mood disturbance and symptoms of stress in cancer out patients . Methods A r and omized , wait-list controlled design was used . A convenience sample of eligible cancer patients enrolled after giving informed consent and were r and omly assigned to either an immediate treatment condition or a wait-list control condition . Patients completed the Profile of Mood States and the Symptoms of Stress Inventory both before and after the intervention . The intervention consisted of a weekly meditation group lasting 1.5 hours for 7 weeks plus home meditation practice . Results Ninety patients ( mean age , 51 years ) completed the study . The group was heterogeneous in type and stage of cancer . Patients ’ mean preintervention scores on dependent measures were equivalent between groups . After the intervention , patients in the treatment group had significantly lower scores on Total Mood Disturbance and subscales of Depression , Anxiety , Anger , and Confusion and more Vigor than control subjects . The treatment group also had fewer overall Symptoms of Stress ; fewer Cardiopulmonary and Gastrointestinal symptoms ; less Emotional Irritability , Depression , and Cognitive Disorganization ; and fewer Habitual Patterns of stress . Overall reduction in Total Mood Disturbance was 65 % , with a 31 % reduction in Symptoms of Stress . Conclusions This program was effective in decreasing mood disturbance and stress symptoms in both male and female patients with a wide variety of cancer diagnoses , stages of illness , and ages Summary : Heart disease is the leading cause of death among Americans each year , yet the misperception still exists that cardiovascular disease is not a serious health problem for women . Evidence indicates that anxiety contributes to the development of heart disease . The primary purpose of this study was to assess the effectiveness of Kabat-Zinn 's mindfulness-based stress reduction program to reduce anxiety in women with heart disease . Anxiety , emotional control , coping styles , and health locus of control were compared in a treatment and control group of women with heart disease . Post-intervention analyses provide initial support for beneficial effects of this program OBJECTIVE Depressive symptoms are common among patients with fibromyalgia , and behavioral intervention has been recommended as a major treatment component for this illness . The objective of this study was to test the effects of the Mindfulness-Based Stress Reduction ( MBSR ) intervention on depressive symptoms in patients with fibromyalgia . METHODS This r and omized controlled trial examined effects of the 8-week MBSR intervention on depressive symptoms in 91 women with fibromyalgia who were r and omly assigned to treatment ( n = 51 ) or a waiting-list control group ( n = 40 ) . Eligible patients were at least 18 years old , willing to participate in a weekly group , and able to provide physician verification of a fibromyalgia diagnosis . Of 166 eligible participants who responded to local television news publicizing , 49 did not appear for a scheduled intake , 24 enrolled but did not provide baseline data , and 2 were excluded due to severe mental illness , leaving 91 participants . The sample averaged 48 years of age and had 14.7 years of education . The typical participant was white , married , and employed . Patients r and omly assigned to treatment received MBSR . Eight weekly 2.5-hour sessions were led by a licensed clinical psychologist with mindfulness training . Somatic and cognitive symptoms of depression were assessed using the Beck Depression Inventory administered at baseline , immediately postprogram , and at followup 2 months after the conclusion of the intervention . RESULTS Change in depressive symptoms was assessed using slopes analyses of intervention effects over time . Depressive symptoms improved significantly in treatment versus control participants over the 3 assessment s. CONCLUSION This meditation-based intervention alleviated Output:	It can be concluded that MBSR has small effects on depression , anxiety and psychological distress in people with chronic somatic diseases . Integrating MBSR in behavioral therapy may enhance the efficacy of mindfulness based interventions
MS22212	*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 interviewed 327 women who had been 50 to 74 years of age when treated for fracture of the hip of lower forearm , to determine their use ( or lack of use ) of estrogen preparations . Their responses were compared with those in a r and om sample of 567 women who were of similar age and from the same region . The risk of fracture was 50 to 60 per cent lower in women who had used these drugs for six years or longer than in women who hadnot used them ( 95 per cent confidence interval of relative risk , 0.3 to 0.6 ) ; those using them for shorter periods received less benefit , if any . A decreased risk of fracture was clearly evident only in women still taking estrogens and evident at either common daily dose ( 0.625 and 1.25 mg ) . In conjunction with the finding that estrogens can retard the development of osteoporosis in postmenopausal women , our data argue that lowering of the risk of hip and forearm fractures must be weighed as a benefit of long-term estrogen use Summary To develop an improved treatment schedule for osteoporosis , a study was undertaken in 100 postmenopausal women using a modified ADFR 90-day cyclical regimen with etidronate . After one year of treatment , the etidronate-treated group showed a significant increase in bone density of the spine , which continued over the following 2 years of treatment and remained stable during the fourth year . In contrast , in the non-etidronate group , bone density decreased significantly after four years . In addition , the fracture rate was significantly lower in the etidronate group than in the non-etidronate group . Side effects were minimal in both groups and no serious adverse reactions were reported . In conclusion , it appears that a cyclical regimen using 1,25-dihydroxyvitamin D3 , etidronate and calcium increases bone mass and reduces fractures with no significant side effects , thus making a useful contribution in the treatment of postmenopausal osteoporosis OBJECTIVE : To define the effects of therapeutic exercise on bone density and back complaints . METHODS : A r and omised controlled trial with parallel groups was conducted in an outpatient clinic , Medical School , University of Vienna . Ninety two sedentary post-menopausal women with back problems were r and omly allocated to either exercise ( groups 1 and 2 ) or control ( group 3 , no exercise , n = 31 ) ; the exercise group was retrospectively subdivided into compliant ( group 1 , n = 27 ) and not fully compliant patients ( group 2 , n = 34 ) . Regular , initially supervised therapeutic exercise aim ed at restoring biomechanical function was performed for four years . Bone density in the forearm was measured by single photon absorptiometry at entry and after four years ; subjective back complaints were documented . RESULTS : A significant decrease in bone density was observed in groups 2 and 3 ; no change was noted in group 1 ; back complaints decreased in group 1 only . CONCLUSIONS : Sedentary postmenopausal women may benefit from regular long term therapeutic exercise in terms of subjective back complaints and slowed loss of bone mass A population -based case-control study was conducted to examine the effects of past and recent physical activity on the risk of hip fracture in women . Cases included females aged 55 - 84 years with a first diagnosis of hip fracture in 1989 in metropolitan Toronto , Canada . Controls were a population -based r and om sample frequency matched by 5-year age groups . Data were collected on 381 cases and 1,138 controls by self-administered mailed question naires or telephone interviews . Past activity was calculated as a compilation of activity scores at ages 16 , 30 , and 50 years . Recent activity was defined as activity in the past year for controls and activity in the year before fracture for cases . Multiple logistic regression was used to control for age , previous fracture , obesity , smoking , osteoporosis , epilepsy , stroke or Parkinson 's disease , daily intake of dietary calcium , and duration of use of supplemental calcium , fluoride , and estrogen . After recent activity was adjusted for , statistically significant effects were found for women who in the past had been active ( odds ratio estimate ( OR ) = 0.66 , 95 % confidence interval ( CI ) 0.45 - 0.96 ) or very active ( OR = 0.54 , 95 % CI 0.33 - 0.88 ) . After past activity was adjusted for , a similar protective effect was found for women who were moderately active recently ( OR = 0.61 , 95 % CI 0.41 - 0.90 ) , but women who were very active recently were not protected from hip fracture ( OR = 1.15 , 95 % CI 0.72 - 1.83 ) . This study showed evidence of independent protective effects of past physical activity and of moderate levels of recent physical activity on the risk of hip fracture in postmenopausal women Because of uncertainty about the place of hormones in the treatment of postmenopausal bone loss vertebral and forearm bone loss was measured by absorptiometry in early post-menopausal women before and after continuous or sequential treatment with combined oestrogen and progestogen in a double blind placebo controlled trial . Treatment with hormones significantly reversed the vertebral bone loss . The net gain in vertebral bone density amounted to 6·4 % a year with continuous supplementation and 5·4 % a year with sequential supplementation ; the net gain in forearm bone density was lower ( 3·6 % with continuous and 3·7 % with sequential supplementation ) . Before a policy of supplementation with hormones can be recommended to all postmenopausal women with the aim of reducing the incidence of vertebral crush fractures further studies with different doses and combinations of hormones , administered over several years , are needed The aims of this study were to ascertain vertebral deformity prevalence in elderly men and women and to describe the association between bone mineral density ( BMD ) at the lumbar spine and femoral neck , severity of spinal degenerative disease and vertebral deformity prevalence . We performed st and ardized spinal radiographs in a r and om sample of 300 elderly men and women participating in the Dubbo Osteoporosis Epidemiology Study , a population -based study of fracture risk factors . Radiographs were read independently by masked observers for the prevalence of vertebral deformity and severity of osteophytosis . BMD was measured by dual-energy X-ray absorptiometry . The prevalence of vertebral deformities was critically dependent on the criterion used . The less strict criteria seemed to overestimate deformities at either end of the spine region analysed . However , irrespective of the criterion used , prevalence of deformity was higher in men than in women ( 25 % vs 20 % for the 3 SD criterion , 17 % vs 12 % for the 4 SD criterion and 27 % vs 25 % for the 25 % criterion ) . Femoral neck BMD was more strongly associated with vertebral deformities than spinal BMD for the 25 % criterion ( OR/SD change in BMD 1.39 ( p=0.02 ) vs 1.20 ( p=0.19 ) ) , 3 SD criterion ( OR/SD change in BMD 1.45 ( p=0.01 ) vs 1.10 ( p=0.34 ) ) and 4 SD criterion ( OR/SD change in BMD 1.98 ( p=0.0002 ) vs 1.68 ( p=0.008 ) ) . BMD was also more strongly associated with biconcave deformities than either wedge or crush deformities and more so in men than in women . Severity of spinal osteophytosis was not associated with vertebral deformity . In conclusion , femoral neck BMD is at least equivalent to the lumbar spine BMD in strength of association with prevalent vertebral fractures . Spinal osteophytosis falsely elevates BMD without a concomitant decrease in fracture risk , indicating that any interpretation of spinal BMD needs to be adjusted for osteophytosis . These findings support the use of femoral neck bone densitometry in older men and women . Moreover , these data indicate that current criteria for radiological assessment of vertebral deformity are sufficiently loose to include a substantial proportion of non-fractures in the elderly , with important implication s for the design of clinical trials . However , irrespective of the criterion used , vertebral deformities in men are at least as common , if not more so , than in women , suggesting that vertebral osteoporotic fractures are overlooked in men OBJECTIVE Oral alendronate sodium is a potent , specific inhibitor of osteoclast-mediated bone resorption . To assess its efficacy and safety , a 3-year , r and omized , double-blind , multicenter study of 478 postmenopausal women with osteoporosis was conducted . PATIENTS AND METHODS Subjects received either placebo , alendronate 5 or 10 mg/day for 3 years , or 20 mg/day for 2 years followed by 5 mg/day for 1 year ( 20/5 mg ) . All subjects received 500 mg/day of supplemental calcium . Bone mineral density ( BMD ) was measured by dual energy x-ray absorptiometry ( DXA ) . RESULTS After 3 years , alendronate 10 mg induced marked increases in BMD of the lumbar spine ( 9.6 + /- 0.4 % ) , femoral neck ( 4.7 + /- 0.7 % ) and trochanter ( 7.4 + /- 0.6 % ) ( mean + /- SE ; each P < or = 0.001 ) versus decreases of 0.8 to 1.6 % with placebo . Progressive increases at these sites in the alendoronate 10 mg group were significant during both the second and third years . Alendronate 10 mg increased total body BMD ( 1.6 + /- 0.3 % , P < or = 0.001 ) , and prevented loss but did not increase BMD at the 1/3 forearm site . Alendronate 20/5 mg was no more effective , whereas alendronate 5 mg was significantly less effective than 10 mg at all sites . Bone turnover decreased to a stable nadir over 3 months for resorption markers ( urine deoxypyridinoline ) and over 6 months for formation markers ( alkaline phosphatase and osteocalcin ) . Mean loss of stature was reduced by 41 % in alendronate treated subjects ( P = 0.01 ) . CONCLUSION The safety profile of alendronate was similar to that of placebo . At 10 mg , there were no trends toward increased frequency of any adverse experience except for abdominal pain , which was usually mild , transient , and resolved with continued treatment . Thus , alendronate appears to be an important advance in the treatment of osteoporosis in postmenopausal women Objective To investigate the magnitude and pattern of the changes in bone mass during five years of continuous and cyclic sequential oestrogen/progestin treatment BACKGROUND Previous studies have shown that alendronate can increase bone mineral density ( BMD ) and prevent radiographically defined ( morphometric ) vertebral fractures . The Fracture Intervention Trial aim ed to investigate the effect of alendronate on the risk of morphometric as well as clinical ly evident fractures in postmenopausal women with low bone mass . METHODS Women aged 55 - 81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture . Results for women with at least one vertebral fracture at baseline are reported here . 2027 women were r and omly assigned placebo ( 1005 ) or alendronate ( 1022 ) and followed up for 36 months . The dose of alendronate ( initially 5 mg daily ) was increased ( to 10 mg daily ) at 24 months , with maintenance of the double blind . Lateral spine radiography was done at baseline and at 24 and 36 months . New vertebral fractures , the primary endpoint , were defined by morphometry as a decrease of 20 % ( and at least 4 mm ) in at least one vertebral height between the baseline and latest follow-up radiograph . Non-spine clinical fractures were confirmed by radiographic reports . New symptomatic vertebral fractures were based on self-report and confirmed by radiography . FINDINGS Follow-up radiographs were obtained for 1946 women ( 98 % of surviving participants ) . 78 ( 8.0 % ) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 ( 15.0 % ) in the placebo group ( relative risk 0.53 [ 95 % Cl 0.41 - 0.68 ] ) . For clinical ly apparent vertebral fractures , the corresponding numbers were 23 ( 2.3 % ) alendronate and 50 ( 5.0 % ) placebo ( relative hazard 0.45 [ 0.27 - 0.72 ] ) . The risk of any clinical fracture , the main secondary endpoint , was lower in the alendronate than in the placebo group ( 139 [ 13.6 % ] vs 183 [ 18.2 % ] ; relative hazard 0.72 [ 0.58 - 0.90 ] ) . The relative hazards for hip fracture and wrist fract Output:	The literature review did not identify any clinical trials of preventive counseling for osteoporosis . Current smoking has been associated with lower bone mineral density ( BMD ) and increased risk for fracture after minimal trauma in most studies ( 2 ) . In a follow-up multivariate analysis of the Study of Osteoporotic Fractures , axial BMD was positively associated with physical activity ( 53 ) .
MS22213	*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 Interleukin-6 ( IL-6 ) plays a central role in inflammation and tissue injury . However , epidemiological data evaluating the role of IL-6 in atherogenesis are sparse . METHODS AND RESULTS In a prospect i ve study involving 14 916 apparently healthy men , we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infa rct ion ( MI ) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up . Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not ( 1.81 versus 1 . 46 pg/mL ; P=0.002 ) . The risk of future MI increased with increasing quartiles of baseline IL-6 concentration ( P for trend < 0.001 ) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile ( 95 % CI 1.3 to 4.3 , P=0.005 ) ; for each quartile increase in IL-6 , there was a 38 % increase in risk (P=0.001).This relationship remained significant after adjustment for other cardiovascular risk factors , was stable over long periods of follow-up , and was present in all low-risk subgroups , including nonsmokers . Although the strongest correlate of IL-6 in these data was C-reactive protein ( r=0.43 , P<0.001 ) , the relationship of IL-6 with subsequent risk remained after control for this factor ( P<0.001 ) . CONCLUSIONS In apparently healthy men , elevated levels of IL-6 are associated with increased risk of future MI . These data thus support a role for cytokine-mediated inflammation in the early stages of atherogenesis Background Significant regression of coronary and femoral atherosclerotic lesions has been documented by angiographic studies using aggressive lipid-lowering treatment . This study tested the applicability and effects of intensive physical exercise and low-fat diet on coronary morphology and myocardial perfusion in nonselected patients with stable angina pectoris . Methods and Results Patients were recruited after routine coronary angiography for stable angina pectoris ; they were r and omized to an intervention group ( n = 56 ) and a control group on “ usual care ” ( n = 57 ) . Treatment comprised intensive physical exercise in group training sessions ( minimum , 2 hr/wk ) , daily home exercise periods ( 20 min/d ) , and low-fat , low-cholesterol diet ( American Heart Association recommendation , phase 3 ) . No lipid-lowering agents were prescribed . After 12 months of participation , repeat coronary angiography was performed ; relative and minimal diameter reductions of coronary lesions were measured by digital image processing . Change in myocardial perfusion was assessed by 201TI scintigraphy . In patients participating in the intervention group , body weight decreased by 5 % ( p<0.001 ) , total cholesterol by 10 % ( p<0.001 ) , and triglycerides by 24 % ( p<0.001 ) ; high density lipoproteins increased by 3 % ( p = NS ) . Physical work capacity improved by 23 % ( p<0.0001 ) , and myocardial oxygen consumption , as estimated from maximal rate-pressure product , by 10 % , ( p<0.05 ) . Stress-induced myocardial ischemia decreased concurrently , indicating improvement of myocardial perfusion . Based on minimal lesion diameter , progression of coronary lesions was noted in nine patients ( 23 % ) , no change in 18 patients ( 45 % ) , and regression in 13 patients ( 32 % ) . In the control group , metabolic and hemodynamic variables remained essentially unchanged , whereas progression of coronary lesions was noted in 25 patients ( 48 % ) , no change in 18 patients ( 35 % ) , and regression in nine patients ( 17 % ) . These changes were significantly different from the intervention group ( p<0.05 ) . Conclusions In patients participating in regular physical exercise and low-fat diet , coronary artery disease progresses at a slower pace compared with a control group on usual care Alterations in circulating angiogenic cells ( CAC ) and endothelial progenitor cells ( EPC ) , known to contribute to endothelial repair , could explain the reversal of endothelial function in response to exercise training . Moreover , training-induced vascular remodeling might affect the acute response of EPC and CAC following a single exercise bout . We studied the impact of exercise training on CAC function and numbers of CD34+/KDR+ EPC in patients with chronic heart failure ( CHF ) and we assessed the effect of acute exercise on CAC and EPC in sedentary and trained patients . Twenty-one sedentary CHF patients underwent 6-month exercise training and were compared to a non-trained control group ( n = 17 ) and 10 healthy age-matched subjects . At baseline and follow-up , flow-mediated dilation was assessed and grade d exercise testing ( GXT ) was performed . Before and immediately after GXT , CAC migratory capacity was assessed in vitro and circulating CD34+/KDR+ EPC were quantified using flow cytometry . At baseline , CAC migration was significantly impaired in sedentary CHF patients but normalized acutely after GXT . Training corrected endothelial dysfunction , which coincided with a 77 % increase in CAC migration ( P = 0.0001 ) . Moreover , the GXT-induced improvement detected at baseline was no longer observed after training . Numbers of CD34+/KDR+ EPC increased following 6-month exercise training ( P = 0.021 ) , but were not affected by GXT , either prior or post-training . In conclusion , the present findings demonstrate for the first time that exercise training in CHF reverses CAC dysfunction and increases numbers of CD34+/KDR+ EPC , which is accompanied by improvement of peripheral endothelial function . The acute exercise-induced changes in CAC function wane with exercise training , suggesting that repetitive exercise bouts progressively lead to functional endothelial repair Background Coronary heart disease as well as major cardiovascular risk factors are associated with elevated levels of proinflammatory markers . There is , however , limited information about how changes in lifestyle improving the cardiovascular risk profile influence these levels . The aim of the study was to evaluate whether changes in lifestyle measures with special attention to physical activity , were associated with the levels of such markers . Design Coronary heart disease patients ( n = 197 ) were r and omized to either a comprehensive lifestyle intervention programme comprising regular physical activity , low fat diet and smoking cessation , or usual care with routine follow-up in the outpatient clinic for 6 months . An exercise test and fasting blood sample s analysed for soluble cell adhesion molecules , C reactive protein and pro-inflammatory cytokines were evaluated before and at the end of the study . Results Improved diet , physical performance and reduction in smoking were obtained in the intervention programme when compared with usual care patients , but no significant group differences in levels of inflammatory markers were observed . In the total population , however , physical performance significantly and inversely predicted levels of soluble cell adhesion molecule 1 , ( P>0.001 ) , C-reactive protein ( P>0.001 ) and interleukin-6 ( P=0.01 ) at 6 months . Smokers had elevated levels of soluble cell adhesion molecule 1 when compared with non-smokers ( P=0.011 ) . Conclusions We demonstrated that physical performance is inversely correlated with levels of pro-inflammatory markers in coronary heart disease patients , possibly retarding the process of atherosclerosis . No effect on inflammatory markers was obtained with a 6-month lifestyle intervention programme when compared with patients who received usual care follow-up . Eur J Cardiovasc Prev Rehabil 13:356 - 362 © 2006 The European Society of Background —C-reactive protein ( CRP ) and interleukin (IL)-6 are important risk factors for atherosclerosis and coronary heart disease . In the present study , we examined serum levels of CRP and IL-6 , IL-6 production by monocytes , and the effect of nasal continuous positive airway pressure ( nCPAP ) in patients with obstructive sleep apnea syndrome ( OSAS ) . Methods and Results —After polysomnography , venous blood was collected at 5 am from 30 patients with OSAS and 14 obese control subjects . Serum levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes were investigated . In addition , the effects of 1 month of nCPAP were studied in patients with moderate to severe OSAS . Levels of CRP and IL-6 were significantly higher in patients with OSAS than in obese control subjects ( CRP P < 0.001 , IL-6 P < 0.05 ) . IL-6 production by monocytes was also higher in patients with OSAS than in obese control subjects ( P < 0.01 ) . In patients with OSAS , the primary factors influencing levels of CRP were severity of OSAS and body mass index and those influencing levels of IL-6 were body mass index and nocturnal hypoxia . nCPAP significantly decreased levels of both CRP ( P < 0.0001 ) and IL-6 ( P < 0.001 ) and spontaneous IL-6 production by monocytes ( P < 0.01 ) . Conclusions —Levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes are elevated in patients with OSAS but are decreased by nCPAP . Therefore , OSAS is associated with increased risks for cardiovascular morbidity and mortality , and nCPAP may be useful for decreasing these risks Background Obesity is characterized by chronic mild inflammation and may influence the risk and progression of cancer . Purpose The current study is an exploratory analysis of the effect of a weight loss intervention that emphasized increased physical activity on inflammatory cytokines ( tumor necrosis factor-α [ TNF-α ] , interleukin-6 [ IL-6 ] , interleukin-8 [ IL-8 ] , and vascular endothelial growth factor [ VEGF ] ) at the end of the 16-week intervention period in overweight breast cancer survivors . Methods Study participants averaged 56 years of age ( N = 68 ) . Intervention participants ( n = 44 vs. 24 controls ) participated in a cognitive behavioral therapy-based weight management program as part of an exploratory r and omized trial . The intervention incorporated strategies to promote increased physical activity and diet modification . Baseline and 16-week data included height , weight , body composition , physical activity level , and biomarkers IL-6 , IL-8 , TNF-α , and VEGF . Results Weight loss was significantly greater in the intervention group than controls ( −5.7 [ 3.5 ] vs. 0.2 [ 4.1 ] kg , P < 0.001 ) . Paired t tests noted favorable changes in physical activity level ( P < 0.001 intervention , P = 0.70 control ) , marginally lower IL-6 levels ( P = 0.06 intervention , P = 0.25 control ) at 16 weeks for participants in the intervention group , and lower TNF-α levels for participants in the intervention ( P < 0.05 ) and control groups ( P < 0.001 ) . Increased physical activity was associated with favorable changes in IL-6 for participants in the intervention group ( R2 = 0.18 ; P < 0.03 ) . Conclusion Favorable changes in cytokine levels were observed in association with weight loss in this exploratory study with overweight breast cancer survivors BACKGROUND The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure ( CHF ) . Endothelial dysfunction is a key feature of CHF , contributing to increased peripheral vasoconstriction and impaired exercise capacity . Local h and grip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF . METHODS AND RESULTS Twenty patients were prospect ively r and omized to a training group ( n=10 , left ventricular ejection fraction [ LVEF ] 24+/-4 % ) or a control group ( n=10 , LVEF 23+/-3 % ) . At baseline and after 6 months , peak flow velocity was measured in the left femoral artery using a Doppler wire ; vessel diameter was determined by quantitative angiography . Peripheral blood flow was calculated from average peak velocity ( APV ) and arterial cross-sectional area . After exercise training , nitroglycerin-induced endothelium-independent vasodilation remained unaltered ( 271 % versus 281 % , P = NS ) . Peripheral blood flow improved significantly in response to 90 microg/min acetylcholine by 203 % ( from 152+/-79 to 461+/-104 mL/min , P<0.05 versus control group ) and the inhibiting effect of L-NMMA increased by 174 % ( from -46+/-25 to -126+/-19 mL/min , P<0.05 versus control group ) . Peak oxygen uptake increased by 26 % ( P<0.01 versus control group ) . The increase in peak oxygen uptake was correlated with the endothelium-dependent change in peripheral blood flow ( r=0.64 , P<0 . 005 ) . CONCLUSIONS Regular physical exercise improves both basal Output:	Aerobic exercise decreased the adhesion molecules , vascular cell adhesion molecule-1 ( VCAM-1 ) and intercellular adhesion molecule-1 ( ICAM-1 ) ( moderate and high evidence , respectively ) , while effects of PA on E- and P-selectin were inconclusive . PA decreases C-reactive protein ( CRP ) ( high evidence ) . The angiogenic actors , endothelial progenitor cells ( EPCs ) are increased ( high evidence ) and VEGF is decreased ( moderate evidence ) by PA . The effect of PA on these factors seems to depend on the type and duration of exercise intervention and patient factors , such as presence of ischemia . As presented in this review , there is a high level of evidence that physical activity positively affects key players in atherosclerosis development . These effects could partly explain the scientifically proven anti-atherogenic effects of PA , and do have important clinical implication
MS22214	*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 study was to project health-economic outcomes relevant to the German setting for the addition of pioglitazone to existing treatment regimens in patients with type 2 diabetes , evidence of macrovascular disease and at high risk of cardiovascular events . Methods Event rates corresponding to macrovascular outcomes from the Prospect i ve Pioglitazone Clinical Trial in Macrovascular Events ( PROactive ) study of pioglitazone were used with a modified version of the CORE Diabetes Model to simulate outcomes over a 35-year time horizon . Direct medical costs were accounted from a healthcare payer perspective in year 2005 values . Germany specific costs were applied for patient treatment , hospitalization and management . Both costs and clinical benefits were discounted at 5.0 % per annum . Results Over patient lifetimes pioglitazone treatment improved undiscounted life expectancy by 0.406 years and improved quality -adjusted life expectancy by 0.120 quality -adjusted life years ( QALYs ) compared to placebo . Direct medical costs ( treatment plus complication costs ) were marginally higher for pioglitazone treatment and calculation of the incremental cost-effectiveness ratio ( ICER ) produced a value of € 13,294 per QALY gained with the pioglitazone regimen versus placebo . Acceptability curve analysis showed that there was a 78.2 % likelihood that pioglitazone would be considered cost-effective in Germany , using a " good value for money " threshold of € 50,000 per QALY gained . Sensitivity analyses showed that the results were most sensitive to changes in the simulation time horizon . After adjustment for the potential stabilization of pancreatic β-cell function with pioglitazone treatment , the ICER was € 6,667 per QALY gained for pioglitazone versus placebo . Conclusion The findings of this modelling analysis indicated that , for patients with a history of macrovascular disease , addition of pioglitazone to existing therapy reduces the long-term cumulative incidence of diabetes-complications at a cost that would be considered to represent good value for money in the German setting OBJECTIVES The aim of this study is to examine the cost-effectiveness of a group-based peer support intervention in general practice for patients with type 2 diabetes . METHODS Incremental cost utility analysis combining within trial and beyond trial components to compare the lifetime costs and benefits of alternative strategies : CONTROL st and ardized diabetes care ; INTERVENTION group-based peer support in addition to st and ardized diabetes care . Within trial analysis was based on a cluster r and omized controlled trial of 395 patients with type 2 diabetes in the east of Irel and . Beyond trial analysis was conducted using the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) Outcomes Model . Uncertainty was explored using a range of sensitivity analyses and cost-effectiveness acceptability curves were generated . RESULTS Compared with the control strategy , the intervention was associated with an increase of 0.09 ( 95 percent confidence interval [ CI ] , -0.05 to 0.25 ) in mean quality -adjusted life-years per patient and savings of € 637.43 ( 95 percent CI , -2455.19 to 1125.45 ) in mean healthcare cost per patient and € 623.39 ( 95 percent CI , -2507.98 to 1298.49 ) in mean total cost per patient respectively . The likelihood of the intervention being cost-effective was appreciably higher than 80 percent for a range of potential willingness-to-pay cost-effectiveness thresholds . CONCLUSIONS Our results suggest that while a group-based peer support intervention shows a trend toward improved risk factor management , we found no significant differences in final cost or effectiveness endpoints between intervention and control . The probabilistic results suggest that the intervention was more cost-effective , with probability values of higher than 80 percent across a range of potential cost-effectiveness threshold values Background : The benefits of self-monitoring blood glucose levels are unclear in patients with type 2 diabetes mellitus who do not use insulin , but there are considerable costs . We sought to determine the cost effectiveness of self-monitoring for patients with type 2 diabetes not using insulin . Methods : We performed an incremental cost-effectiveness analysis of the self-monitoring of blood glucose in adults with type 2 diabetes not taking insulin . We used the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) model to forecast diabetes-related complications , corresponding quality -adjusted life years and costs . Clinical data were obtained from a systematic review comparing self-monitoring with no self-monitoring . Costs and utility decrements were derived from published sources . We performed sensitivity analyses to examine the robustness of the results . Results : Based on a clinical ly modest reduction in hemoglobin A1C of 0.25 % ( 95 % confidence interval 0.15–0.36 ) estimated from the systematic review , the UKPDS model predicted that self-monitoring performed 7 or more times per week reduced the lifetime incidence of diabetes-related complications compared with no self-monitoring , albeit at a higher cost ( incremental cost per quality -adjusted life year $ 113 643 ) . The results were largely unchanged in the sensitivity analysis , although the incremental cost per quality -adjusted life year fell within widely cited cost-effectiveness thresholds when testing frequency or the price per test strip was substantially reduced from the current levels . Interpretation : For most patients with type 2 diabetes not using insulin , use of blood glucose test strips for frequent self-monitoring ( ≥ 7 times per week ) is unlikely to represent efficient use of finite health care re sources , although periodic testing ( e.g. , 1 or 2 times per week ) may be cost-effective . Reduced test strip price would likely also improve cost-effectiveness OBJECTIVE —The efficacy and safety of adding liraglutide ( a glucagon-like peptide-1 receptor agonist ) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes ( OAD ) therapy . RESEARCH DESIGN AND METHODS —In this 26-week , double-blind , double-dummy , placebo- and active-controlled , parallel-group trial , 1,091 subjects were r and omly assigned ( 2:2:2:1:2 ) to once-daily liraglutide ( either 0.6 , 1.2 , or 1.8 mg/day injected subcutaneously ) , to placebo , or to glimepiride ( 4 mg once daily ) . All treatments were in combination therapy with metformin ( 1 g twice daily ) . Enrolled subjects ( aged 25–79 years ) had type 2 diabetes , A1C of 7–11 % ( previous OAD monotherapy for ≥3 months ) or 7–10 % ( previous OAD combination therapy for ≥3 months ) , and BMI ≤40 kg/m2 . RESULTS —A1C values were significantly reduced in all liraglutide groups versus the placebo group ( P < 0.0001 ) with mean decreases of 1.0 % for 1.8 mg liraglutide , 1.2 mg liraglutide , and glimepiride and 0.7 % for 0.6 mg liraglutide and an increase of 0.1 % for placebo . Body weight decreased in all liraglutide groups ( 1.8–2.8 kg ) compared with an increase in the glimepiride group ( 1.0 kg ; P < 0.0001 ) . The incidence of minor hypoglycemia with liraglutide ( ∼3 % ) was comparable to that with placebo but less than that with glimepiride ( 17 % ; P < 0.001 ) . Nausea was reported by 11–19 % of the liraglutide-treated subjects versus 3–4 % in the placebo and glimepiride groups . The incidence of nausea declined over time . CONCLUSIONS —In subjects with type 2 diabetes , once-daily liraglutide induced similar glycemic control , reduced body weight , and lowered the occurrence of hypoglycemia compared with glimepiride , when both had background therapy of metformin BACKGROUND AND OBJECTIVES Exenatide , a GLP-1 receptor agonist for adjuvant treatment of type 2 diabetes mellitus ( T2DM ) , has been shown to be as effective as insulin glargine ( IG ) for reducing glycated hemoglobin levels combined with metformin or/ and sulphonylureas . Exenatide is associated to weight reduction and a higher incidence of gastrointestinal adverse events . The objective of this study was to assess the cost-effectiveness of exenatide as compared to IG in obese patients with T2DM not achieving an adequate blood glucose control from the perspective of the Spanish healthcare system . METHODS Pharmacoeconomic model inputs were obtained from an obese sub population ( BMI ≥ 30 k/m(2 ) ) of an international , r and omized , controlled clinical trial comparing exenatide with IG in poorly controlled T2DM patients , and were supplemented with country-specific data . RESULTS Exenatide was associated to improvements in life-years gained and quality -adjusted life years ( QALYs ) by 0.11 and 0.62 respectively versus IG . Direct costs were € 9,306 higher as compared to IG ( € 47,010 versus € 37,704 , with increased pharmacy costs as the main driver ) . Exenatideís incremental cost-effectiveness ratio was € 15,068 per QALY gained versus IG . CONCLUSIONS Exenatide was associated to greater clinical benefits and higher costs in obese T2DM patients as compared to IG . Considering a willingness-to-pay threshold of € 30,000 per QALY gained in the Spanish setting , exenatide represents an efficient option in comparison with IG OBJECTIVES This analysis provides an early estimate of the cost-effectiveness of adjunctive exenatide in treating type 2 diabetes mellitus in the United States . Data from pivotal phase III 30-week clinical trials and 52 weeks of their subsequent open-label extension studies ( i.e. , 82 weeks total ) were used to project the effects of 30 years of adjunctive exenatide treatment . METHODS This analysis utilized a published and vali date d Markov model incorporating Monte Carlo simulation with tracker variables to estimate the clinical and cost outcomes of adding exenatide to a background of metformin and /or sulfonylurea treatment , with the effects of 30 years of adjunctive exenatide treatment ( projected from data from 82 weeks of exenatide treatment ) compared with no additional treatment beyond metformin and /or a sulfonylurea . Sensitivity analyses were performed on key clinical assumptions , discount rates , and shorter time horizons . RESULTS The base-case scenario ( 30 years of exenatide ) yielded an incremental cost-effectiveness ratio ( ICER ) of $ 35,571 . We found that shortening the time horizons and removing the lipid effects of exenatide had the greatest negative impact on ICERs when performing sensitivity analysis . CONCLUSIONS Our analysis demonstrated that exenatide used for 20 or 30 years compared with no additional treatment beyond metformin and /or a sulfonylurea is cost-effective in the adjunctive treatment of type 2 diabetes with an ICER less than $ 50,000 per life-year gained . Sensitivity analyses suggest that , in addition to sustained reduction in HbA(1c ) , the added clinical effects of improved lipid values , systolic blood pressure , and reduced body mass index all positively contributed to the cost-effectiveness of exenatide OBJECTIVE To develop and vali date a comprehensive computer simulation model to assess the impact of screening , prevention , and treatment strategies on type 2 diabetes and its complications , comorbidities , quality of life , and cost . RESEARCH DESIGN AND METHODS The incidence of type 2 diabetes and its complications and comorbidities were derived from population -based epidemiologic studies and r and omized , controlled clinical trials . Health utility scores were derived for patients with type 2 diabetes using the Quality of Well Being-Self-Administered . Direct medical costs were derived for managed care patients with type 2 diabetes using paid insurance cl aims . Monte Carlo techniques were used to implement a semi-Markov model . Performance of the model was assessed using baseline and 4- and 10-year follow-up data from the older-onset diabetic population studied in the Wisconsin Epidemiologic Study of Diabetic Retinopathy ( WESDR ) . RESULTS Applying the model to the baseline WESDR population with type 2 diabetes , we predicted mortality to be 51 % at 10 years . The prevalences of stroke and myocardial infa rct ion were predicted to be 18 and 19 % at 10 years . The prevalences of nonproliferative diabetic retinopathy , proliferative retinopathy , and macular edema were predicted to be 45 , 16 , and 18 % , respectively ; the prevalences of microalbuminuria , proteinuria , and end-stage renal disease were predicted to be 19 , 39 , and 3 % , respectively ; and the prevalences of clinical neuropathy and amputation were predicted to be 52 and 5 % , respectively , at 10 years . Over 10 years , average undiscounted total direct medical costs were estimated to be USD $ 53,000 per person . Among survivors , the average utility score was estimated to be 0.56 at 10 years . CONCLUSIONS Output:	An inverse exponential relationship was found and fitted between the ratio ( ∆QALY/∆LE ) and ∆HbA1c . Conclusion There is a consistent relationship between ∆HbA1c and ∆QALYs or ∆LE in cost-effectiveness analyses using type 2 diabetes simulation models .
MS22215	*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 assess the efficacy and safety of a copper-salicylate gel in osteoarthritis of the hip and knee . DESIGN R and omised , double-blind , placebo-controlled study . SETTING Rheumatology Clinic of St Vincent 's Hospital , Sydney , New South Wales ( a tertiary referral hospital ) , June 1993 to October 1994 . PATIENTS 116 patients with pain associated with osteoarthritis of the hip and /or knee ( diagnosed by criteria of the European League against Rheumatism ) , drawn from patients attending the Clinic or self-referred after newspaper advertisements . INTERVENTION Copper-salicylate or placebo gel ( 1.5 g ) applied twice daily to the forearm for four weeks . OUTCOME MEASURES Self- assessment of pain before the trial and after two and four weeks of treatment ; patient and investigator assessment s of efficacy ; additional analgesia required ; adverse reactions ; and withdrawal rates . RESULTS Pain scores at rest and on movement decreased in both the copper-salicylate and placebo groups by 13%-20 % . There was no significant difference between the two groups for decrease in pain score , patient and investigator efficacy ratings , number of patients requiring paracetamol for extra analgesia ( active , 77 % ; placebo , 71 % ) and average dose of paracetamol ( active , 555 mg/day ; placebo , 600 mg/day ) . Significantly more patients in the copper-salicylate group reported adverse reactions ( 83 % versus 52 % of the placebo group ) , most commonly skin reactions , and withdrew from the trial because of these reactions ( 17 % versus 1.7 % of the placebo group ) . CONCLUSION Copper-salicylate gel applied to the forearm was no better than placebo gel as pain relief for patients with osteoarthritis of the hip or knee , but produced significantly more skin rashes Objective : To determine the clinical effects of the treatment of lumbar disc herniation with herbal magnetic corsets . Design : A r and omized control trial . Setting : The outpatient and inpatient departments of the Rehabilitation Center of the West China Hospital . Patients : Sixty patients with clinical ly diagnosed lumbar disc herniation were included in the study . Interventions : Both groups received lumbar traction , medium frequency electrotherapy and massage , whereas the experimental group wore herbal magnetic corsets in addition . Main outcome measures : Pain and lumbar function were assessed before treatment and at one week , two weeks and four weeks after intervention . Results : Both groups reported improvements in pain and lumbar function after treatment ( P 0.05 or P 0.001 ) . However , the experimental group reported gradually increasing relief over time leading to a better curative effect than observed in the control group ( P 0.05 for visual analogue scale or P 0.001 for lumbar function ) . Conclusion : Herbal magnetic corsets can facilitate the reduction of pain caused by lumbar disc herniation and can improve lumbar function . This is a safe and effective non-operative therapeutic option for treatment of lumbar disc herniation 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 Enelbin-Rheuma-ointment and a reference ointment were compared with regard to effectiveness in a double-blind trial in 100 patients with gonarthrosis , osteoarthrosis of the spine and humeroscapular periarthropathy . Both ointments showed good results regarding spontaneous pain , pain on pressure and motion , reduction of mobility , swelling and muscular tension . The success of treatment was statistically significantly better in the Enelbin-Rheuma-ointment treated patients Abstract This r and omized , double-blind study was design ed to evaluate the effectiveness of the topical cream Theraflex-TMJ ( NaBob/Rx , San Mateo , CA ) in patients with masseter muscle pain and temporom and ibular joint ( TMJ ) pain . Fifty-two subjects ( 5 males and 47 females ) were instructed to apply a cream over the afflicted masseter muscle(s ) or over the jaw joint(s ) twice daily for two weeks . Theraflex-TMJ cream was used by the experimental group , while a placebo cream was used by the control group . The means of pain ratings were calculated prior to the application of the cream ( baseline ) , after ten days of tx ( period 1 ) , and 15 days of tx ( period 2 ) days of treatment and five days after stopping the treatment ( follow-up ) . There was a significant decrease in reported pain levels from baseline in the experimental group for period 1 ( p<0.01 ) , period 2 ( p<0.001 ) , and follow-up ( p<0.01 ) . For the control group , no significant differences were found between the different time periods ( p>0.05 ) . There was evidence of minor side effects such as skin irritation and /or burning on the site of the application in two subjects in the experimental as well as two subjects in the control groups . The data strongly suggest that Theraflex-TMJ topical cream is safe and effective for reducing pain in the masseter muscle and the temporom and ibular joint Twenty-five patients with symptomatic osteoarthritis ( OA ) of the knee were treated topically for one week with either 10 % trolamine salicylate cream or placebo cream in a r and omized double-blind crossover study . No significant difference was found in subjective or objective measures of pain relief between the treatment and control groups . Eight patients preferred " active " test cream , six preferred placebo , and 11 had no preference . No side effects were reported . Topically applied 10 % trolamine salicylate cream did not relieve the pain of OA of the knee any more than did placebo Forty patients with acute mechanical low-back pain were treated in a double-blind manner with either Rado-Salil ® or placebo for 14 days . Statistically significant improvements in spontaneous pain , muscular contracture and in both the patient 's and physician 's opinions occurred by day 3 . These improvements persisted at day 14 and , in addition , there were statistically significant improvements in the finger – floor distance and the degree of lumbar extension . Treatment with Rado-Salil ® also allowed significant reduction in the use of oral analgesics . Only a few localized transient side-effects , requiring no specific treatment , were observed This study was design ed to evaluate the effectiveness in relief of pain and rigidity of a 10\|X% trolamine salicylate cream compared with a placebo cream identical in smell and appearance , for subjects with osteoarthritis in their h and s. This was a one-application , r and omized , double-blind , placebo-controlled , parallel study conducted in 81 patients . Pain and stiffness were assessed in the morning upon subjects ' awakening ( baseline ) and at 30 , 45 , and 120 min after a 4-min rubbing application . Analgesic response was determined using the sum of pain intensity differences ( SPID ) and the sum of stiffness intensity differences ( SSID ) ; the sum across the observation points derived from a pain/stiffness rating scale . Trolamine salicylate was significantly superior to the placebo in improving SPID ( p = 0.0492 ) and in improving SSID scores for both h and s ( p = 0.0283 ) . Treatment differences in absolute pain and stiffness scores were significant ( p \|Ml 0.05 ) at 45 min after application . A 10\|X% trolamine salicylate cream was shown to be safe and effective for the temporary relief of minor pain and stiffness associated with osteoarthritis in the h and s. This formulation has no smell or counter-irritating properties ; patient acceptability was good In a r and omised , placebo-controlled , double-blind study with parallel group comparison , the efficacy and tolerability of topical treatment with a mucopolysaccharide polysulphate/salicylic acid cream was investigated in 156 patients with acute sprains of the knee or ankle joint . There was a more rapid reduction in pain on movement ( the main parameter ) in the active drug group compared with the placebo group . On day 9 after r and omisation the difference was highly significant . There were no adverse events in the active drug group & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Acute low back pain is a very common condition in Western industrialised countries . In most cases analgesics or topical medications are prescribed at first encounter with the general practitioner ( GP ) . The aim of this study was to investigate whether the homeopathic gel Spiroflor SRL gel ( SRL ) is equally effective and better tolerated than Cremor Capsici Compositus FNA ( CCC ) in patients with acute low back pain . A multi-centre , r and omised , double-blind , controlled clinical trial was conducted in the practice s of 19 GPs in the districts of Bristol and Manchester , UK . One hundred and sixty-one subjects suffering from acute low back pain were treated for one week either with SRL or with CCC . Pain was scored on a 100 mm visual analogue scale ( VAS ) . Main efficacy parameter VAS reduction was compared between treatments . Evaluation of safety was primarily based on the number of subjects with adverse events ( AEs ) , withdrawals due to an AE and adverse drug reactions ( ADRs ) . The mean difference between the VAS reduction in the SRL group and the CCC group adjusted for VAS at baseline and age was -0.6 mm ( 90 % CI = -6.5 - 5.3 mm ) . Fewer subjects in the SRL group ( 11 % ) experienced an AE than in the CCC group ( 26 % ) . The same applies to the number of subjects with an ADR ( 3/81 = 4 % vs 18/74 = 24 % ) and the number of subjects withdrawn due to an ADR ( 0/81 = 0 % vs 8/74 = 11 % ) . In conclusion , SRL and CCC are equally effective in the treatment of acute low back pain , however , SRL has a better safety profile . Spiroflor SRL gel is preferable to Capsicum-based products for the topical treatment of low back pain , because of the lower risk of adverse effects 2-(2-Hydroxyethoxy)ethyl-N-(a , a , a-trifluoro-m-tolyl)anthranilate ( etofenamate , Rheumon Gel ) , a percutaneously active antirheumatic containing etofenamate as active principle has been subjected to clinical studies in both hospitalized and out- patients in various types of rheumatic disease . These trials included double-blind studies against placebo gel , controlled comparative studies against two topical commercial products ( ointmentI : combination of 2-hydroxyethyl salicylate and p-menthan-3-ol ; ointment II : 3,5-d Output:	The evidence does not support the use of topical rubefacients containing salicylates for acute injuries , and suggests that in chronic conditions their efficacy compares poorly with topical non-steroidal antiinflammatory drugs ( NSAIDs ) . Topical salicylates seem to be relatively well tolerated in the short-term , based on limited data . There is no evidence at all for topical rubefacients with other components
MS22216	*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 assess the outcome of endovascular repair ( EVAR ) of small abdominal aortic aneurysms ( AAA , ≤5.5 mm maximum diameter ) in Australia . Summary Background Data : R and omized trials have suggested that small AAAs should not be treated by open surgery . EVAR is associated with less perioperative mortality than open surgery for large AAAs . We assessed the outcome of EVAR of small AAAs as part of a national audit . Methods : ASERNIP-S carried out a prospect i ve audit of EVAR performed between November 1999 and May 2001 in Australia . A total of 478 of the 961 patients entered underwent treatment of a small AAA . Data were collected regarding preoperative characteristics , procedural outcome , and intermediate success . Median follow-up was 3.2 years . Data were analyzed using Kaplan-Meier and Cox proportional hazard analyses . Results : The 30-day mortality and technical success rates were 1.1 % and 98 % , respectively . Postoperative complications occurred in 29 % . Survival was 84 % and 52 % at 3 and 5 years , respectively . Primary , assisted primary , and secondary clinical success rates were 72 % , 79 % , and 82 % , respectively , at 3 years . Reintervention rate was 11 % at 3 years ; however , 15 % of patients continued to have significant aortic sac enlargement . Survival was reduced in patients considered unfit for general anesthesia ( odds ratio = 2.6 ; 95 % confidence interval , 1.4–4.8 , P = 0.002 ) or those who had elevated preoperative serum creatinine ( odds ratio = 2.0 ; 95 % confidence interval , 1.3–3.0 , P = 0.001 ) . Conclusions : EVAR can be carried with good perioperative outcome in patients with small AAA ; however , intermediate success is hampered by the need for reintervention and continued aortic sac enlargement . At present , widespread treatment of small AAAs by EVAR would appear inappropriate OBJECTIVE The effect of population screening for abdominal aortic aneurysm ( AAA ) disease on morbidity and mortality has been comprehensively studied and reported . However , the effect of early AAA detection on suitability for endovascular aneurysm repair ( EVAR ) remains unknown . Considering the importance of such an effect on future health economics , we sought to assess the possible effect of AAA ultrasound surveillance on suitability for EVAR . METHODS This was a prospect i ve cohort study . From January 2002 to August 2003 , consecutive AAA patients selected for open elective repair were placed into one of two groups according to mode of presentation . The first group included patients referred from a local well-established AAA ultrasound screening and surveillance program ( ultrasound surveillance [ AAA-S ] group ) . The second group included patients referred from neighboring unscreened regions with incidentally diagnosed AAA ( incidental [ AAA-I ] group ) . All patients underwent preoperative computed tomographic angiography . By using three-dimensional reconstruction software , computed tomographic images were assessed by two blinded observers for suitability for EVAR by using the criteria for a modular endovascular device . RESULTS Of 74 patients included in the study , 41 were in the AAA-S group , and 31 were in the AAA-I group . The median aneurysm diameter was 72.3 mm ( range , 50.7 - 83.7 mm ) for AAA-I and 65 mm ( range , 50.7 - 79.2 mm ) for AAA-S ( P < .47 ) . Suitability for EVAR was 41 % in the AAA-S group and 45 % in the AAA-I group ( P < .47 ) . CONCLUSIONS Early detection and surveillance of AAA does not seem to increase suitability for EVAR . Suitability for EVAR seems to be determined early on in an aneurysm 's life . On the basis of current device technology , referral for intervention from an AAA surveillance program may need to be initiated at a size well below 5.5 cm if an increase in EVAR suitability is to be expected HYPOTHESIS Small infrarenal abdominal aortic aneurysms have a more favorable clinical and morphologic outcome compared with medium and large abdominal aortic aneurysms following endovascular aneurysm repair(EVAR ) . DESIGN A prospect i ve clinical series of 206 patients undergoing elective EVAR between 1996 and 2001 . SETTING A tertiary care academic health center . PATIENTS Patients were grouped according to aneurysm size : small ( < 50 mm ) , medium ( 50 - 60 mm ) , and large ( > 60 mm ) . INTERVENTIONS Primary EVAR and secondary procedures to secure fixation of the stent graft and surgical conversions . MAIN OUTCOME MEASURES Aneurysm diameter , endoleaks , and long-term morphologic changes were analyzed postoperatively with 3-dimensional reconstructions of computed tomographic angiograms . RESULTS Groups were similar in age , comorbidities , and follow-up ( mean + /- SD , 32.1 + /- 11.8 months ) . There were 30 small aneurysms , 92 medium aneurysms , and 84 large aneurysms , with a mean size of 45.1 + /- 3.7 mm , 53.8 + /- 3.1 mm , and 66.1 + /- 6.8 mm , respectively ( P<.01 ) . There was no significant difference in proximal neck or iliac artery diameter among the 3 groups . The proximal aortic neck length ( 28.1 + /- 11.6 mm [ small ] ; 23.9 + /- 11.3 mm [ medium ] ; and 22.1 + /- 11.6 mm [ large ] ; P<.05 ) was significantly shorter in large aneurysms . Furthermore , there was a significant increase ( 6 % [ small ] ; 15 % [ medium ] ; and 21 % [ large ] ; P<.05 ) in angulated necks in large aneurysms . Following treatment , aneurysm diameter remained stable in most patients ( 83 % [ small ] ; 82 % [ medium ] ; and 83 % [ large ] ) , with a mean decrease of 2.0 + /- 6.5 mm , 2.1 + /- 6.1 mm , and 3.7 + /- 7.7 mm in each group , respectively ( P = .45 ) . There was no difference in the incidence of endoleaks , aneurysm contraction , or aneurysm expansion based on preoperative aneurysm diameter . Secondary procedures were performed in 5 ( 20 % ) of 25 , 9 ( 5.2 % ) of 170 , and 5 ( 36 % ) of 11 aneurysms that contracted , remained stable , or exp and ed , respectively , following EVAR ( P<.05 ) . CONCLUSIONS There is a 15 % increase in neck angulation and a 27 % decrease in neck length in large compared with small infrarenal abdominal aortic aneurysms , with no difference in outcome . Aneurysms that are stable following EVAR have a significantly lower incidence of requiring secondary procedures OBJECTIVE To compare the outcome of patients with small abdominal aortic aneurysms ( AAA ) treated in a prospect i ve trial of endovascular aneurysm repair ( EVAR ) to patients r and omized to the surveillance arm of the UK Small Aneurysm Trial . METHOD All patients with small AAA ( < or = 5.5 cm diameter ) treated with a stent graft ( EVARsmall ) in the multicenter AneuRx clinical trial from 1997 to 1999 were review ed with follow up through 2003 . A subgroup of patients ( EVARmatch ) who met the age ( 60 - 76 years ) and aneurysm size ( 4.0 - 5.5 cm diameter ) inclusion criteria of the UK Small Aneurysm Trial were compared to the published results of the surveillance patient cohort ( UKsurveil ) of the UK Small Aneurysm Trial ( NEJM 346:1445 , 2002 ) . Endpoints of comparison were aneurysm rupture , fatal aneurysm rupture , operative mortality , aneurysm related death and overall mortality . The total patient years of follow-up for EVAR patients was 1369 years and for UK patients was 3048 years . Statistical comparisons of EVARmatch and UKsurveil patients were made for rates per 100 patient years of follow up ( /100 years ) to adjust for differences in follow-up time . RESULTS The EVARsmall group of 478 patients comprised 40 % of the total number of patients treated during the course of the AneuRx clinical trial . The EVARmatch group of 312 patients excluded 151 patients for age < 60 or > 76 years and 15 patients for AAA diameter < 4 cm . With the exception of age , there were no significant differences between EVARsmall and EVARmatch in pre-operative factors or post-operative outcomes . In comparison to the UKsurveil group of 527 patients , the EVARmatch group was slightly older ( 70 + /- 4 vs. 69 + /- 4 years , p = 0.009 ) , had larger aneurysms ( 5.0 + /- 0.3 vs. 4.6 + /- 0.4 cm , p < 0.001 ) , fewer women ( 7 vs. 18 % , p < 0.001 ) , and had a higher prevalence of diabetes and hypertension and a lower prevalence of smoking at baseline . Ruptures occurred in 1.6 % of EVARmatch patients and 5.1 % of UKsurveil patients ; this difference was not significant when adjusted for the difference in length of follow up . Fatal aneurysm rupture rate , adjusted for follow up time , was four times higher in UKsurveil ( 0.8/100 patient years ) than in EVARmatch ( 0.2/100 patient years , p < 0.001 ) ; this difference remained significant when adjusted for difference in gender mix . Elective operative mortality rate was significantly lower in EVARmatch ( 1.9 % ) than in UKsurveil ( 5.9 % , p < 0.01 ) . Aneurysm-related death rate was two times higher in UKsurveil ( 1.6/100 patient years ) than in EVARmatch ( 0.8/100 patient years , p = 0.03 ) . All-cause mortality rate was significantly higher in UKsurveil ( 8.3/100 patient years ) than in EVARmatch ( 6.4/100 patient years , p = 0.02 ) . CONCLUSIONS It appears that endovascular repair of small abdominal aortic aneurysms ( 4.0 - 5.5 cm ) significantly reduces the risk of fatal aneurysm rupture and aneurysm-related death and improves overall patient survival compared to an ultrasound surveillance strategy with selective open surgical repair OBJECTIVE To study the growth rate and factors influencing progression of small infrarenal abdominal aortic aneurysms ( AAA ) . DESIGN Observational , longitudinal , prospect i ve study . PATIENTS AND METHODS We followed patients with AAA < 5 cm in diameter in two groups . Group I ( AAA 3 - 3.9 cm , n = 246 ) underwent annual ultrasound scans . Group II ( AAA 4 - 4.9 cm , n = 106 ) underwent 6-monthly CT scans . RESULTS We included 352 patients ( 333 men and 19 women ) followed for a mean of 55.2+/-37.4 months ( 6.3 - 199.8 ) . The mean growth rate was significantly greater in group II ( 4.72+/-5.93 vs. 2.07+/-3.23 mm/year ; p<0.0001 ) . Group II had a greater percentage of patients with rapid aneurysm expansion ( > 4 mm/year ) ( 36.8 vs. 13.8 % ; p<0.0001 ) . The classical cardiovascular risk factors did not influence the AAA growth rate in group I. Chronic limb ischemia was associated with slower expansion ( < or = 4 mm/year ) ( OR 0.47 ; CI 95 % 0.22 - 0.99 ; p = 0.045 ) . Diabetic patients in group II had a significantly smaller mean AAA growth rate than non-diabetics ( 1.69+/-3.51 vs. 5.22+/-6.11 mm/year ; p = 0.032 ) . CONCLUSIONS The expansion rate of small AAA increases with the AAA size . AAA with a diameter of 3 - 3.9 cm exp and slowly , and they are very unlikely to require surgical repair in 5 years . Many 4 - 4.9 cm AAA can be expected to reach a surgical size in the first 2 years of follow-up . Chronic limb ischemia and diabetes are associated with reduced aneurysm growth rates BACKGROUND Although the initial results of endovascular repair of abdominal aortic aneurysms were promising , current evidence from controlled studies does not convincingly show a reduction in 30-day mortality relative to that achieved with open repair . METHODS We conducted a multicenter , r and omized trial comparing open repair with endovascular repair in 345 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable c Output:	Pooled estimates were not influenced by follow-up length . Conversion and reintervention rates were not significantly lower for small AAA . EVAR in small versus large AAA might be associated with lower operative mortality , aneurysm-related mortality and aneurysm rupture .
MS22217	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To investigate the efficacy of high-frequency whole-body vibration ( WBV ) on balancing ability in elderly women . DESIGN R and omized controlled trial . Subjects were r and omized to either the WBV intervention or the no-treatment control group . SETTING Community-living elderly women . PARTICIPANTS Sixty-nine elderly women aged 60 or above without habitual exercise . INTERVENTION Side alternating WBV at 20Hz with 3 minutes a day and 3 days a week for 3 months in the WBV intervention group . Those in control group remained sedentary with normal daily life for the whole study period . MAIN OUTCOME MEASURES Limits of stability in terms of reaction time , movement velocity , directional control , endpoint excursion , maximum excursion , and the functional reach test were performed at baseline and endpoint . RESULTS Significant enhancement of stability was detected in movement velocity ( P<.01 ) , maximum point excursion ( P<.01 ) , in directional control ( P<.05 ) . CONCLUSIONS WBV was effective in improving the balancing ability in elderly women . This also provides evidence to support our user-friendly WBV treatment protocol of 3 minutes a day for the elderly to maintain their balancing ability and reduce risks of fall OBJECTIVES To investigate the effects of 24 weeks of whole-body-vibration ( WBV ) training on knee-extension strength and speed of movement and on counter-movement jump performance in older women . DESIGN A r and omized , controlled trial . SETTING Exercise Physiology and Biomechanics Laboratory , Leuven , Belgium . PARTICIPANTS Eighty-nine postmenopausal women , off hormone replacement therapy , aged 58 to 74 , were r and omly assigned to a WBV group ( n=30 ) , a resistance-training group ( RES , n=30 ) , or a control group ( n=29 ) . INTERVENTION The WBV group and the RES group trained three times a week for 24 weeks . The WBV group performed unloaded static and dynamic knee-extensor exercises on a vibration platform , which provokes reflexive muscle activity . The RES group trained knee-extensors by performing dynamic leg-press and leg-extension exercises increasing from low ( 20 repetitions maximum ( RM ) ) to high ( 8RM ) resistance . The control group did not participate in any training . MEASUREMENTS Pre- , mid- ( 12 weeks ) , and post- ( 24 weeks ) isometric strength and dynamic strength of knee extensors were measured using a motor-driven dynamometer . Speed of movement of knee extension was assessed using an external resistance equivalent to 1 % , 20 % , 40 % , and 60 % of isometric maximum . Counter-movement jump performance was determined using a contact mat . RESULTS Isometric and dynamic knee extensor strength increased significantly ( P<.001 ) in the WBV group ( mean+/-st and ard error 15.0+/-2.1 % and 16.1+/-3.1 % , respectively ) and the RES group ( 18.4+/-2.8 % and 13.9+/-2.7 % , respectively ) after 24 weeks of training , with the training effects not significantly different between the groups ( P=.558 ) . Speed of movement of knee extension significantly increased at low resistance ( 1 % or 20 % of isometric maximum ) in the WBV group only ( 7.4+/-1.8 % and 6.3+/-2.0 % , respectively ) after 24 weeks of training , with no significant differences in training effect between the WBV and the RES groups ( P=.391 ; P=.142 ) . Counter-movement jump height enhanced significantly ( P<.001 ) in the WBV group ( 19.4+/-2.8 % ) and the RES group ( 12.9+/-2.9 % ) after 24 weeks of training . Most of the gain in knee-extension strength and speed of movement and in counter-movement jump performance had been realized after 12 weeks of training . CONCLUSION WBV is a suitable training method and is as efficient as conventional RES training to improve knee-extension strength and speed of movement and counter-movement jump performance in older women . As previously shown in young women , it is suggested that the strength gain in older women is mainly due to the vibration stimulus and not only to the unloaded exercises performed on the WBV platform OBJECTIVE To test whether training on a high-frequency ( 28Hz ) vibrating platform improves muscle power and bone characteristics in postmenopausal women . DESIGN R and omized controlled trial with 6-month follow-up . SETTING Outpatient clinic in a general hospital in Italy . PARTICIPANTS Twenty-nine postmenopausal women ( intervention group , n=14 ; matched controls , n=15 ) . INTERVENTION Participants stood on a ground-based oscillating platform for three 2-minute sessions for a total of 6 minutes per training session , twice weekly for 6 months . The controls did not receive any training . Both groups were evaluated at baseline and after 6 months . MAIN OUTCOME MEASURES Muscle power , calculated from ground reaction forces produced by l and ing after jumping as high as possible on a forceplate , cortical bone density , and biomarkers of bone turnover . RESULTS Over 6 months , muscle power improved by about 5 % in women who received the intervention , and it remained unchanged in controls ( P=.004 ) . Muscle force remained stable in both the intervention and control groups . No significant changes were observed in bone characteristics . CONCLUSION Reflex muscular contractions induced by vibration training improve muscle power in postmenopausal women According to experimental studies , low-amplitude high-frequency vibration is anabolic to bone tissue , whereas in clinical trials , the bone effects have varied . Given the potential of whole body vibration in bone training , this study aim ed at exploring the transmission of vertical sinusoidal vibration to the human body over a wide range of applicable amplitudes ( from 0.05 to 3 mm ) and frequencies ( from 10 to 90 Hz ) . Vibration-induced accelerations were assessed with skin-mounted triaxial accelerometers at the ankle , knee , hip , and lumbar spine in four males st and ing on a high-performance vibration platform . Peak vertical accelerations of the platform covered a range from 0.04 to 19 in units of G ( Earth 's gravitational constant ) . Substantial amplification of peak acceleration could occur between 10 and 40 Hz for the ankle , 10 and 25 Hz for the knee , 10 and 20 Hz for the hip , and at 10 Hz for the spine . Beyond these frequencies , the transmitted vibration power declined to 1/10th-1/1000 th of the power delivered by the platform . Transmission of vibration to the body is a complicated phenomenon because of nonlinearities in the human musculoskeletal system . These results may assist in estimating how the transmission of vibration-induced accelerations to body segments is modified by amplitude and frequency and how well the sinusoidal waveform is maintained . Although the attenuation of vertical vibration at higher frequencies is fortunate from the aspect of safety , amplitudes > 0.5 mm may result in greater peak accelerations than imposed at the platform and thus pose a potential hazard for the fragile musculoskeletal system Background Whole-body vibration ( WBV ) is a new type of exercise that has been increasingly tested for the ability to prevent bone fractures and osteoporosis in frail people . There are two currently marketed vibrating plates : a ) the whole plate oscillates up and down ; b ) reciprocating vertical displacements on the left and right side of a fulcrum , increasing the lateral accelerations . A few studies have shown recently the effectiveness of the up- and -down plate for increasing Bone Mineral Density ( BMD ) and balance ; but the effectiveness of the reciprocating plate technique remains mainly unknown . The aim was to compare the effects of WBV using a reciprocating platform at frequencies lower than 20 Hz and a walking-based exercise programme on BMD and balance in post-menopausal women . Methods Twenty-eight physically untrained post-menopausal women were assigned at r and om to a WBV group or a Walking group . Both experimental programmes consisted of 3 sessions per week for 8 months . Each vibratory session included 6 bouts of 1 min ( 12.6 Hz in frequency and 3 cm in amplitude with 60 ° of knee flexion ) with 1 min rest between bouts . Each walking session was 55 minutes of walking and 5 minutes of stretching . Hip and lumbar BMD ( g·cm-2 ) were measured using dual-energy X-ray absorptiometry and balance was assessed by the blind flamingo test . ANOVA for repeated measurements was adjusted by baseline data , weight and age . Results After 8 months , BMD at the femoral neck in the WBV group was increased by 4.3 % ( P = 0.011 ) compared to the Walking group . In contrast , the BMD at the lumbar spine was unaltered in both groups . Balance was improved in the WBV group ( 29 % ) but not in the Walking group . Conclusion The 8-month course of vibratory exercise using a reciprocating plate is feasible and is more effective than walking to improve two major determinants of bone fractures : hip BMD and balance This study was design ed to investigate the effects of vibration on muscle performance and mobility in a healthy , untrained , older population . Forty-three participants ( 23 men , 20 women , 66 - 85 y old ) performed tests of sit-to-st and ( STS ) , 5- and 10-m fast walk , timed up- and -go test , stair mobility , and strength . Participants were r and omly assigned to a vibration group , an exercise-withoutvibration group , or a control group . Training consisted of 3 sessions/wk for 2 mo . After training , the vibration and exercise groups showed improved STS ( 12.4 % , 10.2 % ) , 5-m fast walk ( 3.0 % , 3.7 % ) , and knee-extension strength ( 8.1 % , 7.2 % ) compared with the control ( p < 0.05 ) . Even though vibration training improved lower limb strength , it did not appear to have a facilitatory effect on functional-performance tasks compared with the exercise-without-vibration group . Comparable mobility and performance changes between the experimental groups suggest that improvements are linked with greater knee-extension strength and largely attributed to the unloaded squats performed by both exercise groups To determine whether 10 weeks of whole-body vibration ( WBV ) training has a significant effect on strength , muscle mass , muscle power , and mobility in older women , 26 subjects were r and omly assigned to a WBV training group ( n=13 ; mean age 79 years ) and a control ( CON ) group ( n=13 ; mean age 76 years ) . Maximal voluntary isometric contraction ( MVIC ) increased 38.8 % in the WBV group , without changes in the CON group . Electromyographic activity of the vastus medialis ( VM ) , the vastus lateralis , and the biceps femoris ( BF ) did not change in either group . Thigh muscle cross-sectional area increased significantly after training in VM ( 8.7 % ) and BF ( 15.5 % ) . Muscle power at 20 % , 40 % , and 60 % MVIC decreased from pre-test to post-test in the CON group ; however , WBV training prevented the decrease in the WBV group . Consequently , mobility , measured by the Timed Up and Go test , increased significantly after training ( 9.0 % ) only in the WBV group . Ten weeks of lower limb WBV training in older women produces a significant increase in muscle strength induced by thigh muscle hypertrophy , with no change in muscle power . The adaptations to WBV found in the present study may be of use in counteracting the loss of muscle strength and mobility associated with age-induced sarcopenia Background and aims : Exercise may enhance the effect of alendronate on bone mineral density ( BMD ) and reduce chronic back pain in elderly women with osteoporosis . The aim of this study was to determine whether whole-body vibration exercise would enhance the effect of alendronate on lumbar BMD and bone turnover , and reduce chronic back pain in post-menopausal women with osteoporosis . Methods : Fifty post-menopausal women with osteoporosis , 55–88 years of age , were r and omly divided into two groups of 25 patients each : one taking alendronate ( 5 mg daily , ALN ) and one taking alendronate plus exercise ( ALN+EX ) . Exercise consisted of whole-body vibration using a Galileo machine ( Novotec , Pforzheim , Germany ) , at an intensity of 20 Hz , frequency once a week , and duration of exercise 4 minutes . The study lasted 12 months . Lumbar BMD was measured by dual energy X-ray absorptiometry ( Hologic QDR 1500W ) . Urinary cross-linked N-terminal telopeptides of type I collagen ( NTX ) and serum alkaline phos-phatase ( ALP ) levels were measured by enzyme-linked immunosorbent assay and st and ard laboratory techniques , respectively . Chronic back pain was evaluated by face scale score at baseline and every 6 months . Results : There were no significant differences in baseline characteristics , including age , body mass index , years since menopause , lumbar BMD , urinary NTX and serum ALP levels , or face scale score between the two groups . The increase in lumbar BMD and the reduction in urinary NTX and serum ALP levels were similar in the ALN and ALN+EX groups . However , the reduction in chronic back pain was greater in the ALN+EX group than in the ALN Output:	Conclusion : Whole body vibration is beneficial for enhancing leg muscle strength among older adults . However , the review suggests that whole body vibration has no overall treatment effect on bone mineral density in older women . No r and omized trial has examined the effects of whole body vibration on bone mineral density in older men
MS22218	*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 Important barriers to the wider implementation of shared decision making ( SDM ) and risk communication in practice remain . The attitudes of professionals undergoing training in these approaches may inform how to overcome these barriers , but there are few such data yet available . AIM To identify the attitudes of professionals during participation in a large practice -based intervention study with substantial individual exposure to SDM and risk communication , and to assess their confidence with these approaches and reported frequency of implementing them . SETTING AND PARTICIPANTS Twenty general practitioners ( GPs ) who had been in practice between 1 and 10 years , and participated in an explanatory trial lasting 6 months . The trial interventions comprised training in SDM skills and the use of risk communication material s. The doctors consulted with up to 48 patients each ( mean = 40 , half of them audio-taped ) for the study . METHODS Question naire assessment s before and after each training stage . RESULTS The GPs indicated positive attitudes towards involving patients and towards the training interventions . They indicated that the risk information packs were applicable but had used them only occasionally with patients outside the trial . No statistically significant changes were associated with the specific interventions in terms of doctors ' confidence in discussing risk information after the risk communication intervention , or attitudes to patient involvement after the SDM intervention . Most attitudes and confidence ratings showed positive changes during the course of the trial as a cohort effect . Such positive changes were associated with female doctors more than male doctors , but not with MRCGP ( postgraduate vocational ) qualification . Time constraints remained important throughout the study in not implementing the approach more frequently . CONCLUSIONS Professionals appear receptive to patient involvement , and willing to acquire the relevant skills . SDM and risk communication training did not appear to contribute differentially to this . Practical barriers such as time constraints should probably be addressed with greater priority than the precise content of training or continuing professional development initiatives if ' involvement ' is to become a commoner experience for patients in primary care Background — Cardiac stress testing in patients at low risk for acute coronary syndrome is associated with increased false-positive test results , unnecessary downstream procedures , and increased cost . We judged it unlikely that patient preferences were driving the decision to obtain stress testing . Methods and Results — The Chest Pain Choice trial was a prospect i ve r and omized evaluation involving 204 patients who were r and omized to a decision aid or usual care and were followed for 30 days . The decision aid included a 100-person pictograph depicting the pretest probability of acute coronary syndrome and available management options ( observation unit admission and stress testing or 24–72 hours outpatient follow-up ) . The primary outcome was patient knowledge measured by an immediate postvisit survey . Additional outcomes included patient engagement in decision making and the proportion of patients who decided to undergo observation unit admission and cardiac stress testing . Compared with usual care patients ( n=103 ) , decision aid patients ( n=101 ) had significantly greater knowledge ( 3.6 versus 3.0 questions correct ; mean difference , 0.67 ; 95 % CI , 0.34–1.0 ) , were more engaged in decision making as indicated by higher OPTION ( observing patient involvement ) scores ( 26.6 versus 7.0 ; mean difference , 19.6 ; 95 % CI , 1.6–21.6 ) , and decided less frequently to be admitted to the observation unit for stress testing ( 58 % versus 77 % ; absolute difference , 19 % ; 95 % CI , 6%–31 % ) . There were no major adverse cardiac events after discharge in either group . Conclusions — Use of a decision aid in patients with chest pain increased knowledge and engagement in decision making and decreased the rate of observation unit admission for stress testing . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01077037 OBJECTIVE To test the effect of three questions ( what are my options ? what are the benefits and harms ? and how likely are these ? ) , on information provided by physicians about treatment options . METHODS We used a cross-over trial using two unannounced st and ardized patients ( SPs ) simulating a presentation of mild-moderate depression . One SP was assigned the intervention role ( asking the questions ) , the other the control role . An intervention and control SP visited each physician , order allocated r and omly . The study was conducted in family practice s in Sydney , Australia , during 2008 - 09 . Data were obtained from consultation audio-recordings . Information about treatment options and patient involvement were analyzed using the Assessing Communication about Evidence and Patient Preferences ( ACEPP ) tool and the OPTION tool . RESULTS Thirty-six SP visits were completed ( 18 intervention , 18 control ) . Scores were higher in intervention consultations than controls : ACEPP scores 21.4 vs. 16.6 , p<0.001 , difference 4.7 ( 95 % CI 2.3 - 7.0 ) and OPTION scores 36 vs. 25 , p=0.001 , difference 11.5 ( 95 % CI 5.1 - 17.8 ) , indicating greater information provision and behavior supporting patient involvement . CONCLUSION Asking these three questions improved information given by family physicians and increased physician facilitation of patient involvement . Practice implication s. These questions can drive evidence -based practice , strengthen patient-physician communication , and improve safety and quality BACKGROUND Patient involvement in the decision-making process is a key element for good clinical practice . Few data are available on patient involvement in psychiatry . AIMS To assess in a psychiatric out-patient context how psychiatrists involve patients in therapeutic decisions and to determine the extent to which patient and psychiatrist characteristics contribute to patient involvement . METHOD Eighty transcripts from audiotaped first out-patient consultations , conducted by 16 psychiatrists , were rated with the OPTION ( observing patient involvement ) scale . Interrater reliability indices were obtained for 30 r and omly selected interviews . Associations between OPTION scores and some clinical and socio-demographic variables were tested using t-test , ANOVA and Pearson 's correlation coefficient where appropriate . The distribution of scores for each psychiatrist was assessed by intracluster correlation coefficients . RESULTS Interrater reliability and internal consistency of the OPTION scale in the psychiatric setting were satisfactory . The total score and the ratings for the single OPTION items showed a skewed distribution , with a prevalence of scores in the low range of abilities , corresponding to minimal attempts to involve patients or a minimal skill level . CONCLUSIONS The OPTION scale proves to be a reliable instrument to assess patient involvement in a psychiatric setting . Psychiatrists showed poor patient involvement abilities parallel to previous findings in psychiatry and primary care . They need to be encouraged to share treatment decisions with their patients and to apply patient involvement skills . Further research is needed to establish which patient variables and clinical setting s in psychiatry are more amenable to shared decisions , and how participation of psychiatric patients in treatment decisions will affect the outcome BACKGROUND Poor quality of information transfer about the benefits and risks of statin drug use may result in patients not making informed decisions that they can act on in a timely fashion . METHODS The effect of a decision aid about statin drugs on treatment decision making in 98 patients with diabetes was determined in a cluster r and omized trial of decision aid vs control pamphlet , with concealed allocation , blinding of participants to study goals , and adherence to the intention-to-treat principle . Twenty-one endocrinologists conducted specialty outpatient metabolic consultations . Patients in the intervention group received Statin Choice , a tailored decision aid that presents the estimated 10-year cardiovascular risk , the absolute risk reduction with use of statin drugs , and the disadvantages of using statin drugs . Patients in the control group received the institution 's pamphlet about cholesterol management . We measured acceptability , knowledge about options and cardiovascular risk , and decisional conflict immediately after the visit , and adherence to pill taking was measured 3 months later . RESULTS Patients favored using the decision aid ( odds ratio [ OR ] , 2.8 ; 95 % confidence interval [ CI ] , 1.2 - 6.9 ) ; patients who received the decision aid ( n = 52 ) knew more ( difference , 2.4 of 9 points ; 95 % CI , 1.5 - 3.3 ) , had better estimated cardiovascular risk ( OR , 22.4 ; 95 % CI , 5.9 - 85.6 ) and potential absolute risk reduction with statin drugs ( OR , 6.7 ; 95 % CI , 2.2 - 19.7 ) , and had less decisional conflict ( difference , -10.6 ; 95 % CI , -15.4 to -5.9 on a 100-point scale ) than did patients in the control group ( n = 46 ) . Of 33 patients in the intervention group taking statin drugs at 3 months , 2 reported missing 1 dose or more in the last week compared with 6 of 29 patients in the control group taking statin drugs ( OR , 3.4 ; 95 % CI , 1.5 - 7.5 ) . CONCLUSIONS A decision aid enhanced decision making about statin drugs and may have favorably affected drug adherence BACKGROUND Patient involvement in the choice of antihyperglycemic agents could improve adherence and optimize glycemic control in patients with type 2 diabetes mellitus . METHODS We conducted a pilot , cluster r and omized trial of Diabetes Medication Choice , a decision aid that describes 5 antihyperglycemic drugs , their treatment burden ( adverse effects , administration , and self-monitoring dem and s ) , and impact on hemoglobin A(1c ) ( HbA(1c ) ) levels . Twenty-one clinicians were r and omized to use the decision aid during the clinical encounter and 19 to dispense usual care and an educational pamphlet . We used surveys and video analysis to assess postvisit decisional outcomes , and medical and pharmacy records to assess 6-month medication adherence and HbA(1c ) levels . RESULTS Compared with usual care patients ( n = 37 ) , patients receiving the decision aid ( n = 48 ) found the tool more helpful ( clustered-adjusted mean difference [ AMD ] in a 7-point scale , 0.38 ; 95 % confidence interval [ CI ] , 0.04 - 0.72 ) ; had improved knowledge ( AMD , 1.10 of 10 questions ; 95 % CI , 0.11 - 2.09 ) ; and had more involvement in making decisions about diabetes medications ( AMD , 21.8 of 100 ; 95 % CI , 13.0 - 30.5 ) . At 6-month follow-up , both groups had nearly perfect medication use ( median , 100 % of days covered ) , with better adherence ( AMD , 9 % more days covered ; 95 % CI , 4%-14 % ) and persistence ( AMD , 12 more days covered ; 95 % CI , 3 - 21 days ) in the usual care group , and no significant impact on HbA(1c ) levels ( AMD , 0.01 ; 95 % CI , -0.49 to 0.50 ) . CONCLUSION An innovative decision aid effectively involved patients with type 2 diabetes mellitus in decisions about their medications but did not improve adherence or HbA(1c ) levels . Trial Registration clinical trials.gov Identifier : NCT00388050 OBJECTIVE Poor adherence to therapy , perhaps related to unaddressed patient preferences , limits the effectiveness of osteoporosis treatment in at-risk women . A parallel patient-level r and omized trial in primary care practice s was performed . METHODS Eligible postmenopausal women with bone mineral density T-scores less than -1.0 and not receiving bisphosphonate therapy were included . In addition to usual primary care , intervention patients received a decision aid ( a tailored pictographic 10-year fracture risk estimate , absolute risk reduction with bisphosphonates , side effects , and out-of-pocket cost ) , and control patients received a st and ard brochure . Knowledge transfer , patient involvement in decision-making , and rates of bisphosphonate start and adherence were studied . Data came from medical records , post-visit written and 6-month phone surveys , video recordings of clinical encounters , and pharmacy prescription profiles . RESULTS A total of 100 patients ( range of 10-year fracture risk , 6%-60 % ) were allocated r and omly to receive the decision aid ( n=52 ) or usual care ( n=48 ) . Patients receiving the decision aid were 1.8 times more likely to correctly identify their 10-year fracture risk ( 49 % vs 28 % ; 95 % confidence interval [ CI ] , 1.03 - 3.2 ) and 2.7 times more likely to identify their estimated risk reduction with bisphosphonates ( 43 % vs 16 % ; 95 % CI , 1.3 - 5.7 ) . Patient involvement improved with the decision aid by 23 % ( 95 % CI , 13.6 - 31.4 ) . Bisphosphonates were started by 44 % of patients receiving the decision aid and 40 % of patients receiving usual care . Adherence at 6 months was similarly high across both groups , but the proportion with more than 80 % adherence was higher with the decision aid ( n=23 [ 100 % ] vs n=14 [ 74 % ] ; P = .009 ) . CONCLUSION A decision aid improved the quality of clinical decisions about bisphosphonate therapy in at-risk postmenopausal women , did not affect start rates , and may have improved adherence BACKGROUND A consulting method known as ' shared decision making ' ( Output:	Whatever the clinical context , few health-care providers consistently attempt to facilitate patient involvement , and even fewer adjust care to patient preferences . However , both SDM interventions and longer consultations could improve this
MS22219	*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 Benzodiazepines are extensively used in primary care , but their long-term use is associated with adverse health outcomes and dependence . AIMS To analyse the efficacy of two structured interventions in primary care to enable patients to discontinue long-term benzodiazepine use . METHOD A multicentre three-arm cluster r and omised controlled trial was conducted , with r and omisation at general practitioner level ( trial registration IS RCT N13024375 ) . A total of 532 patients taking benzodiazepines for at least 6 months participated . After all patients were included , general practitioners were r and omly allocated ( 1:1:1 ) to usual care , a structured intervention with follow-up visits ( SIF ) or a structured intervention with written instructions ( SIW ) . The primary end-point was the last month self-declared benzodiazepine discontinuation confirmed by prescription cl aims at 12 months . RESULTS At 12 months , 76 of 168 ( 45 % ) patients in the SIW group and 86 of 191 ( 45 % ) in the SIF group had discontinued benzodiazepine use compared with 26 of 173 ( 15 % ) in the control group . After adjusting by cluster , the relative risks for benzodiazepine discontinuation were 3.01 ( 95 % CI 2.03 - 4.46 , P<0.0001 ) in the SIW and 3.00 ( 95 % CI 2.04 - 4.40 , P<0.0001 ) in the SIF group . The most frequently reported withdrawal symptoms were insomnia , anxiety and irritability . CONCLUSIONS Both interventions led to significant reductions in long-term benzodiazepine use in patients without severe comorbidity . A structured intervention with a written individualised stepped-dose reduction is less time-consuming and as effective in primary care as a more complex intervention involving follow-up visits This study examined the potential for cognitive morbidity associated with the long-term use of benzodiazepine ( BZ ) sedative-hypnotics in a sample of healthy older adults . Tests of memory , attention and processing speed were conducted prior to and 1 month after drug discontinuation for 25 BZ-users and at similar intervals for 26 healthy control subjects . After controlling for differences in affective status between BZ-users and controls , there were no significant group differences in cognitive performance . However , BZ-users showed greater gains on tests of attention and speed of processing at repeat testing compared with controls this improvement was not attributable to a change in affective status . These findings suggest that there may be subtle and reversible effects of long-term BZ use on speed-dependent tasks in older adults . However , the magnitude of these effects is quite small and may be of little clinical significance in the healthy elderly BACKGROUND Benzodiazepine use by elderly patients is associated with adverse outcomes including increased risk of falls and fractures , motor vehicle accidents and cognitive impairment . Recent studies suggest that individualized feedback and education to physicians may improve drug prescribing . In this study , we evaluated an intervention to address the inappropriate prescribing of benzodiazepines for elderly patients . METHODS We identified 1624 primary care physicians who wrote at least 10 prescriptions for the target drugs in a 2-month period and r and omly assigned these physicians to the intervention group or the control group . We obtained data from the Ontario Drug Benefit cl aims data base , which covers all Ontario residents aged 65 years and over for drugs selected from a minimally restrictive formulary . Every 2 months for 6 months , confidential profiles of benzodiazepine prescription use coupled with evidence -based educational bulletins were mailed to the intervention group . The control group received feedback and educational bulletins about first-line antihypertension drug prescribing for elderly patients . Our main outcome measures were reductions in the proportion of each physician 's total benzodiazepine prescriptions for long-acting agents , combinations of benzodiazepines with other psychoactive medications ( including other benzodiazepines ) and long-term benzodiazepine therapy . RESULTS After r and omization , 168 physicians agreed to be in the intervention group and 206 in the control group . Their demographic and prescribing characteristics were similar . Although the proportion of long-acting benzodiazepine prescriptions decreased by 0.7 % in the intervention group between the baseline period and the end of the intervention period ( from 20.3 % , or a mean of 29.5 prescriptions , to 19.6 % , or a mean of 27.7 prescriptions ) and increased by 1.1 % in the control group ( from 19.8 % , or a mean of 26.4 prescriptions , to 20.9 % , or a mean of 27.7 prescriptions ) ( p = 0.036 ) , this difference was not clinical ly significant . There was no significant difference over the study period in either combination prescribing of benzodiazepines or in prescriptions for long-term benzodiazepine therapy . INTERPRETATION We did not find that a program of confidential feedback and educational material offered to Ontario primary care physicians had a clinical ly significant impact on their benzodiazepine prescribing 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 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 About two-thirds of long-term users of benzodiazepines in the population are able to discontinue this drug with the aid of supervised programmes for tapering off . Little is known about the long-term outcome of such programmes , and they have never been compared with usual care . After a 15-month follow-up of a r and omised controlled trial comparing such a programme with and without psychotherapy with usual care , we found significantly higher longitudinal abstinence rates in long-term benzodiazepine users who received a benzodiazepine tapering-off programme without psychotherapy ( 25 out of 69 , 36 % ) compared with those who received usual care ( 5 out of 33,15 % ; P=0.03 ) OBJECTIVES To test the effect of an adapted U.S. model of pharmaceutical care on prescribing of inappropriate psychoactive ( anxiolytic , hypnotic , and antipsychotic ) medications and falls in nursing homes for older people in Northern Irel and ( NI ) . DESIGN Cluster r and omized controlled trial . SETTING Nursing homes r and omized to intervention ( receipt of the adapted model of care ; n=11 ) or control ( usual care continued ; n=11 ) . PARTICIPANTS Residents aged 65 and older who provided informed consent ( N=334 ; 173 intervention , 161 control ) . INTERVENTION Specially trained pharmacists visited intervention homes monthly for 12 months and review ed residents ' clinical and prescribing information , applied an algorithm that guided them in assessing the appropriateness of psychoactive medication , and worked with prescribers ( general practitioners ) to improve the prescribing of these drugs . The control homes received usual care . MEASUREMENTS The primary end point was the proportion of residents prescribed one or more inappropriate psychoactive medicine according to st and ardized protocol s ; falls were evaluated using routinely collected falls data m and ated by the regulatory body for nursing homes in NI . RESULTS The proportion of residents taking inappropriate psychoactive medications at 12 months in the intervention homes ( 25/128 , 19.5 % ) was much lower than in the control homes ( 62/124 , 50.0 % ) ( odds ratio=0.26 , 95 % confidence interval=0.14 - 0.49 ) after adjustment for clustering within homes . No differences were observed at 12 months in the falls rate between the intervention and control groups . CONCLUSION Marked reductions in inappropriate psychoactive medication prescribing in residents result ed from pharmacist review of targeted medications , but there was no effect on falls OBJECTIVE To investigate the effectiveness of an educational Quality Use of Medicines program , delivered at the level of general practice , on medicines use , falls and quality of life in people aged > or = 65 years . DESIGN Cluster r and omised controlled trial conducted in 2002 . SETTING General practice s in the Hunter Region , New South Wales , Australia . PARTICIPANTS Twenty general practitioners recruited 849 patients to participate in the study . INTERVENTION Education ( academic detailing , provision of prescribing information and feedback ) ; medication risk assessment ; facilitation of medication review ; financial incentives . MAIN OUTCOME MEASURES PRIMARY MEASURES a composite score reflecting use of benzodiazepines , non-steroidal anti-inflammatory drugs ( NSAIDs ) and thiazide diuretics ; secondary measures : use of medication review s , occurrence of falls , quality of life ( as assessed by SF-12 and EQ-5D survey scores . RESULTS Compared with the control group , participants in the intervention group had increased odds of having an improved medication use composite score ( odds ratio [ OR ] , 1.86 ; 95 % CI , 1.21 - 2.85 ) at 4-month follow-up but not at 12 months . At 4-month follow-up , the intervention group had reduced odds of using NSAIDs ( OR , 0.62 ; 95 % CI , 0.39 - 0.99 ) and showed a non-significant reduction in use of benzodiazepines ( OR , 0.51 ; 95 % CI , 0.20 - 1.30 ) and thiazide diuretics ( OR , 0.70 ; 95 % CI , 0.48 - 1.01 ) . Changes in drug use were not significant at 12-month follow-up . At 12 months , intervention-group participants had lower adjusted ORs ( AORs ) for having a fall ( AOR , 0.61 ; 95 % CI , 0.41 - 0.91 ) , injury ( AOR , 0.56 ; 95 % CI , 0.32 - 0.96 ) , and injury requiring medical attention ( AOR , 0.46 ; 95 % CI , 0.30 - 0.70 ) . Quality -of-life scores were unaffected by the intervention . CONCLUSION Education and systems for medication review conducted by GPs can be used to improve use of medicines . These interventions are associated with a reduction in falls among older people , without adverse effects on quality of life BACKGROUND Although psychoactive medications have substantial side effects in the elderly , these drugs are used frequently in nursing homes . Few interventions have succeeded in changing this situation , and little is known about the clinical effects of such interventions . METHODS We studied six matched pairs of nursing homes ; at one r and omly selected nursing home in each pair , physicians , nurses , and aides participated in an educational program in geriatric psychopharmacology . At base line we determined the type and quantity of drugs received by all residents ( n = 823 ) , and a blinded observer performed st and ardized clinical assessment s of the residents who were taking psychoactive medications . After the five-month program , drug use and patient status were reassessed . RESULTS Scores on an index of psychoactive-drug use , measuring both the magnitude and the probable inappropriateness of medication use , declined significantly more in the nursing homes in which the program was carried out ( experimental nursing homes ) than in the control nursing homes ( decrease , 27 percent vs. 8 percent ; P = 0.02 ) . The use of antipsychotic drugs was dis Output:	Patient-centered interventions that provided patient information effectively increased the appropriate use of BZDs . The educational approaches for HCPs that aim ed to achieve appropriate prescription reported inconsistent results . The methods that combined informing patients and HCPs led to a significant reduction in BZD use . Conclusions This is the first review of studies focused on patient-centered approaches to reducing the inappropriate prescription and use of BZDs and z-drugs . The patient-centered dimension of patient information was responsible for a decrease in BZD and z-drug consumption . Further , in some studies , the patient-centered dimensions responsible for reducing the prescription and use of BZDs and z-drugs were the clinician 's essential characteristics and clinician-patient communication
MS22220	*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 Fast-acting medications for the management of anxiety are important to patients and society . Measuring early onset , however , requires a sensitive and clinical ly responsive tool . This study evaluates the psychometric properties of a patient-reported Global Anxiety - Visual Analog Scale ( GA-VAS ) . Methods Data from a double-blind , r and omized , placebo-controlled study of lorazepam and paroxetine in patients with Generalized Anxiety Disorder were analyzed to assess the reliability , validity , responsiveness , and utility of the GA-VAS . The GA-VAS was completed at clinic visits and at home during the first week of treatment . Targeted psychometric analyses — test-retest reliabilities , validity correlations , responsiveness statistics , and minimum important differences — were conducted . Results The GA-VAS correlates well with other anxiety measures , at Week 4 , r = 0.60 ( p < 0.0001 ) with the Hamilton Rating Scale for Anxiety and r = 0.74 ( p < 0.0001 ) with the Hospital Anxiety and Depression Scale - Anxiety subscale . In terms of convergent and divergent validity , the GA-VAS correlated -0.54 ( p < 0.0001 ) , -0.48 ( p < 0.0001 ) , and -0.68 ( p < 0.0001 ) with the SF-36 Emotional Role , Social Function , and Mental Health subscales , respectively , but correlated much lower with the SF-36 physical functioning subscales . Preliminary minimum important difference estimates cluster between 10 and 15 mm . Conclusions The GA-VAS is capable of validly and effectively capturing a reduction in anxiety as quickly as 24 hours post-dose Cognitive re appraisal can foster emotion regulation , yet less is known about whether cognitive re appraisal alters neuroendocrine stress reactivity . Some initial evidence suggests that although long-term training in cognitive behavioral therapy techniques ( which include re appraisal as a primary training component ) can reduce cortisol reactivity to stress , some studies also suggest that re appraisal is associated with heightened cortisol stress reactivity . To address this mixed evidence , the present report describes two experimental studies that r and omly assigned young adult volunteers to use cognitive re appraisal while undergoing laboratory stressors . Relative to the control condition , participants in the re appraisal conditions showed greater peak cortisol reactivity in response to a socially evaluative speech task ( Experiment 1 , N=90 ) and to a physical pain cold pressor task ( Experiment 2 , N=94 ) . Participants in the cognitive re appraisal group also reported enhanced anticipatory psychological appraisal s of self-efficacy and control in Experiment 2 and greater post-stressor self-efficacy . There were no effects of the re appraisal manipulation on positive and negative subjective affect , pain , or heart rate in either experiment . These findings suggest that although cognitive re appraisal fosters psychological perceptions of self-efficacy and control under stress , this effortful emotion regulation strategy in the short-term may increase cortisol reactivity . Discussion focuses on promising psychological mechanisms for these cognitive re appraisal effects Research ers have theorized that changing the way we think about our bodily responses can improve our physiological and cognitive reactions to stressful events . However , the underlying processes through which mental states improve downstream outcomes are not well understood . To this end , we examined whether reappraising stress-induced arousal could improve cardiovascular outcomes and decrease attentional bias for emotionally negative information . Participants were r and omly assigned to either a re appraisal condition in which they were instructed to think about their physiological arousal during a stressful task as functional and adaptive , or to 1 of 2 control conditions : attention reorientation and no instructions . Relative to controls , participants instructed to reappraise their arousal exhibited more adaptive cardiovascular stress responses-increased cardiac efficiency and lower vascular resistance- and decreased attentional bias . Thus , reappraising arousal shows physiological and cognitive benefits . Implication s for health and potential clinical applications are discussed OBJECTIVE This study sought to examine the relationship among the amount of stress , the perception that stress affects health , and health and mortality outcomes in a nationally representative sample of U.S. adults . METHODS Data from the 1998 National Health Interview Survey were linked to prospect i ve National Death Index mortality data through 2006 . Separate logistic regression models were used to examine the factors associated with current health status and psychological distress . Cox proportional hazard models were used to determine the impact of perceiving that stress affects health on all-cause mortality . Each model specifically examined the interaction between the amount of stress and the perception that stress affects health , controlling for sociodemographic , health behavior , and access to health care factors . RESULTS 33.7 % of nearly 186 million ( unweighted n = 28,753 ) U.S. adults perceived that stress affected their health a lot or to some extent . Both higher levels of reported stress and the perception that stress affects health were independently associated with an increased likelihood of worse health and mental health outcomes . The amount of stress and the perception that stress affects health interacted such that those who reported a lot of stress and that stress impacted their health a lot had a 43 % increased risk of premature death ( HR = 1.43 , 95 % CI [ 1.2 , 1.7 ] ) . CONCLUSIONS High amounts of stress and the perception that stress impacts health are each associated with poor health and mental health . Individuals who perceived that stress affects their health and reported a large amount of stress had an increased risk of premature death Prior research suggests that stress can be harmful in high-stakes context s such as negotiations . However , few studies actually measure stress physiologically during negotiations , nor do studies offer interventions to combat the potential negative effects of heightened physiological responses in negotiation context s. In the current research , we offer evidence that the negative effects of cortisol increases on negotiation performance can be reduced through a re appraisal of anxiety manipulation . We experimentally induced adaptive appraisal s by r and omly assigning 97 male and female participants to receive either instructions to appraise their anxiety as beneficial to the negotiation or no specific instructions on how to appraise the situation . We also measured participants ’ cortisol responses prior to and following the negotiation . Results revealed that cortisol increases were positively related to negotiation performance for participants who were told to view anxiety as beneficial , and not detrimental , for negotiation performance ( appraisal condition ) . In contrast , cortisol increases were negatively related to negotiation performance for participants given no instructions on appraising their anxiety ( control condition ) . These findings offer a means through which to combat the potentially deleterious effects of heightened cortisol reactivity on negotiation outcomes Background The consequences of stress are typically regarded from a deficit-oriented approach , conceptualizing stress to be entirely negative in its outcomes . This approach is unbalanced , and may further hinder individuals from engaging in adaptive coping . In the current study , we explored whether negative views and beliefs regarding stress interacted with a stress framing manipulation ( positive , neutral and negative ) on measures of stress reactivity for both psychosocial and physiological stressors . Method Ninety participants were r and omized into one of three framing conditions that conceptualized the experience of stress in balanced , unbalanced-negative or unbalanced-positive ways . After watching a video on stress , participants underwent a psychosocial ( Trier Social Stress Test ) , or a physiological ( CO2 challenge ) method of stress-induction . Subjective and objective markers of stress were assessed . Results Most of the sample d population regarded stress as negative prior to framing . Further , subjective and objective reactivity were greater to the TSST compared to the CO2 challenge . Additionally , significant cubic trends were observed in the interactions of stress framing and stress-induction method ologies on heart rate and blood pressure . Balanced framing conditions in the TSST group had a significantly larger decrease in heart rate and diastolic blood pressure following stress compared to the positive and negative framing conditions . Conclusion Findings confirmed a deficit-orientation of stress within the sample d population . In addition , results highlighted the relative efficacy of the TSST compared to CO2 as a method of stress provocation . Finally , individuals in framing conditions that posited stress outcomes in unbalanced manners responded to stressors less efficiently . This suggests that unbalanced framing of stress may have set forth unrealistic expectations regarding stress that later hindered individuals from adaptive responses to stress . Potential benefits of alternative conceptualizations of stress on stress reactivity are discussed , and suggestions for future research are made OBJECTIVES Verbally administered numerical rating scales ( NRSs ) from 0 to 10 are often used to measure pain , but they have not been vali date d in the emergency department ( ED ) setting . The authors wished to assess the comparability of the NRS and visual analog scale ( VAS ) as measures of acute pain , and to identify the minimum clinical ly significant difference in pain that could be detected on the NRS . METHODS This was a prospect i ve cohort study of a convenience sample of adults presenting with acute pain to an urban ED . Patients verbally rated pain intensity as an integer from 0 to 10 ( 0 = no pain , 10 = worst possible pain ) , and marked a 10-cm horizontal VAS bounded by these descriptors . VAS and NRS data were obtained at presentation , 30 minutes later , and 60 minutes later . At 30 and 60 minutes , patients were asked whether their pain was " much less , " " a little less , " " about the same , " " a little more , " or " much more . " Differences between consecutive pairs of measurements on the VAS and NRS obtained at 30-minute intervals were calculated for each of the five categories of pain descriptor . The association between VAS and NRS scores was expressed as a correlation coefficient . The VAS scores were regressed on the NRS scores in order to assess the equivalence of the measures . The mean changes associated with descriptors " a little less " or " a little more " were combined to define the minimum clinical ly significant difference in pain measured on the VAS and NRS . RESULTS Of 108 patients entered , 103 provided data at 30 minutes and 86 at 60 minutes . NRS scores were strongly correlated to VAS scores at all time periods ( r = 0.94 , 95 % CI = 0.93 to 0.95 ) . The slope of the regression line was 1.01 ( 95 % CI = 0.97 to 1.06 ) and the y-intercept was -0.34 ( 95 % CI = -0.67 to -0.01 ) . The minimum clinical ly significant difference in pain was 1.3 ( 95 % CI = 1.0 to 1.5 ) on the NRS and 1.4 ( 95 % CI = 1.1 to 1.7 ) on the VAS . CONCLUSIONS The findings suggest that the verbally administered NRS can be substituted for the VAS in acute pain measurement ABSTRACT Background and Objectives : This study examined the effects of arousal re appraisal on cardiovascular responses , dem and and re source evaluations , self-confidence , performance and attention under pressurized conditions . A recent study by Moore et al. [ 2015 . Reappraising threat : How to optimize performance under pressure . Journal of Sport and Exercise Psychology , 37(3 ) , 339–343 . doi:10.1123/jsep.2014 - 0186 ] suggested that arousal re appraisal is beneficial to the promotion of challenge states and leads to improvements in single-trial performance . This study aim ed to further the work of Moore and colleagues ( 2015 ) by examining the effects of arousal re appraisal on cardiovascular responses , dem and and re source evaluations , self-confidence , performance and attention in a multi-trial pressurized performance situation . Design and Methods : Participants were r and omly assigned to either an arousal re appraisal intervention or control condition , and completed a pressurized dart throwing task . The intervention encouraged participants to view their physiological arousal as facilitative rather than debilitative to performance . Measures of cardiovascular reactivity , dem and and re source evaluations , self-confidence , task performance and attention were recorded . Results : The re appraisal group displayed more favorable cardiovascular reactivity and reported higher re source evaluations and higher self-confidence than the control group but no task performance or attention effects were detected . Conclusion : These findings demonstrate the strength of arousal re appraisal in promoting adaptive stress responses , perceptions of re sources and self-confidence Background and objectives : Few studies related to the impact of different emotion regulation strategies on anxiety have used externally and ecologically valid emotion-eliciting stimuli or Eastern population s. The present study compares the effects of re appraisal , suppression , and acceptance on anxiety induced by a simulated job interview in a Chinese sample . Methods : Eighty-two subjects were r and omly assigned to one of four instructions : re appraisal , suppression , acceptance , or no-regulation strategies during a simulated job interview . Anxiety was assessed with an observer-based behavior rating scale during the interview and the State Anxiety Inventory before , during , and after the interview . Results : A repeated- measures MANOVA indicated a significantly greater reduction in anxiety in the re appraisal and acceptance groups compared to the control group during the interview ( re appraisal : d = 1.42 ; acceptance : d = 1.30 ; each p < .001 ) , but not during the recovery stage . The suppression and control group did not differ in any stage . Suppression led to a higher ( pmax < .04 ) anxiety than re appraisal /acceptance in the anticipation ( d = 0.65/0.68 ) , interview ( d = 0.87/0.79 ) , and recovery stages ( d = 0.94/1.03 ) . No significant differences were found between re appraisal and acceptance . Conclusions : Output:	RESULTS Findings from both the meta- analysis and systematic review revealed that overall , re appraisal interventions are effective in attenuating subjective responsivity to stress . On one h and , findings may suggest a promising avenue for the effective management of self-reported stress and optimization of stress responses .
MS22221	*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: Current therapies for chronic hepatitis B ( CHB ) have a number of limitations , and better treatment options are needed . Peginterferon alpha-2a ( 40 kDa ) is superior to conventional interferon alpha-2a in the treatment of chronic hepatitis C. This is the first report on peginterferon alpha-2a ( 40 kDa ) in the treatment of CHB . In this phase II study , 194 patients with CHB not previously treated with conventional interferon-alpha were r and omized to receive weekly subcutaneous doses of peginterferon alpha-2a ( 40 kDa ) 90 , 180 or 270 microg , or conventional interferon alpha-2a 4.5 MIU three times weekly . Twenty-four weeks of therapy were followed by 24 weeks of treatment-free follow-up . All subjects were assessed for loss of hepatitis B e antigen ( HBeAg ) , presence of hepatitis B antibody ( anti-HBe ) , suppression of hepatitis B virus ( HBV ) DNA , and normalization of serum alanine transaminase ( ALT ) after follow-up . At the end of follow-up , HBeAg was cleared in 37 , 35 and 29 % of patients receiving peginterferon alpha-2a ( 40 kDa ) 90 , 180 and 270 microg , respectively , compared with 25 % of patients on conventional interferon alpha-2a . The combined response ( HBeAg loss , HBV DNA suppression , and ALT normalization ) of all peginterferon alpha-2a ( 40 kDa ) doses combined was twice that achieved with conventional interferon alpha-2a ( 24%vs 12 % ; P = 0.036 ) . All treatment groups were similar with respect to frequency and severity of adverse events . These results indicate that peginterferon alpha-2a ( 40 kDa ) is superior in efficacy to conventional interferon alpha-2a in chronic hepatitis B based on clearance of HBeAg , suppression of HBV DNA , and normalization of ALT BACKGROUND Treatment with adefovir dipivoxil for 48 weeks result ed in histologic , virologic , and biochemical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We evaluated the effect of continued therapy as compared with cessation of therapy . METHODS One hundred eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to receive 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks ( ratio , 2:1 ) . After week 48 , patients receiving adefovir dipivoxil were again r and omly assigned either to receive an additional 48 weeks of the drug or to switch to placebo . Patients originally assigned to placebo were switched to adefovir dipivoxil . Patients treated with adefovir dipivoxil during weeks 49 through 96 were subsequently offered continued therapy . The primary end points were changes in hepatitis B virus ( HBV ) DNA and alanine aminotransferase levels . RESULTS Treatment with adefovir dipivoxil result ed in a median decrease in serum HBV DNA of 3.47 log copies per milliliter ( on a base-10 scale ) at 96 weeks and 3.63 log copies per milliliter at 144 weeks . HBV DNA levels were less than 1000 copies per milliliter in 71 percent of patients at week 96 and 79 percent at week 144 . In the majority of patients who were switched from adefovir dipivoxil to placebo , the benefit of treatment was lost ( median change in HBV DNA levels from baseline , -1.09 log copies per milliliter ; only 8 percent of patients had levels below 1000 copies per milliliter at week 96 ) . Side effects during weeks 49 through 144 were similar to those during the initial 48 weeks . Resistance mutations rtN236 T and rtA181V were identified in 5.9 percent of patients after 144 weeks . CONCLUSIONS In patients with HBeAg-negative chronic hepatitis B , the benefits achieved from 48 weeks of adefovir dipivoxil were lost when treatment was discontinued . In patients treated for 144 weeks , benefits were maintained , with infrequent emergence of viral resistance To evaluate the effect of interferon and the benefit of prednisolone pretreatment in Oriental patients with chronic active hepatitis B , 120 male Chinese patients were r and omly allocated to receive : 1 ) group A : a 4-week course of prednisolone followed by 2 weeks of no treatment and then a 12-week course of human lymphoblastoid interferon , 4 to 6 MU/m2 intramuscularly ; 2 ) group B : as group A , but with placebo given instead of prednisolone ; 3 ) group C : an 18-week course of placebo . Clearance of serum hepatitis B virus-DNA and HBeAg ( complete response ) was achieved in 21 % of group A , 5 % of group B and none of group C at the end of therapy ( A vs B : p = 0.054 ; A vs C : p < 0.01 ) . When assessed 12 months after the end of therapy , the complete response rate was 46 % in group A , 24 % in group B and 25 % in group C ( p < 0.05 ) . Those with baseline alanine transaminase < or = 200 U/l showed a better response to interferon following prednisolone withdrawal ( 48 % ) than with interferon therapy alone ( 20 % , p = 0.056 ) and no treatment ( 9 % , p < 0.01 ) . Those with a baseline serum hepatitis B virus-DNA < or = 1000 pg/ml also showed a higher complete response rate when pretreated with prednisolone ( 59 % ) than when treated with interferon alone ( 29 % , p = 0.084 ) or untreated ( 22 % , p < 0.03 ) . The strongest independent predictor of a response to treatment was prednisolone withdrawal ( p < 0.05 ) . None of the responders lost hepatitis B surface antigen . ( ABSTRACT TRUNCATED AT 250 WORDS To assess the impact of sequential therapy with adefovir dipivoxil ( ADV ) and pegylated interferon alfa-2a ( PEG-IFN ) on virological ( serum HBV-DNA ) and serological ( serum HBsAg ) response in 20 consecutive HBeAg-negative patients . Patients received ADV for 20 weeks , then ADV and PEG-IFN for 4 weeks and lastly PEG-IFN for 44 weeks . Serum HBV-DNA and HBsAg were assessed at baseline , during therapy ( weeks 20 , 44 and 68 ) and follow-up ( weeks 92 and 116 ) . Sustained virological response ( SVR ) was defined as serum HBV-DNA < 10 000 copies/mL ( partial ) or < 70 copies/mL ( complete ) 24 weeks after stopping treatment . A serological response was defined as a serum HBsAg decrease ≥1 log(10 ) IU/mL at the end of treatment . Baseline median serum HBV-DNA and HBsAg levels were 7.6 log(10 ) copies/mL and 3.8 log(10 ) IU/mL , respectively . Ten patients ( 50 % ) achieved SVR , six of them had partial response and four complete response . Four patients ( 20 % ) achieved serological response . Complete SVRs showed a major and steep decline in HBsAg level with a median decrease of 0.5 , 1.6 and 2.0 log(10 ) IU/mL at treatment week 20 , 44 and 68 , respectively . Partial SVRs showed a slight and slow decline in serum HBsAg level ( 0.1 , 0.4 , and 0.6 log IU/mL at weeks 20 , 44 and 68 , respectively ) . On-treatment serum HBsAg decrease had a high accuracy to predict SVR ( AUROC = 0.88 ) . Our results suggest that sequential therapy might be an interesting strategy for HBeAg-negative patients . Serum HBsAg kinetics seem to be an accurate tool to predict SVR . Large clinical trials are needed to explore this strategy with more potent analogues 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 Treatment with peginterferon α-2a ( PegIFN ) for 48 weeks is the st and ard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus ( HBV ) , but with limited treatment efficacy . A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population . Methods 128 HBeAg-negative patients ( 120 genotype D ) were r and omised to weekly 180 μg PegIFN for 48 weeks ( group A , n=51 ) , 180 μg PegIFN for 48 weeks followed by 135 μg weekly for an additional 48 weeks ( group B , n=52 ) or 180 μg PegIFN plus lamivudine ( 100 mg/day ) for 48 weeks then 135 μg PegIFN for 48 weeks ( group C , n=25 ) . Endpoints were alanine aminotransferase normalisation plus HBV DNA < 3400 IU/ml ( primary ) , HBV DNA < 2000 IU/ml and HBsAg clearance at 48 weeks after treatment . Results Forty-eight weeks after treatment , six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA < 3400 IU/ml ( 11.8 % vs 25.0 % , p=0.08 ) , 6 vs 15 patients had HBV DNA < 2000 IU/ml ( 11.8 % vs 28.8 % , p=0.03 ) , 0 vs 3 achieved HBsAg clearance ( 0 % vs 5.8 % , p=0.24 ) and 0 vs 5 had HBsAg < 10 IU/ml ( 0 % vs 9.6 % , p=0.06 ) . While extended PegIFN treatment was the strongest independent predictor of response , the combination with lamivudine did not improve responses . Discontinuation rates were similar among the groups ( 19.6 % , 23.1 % , 32.0 % , p=0.81 ) and were mostly due to PegIFN-related adverse events . Conclusions In HBeAg-negative genotype D patients with chronic hepatitis B , PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment . Trial registration number http:// Clinical Trials.gov registration number : NCT01095835 The focus of this study was to evaluate the safety and efficacy of sequential peginterferon α-2a ( Pegasys ) therapy for chronic hepatitis B with acute exacerbation [ ALT > 10 × upper limit of normal ( ULN ) , bilirubin < 2.0 mg/dL ] . Four groups of patients categorized by HBeAg status and treatment regimens were studied since May 2007 . Nineteen HBeAg-positive patients ( Group 1 ) had received entecavir pretreatment ( when ALT > 10 × ULN ) plus Pegasys ( 180 μg/kg/week , when ALT was 5–10 × ULN ) for 24 weeks . Thirteen HBeAg-negative patients ( Group 2 ) had the same protocol for 48 weeks . In both groups , entecavir was then discontinued 14 days after the initiation of Pegasys . The results were compared , respectively , to 35 HBeAg-positive patients ( Group 3 ) and 24 HBeAg-negative patients ( Group 4 ) , all with ALT > 5 × ULN , under continual entecavir monotherapy . The ALT levels of patients in Group 1 and 2 who had received entecavir pretreatment for a duration of 19.63 ± 3.34 days were below four times of ULN following 4 weeks of Pegasys treatment . At week 96 , the rates of sustained virological response were 69.2 % ( 9/13 ) and 80 % ( 8/10 ) , and the relapse rates were 23.1 % ( 3/13 ) and 11.2 % ( 1/9 ) for HBeAg-positive and HBeAg-negative patients with two-step Pegasys treatment , respectively . The HBeAg seroconversion rates were 46.2 % in Group 1 , and 42.1 % in Group 3 ; HBsAg loss rates were 15.4 % ( 2/13 ) in Group 1 , and 30 % ( 3/10 ) in Group 2 , whereas none achieved HBsAg loss with entecavir monotherapy ( Group 3 and 4 ) . The two-step Pegasys treatment offers an alternative , other than the nucleos(t)ides , for treating chronic hepatitis B with acute exacerbation and provides a safe , efficacious , short-term and finite strategy B Output:	Our analysis revealed that PEG-IFNα + lamivudine combination therapy produced better virological and biochemical responses than PEG-IFNα monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment . PEG-IFNα + adefovir dipivoxil achieved better seroconversion rate than PEG-IFNα in HBeAg-positive patients at the end of treatment . The present findings demonstrated a beneficial response rate following PEG-IFNα combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB .
MS22222	*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 Objective : Bioactive food ingredients influence energy balance by exerting weak thermogenic effects . We studied whether the thermogenic effect of a combination of capsaicin , green tea extract ( catechins and caffeine ) , tyrosine , and calcium was maintained after 7-day treatment and whether local effects in the gastric mucosa were involved in the efficacy . Design : The present study was design ed as a 3-way crossover , r and omised , placebo-controlled , double-blinded intervention . Setting : Department of Human Nutrition , RVAU , Denmark . Subjects : A total of 19 overweight to obese men ( BMI : 28.0±2.7 kg/m2 ) were recruited by advertising locally . Intervention : The subjects took the supplements for a period of 7 days . The supplements were administrated as a simple supplement with the bioactive ingredients , a similar enterocoated version , or placebo . In all , 24-h energy expenditure ( EE ) , substrate oxidations , spontaneous physical activity ( SPA ) , and heart rate were measured in respiration chambers on the seventh day of each test period . Results : After adjustment for changes in body weight and SPA , 24-h EE was increased by 160 kJ/day ( 95 % CI : 15–305 ) by the simple preparation as compared to placebo , whereas the enterocoated preparation had no such effect ( 53 kJ/day , −92 to 198 ) ; simple vs enterocoated versions ( P=0.09 ) . The simple preparation produced a deficit in 24-h energy balance of 193 kJ/day ( 49–338 , P=0.03 ) . Fat and carbohydrate oxidation were equally increased by the supplements . Conclusion : A supplement containing bioactive food ingredients increased daily EE by ∼200 kJ or 2 % , without raising the heart rate or any observed adverse effects . The lack of effect of the enterocoated preparation suggests that a local action of capsaicin in the gastric mucosa is a prerequisite for exerting the thermogenic effect . Sponsorship : Supported by Science , Toxicology & Technology , San Francisco , CA , USA 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 The experiments reported here found that judgments of ' burn ' intensity are affected by long-term memory ( LTM ) . The implication of these findings for range-frequency theory and the role of LTM in intensity judgments are discussed OBJECTIVE : To describe the design , methods , and first year results of the Pound of Prevention ( POP ) study , a r and omized trial examining whether weight Output:	Evidence indicates that capsaicin and capsiate both augment energy expenditure and enhance fat oxidation , especially at high doses . Furthermore , the balance of the literature suggests that capsaicin and capsiate suppress orexigenic sensations . The magnitude of these effects is small . Purpose ful inclusion of these compounds in the diet may aid weight management , albeit modestly
MS22223	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns . OBJECTIVE To evaluate the effect of decreasing postpr and ial hyperglycemia with acarbose , an alpha-glucosidase inhibitor , on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance ( IGT ) . DESIGN , SETTING , AND PARTICIPANTS International , multicenter double-blind , placebo-controlled , r and omized trial , undertaken in hospitals in Canada , Germany , Austria , Norway , Denmark , Sweden , Finl and , Israel , and Spain from July 1998 through August 2001 . A total of 1429 patients with IGT were r and omized with 61 patients ( 4 % ) excluded because they did not have IGT or had no postr and omization data , leaving 1368 patients for a modified intent-to-treat analysis . Both men ( 49 % ) and women ( 51 % ) participated with a mean ( SD ) age of 54.5 ( 7.9 ) years and body mass index of 30.9 ( 4.2 ) . These patients were followed up for a mean ( SD ) of 3.3 ( 1.2 ) years . INTERVENTION Patients with IGT were r and omized to receive either placebo ( n = 715 ) or 100 mg of acarbose 3 times a day ( n = 714 ) . MAIN OUTCOME MEASURES The development of major cardiovascular events ( coronary heart disease , cardiovascular death , congestive heart failure , cerebrovascular event , and peripheral vascular disease ) and hypertension ( > or = 140/90 mm Hg ) . RESULTS Three hundred forty-one patients ( 24 % ) discontinued their participation prematurely , 211 in the acarbose-treated group and 130 in the placebo group ; these patients were also followed up for outcome parameters . Decreasing postpr and ial hyperglycemia with acarbose was associated with a 49 % relative risk reduction in the development of cardiovascular events ( hazard ratio [ HR ] , 0.51 ; 95 % confidence interval [ CI ] ; 0.28 - 0.95 ; P = .03 ) and a 2.5 % absolute risk reduction . Among cardiovascular events , the major reduction was in the risk of myocardial infa rct ion ( HR , 0.09 ; 95 % CI , 0.01 - 0.72 ; P = .02 ) . Acarbose was also associated with a 34 % relative risk reduction in the incidence of new cases of hypertension ( HR , 0.66 ; 95 % CI , 0.49 - 0.89 ; P = .006 ) and a 5.3 % absolute risk reduction . Even after adjusting for major risk factors , the reduction in the risk of cardiovascular events ( HR , 0.47 ; 95 % CI , 0.24 - 0.90 ; P = .02 ) and hypertension ( HR , 0.62 ; 95 % CI , 0.45 - 0.86 ; P = .004 ) associated with acarbose treatment was still statistically significant . CONCLUSION This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension OBJECTIVE —Hyperglycemia and Its Effect After Acute Myocardial Infa rct ion on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus ( HEART2D ) is a multinational , r and omized , controlled trial design ed to compare the effects of pr and ial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infa rct ion ( AMI ) . RESEARCH DESIGN AND METHODS — Patients ( type 2 diabetes , aged 30–75 years ) were r and omly assigned within 21 days after AMI to the 1 ) pr and ial strategy ( PR AND IAL ) ( three premeal doses of insulin lispro targeting 2-h postpr and ial blood glucose < 7.5 mmol/l ) or the 2 ) basal strategy ( BASAL ) ( NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose < 6.7 mmol/l ) . RESULTS —A total of 1,115 patients were r and omly assigned ( PR AND IAL n = 557 ; BASAL n = 558 ) , and the mean patient participation after r and omization was 963 days ( range 1–1,687 days ) . The trial was stopped for lack of efficacy . Risks of first combined adjudicated primary cardiovascular events in the PR AND IAL ( n = 174 , 31.2 % ) and BASAL ( n = 181 , 32.4 % ) groups were similar ( hazard ratio 0.98 [ 95 % CI 0.8–1.21 ] ) . Mean A1C did not differ between the PR AND IAL and BASAL groups ( 7.7 ± 0.1 vs. 7.8 ± 0.1 % ; P = 0.4 ) during the study . The PR AND IAL group showed a lower daily mean postpr and ial blood glucose ( 7.8 vs. 8.6 mmol/l ; P < 0.01 ) and 2-h postpr and ial blood glucose excursion ( 0.1 vs. 1.3 mmol/l ; P < 0.001 ) versus the BASAL group . The BASAL group showed lower mean fasting blood glucose ( 7.0 vs. 8.1 mmol/l ; P < 0.001 ) and similar daily fasting/premeal blood glucose ( 7.7 vs. 7.3 mmol/l ; P = 0.233 ) versus the PR AND IAL group . CONCLUSIONS —Treating diabetic survivors of AMI with pr and ial versus basal strategies achieved differences in fasting blood glucose , less-than-expected differences in postpr and ial blood glucose , similar levels of A1C , and no difference in risk for future cardiovascular event rates BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment : any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p<0.0001 ) . The rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin . Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p<0.001 ) , and patients assigned insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED CONTEXT The role of triglycerides in the risk of ischemic stroke remains controversial . Recently , a strong association was found between elevated levels of nonfasting triglycerides , which indicate the presence of remnant lipoproteins , and increased risk of ischemic heart disease . OBJECTIVE To test the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population . DESIGN , SETTING , AND PARTICIPANTS The Copenhagen City Heart Study , a prospect i ve , Danish population -based cohort study initiated in 1976 , with follow-up through July 2007 . Participants were 13,956 men and women aged 20 through 93 years . A cross-sectional study included 9637 individuals attending the 1991 - 1994 examination of the prospect i ve study . MAIN OUTCOME MEASURES Prospect i ve study : baseline levels of nonfasting triglycerides , other risk factors at baseline and at follow-up examinations , and incidence of ischemic stroke . Cross-sectional study : levels of nonfasting triglycerides , levels of remnant cholesterol , and prevalence of ischemic stroke . RESULTS Of the 13,956 participants in the prospect i ve study , 1529 developed ischemic stroke . Cumulative incidence of ischemic stroke increased with increasing levels of nonfasting triglycerides ( log-rank trend , P < .001 ) . Men with elevated nonfasting triglyceride levels of 89 through 176 mg/dL had multivariate-adjusted hazard ratios ( HRs ) for ischemic stroke of 1.3 ( 95 % CI , 0.8 - 1.9 ; 351 events ) ; for 177 through 265 mg/dL , 1.6 ( 95 % CI , 1.0 - 2.5 ; 189 events ) ; for 266 through 353 mg/dL , 1.5 ( 95 % CI , 0.9 - 2.7 ; 73 events ) ; for 354 through 442 mg/dL , 2.2 ( 95 % CI , 1.1 - 4.2 ; 40 events ) ; and for 443 mg/dL or greater , 2.5 ( 95 % CI , 1.3 - 4.8 ; 41 events ) vs men with nonfasting levels less than 89 mg/dL ( HR , 1.0 ; 85 events ) ( P < .001 for trend ) . Corresponding values for women were 1.3 ( 95 % CI , 0.9 - 1.7 ; 407 events ) , 2.0 ( 95 % CI , 1.3 - 2.9 ; 135 events ) , 1.4 ( 95 % CI , 0.7 - 2.9 ; 26 events ) , 2.5 ( 95 % CI , 1.0 - 6.4 ; 13 events ) , and 3.8 Output:	They also showed that CVD events increased linearly , with no threshold , along with 2-h postmeal plasma glucose levels ( 7,8 ) . In this issue of Diabetes Care , Cavalot et al. ( 10 ) add further evidence of the harmful relationship between postmeal glucose levels and
MS22224	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Comprehensive discharge planning by advanced practice nurses has demonstrated short-term reductions in readmissions of elderly patients , but the benefits of more intensive follow-up of hospitalized elders at risk for poor outcomes after discharge has not been studied . OBJECTIVE To examine the effectiveness of an advanced practice nurse-centered discharge planning and home follow-up intervention for elders at risk for hospital readmissions . DESIGN R and omized clinical trial with follow-up at 2 , 6 , 12 , and 24 weeks after index hospital discharge . SETTING Two urban , academically affiliated hospitals in Philadelphia , Pa. PARTICIPANTS Eligible patients were 65 years or older , hospitalized between August 1992 and March 1996 , and had 1 of several medical and surgical reasons for admission . INTERVENTION Intervention group patients received a comprehensive discharge planning and home follow-up protocol design ed specifically for elders at risk for poor outcomes after discharge and implemented by advanced practice nurses . MAIN OUTCOME MEASURES Readmissions , time to first readmission , acute care visits after discharge , costs , functional status , depression , and patient satisfaction . RESULTS A total of 363 patients ( 186 in the control group and 177 in the intervention group ) were enrolled in the study ; 70 % of intervention and 74 % of control subjects completed the trial . Mean age of sample was 75 years ; 50 % were men and 45 % were black . By week 24 after the index hospital discharge , control group patients were more likely than intervention group patients to be readmitted at least once ( 37.1 % vs 20.3 % ; P<.001 ) . Fewer intervention group patients had multiple readmissions ( 6.2 % vs 14.5 % ; P = .01 ) and the intervention group had fewer hospital days per patient ( 1.53 vs 4.09 days ; P<.001 ) . Time to first readmission was increased in the intervention group ( P<.001 ) . At 24 weeks after discharge , total Medicare reimbursements for health services were about $ 1.2 million in the control group vs about $ 0.6 million in the intervention group ( P<.001 ) . There were no significant group differences in post-discharge acute care visits , functional status , depression , or patient satisfaction . CONCLUSIONS An advanced practice nurse-centered discharge planning and home care intervention for at-risk hospitalized elders reduced readmissions , lengthened the time between discharge and readmission , and decreased the costs of providing health care . Thus , the intervention demonstrated great potential in promoting positive outcomes for hospitalized elders at high risk for rehospitalization while reducing costs BACKGROUND Few investigators have targeted elderly patients and monitored outcomes of care in studies on discharge planning interventions after critical illness . OBJECTIVES To pilot test an intensive care unit-based nursing screening intervention to assist in determining the discharge needs and outcomes of critically ill elderly patients . METHOD A r and omized clinical trial with in-hospital and mailed question naires was used . Patients 65 years and older who were hospitalized in 1 of 2 intensive care units at 2 midwestern university-affiliated medical centers were recruited for the study . Control patients ( n = 53 ) received usual discharge planning , experimental patients ( n = 47 ) were screened in the intensive care unit by using the Discharge Planning Question naire . Both groups were assessed for readiness for discharge when discharged from the hospital and were followed up 2 weeks later with a survey completed at home . RESULTS One hundred patients 65 to 90 years old ( mean 73 , SD 5.78 ) completed the study . Sixty-six percent were men . The 2 groups did not differ with regard to age , race , sex , severity of illness , lengths of stay in the intensive care unit or hospital , education level , or income . Patients in the experimental group were more ready than patients in the control group for discharge ( P = .06 ) . Patients in the experimental group were also more likely to report they had adequate information , had less concern about managing their care at home , knew their medicines , and knew danger signals indicating potential complications . CONCLUSION Intensive care unit-based early discharge planning can affect elderly patients ' preparation for discharge OBJECTIVES to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients . DESIGN r and omized controlled trial . SUBJECTS AND SETTING S we r and omized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care . INTERVENTIONS the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient . A copy was given to the patient and to all relevant professionals and carers . This was followed by a domiciliary assessment by a community pharmacist . In the control group , patients were discharged from hospital following st and ard procedures that included a discharge letter to the general practitioner listing current medications . OUTCOMES the primary outcome was re-admission to hospital within 6 months . Secondary outcomes included the number of deaths , attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period , together with patients ' general well-being , satisfaction with the service and knowledge of and adherence to prescribed medication . RESULTS we recruited 362 patients , of whom 181 were r and omized to each group . We collected hospital and general practice data on at least 91 and 72 % of patients respectively at each follow-up point and interviewed between 43 and 90 % of the study subjects . There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months . There were no significant differences in any of the secondary outcomes . CONCLUSIONS we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes The evidence -based medicine ( EBM ) related concepts of hierarchy of evidence , meta-analyses , confidence intervals , study design , etc . are nowadays so widespread , that clinicians willing to use today 's medical literature with underst and ing have no choice but to become familiar with EBM principles and method ologies . Although surgeons may perceive that evidence -based medicine m and ates a strict adherence to r and omised trials , it more accurately involves informed and effective use of all types of evidence ( from meta- analysis of r and omised trials to individual case series and case reports . With the ever-increasing amount of available information , surgeons must consider a shift in paradigm from traditional practice to one that involves question formulation , validity assessment of available studies and appropriate application of research evidence to individual patients OBJECTIVE to prove the effectiveness of geriatric evaluation and management for elderly , hospitalized patients , combined with post-discharge home intervention by an interdisciplinary team . DESIGN r and omized controlled trial with outcome and costs assessed for 12 months after the date of admission . SETTING university-affiliated geriatric hospital and the homes of elderly patients . SUBJECTS 545 patients with acute illnesses admitted from home to the geriatric hospital . INTERVENTIONS patients were r and omly assigned to receive either comprehensive geriatric assessment and post-discharge home intervention ( intervention ) , comprehensive geriatric assessment alone ( assessment ) or usual care . MAIN OUTCOME MEASURES survival , functional status , rehospitalization , nursing home placement and direct costs over 12 months . RESULTS the intervention group showed a significant reduction in length of hospital stay ( 33.49 days vs 40.7 days in the assessment group and 42.7 days in the control group ; P < 0.05 ) and rate of immediate nursing home placement ( 4.4 % vs 7.3 % and 8.1 % ; P < 0.05 ) . There was no difference in survival , acute care hospital readmissions or new admissions to nursing homes but the intervention group had significantly shorter hospital readmissions ( 22.2 days vs 34.2 days and 35.7 days ; P < 0.05 ) and nursing home placements ( 114.7 days vs 161.6 days and 170.0 days ; P < 0.05 ) . Direct costs were lower in the intervention group [ about DM 7000 ( US $ 4000 ) per person per year ] . Functional capacities were significantly better in the intervention group . CONCLUSIONS comprehensive geriatric assessment in combination with post-discharge home intervention does not improve survival , but does improve functional status and can reduce the length of the initial hospital stay and of subsequent readmissions . It can reduce the rate of immediate nursing home admissions and delay permanent nursing home placement . It may also substantially reduce direct costs of hospitalized patients OBJECTIVE To determine the effect of a home-based intervention ( HBI ) on the frequency of unplanned readmission and out-of-hospital death among patients discharged home from acute hospital care . DESIGN A r and omized controlled trial comparing HBI with usual care ( UC ) . SETTING A tertiary referral hospital servicing the northwestern region of Adelaide , South Australia . PARTICIPANTS Medical and surgical patients ( n = 762 ) discharged home after hospitalization . INTERVENTION Home-based intervention ( n = 381 ) consisted of counseling of all patients before discharge followed by a single home visit ( by a nurse and pharmacist ) to those patients considered to be at high risk of readmission ( n = 314 ) in order to optimize compliance with and knowledge of the treatment regimen , identify early clinical deterioration , and intensify follow-up of such patients where appropriate . MEASUREMENTS The primary endpoint was the number of unplanned readmissions plus out-of-hospital deaths over a 6-month follow-up period . RESULTS During the study follow-up , the major endpoint occurred most commonly in the UC group ( 217 vs 155 episodes : P < .001 ) . Overall , the HBI group demonstrated fewer unplanned readmissions ( 154 vs 197 : P = .022 ) , out-of-hospital deaths ( 1 vs. 20 : P < .001 ) , total deaths ( 12 vs. 29 : P = .006 ) , emergency department attendances ( 236 vs 314 : P < .001 ) , and total days of hospitalization ( 1452 vs 1766 : P < .001 ) . There was a disproportionate reduction in multiple events among HBI patients ( P = .035 ) . Hospital-based costs of health care during study follow-up tended to be lower in the HBI group ( $ A2190 vs $ A2680 per patient : P = .102 ) . Mean cost of HBI was $ A190 per patient visited , whereas other community-based health care costs were similar for both groups . CONCLUSIONS Among high-risk patients discharged from acute hospital care , HBI is beneficial in limiting unplanned readmissions and reducing risk of out-of-hospital death . It may be particularly cost-effective if applied selectively to patients with a history of frequent unplanned hospital admission STUDY OBJECTIVE : We determine the cost-effectiveness of a 2-stage emergency department intervention in addition to usual ED care compared with that of usual care alone . METHODS The intervention comprises 2 steps : ( 1 ) identification of high-risk patients by using a screening tool and ( 2 ) a brief st and ardized nursing assessment to identify unresolved problems , followed by referral to an appropriate community provider . The patient population was composed of individuals aged 65 years and older to be released from the EDs of 4 Montreal hospitals . Patients were r and omized by day of ED visit . The perspective of the study is societal , including patients , caregivers , and the formal health care ( government-funded ) system . Outcomes , measured from r and omization to 4 months after r and omization , included ( 1 ) functional decline , as measured by an activities of daily living instrument , or death , and ( 2 ) changes in depressive symptoms . Costs include post-ED care , including hospitalization , physician services , community care , outpatient drugs , and patient and caregiver costs . Cost items were measured with administrative data bases and self-reported question naires . Unit costs for these items were either province-wide rates or else were estimated directly by using provider data . Cost-effectiveness is assessed in qualitative terms , such that outcomes and costs are compared separately . RESULTS The intervention was associated with a reduced rate of functional decline ( including death ) at 4 months . There was no effect of the intervention on change in the patient 's depressive symptoms at 4 months relative to baseline . The estimated ratio of overall costs per patient in the intervention versus the control group , adjusted for covariates , was 0.94 ( 95 % credible interval 0.75 to 1.17 ) . Among patients who had visited the ED during the 30 days before the index visit , the ratio was 0.66 ( 95 % credible interval 0.44 to 0.97 ) . CONCLUSION In this study setting , the intervention is preferred over usual care because beneficial functional outcomes were observed , and overall societal costs were no higher than if usual care only was given The complex chronic health problems and functional limitations common in the elderly population place them at risk for complicated hospitalizations and discharge planning . The purpose of this study was to investigate the effectiveness of a discharge planning protocol in identifying elderly patients ' home care needs . The sample in this quasiexperimental study consisted of 507 hospitalized patients age 65 years or older . The control group received the usual hospital discharge planning protocol . In the experimental group , nurse/social worker teams coordinated the discharge planning process , using an adapted form of the Discharge Planning Question naire ( DPQ ) to identify the home care needs of elderly patients Output:	Large effects were noted for patient satisfaction , while moderate effects were evident for patients ' quality of life and readmission rates .
MS22225	*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 use of low levels of visible or near infrared light for reducing pain , inflammation and edema , promoting healing of wounds , deeper tissues and nerves , and preventing cell death and tissue damage has been known for over forty years since the invention of lasers . Despite many reports of positive findings from experiments conducted in vitro , in animal models and in r and omized controlled clinical trials , LLLT remains controversial in mainstream medicine . The biochemical mechanisms underlying the positive effects are incompletely understood , and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength , fluence , power density , pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones . A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light . The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response . This review will cover the molecular and cellular mechanisms in LLLT , and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response BACKGROUND Experimental evidence suggests that cyclosporine , which inhibits the opening of mitochondrial permeability-transition pores , attenuates lethal myocardial injury that occurs at the time of reperfusion . In this pilot trial , we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention ( PCI ) would limit the size of the infa rct during acute myocardial infa rct ion . METHODS We r and omly assigned 58 patients who presented with acute ST-elevation myocardial infa rct ion to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight ( cyclosporine group ) or normal saline ( control group ) immediately before undergoing PCI . Infa rct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging ( MRI ) on day 5 after infa rct ion . RESULTS The cyclosporine and control groups were similar with respect to ischemia time , the size of the area at risk , and the ejection fraction before PCI . The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group ( P=0.04 ) . The release of troponin I was not significantly reduced ( P=0.15 ) . On day 5 , the absolute mass of the area of hyperenhancement ( i.e. , infa rct ed tissue ) on MRI was significantly reduced in the cyclosporine group as compared with the control group , with a median of 37 g ( interquartile range , 21 to 51 ) versus 46 g ( interquartile range , 20 to 65 ; P=0.04 ) . No adverse effects of cyclosporine administration were detected . CONCLUSIONS In our small , pilot trial , administration of cyclosporine at the time of reperfusion was associated with a smaller infa rct by some measures than that seen with placebo . These data are preliminary and require confirmation in a larger clinical trial Background Remote ischemic preconditioning ( RIPC ) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event . We hypothesized that RIPC reduces postoperative neurocognitive dysfunction ( POCD ) in patients undergoing complex cardiac surgery . Methods We conducted a prospect i ve , r and omized , double-blind , controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass . Patients were r and omized either to RIPC or to control group . Primary endpoint was postoperative neurocognitive dysfunction 5–7 days after surgery assessed by a comprehensive test battery . Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD ( 1 SD criterion ) or if the combined Z score was 1.96 or greater ( Z score criterion ) . Results According to 1 SD criterion , 52 % of control and 46 % of RIPC patients had cognitive deterioration 5–7 days after surgery ( p = 0.753 ) . The summarized Z score showed a trend to more cognitive decline in the control group ( 2.16±5.30 ) compared to the RIPC group ( 1.14±4.02 ; p = 0.228 ) . Three months after surgery , incidence and severity of neurocognitive dysfunction did not differ between control and RIPC . RIPC tended to decrease postoperative troponin T release at both 12 hours [ 0.60 ( 0.19–1.94 ) µg/L vs. 0.48 ( 0.07–1.84 ) µg/L ] and 24 hours after surgery [ 0.36 ( 0.14–1.89 ) µg/L vs. 0.26 ( 0.07–0.90 ) µg/L ] . Conclusions We failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery . Therefore , definitive large-scale multicenter trials are needed . Trial Registration Clinical Trials.gov OBJECTIVE The aim of this r and omized , placebo-controlled , double-blind trial was to investigate changes in the content of 10 cytokines in the human peripheral blood after transcutaneous and in vitro irradiation with polychromatic visible and infrared ( IR ) polarized light at therapeutic dose . BACKGROUND DATA The role of cytokines in development of anti-inflammatory , immunomodulatory , and wound-healing effects of visible and IR light remains poorly studied . METHODS The sacral area of volunteers was exposed ( 480 - 3400 nm , 95 % polarization , 12 J/cm(2 ) ) ; in parallel , the blood sample s of the same subjects were irradiated in vitro ( 2.4 J/cm(2 ) ) . Determination of cytokine content was performed using enzyme-linked immunosorbent assay ( ELISA ) . RESULTS A dramatic decrease in the level of pro-inflammatory cytokines TNF-alpha , IL-6 , and IFN-gamma was revealed : at 0.5 h after exposure of volunteers ( with the initial parameters exceeding the norm ) , the cytokine contents fell , on average , 34 , 12 , and 1.5 times . The reduced concentrations of TNF-alpha and IL-6 were preserved after four daily exposures , whereas levels of IFN-gamma and IL-12 decreased five and 15 times . At 0.5 h and at later times , the amount of anti-inflammatory cytokines was found to rise : that of IL-10 rose 2.7 - 3.5 times ( in subjects with normal initial parameters ) and of TGF-beta1 1.4 - 1.5 times ( in the cases of its decreased level ) . A peculiarity of the light effect was a fast rise of IFN-gamma at 3.3 - 4.0 times in subjects with normal initial values . The content of IL-1beta , IL-2 , IFN-alpha , and IL-4 did not change . Similar regularities of the light effects were recorded after in vitro irradiation of blood , as well as on mixing the irradiated and non-irradiated autologous blood at a volume ratio 1:10 ( i.e. , at modeling the events in a vascular bed of the exposed person when a small amount of the transcutaneously photomodified blood contacts its main circulating volume ) . CONCLUSION Exposure of a small area of the human body to light leads to a fast decrease in the elevated pro-inflammatory cytokine plasma content and to an increase in the the anti-inflammatory factor concentration , which may be an important mechanism of the anti-inflammatory effect of phototherapy . These changes result from transcutaneous photomodification of a small volume of blood and a fast transfer of the light-induced changes to the entire pool of circulating blood Abstract We suggested that low-level laser irradiation ( LLLI ) precondition prior to cell transplantation might remodel the hostile milieu of infa rct ed myocardium and subsequently enhance early survival and therapeutic potential of implanted bone marrow mesenchymal stem cells ( BMSCs ) . Therefore , in this study we wanted to address : ( 1 ) whether LLLI pre-treatment change the local cardiac micro-environment after myocardial infa rct ion ( MI ) and ( 2 ) whether the LLLI preconditions enhance early cell survival and thus improve therapeutic angiogenesis and heart function . MI was induced by left anterior descending artery ligation in female rats . A 635 nm , 5 mW diode laser was performed with energy density of 0.96 J/cm2 for 150 sec. for the purpose of myocardial precondition . Three weeks later , qualified rats were r and omly received with LLLI precondition ( n= 26 ) or without LLLI precondition ( n= 27 ) for LLLI precondition study . Rats that received thoracotomy without coronary ligation were served as sham group ( n= 24 ) . In the cell survival study , rats were r and omly divided into 4 groups : serum-free culture media injection ( n= 8) , LLLI precondition and culture media injection ( n= 8) , 2 million male BMSCs transplantation without LLLI pre-treatment ( n= 26 ) and 2 million male BMSCs transplantation with LLLI precondition ( n= 25 ) group , respectively . Vascular endothelial growth factor ( VEGF ) , glucose-regulated protein 78 ( GRP78 ) , superoxide dismutase ( SOD ) and malondialdehyde ( MDA ) in the infa rct ed myocardium were evaluated by Western blotting , real-time PCR and colorimetry , respectively , at 1 hr , 1 day and 1 week after laser irradiation . Cell survival was assayed with quantitative real-time PCR to identify Y chromosome gene and apoptosis was assayed with transferase-mediated dUTP end labelling staining . Capillary density , myogenic differentiation and left ventricular function were tested by immunohistochemistry and echocardiography , respectively , at 1 week . After LLLI precondition , increased VEGF and GRP78 expression , as well as the enhanced SOD activity and inhibited MDA production , was observed . Compared with BMSC transplantation and culture media injection group , although there was no difference in the improved heart function and myogenic differentiation , LLLI precondition significantly enhanced early cell survival rate by 2-fold , decreased the apoptotic percentage of implanted BMSCs in infa rct ed myocardium and thus increased the number of newly formed capillaries . Taken together , LLLI precondition could be a novel non-invasive approach for intraoperative cell transplantation to enhance cell early survival and therapeutic potential The angioplasty procedure is associated with a release of numerous factors triggering the local inflammatory reaction in vascular wall and leading thus to the restenosis . In this study , we hypothesize that the low-energy laser irradiation may exert beneficial effect by limiting this process . A group of 101 subjects ( 75 men and 26 women , mean age : 59.1 ± 10.3 ) treated with percutaneous coronary intervention ( PCI ) , were recruited to this study . While 52 patients ( 40 men and 12 women ) were subjected to the intravascular low-energy laser irradiation ( λ = 808 nm ) of dilated lesion during the PCI , the remaining patients ( 35 men and 14 women ) constituted the control group . The levels of interleukin 1β , 6 and 10 ( IL 1β , IL 6 and IL 10 ) were measured immediately before the procedure , and then at the 6th , 12th hour as well as after 1 month following the PCI . Significantly lower levels of IL 1β and IL 6 in the irradiated group during each analysis after the procedure were observed . Moreover , significantly lower IL 10 level in irradiated group within 6 and 12 hours after PCI was observed . Irradiation of the lesion with low-energy laser radiation during the PCI procedure results in a decrease in the levels of pro-inflammatory IL 1β and IL 6 as well as in an increase in the levels of anti-inflammatory IL 10 , which may result in decreased risk for restenosis 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 % ) . Card Output:	Photobiomodulation in animal models showed consistently positive effects over a range of wavelengths and application parameters , with reductions in total infa rct size ( up to 76 % ) , decreases in inflammation and scarring , and increases in tissue repair . Multiple molecular pathways were identified , including modulation of inflammatory cytokines , signalling molecules , transcription factors , enzymes and antioxidants .
MS22226	*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 Home-management of malaria ( HMM ) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa . However , limited data are available on the effectiveness of using artemisinin-based combination therapy ( ACT ) within the HMM strategy . The aim of this study was to assess the effectiveness of artemether-lumefantrine ( AL ) , presently the most favoured ACT in Africa , in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania , when provided by community health workers ( CHWs ) and administered unsupervised by parents or guardians at home . Methods An open label , single arm prospect i ve study was conducted in two rural villages with high malaria transmission in Kibaha District , Tanzania . Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test ( RDT ) were provisionally enrolled and provided AL for unsupervised treatment at home . Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and review ed weekly by the CHWs during 42 days . Primary outcome measure was PCR corrected parasitological cure rate by day 42 , as estimated by Kaplan-Meier survival analysis . This trial is registered with Clinical Trials.gov , number NCT00454961 . Results A total of 244 febrile children were enrolled between March-August 2007 . Two patients were lost to follow up on day 14 , and one patient withdrew consent on day 21 . Some 141/241 ( 58.5 % ) patients had recurrent infection during follow-up , of whom 14 had recrudescence . The PCR corrected cure rate by day 42 was 93.0 % ( 95 % CI 88.3%-95.9 % ) . The median lumefantrine concentration was statistically significantly lower in patients with recrudescence ( 97 ng/mL [ IQR 0 - 234 ] ; n = 10 ) compared with reinfections ( 205 ng/mL [ 114 - 390 ] ; n = 92 ) , or no parasite reappearance ( 217 [ 121 - 374 ] ng/mL ; n = 70 ; p ≤ 0.046 ) . Conclusions Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective , which provides evidence base for scaling-up implementation of HMM with AL in Tanzania BACKGROUND Between 1995 and 2000 , KwaZulu-Natal province , South Africa , experienced a marked increase in Plasmodium falciparum malaria , fuelled by pyrethroid and sulfadoxine-pyrimethamine resistance . In response , vector control was strengthened and artemether-lumefantrine ( AL ) was deployed in the first Ministry of Health artemisinin-based combination treatment policy in Africa . In South Africa , effective vector and parasite control had historically ensured low-intensity malaria transmission . Malaria is diagnosed definitively and treatment is provided free of charge in reasonably accessible public-sector health-care facilities . METHODS AND FINDINGS We review ed four years of malaria morbidity and mortality data at four sentinel health-care facilities within KwaZulu-Natal 's malaria-endemic area . In the year following improved vector control and implementation of AL treatment , malaria-related admissions and deaths both declined by 89 % , and outpatient visits decreased by 85 % at the sentinel facilities . By 2003 , malaria-related outpatient cases and admissions had fallen by 99 % , and malaria-related deaths had decreased by 97 % . There was a concomitant marked and sustained decline in notified malaria throughout the province . No serious adverse events were associated causally with AL treatment in an active sentinel pharmacovigilance survey . In a prospect i ve study with 42 d follow up , AL cured 97/98 ( 99 % ) and prevented gametocyte developing in all patients . Consistent with the findings of focus group discussion s , a household survey found self-reported adherence to the six-dose AL regimen was 96 % . CONCLUSION Together with concurrent strengthening of vector control measures , the antimalarial treatment policy change to AL in KwaZulu-Natal contributed to a marked and sustained decrease in malaria cases , admissions , and deaths , by greatly improving clinical and parasitological cure rates and reducing gametocyte carriage Background The Home Management of Malaria ( HMM ) strategy was developed using chloroquine , a now obsolete drug , which has been replaced by artemisinin-based combination therapy ( ACT ) in health facility setting s. Incorporation of ACT in HMM would greatly exp and access to effective antimalarial therapy by the population s living in underserved areas in malaria endemic countries . The feasibility and acceptability of incorporating ACT in HMM needs to be evaluated . Methods A multi-country study was performed in four district-size sites in Ghana ( two sites ) , Nigeria and Ug and a , with population s ranging between 38,000 and 60,000 . Community medicine distributors ( CMDs ) were trained in each village to dispense pre-packaged ACT to febrile children aged 6–59 months , after exclusion of danger signs . A community mobilization campaign accompanied the programme . Artesunate-amodiaquine ( AA ) was used in Ghana and artemether-lumefantrine ( AL ) in Nigeria and Ug and a. Harmonized qualitative and quantitative data collection methods were used to evaluate CMD performance , caregiver adherence and treatment coverage of febrile children with ACTs obtained from CMDs . Results Some 20,000 fever episodes in young children were treated with ACT by CMDs across the four study sites . Cross-sectional surveys identified 2,190 children with fever in the two preceding weeks , of whom 1,289 ( 59 % ) were reported to have received ACT from a CMD . Coverage varied from 52 % in Nigeria to 75 % in Ho District , Ghana . Coverage rates did not appear to vary greatly with the age of the child or with the educational level of the caregiver . A very high proportion of children were reported to have received the first dose on the day of onset or the next day in all four sites ( range 86–97 % , average 90 % ) . The proportion of children correctly treated in terms of dose and duration was also high ( range 74–97 % , average 85 % ) . Overall , the proportion of febrile children who received prompt treatment and the correct dose for the assigned duration of treatment ranged from 71 % to 87 % ( average 77 % ) . Almost all caregivers perceived ACT to be effective , and no severe adverse events were reported . Conclusion ACTs can be successfully integrated into the HMM strategy OBJECTIVE To examine the extent to which district health teams could reduce the burden of malaria , a continuing major cause of mortality and morbidity , in a situation where severe re source constraints existed and integrated care was provided . METHODS Antimalarial drugs were prepackaged into unit doses in an attempt to improve compliance with full courses of chemotherapy . FINDINGS Compliance improved by approximately 20 % in both adults and children . There were 50 % reductions in cost to patients , waiting time at dispensaries and drug wastage at facilities . The intervention , which tended to improve both case and drug management at facilities , was well accepted by health staff and did not involve them in additional working time . CONCLUSION The prepackaging of antimalarials at the district level offers the prospect of improved compliance and a reduction in the spread of resistance A r and omized , controlled , malaria-clinic-based field trial was conducted to compare compliance with a 7-day quinine + tetracycline regimen and a 5-day 700-mg artesunate regimen for the treatment of uncomplicated falciparum malaria in a community in Thail and . Of 137 patients , aged 15 - 60 years attending a malaria clinic , 77 received artesunate and 60 received quinine + tetracycline . Compliance and cure rates were evaluated on days 5 ( artesunate ) and 7 ( quinine + tetracycline ) using patient interview/residual pill counts and peripheral blood smear , respectively . Data were analysed using the intention-to-treat approach , and the reasons for compliance and noncompliance were investigated . Compliance was significantly higher ( 98.4 % ) with artesunate than with quinine + tetracycline ( 71.7 % ) ( relative risk adjusted for sex ( aRR ) = 1.39 ( 95 % C.I. = 1.15 - 1.68 ) ; referent : quinine + tetracycline ) . Cure rate ( 100 % ) was higher in those receiving artesunate than quinine + tetracycline ( 77.4 % ) ( aRR = 1.32 ( 95 % C.I. = 1.12 - 1.55 ) ) . Reasons for compliance included the desire to be cured and to follow the advice of malaria staff/employer , and the simple dosing regimen . Noncompliance was mostly due to adverse reactions and forgetting to take the drugs . These results can serve as a baseline for design ing and evaluating new interventions to improve compliance , as well as for study ing cost-effectiveness to help drug policy decision-making . We recommend a strategy which integrates a short-course , once-a-day regimen ( with minimal adverse reactions ) , a better delivery system for antimalarial drugs and health education , and an enhanced advisory role of malaria staff . Considering the higher compliance rate and curative effectiveness of artesunate , we recommend its use instead of quinine + tetracycline for the treatment of uncomplicated malaria in clinics in Thail and Background Over the years , reports implicate improper anti-malarial use as a major contributor of morbidity and mortality amongst millions of residents in malaria endemic areas , Kenya included . However , there are limited reports on improper use of Artemisinin-based Combination Therapy ( ACT ) which is a first-line drug in the treatment of malaria in Kenya . Knowing this is important for ensured sustainable cure rates and also protection against the emergence of resistant malarial parasites . We therefore investigated ACT adherence level , factors associated with non-adherence and accessibility in households ( n = 297 ) in rural location of Southeast Alego location in Siaya County in western Kenya . Methods ACT Adherence level was assessed with reference to the duration of treatment and number of tablets taken . Using systematic r and om sampling technique , a question naire was administered to a particular household member who had the most recent malaria episode ( < 2 weeks ) and used ACT for cure . Parents/caretakers provided information for children aged < 13 years . Key Informant Interviews ( KIIs ) were also conducted with healthcare providers and private dispensing chemist operators . Results Adherence to ACT prescription remained low at 42.1 % and 57.9 % among individuals above 13 and less than 13 years , respectively . Stratification by demographic and socio-economic characteristics in relation to ACT adherence revealed that age ( P = 0.011 ) , education level ( P < 0.01 ) , ability to read ( P < 0.01 ) and household ( HH ) monthly income ( P = 0.002 ) significantly affected the level of ACT adherence . Consistently , logistic regression model demonstrated that low age ( OR , 0.571 , 95 % CI , 0.360 - 0.905 ; P = 0.017 ) , higher education level ( OR , 0.074 ; 95 % CI 0.017 - 0.322 ; P < 0.01 ) , ability to read ( OR , 0.285 , 95 % CI , 0.167 - 0.486 ; P < 0.01 ) and higher income ( Ksh . > 9000 ; OR , 0.340 ; 95 % CI , 0.167 - 0.694 ; P = 0.003 ) were associated with ACT adherence . In addition , about 52.9 % of the respondents reported that ACT was not always available at the source and that drug availability ( P = 0.020 ) and distance to drug source ( P < 0.01 ) significantly affected accessibility . Conclusions This study demonstrates that more than half of those who get ACT prescription do not take recommended dose and that accessibility is of concern . The findings of this study suggest a potential need to improve accessibility and also initiate programmatic interventions to encourage patient-centred care BACKGROUND Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease . There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border , historically a site of emerging antimalarial-drug resistance . METHODS In two open-label , r and omized trials , we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin , western Cambodia , and Wang Pha , northwestern Thail and : oral artesunate given at a dose of 2 mg per kilogram of body weight per day , for 7 days , and artesunate given at a dose of 4 mg per kilogram per day , for 3 days , followed by mefloquine at two doses totaling 25 mg per kilogram . We assessed in vitro and in vivo Plasmodium falciparum susceptibility , artesunate pharmacokinetics , and molecular markers of resistance . RESULTS We studied 40 patients in each of the two locations . The overall median parasite clearance times Output:	Conclusions This review highlights the weak evidence base on ACT adherence . Results suggest that ACT adherence levels varied substantially between study population s , but comparison between studies was challenging due to differences in study design , definitions , and methods used to measure adherence .
MS22227	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Subjects ( N = 139 ) were assigned to intensive behavioral or to low-contact smoking treatment and to 2-mg nicotine gum or to placebo gum in a 2 X 2 factorial design . The 2-mg gum produced higher abstinence rates than did the placebo . Subjects receiving the low-contact condition plus the 2-mg nicotine gum had excellent abstinence rates at both 26 weeks ( 56 % abstainers ) and 52 weeks ( 50 % abstainers ) . Smokers who scored at the median on a measure of physical dependence to nicotine were more likely to benefit by nicotine gum treatment than subjects who scored either higher or lower , but this relation was nonsignificant . The results of this study are compared with an earlier nonblind trial The authors present results of a r and omized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation . Adult smokers ( N = 362 ) received open-label treatment ( 11 weeks ) that combined relapse prevention training , bupropion SR , and nicotine patch followed by extended treatment ( 14 weeks ) with bupropion SR or matching placebo . Abstinence percentages were relatively high ( week 11 : 52 % ; week 25 : bupropion , 42 % ; placebo , 38 % ; week 52 : bupropion , 33 % ; placebo , 34 % ) , but bupropion SR did not surpass placebo . Gender and baseline craving level were identified as significant , independent moderators of treatment response . Men were more likely to abstain than women ( week 11 : 59 % vs. 43 % , p = .001 ; week 25 : 48 % vs. 31 % , p = .001 ; week 52 : 39 % vs. 27 % , p = .01 ) . Because most smokers suffer relapse with any current cessation treatment , the comparatively high abstinence percentages achieved in this trial are of interest AIMS In an additive design , test the efficacy of cue exposure treatment for smoking relapse prevention as an adjunct to current st and ard cognitive behavioral and pharmacological treatments . DESIGN R and omized , controlled clinical trial . SETTING Outpatient behavioral medicine clinic . PARTICIPANTS One hundred and twenty-nine cigarette smokers recruited through newspaper advertisements . INTERVENTION After receiving an initial counseling session for cessation and setting a quit day , 129 smokers were r and omly assigned to one of four relapse prevention treatment conditions : ( 1 ) brief cognitive behavioral ; ( 2 ) cognitive behavioral and nicorette gum ; ( 3 ) cognitive behavioral and cue exposure ; and ( 4 ) cognitive behavioral and cue exposure with nicorette gum . All smokers met individually with their counselor for six RP sessions . MEASURES Seven-day , point-prevalence abstinence rates ( CO verified ) taken at 1 , 3 , 6 and 12-months post-treatment and time to first slip . FINDINGS All manipulation checks and process measures suggested that the treatments were delivered as intended . There were no significant differences between conditions in point-prevalence abstinence rates or in time to first slip . CONCLUSIONS These results call into question the utility of cue exposure treatment for smoking relapse prevention Internet interventions for smoking cessation are ubiquitous . Yet , to date , there are few r and omized clinical trials that gauge their efficacy . This study is a r and omized clinical trial ( N= 284 , n= 140 in the treatment group , n= 144 in the control group ) of an Internet smoking cessation intervention . Smokers were r and omly assigned to receive either bupropion plus counseling alone , or bupropion and counseling in addition to 12 weeks of access to the Comprehensive Health Enhancement Support System for Smoking Cessation and Relapse Prevention ( CHESS SCRP ; a Web site which provided information on smoking cessation as well as support ) . We found that access to CHESS SCRP was not significantly related to abstinence at the end of the treatment period ( OR= 1.13 , 95 % CI 0.66 - 2.62 ) or at 6 months postquit ( OR= 1.48 , 95 % CI 0.66 - 2.62 ) . However , the number of times participants used CHESS SCRP per week was related to abstinence at both end of treatment ( OR= 1.79 , 95 % CI 1.25 - 2.56 ) and at the 6-month follow-up ( OR= 1.59 , 95 % CI 1.06 - 2.38 ) . Participants with access to CHESS SCRP logged in an average of 33.64 times ( SD=30.76 ) over the 90-day period of access . Rates of CHESS SCRP use did not differ by ethnicity , level of education or gender ( all p>.05 ) . In sum , results suggest that participants used CHESS SCRP frequently , CHESS SCRP use was related to success , but the effects in general did not yield intergroup effects 1,218 smokers able to quit smoking for 48 hr were r and omly assigned to one of 12 cells in a 4 x 3 fully crossed factorial experiment . A pharmacologic factor contained four levels : nicotine polacrilex ( gum ) delivered ad lib or on a fixed regimen , placebo gum , and no gum . A self-guided behavioral treatment factor contained three levels : self-selected relapse prevention modules , r and omly administered modules , and no modules . Those receiving nicotine gum were more likely to be abstinent at the 2- and 6-month follow-ups . The fixed regimen accounted for most of the effect for gum . There was no effect for the relapse prevention module factor . Men and women showed a differential treatment response . Men who received nicotine gum were more likely to be abstinent at each follow-up ( 2 , 6 , and 12 months ) . No treatment was significantly better among women . We conclude that research on different gum chewing regimens is warranted and that further examination of possible gender differences in response to replacement therapy is needed BACKGROUND Pediatric well-care visits provide a clinical opportunity to counsel new mothers about their smoking and the deleterious effects of environmental tobacco smoke ( ETS ) on infant health . METHODS Forty-nine Oregon pediatric offices enrolled 2,901 women who were currently smoking or had quit for pregnancy , using a brief survey at the newborn 's first office visit . R and omly assigned offices provided advice and material s to mothers at each well-care visit during the first 6 months postpartum to promote quitting or relapse prevention . RESULTS The intervention reduced smoking ( 5.9 % vs 2.7 % ) and relapse ( 55 % vs 45 % ) at 6-month follow-up , but logistic regression analysis at 12 months revealed no significant treatment effect . The intervention had a positive effect on secondary outcome variables , such as readiness to quit and attitude toward and knowledge of ETS . Multiple logistic regression analysis indicated that husb and /partner smoking was the strongest predictor of maternal quitting or relapse . CONCLUSIONS A pediatric office-based intervention can significantly affect smoking and relapse prevention for mothers of newborns , but the effect decreases with time . Consistent prompting of the provider to give brief advice and material s at well-care visits could provide a low-cost intervention to reduce infant ETS exposure OBJECTIVE To evaluate the effectiveness of individually tailored smoking cessation advice letters as an adjunct to telephone counselling and generic self-help material s. DESIGN R and omized controlled trial . SETTING The UK Quitline . PARTICIPANTS A total of 1508 current smokers and recent ex-smokers . INTERVENTIONS The control group received usual care ( telephone counselling and an information pack sent through the post ) . The intervention group received in addition a computer-generated individually tailored advice letter . MAIN OUTCOME MEASURES All outcomes were assessed at 6-month follow-up . The primary outcome measure was self-reported prolonged abstinence for at least 3 months . Secondary outcomes were self-reported prolonged abstinence for at least 1 month and 7-day and 24-hour point-prevalence abstinence . RESULTS For the sample as a whole , quit rates did not differ significantly between the two conditions . However , among the majority ( n = 1164 ) who were smokers at baseline , quit rates were consistently higher in the intervention group : prolonged abstinence for 3 months , 12.2 % versus 9.0 % [ odds ratio ( OR ) = 1.40 , 95 % confidence interval ( CI ) = 0.96 - 2.04 , P = 0.080 ) ; prolonged abstinence for 1 month , 16.4 % versus 11.3 % ( OR = 1.53 , 95 % CI = 1.09 - 2.15 , P = 0.013 ) ; 7-day point-prevalence abstinence , 18.9 % versus 12.7 % ( OR = 1.59 , 95 % CI = 1.15 - 2.19 , P = 0.004 ) ; 24-hour point-prevalence abstinence , 20.9 % versus 15.4 % ( OR = 1.45 , 95 % CI = 1.07 - 1.96 , P = 0.015 ) . CONCLUSIONS The results for the smokers are encouraging in showing a small but useful effect of the tailored letter on quit rate . Versions of the tailoring program could be used on the web and in general practice s , pharmacies and primary care trusts AIMS To evaluate relapse prevention ( relapse prevention ) and contingency management ( contingency management ) for optimizing smoking cessation outcomes using nicotine replacement therapy for methadone-maintained tobacco smokers . DESIGN Experimental , 2 ( relapse prevention)x2 ( contingency management ) repeated measures design using a platform of nicotine replacement therapy featuring a 2-week baseline period , followed by r and omization to 12 weeks of treatment , and 6- and 12-month follow-up visits . SETTING Three narcotic treatment centers in Los Angeles . PARTICIPANTS One hundred and seventy-five participants who met all inclusion and no exclusion criteria . INTERVENTION Participants received 12 weeks of nicotine replacement therapy and assignment to one of four conditions : patch-only , relapse prevention + patch , contingency management + patch and relapse prevention + contingency management + patch . MEASUREMENTS Thrice weekly sample s of breath ( analyzed for carbon monoxide ) and urine ( analyzed for metabolites of opiates and cocaine ) and weekly self-reported numbers of cigarettes smoked . FINDINGS Participants ( 73.1 % ) completed 12 weeks of treatment . During treatment , those assigned to receive contingency management showed statistically higher rates of smoking abstinence than those not assigned to receive contingencies ( F3,4680=6.3 , P=0.0003 ) , with no similar effect observed for relapse prevention . At follow-up evaluations , there were no significant differences between conditions . Participants provided more opiate and cocaine-free urines during weeks when they met criteria for smoking abstinence than during weeks when they did not meet these criteria ( F1,2054=14.38 , P=0.0002 ; F1,2419=16.52 , P<0.0001 ) . CONCLUSIONS Contingency management optimized outcomes using nicotine replacement therapy for reducing cigarette smoking during treatment for opiate dependence , although long-term effects are not generally maintained . Findings document strong associations between reductions in cigarette smoking and reductions in illicit substance use during treatment Effects of smoking-cessation treatment combining transdermal nicotine substitution with behavioral therapy were investigated in two studies . A total of 403 smokers underwent nine weeks of behavioral self-control treatment . For seven weeks , groups with transdermal nicotine substitution were also provided with nicotine patches that continuously release nicotine through the skin into the circulatory system . The effects of treatment were measured by total abstinence . The results showed that the nicotine concentration in the patch , special relapse prevention methods , and the type of dosage ( individual versus fixed dose ) had no influence on therapeutic success . Nicotine concentration played a decisive role in the compatibility of the patch . Combining transdermal nicotine substitution with behavioral therapy produced 12-month success rates ( total abstinence ) of about 35 % Abstract Objective : To evaluate a smoking cessation intervention that can be routinely delivered to smokers admitted with cardiac problems . Design : R and omised controlled trial of usual care compared with intervention delivered on hospital wards by cardiac rehabilitation nurses . Setting : Inpatient wards in 17 hospitals in Engl and . Participants : 540 smokers admitted to hospital after myocardial infa rct ion or for cardiac bypass surgery who expressed interest in stopping smoking . Intervention : Brief verbal advice and st and ard booklet ( usual care ) . Intervention lasting 20 - 30 minutes including carbon monoxide reading , special booklet , quiz , contact with other people giving up , declaration of commitment to give up , sticker in patient 's notes ( intervention group ) . Main outcome measures : Continuous abstinence at six weeks and 12 months determined by self report and by biochemical validation at these end points . Feasibility of the intervention and delivery of Output:	On the basis of post hoc subgroup analyses , coping skills training for smoking relapse prevention is effective for motivated community quitters .
MS22228	*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 determine the effectiveness of cerclage pessary in the prevention of preterm birth in asymptomatic Chinese women with a short cervix at 20 to 24 weeks . METHODS Low-risk women carrying singleton pregnancies were screened with transvaginal ultrasound , and those with a cervical length < 25 mm at 20 to 24 weeks were recruited into a r and omized controlled trial , comparing the prophylactic use of cerclage pessary with expectant management . The analysis was by intent-to-treat . The primary outcome measure was preterm delivery before 34 weeks . RESULTS Among 4438 screened women , 203 women ( 4.6 % ) met the inclusion criteria and 108 ( 58 % ) consented for the study . A total of 53 and 55 women were allocated to pessary and control groups , respectively . There was no difference in background demographics , including the mean cervical length ( 19.6 mm versus 20.5 mm ) and the mean gestational age at r and omization ( both 21.9 weeks ) . Delivery before 34 weeks occurred in 9.4 % and 5.5 % ( p = 0.46 ) in the pessary and the control groups , respectively . No differences in major side effects were noted between the groups . CONCLUSION In our population , < 5 % had a cervical length of less than 25 mm at 20 to 24 weeks ' gestation . The prophylactic use of cerclage pessary did not reduce the rate of preterm delivery before 34 weeks Objective : The aim of this study was to evaluate the efficacy and safety of a noninvasive cerclage pessary in the management of cervical incompetence . Methods : This is a prospect i ve cohort study of all pregnant women treated for cervical incompetence during a 4-year period . Women with known risk factors for preterm delivery had transvaginal ultrasonography every 2–3 weeks after 17–19 weeks of gestation . Those with progressive shortening of cervix diagnosed before 30 weeks were treated with a cerclage pessary when the cervical length was ≤25 mm . The pessary was electively removed at 34–36 weeks . The course and outcome of pregnancy were recorded . Results : Thirty-two women were treated with a cerclage pessary . There were nine twin and two triplet pregnancies . Fifteen ( 47 % ) had two or more risk factors for preterm delivery . The mean gestational age at cerclage was 23 ( 17–29 ) weeks , cervical length 17 ( 5–25 ) mm . Two women required delivery before the onset of labor due to severe intrauterine growth restriction and one due to HELLP syndrome . These were excluded from further analysis . In the remaining 29 women , the interval between cerclage and delivery was 10.4 ( 2–19 ) weeks , mean gestational age at delivery 34 ( 22–42 ) weeks , and birth weight 2,255 ( 410–4,045 ) g. Thirteen ( 45 % ) women delivered before 34 weeks . There were a total of 35 live-born infants and four intrapartum fetal deaths ( all between 22 and 25 weeks gestation ) . All women complained of increased vaginal discharge , but no other significant complications were observed that could be attributed to the use of pessary . Conclusion : Cerclage pessary may be useful in the management of cervical incompetence . Whether it can be a noninvasive alternative to surgical cerclage merits further investigation BACKGROUND Most previous studies of the use of cervical pessaries were either retrospective or case controlled and their results showed that this intervention might be a preventive strategy for women at risk of preterm birth ; no r and omised controlled trials have been undertaken . We therefore undertook a r and omised , controlled trial to investigate whether the insertion of a cervical pessary in women with a short cervix identified by use of routine transvaginal scanning at 20 - 23 weeks of gestation reduces the rate of early preterm delivery . METHODS The Pesario Cervical para Evitar Prematuridad ( PECEP ) trial was undertaken in five hospitals in Spain . Pregnant women ( aged 18 - 43 years ) with a cervical length of 25 mm or less were r and omly assigned according to a computer-generated allocation sequence by use of central telephone in a 1:1 ratio to the cervical pessary or expectant management ( without a cervical pessary ) group . Because of the nature of the intervention , this study was not masked . The primary outcome was spontaneous delivery before 34 weeks of gestation . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00706264 . FINDINGS 385 pregnant women with a short cervix were assigned to the pessary ( n=192 ) and expectant management groups ( n=193 ) , and 190 were analysed in each group . Spontaneous delivery before 34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group ( 12 [ 6 % ] vs 51 [ 27 % ] , odds ratio 0·18 , 95 % CI 0·08 - 0·37 ; p<0·0001 ) . No serious adverse effects associated with the use of a cervical pessary were reported . INTERPRETATION Cervical pessary use could prevent preterm birth in a population of appropriately selected at-risk women previously screened for cervical length assessment at the midtrimester scan . FUNDING Instituto Carlos III Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Abstract Objective : The purpose was to determine the effect of vaginal pessaries in patients at risk for spontaneous preterm birth ( SPB ) . Study Design : Transvaginal sonography ( TVS ) was longitudinally performed to measure cervical length ( CL ) in 258 singleton at risk for SPB and 282 twin pregnancies . Pairs with or without treatment were matched for gestational age and the CL at examination . Results : In 4 singleton and 7 twin pregnancies the CL was < 15 mm before 24 weeks , the mean interval between pessary insertion and delivery was 13 + 2 and 12 + 5 weeks respectively . For the matched control analysis , 12 pairs with singleton and 23 pairs with twin pregnancies were compared . For singleton pregnancies , the mean interval between TVS and delivery was 99 ( 70–134 ) days in the treatment and 67 ( 2–130 ) days in the control group ( p = 0.0184 ) , the mean gestational age at delivery was 38 ( 36 + 6–41 ) and 33 + 4 ( 26–38 ) weeks respectively ( p = 0.02 ) . For twin pregnancies , the interval was 85 ( 43–129 ) days in the treatment and 67 ( 21–100 ) days in the control group ( p = 0.001 ) , gestational age at delivery was 35 + 6 ( 33–37 + 4 ) and 33 + 2 ( 24 + 4–37 + 2 ) respectively ( p = 0.02 ) . Within singleton pregnancies with pessary , there was no SPB < 36 weeks compared to 6/12 cases in the control group ( p < 0.001 ) . Within twin pregnancies , the rates were 8/23 cases with SPB < 36 weeks but none < 32 weeks , compared to 12/23 cases with SPB < 36 weeks and 7/23 cases < 32 weeks in the control group ( p < 0.001 ) . Conclusions : Insertion of a vaginal pessary may be a cost-effective preventive treatment in patients at risk for SPB . Prospect i ve controlled trials are needed BACKGROUND The role of the cervix in the pathogenesis of premature delivery is controversial . In a prospect i ve , multicenter study of pregnant women , we used vaginal ultrasonography to measure the length of the cervix ; we also documented the incidence of spontaneous delivery before 35 weeks ' gestation . METHODS At 10 university-affiliated prenatal clinics , we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies . We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery . RESULTS We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks . Spontaneous preterm delivery ( at less than 35 weeks ) occurred in 126 of the women ( 4.3 percent ) examined at 24 weeks . The length of the cervix was normally distributed at 24 and 28 weeks ( mean [ + /- SD ] , 35.2 + /- 8.3 mm and 33.7 + /- 8.5 mm , respectively ) . The relative risk of preterm delivery increased as the length of the cervix decreased . When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile , the relative risks of preterm delivery among the women with shorter cervixes were as follows : 1.98 for cervical lengths at or below the 75th percentile ( 40 mm ) , 2.35 for lengths at or below the 50th percentile ( 35 mm ) , 3.79 for lengths at or below the 25th percentile ( 30 mm ) , 6.19 for lengths at or below the 10th percentile ( 26 mm ) , 9.49 for lengths at or below the 5th percentile ( 22 mm ) , and 13.99 for lengths at or below the 1st percentile ( 13 mm ) ( P < 0.001 for values at or below the 50th percentile ; P = 0.008 for values at or below the 75th percentile ) . For the lengths measured at 28 weeks , the corresponding relative risks were 2.80 , 3.52 , 5.39 , 9.57 , 13.88 , and 24.94 ( P < 0.001 for values at or below the 50th percentile ; P = 0.003 for values at the 75th percentile ) . CONCLUSIONS The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy To evaluate the efficiency of cerclage or pessary a prospect i ve r and om study has been done from 1982 to 1983 . Pelvic score of Bishop and tocolysis index of Baumgarten were used to define the situation at the beginning . Success has been estimated with help of neonatal parameters ( birth weight , Apgar score and RDS-morbidity ) and final gestational week . Both methods are equal in their effects Objective . The Arabin pessary may be beneficial in the treatment of cervical incompetence . The aim of the study was to analyse the efficacy of the treatment method of pregnant women with cervical incompetence . Methods . A non-r and omised study performed in the obstetrical wards in Lodz , Pol and utilising 54 pregnant women with cervical incompetence was developed to assess the efficiency of treatment methods of cervically incompetent women . These women were diagnosed by vaginal ultrasound examination during the course of the study . Patients with a cervical length of 15–30 mm before 28 weeks an Arabin cervical pessary were inserted , women whose cervical length was less than 15 mm were treated with cervical cerclage . The main end points of the study were preterm or term delivery . Results . In the Arabin pessary group , 1.9 % of women delivered before the 29th week of gestation and 83.3 % of women delivered after 37 weeks of pregnancy . Eighty-seven per cent of pregnant women treated for cervical incompetence by Arabin pessary delivered by normal spontaneous labour , 1.9 % delivered by forceps labour and 11.1 % of patients by caesarean section . Among pregnant women treated by Arabin pessary , 3.7 % of newborns were estimated as having a score of 0–4 on the Apgar scale , 13 % a score of 5–7 and 83.3 % a score of 8–10 . Conclusions . Cervical incompetence treatment effectively prolongs the duration of gestation . Application of the Arabin pessary is an effective method of cervical incompetence treatment Output:	Available r and omized and nonr and omized studies indicate potential effectiveness of a cervical pessary in the prevention of preterm birth .
MS22229	*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: Several lines of evidence suggest that patients with essential hypertension have impaired endothelial nitric oxide activity and increased superoxide anion production . However , the mechanisms underlying these abnormalities remain unknown . We measured enzymatic superoxide dismutase ( SOD ) and glutathione peroxidase ( GPX ) activities in erythrocytes and whole blood , respectively , in 30 newly-diagnosed , normolipidaemic untreated mild hypertensive patients and in 164 age-matched healthy controls . SOD and GPX activities in hypertensive patients ( 806 ± 225 U/Hb.g and 5491 ± 2073 U/L , respectively ) were significantly lower than in the control group ( 931 ± 202 U/Hb.g and 6669 ± 1560 U/L , respectively ) ( P < 0.005 ) . no significant association was found between these antioxidant enzyme activities and blood pressure in normotensive controls . in the hypertensives , only log-transformed sod activity showed a significant negative correlation with systolic and diastolic blood pressure ( r = 0.37 , P < 0.05 ; r = 0.64 , P < 0.0001 , respectively ) . the low endogenous antioxidant enzyme activities observed may in turn result in decreased superoxide anion removal leading to nitric oxide inactivation Output:	This meta- analysis suggests that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of hypertension .
MS22230	*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 results of pancreaticogastrostomy versus pancreaticojejunostomy following pancreaticoduodenectomy in a prospect i ve and r and omized setting . Summary Background Data : While several techniques have been proposed for reconstructing pancreatico-digestive continuity , only a limited number of r and omized studies have been carried out . Methods : A total of 151 patients undergoing pancreaticoduodenectomy with soft residual tissue were r and omized to receive either pancreaticogastrostomy ( group PG ) or end-to-side pancreaticojejunostomy ( group PJ ) . Results : The 2 treatment groups showed no differences in vital statistics or underlying disease , mean duration of surgery , and need for intraoperative blood transfusion . Overall , the incidence of surgical complications was 34 % ( 29 % in PG , 39 % in PJ , P = not significant ) . Patients receiving PG showed a significantly lower rate of multiple surgical complications ( P = 0.002 ) . Pancreatic fistula was the most frequent complication , occurring in 14.5 % of patients ( 13 % in PG and 16 % in PJ , P = not significant ) . Five patients in each treatment arm required a second surgical intervention ; the postoperative mortality rate was 0.6 % . PG was favored over PJ due to significant differences in postoperative collection s ( P = 0.01 ) , delayed gastric emptying ( P = 0.03 ) , and biliary fistula ( P = 0.01 ) . The mean postoperative hospitalization period stay was comparable in both groups . Conclusions : When compared with PJ , PG did not show any significant differences in the overall postoperative complication rate or incidence of pancreatic fistula . However , biliary fistula , postoperative collection s and delayed gastric emptying are significantly reduced in patients treated by PG . In addition , pancreaticogastrostomy is associated with a significantly lower frequency of multiple surgical complications OBJECTIVE Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy . External drainage of pancreatic duct with a stent has been shown to reduce pancreatic fistula rate of pancreaticojejunostomy in a few retrospective or prospect i ve nonr and omized studies , but no r and omized controlled trial has been reported thus far . This single-center prospect i ve r and omized trial compared the results of pancreaticoduodenectomy with external drainage stent versus no stent for pancreaticojejunal anastomosis . METHODS A total of 120 patients undergoing pancreaticoduodenectomy with end-to-side pancreaticojejunal anastomosis were r and omized to have either an external stent inserted across the anastomosis to drain the pancreatic duct ( n = 60 ) or no stent ( n = 60 ) . Duct-to-mucosa anastomosis was performed in all cases . RESULTS The 2 groups were comparable in demographic data , underlying pathologies , pancreatic consistency , and duct diameter . Stented group had a significantly lower pancreatic fistula rate compared with nonstented group ( 6.7 % vs. 20 % , P = 0.032 ) . Radiologic or surgical intervention for pancreatic fistula was required in 1 patient in the stented group and 4 patients in the nonstented group . There were no significant differences in overall morbidity ( 31.7 % vs. 38.3 % , P = 0.444 ) and hospital mortality ( 1.7 % vs. 5 % , P = 0.309 ) . Two patients in the nonstented group and none in the stented group died of pancreatic fistula . Hospital stay was significantly shorter in the stented group ( mean 17 vs. 23 days , P = 0.039 ) . On multivariate analysis , no stenting and pancreatic duct diameter <3 mm were significant risk factors of pancreatic fistula . CONCLUSION External drainage of pancreatic duct with a stent reduced leakage rate of pancreaticojejunostomy after pancreaticoduodenectomy The effect of the long-acting somatostatin analogue S and ostatin ( SMS 201 - 995 ) on intestinal absorption and propagation ( mouth-to-caecum transit time ; MCTT ) , on pancreatic secretion and on gall bladder contraction after direct ( secretin-pancreozymin test ) and indirect stimulation ( Lundh meal ) , and on meal-induced responses of seven gastrointestinal regulatory peptides has been investigated . In a double-blind cross-over study , 9 healthy volunteers completed two 7-day periods with subcutaneous injections of either placebo or 25 micrograms SMS 201 - 995 twice daily . Mean faecal fat excretion was increased to 19.2 g/day and MCTT was three times longer during the SMS period . After duodenal infusion of a mixture containing D-galactose , D-xylose and triglycerides , SMS 201 - 995 significantly reduced the serum concentrations of D-galactose but increased serum levels of D-xylose . After 6 days of pretreatment , SMS 201 - 995 completely suppressed duodenal trypsin , lipase and bilirubin increases in response to endogenous stimulation by a Lundh meal . Concomitantly , cholecystokinin ( CCK ) release and gall bladder contraction were almost abolished . Compared with placebo , SMS 201 - 995 significantly diminished pancreatic amylase , trypsin and lipase output after stimulation with CCK , while the secretion of fluid and bicarbonate in response to secretin was unchanged . This inhibition of enzyme response was significantly more marked after a single injection of the analogue than after pretreatment for 7 days and did not reach the level of exocrine pancreatic insufficiency . CCK-induced gall bladder contraction was significantly inhibited by a single dose of 25 micrograms SMS 201 - 995 but not after 7 days of pretreatment with the somatostatin analogue Objective : This study compared the postoperative pancreatic anastomosis leakage rate of a new binding technique with the conventional technique of pancreaticojejunostomy after pancreaticoduodenectomy . Summary Background Data : Leakage from pancreatic anastomoses remains the single most important morbidity after pancreaticoduodenectomy and contributes to prolonged hospitalization and mortality . The reported incidence after conventional pancreaticojejunostomy ranged from 10 % to 29 % . We previously reported a new binding pancreaticojejunostomy technique with a leakage of 0 % . Methods : We conducted a prospect i ve r and omized study on 217 patients who underwent pancreaticoduodenectomy for benign and malignant diseases of the pancreatic head and the periampullary region comparing the 2 techniques of pancreaticojejunostomy . Results : Of the 111 patients r and omized to the conventional group , pancreaticojejunostomy leakage occurred in 8 patients , while no patient in the 106 patients r and omized to the binding group developed leakage ( & khgr;2 test , P = 0.014 ) . The overall postoperative complications developed in 41 patients ( 36.9 % ) in the conventional group compared with 26 patients ( 24.5 % ) in the binding group ( & khgr;2 test , P = 0.048 ) . Seven patients ( 6.3 % ) died in the perioperative period in the conventional group compared with 3 patients ( 2.8 % ) in the binding group ( & khgr;2 test , P = 0.37 ) . The postoperative hospital stay ( mean ± SD ) for the conventional group was 22.4 ± 10.9 days , which was significantly longer than the binding group ( 18.4 ± 4.7 days ) ( Mann-Whitney U test , P < 0.001 ) . Conclusions : Binding pancreaticojejunostomy after panceaticoduodenectomy significantly decreased postoperative complication and pancreaticojejunostomy leakage rates and shortened hospital stay when compared with conventional pancreaticojejunostomy Previous experimental studies have shown that multiple puncturing and stitching of the pancreas results in an increased pancreatic injury response . Furthermore , post-operative pancreatitis , which still is a largely under-diagnosed condition , appears to be an important mediator of many post-operative complications after pancreatic head resection . Stenting has been suggested to improve both short-term and long-term outcome after pancreaticojejunostomy . We have recently developed a biodegradable , radiopaque self-exp and ing stent , which has experimentally been shown suitable for pancreatobiliary applications . In this pilot study we tested the new technique for pancreatico-jejunostomy in 3 patients . In this novel anastomosis technique with a biodegradable stent the pancreatic stump is first sunk into the jejunum and tightened with a purse string in the bowel serosa , without any stitches through the pancreatic tissue , and the patency of the pancreatic duct is secured with a biodegradable stent against the compression of the tightened purse-string . The creation of anastomosis was possible as planned in all 3 patients . They all recovered without complications . The stent was seen in x-ray in all 3 during hospitilization , was found to have disappeared by 1 month in 2 patients , but was still in place at 3 months in 1 patient . The initial experiences described herein encourage progression to a phase I safety study , and later possibly to a phase II r and omized trial to test the efficacy of the new method BACKGROUND The reported pancreatic anastomosis fistula rate for pancreaticoduodenectomy , distal pancreatectomy , or enucleation is 2 % to 27 % . We hypothesized that reinforcement with a vascular pedicle would decrease the number of fistulas . We report a novel technique : the use of the round ligament of the liver to reinforce the pancreatic anastomosis after resection . STUDY DESIGN Patients undergoing resection from January 1 , 2000 until August 8 , 2005 , at a tertiary referral center , were followed in a retrospective cohort study . The round ligament of the liver was disconnected from the abdominal wall , from the umbilicus to the liver . After pancreatic resection , it was sutured to the anastomosis or closure . A pancreatic fistula was defined as follows : Jackson-Pratt ( JP ) drainage>50 mL/d , after the fifth postoperative day , with amylase>3 times the serum level ; reexploration for a fistula ; postoperative pseudocyst ; or death from sepsis with a presumed fistula . RESULTS In 95 patients , we were able to mobilize the round ligament and use it as a vascular pedicle . The overall fistula rate for the series was 5.3 % ( 5 of 95 ) and for pancreaticoduodenectomy it was 8.8 % ( 5 of 57 ) . There were no fistulas within the distal pancreatectomy and enucleation group ( n=38 ) . Importantly , there was no mortality from pancreatic fistula in the studied patients and no need for operative intervention for a fistula . CONCLUSIONS We present a novel technique to prevent pancreatic fistula . Although r and omized trials are necessary , it appears that the use of the round ligament as a vascular pedicle for reinforcing the pancreatic anastomoses and resections results in a very low number of pancreatic fistulas Pancreatic duct stenting remains an attractive strategy to reduce the incidence of pancreatic fistulas following pancreaticoduodenectomy ( PD ) with encouraging results in both retrospective and prospect i ve studies . We performed a prospect i ve r and omized trial to test the hypothesis that internal pancreatic duct stenting reduces the development of pancreatic fistulas following PD . Two hundred thirty-eight patients were r and omized to either receive a pancreatic stent ( S ) or no stent ( NS ) , and stratified according to the texture of the pancreatic remnant ( soft/normal versus hard ) . Four patients were excluded from the study ; in three instances due to a pancreatic duct that was too small to cannulate and in the other instance because a total pancreatectomy was performed . Patients who r and omized to the S group had a 6-cm-long segment of a plastic pediatric feeding tube used to stent the pancreaticojejunostomy anastomosis . In patients with a soft pancreas , 57 r and omized to the S group and 56 r and omized to the NS group . In patients with a hard pancreas , 58 r and omized to the S group and 63 r and omized to the NS group . The S and NS groups for the entire study population , as well as for the subgroup of high-risk patients with soft pancreata , were similar as regard to demographics , past medical history , preoperative symptoms , preoperative procedures , and intraoperative data . The pancreatic fistula rate for the entire study population was 9.4 % . The fistula rates in the S and NS subgroups with hard pancreata were similar , at 1.7 % and 4.8 % ( P=0.4 ) , respectively . The fistula rates in the S and NS subgroups with soft pancreata were also similar , at 21.1 % and 10.7 % ( P=0.1 ) , respectively . A nonstatistically significant increase in the pancreatic fistula rate in the S group persisted after adjusting for the operating surgeon and technical details of the operation ( e.g. , anastomotic technique , anastomotic orientation Output:	The prophylactic use of octreotide after PD does not result in a reduced incidence of POPF . In conclusion , our findings suggest that the successful management of pancreatic anastomoses may depend more on the meticulous surgical technique , surgical volume , and other management parameters than on the type of technique used .
MS22231	*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 an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease COPD , using St . George ’s Respiratory question naire ( SGRQ ) , the 6-minutes walking test ( 6-MWT ) and BODE index as the primary outcome measures . Methods A prospect i ve , parallel-group controlled study of an outpatient rehabilitation program in 80 patients with COPD ( 67 men and 13 women ; mean age 64.8 ± 10.6 years ; FEV1 , 42.8 % ± 7.6 % of the predicted value . The active group ( n = 40 ) took part in a 14-week rehabilitation program [ 3 h/wk , 1.5 h of education and exercise and 1.5 h of cycling ] . The control group ( n = 40 ) was review ed routinely as medical out patients . The following evaluations were carried out at study entry and after14 weeks : ( 1 ) pulmonary function studies ; ( 2 ) 6-minutes walking test 6MWT ; ( 3 ) quality of life ; and ( 4 ) BODE index . Results The following patients completed the study : 35 patients ( 87.5 % ) from the active group ( mean age , 63.7 ± 11.9 years ; mean forced expiratory volume in one second ( FEV1 ) , 41.9 ± 2.6 % of the predicted value ) ; and 36 patients ( 88 % ) from the control group ( mean age , 65.9 ± 10.3 years ; mean FEV1 , 43.33 ± 3.6 % of the predicted value ) . We found no changes in pulmonary function parameters in the active group and the control one at 14weeks . On the other h and , there were significant changes within the components of the SGRQ ( 12.3 for the score total ) for the patients of the active group but not for the patients of the control one ( only 1.5 for the score total ) , we observed also a significant increase in the distance of the 6-MWT in the patients of the active group but not for the patients of the control one , and finally a decrease of two points ( from 6 to 4 ) was noted in the score of the active group ’s BODE index without any change in the control group ’s one . Conclusion An outpatient-based of 14-week rehabilitation program significantly improved the quality of life and exercise tolerance without any change in the pulmonary function in patients with moderate COPD , and there was also a large decrease in the risk of death in rehabilitated patients as measured using the BODE index Background Recently , there has been a surge of international interest in combining qualitative and quantitative methods in a single study – often called mixed methods research . It is timely to consider why and how mixed methods research is used in health services research ( HSR ) . Methods Documentary analysis of proposals and reports of 75 mixed methods studies funded by a research commissioner of HSR in Engl and between 1994 and 2004 . Face-to-face semi-structured interviews with 20 research ers sample d from these studies . Results 18 % ( 119/647 ) of HSR studies were classified as mixed methods research . In the documentation , comprehensiveness was the main driver for using mixed methods research , with research ers wanting to address a wider range of questions than quantitative methods alone would allow . Interviewees elaborated on this , identifying the need for qualitative research to engage with the complexity of health , health care interventions , and the environment in which studies took place . Motivations for adopting a mixed methods approach were not always based on the intrinsic value of mixed methods research for addressing the research question ; they could be strategic , for example , to obtain funding . Mixed methods research was used in the context of evaluation , including r and omised and non-r and omised design s ; survey and fieldwork exploratory studies ; and instrument development . Studies drew on a limited number of methods – particularly surveys and individual interviews – but used methods in a wide range of roles . Conclusion Mixed methods research is common in HSR in the UK . Its use is driven by pragmatism rather than principle , motivated by the perceived deficit of quantitative methods alone to address the complexity of research in health care , as well as other more strategic gains . Methods are combined in a range of context s , yet the emerging method ological contributions from HSR to the field of mixed methods research are currently limited to the single context of combining qualitative methods and r and omised controlled trials . Health services research ers could further contribute to the development of mixed methods research in the context s of instrument development , survey and fieldwork , and non-r and omised evaluations Background Pulmonary rehabilitation ( PR ) is recognized as an evidence -based treatment in improving dyspnea and quality of life in patients with COPD . We evaluated the number needed to treat ( NNT ) to achieve an increase in physical capacity , as defined by a significant improvement in the six-minute walk test ( 6MWT ) in patients with COPD undergoing PR . Methods The study enrolled 284 patients aged 41 to 86 years ( mean age 69.4 years ) divided into two groups : a study group ( 222 patients ) undergoing a PR program , and a control group ( 62 patients ) treated only with drugs . The study group included patients with COPD divided in four subgroups according to GOLD stages . Results In the study group , 142 out of 222 patients ( 64 % ) had an increase of at least 54 m in the 6MWT following PR versus 8 out of 62 patients ( 13 % ) in the control group after the same time interval . The NNT in the overall study group was 2 ; the same NNT was obtained in GOLD stages 2 , 3 , and 4 , but was 8 in stage 1 . Conclusions PR is highly effective in improving the exercise capacity of patients with COPD , as demonstrated by a valuable NNT , with better results in patients with a more severe disease BACKGROUND : A key component in the management of chronic obstructive pulmonary disease ( COPD ) patients is pulmonary rehabilitation ( PR ) , the corner stone of which is exercise training . AIM : This study aims to evaluate the effect of a two-months , home-based PR program with outpatient supervision every two weeks , on exercise tolerance and health-related quality of life ( HRQL ) using Arabic-translated st and ardized generic and specific question naires in COPD patients recently recovered from acute exacerbation , DESIGN : R and omized clinical trial . SETTING AND SUBJECTS : A total of 39 COPD patients who recovered from acute exacerbation were r and omly allocated either a two-month home-based PR program in addition to st and ard medical therapy or st and ard medical therapy alone in the period between July 2008 and March 2009 . METHODS : Pulmonary function tests ( PFTs ) , six-minute walk distance ( 6-MWD ) test , Arabic-translated chronic respiratory disease question naire-self administered st and ardized format ( CRQ-SAS ) and quality of life scale Short Form ( SF-36 ) were compared between 25 patients with moderate to severe COPD who underwent a two-month PR program ( group 1 ) and 14 COPD patients who did not ( group 2 ) . RESULTS : Group 1 showed significant improvement in the 6-MWD , and HRQL scores at two months compared with the usual care patients in group 2 ( P less than 0.05 ) . Improvement in both CRQ-SAS and SF-36 scores were statistically significant and comparable in group 1 . CONCLUSION : The supervised , post discharge , two-month home-based PR program is an effective non pharmacological intervention in the management of stable patients with COPD . The 6-MWD is a simple , inexpensive and safe test to assess physical and functional capabilities among COPD patients . HRQL can be measured in patients with COPD either by disease-specific tools that have been specifically design ed for use in patients with respiratory system disorders or by generic HRQL tools that can be used across population s with a variety of medical conditions . The Arabic-translated CRQ-SAS is a new tool for assessment of Arabic-speaking patients with chronic respiratory diseases OBJECTIVE To examine the effect of an inpatient pulmonary rehabilitation program on functional outcome , supplemental oxygen use , quality of life ( QOL ) , and rehospitalization . DESIGN A prospect i ve study . SETTING Inpatient pulmonary rehabilitation unit . PATIENTS One hundred fifty-seven patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) admitted to an inpatient pulmonary rehabilitation program over a 3-year period . INTERVENTION Comprehensive interdisciplinary inpatient pulmonary rehabilitation program with an average length of stay of 21 days . MAIN OUTCOME MEASURES Improvements in QOL question naire scores , COPD knowledge question naire scores , 6-minute walking test ( with 3 ambulation categories : bed-bound , household ambulators , community ambulators ) , and supplemental oxygen use . Rehospitalization 1 year after completion of the program was also assessed and compared with hospital days for the year before the program . RESULTS On discharge from the program , 88 % of individuals walked farther ( p < .0001 ) , and community ambulators doubled their walking distance , whereas bed-bound patients decreased 10-fold ; supplemental oxygen use dropped 33 % during the day ( p < .0001 ) and 57 % during the night ( p < .0001 ) ; 82 % showed improved QOL ( p < .0001 ) ; 67 % showed improved knowledge of COPD ( p < .0001 ) ; and 67 % of the sample spent less time in the hospital during the 12 months after program completion compared with the 12 months before admission ( p < .001 ) . CONCLUSIONS An inpatient pulmonary rehabilitation program leads to improved endurance and functional ambulation , decreased supplemental oxygen use , and fewer hospitalizations 1 year after discharge for patients with COPD Output:	The psychosocial support of PR contributes to the patients ’ strength and desire for participation and the health education leads to illness-perception learning . Both psychosocial support and health education develop patients ’ empowerment , while PR promotes opportunities to health transitions . The empowerment experienced by the patients in taking advantage of these opportunities leads to positive impacts over time . If they do not exploit these occasions , negative impacts arise in their life , which make the treatment assistance or follow-up more difficult . The COPD patients ’ feedback revealed that PR promotes a better ‘ way of life ’ , well-being and important behavioural changes towards health promotion
MS22232	*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: Despite formal recommendations for dietary change to reduce the incidence of ischaemic heart disease , the acceptability and effectiveness of the proposed diets have not been well investigated in population based studies . In this preliminary investigation of nutritional advice in a well population , subjects in one group practice were r and omized to receive either dietary instruction or simple follow up without instruction . The dietary recommendations were well received , and a substantial proportion of subjects reported altering their diets in accordance with them . There were modest beneficial changes in plasma lipid levels among men . Thus , using general practice as an avenue for promoting dietary change is feasible , and may be effective among men The Minnesota Coronary Survey was a 4.5-year , open enrollment , single end-time , double-blind , r and omized clinical trial that was conducted In six Minnesota state mental hospitals and one nursing home . It Involved 4393 Institutionalized men and 4664 Institutionalized women . The trial compared the effects of a 39 % fat control diet ( 18 % saturated fat , 5 % polyunsaturated fat , 16 % monounsaturated fat , 446 mg dietary cholesterol per day ) with a 38 % fat treatment diet ( 9 % saturated fat , 15 % polyunsaturated fat , 14 % monounsaturated fat , 166 mg dietary cholesterol per day ) on serum cholesterol levels and the Incidence of myocardlal Infa rct ions , sudden deaths , and all-cause mortality . The mean duration of time on the diets was 384 days , with 1568 subjects consuming the diet for over 2 years . The mean serum cholesterol level In the pre-admission period was 207 mg/dl , falling to 175 mg/dl in the treatment group and 203 mg/dl In the control group . For the entire study population , no differences between the treatment and control groups were observed for cardiovascular events , cardiovascular deaths , or total mortality . A favorable trend for all these end-points occurred In some younger age groups Reduction of cumulative exposure to endogenous ovarian steroid hormones is a postulated method for reducing the risk of carcinoma of the breast and other malignancies . Although there are data from trials evaluating the effect of low‐fat and high‐fiber diets on sex hormone levels in premenopausal women , to the authors ' knowledge none of these trials has combined a relatively large number of participants , follow‐up of > 2–3 months , parallel controls receiving a usual diet , and careful timing of blood sampling within the menstrual cycle CONTEXT Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer , necessitating a primary prevention trial . OBJECTIVE To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS The Women 's Health Initiative Dietary Modification Trial , a r and omized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States . INTERVENTIONS Participants were r and omly assigned to the dietary modification intervention ( n = 19,541 ; 40 % ) or the comparison group ( n = 29,294 ; 60 % ) . The intensive behavioral modification program aim ed to motivate and support reductions in dietary fat , to increase consumption of vegetables and fruits , and to increase grain servings by using group sessions , self-monitoring techniques , and other tailored and targeted strategies . Women in the comparison group continued their usual eating pattern . MAIN OUTCOME MEASURE Invasive colorectal cancer incidence . RESULTS A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 ( SD , 1.7 ) years . Intervention group participants significantly reduced their percentage of energy from fat by 10.7 % more than did the comparison group at 1 year , and this difference between groups was mostly maintained ( 8.1 % at year 6 ) . Statistically significant increases in vegetable , fruit , and grain servings were also made . Despite these dietary changes , there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period . There were 201 women with invasive colorectal cancer ( 0.13 % per year ) in the intervention group and 279 ( 0.12 % per year ) in the comparison group ( hazard ratio , 1.08 ; 95 % confidence interval , 0.90 - 1.29 ) . Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status ( P = .01 for each ) . Colorectal examination rates , although not protocol defined , were comparable between the intervention and comparison groups . Similar results were seen in analyses adjusting for adherence to the intervention . CONCLUSION In this study , a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up . CLINICAL TRIALS REGISTRATION Clinical Trials.gov Identifier : NCT00000611 BACKGROUND We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas , which are precursors of most large-bowel cancers . METHODS We r and omly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before r and omization to one of two groups : an intervention group given intensive counseling and assigned to follow a diet that was low in fat ( 20 percent of total calories ) and high in fiber ( 18 g of dietary fiber per 1000 kcal ) and fruits and vegetables ( 3.5 servings per 1000 kcal ) , and a control group given a st and ard brochure on healthy eating and assigned to follow their usual diet . Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps ; they remained in the study for approximately four years , undergoing colonoscopy one and four years after r and omization . RESULTS A total of 1905 of the r and omized subjects ( 91.6 percent ) completed the study . Of the 958 subjects in the intervention group and the 947 in the control group who completed the study , 39.7 percent and 39.5 percent , respectively , had at least one recurrent adenoma ; the unadjusted risk ratio was 1.00 ( 95 percent confidence interval , 0.90 to 1.12 ) . Among subjects with recurrent adenomas , the mean ( + /-SE ) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group . The rate of recurrence of large adenomas ( with a maximal diameter of at least 1 cm ) and advanced adenomas ( defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high- grade dysplasia , including carcinoma ) did not differ significantly between the two groups . CONCLUSIONS Adopting a diet that is low in fat and high in fiber , fruits , and vegetables does not influence the risk of recurrence of colorectal adenomas Background and aim Impaired vasodilatation has been suggested to be caused by inhibition of nitric oxide generation by the recently described asymmetric dimethylarginine ( ADMA ) . In the present study we wanted to explore whether n-3 polyunsaturated fatty acid ( PUFA ) supplementation and /or diet intervention have beneficial influence on endothelial function assessed as plasma levels of ADMA and L-arginine . Methods A male population ( n = 563 , age 70 ± 6 yrs ) with long-st and ing hyperlipidemia , characterized as high risk individuals in 1970–72 , was included , r and omly allocated to receive placebo n-3 PUFA capsules ( corn oil ) and no dietary advice ( control group ) , dietary advice ( Mediterranean type ) , n-3 PUFA capsules , or dietary advice and n-3 PUFA combined and followed for 3 years . Fasting blood sample s were drawn at baseline and the end of the study . Results Compliance with both intervention regimens were demonstrated by changes in serum fatty acids and by recordings from a food frequency question naire . No influence of either regimens on ADMA levels were obtained . However , n-3 PUFA supplementation was accompanied by a significant increase in L-arginine levels , different from the decrease observed in the placebo group ( p < 0.05 ) . In individuals with low body mass index ( < 26 kg/m2 ) , the decrease in L-arginine on placebo was strengthened ( p = 0.01 ) , and the L-arginine/ADMA ratio was also significantly reduced ( p = 0.04 ) . Conclusion In this rather large r and omized intervention study , ADMA levels were not influenced by n-3 PUFA supplementation or dietary counselling . n-3 PUFA did , however , counteract the age-related reduction in L-arginine seen on placebo , especially in lean individuals , which might be discussed as an improvement of endothelial function To study the impact of diet and exercise and the combination thereof on cardiovascular risk factors , 157 healthy men aged 35 - 60 years ( mean + /- S.D. ; 46.2 + /- 5.0 ) with slightly to moderately raised cardiovascular risk factors , were r and omized to 4 groups , diet ( D , n = 40 ) , exercise ( E , n = 39 ) , diet plus exercise ( DE , n = 39 ) , and no active intervention ( controls ( C , n = 39 ) ) , and investigated at baseline and after 6 months . BMI was significantly reduced in Groups E and DE ( mean difference and 95 % confidence intervals ( CI ) , -0.3 ( -0.5 , -0.01 ) and -0.6 ( -0.9 , -0.3 ) kg/m2 , respectively ) . Waist circumference was reduced in all 3 intervention groups ( D , E , and DE ) , -1.3 ( -2.5 , -0.1 ) , -2.2 ( -3.2 , -1.3 ) and -3.0 ( -3.9 , -2.0 ) cm , but not in the control group . Blood pressure ( BP ) was reduced in all 3 intervention groups , systolic BP 4 - 7 mmHg and diastolic BP 2 - 6 mmHg . Serum cholesterol was reduced in Group DE , -0.45 ( -0.77 , -0.13 ) mmol/l . VLDL-cholesterol was reduced in Groups E and DE , -0.14 ( -0.26 , -0.03 ) and -0.09 ( -0.18 , -0.01 ) mmol/l , whereas LDL-cholesterol was reduced in Groups D and DE -0.30 ( -0.54 , -0.06 ) and -0.35 ( -0.64 , -0.05 ) mmol/l . In contrast , neither HDL-cholesterol nor serum triglycerides were influenced by the interventions . According to the coronary risk profile derived from the Framingham study , all 3 intervention groups ( D , E , and DE ) significantly reduced their estimated 10-year risk ( -13 , -12 , and -14 % , respectively ) . We conclude that even with rather moderate changes in diet and exercise , several important cardiovascular risk factors can be affected and that diet and exercise were about equally effective in reducing cardiovascular risk Background : Data are limited on the efficacy of health-fo-cused interventions for young , low-acculturated Latino women . Because breast cancer is the most commonly diagnosed cancer and the most common cause of cancer mortality in this population , combined interventions that address both early detection and dietary patterns could help reduce both morbidity and mortality associated with breast cancer in this underserved population . Purpose : Mujeres Felices por ser Saludables was a r and omized intervention study design ed to assess the efficacy of an 8-month combined dietary and breast health intervention to reduce fat and increase fiber intake as well as to increase the frequency and proficiency of breast self-examination ( BSE ) and reduce anxiety related toBSE among Latinas Methods : Blocked r and omization in blocks of 6 was used to r and omize 256 20- to 40-year-old Latinas to the intervention ( n = 127 ) or control group ( n = 129 ) . The intervention group attended an 8-month multi-component education program design ed specifically for low-acculturated Latinas . The control group received mailed health education material on a schedule comparable to the intervention . A total of 195 women ( 76.2 % ) completed both the baseline and 8-month follow-up interviews . Results : The intervention and control groups were similar on baseline sociodemographic characteristics . At the 8-month follow up , the intervention group reported lower dietary fat ( p > .001 ) and higher fiber intake ( p = .06 ) ; a higher proportion reported practicingBSE at the recommended interval ( p > .001 ) and showed improvedBSE proficiency ( p > .001 ) compared to the control group . BSE-related anxiety was low for both groups at baseline , and no diffirrence in reduction was observed . Conclusions : This project provides a successful model for achirving dietary change and improving breast health behavior Output:	Dietary advice appears to be effective in bringing about modest beneficial changes in diet and cardiovascular risk factors over approximately 9 months but longer term effects are not known
MS22233	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Antenatal counseling and human immunodeficiency virus ( HIV ) testing are not universal in Africa ; thus , women often present in labor with unknown HIV status without receiving the HIVNET 012 nevirapine ( NVP ) regimen ( a single oral dose of NVP to the mother at the start of labor and to the infant within 72 hours of birth ) . OBJECTIVE To determine risk of mother-to-child transmission of HIV when either st and ard use of NVP alone or in combination with zidovudine ( ZDV ) was administered to infants of women tested at delivery . DESIGN , SETTING , AND PARTICIPANTS A r and omized , open-label , phase 3 trial conducted between April 1 , 2000 , and March 15 , 2003 , at 6 clinics in Blantyre , Malawi , Africa . The trial included all infants born to 894 women who were HIV positive , received NVP intrapartum , and were previously antiretroviral treatment-naive . Infants were r and omly assigned to NVP ( n = 448 ) and NVP plus ZDV ( n = 446 ) . Infants were enrolled at birth , observed at 6 to 8 weeks , and followed up through 3 to 18 months . The HIV status of 90 % of all infants was established at 6 to 8 weeks . INTERVENTION Mothers received a 200-mg single oral dose of NVP intrapartum and infants received either 2-mg/kg oral dose of NVP or NVP ( same dose ) plus 4 mg/kg of ZDV twice per day for a week . MAIN OUTCOME MEASURES HIV infection of infant at birth and 6 to 8 weeks , and adverse events . RESULTS The mother-to-child transmission of HIV at birth was 8.1 % ( 36/445 ) in infants administered NVP only and 10.1 % ( 45/444 ) in those administered NVP plus ZDV ( P = .30 ) . A life table estimate of transmission at 6 to 8 weeks was 14.1 % ( 95 % confidence interval [ CI ] , 10.7%-17.4 % ) in infants who received NVP and 16.3 % ( 95 % CI , 12.7%-19.8 % ) in those who received NVP plus ZDV ( P = .36 ) . For infants not infected at birth and retested at 6 to 8 weeks , transmission was 6.5 % ( 23/353 ) in those who received NVP only and 6.9 % ( 25/363 ) in those who received NVP plus ZDV ( P = .88 ) . Almost all infants ( 99%-100 % ) were breastfed at 1 week and 6 to 8 weeks . Grade s 3 and 4 adverse events were comparable ; 4.9 % ( 22/448 ) and 5.4 % ( 24/446 ) in infants receiving NVP only and NVP plus ZDV , respectively ( P = .76 ) . CONCLUSIONS The frequency of mother-to-child HIV transmission at 6 to 8 weeks in our 2 study groups was comparable with that observed for other perinatal HIV intervention studies among breastfeeding women in Africa . The safety of the regimen containing neonatal ZDV was similar to that of a st and ard NVP regimen Almost all childhood HIV-1 is now acquired through vertical transmission . Identifying factors that affect the rate of transmission may lead to the initiation of specific preventive strategies . In this study , antibody levels against different neutralizing epitopes on the envelope glycoprotein of HIV-1 ( gp120 ) were measured in HIV-1-infected pregnant women that either transmitted HIV-1 to their infants ( 18 women ) or did not ( 29 women ) . Differences in levels of antibodies directed against the monomeric gp120 molecule and against the V3 loop region of gp120 were not significantly different between the two groups studied . However , significant differences were observed in the levels of CD4 binding site antibodies , as determined by the ability of diluted maternal plasma to inhibit binding of the CD4 binding site monoclonal antibody F105 ( mAb F105 ) to monomeric gp120 . In addition , more nontransmitting mothers had low viral load as defined by having two or more negative HIV-1 viral cultures during pregnancy compared with transmitters . This pilot study suggests that in addition to higher viral load , low levels of CD4 binding site antibodies correlate with increased risk of HIV-1 vertical transmission . Passive immunotherapy with broadly neutralizing CD4 binding site antibodies should be considered as a strategy to reduce this risk Objectives To study mortality in African children born to HIV-1-infected mothers exposed peripartum to zidovudine . Methods A r and omized placebo-controlled trial in Abidjan and Bobo-Dioulasso . Pregnant women received either 300 mg zidovudine twice daily from 36–38 weeks ’ gestation , 600 mg during labour , and 300 mg twice daily for 7 days post-partum or a matching placebo . Determinants of mortality were studied up to 18 months , overall and among the infected children : treatment , centre , timing of infection , mother and child HIV disease . Results There were 75 infant deaths among 407 live births . The risk of death at 18 months was 176/1000 in the zidovudine arm and 221 for placebo . Relative hazard ( RH , zidovudine versus placebo ) was 0.47 [ 95 % confidence interval ( CI ) 0.2–1.0 ] up to 230 days of life . Maternal CD4 lymphocyte count < 200/mm3 ( RH 2.92 ; CI 1.4–6.1 ) and child HIV-1 infection ( RH 12.6 ; CI 6.6–24.3 ) increased mortality of all children born to HIV-1-infected mothers . There were 101 children infected ( 40 in the zidovudine group ) , and 51 died . Their 18 month probability of death was 590/1000 in the zidovudine group and 510 in the placebo group . Among infected children , maternal zidovudine reduced the risk of death on or before day 230 ( RH 0.18 ; CI 0.1–0.5 ) . Maternal CD4 lymphocyte count < 200/mm3 ( RH 3.25 ; CI 1.3–8.4 ) , maternal death ( RH 9.65 ; CI 1.7–56.0 ) , diagnosis of paediatric infection on or before day 12 ( RH 18.1 ; CI 4.8–69.0 ) and between days 13 and 45 ( RH 7.63 ; CI 2.0–29.5 ) , clinical paediatric AIDS ( RH 5.37 ; CI 2.3–12.7 ) were risk factors for death in HIV-1-infected children . Conclusion Mother-to-child transmission reduction by zidovudine is safe and beneficial to African children . The mortality of HIV-1-infected children is high . Peripartum maternal zidovudine exerts a protective effect for at least 8 months BACKGROUND The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries . We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life . METHODS From November , 1997 , to April , 1999 , we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala , Ug and a. We r and omly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth , or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery , and 4 mg/kg orally twice daily to babies for 7 days after birth . We tested babies for HIV-1 infection at birth , 6 - 8 weeks , and 14 - 16 weeks by HIV-1 RNA PCR . We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis . FINDINGS Nearly all babies ( 98.8 % ) were breastfed , and 95.6 % were still breastfeeding at age 14 - 16 weeks . The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were : 10.4 % and 8.2 % at birth ( p=0.354 ) ; 21.3 % and 11.9 % by age 6 - 8 weeks ( p=0.0027 ) ; and 25.1 % and 13.1 % by age 14 - 16 weeks ( p=0.0006 ) . The efficacy of nevirapine compared with zidovudine was 47 % ( 95 % CI 20 - 64 ) up to age 14 - 16 weeks . The two regimens were well tolerated and adverse events were similar in the two groups . INTERPRETATION Nevirapine lowered the risk of HIV-1 transmission during the first 14 - 16 weeks of life by nearly 50 % in a breastfeeding population . This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries BACKGROUND Short-course zidovudine ( ZDV ) given in the late antenatal period can reduce mother-infant human immunodeficiency virus ( HIV ) transmission by one half . Because this intervention is being implemented in developing countries , evidence of its safety is needed . METHODS In a r and omized , double-blinded , placebo-controlled trial in Bangkok , HIV-infected pregnant women received either ZDV ( 300 mg twice daily from 36 weeks ' gestation until labor , then every 3 hours until delivery ) or an identical placebo regimen . Infants were evaluated at birth and at 1 , 2 , 4 , 6 , 9 , 12 , 15 , and 18 months of age . Growth , clinical events , and hematologic and immunologic measurements were compared between treatment groups . RESULTS Of the 395 children born ( 196 in ZDV group and 199 in placebo group ) , 330 were uninfected , 55 were infected , and 10 had indeterminate infection status . Overall , 319 children ( 81 % ) completed 18 months of follow-up , and 14 ( 4 % ) died before 18 months of age . Among uninfected children , the mean hematocrit was lower in the ZDV group at birth ( 49.1 % vs 51.5 % ) but not at later ages ; mean weight , height , head circumference , and CD4(+ ) and CD8(+ ) T lymphocyte counts were similar in both groups at all ages . Five uninfected children in the ZDV group but only one in the placebo group had a febrile convulsion . No other signs suggestive of mitochondrial dysfunction and no tumors were observed . Among infected children , an estimated 62 % in the ZDV group and 77 % in the placebo group survived free of Centers for Disease Control and Prevention class C disease during the 18-month follow-up . CONCLUSIONS No significant adverse events were associated with short-course ZDV during 18 months of follow-up in this population BACKGROUND The clinical presentation of HIV-1 related diseases could have changed after the introduction of highly active antiretroviral treatment ( HAART ) . We aim ed to assess changes over time in the incidence of ADIs overall and within CD4 lymphocyte count strata , the relationship with treatment and degree of immunodeficiency at diagnosis of ADIs . METHODS We did a prospect i ve observational multicentre study of over 7300 patients in 52 European HIV-1 outpatient clinics . Incidence rates per 100 patient-years of observation were calculated . FINDINGS In total , we recorded 1667 new ADIs ; the incidence of ADIs declined from 30.7 per 100 patient-years of observation during 1994 ( 95 % CI 28.0 - 33.4 ) to 2.5 per 100 patient-years of observation during 1998 ( 95 % CI 2.0 - 3.0 , p<0.0001 , test for trend ) . Median CD4 lymphocyte count at diagnosis of a new ADI increased from 28 cells/microL to 125 cells/microL between 1994 and 1998 ( p<0.0001 ) , yet a steep decline in the rate of ADIs was seen after stratification by latest CD4 lymphocyte count within each year ( < or = 50 , 51 - 200 , and > 200 cells/microL ) . Patients on HAART had a lower rate of ADIs than patients not on this treatment within each CD4 lymphocyte count strata . The proportion of ADIs attributable to cytomegalov Output:	REVIEW ER 'S CONCLUSIONS Implication s for practice The r and omised trials included in this review provide evidence that short course zidovudine and single-dose nevirapine are effective therapies for reducing mother-to-child transmission of HIV .
MS22234	*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: Previous investigations have determined that some individuals have minimal or even ergolytic performance effects after caffeine ingestion . The aim of this study was to analyze the influence of the genetic variations of the CYP1A2 gene on the performance enhancement effects of ingesting a moderate dose of caffeine . In a double-blind r and omized experimental design , 21 healthy active participants ( 29.3 ± 7.7 years ) ingested 3 mg of caffeine per kg of body mass or a placebo in testing sessions separated by one week . Performance in the 30 s Wingate test , visual attention , and side effects were evaluated . DNA was obtained from whole blood sample s and the CYP1A2 polymorphism was analyzed ( rs762551 ) . We obtained two groups : AA homozygotes ( n = 5 ) and C-allele carriers ( n = 16 ) . Caffeine ingestion increased peak power ( 682 ± 140 vs. 667 ± 137 W ; p = 0.008 ) and mean power during the Wingate test ( 527 ± 111 vs. 518 ± 111 W ; p < 0.001 ) with no differences between AA homozygotes and C-allele carriers ( p > 0.05 ) . Reaction times were similar between caffeine and placebo conditions ( 276 ± 31 vs. 269 ± 71 milliseconds ; p = 0.681 ) with no differences between AA homozygotes and C-allele carriers . However , 31.3 % of the C-allele carriers reported increased nervousness after caffeine ingestion , while none of the AA homozygotes perceived this side effect . Genetic variations of the CYP1A2 polymorphism did not affect the ergogenic effects and drawbacks derived from the ingestion of a moderate dose of caffeine INTRODUCTION Caffeine enhances performance of single bouts of endurance exercise , but its effects on repeated bouts typical of those in high-intensity team sports are unclear . PURPOSE To investigate effects of caffeine in a performance test simulating physical and skill dem and s of a rugby union game . METHODS The study was a double-blind , r and omized , crossover design in which nine competitive male rugby players ingested either caffeine ( 6 mg.kg(-1 ) body mass ) or placebo ( dextrose ) 70 min before performing a rugby test . Each test consisted of seven circuits in each of two 40-min halves with a 10-min half-time rest . Each circuit included stations for measurement of sprint time ( two straight-line and three agility sprints ) , power generation in two consecutive drives , and accuracy for passing balls rapidly . Interstitial fluid was sample d transdermally by electrosonophoresis before ingestion of caffeine or placebo and then before testing , at half-time , and immediately after testing ; sample s were assayed chromatographically for caffeine and epinephrine concentrations . RESULTS The effects of caffeine on mean performance ( + /-90 % confidence limits ) over all 14 circuits were : sprint speeds , 0.5 % ( + /-1.7 % ) through 2.9 % ( + /-1.3 % ) ; first-drive power , 5.0 % ( + /-2.5 % ) ; second-drive power , -1.2 % ( + /-6.8 % ) ; and passing accuracy , 9.6 % ( + /-6.1 % ) . The enhancements were mediated partly through a reduction of fatigue that developed throughout the test and partly by enhanced performance for some measures from the first circuit . Caffeine produced a 51 % ( + /-11 % ) increase in mean epinephrine concentration ; correlations between individual changes in epinephrine concentration and changes in performance were mostly unclear , but there were some strong positive correlations with sprint speeds and a strong negative correlation with passing accuracy . CONCLUSION Caffeine is likely to produce substantial enhancement of several aspects of high-intensity team-sport performance PURPOSE The objective of this study is to determine the effects of a caffeine-containing energy drink on female volleyball players ' performance . METHODS Thirteen elite female volleyball players ingested 3 mg·kg of caffeine with an energy drink or the same drink without caffeine ( placebo drink ) in a double-blind and r and omized study . Then , participants performed the following : st and ing spike , jumping spike , spike jump , blocking jump , squat jump , countermovement jump , manual dynamometry , and the agility t-test . A simulated volleyball game was played , videotaped , and notated afterward . RESULTS In comparison to the placebo drink , the ingestion of the caffeinated energy drink increased the ball velocity in the st and ing spike ( 19.2 ± 2.1 vs 19.7 ± 1.9 m·s , P = 0.023 ) and in the jumping spike ( 17.9 ± 2.2 vs 18.8 ± 2.2 m·s , P = 0.038 ) and the jump height in the squat jump ( 28.1 ± 3.2 vs 29.4 ± 3.6 cm , P = 0.028 ) , countermovement jump ( 32.0 ± 4.6 vs 33.1 ± 4.5 cm , P = 0.018 ) , spike jump ( 43.3 ± 4.7 vs 44.4 ± 5.0 cm , P = 0.025 ) , and block jump ( 35.2 ± 5.1 vs 36.1 ± 5.1 cm , P = 0.044 ) . Furthermore , the caffeinated energy drink decreased the time needed to complete the agility t-test ( 11.1 ± 0.5 vs 10.9 ± 0.3 s , P = 0.036 ) . During the game , the volleyball actions categorized as successful were more frequent with the caffeinated energy drink ( 34 % ± 9 % vs 45 % ± 9 % , P < 0.001 ) , whereas imprecise actions decreased ( 28 % ± 7 % vs 14 % ± 9 % , P < 0.001 ) when compared with the placebo drink . CONCLUSION Commercially available energy drinks can significantly improve physical performance in female volleyball players . Increased physical performance led to improved accuracy during an actual volleyball match The purpose of the present study was to examine the duration of caffeine 's ergogenic effect and whether it differs between users and nonusers of the drug . Twenty-one subjects ( 13 caffeine users and 8 nonusers ) completed six r and omized exercise rides to exhaustion at 80 % of maximal oxygen consumption after ingesting either a placebo or 5 mg/kg of caffeine . Exercise to exhaustion was completed once per week at either 1 , 3 , or 6 h after placebo or drug ingestion . Exercise time to exhaustion differed between users and nonusers with the ergogenic effect being greater and lasting longer in nonusers . For the nonusers , exercise times 1 , 3 , and 6 h after caffeine ingestion were 32.7 + /- 8.4 , 32.1 + /- 8.6 , and 31.7 + /- 12.0 min , respectively , and these values were each significantly greater than the corresponding placebo values of 24.2 + /- 6.4 , 25.8 + /- 9.0 , and 23.2 + /- 7.1 min . For caffeine users , exercise times 1 , 3 , and 6 h after caffeine ingestion were 27.4 + /- 7.2 , 28.1 + /- 7.8 , and 24.5 + /- 7.6 min , respectively . Only exercise times 1 and 3 h after drug ingestion were significantly greater than the respective placebo trials of 23.3 + /- 6.5 , 23.2 + /- 7.1 , and 23.5 + /- 5.7 min . In conclusion , both the duration and magnitude of the ergogenic effect that followed a 5 mg/kg dose of caffeine were greater in the nonusers compared with the users PURPOSE The purpose of this study was to determine the oral dose of caffeine needed to increase muscle force and power output during all-out single multijoint movements . METHODS Thirteen resistance-trained men underwent a battery of muscle strength and power tests in a r and omized , double-blind , crossover design , under four different conditions : ( a ) placebo ingestion ( PLAC ) or with caffeine ingestion at doses of ( b ) 3 mg · kg(-1 ) body weight ( CAFF 3 mg ) , ( c ) 6 mg · kg(-1 ) ( CAFF 6 mg ) , and ( d ) 9 mg · kg(-1 ) ( CAFF 9 mg ) . The muscle strength and power tests consisted in the measurement of bar displacement velocity and muscle power output during free-weight full-squat ( SQ ) and bench press ( BP ) exercises against four incremental loads ( 25 % , 50 % , 75 % , and 90 % one-repetition maximum [ 1RM ] ) . Cycling peak power output was measured using a 4-s inertial load test . Caffeine side effects were evaluated at the end of each trial and 24 h later . RESULTS Mean propulsive velocity at light loads ( 25%-50 % 1RM ) increased significantly above PLAC for all caffeine doses ( 5.4%-8.5 % , P = 0.039 - 0.003 ) . At the medium load ( 75 % 1RM ) , CAFF 3 mg did not improve SQ or BP muscle power or BP velocity . CAFF 9 mg was needed to enhance BP velocity and SQ power at the heaviest load ( 90 % 1RM ) and cycling peak power output ( 6.8%-11.7 % , P = 0.03 - 0.05 ) . The CAFF 9 mg trial drastically increased the frequency of the adverse side effects ( 15%-62 % ) . CONCLUSIONS The ergogenic dose of caffeine required to enhance neuromuscular performance during a single all-out contraction depends on the magnitude of load used . A dose of 3 mg · kg(-1 ) is enough to improve high-velocity muscle actions against low loads , whereas a higher caffeine dose ( 9 mg · kg(-1 ) ) is necessary against high loads , despite the appearance of adverse side effects PURPOSE The purpose of this investigation was to assess the acute effects of caffeine ingestion on short-term , high-intensity exercise ( ST ) after a period of oral creatine supplementation and caffeine abstinence . METHODS Fourteen trained male subjects performed treadmill running to volitional exhaustion ( T(lim ) ) at an exercise intensity equivalent to 125 % VO(2max ) . Three trials were performed , one before 6 d of creatine loading ( 0.3 g x kg x d(-1 ) baseline ) , and two further trials after the loading period . One hour before the postloading trials , caffeine ( 5 mg x kg(-1 ) ) or placebo was orally ingested in a cross-over , double-blind fashion . Four measurements of rating of perceived exertion were taken , one every 30 s , during the first 120 s of the exercise . Blood sample s were assayed for lactate , glucose , potassium , and catecholamines , immediately before and after exercise . RESULTS Body mass increased ( P < 0.05 ) over the creatine supplementation period , and this increase was maintained for both caffeine and placebo trials . There was no increase in the maximal accumulated oxygen deficit between trials ; however , total VO(2 ) was significantly increased in the caffeine trial in comparison with the placebo trial ( 13.35 + /- 3.89 L vs 11.67 + /- 3.61 L ) . In addition , caffeine T(lim ) ( 222.1 + /- 48.9 s ) was significantly greater ( P < 0.05 ) than both baseline ( 200.8 + /- 33.4 s ) and placebo ( 198.3 + /- 45.4 s ) T(lim ) . RPE was also lower at 90 s in the caffeine treatment ( 13.8 + /- 1.8 RPE points ) in comparison with baseline ( 14.6 + /- 1.9 RPE points ) . CONCLUSION As indicated by a greater T(lim ) , acute caffeine ingestion was found to be ergogenic after 6-d of creatine supplementation and caffeine abstinence Purpose Many studies have examined the effect of caffeine on exercise performance , but findings have not always been consistent . The objective of this study was to determine whether variation in the CYP1A2 gene , which affects caffeine metabolism , modifies the ergogenic effects of caffeine in a 10-km cycling time trial . Methods Competitive male athletes ( n = 101 ; age = 25 ± 4 yr ) completed the time trial under three conditions : 0 , 2 , or 4 mg of caffeine per kilogram body mass , using a split-plot r and omized , double-blinded , placebo-controlled design . DNA was isolated from saliva and genotyped for the −163A > C polymorphism in the CYP1A2 gene ( rs762551 ) . Results Overall , 4 mg·kg−1 caff Output:	The acute ingestion of a moderate dose of caffeine had a small but significant positive effect on several aspects related to physical performance in team sports
MS22235	*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 Low-dose valganciclovir prophylaxis is still under investigation in renal transplant procedures . Our aim was to assess the cost effectiveness of 450 mg versus 900 mg valganciclovir prophylaxis in kidney transplant recipients . MATERIAL S AND METHODS In this prospect i ve trial , 201 kidney transplant patients were r and omized ( 1:1 ) to receive 450 mg/d ( group 1 , n = 100 ) or 900 mg/d ( group 2 , n = 101 ) valganciclovir prophylaxis for the first 6 months after transplant . Patients were studied for incidence of cytomegalovirus disease , leucopenia episodes , rejection episodes , and graft outcomes along with associated costs over 1 year . Costs ( in US dollars ) of treatment of rejection were also analyzed . RESULTS Demographic features of the studied groups were comparable . We found that the cost of cytomegalovirus care in group 1 patients was significantly lower ( by 50 % at 6 months ; P < .001 ) , with less leukopenia episodes ( P = .04 ) , lower doses of granulocyte colony-stimulating factor ( by 30 % at 6 months ; P = .03 ) , higher doses of mycophenolate mofetil ( P = .04 ) , and less rejection episodes ( P = .01 ) compared with group 2 . In group 2 , there were more episodes of cytomegalovirus infection ( P = .052 ) and BK virus nephropathy ( P = .04 ) . Graft and patient outcomes were satisfactory in both groups . CONCLUSIONS Low-dose valganciclovir for cytomegalovirus prophylaxis after renal transplant is safer , effective and without breakthrough infection , and less costly than using the usual dose Background Few studies have directly compared preemptive therapy ( PET ) and antiviral prophylaxis ( AP ) for prevention of cytomegalovirus ( CMV ) disease in CMV seropositive ( R+ ) orthotopic liver transplant ( OLT ) recipients . Methods We prospect ively assessed CMV disease and clinical outcomes among 160 consecutive R+ OLT recipients who received PET ( weekly plasma CMV PCR for 3 months , oral valganciclovir 900 mg twice daily for CMV viremia > 250 IU/mL , until 2 consecutive negative weekly PCR results ) and compared them with a historical cohort of 156 R+ recipients who received AP ( valganciclovir , 900 mg daily for 3 months ) . Results Patient characteristics were similar between PET and AP cohorts ( P > 0.05 all comparisons ) . In the PET group , 24 % ( 39/160 ) developed CMV viremia greater than 250 IU/mL at a median of 42 ( range , 7 - 93 ) days post-OLT . CMV monitoring adherence in the PET cohort was 85 % ( 1488/1760 required tests ) and 86 % ( 30/36 ) initiated PET within 3 days of the CMV result . By 12 months post-OLT , the incidence of CMV disease , acute allograft rejection , major infection , or death in the PET and AP cohorts was not significantly different : 2 % versus 2 % , 19 % versus 16 % , 10.5 % versus 10.8 % , and 5 % versus 8 % , respectively ( P > 0.05 all comparisons ) . The estimated proportion of drug-exposed patients and average antiviral drug exposure were significantly lower with PET versus AP : 24 % versus 100 % , P < 0.001 , and 15.8 versus 81 g per patient , P < 0.001 , respectively . Conclusions PET is feasible in a non research setting and is associated with similar CMV disease rates and other clinical ly relevant outcomes to AP in CMV seropositive liver transplant recipients OBJECTIVES Invasive fungal infections ( IFIs ) cause significant morbidity and mortality among recipients of hematopoietic stem cell transplantation ( HSCT ) . Although fluconazole is used widely as an antifungal prophylactic agent in these patients , it is not reliably effective against mold infection including invasive aspergillosis . Micafungin provides antifungal activity against C and ida and Aspergillus species , and previous studies have demonstrated its efficacy when used as a prophylactic agent for fungal infection in neutropenic patients . Here , we evaluated and compared the incidence of proven or probable IFIs after antifungal prophylaxis using micafungin or fluconazole . METHODS This was a prospect i ve , single-center , phase II study involving adult patients who received allogeneic or autologous HSCT . Patients were r and omly assigned to micafungin or fluconazole arms in a ratio of 2:1 , and the treatment was initiated within 24 h of HSCT and maintained for up to 21 days . The primary end point was the incidence of proven or probable IFIs during the 100 days after HSCT . The secondary end points were the incidence rates of possible , proven , or probable IFIs , need to change the antifungal agent before engraftment , IFI-related mortality , and survival within 100 days after transplantation . RESULTS Between March 2010 and May 2015 , a total of 257 patients were enrolled . After exclusion of seven patients who did not receive at least one dose of a study treatment , 250 patients ( micafungin , n = 165 ; fluconazole , n = 85 ) were included in the analysis of clinical efficacy . The median age was 47 years ( range , 20 - 64 ) . Allogeneic and autologous transplantations were performed in 56.0 % ( n = 140 ) and 44.0 % ( n = 110 ) of the patients , respectively . Baseline characteristics were well balanced between the two groups . Overall , the incidence of proven and probable IFIs within 100 days of HSCT was 7.6 % ( n = 19 ) . The percentages of patients who experienced proven or probable IFIs did not differ significantly between the micafungin and fluconazole groups : 7.3 % and 8.2 % , respectively ( p = 0.786 ) . Thirteen patients in the micafungin arm ( 7.9 % ) and eight patients in the fluconazole arm ( 9.4 % ) needed a change in antifungal agent before engraftment ( p = 0.824 ) . Mortality within 100 days after HSCT did not differ significantly between groups : 9.1 % vs 12.9 % in the micafungin and fluconazole arms , respectively ( p = 0.345 ) . CONCLUSION Micafungin is comparable to fluconazole for the prevention of IFIs in HSCT recipients Background The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy , safety , and long-term graft outcome in cytomegalovirus (CMV)-positive ( R+ ) renal transplant recipients . Methods Multicenter , open-label , r and omized clinical study with a 12-month study phase and a follow-up of up to 84 months . Patients in the prophylaxis group received 2 × 450 mg/d oral valganciclovir for 100 days adjusted to renal function . Preemptive treatment with 2 × 900 mg/d valganciclovir was initiated at a viral load of 400 CMV copies/mL or greater ( polymerase chain reaction ) and maintained over ≥14 days , followed by secondary prophylaxis . Patients were stratified by donor CMV IgG serostatus ( donor CMV IgG positive [D+]/R+ , donor CMV IgG negative [D−]/R+ ) . Results The 12-month results were reported previously ( Witzke et al Transplantation 2012 ) . The intent-to-treat/safety population comprised 148 patients in the prophylaxis ( 61.5 % D+/R+ ) and 151 patients in the preemptive group ( 52.3 % D+/R+ ) . Overall , 47 % patients completed the follow-up . Significantly fewer patients in the prophylaxis compared with preemptive group experienced a CMV infection or disease up to month 84 ( 11.5 % ; 95 % confidence interval [ 95 % CI ] , 6.8 - 17.8 % ] vs 39.7 % ; 95 % CI , 31.9 - 48.0 % ; P < 0.0001 and 4.7 % ; 95 % CI , 1.9 - 9.5 % vs 15.9 % ; 95 % CI , 10.5 - 22.7 % ; P = 0.002 ) . Incidences of graft loss ( 7.4 % vs 8.6 % ) , death ( 9.5 % vs 11.3 % ) , rejection ( 29.1 % vs 28.5 % ) , and renal function ( estimated glomerular filtration rate [ mean ± SD ] : 58.2 ± 26.3 vs 59.9 ± 25.7 mL/min per 1.73 m2 ) were not significantly different between prophylaxis and preemptive treatment . Tolerability was comparable between groups . Conclusions Prophylaxis was more effective than the preemptive approach , applying a low-intense surveillance protocol in preventing CMV infection and disease in intermediate-risk patients . Both strategies were similarly effective in preventing graft loss and death under the conditions of this long-term trial with a threshold of 400 copies/mL for initiation of anti-CMV treatment ABSTRACT Voriconazole prophylaxis is common following lung transplantation , but the value of therapeutic drug monitoring is unknown . A prospect i ve , observational study of lung transplant recipients ( n = 93 ) receiving voriconazole prophylaxis was performed . Serum voriconazole troughs ( n = 331 ) were measured by high-pressure liquid chromatography . The median initial and subsequent troughs were 1.91 and 1.46 μg/ml , respectively . The age of the patient directly correlated with initial troughs ( P = 0.005 ) . Patients that were ≥60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs , respectively . In 95 % ( 88/93 ) of patients , ≥2 troughs were measured . In 28 % ( 25/88 ) and 32 % ( 28/88 ) of these patients , all troughs were ≤1.5 μg/ml or > 1.5 μg/ml , respectively . Ten percent ( 10/93 ) and 27 % ( 25/93 ) of the patients developed invasive fungal infection ( tracheobronchitis ) and fungal colonization , respectively . The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml ( P = 0.07 ) . Invasive fungal infections or colonization were more likely with troughs of ≤1.5 μg/ml ( P = 0.01 ) and among patients with no trough of > 1.5 μg/ml ( P = 0.007 ) . Other cutoff troughs correlated less strongly with microbiologic outcomes . Troughs correlated directly with aspartate transferase levels ( P = 0.003 ) , but not with other liver enzymes . Voriconazole was discontinued due to suspected toxicity in 27 % ( 25/93 ) of the patients . The troughs did not differ at the times of suspected drug-induced hepatotoxicity , central nervous system ( CNS ) toxicity , or nausea/vomiting and in the absence of toxicity . Voriconazole prophylaxis was most effective at troughs of > 1.5 μg/ml . A cutoff for toxicity was not identified , but troughs of > 4 μg/ml were rare . The data support a target range of > 1.5 to 4 μg/ml ABSTRACT Treatment of solid-organ transplant ( SOT ) patients with ganciclovir (GCV)-valganciclovir ( VGCV ) according to the manufacturer 's recommendations may result in over- or underexposure . Bayesian prediction based on a population pharmacokinetics model may optimize GCV-VGCV dosing , achieving the area under the curve ( AUC ) therapeutic target . We conducted a two-arm , r and omized , open-label , 40 % superiority trial in adult SOT patients receiving GCV-VGCV as prophylaxis or treatment of cytomegalovirus infection . Group A was treated according to the manufacturer 's recommendations . For group B , the dosing was adjusted based on target exposures using a Bayesian prediction model ( NONMEM ) . Fifty-three patients were recruited ( 27 in group A and 26 in group B ) . About 88.6 % of patients in group B and 22.2 % in group A reached target AUC , achieving the 40 % superiority margin ( P < 0.001 ; 95 % confidence interval [ CI ] difference , 47 to 86 % ) . The time to reach target Output:	Our results show that although failure is reported in the studies , the level of detail prohibits a detailed analysis of failure of prophylaxis and pre-emptive therapy .
MS22236	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background and Aim : Chronic abdominal pain ( AP ) is common in children . Recall of symptoms is used clinical ly to determine management , to assess treatment progress , and in drug studies to assess outcomes . Limited data exist on accuracy of AP recall in children . The aim of the present study was to assess ability to accurately recall AP in children . Methods : The study was a secondary analysis of data obtained from a double-blind , r and omized , placebo-controlled trial , evaluating amitriptyline in children with functional gastrointestinal disorders . Children ages 8 to 17 years with AP predominant functional gastrointestinal disorders based on Rome II criteria were recruited from 6 centers . Those with evidence of organic disease were excluded . Patients maintained AP diary daily for 1 month ( presence , frequency , and intensity ) . At the end of the study , patients reported the number of days of AP during previous month . Agreement between daily pain reports and recalled pain was assessed . Univariate analysis was conducted with Spearman rank correlations . Results : We recruited 63 children ( 45 girls , mean age 12.8 years ) . Sixteen percent children had perfect agreement on number of days of AP . Fifty-four percent of children recalled fewer episodes of pain . The average number of days with AP by recall was 17.7/month , whereas by diary it was 23.5/month ( P = 0.001 ) . Correlation between patient recall of the last week of symptoms ( r = 0.47 ) was no better than correlation between recall of the last 30 days of symptoms ( r = 0.48 ) . On comparing AP recall versus various pain intensities , reported AP did not reflect only AP of greater severity . Higher correlation of recall of symptoms was seen in children 11 years or younger ( r = 0.59 ) as compared with children older than 11 years ( r = 0.26 ) . Conclusions : Few children can accurately recall the episodes of AP . Children commonly recall a lower frequency of AP than that assessed by prospect i ve diary reports . Reported recall does not reflect a shorter re collection period . Recall is not related to intensity of pain . Adolescents have worse recall of symptoms Objective : Aerophagia is a functional gastrointestinal disorder characterised by repetitive air swallowing , abdominal distension , belching , and flatulence . In severe cases , it can lead to pneumoperitonium , volvulus of the colon , and intestinal perforation . Little is known about the epidemiology and clinical profile of affected children . The main objective of the present study was to assess the epidemiology of aerophagia in 10- to 16-year-olds in Sri Lanka . Methods : A school-based cross-sectional survey was conducted in 8 r and omly selected schools in 4 r and omly selected provinces in Sri Lanka . Data were collected using a pretested , self-administered question naire , which was distributed in an examination setting and collected on the same day . Trained research assistants were present during completion of the question naire , for any required clarification . Aerophagia was diagnosed using the Rome III criteria . Results : In the present study , aerophagia was seen in 163 ( 7.5 % ) of the 2163 children evaluated . The prevalence was higher in older children ( 10.5 % in 15-year-olds ) and no sex difference was observed ( boys 8.2 % vs girls 6.8 % , P > 0.05 ) . Intestinal-related ( abdominal pain , nausea , and anorexia ) and extraintestinal symptoms ( headache , limb pain , sleeping difficulty , photophobia , and lightheadedness ) were more prevalent among affected children ( P < 0.05 ) . A higher percentage of affected children were found to be exposed to stressful events when compared with controls ( P < 0.05 ) . Conclusions : The present study highlights the high prevalence of aerophagia among Sri Lankan children and adolescents . This condition is more common in those exposed to emotional stress . Intestinal-related symptoms and extraintestinal somatic symptoms are frequently seen in affected children AIM To evaluate the clinical presentation , response to prophylactic therapy and outcome of children with cyclic vomiting syndrome ( CVS ) in Shiraz , Iran . METHODS During a period of 11 years ( March 1994 to March 2005 ) , 181 consecutive children with a final diagnosis of CVS were evaluated , treated and followed in our center . Patients were r and omized to receive either amitriptyline or propranolol as prophylactic treatments . RESULTS There were 88 boys and 93 girls with mean age of onset of symptoms of 4.9 + /- 3.3 years ( range , neonatal period to 14 years ) , the mean age at final diagnosis was 6.9 years ( range , 1.5 to 14 ) , and the mean duration between the onset of the first attack and the final diagnosis of CVS was 2 + /- 1.81 years ( range , 1/6 to 8) . The mean duration of each attack was 4.26 days ( range , from few hours to 10 d ) and the mean interval between the attacks was 1.8 mo ( range , 1 wk to 12 mo ) . The time of onset of the attacks was midnight to early morning in about 70 % of cases . Amitriptyline was effective in 46 out of 81 ( 56 % ) patients ( P < 0.001 ) . Propranolol appeared to have a superior action and was effective in 74 out of 83 ( 92 % ) patients ( P < 0.0001 ) . CONCLUSION There is a significant lag time between the onset of clinical symptoms and the final diagnosis of CVS in our area . In patients with typical clinical presentations of CVS , who are examined by an experienced physician , invasive workup is not necessary . Propranolol appears more effective than amitriptyline for prophylactic use in children with CVS BACKGROUND To date , no patient reported outcomes ( PRO ) instrument is available for evaluation of treatment efficacy in functional dyspepsia (FD)/postpr and ial distress syndrome ( PDS ) . The aim of our study was to perform focus group interviews for the development of a new question naire for assessing symptom pattern and severity in PDS . METHODS R and om ambulatory patients diagnosed with FD/PDS based on Rome III criteria and no predominant gastro-esophageal reflux disease ( GERD ) symptoms were invited to participate . Focus group sessions were organized where patients reported and discussed their symptoms , facilitated by an experienced physician . After reaching saturation of identified symptom items , questions for a pilot PRO instrument were drafted and evaluated in cognitive interviews for relevance , clarity , and consistency . KEY RESULTS Of 225 screened patients , 26 patients were diagnosed with PDS without overlapping GERD as single final diagnosis . Fifteen of these ( 87 % female , 48 ± 3.2 years ) participated in one of three focus groups . All ( 100 % ) confirmed experiencing symptoms that were triggered or aggravated by ingestion of a meal , corresponding to early satiation ( 100 % ) , and postpr and ial fullness ( 100 % ) . In addition reported gastroduodenal symptoms were nausea ( 40 % , postpr and ial in all , interpr and ial in 20 % ) , upper abdominal bloating ( 33 % ) , excessive belching ( 27 % ) , and vomiting ( 13 % ) . Epigastric pain and burning were present in respectively 20 % and 13 % . Non-gastroduodenal symptoms that patients reported included heartburn ( 33 % , but mostly sporadic ) , weight loss ( 93 % , on average 5.0 ± 1.7 kg ) , and fatigue ( 67 % ) . Questions evaluating these symptoms were vali date d in 15 cognitive interviews . CONCLUSIONS & INFERENCES This focus group study confirms symptoms corresponding to postpr and ial fullness and early satiation as the key items for developing a PRO for PDS Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists AIM To look at predictors of consulting behaviour among children with recurrent abdominal pain in a rural community in Malaysia . SUBJECTS AND METHODS A sample of 1462 school-children aged between 9 and 15 years were r and omly selected from all schools in Kuala Langat , a rural district in Malaysia . Those with recurrent abdominal pain , defined according to Apley 's criteria , were recruited and divided into consulters and non-consulters . A consulter was defined as a child who had sought the help of a medical practitioner at least once in the past year for recurrent abdominal pain . A detailed clinical , social and family history was obtained in all recruited children . RESULTS A total of 161 children were recruited : 78 ( 48.4 % ) consulters , 83 ( 51.6 % ) non-consulters . Of the consulters , 40 were boys , 38 were girls ( male : female ratio = 1.1:1 ) . The two sexes did not show a significant difference in prevalence of consulters [ p=0.189 ) . Of the ethnic groups , only Indians had a significantly higher likelihood to consult a doctor ( Indians , p=0.006 ; Malays , p=0.742 ; Chinese , p=0.050 ] . Younger children ( under 12 years ) had a significantly higher chance of having been brought to see a medical practitioner ( p=0.014 ) . Children in whom age of onset of abdominal pain was below ten years were also more likely to have been seen by a doctor ( p=0.012 ) . Children who had consulted a doctor were more likely to be missing school because of abdominal pain ( p<0.001 ) . Pain severity was not a significant factor ( p=0.429 ) . Multiple logistic regression analysis revealed that the only variable that remained significantly associated with health-care consultation was school absence ( p<0.001 ) . CONCLUSIONS Children who saw their doctors for recurrent abdominal pain were also more likely to be those who missed school on account of abdominal pain . Following multiple regression analysis , other factors were no longer significant OBJECTIVES : Functional GI disorders ( FGIDs ) are common in clinical practice , but little is known about the epidemiology of these disorders in the general population . We aim ed to determine the prevalence , association with psychological morbidity , and health care seeking behavior of FGIDs in the population . METHODS : A r and om sample of subjects ( n = 4500 ) aged ≥18 yr and representative of the Australian population were mailed a vali date d question naire . For these subjects we measured all Rome I GI symptoms and physician visits over the past 12 months , as well as neuroticism , anxiety , depression , and somatic distress . RESULTS : The response rate for the study was 72 % . The prevalence of any FGID was 34.6 % , and 62.1 % of these subjects had consulted a physician . There was considerable overlap of the FGIDs ( 19.2 % had more than two disorders ) . Independent predictors for an FGID diagnosis were neuroticism , somatic distress , anxiety , bowel habit disturbance , abdominal pain frequency , and increasing age . However , psychological morbidity did not independently discriminate between consulters and nonconsulters with an FGID . CONCLUSIONS : More than one third of the general population have one or more FGIDs . There seems to be a modest link between psychological morbidity and FGIDs , although other unknown factors seem to be more important in explaining health care seeking for these disorders Objectives : Irritable bowel syndrome is a multisymptom construct , with abdominal pain ( AP ) acting as the driving symptom of patient-reported severity . The Food and Drug Administration considers a > 30 % decrease in AP as satisfactory improvement , but this has not been vali date d in children . We investigated the correspondence of 2 measures for AP assessment , ≥30 % improvement in AP and global assessment of improvement . Methods : Secondary analysis of data from 72 children who completed a r and omized clinical trial for abdominal pain – associated functional gastrointestinal disorders . Children completed daily assessment of AP intensity , functional disability inventory ( FDI ) , question regarding pain 's interference with activities , and 2 global assessment questions . We measured the extent to which ≥30 % improvement of AP and global assessment questions correlated with each other and with disability . Results : The global questions correlated with each other ( r = 0.74 ; P < 0.0001 ) and with a ≥30 % improvement in AP ( P < 0.01 ) . Global outcomes were satisfaction with treatment was inversely related to the child 's report of interference with activities ( P < 0.01 ) and symptom relief was positively associated with ≥3 Output:	CONCLUSIONS Different outcome measures are used in therapeutic trials on functional disorders of the upper gastrointestinal tract .
MS22237	*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 study was to evaluate and compare the cost-effectiveness of varenicline with nicotine replacement therapy ( NRT ) for smoking cessation in four European countries ( Belgium , France , Sweden and the UK ) . METHODS Markov simulations , using the Benefits of Smoking Cessation on Outcomes ( BENESCO ) model , were performed . We simulated the incidence of four smoking-related morbidities : lung cancer , chronic obstructive pulmonary disease , coronary heart disease and stroke . The model computes quality -adjusted life-years gained and incremental cost-effectiveness ratios . Incremental cost-utility ratios were calculated , adopting a lifetime perspective . Efficacy data were obtained from a r and omized open-label trial : Week 52 continuous abstinence rates were 26.1 % for varenicline and 20.3 % for NRT . RESULTS The analyses imply that for countries analysed , smoking cessation using varenicline versus NRT was associated with reduced smoking-related morbidity and mortality . The number of morbidities avoided , per 1000 smokers attempting to quit , ranged from 9.7 in Belgium to 6.5 in the UK . The number of quality -adjusted life-years gained , per 1000 smokers , was 23 ( Belgium ) ; 19.5 ( France ) ; 29.9 ( Sweden ) ; and 23.7 ( UK ) . In all base-case simulations ( except France ) , varenicline dominated ( more effective and cost saving ) NRT regarding costs per quality -adjusted life-year gained ; for France the incremental cost-effectiveness ratio was 2803 . CONCLUSION This cost-effectiveness analysis demonstrated that since varenicline treatment was more effective , the result was increased healthcare cost savings in Belgium , Sweden and the UK . Our results suggest that funding varenicline as a smoking cessation aid is justifiable from a healthcare re source allocation perspective Introduction : School-based smoking prevention programmes can be effective , but evidence on cost-effectiveness is lacking . We conducted a cost-effectiveness analysis of a school-based “ peer-led ” intervention . Methods : We evaluated the ASSIST ( A Stop Smoking In Schools Trial ) programme in a cluster r and omized controlled trial . The ASSIST programme trained students to act as peer supporters during informal interactions to encourage their peers not to smoke . Fifty-nine secondary schools in Engl and and Wales were r and omized to receive the ASSIST programme or usual smoking education . Ten thous and seven hundred and thirty students aged 12–13 years attended participating schools . Previous work has demonstrated that the ASSIST programme achieved a 2.1 % ( 95 % CI = 0%–4.2 % ) reduction in smoking prevalence . We evaluated the public sector cost , prevalence of weekly smoking , and cost per additional student not smoking at 24 months . Results : The ASSIST programme cost of £ 32 ( 95 % CI = £ 29.70–£33.80 ) per student . The incremental cost per student not smoking at 2 years was £ 1,500 ( 95 % CI = £ 669–£9,947 ) . Students in intervention schools were less likely to believe that they would be a smoker at age 16 years ( odds ratio [ OR ] = 0.80 ; 95 % CI = 0.66–0.96 ) . Conclusions : A peer-led intervention reduced smoking among adolescents at a modest cost . The intervention is cost-effective under realistic assumptions regarding the extent to which reductions in adolescent smoking lead to lower smoking prevalence and /or earlier smoking cessation in adulthood . The annual cost of extending the intervention to Year 8 students in all U.K. schools would be in the region of £ 38 million and could result in 20,400 fewer adolescent smokers OBJECTIVES To : evaluate the impact of smoking status on objective productivity and absenteeism measures ; evaluate the impact of smoking status on subjective measures of productivity ; and assess the correlation between subjective and objective productivity measures . DESIGN Prospect i ve cohort study in a workplace environment . SUBJECTS Approximately 300 employees ( 100 each of former , current , and never smokers ) at a reservation office of a large US airline . MAIN OUTCOME MEASURES Objective productivity and absenteeism data were supplied by the employer . Subjective assessment s of productivity were collected using a self report instrument , the Health and Work Question naire ( HWQ ) . RESULTS Current smokers had significantly greater absenteeism than did never smokers , with former smokers having intermediate values ; among former smokers , absenteeism showed a significant decline with years following cessation . Former smokers showed an increase in seven of 10 objective productivity measures as compared to current smokers , with a mean increase of 4.5 % . While objective productivity measures for former smokers decreased compared to measures for current smokers during the first year following cessation , values for former smokers were greater than those for current smokers by 1–4 years following cessation . Subjective assessment s of “ productivity evaluation by others ” and “ personal life satisfaction ” showed significant trends with highest values for never smokers , lowest for current smokers , and intermediate for former smokers . CONCLUSIONS Workplace productivity is increased and absenteeism is decreased among former smokers as compared to current smokers . Productivity among former smokers increases over time toward values seen among never smokers . Subjective measures of productivity provide indications of novel ways of productivity assessment that are sensitive to smoking status Background Although effective smoking cessation interventions exist , information is limited about their cost-effectiveness and cost-utility . Objective To assess the cost-effectiveness and cost-utility of an Internet-based multiple computer-tailored smoking cessation program and tailored counseling by practice nurses working in Dutch general practice s compared with an Internet-based multiple computer-tailored program only and care as usual . Methods The economic evaluation was embedded in a r and omized controlled trial , for which 91 practice nurses recruited 414 eligible smokers . Smokers were r and omized to receive multiple tailoring and counseling ( n=163 ) , multiple tailoring only ( n=132 ) , or usual care ( n=119 ) . Self-reported cost and quality of life were assessed during a 12-month follow-up period . Prolonged abstinence and 24-hour and 7-day point prevalence abstinence were assessed at 12-month follow-up . The trial-based economic evaluation was conducted from a societal perspective . Uncertainty was accounted for by bootstrapping ( 1000 times ) and sensitivity analyses . Results No significant differences were found between the intervention arms with regard to baseline characteristics or effects on abstinence , quality of life , and addiction level . However , participants in the multiple tailoring and counseling group reported significantly more annual health care – related costs than participants in the usual care group . Cost-effectiveness analysis , using prolonged abstinence as the outcome measure , showed that the mere multiple computer-tailored program had the highest probability of being cost-effective . Compared with usual care , in this group € 5100 had to be paid for each additional abstinent participant . With regard to cost-utility analyses , using quality of life as the outcome measure , usual care was probably most efficient . Conclusions To our knowledge , this was the first study to determine the cost-effectiveness and cost-utility of an Internet-based smoking cessation program with and without counseling by a practice nurse . Although the Internet-based multiple computer-tailored program seemed to be the most cost-effective treatment , the cost-utility was probably highest for care as usual . However , to ease the interpretation of cost-effectiveness results , future research should aim at identifying an acceptable cutoff point for the willingness to pay per abstinent participant PURPOSE To evaluate the incremental effectiveness and cost-effectiveness of a staged-based , computerized smoking cessation intervention relative to st and ard care in an urban managed care network of primary care physicians . DESIGN Decision-analytic model based on results of a r and omized clinical trial . METHODOLOGY Patient outcomes and cost estimates were derived from clinical trial data . Effectiveness was measured in terms of 7-day point-prevalence abstinence at 6 months post-intervention . Quality -adjusted life years ( QALYs ) and cost-effectiveness ( CE ) were calculated , with CE measured as cost per patient per life year saved and per quality -adjusted life years saved . CE estimates were adjusted to account for partial behavior change as measured in terms of progression in stage of readiness to quit . Sensitivity analyses were conducted to evaluate the robustness of key model assumptions . PRINCIPAL FINDINGS Intervention patients were 1.77 times more likely to be smoke-free at 6 months follow-up than those in st and ard care ( p=.078 ) . The intervention generated an additional 3.24 quitters per year . Annualized incremental costs were $ 5,570 per primary care practice , and $ 40.83 per smoker . The mean incremental cost-effectiveness ratio was $ 1,174 per life year saved ( $ 869 per QALY ) . When the intervention impact on progression in stage of readiness to quit was also considered , the mean incremental cost-effectiveness ratio declined to $ 999 per life year saved ( $ 739 per QALY ) . CONCLUSIONS From a physician 's practice perspective , the stage-based computer tailored intervention was cost-effective relative to st and ard care . Incorporation of partial behavior change into the model further enhanced favorability of the cost-effectiveness ratio Introduction : An employer-based cost-benefit analysis for varenicline versus bupropion was conducted using clinical outcomes from a recently published trial . Methods : A decision tree model was developed based on the net benefit of treatment to produce a nonsmoker at 1 year . Sensitivity analyses were conducted based on quit rates with placebo and varenicline and the cost of varenicline . Results : Estimated 12-month employer cost savings per non-smoking employee were $ 540.60 for varenicline , $ 269.80 for bupropion SR generic , $ 150.80 for bupropion SR br and , and $ 81.80 for placebo . Varenicline was more cost beneficial than placebo , which had quit rates of 16.9 % or less . The quit rate with varenicline would have to be ≤16.9 % to lose cost benefit over bupropion SR generic . Conclusions : The economic benefit of varenicline is improved over bupropion , despite the increased initial cost of varenicline There is a lack of evidence of the relative cost-effectiveness of proactive telephone counseling ( PTC ) and Web-based delivery of smoking cessation services in conjunction with pharmacotherapy . We calculated the differential cost-effectiveness of three behavioral smoking cessation modalities with varenicline treatment in a r and omized trial of current smokers from a large health system . Eligible participants were r and omized to one of three smoking cessation interventions : Web-based counseling ( n = 401 ) , PTC ( n = 402 ) , or combined PTC-Web counseling ( n = 399 ) . All participants received a st and ard 12-week course of varenicline . The primary outcome was a 7-day point prevalent nonsmoking at the 6 month follow-up . The Web intervention was the least expensive followed by the PTC and PTC-Web groups . Costs per additional 6-month nonsmoker and per additional lifetime quitter were $ 1,278 and $ 2,601 for Web , $ 1,472 and $ 2,995 for PTC , and $ 1,617 and $ 3,291 for PTC-Web . Cost per life-year ( LY ) and quality -adjusted life-year ( QALY ) saved were $ 1,148 and $ 1,136 for Web , $ 1,320 and $ 1,308 for PTC , and $ 1,450 and $ 1,437 for PTC-Web . Based on the cost per LY and QALY saved , these interventions are among the most cost-effective life-saving medical treatments . Web , PTC , and combined PTC-Web treatments were all highly cost-effective , with the Web treatment being marginally more cost-effective than the PTC or combined PTC-Web treatments BACKGROUND Employers have responded to new regulations on the effects of passive smoking by introducing a range of workplace policies . Few policies include provision of smoking cessation intervention . OBJECTIVE To estimate the cost to employers of smoking in the workplace in Scotl and to illustrate the potential gains from smoking cessation provision . Costs vary with type of smoking policy in place ; therefore , to estimate these costs results from a survey were combined with evidence drawn from a literature review . STUDY DESIGN A telephone survey of 200 Scottish workplaces , based on a stratified r and om sample of workplaces with 50 or more employees , was conducted in 1996 . Additional evidence was compiled from a review of the literature of smoking related costs and specific smoking related effects . RESULTS 167 completed responses were received , of which 156 employers ( 93 % ) operated a smoking policy , 57 ( 34 % ) operated smoke free buildings , and 89 ( 53 % ) restricted smoking to a “ smoke room ” . The research literature shows absenteeism to be higher among smokers when compared to non-smokers . The estimated cost of smoking related absence in Scotl and is £ 40 million per annum . Total productivity losses are estimated at approximately £ 450 million per annum . In addition , the re source cost in terms of losses from fires caused by smoking material s is estimated at approximately £ 4 million per annum . In addition , there are costs from sm Output:	Smoking also yields cost savings in pension payments from the premature death of smokers . 3 . The use of pharmacotherapies such as varenicline , NRT , and Bupropion , when combined with GP counseling or other behavioral treatment interventions ( such as proactive telephone counseling and Web-based delivery ) , is both clinical ly effective and cost effective to primary health care providers . 5 . Price-based policy measures such as increase in tobacco taxes are unarguably the most effective means of reducing the consumption of tobacco . 6 . Smoking cessation classes are known to be most effective among community-based measures , as they could lead to a quit rate of up to 35 % , but they usually incur higher costs than other measures such as self-help quit-smoking kits . 7 . Advertising media , telecommunications , and other technology-based interventions ( such as TV , radio , print , telephone , the Internet , PC , and other electronic media ) usually have positive synergistic effects in reducing smoking prevalence especially when combined to deliver smoking cessation messages and counseling support . 9 . Implementing smoke-free workplaces would also produce myriads of new quitters and reduce the amount of cigarette consumption , leading to cost savings in direct medical costs to primary health care providers . Workplace interventions are , however , likely to yield far greater economic benefits over the long term , as reduced prevalence will lead to a healthier and more productive workforce . Conclusions We conclude that the direct costs and externalities to society of smoking far outweigh any benefits that might be accruable at least when considered from the perspective of socially desirable outcomes ( ie , in terms of a healthy population and a productive workforce ) . However , on the balance of probabilities , most of the cessation measures review ed have not only proved effective but also cost effective in delivering the much desired cost savings and net gains to individuals and primary health care providers
MS22238	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVE : Most clinic-based weight control treatments for youth have been design ed for preadolescent children by using family-based care . However , as adolescents become more autonomous and less motivated by parental influence , this strategy may be less appropriate . This study evaluated a primary care – based , multicomponent lifestyle intervention specifically tailored for overweight adolescent females . METHODS : Adolescent girls ( N = 208 ) 12 to 17 years of age ( mean ± SD : 14.1 ± 1.4 years ) , with a mean ± SD BMI percentile of 97.09 ± 2.27 , were assigned r and omly to the intervention or usual care control group . The gender and developmentally tailored intervention included a focus on adoptable healthy lifestyle behaviors and was reinforced by ongoing feedback from the teen ’s primary care physician . Of those r and omized , 195 ( 94 % ) completed the 6-month posttreatment assessment , and 173 ( 83 % ) completed the 12-month follow-up . The primary outcome was reduction in BMI z score . RESULTS : The decrease in BMI z score over time was significantly greater for intervention participants compared with usual care participants ( −0.15 in BMI z score among intervention participants compared with −0.08 among usual care participants ; P = .012 ) . The 2 groups did not differ in secondary metabolic or psychosocial outcomes . Compared with usual care , intervention participants reported less reduction in frequency of family meals and less fast-food intake . CONCLUSIONS : A 5-month , medium-intensity , primary care – based , multicomponent behavioral intervention was associated with significant and sustained decreases in BMI z scores among obese adolescent girls compared with those receiving usual care BACKGROUND Cognitive behavioral therapy ( CBT ) teaches behavioral and cognitive strategies that focus on achieving and maintaining lifestyle changes . OBJECTIVE We examined the effectiveness of a CBT program ( CHOOSE HEALTH ) for improving body composition , diet , and physical activity in overweight and obese adolescents . DESIGN Adolescents [ 16 male , 31 female ; aged 14.5 + /- 1.6 y ; body mass index ( BMI ; in kg/m(2 ) ) 30.9 + /- 4.2 ] were block-matched into 2 groups by age , sex , Tanner stage , BMI , and hip and waist circumferences and were r and omly assigned to CBT or no treatment ( control ) . CBT consisted of 10 weekly sessions , followed by 5 fortnightly telephone sessions . RESULTS Compared with the control , over 20 wk , CBT improved ( significant group x time interactions ) BMI ( CBT , -1.3 + /- 0.4 ; control , 0.3 + /- 0.3 ; P = 0.007 ) , weight ( CBT , -1.9 + /- 1.0 kg ; control , 3.8 + /- 0.9 kg ; P = 0.001 ) , body fat ( CBT , -1.5 + /- 0.9 kg ; control , 2.3 + /- 1.0 kg ; P = 0.001 ) , and abdominal fat ( CBT , -124.0 + /- 46.9 g ; control , 50.1 + /- 53.5 g ; P = 0.008 ) . CBT showed a greater reduction in intake of sugared soft drinks as a percentage of total energy ( CBT , -4.0 + /- 0.9 % ; control , -0.3 + /- 0.9 % ; P = 0.005 for group x time interaction ) , which was related to reductions in weight ( r = 0.48 , P = 0.04 ) , BMI ( r = 0.53 , P = 0.02 ) , and waist circumference ( r = 0.54 , P = 0.02 ) . Physical activity did not change significantly . CONCLUSIONS A 10-wk CBT program followed by 10 wk of fortnightly phone contact improved body composition in overweight and obese adolescents . Changes in soft drink consumption may have contributed to this benefit OBJECTIVE A r and omized controlled trial tested the efficacy of an internet-based lifestyle behavior modification program for African-American girls over a 2-year period of intervention . RESEARCH METHODS AND PROCEDURES Fifty-seven overweight ( mean BMI percentile , 98.3 ) African-American girls ( mean age , 13.2 years ) were r and omly assigned to an interactive behavioral internet program or an internet health education program , the control condition . Overweight parents were also participants in the study . Forty adolescent-parent dyads ( 70 % ) completed the 2-year trial . Outcome data including BMI , body weight , body composition , and weight loss behaviors were collected at baseline and at 6-month intervals . A computer server tracked use of the web sites . RESULTS An intention-to-treat statistical approach was used , with the last observation carried forward . In comparison with the control condition , adolescents in the behavioral program lost more mean body fat ( BF ) ( -1.12 + /- 0.47 % vs. 0.43 + /- 0.47 % BF , p < 0.05 ) , and parents in the behavioral program lost significantly more mean body weight ( -2.43 + /- 0.66 vs. -0.35 + /- 0.64 kg , p < 0.05 ) during the first 6 months . This weight loss was regained over the next 18 months . After 2 years , differences in fat for adolescents ( -0.08 + /- 0.71 % vs. 0.84 + /- 0.72 % BF ) and weight for parents ( -1.1 + /- 0.91 vs. -0.60 + /- 0.89 kg ) did not differ between the behavioral and control programs . DISCUSSION An internet-based weight management program for African-American adolescent girls and their parents result ed in weight loss during the first 6 months but did not yield long-term loss due to reduced use of the web site over time Lifestyle modification programs ( LMP ) for weight loss in adolescents with obesity are effective but not available . Primary care may be a setting for reaching more adolescents . Two models of LMP for use in primary care were examined . Adolescents and caregivers enrolled in a 1-year r and omized trial comparing Group LMP with Self-Guided LMP . All participants ( N = 169 ) received the same treatment recommendations and met with a health coach six times in clinic . Group LMP participants had an additional 17 group sessions ; those in Self-Guided LMP followed the remainder of the program at home with parental support . The primary outcome was percentage change in initial body mass index . The mean ( SE ) 1.31 % ( 0.95 % ) reduction in Group LMP did not differ significantly from the 1.17 % ( 0.99 % ) decrease in the Self-Guided LMP ( p = 0.92 ) . Both treatments were significantly effective in reducing body mass index . Given its brevity , the Self-Guided LMP offers an innovative approach for primary care Using self-determination theory ( SDT ) as an explanatory framework , this r and omised-controlled study evaluates the effect of a motivational interviewing (MI)-based intervention as an addition to a st and ard weight loss programme ( SWLP ) on physical activity ( PA ) practice in obese adolescents over a six-month period . Fifty-four obese adolescents ( mean age = 13 years , mean BMI = 29.57 kg/m² ) were r and omly assigned to an SWLP group ( n = 28 ) or SWLP + MI group ( n = 26 ) . Both groups received two SWLP sessions , supplemented for the SWLP + MI group , by six MI sessions . Perceived autonomy support , perceived competence , motivational regulations , PA and BMI were assessed at baseline , three and six months ( i.e. the end of the programme ) . MLM analyses revealed that compared to SWLP , the SWLP + MI group had a greater BMI decrease and a greater PA practice increase over time . Moreover , the SWLP + MI group reported greater autonomy support from medical staff at the end of the programme , greater increase in integrated and identified regulations and a stronger decrease in amotivation . MI appears as an efficient counselling method as an addition to an SWLP to promote PA in the context of pediatric obesity OBJECTIVE To evaluate the efficacy of Motivational Interviewing ( MI ) as an intervention for promoting self-efficacy and weight loss in a sample of overweight and obese youth . METHODS / Design 40 participants ( aged 10 - 18 years ) were r and omly assigned to control ( social skills training ) or treatment ( MI ) group . Both groups received individual therapy ( ~30 min/month ) in addition to usual care of diet/exercise counseling . Pre- and post- ( at 6 months follow-up ) variables included measures of self-efficacy and anthropometrics . RESULTS Although significant between-group differences were not found , individuals in the MI group attended more sessions . Overall , participants in both groups showed significant increases in self-efficacy and a trend of decreased body mass index z-scores . CONCLUSIONS Health benefits from participation in individual therapy may have been accrued ; however , specific benefits attributable to MI were limited . Findings suggest that more than one type of counseling intervention ( i.e. , MI and social skills training ) may be beneficial when providing integrative treatment for obese youth OBJECTIVE : This study examined the 24-month outcomes of a r and omized controlled trial of a group-based behavioral weight control ( BWC ) program combined with either activity-based peer intervention or aerobic exercise . METHODS : At baseline , 118 obese adolescents ( 68 % female ; BMI = 31.41 ± 3.33 ) ages 13 to 16 years ( mean = 14.33 ; SD = 1.02 ) were r and omized to receive 1 of 2 weight loss interventions . Both interventions received the same 16-week group-based cognitive-behavioral treatment , combined with either aerobic exercise or peer-based adventure therapy . Eighty-nine adolescents ( 75 % of original sample ) completed the 24-month follow-up . Anthropometric and psychosocial measures were obtained at baseline , at the end of the 16-week intervention , and at 12 and 24 months following r and omization . RESULTS : An intent-to-treat mixed factor analysis of variance indicated a significant effect for time on both percent over 50th percentile BMI for age and gender and st and ardized BMI score , with no differences by intervention group . Post hoc comparisons showed a significant decrease in percent overweight at 4 months ( end of treatment ) , which was maintained at both 12- and 24-month follow-up visits . Significant improvements on several dimensions of self-concept were noted , with significant effects on physical appearance self-concept that were maintained through 24 months . CONCLUSIONS : Both BWC conditions were effective at maintaining reductions in adolescent obesity and improvements in physical appearance self-concept through 24-month follow-up . This study is one of the first to document long-term outcomes of BWC intervention among adolescents OBJECTIVE The aim was to evaluate the efficacy of a Family Weight School treatment based on family therapy in group meetings with adolescents with a high degree of obesity . METHODS Seventy-two obese adolescents aged 12 - 19 years old were referred to a childhood obesity center by pediatricians and school nurses and offered a Family Weight School therapy program in group meetings given by a multidisciplinary team . Intervention was compared with an untreated waiting list control group . Body mass index ( BMI ) and BMI z-scores were calculated before and after intervention . RESULTS Ninety percent of the intervention group completed the program ( 34 boys , 31 girls ; baseline age = 14.8 + /- 1.8 years [ mean + /- st and ard deviation , SD ] , BMI = 34 + /- 4.0 , BMI z-score = 3.3 + /- 0.4 ) . In the control group 10 boys and 13 girls ( baseline age = 14.3 + /- 1.6 , BMI = 34.1 + /- 4.8 , BMI z-score = 3.2 + /- 0.4 ) participated in the 1-year follow-up . Adolescents in the intervention group with initial BMI z-score < 3.5 ( n = 49 out of 65 , baseline mean age = 14.8 , mean BMI = 33.0 , mean BMI z-score = 3.1 ) , showed a significant decrease in BMI z-scores in both genders ( -0.09 + /- 0.04 , p = 0.039 ) compared with those in the control group with initial BMI z-score < 3.5 ( n = 17 out of 23 , mean baseline age = 14.1 , mean baseline BMI = 31.6 , mean baseline BMI z-score = 3.01 ) . No difference was found in adolescents with BMI z-scores > 3.5 . CONCLUSIONS Family Weight School treatment model might be suitable for adolescents with BMI z-score < 3.5 treated with a few sessions in a multidisciplinary program AIM This study evaluates the efficacy of the Choose Health program , a family-based cognitive behavioural lifestyle program targeting improved eating and activity habits , in improving body composition , cardiovascular fit Output:	There was considerable variability between the interventions , but they were all multifactorial , with components such as nutritional education , physical activity , family support and psychological therapy . The number of contacts with subjects during the course of the intervention was a predictor of treatment efficacy when the groups were compared . Conclusions Multidisciplinary interventions including family support and guided behavior modification appear to be effective methods of reducing BMI in overweight and obese adolescents
MS22239	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To evaluate the efficacy of the e-learning course " Genetics of Epilepsies " and to assess the experiences of the participants and e-moderators with this new approach . METHODS Prospect i ve , controlled study with waiting group ( control group , n = 18 ) and e-learning group ( n = 20 ) . The control group got the same reference literature list as the e-learning group . Both groups were assessed twice : The e-learning group before and after the course ; the control group was assessed at the same times . PRIMARY OUTCOME MEASURE increase in knowledge about genetics of epilepsies using question naires based on items formulated by experts ( internal consistency , Cronbach 's alpha = 0.86 ) . Main hypothesis : greater increase of knowledge in the e-learning group compared to control group . SECONDARY OUTCOME MEASURES assessment of the educational course and learning environment by participants and by tutors/e-moderators . RESULTS Significant time x group interaction and group effect ( ANOVA , each p < 0.01 ) with regard to knowledge . At baseline , the groups did not differ with respect to knowledge about genetics of epilepsy . In contrast to the control group , the increase of knowledge in the e-learning group was highly significant ( p < 0.001 ) . The majority of the participants of the e-learning course was content with their personal learning process ( 75 % agree , 15 % strongly agree ) . Most of them reported a gain in competence in the treatment and counseling of people with epilepsy ( 38.9 % agree , 50 % strongly agree ) . All participants would recommend this course to others and all but one participant are interested in other e-learning courses . CONCLUSION The study indicates e-learning courses are an appropriate tool to improve knowledge of physicians in genetics of epilepsy BACKGROUND We evaluated the impact of expert instruction during laboratory-based basic surgical skills training on subsequent performance of more complex surgical tasks . METHODS Forty-five junior residents were r and omized to learn basic surgical skills in either a self-directed or faculty-directed fashion . Residents returned to the laboratory 2 days later and were evaluated while performing 2 tasks : skin closure and bowel anastomosis . Outcome measures included Objective Structured Assessment of Technical Skill , time to completion , final product quality , and resident perceptions . RESULTS Objective Structured Assessment of Technical Skill , time to completion , and skin esthetic ratings were not better in the faculty-directed group , although isolated improvement in anastomotic leak pressure was seen . Residents perceived faculty-directed training to be superior . CONCLUSIONS Our data provided minimal objective evidence that faculty-directed training improved transfer of learned skills to more complex tasks . Residents perceived that there was a benefit of faculty mentoring . Curriculum factors related to training of basic skills and subsequent transfer to more complex tasks may explain these contrasting results STUDY OBJECTIVE We conducted a prospect i ve , r and omized , controlled trial to test the hypothesis that a 34-minute video self-instruction ( VSI ) training program for adult CPR would yield comparable or better CPR performance than the current community st and ard , the American Heart Association Heartsaver course . METHODS Incoming freshman medical students were r and omly assigned to VSI or the Heartsaver CPR course . Two to 6 months after training , we tested subjects to determine their ability to perform CPR in a simulated cardiac arrest setting . Blinded observers used explicit criteria to assess our primary outcome , CPR performance skill . In addition , we assessed secondary outcomes including sequential performance of individual skills , ventilation and chest compression characteristics , and written tests of CPR-related knowledge and attitudes . RESULTS VSI trainees displayed superior overall performance compared with traditional trainees . Twenty of 47 traditional trainees ( 43 % ) were judged not competent in their performance of CPR , compared with only 8 of 42 VSI trainees ( 19 % ; absolute difference , 24 % ; 95 % confidence interval , 5 % to 42 % ) . CONCLUSION In a group of incoming freshman medical students , we found that a half-hour of VSI result ed in superior overall CPR performance compared with that in traditional trainees . If vali date d by further research , VSI may provide a simple , quick , and inexpensive alternative to traditional CPR instruction for health care workers and , perhaps , the general population Background To evaluate the educational effects of a clinical ly integrated e-learning course for teaching basic evidence -based medicine ( EBM ) among postgraduates compared to a traditional lecture-based course of equivalent content . Methods We conducted a cluster r and omised controlled trial in the Netherl and s and the UK involving postgraduate trainees in six obstetrics and gynaecology departments . Outcomes ( knowledge gain and change in attitude towards EBM ) were compared between the clinical ly integrated e-learning course ( intervention ) and the traditional lecture based course ( control ) . We measured change from pre- to post-intervention scores using a vali date d question naire assessing knowledge ( primary outcome ) and attitudes ( secondary outcome ) . Results There were six clusters involving teaching of 61 postgraduate trainees ( 28 in the intervention and 33 in the control group ) . The intervention group achieved slightly higher scores for knowledge gain compared to the control , but these results were not statistically significant ( difference in knowledge gain : 3.5 points , 95 % CI -2.7 to 9.8 , p = 0.27 ) . The attitudinal changes were similar for both groups . Conclusion A clinical ly integrated e-learning course was at least as effective as a traditional lecture based course and was well accepted . Being less costly than traditional teaching and allowing for more independent learning through material s that can be easily up date d , there is a place for incorporating e-learning into postgraduate EBM curricula that offer on-the-job training for just-in-time learning . Trial registration Trial registration number : ACTRN12609000022268 This study was design ed to assess whether a self- study interactive computer program is more effective than weekly seminars for teaching fundamental skills of electrocardiographic interpretation to junior medical students . Forty-two students were assigned to the computer and 41 to the seminar group . A test was given to each participant at the beginning and end of each rotation . The computer group used a computer-assisted learning program , and the seminar group met weekly with a cardiologist to review electrocardiograms . Attendance at a minimum of 80 % of the seminars or completion of 80 % of the computer-assisted learning program was required for inclusion in the statistical analysis . The mean difference in test scores before and after study was 5.69 for the computer group and 4.36 for the seminar group ( P less than .02 by one-tailed t-test ) . These results indicate that the computer group performed significantly better than the seminar group . We believe this difference to be educationally important A growing body of literature deals with the use of self-instructional methods for teaching biostatistics to medical students . The University of Tennessee Department of Community Medicine tested the hypothesis that , in controlled , r and omized situations , learning of statistical material by self-instruction is equivalent to learning identical material by the lecture method . An analysis of student performance , in terms of the grade s obtained on two separate examinations , showed that students learning by self-instruction did as well or better than their colleagues taking lectures . On the basis of these results , self-instructional biostatistics for medical students at the University of Tennessee has been selected as the major teaching method of that subject BACKGROUND Although educators agree that the approach to cancer management must be multidisciplinary , medical students usually observe cancer patients through the eyes of a single specialist at any given time . METHODS In order to teach third-year medical students that cancer management is multidisciplinary , we developed the Oncology Game , an interactive , computer-assisted board game built on the principles of self-directed learning and student-student interaction . Eight " patients " with different histologic types of cancer are distributed r and omly to 4 students , who play in teams of 2 . The object is for the team to obtain the best treatment for its patients by advancing them via a roll of dice through surgical , medical , and radiation oncology clinics in the order most logical for the patient 's particular cancer type . To test improvement in cognitive skills as a function of play , 16 students participated in a tournament taking parallel pretest and posttests before and after each round of play . RESULTS Students demonstrated a statistically significant change in the total number of questions answered correctly each time they played the Oncology Game ( F = 4.16 , P = 0.018 ; Pretest Round 1 : 8.88 + /- 0.58 ; Posttest Round 1 : 9.63 + /- 0.42 ; Pretest Round 2 : 10.75 + /- 0.62 ; Posttest Round 2 : 11.5 + /- 0.85 ) . Post hoc pairwise comparison revealed a significant improvement in student performance after playing two rounds of the Oncology Game . Based on the postgame survey , students felt they improved their underst and ing of oncologic principles ( 4.56 + /- 0.13 ) , knowledge of malignancies ( 4.50 + /- 0.13 ) , and appreciation for the multidisciplinary nature of cancer management ( 4.56 + /- 0.13 ) . CONCLUSIONS Improved test scores and postgame survey results demonstrate that third-year medical student students can learn about basic oncology principles and gain an appreciation for oncology as a multidisciplinary field of medicine through an interactive , computer-assisted board game BACKGROUND Procedural sedation guidelines were established for a tertiary care pediatric emergency department ( ED ) . We developed a pediatric procedural sedation course to disseminate these guidelines . OBJECTIVE Our objective was to evaluate the effectiveness of a sedation course in improving physicians ' knowledge of pediatric procedural sedation practice s and guidelines , relative to individual self-directed learning . METHODS We recruited emergency staff physicians and fellows as well as fourth-year pediatric residents in a tertiary care pediatric ED to participate in a r and omized , controlled , educational intervention . All consenting physicians received pediatric sedation educational material for individual study 2 weeks before a learning assessment . Participants were r and omly assigned to one of 2 groups . The self-directed learning group ( n = 24 ) completed a multiple-choice examination without receiving any formal teaching . The study group ( n= 24 ) participated in a 4-hour formal multifaceted sedation course before writing the multiple-choice examination . RESULTS The groups did not differ significantly in demographic characteristics or self-perceived knowledge of pediatric sedation . The formal teaching group 's median examination score ( 83.3 % ; range 75.8%-96.5 % ) was significantly higher ( p < 0.0001 ) than the median examination score of participants in the self-directed study group ( 73.3 % , range 43.5%-86.6 % ) . CONCLUSION The multifaceted sedation course was more effective in improving physician knowledge and underst and ing of sedation guidelines and practice s than unstructured , self-directed learning A study was undertaken to test the hypothesis that self-instructional programs in nutrition and dentistry are as effective a teaching method as traditional lectures . Five programmed self-instructional manuals accompanied by 191 slides were developed and evaluated for effectiveness , as compared to six lectures containing the same information . The study population of 83 freshmen dental students was r and omly assigned to a control ( lecture ) group and an experimental ( self-instruction ) group . Cognitive tests , performance criteria for diet counseling , and an attitudinal question naire were used to compare the two groups . The results of the analysis demonstrated that there was no significant difference in the test scores in the lecture and self-instruction groups A computer-assisted interactive videodisc instructional program , HP-RHEUM was design ed to teach clinical findings in arthritis to occupational and physical therapy students . Using the Rheumatology Image Library videodisc produced by the National Library of Medicine , HP-RHEUM consists of instructional modules which employ advance organizers , examples/nonexamples , summaries , and immediate feedback . To see if HP-RHEUM would be as effective as traditional classroom instruction , control data were collected in 1991 from 52 OT and PT students . Treatment data were collected from 61 students in 1992 when HP-RHEUM entirely replaced lectures . Identical pre- and post-tests consisted of 70 multiple choice questions , with 24 matched to slides . On the slide questions the HP-RHEUM group had significantly higher scores . Otherwise , there was no significant difference in performance between groups . HP-RHEUM provided an independent learning method and enhanced visual comprehension of rheumatologic disease concepts OBJECTIVES The GMC recommends that students become independent learners , while tutor time is an increasingly precious re source . A set of structured learning material s requiring students to undertake and reflect on practical tasks in five learning areas was developed . DESIGN The study used a r and omized control trial to evaluate the effectiveness of using these structured learning material s in place of conventional teaching for 228 third-year undergraduate students and 55 teachers , on both hospital and community based medical and general practice firms . Evaluation involved assessing student performance on an examination question and a writing task , together with a student and tutor satisfaction question naire . SETTING King 's College School of Medicine and Dentistry , London . SUBJECTS Third-year medical ( first-year clinical ) undergraduates . RESULTS No significant difference in learning outcome was found for students on community- and hospital-based medical and general practice firms between students who had used the structured material s and those who had had conventional teaching on the same topic . The packs were acceptable to tutors and students . CONCLUSIONS Such re sources represent a mid-point between formal didactic teaching and self-directed learning . They may be particularly suitable for promoting independent learning for students on traditional medical courses . They offer an appropriate way to cover certain topics in the clinical curriculum and help to protect tutor time for topics which can not be effectively taught in other ways This study evaluated 2 methods of disseminating an empirically vali date d smokeless tobacco intervention delivered during routine dent Output:	When learners were involved in choosing learning re sources , SDL was more effective . Advanced learners seemed to benefit more from SDL . CONCLUSIONS Moderate quality evidence suggests that SDL in health professions education is associated with moderate improvement in the knowledge domain compared with traditional teaching methods and may be as effective in the skills and attitudes domains
MS22240	*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 assessed whether directly observed fluoxetine treatment reduced depression symptom severity and improved HIV outcomes among homeless and marginally housed HIV-positive adults in San Francisco , California , from 2002 to 2008 . METHODS We conducted a nonblinded , r and omized controlled trial of once-weekly fluoxetine , directly observed for 24 weeks , then self-administered for 12 weeks ( n = 137 persons with major or minor depressive disorder or dysthymia ) . Hamilton Depression Rating Scale score was the primary outcome . Response was a 50 % reduction from baseline and remission a score below 8 . Secondary measures were Beck Depression Inventory-II ( BDI-II ) score , antiretroviral uptake , antiretroviral adherence ( measured by unannounced pill count ) , and HIV-1 RNA viral suppression ( < 50 copies/mL ) . RESULTS The intervention reduced depression symptom severity ( b = -1.97 ; 95 % confidence interval [ CI ] = -0.85 , -3.08 ; P < .001 ) and increased response ( adjusted odds ratio [ AOR ] = 2.40 ; 95 % CI = 1.86 , 3.10 ; P < .001 ) and remission ( AOR = 2.97 ; 95 % CI = 1.29 , 3.87 ; P < .001 ) . BDI-II results were similar . We observed no statistically significant differences in secondary HIV outcomes . CONCLUSIONS Directly observed fluoxetine may be an effective depression treatment strategy for HIV-positive homeless and marginally housed adults , a vulnerable population with multiple barriers to adherence Spiritual models of illness causation are common in Africa . This article reports an investigation of some clinical correlates of patients who believe that their problem has a spiritual cause . A cross‐sectional survey of r and om attenders at primary health care clinics and traditional medical practitioners ( TMP ) in Harare ( n= 302 ) was performed . Interviews included eliciting of explanatory models , indigenous and etic psychiatric measures . Spiritual models of illness were held by half the subjects . Patients who hold this model had higher levels of mental disorder and were more likely to have a mental illness as judged by the patient , care provider and psychiatric measures . The symptoms of such patients resemble the construct of anxiety . Such patients are more likely to consult TMP and to have a chronic illness . Spiritual models of illness may represent an indigenous model to explain the distressing symptoms of nonpsychotic mental illness . Including them in training of primary health care providers may improve the recognition of mental illness CONTEXT Depression strongly predicts nonadherence to human immunodeficiency virus ( HIV ) antiretroviral therapy , and adherence is essential to maintaining viral suppression . This suggests that pharmacologic treatment of depression may improve virologic outcomes . However , previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity , which could yield biased estimates of treatment effect . Application of marginal structural modeling to longitudinal observation data can , under certain assumptions , approximate the findings of a r and omized controlled trial . OBJECTIVE To determine whether antidepressant medication treatment increases the probability of HIV viral suppression . DESIGN Community-based prospect i ve cohort study with assessment s conducted every 3 months . SETTING Community-based research field site in San Francisco , California . PARTICIPANTS One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic ( CD4 + T-lymphocyte count , < 350/μL ) and psychiatric ( Beck Depression Inventory II score , > 13 ) inclusion criteria , observed from April 2002 through August 2007 . MAIN OUTCOME MEASURES Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen , 7-day self-reported percentage adherence to antiretroviral therapy , and probability of reporting complete ( 100 % ) adherence . RESULTS Marginal structural models estimated a 2.03 greater odds of achieving viral suppression ( 95 % confidence interval [ CI ] , 1.15 - 3.58 ; P = .02 ) result ing from antidepressant medication treatment . In addition , antidepressant medication use increased the probability of antiretroviral uptake ( weighted odds ratio , 3.87 ; 95 % CI , 1.98 - 7.58 ; P < .001 ) . Self-reported adherence to antiretroviral therapy increased by 25 percentage points ( 95 % CI , 14 - 36 ; P < .001 ) , and the odds of reporting complete adherence nearly doubled ( weighted odds ratio , 1.94 ; 95 % CI , 1.20 - 3.13 ; P = .006 ) . CONCLUSIONS Antidepressant medication treatment increases viral suppression among persons with HIV . This effect is likely attributable to improved adherence to a continuum of HIV care , including increased uptake and adherence to antiretroviral therapy Background This study was conducted to evaluate the diagnostic accuracy and determine the optimum cut-off scores for clinical use of the Center for Epidemiological Studies Depression scale ( CES-D ) and Alcohol Use Disorders Identification Test ( AUDIT ) against a reference psychiatric diagnostic interview , in TB and anti-retroviral therapy ( ART ) patients in primary care in Zambia . Methods This was a cross-sectional study in 16 primary level care clinics . Consecutive sampling was used to select 649 participants who started TB treatment or ART in the preceding month . Participants were first interviewed using the CES-D and AUDIT , and subsequently with a psychiatric diagnostic interview for current major depressive disorder ( MDD ) and alcohol use disorders ( AUDs ) using the Mini-International Neuropsychiatric Interview ( MINI ) . The diagnostic accuracy was calculated using the Area Under the Receiver Operating Characteristic curve ( AUROC ) . The optimum cut-off scores for clinical use were calculated using sensitivity and positive predictive value ( PPV ) . Results The CES-D and AUDIT had high internal consistency ( Cronbach 's alpha = 0.84 ; 0.98 respectively ) . Confirmatory factor analysis showed that the four-factor CES-D model was not a good fit for the data ( Tucker-Lewis Fit Index ( TLI ) = 0.86 ; st and ardized root-mean square residual ( SRMR ) = 0.06 ) while the two-factor AUDIT model fitted the data well ( TFI = 0.99 ; SRMR = 0.04 ) . Both the CES-D and AUDIT demonstrated good discriminatory ability in detecting MINI-defined current MDDs and AUDs ( AUROC for CES-D = 0.78 ; AUDIT = 0.98 for women and 0.75 for men ) . The optimum CES-D cut-off score in screening for current MDD was 22 ( sensitivity 73 % , PPV 76 % ) while that of the AUDIT in screening for AUD was 24 for women ( sensitivity 60 % , PPV 60 % ) , and 20 for men ( sensitivity 55 % , PPV 50 % ) . Conclusions The CES-D and AUDIT showed high discriminatory ability in measuring MINI-defined current MDD and AUD respectively . They are suitable mental health screening tools for use among TB and ART patients in primary care in Zambia OBJECTIVE To assess the feasibility of using community health workers to administer short or ultra-short screening instruments during routine community-based prenatal outreach for detecting probable depression at 12 weeks postpartum . METHODS During pregnancy and at 12 weeks postpartum , the 10-item Edinburgh Postnatal Depression Scale ( EPDS-10 ) was administered to 249 Xhosa-speaking black African women living in Khayelitsha , South Africa . We compared the operating characteristics of the prenatal EPDS-10 , as well as 4 short and ultra-short subscales , with the criterion st and ard of probable postpartum depression . RESULTS Seventy-nine ( 31.7 % ) women were assessed as having probable postpartum depression . A prenatal EPDS-10 score of 13 or higher had 0.67 sensitivity and 0.67 specificity for detecting probable postpartum depression . Briefer subscales performed similarly . CONCLUSION Community health workers successfully conducted community-based screening for depression in a re source -limited setting using short or ultra-short screening instruments . However , overall feasibility was limited because prenatal screening failed to accurately predict probable depression during the postpartum period The authors ’ objective was to estimate the prevalence of major depressive disorder among Rw and ans 5 years after the 1994 genocidal civil war . They interviewed a community-based r and om sample of adults in a rural part of Rw and a using the Hopkins Symptom Checklist and a locally developed functional impairment instrument . The authors estimated current rates of major depression using an algorithm based on the DSM-IV symptom criteria ( A ) , distress/functional impairment criteria ( C ) , and bereavement exclusionary criteria ( E ) . They also examined the degree to which depressive symptoms compromise social and occupational functioning . Three hundred sixty-eight adults were interviewed , of whom 15.5 % met Criteria A , C , and E for current major depression . Depressive symptoms were strongly associated with functional impairment in most major roles for men and women . The authors conclude that a significant part of this population has seriously disabling depression . Work on appropriate , feasible , safe , and effective mental health interventions should be a priority for this population Depressed mood has been associated with HIV transmission risk behavior . To determine whether effective depression treatment could reduce the frequency of sexual risk behavior , we analyzed secondary outcome data from a 36-week , two-arm , parallel- design , r and omized controlled trial , in which homeless and marginally housed , HIV-infected persons with comorbid depressive disorders were r and omized to receive either : ( a ) directly observed treatment with the antidepressant medication fluoxetine , or ( b ) referral to a local public mental health clinic . Self-reported sexual risk outcomes , which were measured at 3 , 6 , and 9 months , included : total number of sexual partners , unprotected sexual intercourse , unprotected sexual intercourse with an HIV-uninfected partner or a partner of unknown serostatus , and transactional sex . Estimates from generalized estimating equations regression models did not suggest consistent reductions in sexual risk behaviors result ing from treatment . Mental health interventions may need to combine depression treatment with specific skills training in order to achieve durable impacts on HIV prevention outcomes The purpose of this study is to evaluate empirical criticism of the psychometric properties of the Hamilton Depression Rating Scale ( HDRS ) by undertaking an " internal construct validity " evaluation . Individual symptom responses for the HDRS were obtained from 370 patients meeting Research Diagnostic Criteria for major depression . A multidimensional normal item response theory ( IRT ) model was used to assess the dimensionality of the HDRS and estimate corresponding item parameters which were then expressed as factor loadings and item thresholds . The analysis yielded a five-dimensional solution . The first dimension ( depressed mood , guilt , suicide , work and interests , agitation , psychic anxiety , somatic anxiety , and loss of libido ) appeared to define global depression severity . These results are consistent with other published factor analytic studies and provide further justification for thinking that the HDRS total score is a weak index of depressive syndrome severity . The findings provide a benchmark by which the adequacy of future results may be judged , because the multidimensional IRT model does not suffer from the statistical limitations that arise when applying traditional factor analytic methods to discrete symptom ratings The objective of this study was to develop an indigenous measure of common mental disorders ( CMD ) in the Shona language in Zimbabwe . Ethnographic and qualitative studies elicited idioms of distress of mental disorder leading to the preliminary Shona Symptom Question naire ( SSQ ) , and items from the Self‐Report Question naire ( SRQ ) were added to it . The 56‐item Preliminary Shona Symptom Question naire ( PSSQ ) was administered to 302 r and omly selected primary care attenders , of whom 100 were classified as cases on the basis of agreement between care provider assessment and a psychiatric interview . Discriminant analysis identified 14 items that were the strongest predictors of mental disorder . The 14‐item SSQ has a high level of internal consistency ( Cronbach 's alpha=0.85 ) . The items are a mixture of emic and etic phenomena . The total score correlates strongly with patients ' self‐ assessment of the emotional nature of their illness . Satisfactory specificity and sensitivity occurred at a cut‐off point of 7/8 . The SSQ is the first indigenous measure of mental disorder developed in sub‐Saharan Africa to have included idioms of distress of primary care attenders and involved patients consulting traditional medical practitioners . It promises to be a useful instrument for epidemiological and clinical research . The methodology used is an innovative way of combining etic and emic methods in the evaluation of CMD Objective : To determine whether earlier initiation of antiretroviral therapy ( ART ) is associated with better economic outcomes . Design : Prospect i ve cohort study of HIV-positive patients on ART in rural Ug and a. Methods : Patients initiating ART at a regional referral clinic in Ug and a were enrolled in the Ug Output:	Depression-screening instruments yielded relatively high false positive rates . Overall , few studies described the reliability and /or validity of depression instruments in sub-Saharan Africa
MS22241	*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 . The prevalence of type 2 diabetes in American adolescents has increased markedly during the past generation . Although the factors that contribute to the development of type 2 diabetes are complex and not wholly eluci date d , the triad of severe obesity , hyperinsulinemia , and a family history of type 2 diabetes places a child at an increased risk for development of the disease . Current approaches to the prevention of type 2 diabetes , including dietary counseling and exercise , have had limited success . We reasoned that drugs that increase glucose tolerance in diabetic patients might prove useful in preventing the progression to glucose intolerance in high-risk patients . To that end , we conducted a double-blind , placebo-controlled study of the effects of metformin on body mass index ( BMI ) , serum leptin , glucose tolerance , and serum lipids in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes . Methods . The study population consisted of 29 white and black adolescents aged 12 to 19 years . All had BMI s exceeding 30 kg/m2 . Criteria for enrollment included : 1 ) a fasting insulin concentration exceeding 15 μU/mL ; and 2 ) at least 1 first- or second-degree relative with type 2 diabetes . All patients had fasting plasma glucose concentrations < 110 mg% and hemoglobin A1c concentrations ≤6.0 % . All had normal linear growth and sexual development for age , with no marked hirsutism , severe acne , or menstrual irregularities characteristic of polycystic ovary syndrome . Eight participants had acanthosis nigricans . After baseline laboratory studies including a rapidly sample d intravenous glucose tolerance test , patients were r and omized to receive metformin ( 500 mg twice daily ) or a placebo for a total of 6 months . The effects of metformin on BMI st and ard deviation score , serum leptin , glucose tolerance , and serum lipids were analyzed . The study was double-blinded and included no specific dietary restrictions . Results . Metformin caused a decline of 0.12 st and ard deviation in BMI in study participants ( −1.3 % from baseline ) , and a 5.5 % reduction in serum leptin in girls . In contrast , BMI and serum leptin rose 0.23 st and ard deviation ( 2.3 % ) and 16.2 % , respectively , in the placebo group during the treatment period . Metformin caused a progressive decline in fasting blood glucose ( from a mean of 84.9 to 75.1 mg% ) and a reduction in fasting insulin levels ( from 31.3 to 19.3 μU/mL ) . In contrast , fasting glucose levels in the placebo group rose slightly from 77.2 to 82.3 mg% , and fasting insulin levels did not change . Insulin sensitivity , as assessed by the ratio of fasting insulin to glucose concentrations and the quantitative insulin sensitivity check index ( 1/[log fasting insulin + log fasting glucose ] ) and homeostasis model assessment insulin resistance index ( fasting insulin × fasting glucose/22.5 ) indices , increased slightly in the metformin-treated participants . However , the insulin sensitivity measured using Bergman 's minimal model did not change . There were also no significant changes in glucose effectiveness , hemoglobin A1c , serum lipids , or serum lactate in the metformin or placebo groups . Metformin was tolerated well by the majority of patients . Transient abdominal discomfort or diarrhea occurred in 40 % of treated participants ; there were no episodes of vomiting or lactic acidosis . Conclusions . The treatment of obesity and insulin resistance in adults often proves ineffective because the vicious cycle leading to type 2 diabetes may have become entrenched and , to some extent , may be irreversible . Early detection and therapy of the obese adolescent with a family history of type 2 diabetes may interrupt the cycle of weight gain and insulin resistance that leads to glucose intolerance in adulthood . Through its ability to reduce fasting blood glucose and insulin concentrations and to moderate weight gain , metformin might complement the effects of dietary and exercise counseling and reduce the risk of type 2 diabetes in selected patients Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors . The " gold st and ard " glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo , but neither is easily implemented in large studies . Thus , it is of interest to develop a simple , accurate method for assessing insulin sensitivity that is useful for clinical investigations . We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sample d iv glucose tolerance tests on 28 nonobese , 13 obese , and 15 type 2 diabetic subjects . We obtained correlations between indexes of insulin sensitivity from glucose clamp studies ( SI(Clamp ) ) and minimal model analysis ( SI(MM ) ) that were comparable to previous reports ( r = 0.57 ) . We performed a sensitivity analysis on our data and discovered that physiological steady state values [ i.e. fasting insulin ( I(0 ) ) and glucose ( G(0 ) ) ] contain critical information about insulin sensitivity . We defined a quantitative insulin sensitivity check index ( QUICKI = 1/[log(I(0 ) ) + log(G(0 ) ) ] ) that has substantially better correlation with SI(Clamp ) ( r = 0.78 ) than the correlation we observed between SI(MM ) and SI(Clamp ) . Moreover , we observed a comparable overall correlation between QUICKI and SI(Clamp ) in a totally independent group of 21 obese and 14 nonobese subjects from another institution . We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research OBJECTIVE Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions , including abnormalities in glucose homeostasis in adolescents , but there are few data evaluating the efficacy of metformin among younger children . Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children , who are insulin-resistant . RESEARCH DESIGN AND METHODS This study was a r and omized double-blind placebo-controlled trial consisting of 100 severely obese ( mean BMI 34.6 ± 6.6 kg/m2 ) insulin-resistant children aged 6–12 years , r and omized to 1,000 mg metformin ( n = 53 ) or placebo ( n = 47 ) twice daily for 6 months , followed by open-label metformin treatment for 6 months . All children and their parents participated in a monthly dietitian-administered weight-reduction program . RESULTS Eighty-five percent completed the 6-month r and omized phase . Children prescribed metformin had significantly greater decreases in BMI ( difference −1.09 kg/m2 , CI −1.87 to −0.31 , P = 0.006 ) , body weight ( difference −3.38 kg , CI −5.2 to −1.57 , P < 0.001 ) , BMI Z score ( difference between metformin and placebo groups −0.07 , CI −0.12 to −0.01 , P = 0.02 ) , and fat mass ( difference −1.40 kg , CI −2.74 to −0.06 , P = 0.04 ) . Fasting plasma glucose ( P = 0.007 ) and homeostasis model assessment ( HOMA ) insulin resistance index ( P = 0.006 ) also improved more in metformin-treated children than in placebo-treated children . Gastrointestinal symptoms were significantly more prevalent in metformin-treated children , which limited maximal tolerated dosage in 17 % . During the 6-month open-label phase , children treated previously with placebo decreased their BMI Z score ; those treated continuously with metformin did not significantly change BMI Z score further . CONCLUSIONS Metformin had modest but favorable effects on body weight , body composition , and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program OBJECTIVE To study whether metformin reduces obesity , homeostasis model assessment for insulin resistance index ( HOMA-IR ) , and the metabolic syndrome ( MtS ) in obese European adolescents in addition to previous unsuccessful lifestyle intervention . DESIGN AND METHODS After 6 months of multiprofessional lifestyle intervention , 70 out of 86 adolescents without improvement in body mass index ( BMI ) and HOMA-IR were r and omized into either the placebo ( n=34 ) or the metformin group ( 2 × 500 mg/day , n=36 ) in addition to ongoing lifestyle intervention for another 6 months . RESULTS Age was 13.8 years , BMI was 33.1 kg/m(2 ) , 65 % were female , and 89 % were Caucasians . During lifestyle intervention alone , BMI and HOMA-IR deteriorated significantly . In the subsequent medication period , HOMA-IR and fasting insulin improved similarly in the placebo and metformin groups ( HOMA-IR decreased 73 vs 54 % respectively in metformin versus placebo ; P=0.048 ) , but BMI remained unchanged . The insulin sensitivity index , however , only improved in the metformin group . High fasting insulin is correlated with a subsequent BMI increase irrespective of the medication . MtS remained unchanged . CONCLUSIONS Obese European adolescents ' insulin sensitivity improved without weight change during placebo or metformin intervention in addition to lifestyle intervention . Most differences did not reach statistical significance , probably due to improved compliance with lifestyle intervention as a placebo effect . In addition , the metformin dose may be too low Background The efficacy of pharmacological treatment in controlling childhood obesity is controversial . We aim ed to compare the effects of three types of drug regimens and placebo on generalized and abdominal obesity among obese children and adolescents who did not succeed to lose weight 3 months after lifestyle modification ( diet and exercise ) . Methods This triple-masked r and omized clinical trial was conducted among 180 participants aged 10–16 years . They were assigned r and omly to 4 groups of equal number to receive metformin , fluoxetine , a combination of the two drugs , or placebo . The trial lasted for 12 weeks and participants were followed up for an additional 12-week period . Results Overall , 91.1 % ( n=164 ) of the enrolled participants completed the trial . After the 12-week trial , the body mass index decreased significantly in all groups receiving medications [ approximately −1.2 ( 0.2 ) kg/m2 , P<0.05 ] . This decrease was not significant in the placebo group . Waist circumference decreased significantly in the groups receiving metformin [ −2.1 ( 0.4 ) cm , P=0.03 ) ] as well as in the group receiving a combination therapy of metformin and fluoxetine [ −2.5 ( 0.4 ) cm , P=0.01 ) ] . In the 24-week follow-up study , these anthropometric indexes were lower than the baseline in the group that had received a combination therapy of metformin and fluoxetine . No serious drug side-effects were reported . Conclusions A limited period of such treatment may help weight control , and might be used to encourage those children who have been refractory to weight loss for continuing the non-pharmacological programs . Our findings should be confirmed in future studies with a longer follow-up period BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent Output:	Conclusions : Short-term metformin treatment appears to moderately affect weight reduction in severely obese children and adolescents , with a concomitant improvement in fasting insulin sensitivity .
MS22242	*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 role of laparoscopic resection ( LR ) in the management of extraperitoneal rectal cancer still is unclear . This study aim ed to compare perioperative and long-term results of laparoscopic and open resection ( OR ) for low and midrectal cancer . Methods A prospect i ve nonr and omized trial comparing patients su bmi tted to OR or LR for low and midrectal cancer at a single institution was conducted . Results The study included 191 consecutive patients : 98 patients who underwent LR and 93 who underwent OR . The mean follow-up period was 46.3 months for LR and 49.7 months for OR . The conversion rate for LR was 18.4 % . With the use of LR , the mean time for complete patient mobilization was shorter ( 1.7 vs 3.3 days ; p < 0.001 ) and patients were earlier in passing flatus ( 2.6 vs 3.9 days ; p < 0.001 ) and stools ( 3.8 vs 4.7 days ; p < 0.01 ) , and in resuming oral intake ( 3.4 vs 4.8 days ; p < 0.001 ) . The mean hospital stay was shorter for LR , but the difference did not reach significance ( 11.4 vs 13 days ) . Morbidity and mortality rates were similar : LR ( 24.4 % and 1 % ) and OR ( 23.6 % and 2.2 % ) . Laparoscopic patients presented a higher rate of anastomotic fistulas ( 13.5 % vs 5.1 % ) and reoperations ( 6.1 % vs 3.2 % ) but the difference was statistically nonsignificant . Laparoscopic resection presented a significantly lower local recurrence rate ( 3.2 % vs 12.6 % ; p < 0.05 ) . The cumulative survival and disease-free rates at 5 years were , respectively , 80 % and 65.4 % after LR and 68.9 % and 58.9 % after OR ( nonsignificant difference ) . Stage-by-stage comparison showed prolonged cumulative survival for stages III and IV cancer in LR ( 82.5 % vs 40.5 % ; p = 0.006 and 15.8 % vs 0 % ; p = 0.013 , respectively ) and a reduced rate of cancer-related death for stage III in LR ( 11.4 % vs 51.9 % ; p = 0.001 ) . Conclusions As compared with conventional open surgery , LR for low and midrectal cancer is characterized by a faster recovery and similar overall morbidity ( but a higher rate of anastomotic leakages ) , and does not present any adverse oncologic effect BACKGROUND Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe . The aim in the COlorectal cancer Laparoscopic or Open Resection ( COLOR II ) trial was to compare laparoscopic and open surgery in patients with rectal cancer . METHODS A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries . Patients ( aged ≥18 years ) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were r and omly assigned to either laparoscopic or open surgery in a 2:1 ratio , stratified by centre , location of tumour , and preoperative radiotherapy . The study was not masked . Secondary ( short-term ) outcomes -including operative findings , complications , mortality , and results at pathological examination-are reported here . Analysis was by modified intention to treat , excluding those patients with post-r and omisation exclusion criteria and for whom data were not available . This study is registered with Clinical Trials.gov , number NCT00297791 . FINDINGS The study was undertaken between Jan 20 , 2004 , and May 4 , 2010 . 1103 patients were r and omly assigned to the laparoscopic ( n=739 ) and open surgery groups ( n=364 ) , and 1044 were eligible for analyses ( 699 and 345 , respectively ) . Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group ( median 200 mL [ IQR 100 - 400 ] vs 400 mL [ 200 - 700 ] , p<0·0001 ) ; however , laparoscopic procedures took longer ( 240 min [ 184 - 300 ] vs 188 min [ 150 - 240 ] ; p<0·0001 ) . In the laparoscopic surgery group , bowel function returned sooner ( 2·0 days [ 1·0 - 3·0 ] vs 3·0 days [ 2·0 - 4·0 ] ; p<0·0001 ) and hospital stay was shorter ( 8·0 days [ 6·0 - 13·0 ] vs 9·0 days [ 7·0 - 14·0 ] ; p=0·036 ) . Macroscopically , completeness of the resection was not different between groups ( 589 [ 88 % ] of 666 vs 303 [ 92 % ] of 331 ; p=0·250 ) . Positive circumferential resection margin ( < 2 mm ) was noted in 56 ( 10 % ) of 588 patients in the laparoscopic surgery group and 30 ( 10 % ) of 300 in the open surgery group ( p=0·850 ) . Median tumour distance to distal resection margin did not differ significantly between the groups ( 3·0 cm [ IQR 2·0 - 4·8 ] vs 3·0 cm [ 1·8 - 5·0 ] , respectively ; p=0·676 ) . In the laparoscopic and open surgery groups , morbidity ( 278 [ 40 % ] of 697 vs 128 [ 37 % ] of 345 , respectively ; p=0·424 ) and mortality ( eight [ 1 % ] of 699 vs six [ 2 % ] of 345 , respectively ; p=0·409 ) within 28 days after surgery were similar . INTERPRETATION In selected patients with rectal cancer treated by skilled surgeons , laparoscopic surgery result ed in similar safety , resection margins , and completeness of resection to that of open surgery , and recovery was improved after laparoscopic surgery . Results for the primary endpoint-locoregional recurrence-are expected by the end of 2013 . FUNDING Ethicon Endo-Surgery Europe , Swedish Cancer Foundation , West Gothia Region , Sahlgrenska University Hospital BACKGROUND Compared with open resection , laparoscopic resection of rectal cancers is associated with improved short-term outcomes , but high-level evidence showing similar long-term outcomes is scarce . We aim ed to compare survival outcomes of laparoscopic surgery with open surgery for patients with mid-rectal or low-rectal cancer . METHODS The Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy ( COREAN ) trial was an open-label , non-inferiority , r and omised controlled trial done between April 4 , 2006 , and Aug 26 , 2009 , at three centres in Korea . Patients ( aged 18 - 80 years ) with cT3N0 - 2M0 mid-rectal or low-rectal cancer who had received preoperative chemoradiotherapy were r and omly assigned ( 1:1 ) to receive either open or laparoscopic surgery . R and omisation was stratified by sex and preoperative chemotherapy regimen . Investigators were masked to the r and omisation sequence ; patients and clinicians were not masked to the treatment assignments . The primary endpoint was 3 year disease-free survival , with a non-inferiority margin of 15 % . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00470951 . FINDINGS We r and omly assigned 340 patients to receive either open surgery ( n=170 ) or laparoscopic surgery ( n=170 ) . 3 year disease-free survival was 72·5 % ( 95 % CI 65·0 - 78·6 ) for the open surgery group and 79·2 % ( 72·3 - 84·6 ) for the laparoscopic surgery group , with a difference that was lower than the prespecified non-inferiority margin ( -6·7 % , 95 % CI -15·8 to 2·4 ; p<0·0001 ) . 25 ( 15 % ) patients died in the open group and 20 ( 12 % ) died in the laparoscopic group . No deaths were treatment related . INTERPRETATION Our results show that laparoscopic resection for locally advanced rectal cancer after preoperative chemoradiotherapy provides similar outcomes for disease-free survival as open resection , thus justifying its use . FUNDING National Cancer Center , South Korea Purpose Laparoscopic surgery of colon cancer has been accepted to be oncologically adequate compared with open resection . However , the situation in rectal cancer remains unclear , because anatomy and complex surgical procedures might specifically influence the long-term outcome . This study was design ed to analyze perioperative and long-term outcome of patients with rectal cancer after laparoscopic vs. open access surgery . Methods A total of 389 patients ( 1998–2005 ) were prospect ively analyzed ; 114 patients had laparoscopic beginning , and 25 patients had conversion and were separately analyzed . Eighty-nine patients remained in the laparoscopic group and 275 had open access surgery . Results Both groups were comparable regarding age , gender , tumor localization , stage , and complications . Differences were found in harvested lymph nodes ( laparoscopic 13.5/open access 16.9 ; P = 0.001 ) and hospitalization ( 15.1/18.7 days ; P = 0.037 ) . Local recurrence rate and metachronous metastasis were comparable . In patients with deep anterior resection with total mesenteric excision , favorable long-term survival in the laparoscopic group was found ( P = 0.035 , log-rank ) . Conclusions Minimally invasive surgery is equivalent in the treatment of rectal cancer and shows advantages of shorter hospitalization and faster recovery . Especially in patients with low rectal cancer , minimally invasive surgery with exact preparation of the total mesenteric excision seems to be favorable compared with open access surgery BACKGROUND Laparoscopic resection of colorectal cancer is widely used . However , robust evidence to conclude that laparoscopic surgery and open surgery have similar outcomes in rectal cancer is lacking . A trial was design ed to compare 3-year rates of cancer recurrence in the pelvic or perineal area ( locoregional recurrence ) and survival after laparoscopic and open resection of rectal cancer . METHODS In this international trial conducted in 30 hospitals , we r and omly assigned patients with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge , not invading adjacent tissues , and without distant metastases to undergo either laparoscopic or open surgery in a 2:1 ratio . The primary end point was locoregional recurrence 3 years after the index surgery . Secondary end points included disease-free and overall survival . RESULTS A total of 1044 patients were included ( 699 in the laparoscopic-surgery group and 345 in the open-surgery group ) . At 3 years , the locoregional recurrence rate was 5.0 % in the two groups ( difference , 0 percentage points ; 90 % confidence interval [ CI ] , -2.6 to 2.6 ) . Disease-free survival rates were 74.8 % in the laparoscopic-surgery group and 70.8 % in the open-surgery group ( difference , 4.0 percentage points ; 95 % CI , -1.9 to 9.9 ) . Overall survival rates were 86.7 % in the laparoscopic-surgery group and 83.6 % in the open-surgery group ( difference , 3.1 percentage points ; 95 % CI , -1.6 to 7.8 ) . CONCLUSIONS Laparoscopic surgery in patients with rectal cancer was associated with rates of locoregional recurrence and disease-free and overall survival similar to those for open surgery . ( Funded by Ethicon Endo-Surgery Europe and others ; COLOR II Clinical Trials.gov number , NCT00297791 . ) Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent Output:	No significant difference were noted between the groups regarding intraoperative complications , TME completeness and harvesting of lymph nodes . Regarding the long-term survival data , the laparoscopic group was not inferior to laparotomy . Some pooled data , such as 3-year DFS , 5-year OS and 5-year local recurrence were even superior for the laparoscopic group .
MS22243	*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 The aim of this study was to investigate the clinical efficacy of oral Pycnogenol ® ( Horphag Research Ltd , UK ) in patients with severe chronic venous insufficiency . Patients with severe venous hypertension ( chronic venous insufficiency , ankle swelling ) and history of venous ulcerations were treated with Pycnogenol . Patients received oral Pycnogenol ( 50 mg capsules , 3 times daily for a total of 150 mg daily ) for 8 weeks . A group of 21 patients was included in the treatment group and 18 equivalent patients were observed as controls ( no treatment during the observation period ) . All 21 patients ( age 53 years ; range , 42 - 60 years ; M : F=11:10 ) in the treatment group completed the 8-week study . Also the 18 controls completed the follow-up period . There were no drop-outs . The average ambulatory venous pressure was 59.3 ( SD 7.2 ; range 50 - 68 ) with a refilling time shorter than 10 seconds ( average 7.6 ; SD 3 ) . There were no differences in ambulatory venous pressure or refilling time between the treatment and control patients . The duration of the disease — from the first signs/symptoms — was on average 5.7 years ( SD 2.1 ) . At 4 and 8 weeks , in all Pycnogenol-treated subjects , microcirculatory and clinical evaluations indicated a progressive decrease in skin flux , indicating an improvement in the level of microangiopathy ; a significant decrease in capillary filtration ; a significant improvement in the symptomatic score ; and a reduction in edema . There were no visible effects in controls . In conclusion , this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy . The study indicates the significant clinical role of Pycnogenol in the management , treatment and control of this common clinical problem . The treatment may be also useful to prevent ulcerations by controlling the level of venous microangiopathy The purpose of this r and omized , double-blind and placebo controlled study was to test the effect of polyphenolic extract of pine bark Pycnogenol ® ( Pyc ) on the level of oxidized purines represented by 8-oxo-7,8-dihydroguanine ( 8-oxoG ) and on the total antioxidant status ( TAS ) in children with attention deficit/hyperactivity disorder ( ADHD ) . We have found significantly increased damage to DNA in ADHD children when compared to controls . 8-oxoG was significantly lower after 1 month of Pyc administration in comparison to the beginning state and to placebo group . TAS in ADHD children was lower in comparison to controls . After Pyc administration , TAS was elevated but statistically significant increase was recorded after 1 month of termination of Pyc application . Improvement of DNA damage and TAS after Pyc administration is associated with the improvement of attention in ADHD children . In conclusion , Pycnogenol ® administration reduces oxidative damage to DNA , normalizes TAS and improves attention of ADHD children . Explanation of mutual relation between oxidative damage to DNA , TAS and symptoms of ADHD and mechanism of Pyc 's action needs further investigations Melasma ( or chloasma ) is a common disorder of cutaneous hyperpigmentation predominantly affecting sun-exposed areas in women . The pathogenesis of melasma is not fully understood and treatments are frequently disappointing and often associated with side effects . Pycnogenol is a st and ardized extract of the bark of the French maritime pine ( Pinus pinaster ) , a well-known , potent antioxidant . Studies in vitro show that Pycnogenol is several times more powerful than vitamin E and vitamin C. In addition , it recycles vitamin C , regenerates vitamin E and increases the endogenous antioxidant enzyme system . Pycnogenol protects against ultraviolet ( UV ) radiation . Therefore its efficacy in the treatment of melasma was investigated . Thirty women with melasma completed a 30-day clinical trial in which they took one 25 mg tablet of Pycnogenol with meals three times daily , i.e. 75 mg Pycnogenol per day . These patients were evaluated clinical ly by parameters such as the melasma area index , pigmentary intensity index and by routine blood and urine tests . After a 30-day treatment , the average melasma area of the patients decreased by 25.86 + /- 20.39 mm(2 ) ( p < 0.001 ) and the average pigmentary intensity decreased by 0.47 + /- 0.51 unit ( p < 0.001 ) . The general effective rate was 80 % . No side effect was observed . The results of the blood and urine test parameters at baseline and at day 30 were within the normal range . Moreover , several other associated symptoms such as fatigue , constipation , pains in the body and anxiety were also improved . To conclude , Pycnogenol was shown to be therapeutically effective and safe in patients suffering from melasma Asthma is characterized as a chronic inflammatory process . Pycnogenol((R ) ) , a bioflavonoid mixture extracted from Pinus maritima , is known to scavenge free radicals while possessing antioxidant and antiinflammatory properties . The objective of this study was to evaluate the efficiency of this agent in a r and omized , double-blinded , placebo-controlled , crossover study in patients with varying asthma severity . Twenty-six patients who fulfilled the American Thoracic Society criteria for asthma were enrolled in the study . Medical history , physical examination , blood sample analyses , and spirometric values were obtained at baseline , 4 weeks , and 8 weeks . The patients were r and omly assigned to receive either 1 mg/lb/day ( maximum 200 mg/day ) Pycnogenol or placebo for the first period of 4 weeks and then crossed over to the alternate regimen for the next 4 weeks . No adverse effects were observed related to the study drug . Within the contingent of 22 patients who completed the study , almost all responded favorably to Pycnogenol in contrast to placebo . Pycnogenol treatment also significantly reduced serum leukotrienes compared with placebo . The results of this pilot study indicate that Pycnogenol may be a valuable nutraceutical in the management of chronic asthma . We recommend that further clinical trials be conducted in larger groups of asthmatics to establish its efficacy The aim of this study was to compare the efficacy of Venostasin ( horse chestnut seed extract ) and Pycnogenol ( French maritime pine bark extract ) in the treatment of chronic venous insufficiency ( CVI ) . In an open , controlled comparative study 40 patients with diagnosed CVI were treated either with 600 mg chestnut seed extract per day or 360 mg Pycnogenol per day over a period of 4 weeks . The following parameters were investigated before the start of treatment and after 2 and 4 weeks of treatment : circumference of the lower legs and rating of subjective symptoms ( scores ) of pain , cramps , night-time swelling , feeling of " heaviness " , and reddening of the skin . In addition , blood levels of cholesterol LDL and HDL were determined before and at the end of treatment . Pycnogenol significantly reduced the circumference of the lower limbs and significantly improved subjective symptoms . Furthermore , Pycnogenol significantly decreased cholesterol and LDL values in the blood , whereas HDL remained unaffected . Venostasin only moderately but not significantly , reduced the circumference of the lower limbs and marginally improved symptoms . Venostasin had no influence on the determined lipid values . Both medications were equally well tolerated . In conclusion , Pycnogenol was found to be more efficacious than Venostasin for the treatment of CVI The aim of this study was to investigate the clinical efficacy of oral Pycnogenol ® ( Horphag Research Ltd , United Kingdom ) in patients with diabetic microangiopathy . Patients without a history of diabetic ulcerations were treated with Pycnogenol . Patients received oral Pycnogenol ( 50 mg capsules , 3 times daily for a total of 150 mg daily for 4 weeks ) . A group of 30 patients was included ( severe microangiopathy ) ; 30 comparable patients were observed as controls ( no treatment during the observation period ) . All patients ( age , 59 years ; range , 55 - 68 years ; male : female = 18:12 ) included in the treatment group completed the 4-week study . Also , all controls completed the follow-up period . There were no drop-outs . All included subjects had signs and symptoms of diabetic microangiopathy . The duration of diabetes — from the first signs/symptoms — was on average 7.5 years ( SD = 3 ) . After 4 weeks , microcirculatory and clinical evaluations showed a progressive decrease in skin flux at rest in the foot ( indicating an improvement in the level of microangiopathy ) , a significant decrease in capillary filtration , and a significant improvement in the venoarteriolar response in all treated subjects . There were no visible effects in controls except a slight reduction in skin flux at rest in the foot . Treatment was well tolerated in both groups . In conclusion , this study confirms the clinical efficacy of Pycnogenol in patients with diabetic microangiopathy . The study indicates the clinical role of Pycnogenol in the management , treatment , and control of this common clinical problem . The treatment may be also useful to prevent diabetic ulcerations by controlling the level of microangiopathy OBJECTIVE The safe and efficacious use of Pycnogenol ( French maritime pine bark extract ) in other inflammatory diseases prompted this study of its antiinflammatory effects in patients with osteoarthritis ( OA ) . The aim of the study was to evaluate whether Pycnogenol reduces the symptoms of OA in a double-blind , placebo-controlled , r and omly allocated trial with patients suffering from knee osteoarthritis stages I and II . METHODS 100 patients were treated for 3 months either by 150 mg Pycnogenol per day at meals or by placebo . Patients had to report any change of use of previously prescribed antiinflammatory medication during the study period . Patients filled the Western Ontario and Mc Masters University ( WOMAC ) question naire for osteoarthritis every 2 weeks and evaluated weekly pain symptoms using a visual analogue scale for pain intensity . RESULTS Following treatment with Pycnogenol patients reported an improvement of WOMAC index ( p < 0.05 ) , and a significant alleviation of pain by visual analogue scale ( p < 0.04 ) , the placebo had no effect . The use of analgesics diminished in the verum group but increased under the placebo . Treatment with Pycnogenol was well tolerated . CONCLUSION Results show that Pycnogenol in patients with mild to moderate OA improves symptoms and is able to spare NSAIDs Patients with type 2 diabetes are at considerable risk of excessive morbidity and mortality from cardiovascular disease ( CVD ) . We investigated the clinical effectiveness of Pycnogenol , a flavonoid-rich dietary supplement , in reducing antihypertensive medication use and CVD risk factors in subjects with type 2 diabetes . Forty-eight individuals were enrolled in a r and omized , double-blind , placebo-controlled trial with parallel-group design . Patients were diagnosed with both type 2 diabetes and mild to moderate hypertension and were undergoing treatment with angiotensin-converting enzyme ( ACE ) inhibitors . Subjects were r and omly assigned to receive either Pycnogenol pill ( 125 mg daily ) or matched placebo for 12 weeks . According to the values of blood pressure ( BP ) measured at 2-week intervals , the pretrial ACE inhibitor dosage was left unchanged , reduced by 50 % , or brought back to the pretrial dosage until a stable BP was obtained . Fasting plasma glucose , low-density lipoprote Output:	Current evidence is insufficient to support Pycnogenol ( ® ) use for the treatment of any chronic disorder .
MS22244	*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 Local failure after radiotherapy can arise with cancer extending beyond the capsule and /or involvement of seminal vesicles or positive surgical margins . METHODOLOGY After undergoing radical prostatectomy 1005 patients were r and omly assigned ( 1999 - 2001 ) to a wait and see policy or an immediate postoperative irradiation ( 60 Gy delivered over 6 weeks ) ; eligible patients had pN0 M0 tumors and one or more pathological risk factors mentioned above . The main end-point was 5-year biochemical progression free survival . RESULTS After a median follow-up of 5-year biochemical progression free survival was significantly improved in the irradiated group ( 74 % , 98 % CI : 68.7 - 79.3 vs 52.6 % , 98 % CI : 46.6 - 58.5 ; P<0.0001 ) Clinical progression free survival was also significantly improved ( P<0.0009 ) . The cumulative rate of loco-regional failure was also significantly improved ( P<0.0009 ) . Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group ( P=0.0005 ) , but severe toxicity ( grade 3 or higher ) were rare with a 5-year rate of 2.6 % in the wait- and -see group and 4.2 % in the postoperative irradiation group ( P=0.07 ) . CONCLUSION Immediate external irradiation after radical prostatectomy improves biochemical progression free survival and local control in patients with positive surgical margin or pT3 prostate cancer who are at high risk of progression . Further follow-up is needed to assess the impact on overall survival BACKGROUND Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule . We did a r and omised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer . METHODS After undergoing radical retropubic prostatectomy , 503 patients were r and omly assigned to a wait- and -see policy , and 502 to immediate postoperative radiotherapy ( 60 Gy conventional irradiation delivered over 6 weeks ) . Eligible patients had pN0M0 tumours and one or more pathological risk factors : capsule perforation , positive surgical margins , invasion of seminal vesicles . Our revised primary endpoint was biochemical progression-free survival . Analysis was by intention to treat . FINDINGS The median age was 65 years ( IQR 61 - 69 ) . After a median follow-up of 5 years , biochemical progression-free survival was significantly improved in the irradiated group ( 74.0 % , 98 % CI 68.7 - 79.3 vs 52.6 % , 46.6 - 58.5 ; p<0.0001 ) . Clinical progression-free survival was also significantly improved ( p=0.0009 ) . The cumulative rate of locoregional failure was significantly lower in the irradiated group ( p<0.0001 ) . Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group ( p=0.0005 ) , but severe toxic toxicity ( grade 3 or higher ) were rare , with a 5-year rate of 2.6 % in the wait- and -see group and 4.2 % in the postoperative irradiation group ( p=0.0726 ) . INTERPRETATION Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression . Further follow-up is needed to assess the effect on overall survival OBJECTIVES To define the optimal role for radiotherapy ( RT ) after radical prostatectomy ( RP ) and to characterize specific patterns of PSA failure in this setting . METHODS The records of 105 patients who underwent RT after RP ( 69 received therapeutic RT because of an elevated prostate-specific antigen [ PSA ] level , 36 received immediate adjuvant RT ) were review ed . The median follow-up was 35 months after RT and 57 months after RP . Radiation success was defined as achievement and maintenance of a PSA less than 0.2 ng/mL. Preoperative , pathologic , and postoperative characteristics were examined for their ability to predict success after RT . Patterns of PSA recurrence after RT were also examined by determining the PSA nadir , PSA velocity , and timing of and rogen-deprivation therapy . RESULTS Of 105 patients , 47 experienced biochemical failure . Actuarial 3 and 5-year progression-free survival estimates for all patients were 55 % and 43 % , respectively . Significant favorable predictors of response to RT by multivariate analysis were preoperative PSA less than 20 ng/mL and the use of adjuvant RT . However , patients who received therapeutic RT with a pre-RT PSA less than 1.0 ng/mL demonstrated progression-free outcome equivalent to those who received adjuvant RT . Two distinct patterns of PSA failure were observed on the basis of PSA nadir after RT . Patients whose PSA failed to reach a nadir less than 0.2 ng/mL after RT had progression with a high PSA velocity ( 1.5 ng/mL/yr ) . Patients whose PSA reached a nadir less than 0.2 ng/mL but who subsequently had treatment failure progressed later with a lower PSA velocity ( 0.36 ng/ml/yr ) . CONCLUSIONS RT is effective in select patients after RP . Given the low PSA velocity consistent with persistent local disease in nearly 50 % of patients in whom RT failed , more effective local therapy is needed after RP in high-risk patients INTRODUCTION A dry run of a clinical trial ( EORTC 22911 ) is presented in which 12 centres have participated . These are the centres which have contributed the largest number of patients to the trial . MATERIAL AND METHODS Each participating centre received data from a suitable patient . Investigators were asked to plan and ' treat ' the patient according to the protocol guidelines and return the data for evaluation of compliance . RESULTS The results show that compliance to the protocol guidelines was generally good . There were a few minor deviations in the dose and fractionation schedule , in the volume reduction for the booster dose and in the dose prescription point . None of these deviations will affect the outcome of the study . The most important observation is the large inter-centre variation in target volumes . CONCLUSIONS The results of this study underlines the need for a strict definition of the target volume and the adoption of the ICRU 50 recommendations in future protocol Pathological staging and surgical margin status of radical prostatectomy specimens are next to grading the most important prognosticators for recurrence . A central review of pathological stage and surgical margin status was performed on a series of 552 radical prostatectomy specimens of patients , participating in the European Organisation for Research and Treatment of Cancer trial 22911 . Inclusion criteria of the trial were pathological stage pT3 and /or positive surgical margin at local pathology . All specimens were totally embedded . Data of the central review were compared with those of local pathologists and related to clinical follow-up . Although a high concordance between review pathology and local pathologists existed for seminal vesicle invasion ( 94 % , κ=0.83 ) , agreement was much less for extraprostatic extension ( 57.5 % , κ=0.33 ) and for surgical margin status ( 69.4 % , κ=0.45 ) . Review pathology of surgical margin status was a stronger predictor of biochemical progression-free survival in univariate analysis [ hazard ratio (HR)=2.16 and p=0.0002 ] than local pathology ( HR=1.08 and p>0.1 ) . The review pathology demonstrated a significant difference between those with and without extraprostatic extension ( HR=1.83 and p=0.0017 ) , while local pathology failed to do so ( HR=1.05 and p>0.8 ) . The observations suggest that review of pathological stage and surgical margin of radical prostatectomy strongly improves their prognostic impact in multiinstitutional studies or trials PURPOSE Southwest Oncology Group ( SWOG ) trial 8794 demonstrated that adjuvant radiation reduces the risk of biochemical ( prostate-specific antigen [ PSA ] ) treatment failure by 50 % over radical prostatectomy alone . In this analysis , we stratified patients as to their preradiation PSA levels and correlated it with outcomes such as PSA treatment failure , local recurrence , and distant failure , to serve as guidelines for future research . PATIENTS AND METHODS Four hundred thirty-one subjects with pathologically advanced prostate cancer ( extraprostatic extension , positive surgical margins , or seminal vesicle invasion ) were r and omly assigned to adjuvant radiotherapy or observation . RESULTS Three hundred seventy-four eligible patients had immediate postprostatectomy and follow-up PSA data . Median follow-up was 10.2 years . For patients with a postsurgical PSA of 0.2 ng/mL , radiation was associated with reductions in the 10-year risk of biochemical treatment failure ( 72 % to 42 % ) , local failures ( 20 % to 7 % ) , and distant failures ( 12 % to 4 % ) . For patients with a postsurgical PSA between higher than 0.2 and < or = 1.0 ng/mL , reductions in the 10-year risk of biochemical failure ( 80 % to 73 % ) , local failures ( 25 % to 9 % ) , and distant failures ( 16 % to 12 % ) were realized . In patients with postsurgical PSA higher than 1.0 , the respective findings were 94 % versus 100 % , 28 % versus 9 % , and 44 % versus 18 % . CONCLUSION The pattern of treatment failure in high-risk patients is predominantly local with a surprisingly low incidence of metastatic failure . Adjuvant radiation to the prostate bed reduces the risk of metastatic disease and biochemical failure at all postsurgical PSA levels . Further improvement in reducing local treatment failure is likely to have the greatest impact on outcome in high-risk patients after prostatectomy 4504 Background : In 1992 , as radical prostatectomy was more frequently applied to clinical T1 - 2N0M0 prostate cancer , the EORTC has undertaken a r and omized trial of immediate post-operative treatment versus wait- and -see policy , for patients with high risk factors of local relapse on pathological specimen . We present the first efficacy results of this study . METHODS Eligible patients were ≤75 years old , WHO performance status ( PS ) 0 - 1 , had T0 - 3N0M0 PC preoperatively and ≥1 pathological risk factor of : capsule invasion , positive surgical margins , invasion of seminal vesicles . P-XRT was 60Gy conventional external radiation delivered over 6 weeks . The trial was powered to detect a hazard ratio ( HR ) of 0.77 with 80 % power with two-sided α=0.05 with regard to clinical or biological progression-free survival . RESULTS 1005 pts were accrued by end 2001 ( P-XRT : 503 , Px : 502 ) . Median age was 65.4 years , PS 0 in 93.8 % , median pre- and post-operative PSA 12.3 and 0.2 ng/ml , respectively . All but 41pts on P-XRT were irradiated with median dose 60Gy ( range : 50 - 74 ) . The trial was review ed by an IDMC in December 2003 , after a median follow-up of 5 years and early disclosure of the trial results was recommended . Biochemical PFS ( time to twice confirmed PSA increase over nadir or first clinical failure or death ) at 5 years was 72.2 % ( CI : 67.7 - 76.8 ) on P-XRT and 51.8 % ( CI : 46.8 - 56.8 ) , HR=0.52 ( CI : 0.42 - 0.64 ) , P<0.0001 . Clinical PFS was improved from 74.8 % to 83.3 % at 5 years ( HR=0.68 , CI : 0.52 - 0.89 , P=0.004 ) . The incidence of loco-regional failure was significantly decreased ( P<0.0001 ) . Further follow-up is needed to assess the impact on distant metastases and overall survival . P-XRT is associated with an increased risk of immediate and late grade 1 - 2 side effects . Grade 3 side effect rates so far were less than 5 % in both groups . CONCLUSIONS Post-operative radiotherapy results in improved biochemical and clinical PFS . This benefit is to be weighed against the treatment side effects . Further follow-up is needed to assess the impact on overall survival . No significant financial relationships to disclose As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better Output:	Adjuvant RT after RP improves overall survival and reduces the rate of distant metastases , but these effects are only evident with longer follow up . At 5 and 10 years it improves local control and reduces the risk of biochemical failure , although the latter is not a clinical endpoint . Moderate or severe acute and late toxicity is minimal . There is an increased risk of urinary stricture and incontinence , but no detriment to quality of life , based on limited data .
MS22245	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We investigated whether a short course in communication skills for physicians would improve the quality of informed consent in a r and omized clinical adjuvant trial on breast cancer . In this prospect i ve , case-controlled intervention study , physicians and research nurses who introduced the cancer treatment trial to patients at three of the participating hospitals first attended a one-day communication skills course . The quality of informed consent was then evaluated by addressing a st and ardized question naire , QuIC , to trial patients at the three intervention hospitals and at control hospitals . Response rate was 90.0 % ( n = 288 ) . Of the patients treated by the intervention group , 73 % were very satisfied with the information received compared with 56 % of those of the control group ( p = 0.003 ) . The patients of the intervention group considered the time given for making their decision sufficient more often than those of the controls ( 98 % vs. 90 % , p=0.004 ) . The patients of the intervention group recalled more often than those of the controls that the physician had also offered other therapeutic options than the trial treatment ( 91 % vs. 97 % , p=0.032 ) . They also understood the main aim of the study better than the patients of the controls ( 89 % vs. 78 % , p=0.030 ) . In conclusion , a short communication skills course for the trial physicians and nurses improved the quality of informed consent and patient satisfaction in the trial There is today a wide consensus regarding the need to improve communication skills ( CS ) of health-care professionals ( HCPs ) dealing with cancer patients . Psychological training programs ( PTPs ) may be useful to acquire the needed CS . Testing the efficacy of PTP will allow to define their optimal content . The present study was design ed to assess the impact of a PTP on HCP stress , attitudes and CS , and on HCP and patients ' satisfaction with HCP communication skills in a r and omised study . A total of 115 oncology nurses were r and omly assigned to a 105-h PTP or to a waiting list . Stress was assessed with the Nursing Stress Scale , attitudes with a Semantic Differential Question naire , CS used during one simulated and one actual patient interview with the Cancer Research Campaign Workshop Evaluation Manual , and satisfaction with the nurses ' CS with a question naire completed by the patients and the nurses . Trained ( TG ) and control ( CG ) groups were compared at baseline , after 3 months ( just following training for TG ) and after 6 months ( 3 months after the end of training for TG ) . Compared to controls , trained nurses reported positive changes on their stress levels ( P⩽0.05 ) and on their attitudes ( P⩽0.05 ) . Positive training effects were found on CS used during the simulated interview : a significant increase in facilitative behaviours ( open questions : P⩽0.001 ; evaluative functions : P⩽0.05 ) and a significant decrease in inhibitory behaviours ( inappropriate information : P⩽0.01 ; false reassurance : P⩽0.05 ) . Less positive training effects were found regarding interviews with a cancer patient : a significant increase in educated guesses ( P⩽0.001 ) was noticed . No training effect was observed on nurses ' satisfaction levels , but a positive training effect was found on patients ' satisfaction levels ( P⩽0.01 ) . Although results outline PTP efficacy , they indicate the need to design PTP , amplifying the transfer of learned CS to clinical practice PURPOSE We wanted to assess the effectiveness of intensive education for physicians compared with a traditional session on communicating with breast cancer patients . METHODS A r and omized controlled trial was conducted in practice s in London , Hamilton , and Toronto , Canada , with 17 family physicians , 16 surgeons , and 18 oncologists , and with 102 patients of the surgeons and oncologists . Doctors were r and omized to 1 of 2 continuing education approaches : a traditional 2-hour version ( control group ) , or a new 6-hour intensive version including exploring the patients ’ perspectives and review ing videotapes and receiving feedback ( intervention group ) . Communication behavior of the physicians was measured objective ly both before and after the intervention . As well , 4 postintervention patient outcomes were measured , by design only for surgeons and oncologists : patient-centerdness of the visit , satisfaction , psychological distress , and feeling better . RESULTS No significant differences were found on the communication score of the intervention vs the control physicians when controlling for preintervention communication scores . Intervention family physicians , however , had significantly higher communication subscores than control family physicians . Also , patients of the intervention surgeons and oncologists were significantly more satisfied ( scores of 82.06 vs 77.78 , P = .03 ) and felt better ( 88.2 % vs 70.6 % , P=.02 ) than patients of the control surgeons and oncologists when controlling for covariates and adjusting for clustering within doctor . CONCLUSIONS The continuing medical education intervention was effective in terms of some but not all physician and patient outcomes The efficacy of a communication skills training programme was shown through a r and omised trial . Oncologists ( N=160 ) from 34 cancer centres were allocated to written feedback plus course ; course alone ; written feedback alone or control . Each clinician had 6 – 10 interviews with patients videotaped at baseline and 3 months postintervention . Analysis of videotapes revealed improvements in the communication skills of clinicians r and omised to training ( n=80 ) compared with others ( n=80 ) . A 12-month follow-up assessment is reported here . Robust Poisson conditional analyses of counts of changes in communication behaviours revealed no demonstrable attrition in those who had shown improvement previously , including fewer leading questions , appropriate use of focused and open-ended questions and responses to patient cues . Additional skills , not apparent at 3 months , were now evident ; the estimated effect sizes corresponded to 81 % fewer interruptions ( P=0.001 ) and increased summarising of information to 38 % ( P=0.038 ) . However , expressions of empathy ( 54 % , P=0.001 ) declined . The overall results show that 12 – 15 months postintervention , clinicians had integrated key communication skills into clinical practice and were applying others . This is the first RCT to show an enduring effect of communication skills training with transfer into the clinic BACKGROUND No study has yet assessed the impact of physicians ' skills acquisition after a communication skills training programme on the evolution of patients ' anxiety following a medical consultation . This study aim ed to compare the impact , on patients ' anxiety , of a basic communication skills training programme ( BT ) and the same programme consoli date d by consolidation workshops ( CW ) , and to investigate physicians ' communication variables associated with patients ' anxiety . PATIENTS AND METHODS Physicians , after attending the BT , were r and omly assigned to CW or to a waiting list . The control group was not a non-intervention group . Consultations with a cancer patient were recorded . Patients ' anxiety was assessed with the State Trait Anxiety Inventory before and after a consultation . Communication skills were analysed according to the Cancer Research Campaign Workshop Evaluation Manual . RESULTS No statistically significant change over time and between groups was observed . Mixed-effects modelling showed that a decrease in patients ' anxiety was linked with screening questions ( P = 0.045 ) , physicians ' satisfaction about support given ( P = 0.004 ) and with patients ' distress ( P < 0.001 ) . An increase in anxiety was linked with breaking bad news ( P = 0.050 ) and with supportive skills ( P = 0.013 ) . No impact of the training programme was observed . CONCLUSIONS This study shows the influence of some communication skills on the evolution of patients ' anxiety . Physicians should be aware of these influences The provision of adequate information in a clear and sensitive manner can improve cancer patients ' experience of care . Satisfaction with the cancer consultation may impact on satisfaction with care in general and adjustment to the disease . This study aims to identify factors that influence patient and clinician satisfaction with the cancer consultation and whether satisfaction can be improved with communication skills training . 160 doctors from 34 UK cancer centres participated . Half were r and omized to attend a communication skills training course . Patient satisfaction data are presented at baseline and following a communication skills course or in the case of the control doctors , three months after baseline . Clinicians also rated their satisfaction with the consultations . Overall patient satisfaction was not related to the speciality , seniority or sex of the clinician or patient , site of primary cancer or type of treatment . Satisfaction was related to patients ' age , psychological morbidity and , most significantly , satisfaction with the length of wait in clinic . Clinician satisfaction was not related to age , sex or cancer site but clinicians were less satisfied following consultations with patients being treated palliatively . Communication skills training had a non-significant positive effect on patient satisfaction . The subtle benefits of improved communication may be overshadowed by practical problems such as waiting too long to see the doctor , which have an adverse effect on satisfaction PURPOSE The purpose of the study was to examine the effect of communication on rectal cancer patients ’ quality of life over four years . Previous studies have either used short follow-up periods or examined only certain aspects of quality of life , such as anxiety and depression . METHODS In a prospect i ve , observational study , rectal cancer patients , recruited by clinicians over a two-year period , were sent question naires over four years . The clinical details of these patients were recorded by the Munich Cancer Registry . The psychological scores from the European Organization for Research and Treatment of Cancer QLQ-C30 and CR38 were the main outcome variables . RESULTS Thirty-nine percent of the sample reported that some aspect of the communication they received was unclear ( incomprehensible or too little ) . More than 60 percent wished to speak more with their physician . Younger patients and those in larger hospitals were more likely to report unclear communication ( P < 0.05 ) . Analyses of covariance , controlled for age , gender , adjuvant therapy , stoma , education , clinic , and comorbidity , demonstrated that role , emotional , and social functioning scores were consistently lower in patients reporting unclear communication . Additionally , these patients experienced more problems sleeping , poorer body image , more financial worries , and a worse future perspective . Repeated measures analyses indicated that sleeping problems and emotional and social functioning difficulties persisted for at least three years . CONCLUSION Reports of unclear communication were associated with poorer quality of life in rectal cancer patients without disease progression The emotional content of health care professionals – cancer patient communication is often considered as poor and has to be improved by an enhancement of health care professionals empathy . One hundred and fifteen oncology nurses participating in a communication skills training workshop were assessed at three different periods . Nurses r and omly allocated to a control group arm ( waiting list ) were assessed a first time and then 3 and 6 months later . Nurses allocated to the training group were assessed before training workshop , just after and 3 months later . Each nurse completed a 20-min clinical and simulated interview . Each interview was analysed by three content analysis systems : two computer-supported content analysis of emotional words , the Harvard Third Psychosocial Dictionary and the Martindale Regressive Imagery Dictionary and an observer rating system of utterances emotional depth level , the Cancer Research Campaign Workshop Evaluation Manual . The results show that in clinical interviews there is an increased use of emotional words by health care professionals right after having been trained ( P=0.056 ) : training group subjects use 4.3 ( std : 3.7 ) emotional words per 1000 used before training workshop , and 7.0 ( std : 5.8 ) right after training workshop and 5.9 ( std : 4.3 ) 3 months later compared to control group subjects which use 4.5 ( std : 4.8 ) emotional words at the first assessment point , 4.3 ( std : 4.1 ) at the second and 4.4 ( std : 3.3 ) at the third . The same trend is noticeable for emotional words used by health care professionals in simulated interviews ( P=0.000 ) . The emotional words registry used by health care professionals however remains stable over time in clinical interviews ( P=0.141 ) and is enlarged in simulated interviews ( P=0.041 ) . This increased use of emotional words by trained health care professionals facilitates cancer patient emotion words expressions compared to untrained health care professionals especially 3 months after training ( P=0.005 ) . This study shows that health care professionals empathy may be improved by communication skills training workshop and that this improvement facilitates cancer patients emotions expression BACKGROUND Doctors ' communication with patients is commonly hampered by lack of training in this core skill . This study aim ed to assess the efficacy of an intensive 3-day training course on communication skills in a r and omised controlled trial with a two-by-two factorial design and several outcomes . METHODS 160 oncologists from 34 UK cancer centres were r and omly allocated to four groups : written feedback followed by course ; course alone ; written feedback alone ; and control . At each of two assessment periods , consultations with six to ten consecutive , consenting patients per doctor were videotaped . 2407 patients participated . Outcome measures included objective and subjective ratings made by research ers , doctors , and patients . The primary outcomes were objective improvements after the intervention in key communication skills . Course content included structured feedback , videotape review of consultations , role-play with simulated patients , interactive group demonstrations , and discussion led by a trained facilitator . FINDINGS In Poisson regression analysis of counts of communication behaviours , course attendance significantly improved key outcomes . The estimated effect sizes corresponded to higher rates of use of focused questions ( difference between course attenders [ n=80 ] and non-attenders [ n=80 ] 34 % , p=0.003 ) , focused and open questions ( 27 % , p=0.005 ) , expressions of empathy ( 69 % , p=0.003 ) , and appropriate responses to patients ' cues ( Output:	No evidence was found for the effectiveness of communication training on patient distress outcomes . We concluded that the current review reveals inconclusive evidence to prove the effectiveness of communication training on patient satisfaction and patient distress .
MS22246	*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 explore the efficacy of a mindfulness-based weight loss intervention for women . Sixty-two women ( ages 19 - 64 ; BMI 22.5 - 52.1 ) who were attempting to lose weight were r and omised to an intervention or control condition . The former were invited to attend four 2-h workshops , the latter were asked to continue with their normal diets . Data were collected at baseline , 4 and 6 months . BMI , physical activity , mental health . At 6 months intervention participants showed significantly greater increases in physical activity compared to controls ( p<.05 ) but no significant differences in weight loss or mental health . However , when intervention participants who reported ' never ' applying the workshop principles at 6 months ( n=7 ) were excluded , results showed both significantly greater increases in physical activity ( 3.1 sessions per week relative to controls , p<.05 ) and significantly greater reductions in BMI ( 0.96 relative to controls , equivalent to 2.32 kg , p<0.5 ) . Reductions in BMI were mediated primarily by reductions in binge eating . Despite its brevity , the intervention was successful at bringing about change . Further refinements should increase its efficacy OBJECTIVE Using self-refilling soup bowls , this study examined whether visual cues related to portion size can influence intake volume without altering either estimated intake or satiation . RESEARCH METHODS AND PROCEDURES Fifty-four participants ( BMI , 17.3 to 36.0 kg/m2 ; 18 to 46 years of age ) were recruited to participate in a study involving soup . The experiment was a between-subject design with two visibility levels : 1 ) an accurate visual cue of a food portion ( normal bowl ) vs. 2 ) a biased visual cue ( self-refilling bowl ) . The soup apparatus was housed in a modified restaurant-style table in which two of four bowls slowly and imperceptibly refilled as their contents were consumed . Outcomes included intake volume , intake estimation , consumption monitoring , and satiety . RESULTS Participants who were unknowingly eating from self-refilling bowls ate more soup [ 14.7+/-8.4 vs. 8.5+/-6.1 oz ; F(1,52)=8.99 ; p<0.01 ] than those eating from normal soup bowls . However , despite consuming 73 % more , they did not believe they had consumed more , nor did they perceive themselves as more sated than those eating from normal bowls . This was unaffected by BMI . DISCUSSION These findings are consistent with the notion that the amount of food on a plate or bowl increases intake because it influences consumption norms and expectations and it lessens one 's reliance on self-monitoring . It seems that people use their eyes to count calories and not their stomachs . The importance of having salient , accurate visual cues can play an important role in the prevention of unintentional overeating How important are visual cues for determining satiation ? To find out , 64 participants were served lunch in a " dark " restaurant where they ate in complete darkness . Half the participants unknowingly received considerably larger " super-size " portions which subsequently led them to eat 36 % more food . Despite this difference , participants ' appetite for dessert and their subjective satiety were largely unaffected by how much they had consumed . Consistent with expectations , participants were also less accurate in estimating their actual consumption quantity than a control group who ate the same meal in the light BACKGROUND Habituation is a form of learning in which repeated exposure to a stimulus leads to a decrease in responding . Eating involves repeated presentation of the same food stimulus in a meal , and habituation is reliably observed within a meal such that faster rates of habituation are associated with less energy intake . It is possible that repeated presentation of the same food over days will lead to long-term habituation , such that subjects habituate to foods repeated over meals . However , no research on long-term habituation to food in humans has been conducted . OBJECTIVE The current study was design ed to assess long-term habituation in 16 obese and 16 nonobese premenopausal women . DESIGN Obese and nonobese women ( aged 20 - 50 y ) were r and omly assigned to receive a macaroni and cheese meal presented 5 times , either daily for 1 wk or once per week for 5 wk . RESULTS In both obese and nonobese women , daily presentation of food result ed in faster habituation and less energy intake than did once-weekly presentation of food . CONCLUSIONS Long-term habituation was observed when the same food was presented at daily meals but not when presented once weekly for 5 wk . These results provide the first evidence of long-term habituation to food in women and show that memory of food over daily meals can increase the rate of habituation and reduce energy intake . This trial was registered at clinical trials.gov as NCT01208870 BACKGROUND The effect of television viewing ( TVV ) with and without advertisements ( ads ) on energy intake is unclear . OBJECTIVE The objectives were to test 1 ) the effect of TVV , with and without ads , on energy intake compared with a control and reading condition and 2 ) the association of distractibility and memory for ads with energy intake and body weight . DESIGN Forty-eight ( 26 female ) adults ( age : 19 - 54 y ) with a body mass index ( in kg/m(2 ) ) of 20 - 35 completed this laboratory-based study . All participants completed 4 buffet-style meals in r and om order in the following conditions : 1 ) control , 2 ) while reading , 3 ) while watching TV with food and nonfood ads ( TV-ads ) , and 4 ) while watching TV with no ads ( TV-no ads ) . Energy intake was quantified by weighing foods . Distractibility and memory for ads in the TV-ads condition were quantified with a norm-referenced test and recognition task , respectively . RESULTS Repeated- measures analysis of variance indicated that energy and macronutrient intake did not differ significantly among the 4 conditions ( P > 0.65 ) . Controlling for sex , memory for ads was associated with body weight ( r = 0.36 , P < 0.05 ) and energy intake but only when viewing TV ( r = 0.39 , P < 0.05 during the TV-no ads condition , and r = 0.29 , P = 0.06 during the TV-ads condition ) . Controlling for sex , distractibility was associated with body weight ( r = 0.36 , P < 0.05 ) but not energy intake . Distractibility , however , accounted for 13 % of the variance in men 's energy intake ( P = 0.11 ) . CONCLUSIONS TVV did not affect energy intake , but individual characteristics ( memory for ads ) were associated with body weight and energy intake in certain conditions . These characteristics should be considered in food intake and intervention studies BACKGROUND Sedentary activities , such as watching television , may disrupt habituation to food cues , thereby increasing motivation to eat and energy intake . OBJECTIVE These experiments were design ed to examine the effect of television watching on habituation of ingestive behavior in children . DESIGN In experiment 1 , all children worked for access to cheeseburgers in trials 1 - 7 ( habituating stimulus ) . In trials 8 - 10 , children in the control group continued to work for cheeseburgers without any dishabituating stimuli , whereas children in the other groups received either a novel food ( French fries ) or television as dishabituating stimuli . Responding for food and amount of food eaten were measured . In experiment 2 , all children had access to 1000 kcal of a preferred snack food . One group watched a continuous television show , and the control groups either watched no television or watched a repeated segment of a television show , which controls for the television stimulus but requires reduced allocation of attention . RESULTS In experiment 1 , both the novel food and the television watching groups reinstated responding for food ( P = 0.009 ) and increased the amount of energy earned ( P = 0.018 ) above the level of the control subjects . In experiment 2 , the continuous television group spent more time eating ( P < 0.0001 ) and consumed more energy than the no television and the repeated segment groups ( P = 0.007 ) . CONCLUSION These experiments show that television watching can dishabituate eating or disrupt the development of habituation , which may provide a mechanism for increased energy intake associated with watching television Long-term behavioral self-regulation is the hallmark of successful weight control . We tested mediators of weight loss and weight loss maintenance in middle-aged women who participated in a r and omized controlled 12-month weight management intervention . Overweight and obese women ( N = 225 , BMI = 31.3 + /- 4.1 kg/m(2 ) ) were r and omly assigned to a control or a 1-year group intervention design ed to promote autonomous self-regulation of body weight . Key exercise , eating behavior , and body image variables were assessed before and after the program , and tested as mediators of weight loss ( 12 months , 86 % retention ) and weight loss maintenance ( 24 months , 81 % retention ) . Multiple mediation was employed and an intention-to-treat analysis conducted . Treatment effects were observed for all putative mediators ( Effect size : 0.32 - 0.79 , P < 0.01 vs. controls ) . Weight change was -7.3 + /- 5.9 % ( 12-month ) and -5.5 + /- 5.0 % ( 24-month ) in the intervention group and -1.7 + /- 5.0 % and -2.2 + /- 7.5 % in controls . Change in most psychosocial variables was associated with 12-month weight change , but only flexible cognitive restraint ( P < 0.01 ) , disinhibition ( P < 0.05 ) , exercise self-efficacy ( P < 0.001 ) , exercise intrinsic motivation ( P < 0.01 ) , and body dissatisfaction ( P < 0.05 ) predicted 24-month weight change . Lower emotional eating , increased flexible cognitive restraint , and fewer exercise barriers mediated 12-month weight loss ( R(2 ) = 0.31 , P < 0.001 ; effect ratio : 0.37 ) , but only flexible restraint and exercise self-efficacy mediated 24-month weight loss ( R(2 ) = 0.17 , P < 0.001 ; effect ratio : 0.89 ) . This is the first study to evaluate self-regulation mediators of weight loss and 2-year weight loss maintenance , in a large sample of overweight women . Results show that lowering emotional eating and adopting a flexible dietary restraint pattern are critical for sustained weight loss . For long-term success , interventions must also be effective in promoting exercise intrinsic motivation and self-efficacy This study compared 2 extended therapy programs for weight management with st and ard behavioral treatment ( BT ) without additional therapy contacts . Participants were 80 obese women who completed 20 weekly group sessions of BT and achieved a mean initial weight loss of 8.74 kg . Participants were r and omly assigned to a no-further-contact condition ( BT only ) or to one of two extended interventions consisting of relapse prevention training ( RPT ) or problem-solving therapy ( PST ) . No significant overall weight-change differences were observed between RPT and BT or between RPT and PST . However , participants who completed the PST intervention had significantly greater long-term weight reductions than BT participants , and a significantly larger percentage of PST participants achieved clinical ly significant losses of 10 % or more in body weight than did BT participants ( 35 % vs. 6 % ) The effect of being reminded of a recent eating episode on subsequent food intake was examined in unrestrained eaters . In Experiment 1 , female participants were exposed to a " lunch cue " ( in which they were asked to think about what they had eaten for lunch ) , or " no cue " ( free thought condition ) , for 5 min prior to eating . Participants ate less following exposure to the " lunch cue " than the " no cue " condition . In Experiment 2 , food intake was measured following exposure to either a " lunch today " cue , " lunch yesterday " cue or " no cue " condition . Intake in the " lunch today " condition was suppressed relative to both the " lunch yesterday " and " no cue " condition . Subjective ratings of hunger , fullness , and desire to eat did not vary as a function of cue type in either Experiment 1 or Experiment 2 . These results are consistent with the suggestion that memory of recent eating is an important cognitive factor influencing food intake Women were divided into those eating at a decelerated or linear rate . Eating rate was then experimentally increased or decreased by asking the women to adapt their rate of eating to curves presented on a computer screen and the effect on food intake and satiety was studied . Decelerated eaters were unable to eat at an increased rate , but ate the same amount of food when eating at a decreased rate as during the control condition . Linear eaters ate more food when eating at an increased rate , but less food when eating at a decreased rate . Decelerated eaters estimated their level of satiety lower when eating at an increased rate but similar to the control condition when eating at a decreased rate . Linear eaters estimated their level of satiety similar to the control level despite eating more food at an increased rate and higher despite eating less food at a decreased rate . The cumulative satiety curve was fitted to a sigmoid curve both in decelerated and linear eater under all conditions . Linear eaters rated their desire to eat and estimated their prospect i ve intake lower than decelerated eaters and scored higher on a scale for restrained eating . It is suggested that linear eaters have difficulty maintaining their intake when eating rate is dissociated from its baseline level and that this puts them at risk of developing disordered eating . It is also suggested that feedback on eating rate can be used as an intervention to Output:	The effect of distraction on immediate intake appeared to be independent of dietary restraint . Evidence indicates that attentive eating is likely to influence food intake , and incorporation of attentive-eating principles into interventions provides a novel approach to aid weight loss and maintenance without the need for conscious calorie counting
MS22247	*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: Long‐term use of calcineurine inhibitors ( CNIs ) may contribute to the development of chronic allograft dysfunction ( CAD ) . We investigate the impact of the introduction of MMF combined with cyclosporine ( CsA ) 50 % dose reduction . An open , r and omized , controlled , multicenter , prospect i ve study was conducted in 103 patients , receiving a CsA‐based therapy with a serum creatinine between 1.7–3.4 mg/dL , more than 1 year after transplantation . They were r and omized to receive MMF with half dose of CsA ( MMF group ) or to continue their maintenance CsA dose ( control group ) . A total of 96 weeks after r and omization , the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group ( positive slope ) vs. the control group ( negative slope ) , 4.2 × 10−4 vs. −3.0 × 10−4 , respectively ( p < 0.001 ) . Concurrently , the absolute renal function improved significantly in the MMF group . No episode of biopsy‐proven acute rejection occurred . One patient in each group lost his graft because of biopsy‐proven chronic allograft nephropathy . There was a significant decrease of triglycerides level in the MMF group . Anemia and diarrhea were statistically more frequent in the MMF group BACKGROUND Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients . This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens . METHODS We r and omly assigned 1645 renal-transplant recipients to receive st and ard-dose cyclosporine , mycophenolate mofetil , and corticosteroids , or daclizumab induction , mycophenolate mofetil , and corticosteroids in combination with low-dose cyclosporine , low-dose tacrolimus , or low-dose sirolimus . The primary end point was the estimated glomerular filtration rate ( GFR ) , as calculated by the Cockcroft-Gault formula , 12 months after transplantation . Secondary end points included acute rejection and allograft survival . RESULTS The mean calculated GFR was higher in patients receiving low-dose tacrolimus ( 65.4 ml per minute ) than in the other three groups ( range , 56.7 to 59.4 ml per minute ) . The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus ( 12.3 % ) than in those receiving st and ard-dose cyclosporine ( 25.8 % ) , low-dose cyclosporine ( 24.0 % ) , or low-dose sirolimus ( 37.2 % ) . Allograft survival differed significantly among the four groups ( P=0.02 ) and was highest in the low-dose tacrolimus group ( 94.2 % ) , followed by the low-dose cyclosporine group ( 93.1 % ) , the st and ard-dose cyclosporine group ( 89.3 % ) , and the low-dose sirolimus group ( 89.3 % ) . Serious adverse events were more common in the low-dose sirolimus group than in the other groups ( 53.2 % vs. a range of 43.4 to 44.3 % ) , although a similar proportion of patients in each group had at least one adverse event during treatment ( 86.3 to 90.5 % ) . CONCLUSIONS A regimen of daclizumab , mycophenolate mofetil , and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function , allograft survival , and acute rejection rates , as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with st and ard-dose cyclosporine without induction . ( Clinical Trials.gov number , NCT00231764 [ Clinical Trials.gov ] . ) Background . This study determined whether cyclosporine A (CsA)-treated renal allograft recipients with deteriorating renal function ( “ creeping creatinine ” ) secondary to chronic allograft nephropathy ( CAN ) benefit from the addition of mycophenolate mofetil ( MMF ) to their immunosuppressive regimen , followed by withdrawal of CsA. Methods . In a controlled , open , multicenter study , CsA-treated renal allograft recipients with progressively deteriorating renal function were r and omized to have their CsA discontinued with the concomitant addition of MMF to their regimen ( group A ) or to continue treatment with CsA ( group B ) . The primary endpoint was the response rate over the 6-month period after withdrawal of CsA in group A or the equivalent time in group B. Response was defined as a stabilization or reduction of serum creatinine ( SCr ) , as evidence d by a flattening or positive slope of the 1/SCr plot and no graft loss . Secondary endpoints included the incidence of acute rejection , graft and patient survival , and changes in selected metabolic parameters . Results . The response rate in the primary intent-to-treat population ( n=122 ) was 58 % ( 36/62 ) in group A versus 32 % ( 19/60 ) in group B ( P=0.0060 ) . The corresponding percentages of responders in the per- protocol population ( n=107 ) were 60 % ( 36/60 ) and 26 % ( 12/47 ) , respectively ( P=0.0008 ) . There were no acute rejections in group A during the study period . Patients in this group also experienced a significant decrease in total cholesterol . Conclusions . In patients with progressively deteriorating renal function secondary to CAN , addition of MMF followed by withdrawal of CsA results in a significant improvement in transplant function without the risk of acute rejection Background . Long-term maintenance immunosuppression with cyclosporine ( CsA ) is associated with chronic transplant nephropathy and adverse effects on blood pressure and lipid profile . Several nonr and omized studies suggest that CsA might safely be withdrawn from immunosuppressive regimens containing mycophenolate mofetil ( MMF ; CellCept ) . Methods . A r and omized , controlled study with 187 patients enrolled from 21 centers was conducted to compare CsA withdrawal with ongoing CsA therapy in stable renal transplant recipients receiving a triple-drug immunosuppressive regimen of MMF ( 2 g/day ) , CsA ( Neoral ) , and corticosteroids . The primary endpoint was creatinine clearance at 6 months after complete withdrawal . Results . In the intent-to-treat population , CsA withdrawal was associated with lower total cholesterol and low-density lipoprotein cholesterol ( −0.3 mmol/L , P = 0.02 ; −0.4 mmol/L , P = 0.015 ) . There was a trend toward improved creatinine clearance ( 4.5 mL/min , P = 0.16 ) and serum creatinine ( −1 vs. + 4 & mgr;mol/L , P = 0.34 ) . In the per- protocol population , which excluded patients with acute rejections , the improvements in creatinine clearance and serum creatinine were statistically significant ( 7.5 mL/min , P = 0.02 ; −11 vs. + 4 & mgr;mol/L , P = 0.0003 ) . Reversible acute rejections , the majority of which were mild , occurred in nine CsA withdrawal versus two CsA continuation patients ( 10.6 % vs. 2.4 % of each group , P = 0.03 ) , with no graft loss . Conclusion . Withdrawal of CsA from an MMF-containing triple-drug immunosuppressive regimen improves renal function and lipid profile at the cost of a modest increase in acute rejections , without graft loss Maintenance immunosuppression with cyclosporine ( CsA ) is associated with nephrotoxicity , hyperlipidemia , and hypertension . This long-term study ( core study + 4 yr of follow-up ) investigated the long-term efficacy and safety of CsA withdrawal from a mycophenolate mofetil (MMF)-based regimen . Seventy-seven patients were maintained on CsA , MMF , and steroids ( CsA-MMF group ) , and 74 were given a CsA-free regimen of MMF and steroids ( MMF group ) . Serum creatinine and creatinine clearance were measured at 6-month intervals . Patient and graft survival , acute rejection episodes , malignancies , BP , and lipid profile were also recorded . At 5 yr , patient and graft survival was 93 and 88 % , respectively , for the MMF group and 95 and 92 % , respectively , for the CsA-MMF group . During follow-up , seven MMF patients experienced acute rejection episodes compared with one CsA-MMF patient ( P = 0.0283 ) . Nine grafts were lost to chronic rejection in the MMF group versus three in the CsA-MMF group . No demographic or immunologic characteristics were associated with acute or chronic rejection in the MMF group , but the doses of both MMF and steroids decreased significantly between 1 and 5 yr . The MMF group showed a trend toward improved creatinine clearance ( 67.4 versus 61.7 ml/min ; P = 0.0500 ) . Withdrawal of CsA from an MMF-containing immunosuppressive regimen result ed in an increased risk for acute rejection episodes and graft loss as a result of rejection throughout the 5-yr study period . The creatinine clearance-confirmed improvement in renal function observed at year 1 was maintained at 5 yr BP and cholesterol levels were well controlled in both groups BACKGROUND This study was conducted to assess the effect of immunosuppression conversion on progression of chronic allograft nephropathy ( CAN ) . METHODS Forty-two cyclosporin-treated renal transplant recipients were studied . Patients were included if they had a negatively sloping reciprocal of creatinine vs time ( ROCT ) plot for > 6 months and biopsy-proven CAN . Patients were excluded if they had previously been treated with tacrolimus/mycophenolate mofetil ( MMF ) or their serum creatinine was > 400 micromol/l . Subjects were r and omly treated with either : ( A ) MMF/reduced dose cyclosporin [ MMF for azathioprine 0.5 - 1.0 g bd ; cyclosporin trough level ( C(0 ) ) : 75 - 100 ng/ml ] ; ( B ) tacrolimus for cyclosporin ( C(0 ) : 5 - 10 ng/ml ) ; or ( C ) continuation of st and ard therapy . Glomerular filtration rate ( GFR ) was measured at baseline and after 6 months . RESULTS Two patients started dialysis within 6 months ( one each from groups A and B ) . One patient in group A was intolerant of MMF , six others reported gastrointestinal symptoms and three developed anaemia . Cyclosporin dose was reduced by 24 % [ interquartile range ( IQR ) : 14 - 27 % ] in group A [ end-of- study C(0 ) : 99 ng/ml ( IQR : 90 - 113 ng/ml ) ] . In group B , the end-of- study tacrolimus C(0 ) was 7 ng/ml ( 5 - 9 ng/ml ) . The end-of- study cyclosporin C(0 ) in group C was 163 ng/ml ( 145 - 215 ng/ml ) . Comparison of ROCT slopes before and after intervention revealed a treatment advantage for group A ( P<0.05 ) . The GFR analysis was supportive ( P = 0.05 ) . When patients with GFR < 20 ml/min/1.73 m(2 ) at enrollment were excluded from the analysis , the treatment advantage for group A reached statistical significance ( n = 27 , P<0.05 ) . CONCLUSIONS MMF/reduced dose cyclosporin is superior to tacrolimus-for-cyclosporin and st and ard dose cyclosporin in patients with CAN , at least in the short term . The cyclosporin dose reduction component is likely to be of particular importance . Other findings suggest that early intervention is beneficial Background . We report the two-year follow-up of a trial comparing the three-month postgraft discontinuation of either cyclosporine ( CsA ) or mycophenolate mofetil ( MMF ) from a triple-drug regimen after de novo renal transplantation . Methods . One hundred and eight patients were enrolled in this study and r and omized to be withdrawn from CsA ( MMF group , n=54 ) or MMF ( CsA group , n=54 ) . Results . Despite an increased risk of acute rejection and a lower , but nonsignificant , two-year graft survival , CsA withdrawal induced a sustained improvement of the renal function . At one year , the chronic allograft damage index was similar in both the MMF and CsA groups . However , CsA elimination result ed in a higher incidence of C4d deposits , irrespective of the occurrence of a prior acute rejection . While this finding could suggest a risk of chronic rejection in the MMF group , the outcome did not appear to be related to the Output:	There were no significant differences in mortality , malignancy or incidence of infections . CONCLUSIONS CNI sparing strategies with adjunctive mycophenolate may play an important role in kidney transplant recipients . Improvements in short-term graft function , and possibly graft survival , are achievable . Longer term studies are needed to substantiate the short-term benefits , and refining elective CNI elimination protocol s may help to reduce the risk of rejection
MS22248	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We investigated whether canalicular occlusion with a lacrimal plug could increase objective and /or subjective comfort in contact lens ( CL ) wearers ( n = 9 ) with both a history of lens intolerance and relative tear fluid deficiency . A modified Schirmer test ( MST ) was performed with the lids closed and under topical anaesthesia . Patients with values of < 10 mm/5 min were included . The plugs were inserted into the inferior canaliculus of the eye with the lower MST result ; the contralateral eye served as a control . Conjunctival hyperaemia , Rose-Bengal and fluorescein scores , as well as subjective irritation , decreased significantly in plugged eyes at the 1 month follow-up visit but had returned to the pre-operative level at the 3 month visit . Tear fluid plasmin activity was elevated prior to plug insertion . Plasmin activity of the plugged eye was significantly lower at the 1 month visit but neither tear fluid flow ( in the collection capillary ) nor plasmin release showed any changes . The mean MST value improved insignificantly , whereas conjunctival chemosis and limbal hyperaemia showed no improvement at the 1 or 3 month follow-up visits after inferior punctal occlusion . Occlusion of the lower canaliculus with a lacrimal plug seems to induce a relatively short-lasting subjective and objective benefit for CL wearers . Plug escape or adaptive changes in lacrimal fluid secretion/ elimination rate probably took place during the follow-up . The association of increased plasmin activity with tear deficiency might lead to enhanced tissue proteolysis , and thus contribute to CL-related ocular surface changes Purpose : To evaluate the clinical efficacy , retention rates , and complications of SmartPlug insertion compared with silicone punctal plugs in patients with dry eye . Methods : Thirty-six eyes with subjective symptoms of dry eye in addition to a tear film breakup time ( TBUT ) < 5 seconds and evidence of ocular surface damage on rose Bengal or fluorescein staining were included . Treated eyes were r and omized to either a silicone plug or SmartPlug inferior punctal occlusion . Pre- and posttreatment evaluations included subjective symptom scoring , tear meniscus height , TBUT , Schirmer test , fluorescein and rose Bengal staining , and artificial tear use . Results : After a mean follow-up period of 11.2 weeks , both the silicone plug- and SmartPlug-treated eyes showed significant improvement in symptom scoring ( P = 0.002 and P = 0.005 , respectively ) , TBUT ( P = 0.035 and P = 0.009 , respectively ) , and fluorescein ( P = 0.024 and P = 0.016 , respectively ) and rose Bengal ( P = 0.008 and P = 0.046 , respectively ) staining . There was no significant difference in these parameters between the 2 plugs . SmartPlug- , but not the silicone plug-treated eyes showed significant improvement in mean tear meniscus height ( P = 0.037 ) . The use of artificial tear supplements was reduced in 10 ( 55.6 % ) silicone- and 11 ( 61.1 % ) SmartPlug-treated eyes . Minor complications related to plug insertion were experienced in 4 ( 22 % ) silicone- and 2 ( 11 % ) SmartPlug-treated eyes . Spontaneous plug loss occurred with 6 ( 33 % ) silicone plugs . Conclusions : This prospect i ve r and omized trial shows that SmartPlug insertion has equivalent clinical efficacy to the use of conventional silicone plugs . Both SmartPlug and silicone plug use can reduce dependency on tear supplements in > 55 % of patients with dry eye PURPOSE To determine the incidence of dry eye and its risk factors after myopic laser-assisted in situ keratomileusis ( LASIK ) . DESIGN Single-center , prospect i ve r and omized clinical trial of 35 adult patients , aged 24 to 54 years , with myopia undergoing LASIK . METHODS setting and study population : Participants were r and omized to undergo LASIK with a superior or a nasal hinge flap . They were evaluated at 1 week and 1 , 3 , and 6 months after surgery . intervention : Bilateral LASIK with either a superior-hinge Hansatome microkeratome ( n = 17 ) or a nasal-hinge Amadeus microkeratome ( n = 18 ) . main outcome measures : The criterion for dry eye was a total corneal fluorescein staining score > or =3 . Visual acuity , ocular surface parameters , and corneal sensitivity were also analyzed . Cox proportional-hazard regression was used to assess rate ratios ( RRs ) with 95 % confidence intervals . RESULTS The incidence of dry eye in the nasal- and superior-hinge group was eight ( 47.06 % ) of 17 and nine ( 52.94 % ) of 17 at 1 week , seven ( 38.89 % ) of 18 and seven ( 41.18 % ) of 17 at 1 month , four ( 25 % ) of 16 and three ( 17.65 % ) of 17 at 3 months , and two ( 12.50 % ) of 16 and six ( 35.29 % ) of 17 at 6 months , respectively . Dry eye was associated with level of preoperative myopia ( RR 0.88/each diopter , P = .04 ) , laser-calculated ablation depth ( RR 1.01/microm , P = 0.01 ) , and combined ablation depth and flap thickness ( RR 1.01/microm , P = 0.01 ) . CONCLUSIONS Dry eye occurs commonly after LASIK surgery in patients with no history of dry eye . The risk of developing dry eye is correlated with the degree of preoperative myopia and the depth of laser treatment PURPOSE Punctal occlusion using punctal plugs is very effective for the treatment of tear-deficient dry eye . We compared the newly marketed Flex Plug ( FP , Eagle Vision Co. , Ltd. ) and the Eagle Plug ( EP , Eagle Vision Co. , Ltd. ) . SUBJECTS AND METHODS The subjects were patients with severe tear-deficient dry eye who were treated in our dry eye clinic . FP plugs in 8 patients ( 9 eyes ) and EP plugs in 29 patients ( 35 eyes ) were compared during over 4 months of observation with regard to the time until extrusion and the possibility for re-insertion of the plugs . RESULTS During the 4 months after insertion of the plugs , the EP plugs were extruded from 35 of 51 puncta ( 68.6 % ) and the FP plugs were extruded from 4 of 13 puncta ( 30.8 % ) . In the 35 EP extrusions and in the 4 FP extrusions , re-insertion was possible . The time period until extrusion was longer for FP than for EP . In all cases , for both EP and FP , pyogenic granuloma was not observed . DISCUSSION The extrusion rate for EP plugs was much greater than for FP plugs ( 68.6 % to 30.8 % ) . Pyogenic granuloma was not observed in any instance for both types of punctal plugs PURPOSE To study the prevalence of dry eye in a hospital-based population and to evaluate the various risk factors attributable to dry eye . MATERIAL S AND METHODS In this cross-sectional study , 500 patients above 20 years of age were screened r and omly for dry eye . A 13-point question naire , Lissamine Green test , Tear film break-up time ( TBUT ) , Schirmer 's test and presence of str and s/filaments were used to diagnose dry eye . The diagnosis was made when at least three of the tests were positive . The role of air pollution , sunlight , excessive winds , smoking , drugs and refractive status as dry eye risk factors was assessed . RESULTS Ninety-two ( 18.4 % ) patients had dry eye . Dry eye prevalence was maximum in those above 70 years of age ( 36.1 % ) followed by the age group 31 - 40 years ( 20 % ) . It was significantly higher ( P = 0.024 ) in females ( 22.8 % ) than in males ( 14.9 % ) , more common in rural residents ( 19.6 % ) than in urban ( 17.5 % ) and highest among farmers/labourers ( 25.3 % ) . A 2.15 fold increase was found in the odds for dry eye in those exposed to excessive wind , 1.91 fold to sunlight exposure , 1.42 to smoking , 1.38 to air pollution and 2.04 for persons on drugs . Dry eye prevalence was 14 % in emmetropes , 16.8 % in myopes and 22.9 % in hypermetropes . It was 15.6 % in those with corrected and 25.3 % in those with uncorrected refractive errors . CONCLUSION Dry eye is an under-diagnosed ocular disorder . Reduction in the modifiable risk factors of dry eye is essential to reduce its prevalence PURPOSE To evaluate the efficacy of a thermosensitive atelocollagen punctal plug in the treatment of dry eye disease . DESIGN Prospect i ve observational case series . METHODS The thermosensitive atelocollagen punctal plug was warmed at 37 C , 39 C , 41 C , and 43 C to evaluate the appropriate temperature and time for solidification . Dry eye patients were divided into 2 groups according to the preparation method of the atelocollagen punctal plug . In the conventional implantation group , atelocollagen gel was kept at room temperature for 15 minutes before implantation ( 27 eyes of 14 patients ) . In the preheating group , atelocollagen was warmed at 41 C for 8 minutes before implantation ( 23 eyes of 13 dry eye patients ) . Strip meniscometry , vital stainings , tear film break-up time ( BUT ) , and symptom scores were evaluated before and 1 month after plug implantation . RESULTS In vitro experiments revealed that heating at 41 C for 8 minutes was sufficient to solidify the gel . The mean fluorescein score in the conventional implantation group significantly improved after treatment ( before , 3.5 ± 2.3 points ; after , 2.5 ± 0.9 points , P < .05 ) . In the preheating group , the mean fluorescein score ( before , 3.7 ± 1.7 points ; after , 1.5 ± 1.2 points ) , strip meniscometry ( before , 0.6 ± 0.7 mm ; after , 1.1 ± 0.3 mm ) , BUT ( before , 3.2 ± 0.7 seconds ; after , 4.8 ± 1.0 seconds ) , and visual analog scale scores ( before , 6.6 ± 1.5 points ; after , 4.1 ± 0.9 points ) significantly improved after treatment ( P < .05 ) . CONCLUSION The thermosensitive atelocollagen punctal plug was effective for dry eye treatment . The preheating method was found to be useful to strengthen the efficacy of the thermosensitive atelocollagen punctal plug OBJECTIVE To compare the efficacy and safety of cyclosporin A ( [ CsA ] 0.05 % and 0.1 % ophthalmic emulsions ) to vehicle in patients with moderate to severe dry eye disease . DESIGN Multicenter , r and omized , double-masked , parallel-group , 6-month , vehicle-controlled . PARTICIPANTS A total of 877 patients with defined moderate to severe dry eye disease ( 292 to 293 in each treatment group ) . METHODS Two identical clinical trials ; patients were treated twice daily with either CsA , 0.05 % or 0.1 % , or vehicle . The results of these two trials were combined for analysis . MAIN OUTCOME MEASURES EFFICACY corneal and interpalpebral dye staining , Schirmer tear test ( with and without anesthesia ) , tear break-up time , Ocular Surface Disease Index ( OSDI ) , facial expression , patient subjective rating scale , symptoms of dry eye , investigator 's evaluation of global response to treatment , treatment success , and daily use of artificial tears . SAFETY occurrence of adverse events , best-corrected visual acuity , intraocular pressure , biomicroscopy , and blood trough CsA concentrations . RESULTS Treatment with CsA , 0.05 % or 0.1 % , gave significantly ( P < or = 0.05 ) greater improvements than vehicle in two objective signs of dry eye disease ( corneal staining and categorized Schirmer values ) . CsA 0.05 % treatment also gave significantly greater improvements ( P < 0.05 ) in three subjective measures of dry eye disease ( blurred vision , need for concomitant artificial tears , and the physician 's evaluation of global response to treatment ) . There was no dose-response effect . Both CsA treatments exhibited an excellent safety profile , and there were no significant topical or systemic adverse safety findings . CONCLUSIONS The novel ophthalmic formulations CsA 0.05 % and 0.1 % were safe and effective in the treatment of moderate to severe dry eye disease yielding improvements in both objective and subjective measures . Topical CsA represents a new pharmacologically based treatment for dry eye disease that may provide significant patient benefits Purpose . To determine whether canalicular occlusion with collagen and silicone pl Output:	Although the investigators of the individual trials concluded that punctal plugs are an effective means for treating dry eye signs and symptoms , the evidence in this systematic review suggests that improvements in symptoms and commonly tested dry eye signs are inconclusive . Although punctal plugs are believed to be relatively safe , their use is commonly associated with epiphora and , less commonly , with inflammatory conditions such as dacryocystitis
MS22249	*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: Amyotrophic Lateral Sclerosis ( ALS ) is a rapidly progressive neurodegenerative disorder with fatal prognosis . Cellular therapy has been studied for ALS in various animal models and these advances have highlighted its potential to be a treatment modality . This is a retrospective controlled cohort study of total 57 patients . Out of these , 37 patients underwent autologous bone marrow mononuclear cell transplantation in addition to st and ard rehabilitation and Riluzole . Control group consisted of 20 patients who did not receive cell transplantation . The survival duration since the onset of the disease for both the groups was computed using a Kaplan-Meier Survival analysis and compared using log-rank test . Effect of age at onset , type of onset and lithium on survival duration in the intervention group was analyzed . Mean survival duration of patients in intervention group was 87.76 months which was higher than the control group mean survival duration of 57.38 months . Survival duration was significantly ( p = 0.039 ) higher in people with the onset of the disease below 50 years of age . Limb onset and lithium also showed positive influence on the survival duration . Mean survival duration of the intervention group was also higher than the survival duration of ALS patients in previous epidemiological studies . In addition to the st and ard treatment with Riluzole , early intervention with combination of BMMNCs transplantation and Lithium may have a positive effect on the survival duration in ALS . Prospect i ve r and omized controlled studies with a larger sample size and rigorous methodology are required for conclusive findings Amyotrophic lateral sclerosis ( ALS ) is the most common adult onset motor neuron disease . The etiology and pathogenic mechanisms of the disease remain unknown , and there is no effective treatment . Here we show that intrathecal transplantation of human motor neurons derived from neural stem cells ( NSCs ) in spinal cord of the SOD1G93A mouse ALS model delayed disease onset and extended life span of the animals . When HB1.F3.Olig2 ( F3.Olig2 ) cells , stable immortalized human NSCs encoding the human Olig2 gene , were treated with sonic hedgehog ( Shh ) protein for 5–7 days , the cells expressed motor neuron cell type-specific phenotypes Hb9 , Isl-1 and choline acetyltransferase ( ChAT ) . These F3.Olig2-Shh human motor neurons were transplanted intrathecally in L5–L6 spinal cord of SOD1G93A mice , and at 4 weeks post-transplantation , transplanted F3.Olig2-Shh motor neurons expressing the neuronal phenotype markers NF , MAP2 , Hb9 , and ChAT were found in the ventral horn of the spinal cord . Onset of clinical signs in ALS mice with F3.Olig2-Shh motor neuron implants was delayed for 7 days and life span of animals was significantly extended by 20 days . Our results indicate that this treatment modality of intrathecal transplantation of human motor neurons derived from NSCs might be of value in the treatment of ALS patients without significant adverse effects OBJECTIVE To evaluate the feasibility , safety , and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells ( MSCs ) ( also called mesenchymal stromal cells ) in patients with multiple sclerosis ( MS ) and amyotrophic lateral sclerosis ( ALS ) . DESIGN A phase 1/2 open-safety clinical trial . Patients Fifteen patients with MS ( mean [ SD ] Exp and ed Disability Status Scale [ EDSS ] score , 6.7 [ 1.0 ] ) and 19 with ALS ( mean [ SD ] Amyotrophic Lateral Sclerosis Functional Rating Scale [ ALSFRS ] score , 20.8 [ 8.0 ] ) were enrolled . Intervention After culture , a mean ( SD ) of 63.2 × 10(6 ) ( 2.5 × 10(6 ) ) MSCs was injected intrathecally ( n = 34 ) and intravenously ( n = 14 ) . In 9 cases , MSCs were magnetically labeled with the superparamagnetic iron oxide ferumoxides ( Feridex ) . MAIN OUTCOME MEASURES The main outcome measure was the recording of side effects . Follow-up ( ≤25 months ) included adverse events evaluation , neurological disability assessment by means of the EDSS , magnetic resonance imaging to exclude unexpected pathologies and track the labeled stem cells , and immunological tests to assess the short-term immunomodulatory effects of MSC transplantation . RESULTS Twenty-one patients had injection-related adverse effects consisting of transient fever , and 15 reported headache . No major adverse effects were reported during follow-up . The mean ALSFRS score remained stable during the first 6 months of observation , whereas the mean ( SD ) EDSS score improved from 6.7 ( 1.0 ) to 5.9 ( 1.6 ) . Magnetic resonance imaging visualized the MSCs in the occipital horns of the ventricles , indicating the possible migration of ferumoxides-labeled cells in the meninges , subarachnoid space , and spinal cord . Immunological analysis revealed an increase in the proportion of CD4(+)CD25(+ ) regulatory T cells , a decrease in the proliferative responses of lymphocytes , and the expression of CD40(+ ) , CD83(+ ) , CD86(+ ) , and HLA-DR on myeloid dendritic cells at 24 hours after MSC transplantation . CONCLUSION Transplantation of MSCs in patients with MS and ALS is a clinical ly feasible and relatively safe procedure and induces immediate immunomodulatory effects . Trial Registration clinical trials.gov Identifier : NCT00781872 BACKGROUND The first US Food and Drug Administration approved clinical trial for a stem cell-based treatment of amyotrophic lateral sclerosis has now been completed . OBJECTIVE Primary aims assessed the safety of a direct microinjection-based technique and the toxicity of neural stem cell transplantation to the ventral horn of the cervical and thoracolumbar spinal cord . Results from thoracolumbar-only microinjection groups have been previously published . Cervical and cervical plus thoracolumbar microinjection group perioperative morbidity results are presented . METHODS Eighteen microinjection procedures ( n = 12 thoracolumbar [ T10/11 ] , n = 6 cervical [ C3 - 5 ] ) delivered NSI-566RSC ( Neuralstem , Inc ) , a human neural stem cell , to 15 patients in 5 cohorts . Each injection series comprised 5 injections of 10 μL at 4-mm intervals . The patients in group A ( n = 6 ) were nonambulatory and received unilateral ( n = 3 ) or bilateral ( n = 3 ) thoracolumbar microinjections . The patients in groups B to E were ambulatory and received either unilateral ( group B , n = 3 ) or bilateral ( group C , n = 3 ) thoracolumbar microinjection . Group D and E patients received unilateral cervical ( group D , n = 3 ) or cervical plus bilateral thoracolumbar microinjection ( group E , n = 3 ) . RESULTS Unilateral cervical ( group D , n = 3 ) and cervical plus thoracolumbar ( group E , n = 3 ) microinjections to the ventral horn have been completed in ambulatory patients . One patient developed a postoperative kyphotic deformity prompting completion of a laminoplasty in subsequent patients . Another required reoperation for wound dehiscence and infection . The solitary patient with bulbar amyotrophic lateral sclerosis required perioperative reintubation . CONCLUSION Delivery of a cellular payload to the cervical or thoracolumbar spinal cord was well tolerated by the spinal cord in this vulnerable population . This encouraging finding supports consideration of this delivery approach for neurodegenerative , oncologic , and traumatic spinal cord afflictions Advances in stem cell biology have generated intense interest in the prospect of transplanting stem cells into the nervous system for the treatment of neurodegenerative diseases . Here , we report the results of an ongoing phase I trial of intraspinal injections of fetal-derived neural stems cells in patients with amyotrophic lateral sclerosis ( ALS ) . This is a first-in-human clinical trial with the goal of assessing the safety and tolerability of the surgical procedure , the introduction of stem cells into the spinal cord , and the use of immunosuppressant drugs in this patient population . Twelve patients received either five unilateral or five bilateral ( 10 total ) injections into the lumbar spinal cord at a dose of 100,000 cells per injection . All patients tolerated the treatment without any long-term complications related to either the surgical procedure or the implantation of stem cells . Clinical assessment s ranging from 6 to 18 months after transplantation demonstrated no evidence of acceleration of disease progression due to the intervention . One patient has shown improvement in his clinical status , although these data must be interpreted with caution since this trial was neither design ed nor powered to measure treatment efficacy . These results allow us to report success in achieving the phase I goal of demonstrating safety of this therapeutic approach . Based on these positive results , we can now advance this trial by testing intraspinal injections into the cervical spinal cord , with the goal of protecting motor neuron pools affecting respiratory function , which may prolong life for patients with ALS BACKGROUND AIMS Mesenchymal stem cells/marrow stromal cells ( MSC ) represent a promising tool for stem cell-based clinical trials in amyotrophic lateral sclerosis ( ALS ) . We present the results of long-term monitoring of 19 ALS patients enrolled in two phase I clinical trials of autologous MSC transplantation . METHODS Nineteen patients ( 11 male and eightfemale ) with ALS were enrolled in two consecutive phase I clinical trials . The patients were followed-up for 6 - 9 months and then treated with autologous MSC isolated from bone marrow and implanted into the dorsal spinal cord with a surgical procedure . The patients were monitored regularly before and after transplantation with clinical , psychological and neuroradiologic assessment s every 3 months , at the tertiary referral ALS center in Novara ( Italy ) , until death . RESULTS Follow-up brain magnetic resonance imaging ( MRI ) revealed no structural changes ( including tumor formation ) relative to the baseline throughout the follow-up . There was no deterioration in the psychosocial status and all patients coped well . No clear clinical benefits were detected in these patients but the recruitment and selection of appropriate patients into larger trials will be needed to test the efficacy of the treatment . CONCLUSIONS This study is the first to show the safety of MSC transplantation in the central nervous system during a follow-up of nearly 9 years , and is in support of applying MSC-based cellular clinical trials to neurodegenerative disorders BACKGROUND AIMS Amyotrophic lateral sclerosis ( ALS ) is characterized by the selective death of motor neurons . CD133(+ ) stem cells are known to have the capacity to differentiate into neural lineages . Stem cells may provide an alternative treatment for ALS and other neurodegenerative diseases . METHODS Five men and five women ( aged 38 - 62 years ) with confirmed ALS were included in this study . Our institutional ethics and research committees approved the protocol . After informed consent was obtained , patients underwent Hidrogen-Magnetic Resonance Imaging ( H-MRI ) spectroscopy and were given scores according to an ALS functional rating scale , Medical Research Council power muscle scale and daily living activities . Bone marrow was stimulated with 300 microg filgrastim subcutaneously daily for 3 days . Peripheral blood mononuclear cells were obtained after admission by leukapheresis . The cell suspension was conjugated with anti-human CD133 superparamagnetic microbeads , and linked cells were isolated in a magnetic field . The isolated cells ( 2.5 - 7.5x10(5 ) ) were resuspended in 300 microL of the patient 's cerebrospinal fluid , and implanted in motor cortexes using a Hamilton syringe . Ten patients with confirmed ALS without transplantation were used as a control group . Patients were followed up for a period of 1 year . RESULTS The autologous transplantation of CD133(+ ) stem cells into the frontal motor cortex is a safe and well-tolerated procedure in ALS patients . The survival of treated patients was statistically higher ( P=0.01 ) than untreated control patients . CONCLUSIONS Stem-cell transplantation in the motor cortex delays ALS progression and improves quality of life BACKGROUND Amyotrophic lateral sclerosis ( ALS ) is a fatal neurodegenerative disorder characterized by progressive loss of spinal cord and cortical motoneurons . Despite improved underst and ing of the mechanisms underlying ALS , in clinical practice the management of ALS remains essentially supportive and focused on symptom relief . However , over the past few years stem cell research has exp and ed greatly as a tool for developing potential new therapies for treating incurable neurodegenerative diseases . METHODS Thirteen patients with sporadic amyotrophic lateral sclerosis ( SALS ) were included in this study , and bone marrow (BM)-derived hematopoietic progenitor stem cells were used . We selected patients with bulbar involvement and severe loss of movement . Our aim was to put the stem cells into the end of the brain stem and at the beginning of the spinal cord because the blood-brain barrier is intact in ALS and this region was the most Output:	In contrast , the number of clinical studies is still insufficient to assess their effectiveness , and these studies only demonstrate the absence of serious adverse events .
MS22250	*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 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 ] . ) BACKGROUND CONTEXT There is mounting evidence supporting the efficacy of bone morphogenetic protein ( BMP ) for both anterior interbody and posterolateral lumbar fusion . However , the relative cost of BMP remains an important concern for physicians , hospitals , and payers . PURPOSE The purpose of this study is to report on the perioperative costs for patients treated with rhBMP-2 as compared with an iliac crest bone graft ( ICBG ) supplemented with graft extenders . STUDY DESIGN / SETTING A prospect i ve r and omized controlled trial of rhBMP-2/ACS ( Infuse Bone Graft ; Medtronic Sofamor Danek , Memphis , TN ) versus ICBG+/-graft extender for lumbar spine fusion in patients over 60 years old . PATIENT SAMPLE One hundred two patients over 60 years old who required a posterolateral lumbar spine fusion r and omized between receiving rhBMP-2/ACS or ICBG . OUTCOME MEASURES All health-care costs over the first 3 months after surgery . METHODS As part of a prospect i ve r and omized trial of rhBMP-2/ACS versus ICBG+/-graft extender for lumbar spine fusion , all costs over the first 3 months after surgery were directly recorded by a dedicated coder funded by Norton Healthcare , Louisville , KY . A dedicated research nurse also followed all patients throughout their hospital stay and posthospitalization recovery to identify any adverse events or additional outpatient medical care . RESULTS Fifty patients received rhBMP-2/ACS and 52 underwent ICBG harvest . The mean hospital cost for the index admission was $ 24,736 for the rhBMP-2/ACS group and $ 21,138 for the ICBG group . Mean inpatient physician costs were $ 5,082 in the rhBMP-2/ACS group and $ 5,316 in the ICBG group . Costs associated with posthospital rehabilitation averaged $ 4,906 in the rhBMP-2/ACS group versus $ 6,820 in the ICBG group . Total payer expenditure for the 3-month perioperative period averaged $ 33,860 in the rhBMP-2/ACS group and $ 37,227 in the ICBG group . CONCLUSIONS The hospital carries the cost burden associated with the utilization of rhBMP-2/ACS . In contrast , the payer in a Diagnosis-Related Group ( DRG ) model achieves a net savings , based primarily on the decreased payment for inpatient rehabilitation , but also on decreased hospital reimbursement , physician costs , and other outpatient services PURPOSE We sought to determine whether percutaneous vertebroplasty -- which involves the injection of cement to stabilize a fractured vertebral body -- may be an effective treatment for vertebral fracture . METHODS We enrolled 79 consecutive osteoporotic patients ( 24 men and 55 women ; ages 51 to 93 years ) presenting with acute vertebral fractures . Clinical characteristics and bone densitometry were measured at baseline . Pain scores ( on a 0 to 25 scale ) and levels of function ( on a 0 to 20 scale ) were recorded on presentation , at 24 hours , at 6 weeks , and 6 to 12 months after therapy . RESULTS Fifty-five patients ( 70 % ) were treated by percutaneous vertebroplasty and 24 ( 30 % ) were treated by conservative therapy alone . They were followed for a mean of 215 days ( range , 57 to 399 days ) . The baseline clinical characteristics , bone densitometry , and fracture data were similar in the two groups . Twenty-four hours after vertebroplasty , there was a 53 % reduction in pain scores ( from 19 to 9 ; P = 0.0001 ) and a 29 % improvement in physical functioning ( from 14 to 18 ; P = 0.0001 ) , whereas pain scores and physical functioning remained unchanged at 24 hours in the patients treated conservatively ( both P = 0.0001 compared with the changes after percutaneous vertebroplasty ) . Thirteen patients ( 24 % ) treated by percutaneous vertebroplasty were able to cease all analgesia after 24 hours ( P = 0.0001 compared with none of the 24 patients treated conservatively ) . Clinical outcomes at 6 weeks and 6 to 12 months were similar in both groups . CONCLUSION When compared with conservative therapy , percutaneous vertebroplasty results in prompt pain relief and rapid rehabilitation . In experienced h and s , it is a safe and effective procedure for treating acute osteoporotic vertebral compression fractures BACKGROUND The management of degenerative spondylolisthesis associated with spinal stenosis remains controversial . Surgery is widely used and has recently been shown to be more effective than nonoperative treatment when the results were followed over two years . Questions remain regarding the long-term effects of surgical treatment compared with those of nonoperative treatment . METHODS Surgical c and i date s from thirteen centers with symptoms of at least twelve weeks ' duration as well as confirmatory imaging showing degenerative spondylolisthesis with spinal stenosis were offered enrollment in a r and omized cohort or observational cohort . Treatment consisted of st and ard decompressive laminectomy ( with or without fusion ) or usual nonoperative care . Primary outcome measures were the Short Form-36 ( SF-36 ) bodily pain and physical function scores and the modified Oswestry Disability Index at six weeks , three months , six months , and yearly up to four years . RESULTS In the r and omized cohort ( 304 patients enrolled ) , 66 % of those r and omized to receive surgery received it by four years whereas 54 % of those r and omized to receive nonoperative care received surgery by four years . In the observational cohort ( 303 patients enrolled ) , 97 % of those who chose surgery received it whereas 33 % of those who chose nonoperative care eventually received surgery . The intent-to-treat analysis of the r and omized cohort , which was limited by nonadherence to the assigned treatment , showed no significant differences in treatment outcomes between the operative and nonoperative groups at three or four years . An as-treated analysis combining the r and omized and observational cohorts that adjusted for potential confounders demonstrated that the clinical ly relevant advantages of surgery that had been previously reported through two years were maintained at four years , with treatment effects of 15.3 ( 95 % confidence interval , 11 to 19.7 ) for bodily pain , 18.9 ( 95 % confidence interval , 14.8 to 23 ) for physical function , and -14.3 ( 95 % confidence interval , -17.5 to -11.1 ) for the Oswestry Disability Index . Early advantages ( at two years ) of surgical treatment in terms of the secondary measures of bothersomeness of back and leg symptoms , overall satisfaction with current symptoms , and self-rated progress were also maintained at four years . CONCLUSIONS Compared with patients who are treated nonoperatively , patients in whom degenerative spondylolisthesis and associated spinal stenosis are treated surgically maintain substantially greater pain relief and improvement in function for four years OBJECTIVE To assess the safety and efficacy of percutaneous vertebroplasty for the treatment of acute osteoporotic vertebral fractures . DESIGN A prospect i ve , non-r and omised , " intention-to-treat " 2-year study . PATIENTS AND SETTING 126 consecutive patients ( 39 men and 87 women , aged 51 - 95 years ) with acute osteoporotic vertebral fractures presenting to St George Hospital from November 2000 to December 2002 . They comprised 88 patients treated by percutaneous vertebroplasty and 38 by conservative therapy . MAIN OUTCOME MEASURES Primary outcomes --changes in patients ' pain score and level of function recorded at 24 hours , 6 weeks , 6 - 12 months and 24 months after therapy . Secondary outcomes --occurrence of new clinical or radiological vertebral fractures and survival at 2 years . RESULTS Three minor complications ( fractured pedicle and psoas muscle haemorrhage ) occurred in the vertebroplasty group during the first year of the study . Outcomes in vertebroplasty-treated patients ( 60 % reduction in visual analogue pain scores from 20 to 8 ; P < 0.001 ) , a rapid return to normal function ( 29 % improvement in physical functioning from 14 to 18 ; P < 0.001 ) and lower rates of hospitalisation ( 43 % reduction in the mean number of hospital bed-days occupied ) were better than those treated conservatively ( P < 0.001 for the comparison of all variables at 24 hours ) . Lower pain scores persisted in the vertebroplasty-treated group at 6 weeks ( P < 0.001 ) , but no differences between the two groups were evident at 12 and 24 months . In the vertebroplasty-treated group compared with the control group , the rates of new vertebral fractures ( clinical ly and by radiographic assessment ) ( hazard ratio , 1.13 ; 95 % CI , 0.52 - 2.46 ; P = 0.76 ) and death ( hazard ratio , 1.07 ; 95 % CI , 0.42 - 2.76 ; P = 0.89 ) showed no significant difference . CONCLUSION The analgesic benefit of percutaneous vertebroplasty and the low complication rates suggest that it is a useful therapy for acute painful osteoporotic vertebral fractures PURPOSE To prospect ively assess the short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures ( VCF ) treated with percutaneous vertebroplasty ( PV ) compared with optimal pain medication ( OPM ) . METHODS R and omization of patients in 2 groups : treatment by PV or OPM . After 2 weeks , patients from the OPM arm could change therapy to PV . Patients were evaluated 1 day and 2 weeks after treatment . Visual analog score ( VAS ) for pain and analgesic use were assessed before , and 1 day and 2 weeks after start of treatment . Quality of Life Question naire of the European Foundation for Osteoporosis ( QUALEFFO ) and Rol and -Morris Disability ( RMD ) question naire scores were assessed before and 2 weeks after start of treatment . Follow-up scores in patients requesting PV treatment after 2 weeks OPM treatment were compared with scores during their OPM period . RESULTS Eighteen patients treated with PV compared with 16 patients treated with OPM had significantly better VAS and used less analgesics 1 day after treatment . Two weeks after treatment , the mean VAS was less but not significantly different in patients treated with OPM , whereas these patients used significantly less analgesics and had better QUALEFFO and RMD scores . Scores in the PV arm were influenced by occurrence of new VCF in 2 patients . After 2 weeks OPM , 14 patients requested PV treatment . All scores Output:	Nonetheless the clinical question remains : is immediate routine lumbar spine imaging more effective than usual care without imaging in patients with low back pain and no suggestion of “ red flags . ”
MS22251	*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 Prehospital resuscitation for patients with major trauma emphasizes a load- and -go principle . For traumatic cardiac arrest ( TCA ) patients , the administration of vasopressors remains under debate . This study evaluated the effectiveness of epinephrine in the prehospital setting for patients with TCA . Methods We conducted a retrospective cohort study using a prospect ively collected registry for out-of-hospital cardiac arrest in Taipei . Enrollees were ≥18 years of age with TCA . Patients with signs of obvious death like decapitation or rigor mortis were excluded . Patients were grouped according to prehospital administration , or lack thereof , of epinephrine . Outcomes were sustained ( ≥2 h ) recovery of spontaneous circulation ( ROSC ) and survival to discharge . A subgroup analysis was performed by stratified total prehospital time . Results From June 1 2010 to May 31 2013 , 514 cases were enrolled . Epinephrine was administered in 43 ( 8.4 % ) cases . Among all patients , sustained ROSC and survival to discharge was 101 ( 19.6 % ) and 20 ( 3.9 % ) , respectively . The epinephrine group versus the non-epinephrine group had higher sustained ROSC ( 41.9 % vs. 17.6 % , p < 0.01 ) and survival to discharge ( 14.0 % vs. 3.0 % , p < 0.01 ) . The adjusted odds ratios ( ORs ) of epinephrine effect were 2.24 ( 95 % confidence interval ( CI ) 1.05 - 4.81 ) on sustained ROSC , and 2.94 ( 95 % CI 0.85 - 10.15 ) on survival to discharge . Subgroup analysis showed increased ORs of epinephrine effect on sustained ROSC with a longer prehospital time . Conclusion Among adult patients with TCA in an Asian metropolitan area , administration of epinephrine in the prehospital setting was associated with increased short-term survival , especially for those with a longer prehospital time Objective : To assess whether intermittent impedance of inspiratory gas exchange improves hemodynamic parameters , 48-hr survival , and neurologic outcome in a swine model of asphyxial cardiac arrest treated with active compression-decompression cardiopulmonary resuscitation . Design : Prospect i ve , r and omized , double-blind study . Setting : Laboratory investigation . Subjects : Thirty healthy L and race/Large-White piglets of both sexes , aged 10 to 15 wks , whose average weight was 19 ± 2 kg . Interventions : At approximately 7 mins following endotracheal tube clamping , ventricular fibrillation was induced and remained untreated for another 8 mins . Before initiation of cardiopulmonary resuscitation , animals were r and omly assigned to either receive active compression-decompression cardiopulmonary resuscitation plus a sham impedance threshold device ( control group , n = 15 ) , or active compression-decompression cardiopulmonary resuscitation plus an active impedance threshold device ( experimental group , n = 15 ) . Electrical defibrillation was attempted every 2 mins until return of spontaneous circulation or asystole . Measurements and Main Results : Return of spontaneous circulation was observed in six ( 40 % ) animals treated with the sham valve and 14 ( 93.3 % ) animals treated with the active valve ( p = .005 , odds ratio 21.0 , 95 % confidence interval 2.16–204.6 ) . Neuron-specific enolase and S-100 levels increased in the ensuing 4 hrs post resuscitation in both groups , but they were significantly elevated in animals treated with the sham valve ( p < .01 ) . At 48 hrs , neurologic alertness score was significantly better in animals treated with the active valve ( 79.1 ± 18.7 vs. 50 ± 10 , p < .05 ) and was strongly negatively correlated with 1- and 4-hr postresuscitation neuron-specific enolase ( r = −.86 , p < .001 and r = −.87 , p < .001 , respectively ) and S-100 ( r = −.77 , p < .001 and r = −0.8 , p = .001 ) values . Conclusions : In this model of asphyxial cardiac arrest , intermittent airway occlusion with the impedance threshold device during the decompression phase of active compression-decompression cardiopulmonary resuscitation significantly improved hemodynamic parameters , 24- and 48-hr survival , and neurologic outcome evaluated both with clinical and biochemical parameters ( neuron-specific enolase , S-100 ) Abstract While therapeutic hypothermia improves the outcomes of individuals in cardiac arrest , the hemodynamic responses and mechanisms which underlie hypothermia-induced cardioprotection are not fully understood . Therefore , we investigated the mechanism by which induced hypothermia preserves cardiac function and protects against mitochondrial damage following cardiac arrest . Cardiac arrest was induced in adult male Wistar rats by asphyxiation for 8.5 min . Following resuscitation , the animals were r and omly assigned to a hypothermia ( 32 ° C ) or normothermia ( 37 ° C ) group . Monitoring results showed that cardiac output at the fourth hour after resuscitation was significantly better in rats treated with hypothermia when compared to rats treated with normothermia ( P < 0.01 ) . Examinations by transmission electron microscopy showed that mitochondria in the left ventricle of rats in the hypothermia group were significantly less swollen compared to such mitochondria in the normothermia group ( P < 0.001 ) . Additionally , opening of mitochondrial permeability transition pores occurred less frequently in the hypothermic group . While complex I/III activity in the electron transport reaction was damaged after cardiac arrest and resuscitation , the degree of injury was ameliorated by hypothermia treatment ( P < 0.05 ) . The amount of STAT-3 phosphorylated at tyrosine 705 and its expression in mitochondria were significantly higher under hypothermia treatment compared to normothermia treatment . In vitro studies showed that inhibition STAT-3 activation abolished the ability of hypothermia to protect H9C2 cardiomyocytes against injury produced by simulated ischemia and reperfusion . Therapeutic hypothermia treatment can ameliorate cardiac dysfunction and help preserve both mitochondrial integrity and electron transport activity BACKGROUND Previous research has demonstrated significant relationships between peri-shock pause and survival to discharge from out-of-hospital shockable cardiac arrest ( OHCA ) . OBJECTIVE To determine the impact of peri-shock pause on survival from OHCA during the ROC PRIMED r and omized controlled trial . METHODS We included patients in the ROC PRIMED trial who suffered OHCA between June 2007 and November 2009 , presented with a shockable rhythm and had CPR process data for at least one shock . We used multivariable logistic regression to determine the association between peri-shock pause duration and survival to hospital discharge . RESULTS Among 2006 patients studied , the median ( IQR ) shock pause duration was : pre-shock pause 15s ( 8 , 22 ) ; post-shock pause 6s ( 4 , 9 ) ; and peri-shock pause 22.0 s ( 14 , 31 ) . After adjusting for Utstein predictors of survival as well as CPR quality measures , the odds of survival to hospital discharge were significantly higher for patients with pre-shock pause < 10s ( OR : 1.52 , 95 % CI : 1.09 , 2.11 ) and peri-shock pause < 20s ( OR : 1.82 , 95 % CI : 1.17 , 2.85 ) when compared to patients with pre-shock pause ≥ 20s and peri-shock pause ≥ 40s . Post-shock pause was not significantly associated with survival to hospital discharge . Results for neurologically intact survival ( Modified Rankin Score ≤ 3 ) were similar to our primary outcome . CONCLUSIONS In patients with cardiac arrest presenting in a shockable rhythm during the ROC PRIMED trial , shorter pre- and peri-shock pauses were significantly associated with higher odds of survival . Future cardiopulmonary education and technology should focus on minimizing all peri-shock pauses IMPORTANCE It is unclear whether advanced airway management such as endotracheal intubation or use of supraglottic airway devices in the prehospital setting improves outcomes following out-of-hospital cardiac arrest ( OHCA ) compared with conventional bag-valve-mask ventilation . OBJECTIVE To test the hypothesis that prehospital advanced airway management is associated with favorable outcome after adult OHCA . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , nationwide , population -based study ( All-Japan Utstein Registry ) involving 649,654 consecutive adult patients in Japan who had an OHCA and in whom resuscitation was attempted by emergency responders with subsequent transport to medical institutions from January 2005 through December 2010 . MAIN OUTCOME MEASURES Favorable neurological outcome 1 month after an OHCA , defined as cerebral performance category 1 or 2 . RESULTS Of the eligible 649,359 patients with OHCA , 367,837 ( 57 % ) underwent bag-valve-mask ventilation and 281,522 ( 43 % ) advanced airway management , including 41,972 ( 6 % ) with endotracheal intubation and 239,550 ( 37 % ) with use of supraglottic airways . In the full cohort , the advanced airway group incurred a lower rate of favorable neurological outcome compared with the bag-valve-mask group ( 1.1 % vs 2.9 % ; odds ratio [ OR ] , 0.38 ; 95 % CI , 0.36 - 0.39 ) . In multivariable logistic regression , advanced airway management had an OR for favorable neurological outcome of 0.38 ( 95 % CI , 0.37 - 0.40 ) after adjusting for age , sex , etiology of arrest , first documented rhythm , witnessed status , type of byst and er cardiopulmonary resuscitation , use of public access automated external defibrillator , epinephrine administration , and time intervals . Similarly , the odds of neurologically favorable survival were significantly lower both for endotracheal intubation ( adjusted OR , 0.41 ; 95 % CI , 0.37 - 0.45 ) and for supraglottic airways ( adjusted OR , 0.38 ; 95 % CI , 0.36 - 0.40 ) . In a propensity score-matched cohort ( 357,228 patients ) , the adjusted odds of neurologically favorable survival were significantly lower both for endotracheal intubation ( adjusted OR , 0.45 ; 95 % CI , 0.37 - 0.55 ) and for use of supraglottic airways ( adjusted OR , 0.36 ; 95 % CI , 0.33 - 0.39 ) . Both endotracheal intubation and use of supraglottic airways were similarly associated with decreased odds of neurologically favorable survival . CONCLUSION AND RELEVANCE Among adult patients with OHCA , any type of advanced airway management was independently associated with decreased odds of neurologically favorable survival compared with conventional bag-valve-mask ventilation OBJECT To examine the efficacy of a new method of cardiac resuscitation , active compression-decompression cardiopulmonary resuscitation ( ACD CPR ) , in prehospital cardiac arrest . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Physician-manned Mobile Intensive Care Unit ( MICU ) of a university hospital , serving a population of 200,000 . PARTICIPANTS Adult patients with prehospital nontraumatic cardiac arrest treated by the MICU . INTERVENTIONS Patients were r and omized to st and ard chest compression according to American Heart Association ( AHA ) recommendations ( group 1 , 30 patients ) or to the new technique ( group 2 , 26 patients ) . ACD was performed by use of a h and -held suction device . In both groups , advanced life support was performed as recommended by the AHA . MEASUREMENTS AND MAIN RESULTS Rate of patients regaining a spontaneous circulation ( ROSC ) , hospital discharge rate , and mean carbon dioxide content during resuscitation were recorded . ROSC rates in groups 1 and 2 were 40 % and 38.5 % , respectively . Four patients ( 13.3 % ) in group 1 and three patients ( 11.5 % ) in group 2 were discharged ( group 1 v group 2 : n.s . ) . Anatomic conditions precluded the application of ACD CPR in 5 patients . The new technique was found to impose greater physical efforts than STD CPR . Capnography was performed in 23 patients ( mean value : STD CPR : 11.9 + /- 4.7 mmHg , ACD CPR : 13.7 + /- 4.9 mmHg [ n.s . ] ) . CONCLUSIONS ACD CPR did not improve , outcome and practical performance was complicated . Therefore , this technique should not be performed routinely , or without strict supervision in prehospital cardiac arrest Background —Active compression-decompression ( ACD ) CPR combined with an inspiratory imped Output:	There was also no significant difference in survival or neurologic outcome at hospital discharge between active compression-decompression resuscitation or impedance threshold device and st and ard cardiopulmonary resuscitation . The meta-regression indicated that this minimal effect might be modified by two important prognostic factors , that is , witnessed status and response time . After adjustment of these two factors , impedance threshold device appeared to improve return of spontaneous circulation , which could be further augmented by advanced airway use . Active compression-decompression resuscitation or impedance threshold device seemed not to improve return of spontaneous circulation in out-of-hospital cardiac arrest patients . The meta-regression indicated two probable prognostic factors causing this minimal effect .
MS22252	*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 Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease . There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border , historically a site of emerging antimalarial-drug resistance . METHODS In two open-label , r and omized trials , we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin , western Cambodia , and Wang Pha , northwestern Thail and : oral artesunate given at a dose of 2 mg per kilogram of body weight per day , for 7 days , and artesunate given at a dose of 4 mg per kilogram per day , for 3 days , followed by mefloquine at two doses totaling 25 mg per kilogram . We assessed in vitro and in vivo Plasmodium falciparum susceptibility , artesunate pharmacokinetics , and molecular markers of resistance . RESULTS We studied 40 patients in each of the two locations . The overall median parasite clearance times were 84 hours ( interquartile range , 60 to 96 ) in Pailin and 48 hours ( interquartile range , 36 to 66 ) in Wang Pha ( P<0.001 ) . Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients ( 30 % ) receiving artesunate monotherapy and 1 of 20 ( 5 % ) receiving artesunate-mefloquine therapy in Pailin , as compared with 2 of 20 ( 10 % ) and 1 of 20 ( 5 % ) , respectively , in Wang Pha ( P=0.31 ) . These markedly different parasitologic responses were not explained by differences in age , artesunate or dihydroartemisinin pharmacokinetics , results of isotopic in vitro sensitivity tests , or putative molecular correlates of P. falciparum drug resistance ( mutations or amplifications of the gene encoding a multidrug resistance protein [ PfMDR1 ] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [ PfSERCA ] ) . Adverse events were mild and did not differ significantly between the two treatment groups . CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thail and . Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing . Containment measures are urgently needed . ( Clinical Trials.gov number , NCT00493363 , and Current Controlled Trials number , IS RCT N64835265 . Output:	Experimental studies have shown that the virus can be transferred from contaminated h and s to food and surfaces .
MS22253	*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 contribution of acute respiratory infection control project within the framework of micro-credit-based development intervention in promoting maternal knowledge of ARIs in children was assessed . Data came from a cross-sectional survey of 2814 mothers of under 5-y-old children residing in 200 r and omly selected villages in five districts in Bangladesh . Findings revealed that the ARI control project had significant positive effects in raising knowledge of clinical signs and preventive measures . When ARI control project activities were integrated with the credit-based development initiative , maternal knowledge improved even further . The study concludes that the micro-credit programme can be a catalytic agent in raising health knowledge among poor women in developing countries BACKGROUND The Integrated Management of Childhood Illness ( IMCI ) strategy is design ed to address major causes of child mortality at the levels of community , health facility , and health system . We assessed the effectiveness of facility-based IMCI in rural Tanzania . METHODS We compared two districts with facility-based IMCI and two neighbouring comparison districts without IMCI , from 1997 to 2002 , in a non-r and omised study . We assessed quality of case-management for children 's illness , drug and vaccine availability , and supervision involving case-management , through a health-facility survey in 2000 . Household surveys were used to assess child-health indicators in 1999 and 2002 . Survival of children was tracked through demographic surveillance over a predefined 2-year period from mid 2000 . Further information on context ual factors was gathered through interviews and record review . The economic cost of health care for children in IMCI and comparison districts was estimated through interviews and record review at national , district , facility , and household levels . FINDINGS During the IMCI phase-in period , mortality rates in children under 5 years old were almost identical in IMCI and comparison districts . Over the next 2 years , the mortality rate was 13 % lower in IMCI than in comparison districts ( 95 % CI -7 to 30 or 5 to 21 , depending on how adjustment is made for district-level clustering ) , with a rate difference of 3.8 fewer deaths per 1000 child-years . Context ual factors , such as use of mosquito nets , all favoured the comparison districts . Costs of children 's health care with IMCI were similar to or lower than those for case-management without IMCI . INTERPRETATION Our findings indicate that facility-based IMCI is good value for money , and support widespread implementation in the context of health-sector reform , basket funding , good facility access , and high utilisation of health facilities OBJECTIVES To characterize community health worker ( CHW ) performance using an algorithm for managing common childhood illnesses in Siaya District , Kenya , we conducted CHW evaluations in 1998 , 1999 , and 2001 . METHODS R and omly selected CHWs were observed managing sick outpatient and inpatient children at a hospital , and their management was compared with that of an expert clinician who used the algorithm . RESULTS One hundred , 108 , and 114 CHWs participated in the evaluations in 1998 , 1999 , and 2001 , respectively . The proportions of children treated " adequately " ( with an antibiotic , antimalarial , oral rehydration solution , or referral , depending on the child 's disease classifications ) were 57.8 % , 35.5 % , and 38.9 % , respectively , for children with a severe classification and 27.7 % , 77.3 % , and 74.3 % , respectively , for children with a moderate ( but not severe ) classification . CHWs adequately treated 90.5 % of malaria cases ( the most commonly encountered classification ) . CHWs often made mistakes assessing symptoms , classifying illnesses , and prescribing correct doses of medications . CONCLUSIONS Deficiencies were found in the management of sick children by CHWs , although care was not consistently poor . Key reasons for the deficiencies appear to be guideline complexity and inadequate clinical supervision ; other possible causes are discussed OBJECTIVE The objective of this study was to assess the effect of Integrated Management of Childhood Illness ( IMCI ) case management training on the use of antimicrobial drugs among health-care workers treating young children at first-level facilities . Antimicrobial drugs are an essential child-survival intervention . Ensuring that children younger than five who need these drugs receive them promptly and correctly can save their lives . Prescribing these drugs only when necessary and ensuring that those who receive them complete the full course can slow the development of antimicrobial resistance . METHODS Data collected through observation-based surveys in r and omly selected first-level health facilities in Brazil , Ug and a and the United Republic of Tanzania were statistically analysed . The surveys were carried out as part of the multi-country evaluation of IMCI effectiveness , cost and impact ( MCE ) . FINDINGS Results from three MCE sites show that children receiving care from health workers trained in IMCI are significantly more likely to receive correct prescriptions for antimicrobial drugs than those receiving care from workers not trained in IMCI . They are also more likely to receive the first dose of the drug before leaving the health facility , to have their caregiver advised how to administer the drug , and to have caregivers who are able to describe correctly how to give the drug at home as they leave the health facility . CONCLUSIONS IMCI case management training is an effective intervention to improve the rational use of antimicrobial drugs for sick children visiting first-level health facilities in low-income and middle-income countries BACKGROUND No satisfactory strategy for reducing high child mortality from malaria has yet been established in tropical Africa . We compared the effect on under-5 mortality of teaching mothers to promptly provide antimalarials to their sick children at home , with the present community health worker approach . METHODS Of 37 tabias ( cluster of villages ) in two districts with hyperendemic to holoendemic malaria , tabias reported to have the highest malaria morbidity were selected . A census was done which included a maternity history to determine under-5 mortality . Tabias ( population 70,506 ) were paired according to under-5 mortality rates . One tabia from each pair was allocated by r and om number to an intervention group and the other was allocated to the control group . In the intervention tabias , mother coordinators were trained to teach other local mothers to recognise symptoms of malaria in their children and to promptly give chloroquine . In both intervention and control tabias , all births and deaths of under-5s were recorded monthly . FINDINGS From January to December 1997 , 190 of 6383 ( 29.8 per 1000 ) children under-5 died in the intervention tabias compared with 366 of 7294 ( 50.2 per 1000 ) in the control tabias . Under-5 mortality was reduced by 40 % in the intervention localities ( 95 % CI from 29.2 - 50.6 ; paired t test , p<0.003 ) . For every third child who died , a structured verbal autopsy was undertaken to ascribe cause of mortality as consistent with malaria or possible malaria , or not consistent with malaria . Of the 190 verbal autopsies , 13 ( 19 % ) of 70 in the intervention tabias were consistent with possible malaria compared with 68 ( 57 % ) of 120 in the control tabias . INTERPRETATION A major reduction in under-5 mortality can be achieved in holoendemic malaria areas through training local mother coordinators to teach mothers to give under-5 children antimalarial drugs A survey was done in June 1983 in Saradidi , Kenya , one year after the inception of a community-based malaria control programme to determine if people were obtaining malaria treatment from volunteer village health helpers ( VHH 's ) chosen by the community . Ten of 36 villages were r and omly chosen . From these ten villages , 100 households were r and omly selected and 222 people ten years of age or more were interviewed ; 113 ( 50.9 % ) had a history of malaria in the previous two weeks and 82 ( 72.6 % of 113 ) had taken medicine for malaria in that period . Of these 82 , 51.2 % obtained drug from the VHH , 28 % purchased it from a shop , 12.2 % from a health facility , 4.9 % from family members and 3.7 % from a private practitioner or a shop outside Saradidi . Reasons given for not obtaining treatment from the VHH 's among the 40 people who went elsewhere for treatment included : the VHH was not at home when needed ( 35 % ) ; the VHH had no drugs ( 22.5 % ) ; the patient was too sick for the VHH to treat ( 10 % ) ; had drugs already in the home ( 10 % ) ; ' not registered ' with VHH ( 10 % ) ; VHH ' no good ' ( 7.5 % ) ; and more ' convenient ' to go elsewhere ( 5 % ) . Similar results found on question ing the mother were obtained for 103 children under nine years old in these households ; 67 ( 65.0 % ) children had a history of malaria in the previous two weeks and 59 ( 88.1 % ) of these 67 children had received antimalarial treatment . The VHH was the principal source of treatment ( 50.8 % of 59 ) , followed by health facilities ( 20.3 % ) and shops ( 18.6 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS Save the Children/USA in collaboration with the Ministry of Health of Mali has established over 300 village drug kits in southern Mali since 1996 . A cluster-r and omized trial was conducted between November 2001 and February 2002 in 10 health zones of Bougouni District to evaluate an intervention to ( i ) improve the skills of the village drug kit managers to counsel parents on correct home administration of chloroquine ( CQ ) , and ( ii ) increase the referral of sick children to community health centres ( CHC ) . Children 's carers were interviewed 5 d after the sale of CQ about knowledge of danger signs requiring referral , quality of counselling , administration of CQ , and referral . The intervention was associated with significant increases in knowledge of danger signs requiring referral , reported quality of counselling by the manger of the drug kit , and correct administration of CQ in the home . Parents reported that 42.1 % of children in the intervention group were referred to the CHC by the drug kit manager compared with 11.2 % in the comparison group ( odds ratio = 7.12 , 95 % CI 2.62 - 19.38 ) . CHC registers indicated that 87.0 % of referrals recorded in drug kit referral notebooks arrived at the health centre . Further research is needed to increase the effectiveness of the counselling and the community referral mechanism tested in this study In rural , malaria-endemic Burkina Faso , we evaluated the impact of the use of pre-packaged antimalarial drugs ( PPAM ) , by mothers in the home , on the progression of disease in children from uncomplicated fever to severe malaria . In each village of one province , a core group of opinion leaders ( mainly older mothers ) was trained in the management of uncomplicated malaria , including the administration of PPAM . Full courses of antimalarial ( chloroquine ) and antipyretic ( aspirin ) drugs were packaged in age-specific bags and made widely available through community health workers who were supplied through the existing drug distribution system . Drugs were sold under a cost-recovery scheme . Local schoolteachers conducted surveys in a r and om sample of 32 villages at the end of the high transmission seasons in 1998 and 1999 . Disease history and the treatment received were investigated for all children under the age of 6 years having suffered from a fever episode in the previous 4 weeks . ' Uncomplicated malaria ' was defined as every episode of fever and ' severe malaria ' as every episode of fever followed by convulsions or loss of consciousness . During the study period , 56%[95 % confidence interval ( CI ) 50 - 62 % ] of 3202 fever episodes in children under 6 years of age were treated promptly by mothers with the pre-packaged drugs made available by the study . A total of 59 % of children receiving PPAM were reported to have received the drugs over the prescribed 3-day period , while 52 % received the correct age-specific dose . PPAM use was similar among literate ( 61 % ) and non-literate mothers ( 55 % ) ( P = 0.08 ) . The overall reported risk of developing severe malaria was 8 % . This risk was lower in children treated with PPAM ( 5 % ) than in children not treated with PPAM ( 11 % ) ( risk ratio = 0.47 ; 95 % CI 0.37 , 0.60 ; P < 0.0001 ) . This estimate of the impact of PPAM was largely unchanged when account was taken of potential confounding by age , sex , maternal literacy status , year or village . Our findings support the view that , after appropriate training and with adequately packaged drugs made available , mothers can recognize and treat promptly and correctly malarial episodes in their children and , by doing so , reduce the incidence of severe disease BACKGROUND We report the preliminary findings from a continuing cluster r and omised evaluation of the Integrated Management of Childhood Illness ( IMCI ) strategy in Bangladesh . METHODS 20 first-level outpatient facilities in the Matlab sub-district and their catchment areas were r and omised to either IMCI or st and ard care . Surveys were done in households and in health facilities at baseline and were repeated about 2 years after implementation . Data on use of health facilities were recorded . IMCI implementation included health worker training , health systems support , and community level activities guided by formative research . F Output:	Of the seven models , that of CHW pneumonia case management ( Model 6 ) has the strongest evidence for an impact on mortality .
MS22254	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A classical treatment for chronic adult periodontitis consists of four to six consecutive sessions of scaling and root planing at a 1- to 2-week interval . Such a so-called " quadrant or sextant therapy " might result in a reinfection of a previously disinfected area by bacteria from an untreated region . The purpose of this study was to investigate , over an 8-month period , the clinical benefits of full-mouth disinfection within a 24-hour period in the control of chronic periodontitis . Ten adult patients with advanced chronic periodontitis were r and omly assigned to a test and a control group . The control group received the st and ard scheme of initial periodontal therapy , consisting of scaling and root planing of the four quadrants was performed within 24 hours and immediately followed by a thorough supra- and subgingival chlorhexidine application to limit any transfer of bacteria . The latter involved tongue brushing with a 1 % chlorhexidine gel for 60 seconds , mouthrinsing with a 0.2 % chlorhexidine solution twice for 60 seconds , repeated subgingival irrigation of all pockets with a 1 % chlorhexidine gel ( 3 times within 10 minutes ) , and mouthrinsing twice daily with a 0.2 % chlorhexidine solution during 2 weeks . In addition , both groups received thorough oral hygiene instructions . The plaque index , gingival index , probing depth , gingival recession , and bleeding on probing were recorded prior to professional cleaning and at 1 , 2 , 4 , and 8 months afterwards . Although the test group scored higher plaque indices than the control group , especially at months 2 and 4 , the gingival index and bleeding tendency showed similar improvements with time . However , when the gingival/plaque ratio was considered , the latter was lower in the test group at all follow-up visits . For pockets > or = 7 mm , full-mouth disinfection showed a significantly ( P = 0.01 ) higher reduction in probing depth at each follow-up visit with , at month 8 , a reduction of 4 mm ( from 8 mm to 4 mm ) , in comparison to 3 mm ( from 8 mm to 5 mm ) for the classical therapy . The increase in gingival recession in the full-mouth disinfection group remained below 0.7 mm , while in the control group it reached 1.9 mm after 8 months . This result ed in a gain of clinical attachment level of 3.7 mm for the test group versus 1.9 mm for the control group . A radiographical examination also indicated a superior improvement for the test group when compared to the control group . This pilot study suggests that a full-mouth disinfection in one day results in an improved clinical outcome in chronic periodontitis as compared to scalings per quadrant at 2-week intervals over several weeks A treatment for periodontal infections often consists of consecutive rootplanings ( per quadrant , at a 1- to 2-week interval ) , without a proper disinfection of the remaining intra-oral niches ( untreated pockets , tongue , saliva , mucosa and tonsils ) . Such an approach , could theoretically lead to a reinfection of previously-treated pockets . The present study aims to examine the effect of a full-mouth disinfection on the microbiota in the above-mentioned niches . Moreover , the clinical benefit of such an approach was investigated . 16 patients with severe periodontitis were r and omly allocated to a test and a control group . The patients from the control group were scaled and rootplaned , per quadrant , at 2-week intervals and obtained oral hygiene instructions . The patients from the test group received a full-mouth disinfection consisting of : scaling and rootplaning of all pockets in 2 visits within 24 h , in combination with tongue brushing with 1 % chlorhexidine gel for 1 min , mouth rinsing with a 0.2 % chlorhexidine solution for 2 min and subgingival irrigation of all pockets ( 3x in 10 min ) with 1 % chlorhexidine gel . Besides oral hygiene , the test group rinsed 2x daily with 0.2 % chlorhexidine and sprayed the tonsils with a 0.2 % chlorhexidine for 2 months . Plaque sample s ( pockets , tongue , mucosa and saliva ) were taken at baseline and after 2 and 4 months , and changes in probing depth , attachment level and bleeding on probing were reported . The full-mouth disinfection result ed in a statistically significant additional reduction/elimination of periodontopathogens , especially in the subgingival pockets , but also in the other niches . These microbiological improvements were reflected in a statistically-significant higher probing depth reduction and attachment gain in the test patients . These findings suggest that a disinfection of all intra-oral niches within a short time span leads to significant clinical and microbiological improvements for up to 4 months OBJECTIVES The beneficial effects of the one-stage , full-mouth disinfection remain controversial in the scientific literature . This might be due to the fact that an entire mouth disinfection with the use of antiseptics has been confused with a full-mouth scaling and root planing . This parallel , single blind RCT study aim ed to compare several full-mouth treatment strategies with each other . MATERIAL AND METHODS Seventy-one patients with moderate periodontitis were r and omly allocated to one of the following treatment strategies : scaling and root planing , quadrant by quadrant , at two-week intervals ( negative control , NC ) , full-mouth scaling and root planing within 2 consecutive days ( FRP ) , or three one-stage , full-mouth disinfection ( FM ) protocol s within 2 consecutive days applying antiseptics to all intra-oral niches for periopathogens using as antiseptics : chlorhexidine ( FMCHX ) for 2 months , amine fluoride/stannous fluoride for 2 months ( FMF ) , or chlorhexidine for 2 months followed by amine fluoride/stannous fluoride for another 6 months ( FMCHX+F ) . At baseline and after 2 , 4 , and 8 a series of periodontal parameters were recorded . RESULTS All treatment strategies result ed in significant ( p<0.05 ) improvements of all clinical parameters over the entire duration of the study . Inter-treatment differences were often encountered . The NC group nearly always showed significant smaller improvements than the two CHX groups . The differences between the FRP or FM groups , and the two CHX groups only sporadically reached a statistical significance . CONCLUSION These observations indicate that the benefits of the " OSFMD " protocol are partially due to the use of the antiseptics and partially to the completion of the therapy in a short time BACKGROUND / AIMS Recent studies reported significant additional clinical and microbiological improvements when severe adult periodontitis was treated by means of a " one-stage full-mouth " disinfection instead of a st and ard treatment strategy with consecutive root planings quadrant per quadrant . The one stage full-mouth disinfection procedure involves scaling and root planing of all pockets within 24 h in combination with an extensive application of chlorhexidine to all intra-oral niches such as periodontal pockets , tongue dorsum , tonsils ( chairside , and at home for 2 months ) . This study aims to examine the relative importance of the use of chlorhexidine in the one stage full-mouth disinfection protocol . METHODS Therefore , 3 groups of 12 patients each with advanced periodontitis were followed , both from a clinical and microbiological point of view , over a period of 8 months . The patients from the control group were scaled and root planed , quadrant per quadrant . at two-week intervals . The 2 other groups underwent a one stage full-mouth scaling and root planing ( all pockets within 24 h ) with ( Fdis ) or without ( FRp = full-mouth root planing ) the adjunctive use of chlorhexidine . At baseline and after 1 , 2 , 4 and 8 months , the following clinical parameters were recorded : plaque and gingivitis indices , probing depth , bleeding on probing and clinical attachment level . Microbiological sample s were taken from different intra-oral niches ( tongue , mucosa , saliva and pooled sample s from single- and multi-rooted teeth ) . The sample s were cultured on selective and non-selective media in order to evaluate the number of CFU/ml for the key-periodontopathogens . At baseline , an anonymous question naire was given to the patients to record the perception of each treatment ( post operative pain , fever , swelling etc . ) . RESULTS All 3 treatment strategies result ed in significant improvements for all clinical parameters , but the Fdis and FRp patients reacted always significantly more favourably than the control group , with an additional probing depth reduction of + /- 1.5 mm and an additional gain in attachment of + /- 2 mm ( for pockets > or = 7 mm ) . Also from a microbiological point of view both the FRp and Fdis patients showed additional improvements when compared to the control group , as well in the reduction of spirochetes and motile organisms as in the number of CFU/ml of the key-pathogens , especially when the subgingival plaque sample s were considered . The differences between FRp and Fdis patients were negligible . CONCLUSIONS These findings suggest that the benefits of a " one-stage full-mouth disinfection " in the treatment of patients suffering from severe adult periodontitis probably results from the full-mouth scaling and root planing within 24 h rather than the beneficial effect of chlorhexidine . The raise in body temperature the second day after the full-mouth scaling and root planing seems to indicate a Shwartzman reaction BACKGROUND The aim of the present study was to evaluate the effectiveness of non-surgical mechanical instrumentation at 2 different time intervals on short-term healing and to assess patient reactions following non-surgical periodontal therapy . METHODS The study population consisted of 100 patients with moderate periodontal disease . Patients were equally distributed into 2 groups , treated daily or weekly . The daily group received full-mouth daily scaling and root planing for 4 consecutive days . The weekly group was treated once a week for 4 weeks . All patients were asked for objective ( lymphadenopathy , aphthous stomatitis , and edema ) and subjective ( fatigue , pain , pruritus , burning sensation , and dentinalgia ) reactions . Clinical measurements of plaque index ( PI ) , gingival index ( GI ) , probing depth ( PD ) , bleeding on probing ( BOP ) , and gingival recession ( GR ) were taken at baseline and 3 months after treatment . All of the objective and subjective reactions were recorded after each treatment session . RESULTS The results of our study revealed a significant decrease in PI , GI , BOP , and PD measurements at the end of the third month , but no significant changes in GR . The incidence of subjective and objective reactions was higher in the daily treated group compared to those in the weekly group . Most of these complaints were observed after the third treatment session . CONCLUSIONS Within the limits of this study , no differences were observed between the study groups when the clinical parameters were evaluated . However , taking the subjective and objective reactions into consideration , the smallest time interval for non-surgical periodontal procedures might be 1 week BACKGROUND The aim of the present study was to evaluate the clinical effects of one-stage periodontal debridement with an ultrasonic instrument , associated with 0.5 % povidone (pvp)-iodine irrigation in patients with chronic periodontitis . METHODS Forty-five patients were r and omly assigned into three groups : the control group ( CG ) received quadrant root planing at 1-week intervals over four consecutive sessions ; the periodontal debridement plus pvp-iodine group ( PD-PIG ) received a 45-minute full-mouth debridement with an ultrasonic instrument , associated with 0.5 % pvp-iodine irrigation ; and the periodontal debridement group ( PDG ) received a 45-minute full-mouth periodontal debridement with an ultrasonic instrument , associated with NaCl irrigation . RESULTS At the 3-month evaluation , the mean probing depth ( PD ) reduction in CG was 2.51+/-0.52 mm , 2.53+/-0.50 mm in PD-PIG , and 2.58+/-0.60 mm in PDG ( P<0.05 ) . The clinical attachment level ( CAL ) analysis showed a statistically significant gain in all groups compared to baseline ( 1.87+/-0.56 mm [ CG ] , 1.94+/-0.70 mm [ PD-PIG ] , and 1.99+/-0.92 mm [ PDG ] ) . Intergroup analysis of PD and CAL at 1 and 3 months showed no differences ( P>0.05 ) . The N-benzoyl-L-arginine-p-nitroanilide ( BAPNA ) test showed a significant reduction in trypsin activity only during the first month ( P<0.05 ) ; at 3 months there were no differences compared to baseline ( P=0.80 ) . CONCLUSION This study provides no evidence that pvp-iodine is effective as an adjunct for one-stage periodontal debridement In a st and ard periodontal treatment strategy with consecutive root planings ( per quadrant at a one- to two-week interval ) , re-infection of a disinfected area might occur before completion of the treatment . This study examines , both clinical ly and microbiologically , whether a full-mouth disinfection within 24 hours significantly improves the outcome of periodontal treatment . Ten patients with advanced chronic periodontitis were r and omly allocated to a test and a control group . The patients from the control group received scalings and root planings as well as oral hygiene instructions per quadrant at two-week intervals . Full-mouth disinfection in the test group was sought by the removal of all plaque and calculus ( in two visits within 24 hours ) . In addition , at each of these visits , the tongue was brushed with a 1 % chlorhexidine gel for one min and the mouth rinsed with a 0.2 % chlorhexidine solution for two min . Furthermore , subgingival chlorhexidine ( 1 % ) irrigation was performed Output:	The primary outcome measure was tooth loss , secondary outcomes were reduction of probing depth , bleeding on probing and gain in probing attachment . All treatment modalities led to significant improvements in clinical parameters after a follow up of at least 3 months . No significant differences were observed for any of the outcome measures , when comparing FMS and control . AUTHORS ' CONCLUSIONS In patients with chronic periodontitis in moderately deep pockets slightly more favourable outcomes for pocket reduction and gain in probing attachment were found following FMD compared to control . However , these additional improvements were only modest and there was only a very limited number of studies available for comparison , thus limiting general conclusions about the clinical benefit of full-mouth disinfection
MS22255	*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 : Pain following spinal cord injury ( SCI ) is a therapeutic challenge . Only a few treatments have been assessed in r and omized , controlled trials . The primary objective of the present study was to examine the analgesic effect of ketamine and lidocaine in a group of patients with neuropathic pain below the level of spinal cord injury . We also wanted to assess sensory abnormalities to see if this could help us to identify responders and if treatments result ed in changes of sensibility Background Several lines of evidence suggest that neuropathic pain ( including Complex Regional Pain Syndrome [ CRPS ] I and CRPS II ) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons . This study sought to characterize the effects of intravenous lidocaine ( a sodium channel blocker ) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II . Methods This study used a r and omized , double-blind , placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia . Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week . A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1 , 2 , and 3 & mgr;g/ml . At baseline and at each plasma level , spontaneous and evoked pain scores and neurosensory testing within the painful area were measured . The neurosensory testing consisted of thermal thresholds , tactile thresholds and the area of allodynia to punctate , and stroking and thermal stimuli . Results Intravenous lidocaine and diphenhydramine had no significant effect on the cool , warm , or cold pain thresholds . However , lidocaine caused a significant elevation of the hot pain thresholds in the painful area . Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area . There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level . Conclusions This study demonstrates that intravenous lidocaine affects pain in response to cool stimuli more than mechanical pain in subjects with neuropathic pain . There is a lesser effect on spontaneous pain and pain induced by stroking stimuli and no effect on the pain induced by punctate stimuli & NA ; In a double‐blind controlled design , 7 patients with painful diabetic neuropathy received lidocaine 5 mg/kg or saline intravenously over a period of 30 min . Thermal sensibility quantified by thermotest was not affected by lidocaine . In 3 of the patients nociceptive flexion reflex thresholds could be determined . The threshold was increased by lidocaine and returned to pre‐infusion level within 10 days . Lidocaine also increased the threshold in 4 healthy subjects , but did not affect the Hoffmann reflex . These results suggest that lidocaine exerts its pain‐relieving effect on the spinal level in diabetic neuropathy In a few uncontrolled studies intravenous lidocaine has been used in the treatment of chronic pain . In a controlled study we used intravenous lidocaine in 18 patients with severe chronic pain states due to various but mainly neurological diseases . After the infusion of lidocaine 14 patients ( 78 % ) had significant pain relief ranging from 2 hours to 25 days . There was no significant effect of placebo infusion with isotonic saline . The mechanism of the pain relieving ability of intravenous lidocaine is unknown Background and Objectives Mexiletine is a sodium channel blocker that has been used for the treatment of a variety of neuropathic pain syndromes . A recent double-blinded placebo-controlled study concluded that it was ineffective in the treatment of allodynia associated with neuropathic pain . However , this study failed to achieve adequate plasma levels of mexiletine . This was a study in healthy volunteers that sought to push the drug to dose-limiting side effects and then evaluate the effects on human experimental pain . Methods Twelve healthy volunteers were studied using a r and omized , double-blind , placebo-controlled crossover study . The subjects were titrated to a maximum dose of 1,350 mg/d or dose-limiting side effects , whichever occurred first . At baseline and day 10 and 17 , neurosensory testing , train-of-three thermal pulses , and side-effect measurements were performed and on day 17 , intradermal capsaicin was injected on the volar aspect of the forearm and the pain and secondary hyperalgesia to von Frey hair , stroking , and thermal stimuli were measured . Results Peak plasma levels occurred on day 10 and were 0.36 ± 0.21 μg/mL. All subjects experienced dose-limiting side effects . The mean maximum tolerable daily dose achieved was 859 mg ( range , 300 to 1,350 mg ) . The side effects reported by the subjects included nausea , lightheadedness , muscle twitching and weakness , blurred vision , headache , tremors , difficulty concentrating , dysphoria , sedation , pruritis , and rash . These side effects occurred at an average daily dose of 993 mg ( range , 600 to 1,350 mg ) . Compared with placebo , mexiletine had no significant effects on any of the neurosensory thresholds and pain scores after intradermal capsaicin . There was a significant reduction in the area of secondary hyperalgesia to von Frey hair stimulation only . There was a significant correlation between plasma mexiletine level and flare response . Conclusions Mexiletine has minimal effects on human experimental pain . It is severely limited by side effects and tolerable doses seem to be void of effects on normal neurosensation and facilitated pain induced by capsaicin and thermal heat pulses Background and Objectives Mexiletine is an oral sodium channel antagonist that has been reported to be effective in a variety of neuropathic pain syndromes . However , recent reports question the efficacy of oral mexiletine in neuropathic pain . The objectives of this study were to examine the effect of oral mexiletine on pain , neurosensation , allodynia , and quality of life . Methods Twenty subjects suffering from neuropathic pain with prominent allodynia were enrolled in a r and omized placebo-controlled crossover study . Patients were titrated to a maximum dose of 900 mg/d or doselimiting side effects , whichever occurred first . At baseline and on days 0 , 4 , 7 , and 10 , the following tests were performed : ( 1 ) Quality of Life Question naires ; ( 2 ) pain scores ; ( 3 ) area of allodynia ; ( 4 ) side effects ; ( 5 ) neurosensory testing ; and ( 6 ) peak and trough plasma mexiletine levels . Results Peak plasma levels occurred on day 10 and were 0.54 μg/mL. There was no significant effect on any quality of life measurement . There was no significant effect on any neurosensory threshold or the area of allodynia . There was a significant effect of mexiletine on stroking-induced pain . There were no significant effects on any other pain score . Side effects were negligible . Conclusions At doses of up to 900 mg/d , mexiletine has minimal effects on pain and allodynia of neuropathic pain . However , side effects may preclude higher doses & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies & NA ; Ten patients with organic nerve injury causing chronic neuropathic pain were tested for the effects of intravenous lidocaine versus saline upon psychophysical somatosensory variables . The variables assessed were the subjective magnitude of pain , area of mechanical hyperalgesia and presence and magnitude of thermal heat/cold hyperalgesia . The study methods applied to evaluate these conditions were the conventional testing of somatosensory submodalities with area mapping and the subjective magnitude estimation of spontaneous pain . It was found that spontaneous pain and mechanical hyperalgesia were consistently improved , transiently , by intravenous administration of lidocaine in all 10 patients ; areas of hyperalgesia which extended beyond the territory of the nerve also improved transiently . Spontaneous pain and mechanical hyperalgesia , but not hypoesthesia , were transiently improved by injection of saline in only 1 of the 10 patients . This outcome is probably due to a placebo effect . This improvement is in keeping with the inhibition of anomalous neural impulses which can be generated anywhere along the sensory channels responsible for generating spontaneous pain and hyperalgesia . Thus , intravenous lidocaine is proposed as a diagnostic aid in the examination of patients complaining of complex sensory disorders associated with nerve injury . The transient pain relief may allow a fuller identification of the area of sensory loss Severe pain occurs in 5 - 30 % of the spinal cord-injured ( SCI ) population and is difficult to treat . Subarachnoid lidocaine has been used in selected patients with some success . Mexiletine , an analog of lidocaine that acts at Na+/K+ channels in the peripheral nerve , has been found effective in persons with diabetic dysesthetic neuropathy . The effect of mexiletine in the treatment of spinal cord dysesthetic pain was examined in this study . Fifteen patients were enrolled , and 11 patients completed the prospect i ve , r and omized , placebo-controlled , double-blind , crossover design trial . Inclusion /exclusion criteria were carefully defined . A 1-wk washout period was followed by a 4-wk drug trial of either mexiletine ( 450 mg/day ) or placebo . This was repeated for the second medication in the second arm of the study . Patients were followed weekly with McGill and visual analog pain scales . Baseline , midpoint , and endpoint Barthel function scores were recorded . The Wilcoxon 's signed-rank test and paired t test were used for statistical analysis . Results showed no significant effect of mexiletine on SCI dysesthetic pain scales or Barthel index . In conclusion , in this trial , mexiletine did not appear to decrease spinal cord injury-related dysesthetic pain We studied the analgesic efficacy of an intravenous infusion of lidocaine and morphine in 19 adults with well-established postherpetic neuralgia in a three-session , r and omized , double-blind , placebo-controlled trial . Compared with saline placebo , both lidocaine and morphine reduced pain intensity . Reductions in pain did not correlate with side effects produced by the infusions . For morphine , there was a significant correlation between reductions in pain intensity and blood level achieved . In the majority of subjects who reported definite pain relief , allodynia also disappeared . The results show that neuropathic pain can respond to opioids and to systemically administered local anesthetic drugs The objective of this double-blind placebo controlled multicenter study was to prove the efficacy of mexiletine in painful diabetic neuropathy . Treatment was provided for in three dosages . For pain measurements a visual analogue scale ( VAS ) and McGill 's verbal rating scale were chosen . 95 patients were included . A global assessment of the VAS showed no differences in treatment . The total evaluation ( PRIT = Pain Rating Index Total ) of the McGill scale just failed the level of significance . More specific exploratory evaluation of subclasses of the McGill scale , representing different qualities of pain , gave remarkable differences between mexiletine and placebo . According to types of complaints an evaluation showed substantial advantages of the mexiletine treatment with both the VAS and the McGill scale . There is strong evidence that particularly patients with stabbing or burning pain , heat sensations or formication will benefit most by mexiletine therapy . Concerning the dosage , a medium regimen of 450 mg per day seems to be appropriate in this indication . With an increase in dosage the efficacy does not rise proportionally . Mexiletine proved Output:	In these trials , systemic local anesthetics were safe , with no deaths or life-threatening toxicities . Lidocaine and oral analogs were safe drugs in controlled clinical trials for neuropathic pain , were better than placebo , and were as effective as other analgesics . More emphasis is necessary on outcomes measuring patient satisfaction to assess if statistically significant pain relief is clinical ly meaningful
MS22256	*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 — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies Introduction Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis ( MS ) . The impact of high intensity exercise remains unknown . Methods Thirty-four MS patients were r and omized into a sedentary control group ( SED , n = 11 ) and 2 exercise groups that performed 12 weeks of a high intensity interval ( HITR , n = 12 ) or high intensity continuous cardiovascular training ( HCTR , n = 11 ) , both in combination with resistance training . M.vastus lateralis fiber cross sectional area ( CSA ) and proportion , knee-flexor/extensor strength , body composition , maximal endurance capacity and self-reported physical activity levels were assessed before and after 12 weeks . Results Compared to SED , 12 weeks of high intensity exercise increased mean fiber CSA ( HITR : + 21±7 % , HCTR : + 23±5 % ) . Furthermore , fiber type I CSA increased in HCTR ( + 29±6 % ) , whereas type II ( + 23±7 % ) and IIa ( + 23±6 % , ) CSA increased in HITR . Muscle strength improved in HITR and HCTR ( between + 13±7 % and + 45±20 % ) and body fat percentage tended to decrease ( HITR : -3.9±2.0 % and HCTR : -2.5±1.2 % ) . Furthermore , endurance capacity ( Wmax + 21±4 % , time to exhaustion + 24±5 % , VO2max + 17±5 % ) and lean tissue mass ( + 1.4±0.5 % ) only increased in HITR . Finally self-reported physical activity levels increased 73±19 % and 86±27 % in HCTR and HITR , respectively . Conclusion High intensity cardiovascular exercise combined with resistance training was safe , well tolerated and improved muscle contractile characteristics and endurance capacity in MS . Trial Registration Clinical Trials.gov Abstract Purpose A better underst and ing of how people with multiple sclerosis ( pwMS ) recover from exercise may help inform interventions . Methods We explored physiological and perceptual responses following exercise of different intensities , using a crossover exposure-response design , in 14 adults with multiple sclerosis ( MS ) and 9 controls . A cycling exercise test determined maximum capacity ( Wpeak ) . Participants then performed 20-min exercise sessions relative to Wpeak ( r and om order separated by 7 days ) : ( 1 ) 45 % and ( 2 ) 60 % continuous cycling and ( 3 ) 90 % intermittent cycling ( 30 s cycling , 30 s rest ) . During a 45-min recovery period , tympanic temperature ( Temp ° C ) , exertion in breathing ( RPEbr ) and legs ( RPEleg ) , and cortical excitability ( MEParea ) were measured . Results Eleven pwMS and eight controls completed the study . Controls performed better on the exercise test ( p < 0.05 ) , thus more absolute work during subsequent sessions . PwMS took longer to recover RPEleg with recovery time increasing with intensity ( 45%-6 min ; 60%-15 min ; 90%-35 min ) and correlating with Temp ° C . MEParea was significantly depressed in both groups at 45 % and 60 % ( p < 0.001 ) , in the MS group this also correlated with RPEleg . Conclusions Feelings of leg exertion may persist after exercise in some pwMS , especially at high intensities . This may relate to body temperature and , after continuous exercise , cortical excitability . These results support considering the recovery period post exercise and provide an insight into potential correlates of post-exercise fatigue . Implication s for Rehabilitation A better underst and ing of how pwMS recover following exercise may help inform exercise prescription a long side fatigue management . This study showed that , in pwMS , the time taken to recover from feelings of leg fatigue increased with the intensity of the exercise session rather that total work performed and was related to increase in body temperature . The results of this relatively small study support the need to consider a recovery period after exercise and provide an insight into potential physiological Introduction The prevalence of impaired glucose tolerance ( IGT ) is higher in persons with multiple sclerosis ( MS ) compared to healthy controls , indicating metabolic deficits that may increase comorbidity . In other population s , IGT can , at least partly , be reversed by intense physical exercise , but this is never investigated before in MS . Aim To investigate the effect of high intensity aerobic and resistance training on glucose tolerance and skeletal muscle GLUT4 content in MS . Methods Thirty-four persons with MS ( aged 45 ± 3 years , EDSS 2.5 ± 1.07 ) were r and omized into three groups , including a ( 1 ) sedentary control group ( SED , n = 11 ) , ( 2 ) 12-week high intensity interval plus resistance training group ( HITR , n = 12 ) , or ( 3 ) 12-week high intensity continuous aerobic training plus resistance training group ( HCTR , n = 11 ) . Before and after 12 weeks , glucose tolerance and skeletal muscle GLUT4 content were determined by an oral glucose tolerance test and analysis of a m.vastus lateralis biopsy , respectively . Results There were no significant changes for subjects of SED . From pre- to post-intervention , total area under the glucose curve ( tAUC ) decreased significantly in both HITR ( −6.9 ± 6.2 % ) and HCTR ( −11.0 ± 7.7 % ) ( P < 0.05 ) . Insulin tAUC decreased ( −12.3 ± 14.7 % ) within HCTR and muscle GLUT4 content increased ( + 6.6 ± 4.5 % ) in HITR . Conclusion Twelve weeks of high intensity aerobic exercise in combination with resistance training improved glucose tolerance in persons with MS Background Poststroke guidelines recommend moderate-intensity , continuous aerobic training ( MCT ) to improve aerobic capacity and mobility after stroke . High-intensity interval training ( HIT ) has been shown to be more effective than MCT among healthy adults and people with heart disease . However , HIT and MCT have not been compared previously among people with stroke . Objective The purpose of this study was to assess the feasibility and justification for a definitive r and omized controlled trial ( RCT ) comparing HIT and MCT in people with chronic stroke . Design A preliminary RCT was conducted . Setting The study was conducted in a cardiovascular stress laboratory and a rehabilitation research laboratory . Patients Ambulatory people at least 6 months poststroke participated . Intervention Both groups trained 25 minutes , 3 times per week , for 4 weeks . The HIT strategy involved 30-second bursts at maximum-tolerated treadmill speed alternated with 30- to 60-second rest periods . The MCT strategy involved continuous treadmill walking at 45 % to 50 % of heart rate reserve . Measurements Measurements included recruitment and attendance statistics , qualitative HIT acceptability , adverse events , and the following blinded outcome variables : peak oxygen uptake , ventilatory threshold , metabolic cost of gait , fractional utilization , fastest treadmill speed , 10-Meter Walk Test , and Six-Minute Walk Test . Results During the 8-month recruitment period , 26 participants consented to participate . Eighteen participants were enrolled and r and omly assigned to either the HIT group ( n=13 ) or the MCT group ( n=5 ) . Eleven out of the 13 HIT group participants attended all sessions . Participants reported that HIT was acceptable and no serious adverse events occurred . St and ardized effect size estimates between groups were moderate to very large for most outcome measures . Only 30 % of treadmill speed gains in the HIT group translated into overground gait speed improvement . Limitations The study was not design ed to definitively test safety or efficacy . Conclusions Although further protocol optimization is needed to improve overground translation of treadmill gains , a definitive RCT comparing HIT and MCT appears to be feasible and warranted UNLABELLED Poststroke hemiparesis often leads to a vicious cycle of limited activity , deconditioning , and poor cardiovascular health . Accumulating evidence suggests that exercise intensity is a critical factor determining gains in aerobic capacity , cardiovascular protection , and functional recovery after stroke . High-intensity interval training ( HIT ) is a strategy that augments exercise intensity using bursts of concentrated effort alternated with recovery periods . However , there was previously no stroke-specific evidence to guide HIT protocol selection . PURPOSE This study aim ed to compare within-session exercise responses among three different HIT protocol s for persons with chronic ( > 6 months after ) stroke . METHODS Nineteen ambulatory persons with chronic stroke performed three different 1-d HIT sessions in a r and omized order , approximately 1 wk apart . HIT involved repeated 30-s bursts of treadmill walking at maximum tolerated speed , alternated with rest periods . The three HIT protocol s were different on the basis of the length of the rest periods , as follows : 30 s ( P30 ) , 60 s ( P60 ) , or 120 s ( P120 ) . Exercise tolerance , oxygen uptake ( V˙O2 ) , HR , peak treadmill speed , and step count were measured . RESULTS P30 achieved the highest mean V˙O2 , HR , and step count but with reduced exercise tolerance and lower treadmill speed than P60 or P120 ( P30 : 70.9 % V˙O2peak , 76.1 % HR reserve ( HRR ) , 1619 steps , 1.03 m·s(-1 ) ; P60 : 63.3 % V˙O2peak , 63.1 % HRR , 1370 steps , 1.13 m·s(-1 ) ; P120 : 47.5 % V˙O2peak , 46.3 % HRR , 1091 steps , 1.10 m·s(-1 ) ) . P60 achieved treadmill speed and exercise tolerance similar to those in P120 , with higher mean V˙O2 , HR , and step count . CONCLUSIONS For treadmill HIT in chronic stroke , a combination of P30 and P60 may optimize aerobic intensity , treadmill speed , and stepping repetition , potentially leading to greater improvements in aerobic capacity and gait outcomes in future studies 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 int Output:	HIIT appears to be safe and effective in increasing fitness in people with MS and low levels of disability .
MS22257	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVE To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review Background Chronic non-specific low-back pain ( LBP ) is one of the most common and expensive musculoskeletal disorders in industrialized countries . Similar to other countries in the world , LBP is a common health and socioeconomic problem in Iran . One of the most widely used modalities in the field of physiotherapy for treating LBP is therapeutic ultrasound . Despite its common use , there is still inconclusive evidence to support its effectiveness in this group of patients . This r and omised trial will evaluate the effectiveness of continuous ultrasound in addition to exercise therapy in patients with chronic LBP . Methods and design A total of 46 patients , between the ages 18 and 65 years old who have had LBP for more than three months will be recruited from university hospitals . Participants will be r and omized to receive continuous ultrasound plus exercise therapy or placebo ultrasound plus exercise therapy . These groups will be treated for 10 sessions during a period of 4 weeks . Primary outcome measures will be functional disability and pain intensity . Lumbar flexion and extension range of motion , as well as changes in electromyography muscle fatigue indices , will be measured as secondary outcomes . All outcome measures will be measured at baseline , after completion of the treatment sessions , and after one month . Discussion The results of this trial will help to provide some evidence regarding the use of continuous ultrasound in chronic LBP patients . This should lead to a more evidence -based approach to clinical decision making regarding the use of ultrasound for LBP.Trial registration Netherl and s Trial Register ( NTR ) : Abstract . The literature on the efficacy of traction in the treatment of low back pain ( LBP ) is conflicting . The aim of this study was to examine its efficacy in this disorder . Forty-two patients with at least 6 weeks of nonspecific LBP were selected . Demographic data were obtained . All patients completed the Oswestry disability index ( ODI ) to assess disability and the 10-cm visual analog scale ( VAS ) for evaluation of pain . Subjects were r and omly assigned into group 1 , receiving only st and ard physical therapy , or group 2 , receiving st and ard physical therapy with conventional lumbar traction . St and ard physical therapy consisted of local heat , ultrasound for the lumbar region , and an active exercise program , given for ten sessions in all . The subjects received instruction on correct posture and recommended therapeutic exercises . They were reevaluated at the end of treatment and at 3-month follow-up . The mean outcome measures were global improvement and satisfaction with the therapy , as well as disability by ODI and pain by VAS . There were no group differences in terms of demographic and baseline clinical characteristics . There was a significant reduction in pain intensity and disability at the end of treatment in both groups . There was complete or mild improvement in 47.6 % of group 1 and 40 % of group 2 . The satisfaction rate with both treatments was more than 70 % immediately after the therapies . During the 3-month period , the outcome measures except disability remained statistically stable , with no difference amongst groups . Disability was significantly reduced at follow-up in both groups . Of the patients , 51 % continued with the recommended exercises and had significantly lower disability scores than those who did not continue with the exercises . Pain and global improvement were also better in this group , but the difference was not statistically significant . In conclusion , no specific effect of traction on st and ard physical therapy was observed in our study group . We suggest focusing on back education and exercise therapy in the management of patients suffering from this chronic condition Our aim is to investigate the effects of three therapeutic approaches in the chronic low back pain on pain , spinal mobility , disability , psychological state , and aerobic capacity . Sixty patients with chronic low back pain were r and omized to three groups : group 1 , aerobic exercise + home exercise ; group 2 , physical therapy ( hot pack , ultrasound , TENS ) + home exercise ; group 3 , home exercise only . Spinal mobility , pain severity , disability , and psychological disturbance of the patients were assessed before and after the treatment and at 1-month follow-up . Aerobic capacities of the patients were measured before and after treatment . All of the groups showed similar decrease in pain after the treatment and at 1-month follow-up , and there was no significant difference between the groups . In group 2 , a significant decrease in Beck Depression Inventory scores was observed with treatment . At 1-month follow-up , group 1 and 2 showed significant decreases in General Health Assessment Question naire scores . In group 2 , there was also a significant improvement in Rol and Morris Disability scores . There were similar improvements in exercise test duration and the MET levels in all the three groups . All of the three therapeutic approaches were found to be effective in diminishing pain and thus increasing aerobic capacity in patients with chronic low back pain . On the other h and , physical therapy + home exercise was found to be more effective regarding disability and psychological disturbance OBJECTIVE --To compare the effectiveness of manipulative therapy , physiotherapy , treatment by the general practitioner , and placebo therapy in patients with persistent non-specific back and neck complaints . DESIGN --R and omised clinical trial . SETTING -- Primary health care in the Netherl and s. PATIENTS --256 patients with non-specific back and neck complaints of at least six weeks ' duration who had not received physiotherapy or manipulative therapy in the past two years . INTERVENTIONS --At the discretion of the manipulative therapists , physiotherapists , and general practitioners . Physiotherapy consisted of exercises , massage , and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manipulative therapy consisted of manipulation and mobilisation of the spine . Treatment by general practitioners consisted of drugs ( for example , analgesics ) , advice about posture , home exercises , and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 minutes ) and detuned ultrasound ( 10 minutes ) . MAIN OUTCOME MEASURES --Changes in severity of the main complaint and limitation of physical functioning measured on 10 point scales by a blinded research assistant and global perceived effect measured on a 6 point scale by the patients . RESULTS --Many patients in the general practitioner and placebo groups received other treatment during follow up . Improvement in the main complaint was larger with manipulative therapy ( 4.5 ) than with physiotherapy ( 3.8 ) after 12 months ' follow up ( difference 0.9 ; 95 % confidence interval 0.1 to 1.7 ) . Manipulative therapy also gave larger improvements in physical functioning ( difference 0.6 ; -0.1 to 1.3 ) . The global perceived effect after six and 12 months ' follow up was similar for both treatments . CONCLUSIONS --Manipulative therapy and physiotherapy are better than general practitioner and placebo treatment . Furthermore , manipulative therapy is slightly better than physiotherapy after 12 months Background Non-specific chronic low back pain ( NSCLBP ) is one of the most common musculoskeletal disorders around the world including Iran . One of the most widely used modalities in the field of physiotherapy is therapeutic ultrasound ( US ) . Despite its common use , there is still inconclusive evidence to support its effectiveness in patients with NSCLBP . The objective of this study was to evaluate the effect of continuous US compared with placebo US additional to exercise therapy for patients with NSCLBP . Methods In this single blind placebo controlled study , 50 patients with NSCLBP were r and omized into two treatment groups : 1 ) continuous US ( 1 MHz & 1.5 W/cm2 ) plus exercise 2 ) placebo US plus exercise . Patients received treatments for 4 weeks , 10 treatment sessions , 3 times per week , every other day . Treatment effects were assessed in terms of primary outcome measures : 1 ) functional disability , measured by Functional Rating Index , and 2 ) global pain , measured by a visual analog scale . Secondary outcome measures were lumbar flexion and extension range of motion ( ROM ) , endurance time and rate of decline in median frequency of electromyography spectrum during a Biering Sorensen test . All outcome variables were measured before , after treatment , and after one-month follow-up . An intention to treat analysis was performed . Main effects of Time and Group as well as their interaction effect on outcome measures were investigated using repeated measure ANOVA . Results Analysis showed that both groups had improved regarding function ( FRI ) and global pain ( VAS ) ( P < .001 ) . Lumbar ROM as well as holding time during the Sorensen test and median frequency slope of all measured paravertebral muscles did not change significantly in either group ( P > .05 ) . Improvement in function and lumbar ROM as well as endurance time were significantly greater in the group receiving continuous US ( P < .05 ) . Conclusions The study showed that adding continuous US to a semi supervised exercise program significantly improved function , lumbar ROM and endurance time . Further studies including a third group of only exercise and no US can establish the possible effects of placebo US.Trial registration Study Design . Multicenter r and omized , controlled trial . Objective . To compare two physical therapy programs for patients with lumbar spinal stenosis . Summary of Background Data . Scant evidence exists regarding effectiveness of nonsurgical management programs for lumbar spinal stenosis . Methods . Fifty-eight patients with lumbar spinal stenosis were r and omized to one of two 6-week physical therapy programs . One program included manual physical therapy , body weight supported treadmill walking , and exercise ( Manual Physical Therapy , Exercise , and Walking Group ) , while the other included lumbar flexion exercises , a treadmill walking program , and subtherapeutic ultrasound ( Flexion Exercise and Walking Group ) . Perceived recovery was assessed with a global rating of change scale . Secondary outcomes included : Oswestry , a numerical pain rating scale , a measure of satisfaction , and a treadmill test . Testing occurred at baseline , 6 weeks , and 1 year . Perceived recovery , pain , and other healthcare re sources used were collected with a long-term follow-up question naire . Results . A greater proportion of patients in the manual physical therapy , exercise , and walking group reported recovery at 6 weeks compared with the flexion exercise and walking group ( P = 0.0015 ) , with a number needed to treat for perceived recovery of 2.6 ( confidence interval , 1.8–7.8 ) . At 1 year , 62 % and 41 % of the manual therapy , exercise , and walking group and the flexion exercise and walking group , respectively , still met the threshold for recovery . Improvements in disability , satisfaction , and treadmill walking tests favored the manual physical therapy , exercise , and walking group at all follow-up points . Conclusions . Patients with lumbar spinal stenosis can benefit from physical therapy . Additional gains may be realized with the inclusion of manual physical therapy interventions , exercise , and a progressive body-weight supported treadmill walking program For ultrasound to be effective , a conducting medium must be placed between the soundhead and the skin . Little research has been performed to test whether or not these mediums actually work . The purpose of this study was to compare the effect of tap water immersion and ultrasound gel conducting mediums on tissue temperature rise in the human leg . A 23-gauge hypodermic needle microprobe was inserted 3 cm deep into the medial portion of the gastrocnemius muscle of 20 subjects . Each subject participated in two r and om order treatments using tap water immersion and topical gel conducting mediums . Each treatment consisted of continuous ultrasound delivered topically at 1.5 W/cm2 for 10 minutes . During both treatments , the soundhead was moved at a speed of 4 cm per second , and the temperature was recorded every 30 seconds . A significant difference was found between the two treatment methods [ t(19 ) = 9.18 , p < .001 ] . The topical gel increased tissue temperature 4.8 degrees C , whereas the underwater treatment increased tissue temperature only 2.1 degrees C. Therefore , at a tissue depth of 3 cm , ultrasound gel is a better conducting medium than water . Also , the authors discovered that it took nearly 8 minutes for the temperature to reach therapeutic levels during the gel technique . These findings should be of clinical significance to clinicians who regularly use ultrasound OBJECTIVES Some occupations are more prone to low back pain ( LBP ) due to their static work postures and work place design . Multidisciplinary pain programs have shown their effectiveness in the management of LBP in general population but which treatment and which segment of the population will be benefited more was not investigated yet . This study determines the effect of two treatment protocol s on five occupationally subgrouped male LBP patients . METHODS A total of 102 occupational male , 20 - 4 Output:	The studies comparing therapeutic ultrasound versus placebo or versus exercise alone did not report on overall satisfaction with treatment , or quality of life . There was low quality evidence that spinal manipulation reduces pain and functional disability more than ultrasound over the short to medium term . There is also very low quality evidence that there is no clear benefit on any outcome measure between electrical stimulation and therapeutic ultrasound ; and that phonophoresis results in improved SF-36 scores compared to therapeutic ultrasound . None of the included studies reported on adverse events related to the application of therapeutic ultrasound . AUTHORS ' CONCLUSIONS No high quality evidence was found to support the use of ultrasound for improving pain or quality of life in patients with non-specific chronic LBP . There is some evidence that therapeutic ultrasound has a small effect on improving low-back function in the short term , but this benefit is unlikely to be clinical ly important .
MS22258	*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 : The reproducibility of clinical tests for skin extensibility and consistency , essential for differentiating between types of Ehlers – Danlos syndrome ( EDS ) and benign joint hypermobility syndrome ( BJHS ) , is unknown . Para clinical methods may provide objective differential diagnostic methods . Methods : Six EDS , 11 BJHS , and 19 controls completed the trial . We analysed the overall inter‐examiner agreement on clinical tests for skin extensibility and consistency , in addition to analyses on suction cup ( SC ) and soft tissue stiffness meter ( STSM ) methods . Results : Overall agreement on tests for skin extensibility and consistency varied between 0.44 and 0.72 . Extensibility evaluated by SC showed an insignificant difference between EDS patients and controls ( p = 0.056 ) . Consistency evaluated by STSM showed significant differences ( p = 0.001 ) . Conclusions : Overall inter‐examiner agreement on clinical tests for skin extensibility and consistency was below 0.80 , which was required a priori to conduct a reproducibility study . Further refinement of tests and a training phase are necessary . The SC and STSM results are encouraging but must be reproduced in a larger study population Simple but objective measurement of soft tissue consistency would be advantageous in the assessment of many neurological , lymphostatic and venous disorders . The aim of the present study was to evaluate the feasibility of using a novel h and -held computerized soft tissue stiffness meter ( STSM ) . The STSM describes the soft tissue stiffness ( STS ) in the form of the instantaneous force ( N ) by which the tissue resists the constant deformation produced by a cylindrical intender . Firstly , the STSM was used to test elastomer sample s with known mechanical properties . In the in vivo assessment , 12 healthy , nondisabled adults ( age range , 24 - 57 years ) and 16 subjects with chronic myofascial neck pain syndrome ( age range , 27 - 55 years ) were studied . To study the reproducibility ( coefficient of variation ( CV(% ) ) ) of the method , the measurement sites were either marked with a marker pen ( marked points ) or localized anatomically ( unmarked points ) . Measurements were made from the dorsal forearm ( Arm ) , trapezius ( Tra ) , levator scapulae ( Lev ) , infraspinatus ( Inf ) and deltoideus ( Del ) muscle areas . STS in the forearm was studied during different types of short-term relative isometric loading of the muscle as well as during venous occlusion . STS values of the myofascial trigger points in the Lev muscles were evaluated bilaterally . A linear , positive relationship was found between the indenter force ( N ) and the dynamic compressive modulus ( MPa ) of elastomer stiffness ( r(2 ) = 0.90 , n = 9 ) . Intra- and interrater CVs of marked and unmarked sites varied between 4.31 % and 12.06 % . STS increased linearly along the relative muscle load ( r(2 ) = 0.96 ) and nonlinearly during the venous occlusion ( r(2 ) = 0.97 ) . Statistically significant regional variation of STS was found between the different measurement sites ( p < 0.05 ) . In conclusion , STSM can evaluate tissue stiffness quantitatively and yield reproducible data Output:	Quantitative measures of tissue mechanics have the potential to contribute towards more objective diagnosis of hEDS/HSD .
MS22259	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives To determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom . Design Quantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) study to a lifetime horizon . Setting UK National Health Service . Population Cohorts of 50 000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS2 ( Congestive heart failure , Hypertension , Age≥75 years , Diabetes mellitus , previous Stroke/transient ischaemic attack ) score of 2.1 . Main outcome measures Quality adjusted life years ( QALYs ) gained and incremental cost per QALY of dabigatran compared with warfarin . Results Compared with warfarin , low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 ( 95 % central range −0.083 to 0.267 ) and 0.146 ( −0.029 to 0.322 ) QALYs . Positive incremental net benefits result ed for high dose dabigatran in 94 % of simulations versus warfarin and in 76 % of those versus low dose dabigatran . In the economic analysis , high dose dabigatran dominated the low dose , had an incremental cost effectiveness ratio of £ 23 082 ( € 26 700 ; $ 35 800 ) per QALY gained versus warfarin , and was more cost effective in patients with a baseline CHADS2 score of 3 or above . However , at centres that achieved good control of international normalised ratio , such as those in the UK , dabigatran 150 mg was not cost effective , at £ 42 386 per QALY gained . Conclusions This analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin . However , no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified . High dose dabigatran will be cost effective only for patients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers ABSTRACT Endothelial dysfunction is a surrogate marker of cardiovascular risk . Resveratrol is known to improve endothelial function in animals , however , clinical trials are limited . We hypothesized that the acute trans-resveratrol supplementation improves endothelial function in treated hypertensive patients with endothelial dysfunction . Twenty-four hypertensive patients between 45 and 65 years-old with baseline endothelial dysfunction were enrolled in a r and omized , cross-over , double-blind , placebo-controlled trial . Individuals received either a single dose of trans-resveratrol ( 300 mg ) or placebo and were crossed-over after a one-week washout period . Blood pressure ( BP ) measurements , aortic systolic blood pressure ( SBP ) and brachial flow-mediated dilation ( FMD ) were performed before and 1.5 hours after the intervention . FMD was significantly increased in women ( 4.2 ± 0.5 vs 7.1 ± 1.3 % , p = 0.026 ) but not in men ( 4.4 ± 0.9 vs 4.9 ± 0.8 % , p = 0.588 ) in the trans-resveratrol group . There was no statistical difference between baseline and final values of brachial BP and also no changes in aortic SBP . Patients with higher low-density lipoprotein ( LDL ) cholesterol had better FMD response to trans-resveratrol than patients with lower LDL cholesterol ( 7.4 ± 1.2 vs 4.3 ± 1.0 % , p = 0.004 ) . Our study demonstrated that the acute supplementation of trans-resveratrol promoted an improvement in endothelial function , especially in women and those with higher LDL-cholesterol , despite no changes in BP . List of Abbreviation : Aix : augmentation index ; AP : augmentation pressure ; BP : blood pressure ; BMI : body Mass Index ; CVD : cardiovascular disease ; FMD : flow-mediated dilation ; FRS : Framingham Risk Score ; HDL : high-density lipoprotein ; LDL : low-density lipoprotein ; NO : nitric oxide ; SPSS : Statistical Package for Social Sciences ; ROS : reactive oxygen species ; SBP : systolic blood pressure ; TG : triglycerides Abstract Aims Oxidative stress plays a pivotal role in the pathogenesis of type 2 diabetes ( T2D ) . In vitro and animal studies have shown that resveratrol exerts an antioxidant effect , but clinical trials addressing this effect in patients with T2D are limited . The aim of this study was to determine whether resveratrol supplementation affects oxidative stress markers in a r and omized , placebo-controlled , double-blind clinical trial . Methods A total of 48 patients with T2D r and omly were assigned to receive 800 mg/day resveratrol or placebo for 2 months . Plasma total antioxidant capacity , malondialdehyde concentration , protein carbonyl and total thiol contents , intracellular superoxide anion ( O2− · ) and hydrogen peroxide ( H2O2 ) in P BMC s , the expression of genes involved in oxidative stress responses ( Nrf2 , SOD , Cat , HO-1 , RAGE , NOS ) in P BMC s , and metabolic and anthropometric parameters were measured at the baseline and at the trial end . Results Compared with the placebo group , resveratrol reduced plasma protein carbonyl content and P BMC s O2− · level and significantly increased plasma total antioxidant capacity and total thiol content . Furthermore , the expression of Nrf2 and SOD was significantly increased after resveratrol consumption . Resveratrol had no significant effects on the metabolic and anthropometric parameters except for a significant reduction in weight , BMI , and blood pressure levels . Resveratrol was well tolerated , and no serious adverse event was occurred . Conclusions Our study demonstrated that 8 weeks of supplementation with 800 mg/day resveratrol has an antioxidant effect in the blood and P BMC s of patients with T2D . Clinical Trial Registry number and website I RCT registration number : I RCT 2015072523336N1 and http://en . search .i rct .ir/view/24752 Studies on the effects of the long-term intake of trans-resveratrol on vascular function are conflicting . In addition , postpr and ial effects of long-term trans-resveratrol intake on endothelial function are not known . We therefore supplemented 45 overweight and slightly obese volunteers ( 25 men and 20 women ) with a mean ( ±SD ) age of 61 ± 7 years and body mass index of 28.3 ± 3.2 kg/m2 in r and om order trans-resveratrol ( 2 × 75 mg/day ) or placebo capsules for 4 weeks , separated by a washout period of at least 4 weeks . At the end of each intervention period , brachial artery flow-mediated vasodilation ( FMD ) was measured before and after meal consumption . Plasma biomarkers for endothelial function , inflammation , and glucose and lipid metabolism were also determined . Compared with the placebo , trans-resveratrol did not affect fasting FMD ( 2.9 ± 1.4 % vs. 3.0 ± 1.9 % ; p = 0.69 ) . After the postpr and ial test , changes in FMD ( −0.7 ± 2.3 % vs. 0.2 ± 2.6 % ; p = 0.13 ) were also not significantly different . Postpr and ial changes in biomarkers were also comparable . In conclusion , for overweight and slightly obese volunteers , a daily intake of 150 mg of trans-resveratrol for 4 weeks does not change plasma biomarkers of endothelial function or inflammation in the fasting state or postpr and ial phase BACKGROUND The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses , modulate nitric oxide synthesis , and promote vasodilation , which thereby improves blood flow . Resveratrol may therefore modulate aspects of brain function in humans . OBJECTIVE The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults . DESIGN In this r and omized , double-blind , placebo-controlled , crossover study , 22 healthy adults received placebo and 2 doses ( 250 and 500 mg ) of trans-resveratrol in counterbalanced order on separate days . After a 45-min resting absorption period , the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min . Cerebral blood flow and hemodynamics , as indexed by concentration changes in oxygenated and deoxygenated hemoglobin , were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy . The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort ( n = 9 ) . RESULTS Resveratrol administration result ed in dose-dependent increases in cerebral blood flow during task performance , as indexed by total concentrations of hemoglobin . There was also an increase in deoxyhemoglobin after both doses of resveratrol , which suggested enhanced oxygen extraction , that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance . Cognitive function was not affected . Resveratrol metabolites were present in plasma throughout the cognitive task period . CONCLUSION These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables ABSTRACT Objective “ The obesity epidemic ” has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease ( NAFLD ) , for which effective treatments are in dem and . The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction . We aim ed to test the hypothesis that resveratrol alleviates NAFLD in a r and omised , clinical trial . Material s and methods A total of 28 overweight patients with transaminasemia and histological NAFLD were r and omised 1:1 to placebo or resveratrol 1.5 g daily for 6 months . Twenty-six participants completed the trial and underwent repeated clinical investigation , blood work , MR spectroscopy ; and 19 participants agreed to a repeat liver biopsy . Results Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury ( primary outcome : alanine transaminase , p = 0.51 ) . Resveratrol-treated patients showed a 3.8 % decrease in liver lipid Output:	No significant effects of RWP were seen in diastolic blood pressure or flow-mediated dilation ( FMD ) of the brachial artery . RWP have the potential to improve vascular health in at risk human population s , particularly in regard to lowering systolic blood pressure ; however , such benefits are not as prevalent as those observed in animal models
MS22260	*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 —Numerous studies have suggested that microbial agents may promote atherosclerosis . A smaller body of research has suggested that acute respiratory infection may be a risk factor for myocardial infa rct ion ( MI ) . We hypothesized that influenza vaccine might reduce the risk of recurrent MI in patients with documented coronary heart disease ( CHD ) . Methods and Results —A case-control study was performed on 218 CHD patients seen at Memorial Hermann Hospital during the influenza season of October 1997 through March 1998 . Patients who experienced new MI were included in the case group , and those who did not experience new MI or unstable angina were assigned to the control group . Data were collected by structured review of patients ’ charts and through a subsequent telephone survey . Adjusted for history of influenza vaccination in previous years , multivariate logistic regression revealed risk of MI to be associated with current hypertension ( OR 4.96 , 95 % CI 2.06 to 11.96 , P < 0.0001 ) , hypercholesterolemia ( OR 4.08 , 95 % CI 1.67 to 9.99 , P = 0.002 ) , smoking ( OR 3.75 , 95 % CI 1.76 to 7.98 , P = 0.001 ) , and influenza vaccination ( OR 0.33 , 95 % CI 0.13 to 0.82 , P = 0.017 ) . Despite significant association in univariate analysis , multivitamin therapy and physical exercise were not associated with risk of reinfa rct ion in multivariate analysis . Conclusions —In this study in patients with chronic CHD , vaccination against influenza was negatively associated with the development of new MI during the same influenza season . However , to address causal inference , examination of prospect i ve data sets will be needed We have previously determined that there is a significant benefit of vaccination against influenza in patients hospitalized due to an acute coronary event . The purpose of this study is to determine whether the observed benefits of vaccination were maintained over a 2-year follow-up among those who were re-vaccinated during the subsequent winter season . During the winter season of 2001 , a total of 301 acute coronary patients were prospect ively enrolled within 72 hours of the onset of symptoms . Follow-up was conducted at 6 and 12 months . Patients who survived participated in a registry 1 year after the 2nd influenza vaccination period ( winter 2002 ) , as a cohort of chronic and stable coronary patients . The incidence of the primary endpoint cardiovascular death at 1 year was significantly lower in patients receiving vaccination than in controls ( 6 % vs 17 % , respectively ) by intention-to-treat analysis . The relative risk with vaccination in comparison with controls was 0.34 ; 95 % confidence interval , 0.17 - 0.71 ; P = 0.002 . In the winter of 2002 , 116 patients were vaccinated according to their physicians ' instructions , and 114 subjects remained unvaccinated . The combined endpoints of total death plus myocardial infa rct ion 1 year later were 4 ( 3.4 % ) in the vaccinated group vs 11 ( 9.7 % ) among those who were not vaccinated ( P = 0.05 ) . Influenza vaccination may reduce the risk of death and ischemic events in patients admitted with acute coronary syndromes . There is also a beneficial trend in the quiescent phase of ischemia OBJECTIVES Our objective was to assess endogenous thrombolytic activity in acute coronary syndrome ( ACS ) patients and relate this to their likelihood of future adverse cardiovascular events . BACKGROUND Spontaneous lysis of platelet-rich thrombi is an important defense mechanism against lasting occlusion . Despite convincing evidence for the role of endogenous fibrinolysis in ACS , the prognostic value of plasma fibrinolytic markers in assessing risk is limited . We employed a novel global test which , in addition to platelet reactivity , allows assessment of endogenous thrombolytic activity to identify ACS patients who remain at risk of cardiovascular events . METHODS We used the global thrombosis test ( GTT ) to assess thrombotic and thrombolytic status in 300 ACS patients receiving dual-antiplatelet therapy . The test assesses the time required to form an occlusive thrombus , the occlusion time ( OT ) , and the time to lyse this , the lysis time ( LT ) . The end point of the study at 12 months ' follow-up was the composite of death , nonfatal myocardial infa rct ion , or stroke . RESULTS The OT and LT were both prolonged in ACS patients compared with normal volunteers ( p < 0.001 ) . LT > or = 3,000 s occurred in 23 % of ACS patients versus none of the normal subjects and was a significant and independent predictor of cardiovascular death and nonfatal myocardial infa rct ion in a multivariate model adjusted for cardiovascular risk factors . LT > or = 3,000 s was the optimal cutoff value for predicting 12-month major adverse cardiovascular events ( hazard ratio [ HR ] : 2.52 , 95 % confidence interval : 1.34 to 4.71 , p = 0.004 ) and cardiovascular death ( HR : 4.2 , 95 % confidence interval : 1.13 to 15.62 , p = 0.033 ) . HR increased further as LT increased . No association was found between OT and the risk of major adverse cardiovascular events . CONCLUSIONS Assessment of endogenous thrombolytic status based on the lysis of platelet-rich thrombi from native blood using the point-of-care GTT can identify ACS patients at risk of future cardiac events Output:	IgG antibodies that recognize epitope Gly40-Arg43 in domain I of b2–glycoprotein I cause LAC , and their presence correlates strongly with thrombosis . 3 Galli M , Luciani D , Bertolini G , Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome : a systematic review of the literature . 9 Moore GW , Smith MP , Savidge GF . 12 Burns ER , Goldberg SN , Wenz B. Paradoxic effect of multiple mild coagulation factor deficiencies on the prothrombin time and activated partial thromboplastin time .
MS22261	*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 contrast the efficacy of two exercise programs , segmental stabilization and strengthening of abdominal and trunk muscles , on pain , functional disability , and activation of the transversus abdominis muscle ( TrA ) , in individuals with chronic low back pain . DESIGN : Our sample consisted of 30 individuals , r and omly assigned to one of two treatment groups : segmental stabilization , where exercises focused on the TrA and lumbar multifidus muscles , and superficial strengthening , where exercises focused on the rectus abdominis , abdominus obliquus internus , abdominus obliquus externus , and erector spinae . Groups were examined to discovere whether the exercises created contrasts regarding pain ( visual analogical scale and McGill pain question naire ) , functional disability ( Oswestry disability question naire ) , and TrA muscle activation capacity ( Pressure Biofeedback Unit = PBU ) . The program lasted 6 weeks , and 30‐minute sessions occurred twice a week . Analysis of variance was used for inter‐ and intra‐group comparisons . The significance level was established at 5 % . RESULTS : As compared to baseline , both treatments were effective in relieving pain and improving disability ( p<0.001 ) . Those in the segmental stabilization group had significant gains for all variables when compared to the ST group ( p<0.001 ) , including TrA activation , where relative gains were 48.3 % and ‐5.1 % , respectively . CONCLUSION : Both techniques lessened pain and reduced disability . Segmental stabilization is superior to superficial strengthening for all variables . Superficial strengthening does not improve TrA activation capacity STUDY DESIGN R and omized clinical trial . OBJECTIVES To determine the efficacy of trunk balance exercises for individuals with chronic low back pain . BACKGROUND The majority of exercises focusing on restoring lumbopelvic stability propose targeting the feedforward control of the lumbopelvic region . Less attention has been paid to feedback control during balance adjustments . METHODS Seventy-nine patients were r and omly allocated to 2 different groups . The experimental group performed trunk balance exercises in addition to st and ard trunk flexibility exercises . The control group performed strengthening exercises in addition to the same st and ard trunk flexibility exercises . The primary outcome measures were pain intensity ( visual analogue scale ) , disability ( Rol and -Morris Question naire ) , and quality of life ( 12-Item Short-Form Health Survey ) . Secondary outcomes were painful positions , use of analgesic drugs , and referred pain . Analysis of variance and relative risk were used to analyze the data for the primary and secondary outcome measures , respectively . The number of participants reaching the minimal clinical ly important difference in the 2 groups for each outcome measure was compared using relative risk . RESULTS A significant difference in scores on the Rol and -Morris Question naire ( P = .011 ) and the physical component of the 12-Item Short-Form Health Survey ( P = .048 ) , and in the number of participants reaching the minimal clinical ly important difference for the Rol and -Morris Question naire ( relative risk , 1.79 ; 95 % confidence interval [ CI ] : 1.05 , 3.04 ) and the secondary outcome of painful positions ( relative risk , 1.37 ; 95 % CI : 1.03 , 1.83 ) were found in favor of the experimental treatment . CONCLUSIONS Trunk balance exercises combined with flexibility exercises were found to be more effective than a combination of strength and flexibility exercises in reducing disability and improving the physical component of quality of life in patients with chronic low back pain [ Purpose ] The purpose of this study was to compare two methods for the muscle stabilization of the trunk of patients with chronic low back pain . The methods comprised combination patterns of proprioceptive neuromuscular facilitation ( PNF ) and ball exercise . [ Subjects and Methods ] The subjects were 40 volunteers who had low back pain . All subjects were r and omly assigned to either a group which received proprioceptive neuromuscular facilitation or a group which performed ball exercise . Measurements were taken four times in total , at pre-intervention , two weeks later , four weeks later , and six weeks later . The main measurement methods used were the visual analogue scale ( VAS ) for pain and electromyography ( EMG ) for muscle activity . [ Results ] VAS and EMG activity were significantly reduced in the PNF combination pattern group and the ball exercise group . A comparison of the groups showed significant differences . In VAS and EMG activity ; in particular , the combination pattern group using PNF increased EMG activity more than the ball exercise group did after six weeks of intervention . [ Conclusion ] This study showed that PNF combination pattern training for six weeks was more effective for patients with low back pain than performing ball exercise Background : Lumbar segmental stability is an important biomechanical component that influences symptoms amongst patients with Mechanical low back pain . Aims : To compare the efficacy of segmental stabilization exercises utilizing multifidus and transversus abdominis muscles versus a placebo treatment in patients with lumbar segmental instability . Material s and methods : The study was an observer-blinded r and omized placebo-controlled cross-over study of 18 adults ( 12 men , 6 women ) , of mean age 22.5 ± 1.09 yrs who scored 7/13 in subjective aspects and 8/14 in objective aspects of Delphi criteria for lumbar segmental instability . The selected subjects were then r and omized to receive either placebo-control ( prone lying ) or experimental ( lumbar segmental stabilization ) as a first treatment . Each treatment was followed by a wash-out period of 24 hours . Outcomes were measured four times- pre- and post- first intervention , pre- and post- second intervention . The outcome measures used were pain on Visual analogue scale , Pressure pain threshold and Joint play grading scale ( 0 - 6 scale ) on that level . Results : Two-way analysis of variance and post-hoc analysis using Bonferonni test were used with level of significance set at p<.05 using Statistical package for social sciences version 12.0.1 for Windows . Visual analogue scale changed significantly in both the periods of intervention- in control ( P = .016 ) and experimental ( P = .000 ) periods . However this improvement was more significant in the experimental period . The Joint play grading scale scores improved only in the experimental condition compared to the control condition significantly . The Pressure pain threshold also improved significantly in the experimental condition ( P = .000 ) while the changes in control condition was not statistically significant ( P=.816 ) . Conclusion : Segmental stabilization exercise was more effective than placebo intervention in symptomatic lumbar segmental instability OBJECTIVE The purpose of this preliminary study was demonstrate if it was feasible to evaluate variations in acceleration of trunk movement , pain , and disability during an episode of acute nonspecific low back pain comparing regular trunk exercises to regular exercises in addition to core stability exercises . METHODS A pilot r and omized controlled trial was used to evaluate 33 participants recruited from a National Health Service physiotherapy musculoskeletal provider in the London district of Hillingdon . Participants were allocated to 2 groups ; a regular exercise group ( male , 2 ; female , 15 ) with a mean ( SD ) age of 35.8 ( 9.1 ) years and intervention group ( male , 3 ; female , 13 ) with a mean ( SD ) age of 36.2 ( 9.8 ) years . The regular exercise group received exercise that consisted of a core stability class including both specific and global trunk exercises . The intervention group , in addition to these core exercises , received further instruction on 8 specific stabilization muscles involving the transversus abdominis and the lumbar multifidus . Trunk sagittal acceleration , pain , and disability were measured using a Lumbar Motion Monitor , pain visual analog scale , and Rol and Morris Disability Question naire , respectively . Measures were taken at baseline , 3 and 6 weeks , and a 3-month follow-up . Multiple regression with adjustment for baseline value was used to analyze each outcome . All outcomes were log transformed to correct skewness and so presented as ratio of geometric means with 95 % confidence interval . RESULTS Differences in mean trunk sagittal acceleration between the regular exercise and intervention groups was not statistically significant at any time point ( ratio of means [ 95 % confidence interval ] : 3 weeks 1.2 [ 0.9 - 1.6 ] , P = .2 ; 6 weeks 1.1 [ 0.8 - 1.5 ] , P = .7 ; 3 months : 1.2 [ 0.8 - 1.9 ] , P = .9 ) . Similarly , the effects on neither pain score nor disability score were significant ( pain score : 3 weeks 1.3 [ 0.8 - 2.2 ] , P = .3 ) ; 6 weeks 1.2 [ 0.7 - 2.0 ] , P = .6 ; 3 months 1.0 [ 0.5 - 1.9 ] , P = 1.0 ) ; disability score : 6 weeks 1.0 [ 0.7 - 1.5 ] , P = 1.0 ; 3 months 1.3 [ 0.8 - 1.9 ] , P = .3 ) . Outcome measures for both groups improved over time . CONCLUSIONS This pilot study demonstrated that a study of this nature is feasible . Both the regular exercise and the intervention groups demonstrated improvements in mean trunk sagittal acceleration at 3 , 6 , and 12 weeks . The preliminary findings showed that evidence was inconclusive for the beneficial effect of adding specific core stability exercises for acute low back pain . The results of this study demonstrated an increase in acceleration accompanied by a reduction in pain , which may suggest that acute nonspecific low back pain may induce the pain-spasm-pain model rather than the pain adaptation model Core training continues to be emphasized with the proposed intent of improving athletic performance . The purpose of this investigation was to discover if core isometric endurance exercises were superior to core isotonic strengthening exercises and if either influenced specific endurance , strength , and performance measures . Ten untrained students were r and omly assigned to core isometric endurance ( n = 5 ) and core isotonic strength training ( n = 5 ) . Each performed three exercises , two times per week for six weeks . A repeated measures ANOVA was used to compare the measurements for the dependent variables and significance by bonferroni post-hoc testing . The training protocol s were compared using a 2 × 3 mixed model ANOVA . Improvement in trunk flexor and extensor endurance ( p < 0.05 ) along with squat and bench press strength ( p < 0.05 ) occurred with the strength group . Improvement in trunk flexor and right lateral endurance ( p < 0.05 ) along with strength in the squat ( p < 0.05 ) were found with the endurance group . Neither training protocol cl aim ed superiority and both were ineffective in improving performance STUDY DESIGN Prospect i ve , single-group , repeated- measures design . OBJECTIVE To identify exercises that could be used for strength development and the exercises that would be more appropriate for endurance or stabilization training . BACKGROUND The exercises analyzed are often used in rehabilitation programs for the spine , hip , and knee . They are active exercises using body weight for resistance ; thus a clinician is unable to determine the amount of resistance being applied to a muscle group . Electromyographic ( EMG ) analysis can provide a measure of muscle activation so that the clinician can have a better idea about the effect the exercise may have on the muscle for strength , endurance , or stabilization . METHODS AND MEASURES Surface EMG analysis was carried out in 19 males and 11 females while performing the following 9 exercises : active hip abduction , bridge , unilateral-bridge , side-bridge , prone-bridge on the elbows and toes , quadruped arm/lower extremity lift , lateral step-up , st and ing lunge , and using the Dynamic Edge . The rectus abdominis , external oblique abdominis , longissimus thoracis , lumbar multifidus , gluteus maximus , gluteus medius , vastus medialis obliquus , and hamstring muscles were studied . RESULTS In healthy subjects , the lateral step-up and the lunge exercises produced EMG levels greater than 45 % maximum voluntary isometric contraction ( MVIC ) in the vastus medialis obliquus , which suggests that they may be beneficial for strengthening that muscle . The side-bridge exercise could be used for strengthening the gluteus medius and the external oblique abdominis muscles , and the quadruped arm/lower extremity lift exercise may help strengthen the gluteus maximus muscle . All the other exercises produced EMG levels less than 45 % MVIC , so they may be more beneficial for training endurance or stabilization in healthy subjects . CONCLUSION Our results suggest these exercises could be used for a core rehabilitation or performance enhancement program . Depending on the individual needs of a patient or athlete , some of the exercises may be more beneficial than others for achieving strength Output:	According to the results of various scales and evaluation instruments , core strength training is more effective than typical resistance training for alleviating chronic low back pain .
MS22262	*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 Early inflammatory lesions and bronchial hyperresponsiveness are characteristics of the respiratory distress in premature neonates and are susceptible to aggravation by assisted ventilation . We hypothesized that treatment with inhaled salbutamol and beclomethasone might be of clinical value in the prevention of bronchopulmonary dysplasia ( BPD ) in ventilator-dependent premature neonates . The study was double-blinded and placebo controlled . We studied 173 infants of less than 31 weeks of gestational age , who needed ventilatory support at the 10th postnatal day . They were r and omised to four groups and received either placebo + placebo , placebo + salbutamol , placebo + beclomethasone or beclomethasone + salbutomol , respectively for 28 days . The major criteria for efficacy were : diagnosis of BPD ( with score of severity ) , mortality , duration of ventilatory support and oxygen therapy . The trial groups were similar with respect to age at entry ( 9.8–10.1 days ) , gestational age ( 27.6–27.8 weeks ) , birth weight and oxygen dependence . We did not observe any significant effect of treatment on survival , diagnosis and severity of BPD , duration of ventilatory support or oxygen therapy . For instance , the odds-ratio ( 95 % confidence interval ) for severe or moderate BPD were 1.04 ( 0.52–2.06 ) for inhaled beclomethasone and 1.54 ( 0.78–3.05 ) for inhaled salbutamol . Conclusion This r and omised prospect i ve trial does not support the use of treatment with inhaled beclomethasone , salbutamol or their combination in the prevention of BPD in premature ventilated neonates An imbalance of proinflammatory cytokines such as TNF-alpha , IL-1 beta , and the neutrophil chemotactic factor IL-8 and inhibitors ( e.g. , soluble TNF receptors and IL-1ra ) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia ( BPD ) . Disodium cromoglycate ( DSCG ) has anti-inflammatory effects in asthma , a disease with many similarities with BPD . In a prospect i ve , r and omized , blinded study , we examined whether early DSCG therapy inhibits proinflammatory cytokines in infants at risk for BPD . Twenty-six infants who were identified as high risk ( > or = 75 % probability ) for oxygen-dependency at 28 d by a 12-h predictive score and survived 48 h were r and omized to nebulized DSCG 20 mg ( n = 13 ) or 2 cc NS ( control , n = 13 ) every 6 h from Day 3 to Day 28 . Lung lavage was collected on Day 3 ( pre- study ) and Day 7 and analyzed for cell count and differential and TNF-alpha , sTNFR1 , sTNFR2 , IL-1 beta , IL-1ra , and IL-8 concentrations . The groups ' pre- study lavage cytokine concentrations were similar , but TNF-alpha and IL-8 concentrations were 3.6- and 4.9-fold lower in the DSCG group on Day 7 compared with levels in the control group . Soluble TNF receptors were unaffected by DSCG . There was a trend towards lower IL-1 beta levels in DSCG-treated infants on Day 7 , but IL-1ra levels were unaffected by DSCG therapy . Three control subjects , but no DSCG-treated infants , died during the study period ( p = 0.07 ) . There were no significant differences between survivors of the two groups for oxygen-dependency at 28 d ( 100 % control subjects ; 85 % DSCG ) . These results suggest that nebulized DSCG may exert an anti-inflammatory effect in the lungs of infants < or = 1,000 g at risk for BPD Background . Although several trials of early dexamethasone therapy have been completed to determine if such therapy would reduce mortality and chronic lung disease ( CLD ) in infants with respiratory distress , optimal duration and side effects of such therapy remain unknown . Purpose . The purpose of this study was : 1 ) to determine if a 3-day course of early dexamethasone therapy would reduce CLD and increase survival without CLD in neonates who received surfactant therapy for respiratory distress syndrome and 2 ) to determine adverse effects associated with such therapy . Design . This was a prospect i ve multicenter r and omized trial comparing a 3-day course of dexamethasone therapy beginning at 24 to 48 hours of life to placebo therapy . Two hundred forty-one neonates ( dexamethasone n = 118 , placebon = 123 ) , who weighed between 500 g and 1500 g , received surfactant therapy , and were at significant risk for CLD or death using a model to predict CLD or death at 24 hours of life , were enrolled in the trial . Infants r and omized to receive early dexamethasone were given 6 doses of dexamethasone at 12-hour intervals beginning at 24 to 48 hours of life . The primary outcomes compared were survival without CLD and CLD . CLD was defined by the need for supplemental oxygen at the gestational age of 36 weeks . Complication rates and adverse effects of study drug therapy were also compared . Results . Neonates r and omized to early dexamethasone treatment were more likely to survive without CLD ( RR : 1.3 ; 95 % CI : 1.03 , 1.7 ) and were less likely to develop CLD ( RR : 0.6 ; CI : 0.3 , 0.98 ) . Mortality rates were not significantly different . Subsequent dexamethasone therapy use was less in early dexamethasone-treated neonates ( RR : 0.8 ; CI : 0.7 , 0.96 ) . Very early ( ≤7 days of life ) intestinal perforations were more common among dexamethasone-treated neonates ( 8 % vs 1 % ) . Conclusion . We conclude that an early 3-day course of dexamethasone therapy increases survival without CLD , reduces CLD , and reduces late dexamethasone therapy in high-risk , low birth weight infants who receive surfactant therapy for respiratory distress syndrome . Potential benefits of early dexamethasone therapy at the dosing schedule used in this trial need to be weighed against the risk for early intestinal perforation OBJECTIVE Since preventive therapies for bronchopulmonary dysplasia ( BPD ) are limited we treated preterm infants with azithromycin to decrease the incidence of BPD . METHODS Infants less than 1,250 g birth weight were r and omized to azithromycin or placebo within 12 hr of beginning mechanical ventilation and within 72 hr of birth . The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for a maximum of 6 weeks . Aspirates were collected during the study to assay for Ureaplasma . The primary endpoints were incidence of BPD or mortality . ( Clinical Trials Identifier : NCT00319956 . ) RESULTS A total of 220 infants were enrolled ( n=111 azithromycin , and 109 placebo ) . Mortality was 18 % for the azithromycin group versus 22 % for the placebo group ( P = 0.45 ) . Incidence of BPD was 76 % for the azithromycin group versus 84 % for the placebo group ( P=0.2 ) . The multiple logistic regression analysis demonstrated an odds ratio of 0.46 decrease in the chance of developing BPD or death for the azithromycin group , but was not statistically significant . The incidence of BPD in the Ureaplasma subgroup was 73 % in the azithromycin group versus 94 % in the placebo group ( P=0.03 ) . Analysis of patients in the Ureaplasma subgroup only , using the exact logistic model demonstrated a decrease in BPD or death in the azithromycin group with an estimated odds ratio of 0.026 ( 0.001 - 0.618 , 95 % confidence interval ) . CONCLUSIONS Routine use of azithromycin therapy for the prevention of BPD can not be recommended . The early treatment of Ureaplasma colonized/infected patients might be beneficial , but a larger multi-centered trial is required to assess this more definitively OBJECTIVES To assess the safety-efficacy balance of low-dose inhaled nitric oxide ( iNO ) in hypoxemic premature infants because no sustained beneficial effect has been demonstrated clearly and there are concerns about side effects . STUDY DESIGN Eight hundred and sixty infants < 32 weeks were r and omized at birth to receive 5 ppm iNO or placebo when they presented with hypoxemic respiratory failure ( HRF ) defined by a requirement for mechanical ventilation , fraction of inspired oxygen ( FIO 2 ) > 40 % , and arterio-alveolar ratio in oxygen ( aAO 2 ) < 0.22 . The primary end point was intact survival at 28 days of age . RESULTS Sixty-one of 415 infants presented with HRF and were compared with 84 of 445 controls who presented with HRF . There was no difference in the primary end point ( 61.4 % in infants [ 23 % with HRF who were treated with iNO ] vs 61.1 % in controls [ 21.4 % in controls with HRF ] ; P = .943 ) . For the infants with HRF who were treated with iNO , there was no significant difference from controls for intraventricular hemorrhage ( IVH ) ( 6 % vs 7 % ) , necrotizing enterocolitis ( 8 % vs 6 % ) , or patent ductus arteriosus ( PDA ) ( 34 % vs 37 % ) . Compared with nonhypoxemic infants , the risk of bronchopulmonary displasia ( BPD ) increased significantly in HRF controls ( OR = 3.264 [ CI 1.461 - 7.292 ] ) but not in infants with HRF who were treated with iNO ( OR = 1.626 [ CI 0.633 - 4.178 ] ) . CONCLUSIONS iNO appears to be safe in premature infants but did not lead to a significant improvement in intact survival on day 28 BACKGROUND AND OBJECTIVE : Effective health care for children must be based on thorough analyses of the best research evidence . The objective of this study was to examine registration , completeness , and publication of studies involving children . METHODS : We search ed the Clinical Trials.gov registry to identify all closed studies involving children and examined them for completeness and availability of results . We examined publication in peer- review ed journals for 160 r and omly selected National Institutes of Health (NIH)–funded studies from 2000 through 2010 and for 758 r and omly selected completed studies . RESULTS : Of 3428 closed studies involving children identified in Clinical Trials.gov , 2385 ( 70 % ) were completed , 28 ( 0.8 % ) suspended , 152 ( 4.4 % ) terminated , and 38 ( 1.1 % ) withdrawn . The proportion of non-completed studies ( terminated and suspended ) increased linearly by 186 % between 2001 and 2009 , from 1.9 % to 8.4 % . Of the 152 terminated studies , 48 did not report reasons for termination , 21 cited safety concerns , and 83 cited poor recruitment or other administrative reasons . Only 29 % of completed studies were published . Publication that did occur was an average of 2 years after study completion . Completed interventional studies were published more often than observational studies . Completed industry-funded studies were published less often than studies funded by the NIH . Registered NIH-funded trials were published more often than unregistered . CONCLUSIONS : Results are unavailable for more than half of the studies involving children , revealing a substantial publication bias . Registration and posting of results on Clinical Trials.gov should be m and atory for all studies involving children Abstract Background : Reactive oxygen species have been considered to play a role in several clinical complications in pre-term infants . The aim of this study was to determine the pharmacokinetics of intravenous N-acetylcysteine in pre-term neonates . This information is needed to evaluate the use of N-acetylcysteine as an antioxidant in this patient group . Methods : N-acetylcysteine was infused intravenously in ten patients ( gestational age 24.9–31.0 weeks , weight 500–1384 g ) for 24 h ( 3.4–4.6 mg/kg/h ) , starting 2.0–11.2 h from birth ( study I ) and in six patients ( gestational age 25.9–29.7 weeks , weight 520–1335 g ) for 6 days ( 0.3–1.3 mg/kg/h ) , starting at the age of 24 h ( study II ) . Arterial plasma N-acetylcysteine and cyst(e)ine concentrations were determined from timed sample s taken during ( study I and II ) and after ( study Output:	Conclusion : The majority of the drugs studied in RCTs failed to reduce the incidence of BPD .
MS22263	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS The aim of this study was to determine the occurrence and role of yeasts , enteric gram-negative rods and Enterococcus species in root-filled teeth with chronic apical periodontitis , and the antimicrobial effect of iodine potassium iodide ( IKI ) irrigation . METHODOLOGY Forty symptom-free root-filled teeth with chronic apical periodontitis were included in the study . The patients were divided into two groups . In group A the canals were filled with calcium hydroxide for 10 - 14 days after cleaning and shaping ; in group B the canals were irrigated with IKI for 5 min after cleaning and shaping followed by a permanent root filling . Microbiological sample s were taken from the canals before and after the chemomechanical preparation and after iodine irrigation ( group B ) . RESULTS Microbes were isolated from 33 of 40 teeth in the initial sampling . Yeasts were isolated from six teeth , three of them together with E. faecalis . Enteric rods ( Escherichia coli , Klebsiella pneumoniae and Proteus mirabilis ) were present in three teeth and E. faecalis was isolated from 21 of the 33 culture positive teeth , 11 in pure culture . Growth was detected in 10 teeth of the second sample s. Six of the 10 cases were E. faecalis , with five being a pure culture . All third sample s ( after IKI ) except one were negative . The number of microbial cells per sample did not correlate with lesion size . Two flare-ups were recorded , both in teeth with a mixed infection . CONCLUSION The high prevalence of enteric bacteria and yeasts in root-filled teeth with chronic apical periodontitis was established . IKI improved the antimicrobial effect of the treatment Traditional clinical review articles , also known as up date s , differ from systematic review s and meta-analyses . Up date s selectively review the medical literature while discussing a topic broadly . Non-quantitative systematic review s comprehensively examine the medical literature , seeking to identify and synthesize all relevant information to formulate the best approach to diagnosis or treatment . Meta-analyses ( quantitative systematic review s ) seek to answer a focused clinical question , using rigorous statistical analysis of pooled research studies . This article presents guidelines for writing an evidence -based clinical review article for American Family Physician . First , the topic should be of common interest and relevance to family practice . Include a table of the continuing medical education objectives of the review . State how the literature search was done and include several sources of evidence -based review s , such as the Cochrane Collaboration , BMJ 's Clinical Evidence , or the InfoRetriever Web site . Where possible , use evidence based on clinical outcomes relating to morbidity , mortality , or quality of life , and studies of primary care population s. In articles su bmi tted to American Family Physician , rate the level of evidence for key recommendations according to the following scale : level A ( r and omized controlled trial [ RCT ] , meta- analysis ) ; level B ( other evidence ) ; level C ( consensus/expert opinion ) . Finally , provide a table of key summary points In many areas of medicine the amount of published information is increasing at an exponential rate , making it difficult for the clinician to condense the data to a manageable amount of valuable and useful information . Systematic review s have been suggested as a remedy for this information overload . Such review s are regarded as the highest level of evidence . Certain statistical methods , e.g. , meta- analysis , have also been introduced for the calculation of a more comprehensive summation of the compiled results from studies with small sample sizes . These findings would then serve as an authoritarian guide for evidence -based practice . Endodontists have lately jumped on the b and wagon of systematic review s and meta-analyses , and papers on various topics are being published . Well done , such comprehensive information would be very useful and authoritative for the practitioner . Alarmingly , the quality of these recent publications is negatively correlated to the frequency . This can have serious consequences in the clinical arena if spurious information is given a seal of approval when communicated as facts in refereed journals . A systematic literature review is design ed to focus on a single question and to synthesize all high- quality research reports relevant to the question . In these studies , however , sources of bias are often not controlled . Therefore , even the best review and meta- analysis becomes useless if it is based on poorly design ed research . Furthermore , these review s are mostly based on published data which are too often biased toward studies that show significant differences in results and /or outcome . “ Uninteresting ” conclusions tend not to be published . Endodontic literature , thus far , is short on well design ed and executed r and omized clinical trials . Furthermore , clinical protocol s often have many important “ proprietary ” modifications that make comparison difficult . This makes it very hard to undertake a systematic review to answer a narrow question . Such GIGO ( garbage in , garbage out ) can easily lead to biased conclusions and reinforce already existing biased comclusions . An example of such bias can be illustrated by a meta- analysis recently published . The study focused on assessing if there were differences in outcome between 1 and 2 treatment visits when treating teeth with apical periodontitis . Relevant publications on this topic are rare , and with the narrow inclusion criteria only 3 investigations were available for the review . However , the only factors connecting these 3 studies was the words “ single ” and “ two visits ” in the title . Beyond that , the selected studies are too different and inadequate for the study . Only 1 study is somewhat demonstrably r and omized , and outcome assessment s are based on 3 vastly different criteria . Two of the studies use calcium hydroxide as intracanal dressing , whereas the third uses no intervisit medication . Complexity of initial pathology and healing time are also clearly factors of great importance but not controlled . In addition , sample sizes in the component studies as well as the final cohort are all too small for the conclusions that there was no significant difference between 1or 2-visit treatment protocol s. To undertake and publish a meta- analysis on such an incomplete sample is counterproductive . Although the publication noted its numerous limitations , it will still communicate erroneous conclusions with a poor scientific foundation to the less informed reader . There are other examples of recently published systematic review s that are very ambiguous and tend to communicate spurious facts . One of these studies looks at the effect of smear-layer removal on sealing ability of root canal obturation . The study is entirely limited to laboratory experiments , with the majority of evaluations using dye leakage which is generally considered to be unreliable . This is an example of review ers lacking content expertise . The authors draw the conclusion , using defective review material , that removal of smear layer enhances the seal of the root filling . We may generally believe that this is the truth Output:	In conclusion , NaOCl or CHX showed low ability to eliminate E. faecalis when evaluated by either PCR or culture techniques
MS22264	*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: Traumatic stress due to conflict and war causes major mental health problems in many re source -poor countries . The objective of this study was to examine whether trained lay counselors can carry out effective treatment of posttraumatic stress disorder ( PTSD ) in a refugee settlement . In a r and omized controlled dissemination trial in Ug and a with 277 Rw and an and Somalian refugees who were diagnosed with PTSD the authors investigated the effectiveness of psychotherapy administered by lay counselors . Strictly manualized narrative exposure therapy ( NET ) was compared with more flexible trauma counseling ( TC ) and a no-treatment monitoring group ( MG ) . Fewer participants ( 4 % ) dropped out of NET treatment than TC ( 21 % ) . Both active treatment groups were statistically and clinical ly superior to MG on PTSD symptoms and physical health but did not differ from each other . At follow-up , a PTSD diagnosis could not be established anymore in 70 % of NET and 65 % TC participants , whereas only 37 % in MG did not meet PTSD criteria anymore . Short-term psychotherapy carried out by lay counselors with limited training can be effective to treat war-related PTSD in a refugee settlement We examined the feasibility , acceptability , and therapeutic efficacy of a culturally adapted cognitive – behavior therapy ( CBT ) for twelve Vietnamese refugees with treatment-resistant posttraumatic stress disorder ( PTSD ) and panic attacks . These patients were treated in two separate cohorts of six with staggered onset of treatment . Repeated measures Group × Time ANOVAs and between-group comparisons indicated significant improvements , with large effect sizes ( Cohen 's d ) for all outcome measures : Harvard Trauma Question naire ( HTQ ; d=2.5 ) ; Anxiety Sensitivity Index ( ASI ; d=4.3 ) ; Hopkins Symptom Checklist-25 ( HSCL-25 ) , anxiety subscale ( d=2.2 ) ; and Hopkins Symptom Checklist-25 , depression subscale ( d=2.0 ) scores . Likewise , the severity of ( culturally related ) headache- and orthostasis-cued panic attacks improved significantly across Little is known about the usefulness of psychotherapeutic approaches for traumatized refugees who continue to live in dangerous conditions . Narrative exposure therapy ( NET ) is a short-term approach based on cognitive-behavioral therapy and testimony therapy . The efficacy of narrative exposure therapy was evaluated in a r and omized controlled trial . Sudanese refugees living in a Ug and an refugee settlement ( N = 43 ) who were diagnosed as suffering from posttraumatic stress disorder ( PTSD ) either received 4 sessions of NET , 4 sessions of supportive counseling ( SC ) , or psychoeducation ( PE ) completed in 1 session . One year after treatment , only 29 % of the NET participants but 79 % of the SC group and 80 % of the PE group still fulfilled PTSD criteria . These results indicate that NET is a promising approach for the treatment of PTSD for refugees living in unsafe conditions Concentration camp survivors from Bosnia-Herzegovina , now refugees in the Netherl and s , were given early outpatient treatment for posttraumatic stress disorder ( PTSD ) for 6 months . They were tested with the Watson Question naire before entering therapy , after 6 months and 3 years later when a structured interview design ed to obtain information on psychosocial status was administered . Data were analyzed with PCA-STAT 1.1 statistical package . The treatment was effective on a short-term basis with some long-term effects . Elderly people were no more vulnerable to the onset of PTSD than younger ones but were more resistant to therapy . Psychosocial factors had neither protective nor risk value for the development of PTSD in this group The present study was design ed to evaluate the effects on children ( age : M = 5.5 years ) in war-torn Bosnia and Herzegovina of a psychosocial intervention program consisting of weekly group meetings for mothers for 5 months . An additional aim was to investigate the children 's psychosocial functioning and the mental health of their mothers . Internally displaced mother-child dyads were r and omly assigned to an intervention group receiving psychosocial support and basic medical care ( n = 42 ) or to a control group receiving medical care only ( n = 45 ) . Participants took part in interviews and tests to provide information about war exposure , mental health , psychosocial functioning , intellectual abilities , and physical health . Results showed that although all participants were exposed to severe trauma , their manifestations of distress varied considerably . The intervention program had a positive effect on mothers ' mental health , children 's weight gain , and several measures of children 's psychosocial functioning and mental health , whereas there was no difference between the two groups on other measures . The findings have implication s for policy Rates of posttraumatic stress disorder ( PTSD ) are exceptionally high among asylum-seekers . Reportedly , stressors caused by the asylum procedure and psychological consequences of torture contribute to the maintenance of symptoms and interfere with treatment . In a pilot r and omized controlled trial , the authors examined the efficacy of trauma-focused treatment in 32 asylum-seekers with PTSD result ing from state-sponsored violence and other traumatic events . Narrative exposure therapy ( NET ) was compared with treatment as usual ( TAU ) , with a focus on stabilization and psychoactive medication . Six months after treatment , a significant reduction of posttraumatic stress symptoms was found in the NET participants but not in the TAU group . Although treatment gains were moderate , these results indicate that NET is a promising approach for the treatment of PTSD in asylum-seekers living in unstable conditions This article examines the ability of the panic attack – posttraumatic stress disorder ( PTSD ) model to predict how panic attacks are generated and how panic attacks worsen PTSD . The article does so by determining the validity of the panic attack – PTSD model in respect to one type of panic attack among traumatized Cambodian refugees : orthostatic panic ( OP ) attacks ( i.e. panic attacks generated by moving from lying or sitting to st and ing ) . Among Cambodian refugees attending a psychiatric clinic , the authors conducted two studies to explore the validity of the panic attack – PTSD model as applied to OP patients ( i.e. patients with at least one episode of OP in the previous month ) . In Study 1 , the panic attack – PTSD model accurately indicated how OP is seemingly generated : among OP patients ( N = 58 ) , orthostasis‐associated flashbacks and catastrophic cognitions predicted OP severity beyond a measure of anxious – depressive distress ( Symptom Checklist‐90‐R subscales ) , and OP severity significantly mediated the effect of anxious – depressive distress on Clinician‐Administered PTSD Scale severity . In Study 2 , as predicted by the panic attack – PTSD model , OP had a mediational role in respect to the effect of treatment on PTSD severity : among Cambodian refugees with PTSD and comorbid OP who participated in a cognitive behavioural therapy study ( N = 56 ) , improvement in PTSD severity was partially mediated by improvement in OP severity The present study investigated the efficacy of cognitive-behavior therapy ( CBT ) and exposure therapy ( E ) in the treatment of post-traumatic stress disorder ( PTSD ) in refugees . Sixteen out patients fulfilling the DSM-IV criteria for PTSD were r and omized to one of the two treatments . Assessor and self-report measures of PTSD-symptoms , generalized anxiety , depression , quality of life and cognitive schemas were administered before and after treatment , and at a 6-month follow-up . The patients were treated individually for 16 - 20 weekly sessions . The results showed that both treatments result ed in large improvements on all the measures , which were maintained at the follow-up . There was no difference between E and CBT on any measure . E and CBT led to a 48 and 53 % reduction on PTSD-symptoms , respectively , a 49 and 50 % reduction on generalized anxiety , and a 54 and 57 % reduction on depression . The results were maintained at the 6-month follow-up . The conclusion that can be drawn is that both E and CBT can be effective treatments for PTSD in refugees Based on the results of a r and omized controlled trial , we examined a model of the mechanisms of efficacy of culturally adapted cognitive‐behavior therapy ( CBT ) for Cambodian refugees with pharmacology‐resistant posttraumatic stress disorder ( PTSD ) and comordid orthostatic panic attacks ( PAs ) . Twelve patients were in the initial treatment condition , 12 in the delayed treatment condition . The patients r and omized to CBT had much greater improvement than patients in the waitlist condition on all psychometric measures and on one physiological measure — the systolic blood pressure response to orthostasis ( d = 1.31)—as evaluated by repeated‐ measures MANOVA and planned contrasts . After receiving CBT , the Delayed Treatment Group improved on all measures , including the systolic blood pressure response to orthostasis . The CBT treatment 's reduction of PTSD severity was significantly mediated by improvement in orthostatic panic and emotion regulation ability . The current study supports our model of the generation of PTSD in the Cambodian population , and suggests a key role of decreased vagal tone in the generation of orthostatic panic and PTSD in this population . It also suggests that vagal tone is involved in emotion regulation , and that both vagal tone and emotion regulation improve across treatment Cambodian refugees with posttraumatic stress disorder ( PTSD ) represent a cohort in severe need of treatment , but little information is available to guide treatment choices . We selected a sample of pharmacotherapy-refractory individuals to test the efficacy of combination treatment with sertraline and cognitive-behavior therapy ( CBT ) for treating PTSD . Participants in this pilot study were ten Khmer-speaking women who had been at a mean age of 22 - 26 years during the Pol Pot period ( 1975 - 1979 ) . These patients were r and omly assigned to either sertraline alone or combined treatment . We found that combined treatment offered additional benefit in the range of medium to large effect sizes for PTSD and associated symptoms . Our findings indicate that substantial gains can be achieved by adding CBT to pharmacotherapy for PTSD , and that a program of CBT emphasizing information , exposure , and cognitive-restructuring can be successfully modified for Khmer-speaking refugees Output:	Very large effect sizes were obtained in some of the CBT studies , indicating a broad suitability of CBT in the treatment of core symptoms of PTSD in adult refugees . Empirical evidence also points to the possibility that the maladaptive traumatic reactions in refugees can take shape of more complex reactions than those strictly specified in the diagnostic category of PTSD . Effectiveness of CBT treatments has as yet not been tested on the whole range of symptoms in these complex cases .
MS22265	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND We tested the hypothesis that impairment in the ability to take medication independently predicts early functional decline . METHODS A 12-month , prospect i ve cohort study was performed at two continuing-care retirement facilities using the Drug Regimen Unassisted Grading Scale ( DRUGS ) . This geriatric screening tool utilizes a stepwise progression of four tasks : ( i ) identification , ( ii ) access . ( iii ) dosage , and ( iv ) timing . RESULTS Forty-seven ( 86 % ) of the eligible participants completed the 12-month follow-up assessment ; three were transferred to skilled nursing facilities . The mean age at study entry was 84.2+/-5.1 years ; 72 % of the participants were women , and 68 % were college educated . At 12 months there was a decline in the Mini-Mental State Examination ( MMSE ) score ( p = .029 ) , an increase in the timed " Up and Go " test ( p = .023 ) , and a decline in the DRUGS score ( p .029 ) . Nine ( 18 % ) of the participants resided in assisted- versus independent-living situations compared with three participants ( 5 % ) at study entry ( p = .031 ) . Both 12-month DRUGS score and 12-month self-reported medication management capacity were associated with 12-month MMSE ( p = .0001 and p = .019 , respectively ) . Baseline DRUGS score was associated with 12-month MMSE and Geriatric Depression Scale scores ( p = .0002 and p = .002 , respectively ) . Both baseline DRUGS score and self-reported medication management capacity were also associated with residence in assisted-living communities at 6 months ( p = .029 and p = .040 , respectively ) . MMSE was not associated with any of the clinical outcomes Abstract BACKGROUND : Patients ’ ability to manage medications is critical to chronic disease control . Also known as medication management capacity ( MMC ) , it includes the ability to correctly identify medications and describe how they should be taken . OBJECTIVE : To evaluate the effects of low literacy , medication regimen complexity , and sociodemographic characteristics on MMC . DESIGN : Cross-sectional analysis of enrollment data from participants in a r and omized trial . PARTICIPANTS : Patients with coronary heart disease in an inner-city clinic . MEASUREMENTS : Medication management capacity was measured with the Drug Regimen Unassisted Grading Scale ( DRUGS ) , which scores subjects ’ ability to identify , open , describe the dose , and describe the timing of their medications . DRUGS overall and component scores were compared by literacy . Mini Mental State Exam score , regimen complexity ( number of prescription medications ) , and sociodemographic characteristics . RESULTS : Most of the 152 participants were elderly ( mean age 65.4 years ) , women ( 54.6 % ) , and African American ( 94.1 % ) . Approximately half ( 50.7 % ) had inadequate literacy skills , and 28.9 % had marginal skills . In univariate analysis , MMC was significantly associated with literacy ( P<.001 ) , and this effect was driven by the ability to identify medications . In multivariable models , patients with inadequate literacy skills had 10 to 18 times the odds of being unable to identify all of their medications , compared with those with adequate literacy skills ( P<.05 ) . CONCLUSIONS : Adults with inadequate literacy skills have less ability to identify their medications . Techniques are needed to better educate low-literacy patients about their medications , as a potential strategy to enhance adherence OBJECTIVE To examine whether reduced ability to self-administer medication can accurately classify living placement ( independent or assisted living ) in a continuing care retirement community ( CCRC ) . DESIGN Convenience sample of consecutive patients seen in a medical clinic . SETTING An outpatient medical clinic at a CCRC . PARTICIPANTS A group of 78 consecutive patients ( aged 68 - 98 years ) scheduled for a geriatric medical evaluation between May 1 , 2001 , and August 31 , 2001 , residing in an independent ( IL ) or assisted living ( AL ) apartment . MEASUREMENTS Ability to self-administer medication was assessed by asking residents to respond to a medication administration question based on a 5-point Likert scale . Residents were also given measures of cognitive status ( MMSE ) , activities of daily living ( ADL ) , and depression ( GDS ) . Further , age of residents as well as number of falls within the previous 6 months were recorded . RESULTS A discriminant function analysis accurately classified living placement ( IL or AL ) in 89.7 % of the cases based on the ability of residents to self-administer medication . The additions of MMSE score , ADL performance , GDS score , number of falls , and age of the residents to the analyses did not improve the number of cases that were correctly classified . CONCLUSION Ability to self-administer medication emerged as the main predictor of current living environment within the CCRC in the present study . These results underscore the importance of considering a resident 's ability to independently manage his or her medications when placement decisions are being made within CCRCs Background : Consumer participation in planning and implementing health care is actively encouraged as a means of improving patient outcomes . In assessing the ability of patients to self-medicate , health professionals can identify areas in which patients need assistance , education , and intervention to optimize their health outcomes after discharge . Objective : To develop and vali date a tool to quantify the ability of patients to administer their regularly scheduled medications while they are hospitalized . Methods : Past research enabled us to develop the Self-Administration of Medication ( SAM ) tool . Using a Delphi technique of 3 rounds , a panel of expert health professionals established the content validity of the tool . For determining level of agreement in using the SAM tool , 56 patients were selected ; for each patient , 2 r and omly selected nurses completed an assessment . Construct validity and internal consistency were examined by testing the tool in 50 patients and comparing with other vali date d scales . Results : The 29-item SAM tool had high content validity scores for clarity , representation , and comprehensiveness , with content validity index values ranging from 0.95–1.0 . In testing the level of agreement between 2 nurses , out of 43 valid cases , 95.3 % of nurses overwhelmingly agreed about the patients ’ competence to self-administer their drugs . The intraclass correlation coefficient was 0.819 ( 95 % Cl 0.666 to 0.902 ) . Internal consistency for the SAM tool was high , with a Cronbach 's alpha of 0.899 . A moderate to strong correlation was obtained when comparing the SAM tool with other vali date d measures . Conclusions : The SAM tool is valid and reliable for quantifying patients ’ ability to manage their regularly scheduled medications in the hospital setting This study used performance tests to assess the cognitive , visual and physical abilities related to taking medicines in the elderly population . The study population consisted of the Swedish Panel Study of Living Conditions of the Oldest Old ( SWEOLD II ) , a nationally representative interview survey . SWEOLD II is a r and om sample of all community-based and institutionalized persons aged 77 + in Sweden . Five tests related to medication management were administered in the direct interviews ( n=492 ) : h and function ( opening bottle ) , vision ( reading label ) , and medication competence ( comprehension and calculation ) . Results showed that 9.4 % could not read instructions on a medicine container and 14.6 % had difficulty opening a plastic flip-top medicine bottle . The three cognitive tests related to taking medicine result ed in 30.7 , 47.4 and 20.1 % errors . Combining all the tests revealed that 66.3 % of the sample had at least one limitation of capacity related to taking medicine . There were no significant gender differences . Among those people who did not pass all the tests , 31.8 % lived alone with no home-help . Taking medicines is a complex task and a large proportion of the Swedish elderly population has cognitive , visual or physical limitations that may hinder their ability to take medicines accurately . Awareness of these limitations is essential to concordance OBJECTIVE To study the relationship between four cognitive screens ( Mini-Mental State Examination [ MMSE ] , Mini-Cog , Medication Transfer Screen [ MTS ] , and Medi-Cog [ Mini-Cog + MTS ] ) and pillbox concordance . DESIGN Prospect i ve cross-sectional pilot study . SETTING Primary care federal health care system . PARTICIPANTS English literate in patients not previously diagnosed or treated for dementia and without physical h and icap preventing use of a pillbox . MAIN OUTCOME MEASURE Correlation between cognitive screens and prospect i ve pill-count scores ( PPCS ) . INTERVENTIONS Mini-Cog , MTS , and MMSE screening was followed by a 28-compartment pillbox skills assessment . A passing PPCS was defined as correctly loading 80 % of the medications in the pillbox . A PPCS of < 80 % identified patients for pillbox-organization education or supportive intervention . Variables associated with total and passing PPCS were analyzed by multivariate linear and logistic regression , respectively . RESULTS Fifty-three patients discharged on > 1 medication completed all screenings . Other than cognitive screening , only age was associated with total and passing PPCS . After adjustment for age , Medi-Cog had the highest correlation with total PPCS [ r2=0.53 ; P<0.001 ) , whereas Mini-Cog was the single cognitive assessment that remained significantly associated with a passing PPCS ( r2=0.23 ; P=0.023 ) . Age-adjusted models , including MMSE , had relatively poor association with total PPCS ( r2=0.23 ; P=0.046 ) and no association with passing PPCS ( r2=0.15 ; P=0.46 ) . The Medi-Cog exhibited modest highest overall sensitivity ( 72 % ) and specificity ( 61 % ) to detect a passing PPCS . CONCLUSION MMSE is a relatively poor measure of the ability of patients to fill a pillbox . The Medi-Cog and Mini-Cog may have value for assessing pillbox concordance for patients who load their own pillboxes OBJECTIVES To assess relationships between vision ( contrast sensitivity , stereopsis , visual acuity ) and a performance-based measure of ability to implement new medications . DESIGN Cross-sectional analysis ; prospect i ve cohort study . SETTING Community-based . PARTICIPANTS Three hundred thirty-five participants aged 73 to 82 in Year 3 of the Women 's Health and Aging Study II , a representative sample of the two-thirds least-disabled community-dwelling women . MEASUREMENTS Hopkins Medication Schedule Pillbox Ratio , a joint measure of accuracy and time , and a performance-based measure of ability to implement a prescription . Participants received written and verbal instructions for taking two medications and were directed to place pills in a pillbox accordingly . Vision assessment s : contrast sensitivity ( Pelli-Robson letter sensitivity chart ) , stereopsis ( R and ot Circles ) , and visual acuity ( Early Treatment Diabetic Retinopathy Study eye chart ) . RESULTS Forty-four percent ( 148/335 ) of women incorrectly placed one or both medications . Each vision measure was positively associated with Pillbox Ratio scores and varied with cognition and time to completion . Better visual acuity , contrast sensitivity , and stereopsis were each associated with better performance in women with poor cognition who filled the pillbox quickly . Additionally , better visual acuity was associated with better performance in participants with good cognition who filled the pillbox slowly ; better stereopsis was associated with better performance in participants with poor cognition who filled the pillbox slowly and whose stereoacuity was below normal . CONCLUSION Visual acuity , contrast sensitivity , and stereopsis should be considered potential risk factors for impaired ability to implement a medication regimen in older adults . Future research should investigate the role of vision , including contrast sensitivity and stereopsis , on performance of other instrumental activities of daily living OBJECTIVES To clarify the association between unmet medication management need and 3-year mortality and hospitalization for community-dwelling older people with various levels of disabilities . DESIGN Prospect i ve cohort study ( the Nagoya Longitudinal Study for Frail Elderly ) . SETTING Community-based . PARTICIPANTS One thous and seven hundred seventy-two community-dwelling elderly subjects ( 611 men , 1,161 women ) . MEASUREMENTS Data included the clients ' demographic characteristics , a rating for basic and instrumental activities of daily living ( ADLs ) , number of prescribed medications and physician-diagnosed chronic diseases , medication adherence , ability to manage medication , and presence or absence of medication assistance . Cox proportional hazard models and the Kaplan-Meier method were used to assess the association between the medication management at baseline and mortality or hospitalization during a 3-year period . RESULTS Of 1,772 participants , 681 reported no difficulty with self-medication management , and 1,091 experienced difficulty with self-medication . Of participants with difficulty with self-medication management , 929 had medication assistance , and 162 did not . During a 3-year follow up , 424 participants died , and 758 were admitted to hospitals . The baseline data demonstrated that participants not receiving medication assistance were younger and had better ADL status and fewer comorbidities . Multivariate Cox regression models adjusting for potential confounders showed that the lack of assistance in those who needed medication assistance was associated with hospitalization but not mortality during the study period . CONCLUSION In community-dwelling disabled elderly people , lack of medication assistance in those needing medication support was associated with higher risk of hospital Output:	Most instruments had some evidence of construct validity , through associations with tests of cognitive function , health literacy , activities of daily living or measures of medication management or adherence . Conclusion A number of performance-based instruments exist to assess patients ' capacity to manage their own medications .
MS22266	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To investigate whether protein intake influences the decline in energy expenditure during energy restriction . DESIGN Cross-over study of three diets of 4.2 MJ/d for 7 days : one diet with 36 % energy as protein and two with 15 % energy as protein , one high in carbohydrate and the other high in fat . SUBJECTS Two men and six women aged 31 - 57 y. BMI 27.B-34.1 kg/m2 . MEASUREMENTS 24-h energy expenditure ( 24-h EE ) , sleeping metabolic rate ( SMR ) and body weight on days 0 and 7 of each diet ; 24-h urinary nitrogen excretion ( 24-h UN ) on days 0 - 7 of each diet . RESULTS 24-h EE and SMR declined on all three diets but the decrease was significantly less on the high protein diet than on the two low protein diets . Weight loss was similar on all three diets . 24-h UN was less than N intake on the high protein diet but greater than N intake on the two low protein diets . CONCLUSIONS Maintaining protein intake reduces the decrease in energy expenditure during energy restriction We measured energy expenditure ( MREE ) and nitrogen excretion ( UUN ) in patients with severe head injury r and omized to early parenteral ( TPN , n = 21 ) or jejunal ( ENT , n = 27 ) feeding with identical formulations . The MREE rose to 2400 + /- 531 kcal/day in both groups and remained at 135 % + /- 26 % to 146 % + /- 42 % of predicted energy expenditure over 4 weeks . Nitrogen excretion peaked the second week at 33.4 + /- 10 ( TPN ) and 31.2 + /- 7.5 ( ENT ) g N/day . Both routes were equally effective at meeting nutritional goals ( 1.2 x MREE , 2.5 g protein/kg/day intake , stabilized albumin and transferrin levels ) . Infections were equally frequent : 1.86 episodes/TPN patient versus 1.89 episodes/ENT patient . While patient charges were much greater for TPN , the hospital costs were similar for TPN and ENT support regimens . These findings show that patients with head injuries are hypermetabolic for weeks , that only 27 % are capable of spontaneously eating nutritional requirements by discharge , and that either TPN or ENT support is equally effective when prescribed according to individual measurements of MREE and nitrogen excretion Metabolic effects of increasing nitrogen intake during total parenteral nutrition ( TPN ) were studied in nine septic patients . The patients were given 5 % dextrose ( D5W ) for 1 d. For the next 6 d they received total parenteral nutrition ( TPN ) , at 1.35 times resting energy expenditure ( REE ) , containing either 191 or 366 mg N/(kg.d ) Non-protein calories were divided equally between glucose and lipid emulsion . Three patients were studied on both diets ( n = 6 for each diet ) . On the high- but not the low-N diet were significant increases in protein oxidation , blood urea N , O2 consumption , and CO2 production . TPN normalized most plasma amino acid levels but intramuscular amino acids remained unchanged . Transient positive N balance occurred during days 1 - 3 on the high- but not the low-N intake ; on days 5 - 6 N balance did not differ significantly from zero on either diet and the improvement ( 165 mg N/[kg.d ] ) was the same for both diets The aim of the study was to assess the total energy expenditure ( TEE ) , resting energy expenditure ( REE ) and physical activity level ( PAL ) in home-living cachectic patients with advanced pancreatic cancer . The influence of an energy and protein dense oral supplement either enriched with or without the n-3 fatty acid eicosapentaenoic acid ( EPA ) and administered over an 8-week period was also determined . In total , 24 patients were studied at baseline . The total energy expenditure was measured using doubly labelled water and REE determined by indirect calorimetry . Patients were studied at baseline and then r and omised to either oral nutritional supplement . Measurements were repeated at 8 weeks . At baseline , REE was increased compared with predicted values for healthy individuals ( 1387(42 ) vs 1268(32 ) kcal day−1 , P=0.001 ) , but TEE ( 1732(82 ) vs 1903(48 ) kcal day−1 , P=0.023 ) and PAL ( 1.24(0.04 ) vs 1.50 ) were reduced . After 8 weeks , the REE , TEE and PAL of patients who received the control supplement did not change significantly . In contrast , although REE did not change , TEE and PAL increased significantly in those who received the n-3 ( EPA ) enriched supplement . In summary , patients with advanced pancreatic cancer were hypermetabolic . However , TEE was reduced and this was secondary to a reduction in physical activity . The control energy and protein dense oral supplement did not influence the physical activity component of TEE . In contrast , administration of the supplement enriched with EPA was associated with an increase in physical activity , which may reflect improved quality of life A prospect i ve trial was conducted in 20 surgical intensive care unit patients receiving mechanical ventilation to compare estimates of resting energy expenditure ( REE ) with the measured values . The 12 women and 8 men ( mean age 61.7±2.8 ( s.e.m . ) years ) underwent a full nutritional assessment before measurement of their REE by indirect calorimetry using the MGM II metabolic cart ( Utah Medical ) . Their REE was estimated by the Harris‐Benedict formula ( mean 1324±53 ( s.e.m . ) kcal/day ) as well as an empirical formula ( where empirical formula = 22 × body weight in kg ) ( 1370 ± 68 ( s.e.m . ) kcal/day ) . Results by either estimate were not statistically different from the measured resting energy expenditure ( MREE ) ( 1382±130 ( s.e.m . ) kcal/day ) , by one‐way analysis of variance . No multiplication factors were needed to relate the Harris–‐Benedict formula to MREE in this critically ill population and the estimate by the empirical formula was as good and simpler to perform . Although values by the Harris — Benedict formula and empirical formula correlated significantly with MREE ( P<0.05 ) the correlation coefficients were low : 0.48 and 0.45 respectively . Thus , mean estimates were excellent for the group but less predictive for the individual . Multiple linear regressions did reveal that body composition and metabolic stress were of greater predictive value , since an equation relating weight ( P<0.003 ) , sex ( P<0.003 ) , white blood cell count ( P < 0.003 ) and 24‐h urinary creatinine excretion ( P < 0.05 ) could predict 76 per cent of the variation ( r = 0.87 ) in the MREE with an overall significance of P = 0.0002 . Given the importance of matching energy intake to needs in many critically ill patients who are mechanically ventilated , accurate measurement of the REE is recommended now that instrumentation is equal to the task OBJECTIVES We measured the energy and protein needs in 50 sequential , critically ill , ventilated patients requiring continuous renal replacement therapy ( CRRT ) for renal failure by using indirect calorimetry and three sequential isocaloric protein-feeding regimes of 1.5 , 2.0 , and 2.5 g. kg(-1 ) . d(-1 ) . We also assessed the compliance of actual feeding with target feeding and correlated the predictive energy requirements of the formulae with the actual energy expenditure ( EE ) measured by indirect calorimetry . We also determined whether these feeding regimes affected patient outcome . METHODS The energy and protein needs of 50 consecutive , critically ill patients ( 31 male ; age 53.3 + /- 17.4 y ; Acute Physiology and Chronic Health Evaluation ( APACHE II ) score : 26.0 + /- 8.0 ; Acute Physiology and Chronic Health Evaluation score predicted risk of death : 50.0 + /- 25.0 % ) were assessed by using indirect calorimetry and ultrafiltrate nitrogen loss . Entry into this study was on commencement of CRRT . To eliminate any beneficial effect from the passage of time on nitrogen balance , 10 of the 50 patients were r and omized to receive 2.0 g. kg(-1 ) . d(-1 ) throughout the study , and the others received an escalating isocaloric feeding regime ( 1.5 , 2.0 , and 2.5 g. kg(-1 ) . d(-1 ) ) at 48-h intervals . Enteral feeding was preferred , but if this was not tolerated or unable to meet target , it was supplemented or replaced by a continuous infusion of total parenteral nutrition . Energy was given to meet caloric requirements as predicted by the Schofield equation corrected by stress factors or based on the metabolic cart readings of EE and was kept constant for all patients throughout the trial . Patients were stabilized on each feeding regime for at least 24 h before sample s of dialysate were taken for nitrogen analysis at 8-h intervals on the second day . CRRT was performed by using a blood pump with a blood flow of 100 to 175 mL/min . Dialysate was pumped in and out counter-currently to the blood flow at 2 L/h . A biocompatible polyacrylonitrile hemofilter was used in all cases . RESULTS EE was 2153 + /- 380 cal/d and increased by 56 + /- 24 cal/d ( P < 0.0001 ) throughout the 6-d study period to 2431 + /- 498 cal/d . At study entry , the mean predicted ( Schofield ) caloric requirement was 2101 + /- 410 . Patients received 99 % of the predicted energy requirements . However , the mean EE was 11 % higher at 2336 + /- 482 calories . This difference was not uniform . If the predicted caloric requirement was less than 2500 , the EE exceeded the predicted by an average of 19 % . If the predicted caloric requirement was greater than 2500 , the EE on average was 6 % less than predicted . This relation was significant ( P = 0.025 ) and has not been described previously . Nitrogen balance was inversely related to EE ( P = 0.05 ) , positively related to protein intake ( P = 0.0075 ) , and more likely to be attained with protein intakes larger than 2 g. kg(-1 ) . d(-1 ) ( P = 0.0001 ) . Nitrogen balance became positive in trial patients over time but were negative in control patients over time ( P = 0.0001 ) . Nitrogen balance was directly associated with hospital outcome ( P = 0.03 ) and intensive care unit outcome ( P = 0.02 ) . For every 1-g/d increase in nitrogen balance , the probability of survival increased by 21 % ( P = 0.03 ; odds ratio , 1.211 ; 95 % confidence limits , 1.017,1.443 ) . Further , although enterally and parenterally fed patients had lower mortalities than predicted , the presence of enteral feeding , even after adjusting for predicted risk of death , had a statistically significant benefit to patient outcome ( P = 0.04 ) . CONCLUSIONS This study found that a metabolic cart can improve the accuracy of energy provision and that a protein intake of 2.5 g. kg(-1 ) . d(-1 ) in these patients increases the likelihood of achieving a positive nitrogen balance and improving survival . Enteral feeding is preferable , but if this is not possible or does not achieve the target , then it should be supplemented by parenteral feeding The metabolic effects of TPN were studied in a selected group of trauma patients . Nineteen patients were r and omly divided into two groups : the first was treated with glucose and insulin , the second with glucose , insulin and amino acids . Each patient in both groups received TPN isocaloric with respect to daily energy output and the treatment lasted five days . Each group was further divided into two subsets ( severe or moderate catabolism ) according to fasting energy output with respect to the expected energy expenditure . During the acute flow phase , both in moderate as well as in severe catabolism , glucose and insulin were effective for protein sparing ; the maximum protein sparing effect was reached when giving a caloric intake equal to 130 % of daily energy output . Glucose , insulin and amino acids were effective in replacement of nitrogen losses . In moderately catabolic patients nitrogen balance was significantly better than in severely catabolic patients . This study shows that early and short-term TPN is effective in controlling the flow phase of trauma . Glucose and insulin appear to be the determinants of the protein sparing effect when given in amounts equal to those needed ; amino acids provided protein replacement when given in amounts equal to about 20 % of energy output . Energy supply higher than 120–130 % of daily energy output does not increase protein sparing and protein replacement , the only effect being a further increase in metabolism , which is possibly dangerous in critically ill patients The effects of increasing nitrogen intake were studied in 10 nutritionally depleted patients receiving total parenteral nutrition . After 1 to 2 days on 5 % dextrose , the patients received , in r and om order , intravenous diets containing either a low ( 18 Output:	The E/N ratio is not a constant value but decreases continuously with increasing protein loss .
MS22267	*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: ObjectOur objective was to investigate the effect of a long-term moderate exercise program on cardiac autonomic nervous system ( ANS ) activity in healthy children . Methods Three hundred and five children aged 6–11 years participated in a 12-month school-based exercise training program ( 130–140 bpm , 20 min/day , 5 days/week ) . Cardiac ANS activities were measured using heart rate variability ( HRV ) power spectral analysis in resting conditions . Following the first measurement , 100 children from the lowest total power ( TP ) HRV were chosen as experimental sample s and the same number of age- , height- , and weight-matched controls ( CG ) was r and omly selected from the remaining children . Results In the low group ( LG ) , all the frequency components of the HRV were significantly increased after the training period , whereas only low-frequency power was augmented in the control group ( CG ) . Conclusion Our data suggest that the 12-month moderate exercise training has a positive effect on cardiac ANS activity in the children who initially had low HRV Despite their extensive use , the reproducibility of cardiac autonomic measurements in children is not well-known . We investigated the reproducibility of short-term continuous measurements of heart rate ( HR ) , heart rate variability ( HRV , time and frequency domain ) , and spontaneous baroreflex sensitivity ( BRS , frequency domain ) in the supine and st and ing position in 57 children ( 11.2+/-0.7 years , 52.6 % boys ) . Reproducibility between two sessions within a two-week interval was evaluated by intraclass correlation coefficients ( ICCs ) , st and ard error of measurement , coefficients of variation ( CVs ) , limits of agreement , and Bl and -Altman plots . HR and HRV were moderately-to-highly ( ICC=.63-.79 ; CV=5.7%-9.7 % ) and BRS moderately ( ICC=.49-.63 ; CV=11.4%-14.0 % ) reproducible . While the BRS measurements were slightly less reproducible than the HR and HRV measurements , all can be reliably applied in research , thus implicating sufficient capacity to detect real differences between children . Still , clinical studies focusing on individual changes in cardiac autonomic functioning need to address the considerable r and om variations that may occur between test-retest measurements The aim of the present investigation was to compare the accuracy of the heart-rate ( HR ) deflection point ( HRDP ) and the second HR variability threshold ( HRVTh2 ) to predict anaerobic threshold in boys . HRDP was determined from slope trends of successive linear regressions . HRVTh2 was determined from the high frequency 's peak and power-density trends . The second ventilatory threshold ( VTh2 ) corresponding to the first decrease in PETCO2 , with an increase in VE /VCO2 , was used as the reference measure of AnT. Results show that VO2 and HR were similar at HRDP , HRVTh2 , and VTh2 . HRVTh2 and HRDP were highly correlated . It appears that HRVTh2 is a good alternative to HRDP for assessing anaerobic threshold . HRVTh2 and HRDP might rely on similar mechanisms Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Objectives : To investigate the reliability of heart rate variability ( HRV ) measures at rest and during light exercise in children . Methods : Short term ( five minute ) HRV was assessed in 12 children ( 11–12 years of age ) . HRV measures were collected at rest with the children supine , breathing at 12 breaths/min , and during exercise on a cycle ergometer while exercising at 25 % of peak oxygen uptake . Both resting and exercise data were collected twice from each child . Results : Intraclass correlation coefficients were low to moderate for most measures with wide confidence intervals for each variable in both resting and exercise conditions . R and om variation ( typical error ) within repeated measurements ranged from 31 % to 187 % . Conclusions : These preliminary findings suggest that HRV measures are unreliable at rest and during light exercise in children aged 11–12 years . Tighter control of extraneous influences is recommended Aging results in marked abnormalities of cardiovascular regulation . Regular exercise can improve many of these age-related abnormalities . However , it remains unclear how much exercise is optimal to achieve this improvement or whether the elderly can ever improve autonomic control by exercise training to a degree similar to that observed in healthy young individuals . Ten healthy sedentary seniors [ 71 + /- 3 ( SD ) yr ] trained for 12 mo ; training involved progressive increases in volume and intensity . Static hemodynamics were measured , and R-wave-R-wave interval ( RRI ) , beat-to-beat blood pressure ( BP ) variability , and transfer function gain between systolic BP and RRI were calculated at baseline and every 3 mo during training . Data were compared with those obtained in 12 Masters athletes ( 68 + /- 3 yr ) and 11 healthy sedentary young individuals ( 29 + /- 6 yr ) at baseline . Additionally , the adaptation of these variables after completion of identical training loads was compared between the seniors and the young . Indexes of RRI variability and baroreflex gain were decreased in the sedentary seniors but preserved in the Masters athletes compared with the young at baseline . With training in the seniors , baroreflex gain and resting BP showed a peak adaptation after moderate doses of training following 3 - 6 mo . Indexes of RRI variability continued to improve with increasing doses of training and increased to the same magnitude as the young at baseline after heavy doses of training for 12 mo ; however , baroreflex gain never achieved values equivalent to the young at baseline , even after a year of training . The magnitude of the adaptation of these variables to identical training loads was similar ( no interaction effects of age x training ) between the seniors and the young . Thus RRI variability in seniors improves with increasing " dose " of exercise over 1 yr of training . In contrast , more moderate doses of training for 3 - 6 mo may optimally improve baroreflex sensitivity , associated with a modest hypotensive effect ; however , higher doses of training do not lead to greater enhancement of these changes . Seniors retain a similar degree of " trainability " as young subjects for cardiac autonomic function to dynamic exercise The risk of sudden death is increased in athletes with a male predominance . Regular physical activity increases vagal tone , and may protect against exercise-induced ventricular arrhythmias . We investigated training-related modulations of the autonomic nervous system in female and male endurance athletes . Runners of a 10-mile race were invited . Of 873 applicants , 68 female and 70 male athletes were r and omly selected and stratified according to their average weekly training hours in a low ( ≤4 h ) and high ( > 4 h ) volume training group . Analysis of heart rate variability was performed over 24 h. Spectral components ( high frequency [ HF ] and low frequency [ LF ] power in normalized units ) were analyzed for hourly 5 min segments and averaged for day- and nighttime . One hundred and fourteen athletes ( 50 % female , mean age 42 ± 7 years ) were included . No significant gender difference was observed for training volume and 10-mile race time . Over the 24-h period , female athletes exhibited a higher HF and lower LF power for each hourly time-point . Female gender and endurance training hours were independent predictors of a higher HF and lower LF power . In female athletes , higher training hours were associated with a higher HF and lower LF power during nighttime . In male athletes , the same was true during daytime . In conclusion , female and male athletes showed a different circadian pattern of the training-related increase in markers of vagal tone . For a comparable amount of training volume , female athletes maintained their higher markers of vagal tone , possibly indicating a superior protection against exercise-induced ventricular arrhythmias OBJECTIVE The beat-to-beat variability in electrocardiogram intervals ( RR , i.e. , heart-period variability ) provides information on cardiac autonomic activity that predicts arrhythmias and mortality rate in animals and adults . We determined the effect of physical training on heart-period variability in obese children . METHODS Thirty-five subjects were r and omly assigned to physical training and control groups . The training involved 4 months of exercise , 5 days per week , 40 minutes per day . Cardiovascular fitness was measured with submaximal heart rate during supine cycling ; percentage of body fat was measured with dual-energy absorptiometry ; and resting heart-period variability parameters were measured in a supine position . A pretraining to posttraining change score was computed for each variable . The effect of the training was determined by comparing the changes of the training and control groups . RESULTS Compared with the control group , the trained group ( 1 ) reduced submaximal heart rate and percentage of body fat ( p < 0.01 ) ; ( 2 ) increased in the root mean square of successive differences , a time-domain parameter reflective of vagal tone ( p < 0.05 ) ; ( 3 ) decreased in low-frequency power expressed as a percentage of total power , a frequency-domain index of combined sympathetic and vagal activity ( p < 0.03 ) ; and ( 4 ) decreased in the ratio of low- to high-frequency power , an index of sympathetic-parasympathetic balance ( p < 0.01 ) . CONCLUSIONS In obese children , physical training alters cardiac autonomic function favorably by reducing the ratio of sympathetic to parasympathetic activity OBJECTIVE Heart rate variability provides non-invasive information about cardiac parasympathetic activity ( PSA ) . We determined in obese children : ( 1 ) relations of baseline PSA to body composition and hemodynamics ; ( 2 ) effects of physical training ( PT ) and cessation of PT ; and ( 3 ) which factors explained individual differences in responsivity of PSA to the PT . RESEARCH METHODS AND PROCEDURES The root mean square of successive differences ( RMSSD ) was the index of PSA . Obese children ( n = 79 ) were r and omly assigned to groups that participated in PT during the first or second 4-month periods of the study . RESULTS Baseline RMSSD was significantly ( p<0.05 ) associated with lower levels of : fat mass , fat-free mass , subcutaneous abdominal adipose tissue , resting heart rate ( HR ) , resting systolic blood pressure , and exercise HR . Stepwise multiple regression produced a final model ( R2 = 0.36 ) that included only resting HR . The analysis of changes over the three time points of the study found a significant ( p = 0.026 ) time by group interaction , such that RMSSD increased during periods of PT and decreased following cessation of PT . Greater individual increases in response to the PT ( p<0.05 ) were seen in those who had lower pre-PT RMSSD levels , showed the greatest decreases in resting HR , and increased most in vigorous physical activity . The final regression model retained only the change in resting HR as a significant predictor of the changes in the RMSSD ( R2 = 0.23 ) . DISCUSSION Regular exercise that improved fitness and body composition had a favorable effect on PSA in obese children The aim of this study was to determine the influence of breathing frequency and tidal volume on resting heart rate variability in children aged 9 years ( n = 29 ) and 16 years ( n = 19 ) . Heart rate variability was measured in four conditions : ( 1 ) without the control of ventilation followed at r and om by ( 2 ) a fixed breathing frequency of 12 breaths · min -1 , ( 3 ) a breathing frequency of 12 breaths · min -1 but with a fixed tidal volume of 30 % vital capacity and ( 4 ) a fixed breathing frequency of 6 breaths·min -1 and a tidal volume of 30 % vital capacity . A total of 128 RR intervals ( the time between two spikes in the heart rate ) were detected and absolute high- and low-fre Output:	In conclusion , the available results from r and omized controlled trials do not support the hypothesis that physical training improves HRV in healthy children[AUQ2 ]
MS22268	*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 Although sun exposure is an established cause of cutaneous malignant melanoma , possible interactions with host factors remain incompletely understood . Here we report the first results from a large prospect i ve cohort study of pigmentation factors and sun exposure in relation to melanoma risk . METHODS The Women 's Lifestyle and Health Cohort Study included 106 379 women from Norway and Sweden who were aged 30 - 50 years in 1991 or 1992 when they completed an extensive question naire on personal characteristics and exposures . Linkages to national registries ensured complete follow-up through December 31 , 1999 . Poisson regression models were used to estimate relative risks ( RRs ) . All statistical tests were two-sided . RESULTS During an average follow-up of 8.1 years , 187 cases of melanoma were diagnosed . Risk of melanoma was statistically significantly associated with increasing body surface area ( RR for > or = 1.79 m2 versus < or = 1.61 m2 = 1.60 , 95 % confidence interval [ CI ] = 1.03 to 2.48 ; P(trend ) = .02 ) , number of large asymmetric nevi on the legs ( RR for > or = 7 nevi versus 0 nevi = 5.29 , 95 % CI = 2.33 to 12.01 ; P(trend)<.001 ) , hair color ( RR for red versus dark brown or black = 4.05 , 95 % CI = 2.11 to 7.76 ; P(trend)<.001 ) , sunburns per year at ages 10 - 19 , 20 - 29 , and 30 - 39 years ( P(trend)<.001 , P(trend ) = .03 , and P(trend ) = .05 , respectively ) , and use of a device that emits artificial light ( solarium ) one or more times per month ( P = .04 ) . CONCLUSIONS Our results confirm previous findings that hair color , number of nevi on the legs , and history of sunburn are risk factors for melanoma and suggest that use of a solarium is also associated with melanoma risk . Adolescence and early adulthood appear to be among the most sensitive age periods for the effects of sunburn and solarium use on melanoma risk . However , it may be too early to see the full effect of adult exposures in this cohort Background : The incidence of skin cancer , the most common type of cancer in the Western world , has been shown to be associated with the degree of exposure to solar radiation . However , little is known on how human skin can be protected against UV-induced DNA damage by constitutive and induced pigmentation . Objective : To study the effect of skin pigmentation induced by a sunbed-type of treatment on the formation of UV-induced DNA damage in human skin in situ . Methods : A photoproduct assay was performed in untanned and tanned skin of healthy volunteers . Results : There is no significant difference in the induction of photoproducts between untanned and tanned skin . Conclusion : Our data demonstrate that constitutive skin pigmentation is more efficient than the induced one in protection against formation of photoproducts The incidence of cutaneous malignant melanoma ( melanoma ) and of basal cell carcinoma is still increasing in most fair-skinned population s. The fashion of intermittent exposure to solar ultraviolet ( UV ) radiations is considered the main cause of this increase . In 20 years time , tan acquisition through exposure to artificial sources of UV radiations has become frequent among fair-skinned adolescents and young adults . Modern sunbeds are powerful sources of UV radiations that do not exist in the nature , and repeated exposures to high doses of UVA constitute a new phenomenon in humans . A large prospect i ve cohort study on 106,379 Norwegian and Swedish women conducted between 1991 and 1999 has provided evidence for a significant , moderate increase in melanoma risk among regular sunbed users . Failure of past case-control studies to document with consistency the sunbed-melanoma association was probably due to a too short latency period between sunbed use and melanoma diagnosis , and to too few subjects with high total duration s of sunbed use . Regulations of sunbed installation , operation and use should become st and ardised across the 25 European Union countries . Enforcement of regulations in tanning parlours remains inadequate . In contrast , the existence of regulations is presented by many tanning salon operators as a guarantee that sunbed use is safe . We stress the need for the control of information disseminated by the " tanning industry " on suppositions that sunbed use is safer than sun exposure , and on the hypothetical health benefits of tanning . New fluorescent UV lamps are proposed that have a spectrum similar to the midday sun . Given the known association between intermittent sun exposure and melanoma , public-health authorities should reconsider the soundness of the commercialisation of these lamps BACKGROUND Indoor tanning is a popular behavior that may increase skin cancer risk . OBJECTIVE To examine characteristics associated with use or intention to use indoor tanning among adolescents . METHODS A telephone interview was conducted with 1273 adolescents , aged 14 to 17 years , in the Minneapolis-St Paul , Minn , and Boston , Mass , metropolitan areas . Questions included demographic and phenotypic characteristics , knowledge , attitudes , social factors , use of indoor tanning , and intention to tan indoors . RESULTS Twelve percent of boys and 42 % of girls had tanned indoors . Among nontanners , 22.4 % planned to start , and 77.2 % of tanners planned to continue tanning indoors . Nontanners and tanners at risk for future indoor tanning use were each significantly more likely to be female , less likely to use sun protection , less knowledgeable about skin cancer risks , more likely to agree that tans were attractive , and more strongly influenced by social factors compared with their low-risk counterparts . CONCLUSIONS Our data suggest that intention to tan indoors may identify a group of adolescents at risk for adopting the behavior ; prospect i ve studies are needed for confirmation BACKGROUND The relationship between cutaneous malignant melanoma and sunlamp use is examined in a Caucasian population in Connecticut , United States . METHODS Cases were diagnosed between 15 January 1987 and 15 May 1987 with a first primary cutaneous melanoma . Controls were obtained from the general population , frequency matched to cases by sex and age , through r and om digit dialling of Connecticut telephone numbers . RESULTS Of all study subjects , 141 ( 23 % ) cases and 95 ( 19 % ) controls reported ever having used sunlamps . The crude odds ratio ( OR ) for developing malignant melanoma after ever having used sunlamps was 1.30 ( 95 % confidence interval [ CI ] : 0.97 - 1.74 ) . This was reduced to 1.13 ( 95 % CI : 0.82 - 1.54 ) after further adjusting for cutaneous phenotype and recreational sun exposure . Those who used more than one type of sunlamp had a threefold higher risk for melanoma compared to never users . Subgroup analyses showed that sunlamp use was associated with a greater increase in risk for melanoma among those who used sunlamps at home and those who were first exposed to sunlamps prior to 1971 . The first use of sunlamps before the age of 25 showed somewhat higher risk for melanoma compared to first use later in life . CONCLUSION The current study provides limited evidence that use of sunlamps increases the risk of melanoma . For future studies , it is crucial that type of sunlamp , year of first use and amount of exposure are all taken into account . The association between melanoma and tanning with both UV-A and UV-B lamps and tanning under sunlamps early in life merits further investigation BACKGROUND The US Food and Drug Administration ( FDA ) recommends exposure limits for tanning bed use . Tanning patrons may not be following these recommendations and may be overexposed to damaging ultraviolet radiation ( UV ) . OBJECTIVE This study was conducted to assess tanning patrons ' adherence to FDA -recommended exposure limits and to measure the amount of UVA and UVB radiation emitted by tanning beds . METHODS A community-based survey was administered during routine state inspections of North Carolina tanning facilities ( n = 50 ) . At each facility , patron records were r and omly selected ( n = 483 ) for a survey of exposure records , and UVA and UVB outputs were measured for each tanning bed . RESULTS The recommended limits were exceeded by 95 % of patrons , and 33 % of patrons began tanning at the maximum doses recommended for maintenance tanning . Average tanning bed output was 192.1 W/m(2 ) UVA and 0.35 W/m(2 ) erythemally weighted UVB . CONCLUSIONS Interventions for tanning bed operators and patrons are needed to increase compliance with federally recommended exposure limits Summary Sunbed use was studied in relation to phenotype , erythema , sunscreen use and skin disease . The study population comprised 14–19 year‐old Stockholm adolescents in 60 r and omly selected classes , with 1252 students providing information . More than half ( 57 % ) reported sunbed use ± 4 times during the previous year . Skin type III dominated ( 64 % ) . Excessive exposure ( ± 10 times/year ) was not correlated to skin type . Sunscreens were most commonly used by sunbed users . Of all sunbed users , 44 % reported erythema . Adolescents with acne/seborrhoea , eczema or psoriasis used sunbeds more than others without skin diseases . The proportion with sunbed erythema ( 44 % ) indicates an unrecognized susceptibility to artificial ultraviolet radiation ( UVR ) among adolescents . The association between high exposure to UVR and sunscreen use stresses the importance of sunscreens being used as supplementary protection , not as a tool for tanning BACKGROUND The prevalence rates of both skin cancers and indoor tanning among the US population are high and have increased substantially in recent years . Low compliance by indoor tanning facilities with safety regulations may place consumers at greater risk of skin and ocular damage . OBJECTIVE This study quantified the level of compliance by indoor tanning facilities with selected federal and state regulations and recommendations . METHODS Tanning facilities ( N = 54 ) in San Diego County , California , were visited by a confederate posing as a prospect i ve customer . Compliance with 13 regulations/ recommendations were assessed by either direct query or observation of the presence/absence of signs and warning labels . Operators ' responses to 5 risk-based questions also were noted . RESULTS No facility complied with all 13 regulations/ recommendations . Compliance with 3 protective eyewear regulations was high ( 89%-100 % ) . In contrast , compliance with maximum tanning frequency recommendations ( approximately 6 % ) and parental consent regulations ( approximately 43 % ) was disturbingly low . CONCLUSION The investigators recommend instituting m and atory , comprehensive training for operators , as well as systematic compliance monitoring with enforcement of penalties for noncompliance The effects on 31 normal subjects following exposure to sunbeds containing UVA lamps with minimal UVB emission have been compared in a double‐blind study with the effects on nine control subjects of a similar exposure course three times weekly for 4 weeks to sunbeds emitting visible light . On previously untanned areas , all those subjects on active treatment developed a mild tan ; in tanned areas they all developed a moderate tan , while all control subjects developed a minimal to mild tan . The mean protection factor against later UVB‐induced erythema was 3.2±0.3 after the active course and 1.6±0.2 among the controls . Significantlsy more frequent adverse cutaneous effects for active subjects were pruritus , erythema , freckling , burning sensation , dryness and polymorphic light eruption . Cutaneous Langerhans cell numbers , and blood CD3 + ( pan T‐cell ) and CD4 + ( helper T‐cell ) lymphocyte subsets were reduced in both active and control groups . CD8 + ( cytotoxic/suppressor T‐cell ) counts were significantly reduced in both groups . The changes found in both groups seem attributable to small amounts of UVB emission from both active and control lamps UVA- and UVB-induced tans which were visually identical with each other were induced in separate sites on the lower back of 5 normal human volunteers of good tanning ability . Tanning was achieved by 4 exposures to UVA and UVB administered over an 8-day period . One week after the last exposure the protection afforded by the two types of tan against UVB-induced erythema and against UVB-induced DNA damage was measured . Protection against erythema was measured by comparison of the minimal erythema doses of UVB in tanned and untanned skin . Protection against DNA damage was assessed by comparing the numbers of endonuclease-sensitive sites in epidermal DNA extracted from biopsies taken from tanned and untanned sites exposed to the same dose of UVB . The UVB tans conferred significant protection ( mean 2.98-fold ) against UVB-induced erythema . UVA tans were not associated with significant protection ( mean 1.4-fold ) . In contrast , both UVA- and UVB-induced tans were associated with a similar reduction in yield of endonuclease-sensitive sites in epidermal DNA ( in UVA tan to 47 % and in UVB tan to 45 % of the yield in untanned skin ) . Protection conferred by the tans against erythema was therefore not paralleled by protection against DNA damage Output:	The evidence does not support a protective effect of the use of sunbeds against damage to the skin from subsequent sun exposure .
MS22269	*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: Malaria accounts for over 40 % of all outpatient consultations in Ghana . A common drug use problem associated with its treatment with chloroquine is over- and under-dosage and a preference for the intramuscular route of administration . Inadequate treatment is an important factor in the selection of resistant strains of malaria parasites . To ensure the proper management of diseases at health centres the Ministry of Health instituted an in-service training programme for medical assistants in 1987 . We evaluated the effect of this training on the clinical management of malaria using a quasi-experimental design . Three methods of data collection were used ; prescription survey , assessment question naires and focus group discussion s. Our findings revealed that gains in knowledge following the training had deteriorated within a year . There was also a discrepancy between knowledge and practice of malaria treatment . This was shown by over- and under-dosing of chloroquine in children and adults respectively . There was also overwhelming preference ( 85 % of all cases ) for injections and a high tendency towards polypharmacy ( average of five drugs per visit ) . The motivating reasons for these were mainly socio-cultural and included patient dem and and attitudes , prescriber self interests and stereotypes and the daily practical challenges of the community . While paying greater attention to supervision of clinical work at health posts , consideration must be given to socio-cultural context of drug use in any such future training programmes if rational use of drugs is to be achieved Objective Diabetes mellitus is a serious health problem associated with an increased mortality and morbidity . The association of improved glycemic control with sustained decrease in the rate of complications has been shown in r and omized clinical trials . Pharmaceutical care is a relatively new concept in Turkey ; yet , there are no recorded routine pharmaceutical care programs . Therefore , we aim ed to assess the impact of a short pharmaceutical care program conducted in the community pharmacy setting , on the indices of diabetes care of type 2 diabetic patients , particularly those regarding glycemic control and high blood pressure management . Setting The study was carried out at eight community pharmacies in Pendik district of Istanbul . Method All patients who visited any of the eight pharmacies through the pre-determined 1-week period were question ed for the presence of type 2 diabetes . Patients who reported to be type 2 diabetic ( n = 67 ) were informed about the study and invited to involve . During this prospect i ve longitudinal study , pharmaceutical care was provided to the patients by the same clinical pharmacist . The 3 month pharmaceutical care period consisted of six pharmacy visits . Main outcome measure : The main outcome measures were the improvement in glycemic control and blood pressure control ; while , weight control , self-monitoring of blood glucose , compliance and being under physician-control were also assessed . Results The study was conducted on 43 patients who accepted to involve . Fasting blood glucose was lowered by a mean of 23 % over 3-months from an initial value of 167.2 mg/dl . Number of patients reaching the desired blood glucose goals increased from 16.3 % to 39.5 % . Systolic and diastolic blood pressures also significantly fell over 3 months ( mean reductions were 10.9 mmHg for the systolic and 9.3 mmHg for the diastolic blood pressure ) . Number of patients reaching the desired blood pressure goal increased from 30.2 % to 51.2 % . Conclusion Our short-course pharmaceutical care program yielded measurable improvements in clinical indicators of diabetes and comorbidity management . The results suggest that the pharmacist is a beneficial key component of integrated care for patients with type 2 diabetes . We think that the positive results observed in this first reported pharmaceutical care program on diabetes in Turkey can be motivating and encouraging for all community pharmacists BACKGROUND type 2 diabetes mellitus continues to increase in prevalence worldwide . Many factors have been cited as contributing to compliance , such as family and social support , education , number of tablets per dose , frequency of administration and health care provider communication . Toward these goals , the present study was developed to measure the effect offactors on glycemic control such as diabetes education by pharmacists , a diabetes disease booklet and special medication containers . MATERIAL AND METHOD A total of 360 volunteers with type 2 DM patients were recruited , participants were simple r and omized to control 180 and intervention 180 patients . Which intervention categorized to 4 groups ; all intervention groups received diabetes drug counseling by a pharmacist , one group received plus a diabetes booklet , one received plus special medical containers and the last group received all of them . The interventions were done at the 1st time of visit . Both the control and intervention groups were monitored for fasting plasma glucose and HbA1c at 0 , 3 , 6 months and glycemic level in both groups was compared . RESULTS After 3 months , mean fasting plasma glucose and HbA1c decreased wiih the intervention group vs. control group ( 152.36 + /- 39.73 to 131.52 + /- 35.22 mg% ) and ( 150.16 + /- 41.78 to 153.98 + /- 47.95 mg% ) respectively ; ( p < 0.001 ) . HbA1c level 8.16 + /- 1.44 to 7.72 + /- 1.26 vs 8.01 + /- 1.51 to 8.38 + /- 1.46 respectively ; ( p < 0.001 ) . After 6 months , mean fasting plasma glucose and HbA1c decreased with the intervention group vs. control group ( 152.36 + /- 39.73 to 145.20 + /- 46.07 mg% ) and ( 150.16 + /- 41.78 to 159.16 + /- 54.90 mg% ) respectively ; ( p < 0.013 ) . HbA1c level 8.16 + /- 1.44 to 7.91 + /- 1.27 vs. 8.01 + /- 1.51 to 8.80 + /- 1.36 respectively ; ( p < 0.001 ) . The most favorable glycemic outcome was the group that received all of the interventions ; mean FPG was reduced from 147.46 + /- 36.07 to 125.38 + /- 31.12 mg% ( p < 0.000 ) in 1nd visit ( 3 months later ) and still reducing effect on the 2nd visit ( 6 month later ) mean FPG from 147.46 + /- 36.07 to 130.21 + /- 33.96 mg% ( p < 0.016 ) also the same way in HbA 1c level . The group that received only drug counseling by pharmacist had no significant reduction in FPG and HbA1c . ( p > 0.05 ) . CONCLUSION Drug counseling by a pharmacist has little beneficial effect on diabetes management outcome compared to the diabetes booklet and special drug container . To improve glycemic control of type 2 DM is to integrate self-management in daily life , wide a variety of education , drug taken behavior and health care provider available communication produce improvement in patient management and is somewhat better when used in combination Background Childhood asthma is common in Cape Town , a province of South Africa , but is underdiagnosed by general practitioners . Medications are often prescribed inappropriately , and care is episodic . The objective of this study is to assess the impact of educational outreach to general practitioners on asthma symptoms of children in their practice . Methods This is a cluster r and omised trial with general practice s as the unit of intervention , r and omisation , and analysis . The setting is Mitchells Plain ( population 300,000 ) , a dormitory town near Cape Town . Solo general practitioners , without nurse support , operate from storefront practice s. Caregiver-reported symptom data were collected for 318 eligible children ( 2 to 17 years ) with moderate to severe asthma , who were attending general practitioners in Mitchells Plain . One year post-intervention follow-up data were collected for 271 ( 85 % ) of these children in all 43 practice s. Practice s r and omised to intervention ( 21 ) received two 30-minute educational outreach visits by a trained pharmacist who left material s describing key interventions to improve asthma care . Intervention and control practice s received the national childhood asthma guideline . Asthma severity was measured in a parent-completed survey administered through schools using a symptom frequency and severity scale . We compared intervention and control group children on the change in score from pre-to one-year post-intervention . Results Symptom scores declined an additional 0.84 points in the intervention vs. control group ( on a nine-point scale . p = 0.03 ) . For every 12 children with asthma exposed to a doctor allocated to the intervention , one extra child will have substantially reduced symptoms . Conclusion Educational outreach was accepted by general practitioners and was effective . It could be applied to other health care quality problems in this setting Objective The study aim ed at evaluating the effect of pharmaceutical care programme on blood pressure and quality of life of patients who visit a Nigerian community pharmacy . Method A non-r and omised , single-site , crossover design was used . Patients served as their own control . They underwent 5 months of usual care and another 5 months of pharmaceutical care . Main outcome measure Blood pressure and quality of life measured before implementation of pharmaceutical care and at the end served as main outcome measures . Other end-points assessed at baseline and at the end of investigation included smoking cessation , adherence to therapy , exercise , salt restriction , alcohol moderation and self blood pressure measurement . Results Twenty four ( 24 ) patients out of the 40 recruited completed the study . Mean reductions were significant after pharmaceutical care intervention for systolic BP ( 14.3 ± 14.4 mmHg ) and diastolic BP ( 10.8 ± 10.7 mmHg ) . There was a significant mean increase in number of patients that adhered to salt restriction ( −36 % ) , aerobic exercise ( −46 % ) , self BP measurement ( −46 % ) , alcohol moderation ( −33 % ) and drug adherence ( −16.7 % ) . There was a positive increase of −11.4 and −3.2 for physical health and social health domain of quality of life evaluation respectively . Conclusion Pharmaceutical care programme could produce a beneficial effect on hypertensive patients BACKGROUND The practice of pharmaceutical care in primary care setting s in Thail and is currently not generally accepted . OBJECTIVE To evaluate the effect of pharmacist involvement in treatment with hypertensive patients in primary care setting s. METHODS The treatment objective was to stabilize the blood pressure ( BP ) of hypertensive patients in accordance with the Joint National Committee on Prevention , Detection , Evaluation and Treatment of High Blood Pressure guidelines . Patients were r and omly assigned to a pharmacist-involved group ( treatment ) or a group with no pharmacist involvement ( control ) . Pre- and post-test BPs , tablet counts , lifestyle modifications , and pharmacists ’ recommendations were recorded . The 6-month study was carried out in Mahasarakham University pharmacy and 2 primary care units . Patients were monitored monthly by review ing their medications and supported by providing pharmaceutical care and counseling . RESULTS From a total of 235 patients , the treatment group ( n = 118 ) had a significant reduction in both systolic ( S ) and diastolic ( D ) BP compared with the 117 patients of the control group ( p = 0.037 , 0.027 , respectively ) . The 158 patients ( 76 treatment , 82 control ) with BPs 140/90 mm Hg at the beginning of the study showed significant BP reductions ( p = 0.002 SBP , 0.008 DBP ) . The proportion of 158 patients whose BP became stabilized was higher in the treatment group ( p = 0.017 ) . The treatment group showed significantly better adherence ( p = 0.014 ) and exercise control ( p = 0.012 ) at the end of the study . Physicians accepted 42.72 % of medication modifications and 5.34 % of the suggestions for additional investigations . CONCLUSIONS Hypertensive patients who received pharmacist input achieved a significantly greater benefit in BP reduction , BP control , and improvement in adherence rate and lifestyle modification Background : The number of inappropriate prescriptions for sexually transmitted infections ( STIs ) in Sudan is suspected to be high . Simple multifaceted interventions directed at prescribers may improve prescribing patterns in the Sudan . Objective : To evaluate the effect of multifaceted interventions on prescribing for STIs in the White Nile State , Sudan . Methods : The study involved 20 health centres r and omly assigned to four different multifaceted interventions to improve prescribing . Results : Prescriber targeted interventions involving audit and feedback together with academic detailing and practice guidelines reduced the number of inappropriate prescriptions by 50 % ( p<0.001 ) . Audit and feedback together with seminars and practice guidelines reduced inappropriate prescriptions by 43 % ( p<0.001 ) . Audit and feedback alone Output:	Health service utilisation , such as rate of hospitalisation and general practice and emergency room visits , was also found to be reduced by the patient targeted pharmacist-provided services . Pharmacist-provided services that target patients may improve clinical outcomes such as management of high glucose levels among diabetic patients , management of blood pressure and cholesterol levels and may improve the quality of life of patients with chronic conditions such as diabetes , hypertension and asthma . Pharmacist services may reduce health service utilisation such as visits to general practitioners and hospitalisation rates .
MS22270	*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 raised score in the revised Hasegawa dementia scales ( HDS ) demonstrated that the effect of Yi Zhi Capsules ( YZC ) in treating loss of intellectual function after cerebrovascular diseases was significantly better than that of the western drug Piracetam [ symbol : see text ] ( P < 0.01 ) . The morbidity of vascular dementia was much lower in the treatment group than that of the control group ( P < 0.05 ) after a one-year follow-up ; and the blood lipid level and some indexes in rheological examinations were also improved significantly ( P < 0.05 , or < 0.01 ) . The data indicate that YZC is a relatively good preparation for prevention of vascular dementia OBJECTIVES To evaluate whether a traditional Chinese herbal medicine , ba wei di huang wan ( BDW ) , improves cognitive and physical functioning in dementia patients . DESIGN An 8-week r and omized , double-blind , placebo-controlled trial . SETTING Long-term-care facility in Japan . PARTICIPANTS Thirty-three patients with mild to severe dementia ( 7 men and 26 women ; mean age + /- st and ard deviation=84.4 + /- 7.8 ) were recruited and enrolled from May 2002 through September 2002 . INTERVENTION Participants were r and omly assigned to the active drug ( BDW ) group ( n=16 ) or the placebo group ( n=17 ) and treated for 8 weeks . MEASUREMENT Cognitive function and activities of daily living ( ADLs ) ; palsatility index . RESULTS After the trial , cognitive function as assessed using the Mini-Mental State Examination ( MMSE ) significantly improved from 13.5 + /- 8.5 to 16.3 + /- 7.7 ( P<.01 , 95 % confidence interval (CI)=-4.1 to -1.4 ) in the BDW group . The ADL score in the Barthel Index also significantly changed , from 61.8 + /- 34.6 to 78.9 + /- 21.1 ( P<.01 , 95 % CI=-26.2 to -7.9 ) . In contrast , MMSE and Barthel Index scores of the placebo group showed no significant change . Eight weeks after the end of the administration , MMSE and Barthel Index scores of the BDW group declined to the baseline level . The pulsatility index in the internal carotid artery as measured using Doppler sonography significantly decreased in the BDW group ( 2.5 + /- 1.7 to 1.9 + /- 0.5 , P<.05 ) but not in the placebo group . CONCLUSION These results argue the benefits of BDW in the treatment of dementia OBJECTIVE To investigate the therapeutic effects of modified Sanjiasan decoction ( MSD ) on vascular dementia ( VD ) . METHODS Thirty-seven patients in the treated group were given MSD , one dosage each day , and 31 patients in the control group were administered orally Naofukang 0.8 g three times a day . The treatment course for both groups was three months . The indices as Hasegawa dementia scale ( HDS ) , mini mental state examination ( MMSE ) and its subentries , intelligence quotient ( IQ ) and memory quotient ( MQ ) were examined . RESULTS MSD could improve the scores of HDS , MMSE and its subentries ( P<0.05 or P<0.01 ) , ameliorate dementia state and enhance IQ ( P<0.05 ) and MQ ( P<0.01 ) in patients with VD . CONCLUSION MSD has a certain effect on intelligence benefiting and dementia antagonizing OBJECTIVE To observe the effect of Kangxin capsule ( KXC ) on homocysteine ( HCY ) and beta-amyloid protein ( beta-Ap ) in patients with vascular dementia . METHODS Sixty-three patients with vascular dementia were r and omly divided into two groups , the 33 patients in the treated group and the 30 in the control group . Basal treatment were given to both groups , besides , KXC was given to the treated group and Hydergine was given to the control group . The levels of plasma HCY , beta-Ap as well as the changes of mini mental state examination ( MMSE ) , activity of daily living ( ADL ) and TCM Syndrome scoring were observed before and after treatment . RESULTS KXC could significantly decrease the levels of HCY and beta-Ap ( P < 0.01 ) , rise the MMSE scores , reduce ADL scores and ameliorate TCM Syndrome . CONCLUSION KXC can effectively regulate the levels of HCY , beta-Ap in vascular dementia patients OBJECTIVE To observe the validity and safety of Kangxin capsule curing the patients with vascular dementia ( VaD ) . PATIENTS AND METHODS Fifty-six patients with vascular dementia of kidney deficiency and blood stagnation type were selected on the basis of defined diagnostic criteria and were r and omly divided into Kangxin group ( 29 ) and control group ( 27 ) , observing the relevant accumulation scores in dementia scale before and after treatment and changes of endothelin ( ET ) , sex hormone , immunity and routine examinations . RESULTS Kangxin capsule can effectively improve the symptom of patients with VaD of senile kidney deficiency and blood stagnation type , and the average value of curative effect index of 29 patients in the treatment group is 23.01>/=20 % , i.e. effective ; compared with that before treatment , both CD(4 ) and CD(4).CD(8)(-1 ) rises ( P<0.05 ) after the treatment with Kangxin capsule ; for the male VaD patients of the Kangxin group , T level increases ( P<0.05 ) and estrodial ( E(2)).testerone (T)(-1 ) value decreases ( P<0.05 ) after the treatment ; for the female VaD patients of the Kangxin group , E(2 ) , E(2).T(-1 ) value increases a great deal ( P<0.05 ) compared with that before treatment ; ET level of both groups decreased on average ( P<0.01 ) , and did not demonstrate any obvious toxic side effect . CONCLUSIONS Kangxin capsule is a valid and safe preparation of Chinese traditional medicine for curing VaD of senile kidney deficiency and blood stagnation type OBJECTIVE To observe the clinical therapeutic effect of Shuizhitong capsule ( SZT ) in treating senile vascular dementia ( VD ) and on changes of related physio-chemical criteria . METHODS Eighty-five patients with VD were r and omly divided into the treated group ( n = 51 ) and the control group ( n = 34 ) in the ratio of 3:2 , treated with SZT and Piracetam respectively . Before and after treatment , the Zhang 's Dementia Scoring ( HDS ) and Function of Social Activity Question naire ( FAQ ) scoring , cerebral blood flow and hemorrheologic properties were determined . RESULTS SZT could significantly improve the patients ' clinical symptoms , intracranial hemodynamic condition and the hyperviscosity , hypercoagulation and hyperaggregation status , lower the whole blood and plasma specific viscosity , raise the living st and ard of partial patients , with significant difference between before and after treatment ( P < 0.05 ) . CONCLUSION The therapeutic effect of SZT in treating senile VD is definite OBJECTIVE To investigate the effects of scalp-acupuncture on intelligence in patients with vascular dementia ( VaD ) . METHODS A total of 108 VaD patients were r and omly divided into two groups : scalp-acupuncture group and Western medicine group . The scores of Mini-Mental State Examination ( MMSE ) , Blesse Dementia Scale ( BDS ) , Hasegawa Dementia Scale ( HDS ) , Abilities of Daily Life ( ADL ) before and after treatment in the two groups were detected . RESULTS A total of 92 patients completed the treatment . The scores of MMSE , BDS and HDS in the two groups were significantly increased , and the ADL scores significantly declined ( P<0.05 ) . There was no difference in the scores of MMSE , BDS , HDS and ADL between the two groups before and after the treatment . There was no difference in the total effectiveness between the two groups ( P>0.05 ) . CONCLUSION Scalp-acupuncture therapy could improve the clinical intelligence level of VaD patients BACKGROUND Vascular dementia ( VaD ) is the second most prevalent type of dementia among the aged , for whom limited pharmacologic options are available so far . SaiLuoTong capsule is a modern traditional Chinese medicine formula , which has been demonstrated to improve cognition of VaD by the reports of animal experiments and preliminary clinical trial . However , evaluation of this therapy in r and omized multicenter trials is needed . In this article , we present the rationale and design of the SaiLuoTong in Vascular Dementia Study . METHODS This phase 2 clinical trial of SaiLuoTong among patients with mild-to-moderate VaD is a 26-week , multicenter , r and omized , double-blind , placebo-controlled study with a subsequent 26-week , open-label extension . After a 4-week placebo run-in period , participants are central ly r and omized ( 1:1:1 ) to 3 groups : group A receives SaiLuoTong 360 mg per day for 52 weeks ; group B receives SaiLuoTong 240 mg per day for 52 weeks ; group C ( the control group ) are further r and omly assigned to 2 groups in a 1:1 ratio and receives placebo during the double-blind phase , then SaiLuoTong 360 mg per day or SaiLuoTong 240 mg per day during the extension phase . The primary outcome measures include the VaD assessment scale cognitive subscale and the Alzheimer Disease Cooperative Study - clinical global impression of change . Safety measures include body weight , vital signs , electrocardiography , laboratory tests , and records of adverse events . Assuming an attrition rate of 20 % , at least 372 patients are required to obtain a statistical power of 80 % . RESULTS The first patient was enrolled into the study in April 2012 and the completion of the study is expected in September 2014 . CONCLUSIONS The rigorous methodology of the study will hopefully move forward the scientific evaluation of traditional Chinese medicine in treatment of VaD. The results of the present study will provide high- quality evidence on the effect of SaiLuoTong in patients with VaD and has the potential to establish a novel therapeutic approach for this disorder Background and Objective : There are currently no drugs approved to treat vascular dementia (VaD).The objective of this study was to determine if treatment with donepezil , an acetylcholinesterase inhibitor , may provide benefit for VaD patients . Methods : Combined analysis of 2 identical r and omized , double-blind , placebo-controlled , 24-week studies involving 1,219 patients enrolled at 109 investigational sites in the USA , Europe , Canada and Australia . Patients were r and omized to receive donepezil 5 mg/day ( n = 406 ) or 10 mg/day ( after brief titration ; n = 421 ) or placebo ( n = 392 ) . Patients were assessed on cognition [ Alzheimer ’s Disease Assessment Scale – cognitive subscale ( ADAS[-]cog ) , Mini-Mental State Examination ( MMSE ) ] , global function [ Clinician ’s Interview- Based Impression of Change plus ( CIBIC[-]plus ) , Clinical Dementia Rating – Sum of the Boxes ( CDR[-]SB ) ] and function [ Alzheimer ’s Disease Functional Assessment and Change Scale ( ADFACS ) ; instrumental activities of daily living ( ADFACS[-]IADL ) ] . Results : Both donepezil groups showed significant improvements in cognition compared with placebo ( ADAS-cog , MMSE , p < 0.01 ) . Significant global function benefits were seen on the CIBIC-plus in the 5 mg/day group ( placebo vs. 5 mg/day , p < 0.001 ; vs. 10 mg/day , p = 0.006 ) and on the CDR-SB in the 10 mg/day group ( placebo vs. 5 mg/day , p = 0.09 ; vs. 10 mg/day , p < 0.01 ) . Significant functional benefits were also seen ( ADFACS , placebo vs. 5 mg/day , p = 0.08 ; vs. 10 mg/day , p = 0.02 ; ADFACS-IADL , p < 0.05 for both donepezil groups ) . Donepezil was well tolerated , with low withdrawal rates due to adverse events . Conclusions : This combined analysis of the largest trial on VaD to date showed that donepezil-treated patients had significant benefits in cognition , global function and ability to perform IADL . Based on these findings and reported tolerability , donepezil should be considered as an important therapeutic element in the overall management of patients with OBJECTIVE To find a good way to diagnose VD , value the effect of Yishen Yangnao capsule on VD and try to find some rules of changes in Chinese medicine syndromes . METHOD Patients were r and omly divided into treating group and western medicine comparison group . It 's the phase III clinical research of Rishen Yangnao capsule curing VD , judging the validity and security of it , using dukexi slice as comparison drug Output:	The results showed that medicinal plants , particularly Sancaijiangtang and Ginkgo biloba could improve behavioral and psychological symptoms , working memory , Mini-Mental State Examination , and activities of daily living as well as neuropsychiatric features .
MS22271	*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 if high doses of oral iron could shorten the duration of therapy necessary to treat Fe deficiency anemia , high-dose Fe 600 mg three times per day ( given as nontoxic carbonyl Fe ) was compared with st and ard ferrous sulfate 60 mg Fe++ three times per day in a r and omized , double-blind , 3-wk trial involving 36 female blood donors with mild Fe deficiency anemia . In animal studies , both forms of Fe have similar bioavailability when administered in equal amounts . High-dose carbonyl Fe was well tolerated with gastrointestinal side effects similar those observed with st and ard FeSO4 therapy . The 10-fold larger amount of Fe result ed in a mean 1.5-fold increase in estimated Fe absorption . Both regimens corrected anemia but neither replenished storage Fe . These results suggest that the principal advantage to the use of carbonyl Fe would derive from its safety rather than from the large doses that can be given We assessed changes in iron stores and iron absorption after repeat blood donations using a combination of biochemical measures of iron status : ferritin , hemoglobin , and transferrin saturation . Thirty-six volunteers with a mean ( + /- SD ) age of 67.7 + /- 3.7 y donated an average of 15 units of blood over 3.5 y. Initial iron stores were 12.45 + /- 3.09 mg/kg for men and 12.53 + /- 3.24 mg/kg for women . Of the 20 men and 16 women who completed the study , 6 men and 10 women were taking a self-selected supplement providing approximately 20 mg Fe/d . Dietary iron intake was determined to be approximately 20 mg/d for men and approximately 18 mg/d for women . Decreases in iron stores in supplemented men were not significantly different from those in nonsupplemented men : 9.52 + /- 2.57 and 11.31 + /- 2.74 mg/kg , respectively . Nonsupplemented women showed a significantly ( P < 0.05 ) greater decline in iron stores than did supplemented women : 13.09 + /- 2.46 and 10.60 + /- 4.15 mg/kg , respectively . Mean maximal iron absorption was approximately 4.10 mg/d for men and approximately 3.55 mg/d for women regardless of iron intake BACKGROUND Iron depletion or deficiency in blood donors frequently results in deferrals for low hemoglobin ( Hb ) , yet blood centers remain reluctant to dispense iron replacement therapy to donors . STUDY DESIGN AND METHODS During a 39-month period , 1236 blood donors deferred for a Hb level of less than 12.5 g/dL and 400 nondeferred control donors underwent health history screening and laboratory testing ( complete blood counts , iron studies ) . Iron depletion and deficiency were defined as a ferritin level of 9 to 19 and less than 9 µg/L in females and 18 to 29 and less than 18 µg/L in males . Deferred donors and iron-deficient control donors were given a 60-pack of 325-mg ferrous sulfate tablets and instructed to take one tablet daily . Another 60-pack was dispensed at all subsequent visits . RESULTS In the low-Hb group , 30 and 23 % of females and 8 and 53 % of males had iron depletion or deficiency , respectively , compared with 29 and 10 % of females and 18 and 21 % of males in the control group . Iron-depleted or -deficient donors taking iron showed normalization of iron-related laboratory parameters , even as they continued to donate . Compliance with oral iron was 68 % . Adverse gastrointestinal effects occurred in 21 % of donors . The study identified 13 donors with serious medical conditions , including eight with gastrointestinal bleeding . No donors had malignancies or hemochromatosis . CONCLUSION Iron depletion or deficiency was found in 53 % of female and 61 % of male low-Hb donors and in 39 % of female and male control donors . Routine administration of iron replacement therapy is safe and effective and prevents the development of iron depletion and deficiency in blood donors BACKGROUND The consequences of temporary deferral are not well understood . This study sought to investigate blood donor return after deferral expiration . STUDY DESIGN AND METHODS A retrospective cohort analysis of allogeneic whole-blood donation was conducted . All deferred donors and a r and om sample of eligible donors were identified from the year 2000 , with subsequent blood center visits through December 2005 captured . Stratified results are reported as the percentage returning , rates of return , and time to return . Measures of statistical association and Cox regression modeling are reported . RESULTS For first-time ( FT ) donors , 25 percent of temporarily deferred donors returned during the 5-year follow-up period compared to 47 percent of eligible donors ( p < 0.0001 ) ; for repeat donors , 81 and 86 percent of deferred and eligible donors returned , respectively ( p < 0.0001 ) . Depending on the deferral category , 14 to 31 percent of FT and 58 to 90 percent of repeat donors returned . Rates ( per year ) of successful donation during the follow-up period were 0.09 for index-deferred FT donors , 0.28 for eligible FT donors , 1.0 for deferred repeat donors , and 1.45 for eligible repeat donors . Multivariate modeling indicated that in addition to deferral , age , sex , race , and education were associated with return in both FT and repeat donors . CONCLUSION The effects of deferral were more pronounced than expected , affecting both FT and repeat donors . For FT donors , the type and duration of deferral , while important , were not as relevant as hypothesized because so few returned , suggesting the need to develop appropriate interventions to recapture those donors likely to be eligible Absolute iron deficiency is treated by correcting the causative lesion and then , traditionally , administering sufficient amounts of ferrous salt to return the haemoglobin level to normal and replenish body stores . The bioavailability of ferric compounds has been question ed and accordingly their therapeutic role remains controversial . A special problem is posed by regular blood donation , where the frequency of phlebotomy is limited by the haemoglobin level , which , in turn , requires maintenance of an adequate supply of iron from dietary sources . Since this latter situation may not always occur , it would be of practical benefit to have a form of supplementation that is effective and can be taken without side effects . These issues were prospect ively examined in a consecutive series of otherwise healthy blood donors who developed absolute iron deficiency anaemia and were then r and omly allocated to receive 60 mg of this metal as ferrous sulphate twice a day ( Group 1 : n = 51 ) , 100 mg as chewable ferric polymaltose daily ( Group 2 : n = 53 ) , or the latter product twice a day ( Group 3 : n = 55 ) . Serial studies showed that 80 % of patients in Groups 1 and 3 had reached normal haemoglobin levels by 12 weeks , but this figure was only 50 % in Group 2 . Similarly , the proportion of patients improving their percentage saturation of transferrin to within the normal range was significantly better in Groups 1 and 3 than in Group 2 ( P < .01 ) . However , body iron stores , reflected in serum ferritin level , was significantly better in Group 1 ( P < .01 ) ; there was no difference in this respect between Groups 2 and 3 . ( ABSTRACT TRUNCATED AT 250 WORDS Background Iron deficiency without anemia is related to adverse symptoms that can be relieved by supplementation . Since a blood donation can induce such an iron deficiency , we investigated the clinical impact of iron treatment after a blood donation . Methods One week after donation , we r and omly assigned 154 female donors with iron deficiency without anemia , aged below 50 years , to a four-week oral treatment of ferrous sulfate versus a placebo . The main outcome was the change in the level of fatigue before and after the intervention . Aerobic capacity , mood disorder , quality of life , compliance and adverse events were also evaluated . Hemoglobin and ferritin were used as biological markers . Results The effect of the treatment from baseline to four weeks of iron treatment was an increase in hemoglobin and ferritin levels to 5.2 g/L ( P < 0.01 ) and 14.8 ng/mL ( P < 0.01 ) , respectively . No significant clinical effect was observed for fatigue ( -0.15 points , 95 % confidence interval -0.9 points to 0.6 points , P = 0.697 ) or for other outcomes . Compliance and interruption for side effects was similar in both groups . Additionally , blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces . Conclusions These data are valuable as they enable us to conclude that donors with iron deficiency without anemia after a blood donation would not clinical ly benefit from iron supplementation . Trial Registration Clinical Trials.gov : Regular blood donors were enrolled in a double-blind , parallel group study to evaluate the side effects of two iron supplements , one containing both heme iron and non-heme iron ( Hemofer , 2 tablets = 18 mg iron/day ) , the other non-heme iron only ( Erco-Fer ; 1 tablet = 60 mg iron/day ) . No differences were found between the two alternatives in regaining predonation iron status as measured by serum ferritin and hemoglobin levels . Despite this therapeutic equivalence , participants ' symptom diaries showed substantial differences in the side effects for the two treatments . The frequency of constipation ( p < 0.05 ) and the total incidence of all side effects ( p < 0.01 ) were significantly higher for non-heme iron when compared with the heme iron-non-heme iron combination and a placebo . The study demonstrates that a low-dose iron supplement containing both heme iron and non-heme iron ( Hemofer ) has fewer side effects when compared with an equipotent , traditional non-heme iron supplement Seventeen conscripts gave blood every second month , the amount representing an average iron loss of 3.5 mg daily . Seven of them were given 20 mg and ten 100 mg iron as ferrous carbonate once daily throughout the study . Before the first and after the fourth and sixth blood donations they were examined with regard to packed red cell volume , serum iron , total iron-binding capacity and stainable bone marrow iron , and a diagnostic iron absoprtion test was performed . Ten conscripts receiving no iron and giving no blood but comparable to those in the test groups with regard to age , exercise and diet served as controls . The stainable bone marrow iron was found to become stabilized at a level with reduced but still perceptible amounts when 20 mg iron was given , and at a level with somewhat greater amounts when the daily dose was 100 mg . Both levels were lower than before blood donation in most subjects , and the negative iron balance was also reflected in the diagnostic iron absorption test . When a healthy person loses 3.5 mg iron daily , supplementation with a 100 mg tablet per day is therefore insufficient to maintain the iron stores at their previous level . The decrease in storage iron is not progressive , however . When the storage iron is reduced , iron absorption seems to be stimulated sufficiently to establish a balance at a reduced storage iron level Background There is no recommendation to screen ferritin level in blood donors , even though several studies have noted the high prevalence of iron deficiency after blood donation , particularly among menstruating females . Furthermore , some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation . Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia , but with a mean serum ferritin ≤ 30 ng/ml . Methods / Design In a double blind r and omised controlled trial , we will measure blood count and ferritin level of women under age 50 yr , who donate blood to the University Hospital of Lausanne Blood Transfusion Department , at the time of the donation and after 1 week . One hundred and forty donors with a ferritin level ≤ 30 ng/ml and haemoglobin level ≥ 120 g/l ( non-anaemic ) a week after the donation will be included in the study and r and omised . A one-month course of oral ferrous sulphate ( 80 mg/day of elemental iron ) will be introduced vs. placebo . Self-reported fatigue will be measured using a visual analogue scale . Secondary outcomes are : score of fatigue ( Fatigue Severity Scale ) , maximal aerobic power ( Chester Step Test ) , quality of life ( SF-12 ) , and mood disorders ( Prime-MD ) . Haemoglobin and ferritin concentration will be monitored before and after the intervention . Discussion Iron deficiency is a potential problem for all blood donors , especially menstruating women . To our knowledge , no other intervention study has yet evaluated the impact of iron supplementation on subjective symptoms after a blood donation . Trial registration BACKGROUND AND OBJECTIVES Iron depletion is common in regular blood donors . The objective of the study was to investigate the frequency and severity of iron depletion in regular blood donors and whether IV iron is more effective than oral to avoid iron depletion and symptoms thereof , especially restless legs syndrome ( RLS ) . METHOD Output:	There is moderate quality evidence that rates of donor deferral due to low haemoglobin are considerably less in those taking iron supplements compared with those without iron supplementation , both at the first donation visit and at subsequent donation . Iron-supplemented donors also show elevated haemoglobin and iron stores .
MS22272	*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 Inhibitors of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin ( PI3K/AKT/mTOR ) pathway can overcome endocrine resistance in estrogen receptor ( ER ) α-positive breast cancer , but companion diagnostics indicating PI3K/AKT/mTOR activation and consequently endocrine resistance are lacking . PIK3CA mutations frequently occur in ERα-positive breast cancer and result in PI3K/AKT/mTOR activation in vitro . Nevertheless , the prognostic and treatment-predictive value of these mutations in ERα-positive breast cancer is contradictive . We tested the clinical validity of PIK3CA mutations and other canonic pathway drivers to predict intrinsic resistance to adjuvant tamoxifen . In addition , we tested the association between these drivers and downstream activated proteins . Methods Primary tumors from 563 ERα-positive postmenopausal patients , r and omized between adjuvant tamoxifen ( 1 to 3 years ) versus observation were recollected . PIK3CA hotspot mutations in exon 9 and exon 20 were assessed with Sequenom Mass Spectometry . Immunohistochemistry was performed for human epidermal growth factor receptor 2 ( HER2 ) , phosphatase and tensin homolog ( PTEN ) , and insulin-like growth factor 1 receptor ( IGF-1R ) . We tested the association between these molecular alterations and downstream activated proteins ( like phospho-protein kinase B ( p-AKT ) , phospho-mammalian target of rapamycin ( p-mTOR ) , p-ERK1/2 , and p-p70S6 K ) . Recurrence-free interval improvement with tamoxifen versus control was assessed according to the presence or absence of canonic pathway drivers , by using Cox proportional hazard models , including a test for interaction . Results PIK3CA mutations ( both exon 9 and exon 20 ) were associated with low tumor grade . An enrichment of PIK3CA exon 20 mutations was observed in progesterone receptor- positive tumors . PIK3CA exon 20 mutations were not associated with downstream-activated proteins . No significant interaction between PIK3CA mutations or any of the other canonic pathway drivers and tamoxifen-treatment benefit was found . Conclusion PIK3CA mutations do not have clinical validity to predict intrinsic resistance to adjuvant tamoxifen and may therefore be unsuitable as companion diagnostic for PI3K/AKT/mTOR inhibitors in ERα- positive , postmenopausal , early breast cancer patients Background African-American women have higher mortality from breast cancer than other ethnic groups . The association between poor survival and differences with tumor phenotypes is not well understood . The purpose of this study is to assess the clinical significance of ( 1 ) Stem cell-like markers CD44 and CD24 ; ( 2 ) PI3K/Akt pathway associated targets PTEN , activation of Akt , and FOXO1 ; and ( 3 ) the Insulin-like growth factor-1 ( IGF-I ) and IGF binding protein-3 ( IGFBP3 ) in different breast cancer subtypes , and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status . Methods A total of N=318 African-American and Hispanic/Latina women , with clinical ly-annotated information within the inclusion criteria were included . Formalin fixed paraffin embedded tissues from these patients were tested for the different markers using immunohistochemistry techniques . Kaplan-Meier survival-curves and Cox-regression analyses were used to assess Relative Risk and Disease-Free-Survival ( DFS ) . Results The triple-negative-breast-cancer ( TNBC ) receptor-subtype was more prevalent among premenopausal women , and the Hormonal Receptor ( HR ) positive subtype was most common overall . TNBC tumors were more likely to have loss of PTEN , express high Ki67 , and have increased CD44+/CD24- expression . TNBC was also associated with higher plasma-IGF-I levels . HR-/HER2 + tumors showed high pAkt , decreased FOXO1 , and high CD24 + expression . The loss of PTEN impacted DFS significantly in African Americans , but not in Hispanics/Latinas after adjusted for treatment and other tumor pathological factors . The CD44+/CD24- and CD24+/CD44- phenotypes decreased DFS , but were not independent predictors for DFS . HER2-positive and TNBC type of cancers continued to exhibit significant decrease in DFS after adjusting for the selected biomarkers and treatment . Conclusions TNBC incidence is high among African-American and Hispanic/Latino women residing in South Los Angeles . Our study also shows for the first time that TNBC was significantly associated with PTEN loss , high Ki67 and the CD44+/CD24- phenotype . The loss of PTEN impacts DFS significantly in African Americans Introduction Worldwide , many patients with HER2 + ( human epidermal growth factor receptor 2-positive ) early breast cancer ( BC ) do not receive adjuvant trastuzumab . Hazards of recurrence of these patients with respect to hormone receptor status of the primary tumor have not been described . Methods Using data from 1,260 patients r and omized to placebo in the adjuvant TEACH trial , we report 10-year annual hazards of recurrence in HER2 + patients not treated with anti-HER2 therapy . Results Disease-free survival ( DFS ) was 75 % after 5 and 61 % after 10 years , respectively . Patients with HER2 + hormone receptor-positive ( HR+ ( hormone receptor-positive ) ; ER+ ( estrogen receptor-positive ) or PR+ ( progesterone receptor-positive ) ) disease had a significantly better DFS than patients with HER2 + HR- ( ER-/PR- ) disease ( hazard ratio 0.72 , P = 0.02 ) . This difference was explainable by a significantly higher hazard of recurrence in years 1 to 5 in HER2 + HR- compared to HER2 + HR+ patients , with a mean risk of recurrence of 9%/year for HR- versus 5%/year in HR+ patients ( hazard ratio 0.59 , P = 0.002 for years 1 to 5 ) . The high early risk of recurrence of HER2 + HR- patients declined sharply over time , so that it was similar to that seen in HER2 + HR+ patients in years 6 to 10 ( hazard ratio 0.97 , P = 0.92 for years 6 to 10 ) . Conclusions Our results show that outcomes in HER2 + patients with early BC not receiving anti-HER2 therapy strongly depend on HR expression . The very high early risk of relapse seen in HER2 + HR- patients is particularly relevant in health care setting s with limited access to adjuvant anti-HER2 treatment . The event rates shown for sub population s of HER2 + BC patients suggest that in re source -constrained environments patients with HER2 + HR- early BC should be prioritized for consideration of adjuvant anti-HER2 therapy PURPOSE It has been suggested that PTEN , a negative regulator of PI3K/AKT signaling , is involved in tumor sensitivity to trastuzumab . We investigated the association between tumor PTEN protein expression and disease-free survival ( DFS ) of patients r and omly assigned to receive chemotherapy alone ( arm A ) or chemotherapy with sequential ( arm B ) or concurrent trastuzumab ( arm C ) in the phase III early-stage human epidermal growth factor receptor 2 ( HER2 ) -positive trial-North Central Cancer Treatment Group ( NCCTG ) N9831 . PATIENTS AND METHODS The intensity and percentage of invasive cells with cytoplasmic PTEN staining were determined in tissue microarray sections containing three cores per block ( n = 1,286 ) or in whole tissue sections ( WS ; n = 516 ) by using st and ard immunohistochemistry ( 138G6 monoclonal antibody ) . Tumors were considered positive for PTEN ( PTEN-positive ) if any core or WS had any invasive cells with ≥ 1 + staining . Median follow-up was 6.0 years . RESULTS Of 1,802 patients included in this analysis ( of 3,505 patients registered to N9831 ) , 1,342 ( 74 % ) had PTEN-positive tumors . PTEN positivity was associated with hormone receptor negativity ( χ(2 ) P < .001 ) and nodal positivity ( χ(2 ) P = .04 ) . PTEN did not have an impact on DFS within the various arms . Comparing DFS of arm C to arm A , patients with PTEN-positive and PTEN-negative tumors had hazard ratios ( HRs ) of 0.65 ( P = .003 ) and 0.47 ( P = .005 ) , respectively ( interaction P = .16 ) . For arm B versus arm A , patients with PTEN-positive and PTEN-negative tumors had HRs of 0.70 ( P = .009 ) and 0.85 ( P = .44 ) , respectively ( interaction P = .47 ) . CONCLUSION In contrast to selected pre clinical and limited clinical studies suggesting a decrease in trastuzumab sensitivity in patients with PTEN-negative tumors , our data show benefit of adjuvant trastuzumab for patients with HER2-positive breast cancer , independent of tumor PTEN status Output:	: This study confirmed PTEN loss is an important independent factor for breast cancer prognosis
MS22273	*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 Athletes often use weight training to prepare for sprint events , but the effectiveness of different types of weight training for sprinting is unclear . We have therefore investigated the effect of slow and explosive weight training on kayak sprint performance . METHODS Twenty-seven male and 11 female experienced sprint kayakers were r and omized to slow weight training , explosive weight training , or control ( usual training ) groups . Weight training consisted of two sessions per week for 6 wk ; in each session the athletes performed 3 - 4 sets of two sport-specific exercises with a load of 80 % 1-repetition-maximum . The two training programs differed only in the time taken to complete the concentric phase of the exercises : slow , 1.7 s ; explosive , < 0.85 s. To determine the effects of training on sprint acceleration and speed maintenance , the athletes performed 15-m kayaking sprints pre- and posttraining ; an electronic timing system provided sprint times at 3.75- , 7.5- , and 15-m marks . RESULTS Relative to control , both types of weight training substantially improved strength and sprint performance . The improvements in mean sprint time over 15 m in each group were : slow , 3.4 % ; explosive , 2.3 % ; control , -0.2 % ( 90 % confidence limits for pairwise differences , approximately + /-1.4 % ) . Over the first 3.75 m , the improvements were : slow , 7.1 % ; explosive , 3.2 % ; control , 1.4 % ( approximately + /-2.6 % ) . Over the last 7.5 m , the improvements were : slow , 2.1 % ; explosive , 3.0 % ; control , -0.8 % ( approximately + /-1.9 % ) . CONCLUSIONS Slow weight training is likely to be more effective than explosive training for improving the acceleration phase of sprinting , when force is high throughout the length of the stroke . Explosive weight training may be more effective in speed maintenance , when forces are developed rapidly over a short period at the start of the stroke Sayers , SP and Gibson , K. A comparison of high-speed power training and traditional slow-speed resistance training in older men and women . J Strength Cond Res 24(12 ) : 3369 - 3380 , 2010-Muscle power , the product of force × velocity , is a critical determinant of function in older adults . Resistance training ( RT ) at high speed has been shown to improve peak muscle power in this population ; however , different functional tasks may benefit from the improvement of power at values other than “ peak ” values , for example , tasks that require a greater velocity component or a greater force component . This study compared the effect of high-speed RT on muscle performance ( peak power [ PP ] and its components [ PP force and PP velocity ] and overall peak velocity [ VEL ] ) across a broad range of external resistances . Thirty-eight older men and women were r and omized to high-speed power training at 40 % of the 1-repetition maximum ( 1RM ) ( n = 13 [ 74.1 ± 6.4 years ] ) ; traditional RT at 80 % 1RM ( n = 13 [ 70.1 ± 7.0 years ] ) ; or control ( n = 12 [ 72.8 ± 4.1 years ] ) . Measures of muscle performance were obtained at baseline and after the 12-week training intervention . Muscle power and 1RM strength improved similarly with both high-speed and traditional slow-speed RT . However , speed-related muscle performance characteristics , PP velocity and overall VEL , were most positively impacted by high-speed power training , especially at lower external resistances . Because gains in speed-related measures with high-speed training compared to traditional RT do not come at the expense of other muscle performance outcomes , we recommend using an RT protocol in older adults that emphasizes high-speed movements at low external resistances OBJECTIVE To determine the effect of training intensity on the contributions of force and velocity to improvements in peak power ( PP ) after explosive resistance training in older adults . METHODS 112 healthy older adults ( 69 + /- 6 yr ) were r and omized to explosive resistance training at 20 % ( G20 ) , 50 % ( G50 ) , or 80 % ( G80 ) maximal strength ( 1-repetition maximum ) for 8 - 12 wk ( twice weekly , 5 exercises , 3 sets of 8 explosive concentric/slow eccentric repetitions ) using pneumatic resistance machines or a nontraining control group ( CON ) . RESULTS Force at peak power ( FPP ) increased significantly and similarly among training groups compared with CON . Velocity at peak power ( VPP ) did not improve significantly and remained similar between all groups . Force contributed significantly more to PP production in G80 and G50 than in CON . The change in PP was independently predicted by changes in fat-free mass in G80 and by changes in both FPP and VPP in G50 and G20 . CONCLUSION Explosive resistance training in older adults results in the ability to produce higher PP outputs with heavier loads without loss of movement velocity . Moderate- to high-intensity training induced a greater relative contribution of force to PP production in this cohort 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 The authors investigated the effects of low-intensity resistance training on muscle size and strength in older men and women . Thirty-five participants ( age 59 - 76 yr ) were r and omly assigned to 2 groups and performed low-intensity ( 50 % of 1-repetition maximum ) knee-extension and -flexion exercises with either slow movement and tonic force generation ( LST ; 3-s eccentric , 3-s concentric , and 1-s isometric actions with no rest between repetitions ) or normal speed ( LN ; 1-s concentric and 1-s eccentric actions with 1-s rests between repetitions ) twice a week for 12 wk ( 2-wk preparation and 10-wk intervention ) . The LST significantly increased thigh-muscle thickness , as well as isometric knee-extension and -flexion strength . The LN significantly improved strength , but its hypertrophic effect was limited . These results indicate that even for older individuals , the LST can be an effective method for gaining muscle mass and strength Initial strength gains were examined in the context of learning a new skill . Forty female volunteers were r and omly assigned to one of four groups : a bench-press training group utilizing heavy loads in its training , a bench-press training group utilizing almost no load , an alternative training group using different exercises , or a control group that did not train . Training period was 6 wk , with three training sessions per week . Emphasis was put on keeping the coordination and muscular adaptation dem and s in the bench-press groups as invariant as possible . Bench-press training with a light or with a heavy weight was shown to be equally effective in improving the maximal velocity of contraction for a given absolute resistance . Mean velocity with loads of 0.37 , 6.6 , 16.6 , and 20 kg improved by 21.1 , 15.8 , 16.9 , and 19.5 % , respectively . No significant differences in the percent improvement at the four different loads were apparent , indicating that no significant velocity-specific adaptations were present . The bench-press training group , utilizing heavy loads in its training , was the only group with improved one repetition maximum . Overall , findings point to the development of coordination as the determining factor in early velocity-specific strength gains 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 PURPOSE To compare effects on strength in the early phase of resistance training with one or three sets and fast or slow speeds . METHODS A total of 115 healthy , untrained subjects were r and omized to a control group or one of four training groups : one set fast ( approximately 140 degrees.s(-1 ) ) , three sets fast , one set slow ( approximately 50 degrees.s(-1 ) ) , or three sets slow . All subjects attended training 3 x wk(-1 ) for 6 wk . Subjects in the training groups performed unilateral elbow flexion contractions with a target six- to eight-repetition maximum load . Control subjects sat at the training bench but did not train . One repetition maximum strength , arm circumference , and biceps skinfold thickness were measured before and after training . RESULTS One slow set increased strength by 25 % ( 95 % CI 13 - 36 % , P < 0.001 ) . Three sets of training produced greater increases in strength than one set ( difference = 23 % of initial strength , 95 % CI 12 - 34 % , P < 0.001 ) and fast training result ed in a greater increase in strength than slow training ( difference = 11 % , 95 % CI 0.2 - 23 % , P = 0.046 ) . The interaction between sets and speed was negative ( -15 % ) and of borderline significance ( P = 0.052 ) , suggesting there is a benefit of training with three sets or fast speeds , but there is not an additive benefit of training with both . CONCLUSIONS Three sets of exercise produce twice the strength increase of one set in the early phase of resistance training . Training fast produces greater strength increases than training slow ; however , there does not appear to be any additional benefit of training with both three sets and fast contractions We previously reported that low‐intensity [ 50 % of one repetition maximum ( 1RM ) ] resistance training with slow movement and tonic force generation ( LST ) causes muscle hypertrophy and strength gain in older participants . The aim of this study was to determine whether resistance training with slow movement and much more reduced intensity ( 30%1RM ) increases muscle size and strength in older adults . Eighteen participants ( 60–77 years ) were r and omly assigned to two groups . One group performed very low‐intensity ( 30 % 1RM ) knee extension exercise with continuous muscle contraction ( LST : 3‐s eccentric , 3‐s concentric , and 1‐s isometric actions with no rest between each repetition ) twice a week for 12 weeks . The other group underwent intermitted muscle contraction ( CON : 1‐s concentric and 1‐s eccentric actions with 1‐ Output:	Strength gains between conditions were not influenced by training status and age . Conclusions Overall , the results suggest that fast and moderate-slow resistance training improve dynamic muscular strength similarly in individuals within a wide range of training statuses and ages . Resistance training performed at fast movement velocities using moderate intensities showed a trend for superior muscular strength gains as compared to moderate-slow resistance training .
MS22274	*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 report the outcomes of high-dose-rate ( HDR ) brachytherapy and hypofractionated external beam radiotherapy ( EBRT ) combined with long-term and rogen deprivation therapy ( ADT ) for National Comprehensive Cancer Network ( NCCN ) criteria -defined high-risk ( HR ) and very high-risk ( VHR ) prostate cancer . Data from 178 HR ( n = 96 , 54 % ) and VHR ( n = 82 , 46 % ) prostate cancer patients who underwent 192Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed . The mean dose to 90 % of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy . After five fractions of HDR treatment , EBRT with 10 fractions of 3 Gy was administered . All patients initially underwent ≥6 months of neoadjuvant ADT , and adjuvant ADT was continued for 36 months after EBRT . The median follow-up was 61 months ( range , 25–94 months ) from the start of radiotherapy . The 5-year biochemical non- evidence of disease , freedom from clinical failure and overall survival rates were 90.6 % ( HR , 97.8 % ; VHR , 81.9 % ) , 95.2 % ( HR , 97.7 % ; VHR , 92.1 % ) , and 96.9 % ( HR , 100 % ; VHR , 93.3 % ) , respectively . The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3 % of patients and Grade 3 in 9.6 % . The highest late gastrointestinal toxicities were Grade 2 in 2.8 % of patients and Grade 3 in 0 % . Although the 5-year outcome of this tri-modality approach seems favorable , further follow-up is necessary to vali date clinical and survival advantages of this intensive approach compared with the st and ard EBRT approach PURPOSE A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy ( IMRT ) with a single-fraction high-dose-rate ( HDR ) brachytherapy implant . METHODS AND MATERIAL S From 2001 through 2006 , 26 consecutive patients were treated on the trial . The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity . Eligibility was limited to patients with T stage ≤2b , prostate-specific antigen ( PSA ) ≤20 , and Gleason score ≤7 . Treatment began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the peripheral zone , followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70Gy . Patients received 50.4Gy to the pelvic lymph node . The prostate dose ( IMRT and HDR ) result ed in an average biologic equivalent dose > 128Gy ( α/β=3 ) . Patients whose pretreatment PSA was ≥10ng/mL , Gleason score 7 , or stage ≥T2b received short-term and rogen ablation . RESULTS Median followup was 53 months ( 9 - 68 months ) . There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions . The median nadir PSA was 0.32ng/mL. All the 26 patients completed the treatment as prescribed . The rate of Grade 3 late genitourinary toxicity was 3.8 % consisting of a urethral stricture . There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities . CONCLUSIONS Single-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer PURPOSE We compared acute and late genitourinary ( GU ) and gastrointestinal ( GI ) toxicities in prostate cancer patients treated with three different high-dose radiation techniques . METHODS AND MATERIAL S A total of 1,903 patients with localized prostate cancer were treated with definitive RT at William Beaumont Hospital from 1992 to 2006 : 22 % with brachytherapy alone ( BT ) , 55 % with image-guided external beam ( EB-IGRT ) , and 23 % external beam with high-dose-rate brachytherapy boost ( EBRT+HDR ) . Median dose with BT was 120 Gy for LDR and 38 Gy for HDR ( 9.5 Gy × 4 ) . Median dose with EB-IGRT was 75.6 Gy ( PTV ) to prostate with or without seminal vesicles . For EBRT+HDR , the pelvis was treated to 46 Gy with an additional 19 Gy ( 9.5 Gy × 2 ) delivered via HDR . GI and GU toxicity was evaluated utilizing the NCI-CTC criteria ( v.3.0 ) . Median follow-up was 4.8 years . RESULTS The incidences of any acute ≥ Grade 2 GI or GU toxicities were 35 % , 49 % , and 55 % for BT , EB-IGRT , and EBRT+HDR ( p < 0.001 ) . Any late GU toxicities ≥ Grade 2 were present in 22 % , 21 % , and 28 % for BT , EB-IGRT , and EBRT+HDR ( p = 0.01 ) , respectively . Patients receiving EBRT+HDR had a higher incidence of urethral stricture and retention , whereas dysuria was most common in patients receiving BT . Any Grade ≥ 2 late GI toxicities were 2 % , 20 % , and 9 % for BT , EB-IGRT , and EBRT+HDR ( p < 0.001 ) . Differences were most pronounced for rectal bleeding , with 3-year rates of 0.9 % , 20 % , and 6 % ( p < 0.001 ) for BT , EB-IGRT , and EBRT+HDR respectively . CONCLUSIONS Each of the three modern high-dose radiation techniques for localized prostate cancer offers a different toxicity profile . These data can help patients and physicians to make informed decisions regarding radiotherapy for prostate and enocarcinoma PURPOSE To report the genitourinary ( GU ) and gastrointestinal ( GI ) morbidity and erectile dysfunction in a r and omized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer . METHODS AND MATERIAL S ASCENDE-RT ( And rogen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy ) enrolled 398 men , median age 68 years , who were then r and omized to either a st and ard arm that included 12 months of and rogen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy ( DE-EBRT ) boost to 78 Gy , or an experimental arm that substituted a low-dose-rate prostate brachytherapy ( LDR-PB ) boost . At clinic visits , investigators recorded GU and GI morbidity and information on urinary continence , catheter use , and erectile function . Exclusion of 15 who received non protocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188 , an LDR-PB boost . Median follow-up was 6.5 years . RESULTS The LDR-PB boost increased the risk of needing temporary catheterization and /or requiring incontinence pads . At 5 years the cumulative incidence of grade 3 GU events was 18.4 % for LDR-PB , versus 5.2 % for DE-EBRT ( P<.001 ) . Compared with the cumulative incidence , the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms ( 8.6 % vs 2.2 % , P=.058 ) . The 5-year cumulative incidence of grade 3 GI events was 8.1 % for LDR-PB , versus 3.2 % for DE-EBRT ( P=.124 ) . The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms ( 1.0 % vs 2.2 % , respectively ) . Among men reporting adequate baseline erections , 45 % of LDR-PB patients reported similar erectile function at 5 years , versus 37 % after DE-EBRT ( P=.30 ) . CONCLUSIONS The incidence of acute and late GU morbidity was higher after LDR-PB boost , and there was a nonsignificant trend for worse GI morbidity . No differences in the frequency of erectile dysfunction were observed Output:	Receiving both EBRT and BT increased the risk of stricture formation .
MS22275	*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 prospect ively compare oral contrast-enhanced T2-weighted half-Fourier rapid acquisition with relaxation enhancement ( RARE ) magnetic resonance ( MR ) imaging with T1-weighted gadolinium-enhanced fast low-angle shot ( FLASH ) MR and st and ard examinations in the evaluation of Crohn disease . MATERIAL S AND METHODS Institutional review board approval and informed consent were obtained . Fifty-nine patients with Crohn disease underwent MR imaging after oral administration of a superparamagnetic contrast agent ; RARE plain and fat-suppressed sequences and FLASH sequences were performed before and after intravenous injection of gadolinium chelate . References were endoscopic , small-bowel barium , computed tomographic , ultrasonographic , and clinical -biochemical scoring of disease activity . Two radiologists analyzed MR images for presence and extent of Crohn disease lesions , presence of strictures or other complications , and degree of local inflammation . MR findings were correlated with endoscopic , radiologic , and clinical data ( kappa statistic and Spearman rank correlation test ) . RESULTS T2-weighted MR was 95 % accurate , 98 % sensitive , and 78 % specific for detection of ileal lesions . Agreement between T1- and T2-weighted images ranged from 0.77 for ileal lesions to 1.00 for colic lesions . T2-weighted MR enabled detection of 26 of 29 severe strictures , 17 of 24 enteroenteric fistulas , and all adhesions and abscesses ; T1-weighted MR enabled detection of 20 of 29 severe strictures , 16 of 24 enteroenteric fistulas , and all adhesions and abscesses . Complications leading to surgery were found in 12 ( 20 % ) patients ; these were assessed correctly with either T1- or T2-weighted images . T2-weighted signal intensities of the wall and mesentery correlated with biologic activity ( P < .001 , r of 0.774 and 0.712 , respectively ) . Interobserver agreement was 0.642 - 1.00 for T2-weighted and 0.711 - 1.00 for T1-weighted images . CONCLUSION T2-weighted MR can depict Crohn disease lesions and help assess mural and transmural inflammation with the same accuracy as gadolinium-enhanced T1-weighted MR . Combination of gadolinium-enhanced T1- and T2-weighted sequences is useful in the assessment of Crohn disease Background : Studies comparing magnetic resonance enterography ( MRE ) and computerized tomography enterography ( CTE ) for Crohn 's disease ( CD ) are scarce . Methods : The aim of this study was to prospect ively compare the sensitivity , specificity , and accuracy of abdominal MRE and CTE to assess disease activity and complications ( fistulas , strictures ) in ileocolonic CD . A total of 44 patients ( 23 male ; 21 female ; mean age 44 ) with ileocolonic CD underwent both MR and CT in a short time interval ( mean 5 days ) . A 16‐slice CT with intravenous contrast and an MRI with oral and paramagnetic intravenous contrast were performed . Ileocolonoscopy was used as the reference st and ard . Sensitivity values of CT and MR for detection of extraenteric signs of disease were compared with the McNemar test , with results of imaging studies , surgery , and physical examination as reference st and ards . Results : No significant differences in sensitivity , specificity , and accuracy were observed between MRE and CTE regarding the following parameters at the patient level : localization of CD ( P = 1.0 ) , bowel wall thickening ( P = 1.0 ) , bowel wall enhancement ( P = 1.0 ) , enteroenteric fistulas ( P = 0.08 ) , detection of abdominal nodes ( P = 1.0 ) , and perivisceral fat enhancement ( P = 0.31 ) . MR was significantly superior compared to CT in detecting strictures ( P = 0.04 ) . Per segment analysis showed that MRE was significantly superior to CTE in detecting ileal wall enhancement ( P = 0.02 ) . Conclusions : MR and CT are equally accurate to assess disease activity and bowel damage in CD . MR may be superior to CT in detecting intestinal strictures and ileal wall enhancement . MR may represent an alternative technique to CT in assessing ileocolonic CD . ( Inflamm Bowel Dis 2010 PURPOSE To evaluate activity staging of Crohn 's disease ( CD ) measured with MR-enterography using ileoscopy as reference st and ard . MATERIAL S AND METHODS A prospect i ve study was made of 61 patients with CD . All patients underwent MR-enterography and ileoscopy . MRI activity was measured by means of an ad hoc developed score , as well as by analysis of the imaging findings , and was compared with the SES-CD score obtained via ileoscopy . Examinations were performed using a 1.0 T scanner . RESULTS MRI score discriminates between active and inactive disease with an area under the ROC curve of 0.941 . Overall correlation with the st and ard reference SES-CD score was moderate to strong ( Spearman 's r=0.62 p<0.001 ) . Agreement between both methods in staging patients with ileal CD as inactive , mild or moderate to severe was good ( Cohen 's κ=0.60 ) . Differences in means of the MRI activity scores of the three groups showed statistical significance ( p<0.01 ) . CONCLUSIONS The MRI score is a reliable predictor of activity in ileal CD and can stage patients in a way comparable to endoscopy . 1.0 T scans are valid for performing radiological evaluation of ileal Crohn 's disease BACKGROUND & AIMS Magnetic resonance ( MR ) enterography is a recommended imaging technique for detecting intestinal involvement in Crohn 's disease ( CD ) . However , the diagnostic accuracy of MR enterography has not been compared directly what that of enteroscopy of the jejunum and proximal ileum . We evaluated the usefulness of MR enterocolonography ( MREC ) by comparing its findings with those from balloon-assisted enteroscopy . METHODS In a prospect i ve study , MREC and enteroscopy were performed within 3 days of each other on 100 patients . Ulcerative lesions and all mucosal lesions were evaluated . Physicians and radiologists were blinded to results from other studies . Findings from MREC were compared directly with those from enteroscopy ; the sensitivity and specificity with which MREC detected CD lesions were assessed . RESULTS MREC detected ulcerative lesions and all mucosal lesions in the small intestine with 82.4 % sensitivity ( 95 % confidence interval [ CI ] , 75.4%-87.7 % ) and 67.5 % sensitivity ( 95 % CI , 63.1%-70.0 % ) ; specificity values were 87.6 % ( 95 % CI , 83.7%-90.6 % ) and 94.8 % ( 95 % CI , 90.1%-97.5 % ) . MREC detected major stenosis with 58.8 % sensitivity ( 95 % CI , 37.6%-77.2 % ) and 90.0 % specificity ( 95 % CI , 88.4%-91.5 % ) and all stenoses with 40.8 % sensitivity ( 95 % CI , 30.8%-49.4 % ) and 93.7 % specificity ( 95 % CI , 91.1%-95.9 % ) . CONCLUSIONS MREC is useful for detecting active lesions in the small intestine . However , MR imaging is less sensitive for detecting intestinal damage , such as stenoses . Enteroscopy is preferred for identifying intestinal damage . Suitable imaging approaches should be selected to assess CD lesions in deep small intestine In the European Cooperative Crohn 's Disease Study patients from 14 centers were included in whom diagnosis was made within 2 years before study entry on the basis of generally accepted radiological , endoscopical and /or histological criteria or a combination of all . Reasons for exclusion were : diagnosis older than 2 years in patients who did not require active treatment , age less than 18 years , duration of symptoms less than 3 months , presence of complications which potentially required emergency surgery . Data on clinical features were obtained in 633 patients , of whom 452 were eligible to participate in the study . In 110 patients r and omized to placebo the natural course of Crohn 's disease was studied . Patients with ileocolonic involvement were younger than patients with either colonic or small intestinal involvement only . Classic ileitis terminalis was present in 14 % of the patients . 49 % of the patients had combined involvement of both the small and large intestine . 30 % of patients had only small intestinal involvement , and in 21 % colonic disease was present . Small intestinal involvement was associated with a significantly lower Crohn 's Disease Activity Index ( CDAI ) than other anatomical locations of the disease . Perianal disease was more often associated with colonic than with small intestinal involvement . 60 % of placebo patients with active disease at entry achieved at least a transient remission within the initial 5 months of study . After 2 years , 23 % of patients with active disease at entry and 68 % of patients with quiescent disease had reached or maintained a remission , respectively . By stepwise multiple linear regression analysis long duration of disease between diagnosis and r and omization , normal serum albumin and combined involvement of small intestine and colon were identified as predictors of a more favorable outcome of patients treated with placebo . In contrast , extensive small bowel disease , treatment with steroids and bowel resection prior to study entry correlated with a less favorable outcome . However , by life table analysis outcome of previously untreated and treated patients in the placebo group was similar Objectives To prospect ively compare conventional MRI sequences , dynamic contrast enhanced ( DCE ) MRI and diffusion weighted imaging ( DWI ) with histopathology of surgical specimens in Crohn ’s disease . Methods 3-T MR enterography was performed in consecutive Crohn ’s disease patients scheduled for surgery within 4 weeks . One to four sections of interest per patient were chosen for analysis . Evaluated parameters included mural thickness , T1 ratio , T2 ratio ; on DCE-MRI maximum enhancement ( ME ) , initial slope of increase ( ISI ) , time-to-peak ( TTP ) ; and on DWI apparent diffusion coefficient ( ADC ) . These were compared with location-matched histopathological grading of inflammation ( AIS ) and fibrosis ( FS ) using Spearman correlation , Kruskal – Wallis and Chi-squared tests . Results Twenty patients ( mean age 38 years , 12 female ) were included and 50 sections ( 35 terminal ileum , 11 ascending colon , 2 transverse colon , 2 descending colon ) were matched to AIS and FS . Mural thickness , T1 ratio , T2 ratio , ME and ISI correlated significantly with AIS , with moderate correlation ( r = 0.634 , 0.392 , 0.485 , 0.509 , 0.525 , respectively ; all P < 0.05 ) . Mural thickness , T1 ratio , T2 ratio , ME , ISI and ADC correlated significantly with FS ( all P < 0.05 ) . Conclusions Quantitative parameters from conventional , DCE-MRI and DWI sequences correlate with histopathological scores of surgical specimens . DCE-MRI and DWI parameters provide additional information . Key points• Conventional MR enterography can be used to assess Crohn ’s disease activity.• Several MRI parameters correlate with inflammation and fibrosis scores from histopathology.• Dynamic contrast enhanced imaging and diffusion weighted imaging give additional information.• Quantitative MRI parameters can be used as biomarkers to evaluate Crohn ’s disease activity Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research , derived from extensive review of published literature . When data that will withst and objective scrutiny are not available , a recommendation may be made based on a consensus of experts . Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty . Guidelines are intended to be flexible , not necessarily indicating the only acceptable approach , and should be distinguished from st and ards of care that are inflexible and rarely violated . Given the wide range of choices in any health-care problem , the physician should select the course best suited to the individual patient and the clinical situation presented . These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee . Expert opinion is solicited from the outset for the document . The quality of evidence upon which a specific recommendation is based is as follows : Grade A : Homogeneous evidence from multiple well- design ed r and omized ( therapeutic ) or cohort ( descriptive ) controlled trials , each involving a number of participants to be of sufficient statistical power . Grade B : Evidence from at least one large well- design ed clinical trial with or without r and omization , from cohort or case – control analytic studies , or well- design ed meta- analysis . Grade C : Evidence based on clinical experience , descriptive studies , or reports of expert committees . The Committee review s guidelines in depth , with participation from experienced clinicians and others in related fields . The final recommendations are based on the data available at the time of the production of the document and may be up date d with pertinent scientific developments at a later time Background : We developed novel magnetic resonance enterocolonography ( MREC ) for simultaneously evaluating both small and large bowel lesions in patients with Crohn 's disease ( CD ) . The aim of this study was to evaluate the diagnostic performance of MREC by comparing results of Output:	MR imaging provides a reliable alternative in detecting small bowel activity in patients with Crohn 's disease . Its advantages include high diagnostic accuracy and no radiation exposure while its disadvantages include high cost and limited availability
MS22276	*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 Objective : To evaluate the effect of simultaneous zinc and vitamin A supplementation on diarrhoea and acute lower respiratory infections in children . Study design : R and omised double blind placebo controlled trial . Setting : Urban slums of Dhaka , Bangladesh . Participants and methods : 800 children aged 12 - 35 months were r and omly assigned to one of four intervention groups : 20 mg zinc once daily for 14 days ; 200 000 IU vitamin A , single dose on day 14 ; both zinc and vitamin A ; placebo . The children were followed up once a week for six months , and morbidity information was collected . Results : The incidence and prevalence of diarrhoea were lower in the zinc and vitamin A groups than in the placebo group . Zinc and vitamin A interaction had a rate ratio ( 95 % confidence interval ) of 0.79 ( 0.66 to 0.94 ) for the prevalence of persistent diarrhoea and 0.80 ( 0.67 to 0.95 ) for dysentery . Incidence ( 1.62 ; 1.16 to 2.25 ) and prevalence ( 2.07 ; 1.76 to 2.44 ) of acute lower respiratory infection were significantly higher in the zinc group than in the placebo group . The interaction term had rate ratios of 0.75 ( 0.46 to 1.20 ) for incidence and 0.58 ( 0.46 to 0.73 ) for prevalence of acute lower respiratory infection . Conclusions : Combined zinc and vitamin A synergistically reduced the prevalence of persistent diarrhoea and dysentery . Zinc was associated with a significant increase in acute lower respiratory infection , but this adverse effect was reduced by the interaction between zinc and vitamin A. What is already known on this topic Trials of vitamin A supplementation have failed to show a beneficial effect on morbidity in children Experimental studies have shown that , in the presence of zinc deficiency , vitamin A supplementation fails to reverse vitamin A deficiency Coexistence of deficiencies of zinc and vitamin A could be a reason for the failure of vitamin A supplementation , but data in humans are limited What this paper adds Combined zinc and vitamin A supplementation is more effective in reducing persistent diarrhoea and dysentery than either vitamin A or zinc alone Zinc alone increased respiratory illnesses , but interaction between zinc and vitamin A reduced this adverse There is uncertainty over whether vitamin A supplementation reduces morbidity among children with sub clinical deficiency of the vitamin . Hence a double-blind , placebo-controlled trial of the effect of vitamin A supplementation on childhood morbidity was conducted among 11,124 children aged 6 - 83 months in the northwest of Haiti . After a r and om start , children were sequentially assigned by household units to receive either megadose vitamin A or placebo in three distribution cycles 4 months apart . 2 to 8 weeks after each administration of the vitamin A and placebo capsules , indicators of childhood morbidity were reassessed through interviews conducted in the homes of participating families . The vitamin A group was found to have an increased 2-week prevalence of all symptoms and signs of childhood morbidity assessed , including diarrhoea ( rate ratio [ RR ] = 1.09 , 95 % confidence interval 1.05 - 1.14 ) , rhinitis ( RR = 1.02 , 95 % confidence interval 1.00 - 1.04 ) , cold/flu symptoms ( RR = 1.04 , 95 % confidence interval 1.01 - 1.06 ) , cough ( RR = 1.07 , 95 % confidence interval 1.03 - 1.11 ) , and rapid breathing ( RR = 1.18 , 95 % confidence interval 1.09 - 1.27 ) . The study shows an increased 2-week prevalence of diarrhoea and the symptoms of respiratory infections after vitamin A supplementation OBJECTIVES --To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme . DESIGN --Opportunistic controlled trial . SETTING --Jumla district , Nepal . SUBJECTS -- All children aged under 5 years ; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation . MAIN OUTCOME MEASURES --Mortality and cause of death in the five months after supplementation . RESULTS --Risk of death for children aged 1 - 59 months in supplemented communities was 26 % lower ( relative risk 0.74 , 95 % confidence interval 0.55 to 0.99 ) than in unsupplemented communities . The reduction in mortality was greatest among children aged 6 - 11 months : death rate ( deaths/1000 child years at risk ) was 133.8 in supplemented children and 260.8 in unsupplemented children ( relative risk 0.51 , 0.30 to 0.89 ) . The death rate from diarrhoea was also reduced ( 63.5 supplemented v 97.5 unsupplemented ; relative risk 0.65 , 0.44 to 0.95 ) . The extra cost per death averted was about $ 11 . CONCLUSION --The results support a role for Vitamin A in increasing child survival . The supplementation programme was readily integrated with the ongoing community health programme at little extra cost BACKGROUND R and omized controlled trials have shown inconsistent responses of childhood pneumonia to the use of vitamin A as an adjunct to the st and ard treatment of pneumonia . OBJECTIVE We evaluated the effect of a moderate dose of vitamin A as an adjunct to st and ard antimicrobial treatment on the duration of respiratory signs in children with pneumonia . DESIGN Children , aged 2 - 59 mo , with pneumonia and weight-for-age < 50th percentile who had been admitted to the Baca Ortíz Children 's Hospital in Quito , Ecuador , were r and omly assigned to receive 50,000 IU ( aged 2 - 12 mo ) or 100,000 IU ( aged > 12 - 59 mo ) vitamin A or a placebo . RESULTS Of the 287 children enrolled , 145 received vitamin A and 142 received placebo . No overall differences were observed between the 2 groups in the duration of signs of pneumonia . Multiple linear regression showed a significant interaction between basal serum retinol concentration and vitamin A group for the time ( in h ) to remission of respiratory signs ( beta = -3.57 , SE = 1.09 , P = 0.001 ) . Duration of clinical signs was less in children with basal serum retinol concentrations > 200 microg/L who received vitamin A supplements than in children with similar concentrations who received placebo ( 69.9 + /- 49.9 h compared with 131.3 + /- 143.9 h ; P = 0.049 ) . CONCLUSIONS Overall , we found no effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged < 5 y. However , a beneficial effect was seen in children with high basal serum retinol concentrations Because the clinics in a multiclinic r and omized clinical trial represent neither fixed stratification effects nor r and om classificatory effects , the appropriate analysis of data from such a trial has been the subject of controversy and debate . The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed . Is it ever valid to ignore the effects of clinics in the analysis ? Is it ever valid to drop clinics from the analysis ? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor ? Assuming that clinics will be taken account of in the analysis , should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments ? How should the data be analyzed if there is evidence of treatment-by-clinic interaction Vitamin A supplementation of population s of vitamin A-deficient preschool-age children has been shown to reduce childhood mortality , but the primary preventive effects of such supplements on childhood infectious diseases have not been carefully evaluated . We conducted an individually r and omized , placebo-controlled , double-masked trial among 1,407 Indonesian preschool-age children , to measure the effects of high dose vitamin A on acute respiratory and diarrheal illnesses . Signs and symptoms of morbidity were monitored using every other day home surveillance by trained interviewers . High dose vitamin A supplements increased the incidence of acute respiratory illnesses ( ARI ) by 8 % , and acute lower respiratory illnesses ( ALRI ) by 39 % . These detrimental effects on acute lower respiratory illnesses were most marked in children with adequate nutritional status ( rate ratio 1.83 , 95 % confidence interval 1.257 - 2.669 ) . In contrast , vitamin A tended to be protective of ALRI in chronically malnourished children ( rate ratio 0.71 , 95 % confidence interval 0.375 - 1.331 ) . There was no overall effect of high-dose vitamin A supplements on the incidence of diarrheal disease ( rate ratio 1.06 , 95 % confidence interval 0.920 - 1.225 ) . However , we found a significant interaction between supplementation and age : vitamin A increased the incidence of diarrhea in children < 30 mo of age , but tended to reduce the incidence in older children . The finding of a significant adverse effect of vitamin A supplements in adequately nourished children highlights the need to review the criteria for selecting population s of preschool-age children for vitamin A supplementation BACKGROUND The relative-dose-response ( RDR ) test is used to identify subjects with marginal liver vitamin A stores , but its use has not been evaluated during episodes of infection . OBJECTIVE The objective was to assess , with the RDR test , the vitamin A status of children recovering from pneumonia . DESIGN As part of a double-blind , placebo-controlled clinical trial of high-dose vitamin A supplements among children hospitalized with pneumonia in Lima , Peru , we examined the association of treatment group , nutritional status , severity of disease , and induction of the acute phase response [ on the basis of serum C-reactive protein ( CRP ) ] on serum retinol and the RDR test . RESULTS Serum retinol was low at admission and increased significantly in both the vitamin A and placebo groups during recovery . Serum CRP had a significant , inverse association with retinol at both admission and discharge . Serum retinol and CRP concentrations never differed significantly between the treatment groups . Among subjects with CRP > or = 10 mg/L , 21 % in the vitamin A group and 20 % in the placebo groups ( P = 0.83 ) had a positive RDR test result . Among subjects with CRP < 10 mg/L , 56 % in the placebo group but only 6 % in the vitamin A group had positive RDR test results ( P = 0.002 ) . CONCLUSION The RDR test was useful in assessing the vitamin A status of children recovering from pneumonia when CRP concentrations were < 10 mg/L but not when CRP concentrations were higher Vitamin A deficiency and acute lower respiratory tract infections coexist as important public health problems in many developing countries . We carried out a r and omized , double-blind , placebo-controlled trial to examine whether large doses of vitamin A given to Tanzanian children who are admitted to the hospital with nonmeasles pneumonia would reduce the severity of respiratory disease . Six hundred eighty-seven children were r and omly assigned to receive either placebo or vitamin A [ 200 000 IU ( 60 mg retinol equivalents ) for children > 1 y of age and 100000 IU ( 30 mg retinol equivalents ) for infants ] on the day of admission and another dose on the following day . Of the 346 children in the vitamin A group , 13 died in the hospital , compared with 8 of 341 children in the placebo group ; the relative mortality was 1.63 ( 95 % CI : 0.67 , 3.97 ; P = 0.28 ) . The mean number of days of hospitalization was the same in both groups ( 4.2 d ) . There were no differences between the vitamin A and placebo groups in the duration of hospital stay when examined within categories of children stratified by age , sex , breast-feeding status , nutritional status at baseline , or quartile of dietary vitamin A intake in the 4 mo before admission to the hospital . There were also no differences in the mean number of days of fever , rapid respiratory rate , or hypoxia , whether these endpoints were examined in the total number of subjects or in a subset with more severe clinical conditions at baseline . Large doses of vitamin A had no protective effect on the course of pneumonia in hospitalized Tanzanian children The effect of high-dose vitamin A supplementation on recovery from morbidity and on recovery from nosocomial morbidity of hospitalized children has been poorly studied and results are conflicting . The effect of daily , low doses has never been assessed . We investigated the effect of a single high Output:	Disease severity after supplementary high-dose vitamin A was significantly worse in children who received vitamin A compared with placebo . The evidence did not suggest a significant reduction with vitamin A adjunctive treatment in mortality , measures of morbidity , nor an effect on the clinical course of pneumonia in children with non-measles pneumonia .
MS22277	*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: Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials Background Osteoarthritis ( OA ) is a degenerative disease , considered to be one of the major public health problems . Research suggests that patient education is feasible and valuable for achieving improvements in quality of life , in function , well-being and improved coping . Since 1994 , Primary Health Care in Malmö has used a patient education programme directed towards OA . The aim of this study was to evaluate the effects of this education programme for patients with OA in primary health care in terms of self-efficacy , function and self-perceived health . Method The study was a single-blind , r and omized controlled trial ( RCT ) in which the EuroQol-5D and Arthritis self-efficacy scale were used to measure self-perceived health and self-efficacy and function was measured with Grip Ability Test for the upper extremity and five different functional tests for the lower extremity . Results We found differences between the intervention group and the control group , comparing the results at baseline and after 6 months in EuroQol-5D ( p < 0.001 ) and in st and ing one leg eyes closed ( p = 0.02 ) in favour of the intervention group . No other differences between the groups were found . Conclusion This study has shown that patient education for patients with osteoarthritis is feasible in a primary health care setting and can improve self-perceived health as well as function in some degree , but not self-efficacy . Further research to investigate the effect of exercise performance on function , as well as self-efficacy is warranted . Trial registration The trial is registered with Clinical Trials.gov . Registration number : OBJECTIVE To assess the effect of an insole with subtalar strapping on patients with medial compartment osteoarthritis ( OA ) of the knee . METHODS Novel lateral wedged insoles with elastic subtalar strapping ( the subtalar strapping support group ) and ankle supporters with a lateral wedged heel insert ( the sock-type ankle support group ) were prepared . Eighty-eight female out patients with knee OA were treated with 1 of the 2 insoles for 8 weeks . Femorotibial angle was assessed by st and ing radiographs with and without unilateral insole use for each subject . Symptoms of knee OA were evaluated according to the severity index of Lequesne et al at baseline and at the final assessment . RESULTS Participants wearing the insole with subtalar strapping ( n = 42 ) demonstrated significantly decreased femorotibial angle ( an average of change : -3.1 degrees + /- 2.5 degrees , P < 0.0001 ) , but a significant difference was not found in the sock-type ankle support group ( n = 46 ; -0.4 degrees + /- 1.1 degrees , P > 0.05 ) . In the subtalar strapping support group , pain during bed rest with full extension of the knee ( P < 0.0001 ) , pain after getting up ( P = 0.04 ) , pain on getting up from a seated position ( P = 0.021 ) , maximum distance walked ( P = 0.009 ) , and aggregate severity score ( P < 0.0001 ) were significantly improved compared with baseline . In contrast , significant symptomatic improvement was detected only in the aggregate score ( P = 0.016 ) in the sock-type ankle support group , but not in any of the 10 specific categories . CONCLUSION The lateral wedged insole with subtalar strapping induces correction of the femorotibial angle and symptomatic relief in patients with varus-deformity knee OA R and omized controlled trials often suffer from two major complications , i.e. , noncompliance and missing outcomes . One potential solution to this problem is a statistical concept called intention-to-treat ( ITT ) analysis . ITT analysis includes every subject who is r and omized according to r and omized treatment assignment . It ignores noncompliance , protocol deviations , withdrawal , and anything that happens after r and omization . ITT analysis maintains prognostic balance generated from the original r and om treatment allocation . In ITT analysis , estimate of treatment effect is generally conservative . A better application of the ITT approach is possible if complete outcome data are available for all r and omized subjects . Per- protocol population is defined as a subset of the ITT population who completed the study without any major protocol violations Lateral wedges were originally proposed to manage medial compartment osteoarthritis of the knee but recent review s suggest that lateral wedges do not affect disease progression . We performed a systematic review to analyse the recent literature and define how effective , if at all , lateral wedges are in the management of medial compartment osteoarthritis of the knee . The inclusion criteria were defined as any study published within the last decade , using a sample size of at least twenty patients , and investigating the effect of insoles or wedges on either unilateral or bilateral knee varus osteoarthritis . The st and ardised keyword term ‘ lateralwedgeOR insoleOR orthotic OR medial compartment OR varus OR osteoarthri * OR knee * ’ was used . We identified 10 studies that fitted our inclusion criteria . Although there is not enough evidence in the literature to prove that lateral wedge orthotics are an effective treatment for varus osteoarthritis of the knee , there is some evidence to suggest that they do have some symptomatic effect . Patients with early osteoarthritis and higher BMI may benefit to a greater extent than those with a greater extent of degenerative changes and lower BMI . The literature is unclear as to what the optimal duration for the use of lateral wedges is , but does support the prolonged use of the wedges as the benefits at one month are maintained at one year . Future studies should be r and omised controlled trials with a large sample size with long follow-up , and use objective clinical , biomechanical and radiological outcome measures The index for hip disease ( ISH ) was established , vali date d and appraised as a new assessment test for the trial of new drugs as well as for long-term follow-up of patients , and to help with future indications for surgery . The ISH deals with pain , maximum walking distance , and some activities of daily living . Inter-observer reproducibility is good ( mean deviation 0.55 points ; p less than 0.05 ) . In a short-term , double-blind crossover trial , the ISH , judged according to its power to distinguish between the active drug period and the placebo period , appears as one of the best assessment tests . In the long term , total hip prosthesis is most often justified when the ISH score reaches 10 - 12 points . The index of severity for knee disease ( ISK ) was vali date d and appraised by the same statistical methods . Its value in non-steroidal anti-inflammatory drug ( NSAID ) or analgesic trials is lower than the value of the ISH . However , its use is still justified for that purpose , and for long-term follow-up of osteoarthritis of the knee OBJECTIVES To identify factors that predicted incident use of assistive walking devices ( AWDs ) and to explore whether AWD use was associated with changes in osteoarthritis of the knee . DESIGN Prospect i ve cohort study . SETTING Community . PARTICIPANTS Older adults ( N=2639 ) in the Health , Aging and Body Composition ( Health ABC ) Study including a subset of 874 patients with prevalent knee pain . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Incident use of AWDs , mean Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain scores , and the frequency of joint space narrowing on knee radiographs over a 3-year time period . RESULTS AWD use was initiated by 9 % of the entire Health ABC cohort and 12 % of the knee pain subset . Factors that predicted use in both groups were age ≥73 ( entire cohort : odds ratio [OR]=2.07 ; 95 % confidence interval [ CI ] , 1.43 - 3.01 ; knee pain subset : OR=1.87 ; 95 % CI , 1.16 - 3.03 ) , black race ( entire cohort : OR=2.95 ; 95 % CI , 2.09 - 4.16 ; knee pain subset : OR=3.21 ; 95 % CI , 2.01 - 5.11 ) , and lower balance ratios ( entire cohort : OR=3.18 ; 95 % CI , 2.21 - 4.59 ; knee pain subset : OR=3.77 ; 95 % CI , 2.34 - 6.07 ) . Mean WOMAC pain scores decreased slightly over time in both AWD and non-AWD users . Twenty percent of non-AWD users and 28 % of AWD users had radiographic progression in joint space narrowing of the tibiofemoral joint in at least 1 knee . Fourteen percent of non-AWD users and 12 % of AWD users had radiographic progression in joint space narrowing in the patellofemoral joint in at least 1 knee . CONCLUSIONS AWDs are frequently used by older adults . Knee pain and balance problems are significant reasons why older adults initiate use of an AWD . In an exploratory analysis , there was no consistent relation between the use or nonuse of an AWD and WOMAC pain scores or knee joint space narrowing progression . Further studies of the relation of use of AWDs to changes in knee osteoarthritis are needed OBJECTIVE To assess the contribution of radiological osteoarthritis of the hips and knees to disabilities in the activities of daily living related to lower limb function . METHODS During a home interview 1156 men and 1739 women , r and omly chosen from the source population of all independently living residents aged 55 years and over living in a district of Rotterdam ( the Rotterdam Study ) were asked about locomotor disability by six questions of the Health Assessment Question naire ( HAQ ) and about pain in the hips and knees in the past month . Radiographs of hips and knees were scored according to the Kellgren grading system for osteoarthritis . RESULTS The prevalence of locomotor disability , defined as at least some difficulty with three or more out of six lower limb functions , was 20.2 % for men and 31.9 % for women ; hip pain was present in 8.3 % of the men and 16.6 % of the women ; knee pain in 12.6 % of the men and 22.3 % of the women . The prevalence of radiological osteoarthritis grade 2 + of the hip was 14.1 % for men and 15.9 % for women , and of the knee 16.3 % and 29.1 % respectively . The odds ratio ( OR ) ( 95 % confidence intervals ) of hip radiological osteoarthritis for locomotor disability adjusted for age and all other variables was for men : 1.4 ( 0.9 , 2.1 ) and for women : 2.2 ( 1.6 , 2.9 ) . The ORs of knee radiological osteoarthritis adjusted for age and all other variables were 1.1 ( 0.9 , 2.1 ) and 1.4 ( 1.1 , 1.8 ) respectively . Severe radiological osteoarthritis ( grade 3 + ) was stronger associated . The ORs of pain in the hips or knees and morning stiffness were much higher ( between 2.7 and 5.5 for men and between 2.1 and 5.1 for women ) . CONCLUSIONS Radiological osteoarthritis of the hip and knee are only weak independent predictors of locomotor disability in women , and not at all independently associated with locomotor disability in men . Age , pain of the hips and knees , and morning stiffness seem to be the most important independent determinants of locomotor disability Overemphasis on hypothesis testing-- and the use of P values to dichotomise significant or non-significant results --has detracted from more useful approaches to interpreting study results , such as estimation and confidence intervals . In medical studies investigators are usually interested in determining the size of difference of a measured outcome between groups , rather than a simple indication of whether or not it is statistically significant . Confidence intervals present a range of values , on the basis of the sample data , in which the population value for such a difference may lie . Some methods of calculating confidence intervals for means and differences between means are given , with similar information for proportions . The paper also gives suggestions for graphical display . Confidence intervals , if appropriate to the type of study , should be used for major findings in both the main text of a paper and its abstract The prevalence of osteoarthritis ( OA ) is greater in women then men . Weight , a factor strongly associated with osteoarthritis , is significantly increased over the menopausal transition . Despite the high prevalence of osteoarthritis , a disabling disease with limited treatment options , there is a paucity of studies in women . The longitudinal phase of the Melbourne Women ' Output:	Limited evidence supported the positive effects of short-lever elastic knee braces to improve pain and functional disability in specific outcomes . No evidence was found to support the use of foot orthoses , such as laterally wedged insoles , medial arch support and metatarsal arch pad . Conclusion : Our systematic review found no conclusive evidence about the effectiveness of any braces and orthoses for patients with medial knee osteoarthritis . Clinical relevance This is the first systematic review of Japanese- language r and omised controlled trials investigating orthoses for patients with knee osteoarthritis . Clinicians can consider the use of short-lever elastic knee braces to improve specifically pain on squat or walking . Evidence found in this review does not support the use of foot orthoses
MS22278	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE This study examined the effectiveness of three peer-facilitated brief alcohol interventions -small group motivational interviewing , motivationally enhanced peer theater , and an interactive alcohol-education program-with students engaging in high-risk drinking who were referred for alcohol policy violations . METHOD Undergraduate students referred for alcohol policy violations ( N = 695 ) at a large northeastern public university were r and omized to one of the three conditions . Six-month follow-up data were collected on drinking frequency and quantity , negative consequences , use of protective behaviors , and perceptions of peers ' drinking norms . RESULTS There were no statistically significant overall pre-post effects or treatment effects . However , exploratory analyses indicated that decreases in perceived norms and increases in use of protective behavioral strategies were associated with reductions in alcohol use and alcohol-related problems at follow-up ( p < .01 ) . CONCLUSIONS The presence of nonsignificant pre-post or main effects is , in part , consistent with recent research indicating that sanctioned college students may immediately reduce drinking in response to citation and that brief interventions may not contribute to additional behavioral change . The presence of statistically significant correlations between alcohol use and related problems with corrections in norms misperceptions and increased use of protective behaviors at the individual level holds promise for both research and practice . The integration of elements addressing social norms and use of protective behaviors within brief cognitive-behavioral intervention protocol s delivered by trained peer facilitators warrants further study using r and omized clinical trials AIM To establish the efficacy of a brief motivational intervention compared to feedback only when delivered in an emergency department for reducing alcohol use and problems among young adults . DESIGN Two-group r and omized controlled trial with follow-up assessment s at 6 and 12 months . SETTING Level I Trauma Center . PARTICIPANTS A total of 198 18 - 24-year-old patients who were either alcohol positive upon hospital admission or met screening criteria for alcohol problems . INTERVENTION Participants were assigned r and omly to receive a one-session motivational intervention ( MI ) that included personalized feedback , or the personalized feedback report only ( FO ) . All participants received additional telephone contact 1 month and 3 months after baseline . MEASUREMENTS Demographic information , alcohol use , alcohol problems and treatment seeking . FINDINGS Six months after the intervention MI participants drank on fewer days , had fewer heavy drinking days and drank fewer drinks per week in the past month than did FO patients . These effects were maintained at 12 months . Clinical significance evaluation indicated that twice as many MI participants as FO participants reliably reduced their volume of alcohol consumption from baseline to 12 months . Reductions in alcohol-related injuries and moving violations , and increases in alcohol treatment-seeking were observed across both conditions at both follow-ups with no differences between conditions . CONCLUSIONS This study provides new data supporting the potential of the motivational intervention tested to reduce alcohol consumption among high-risk youth AIMS This study aim ed at testing the effectiveness of a brief motivational intervention ( BI ) compared with a minimal intervention ( MI ) for reducing alcohol consumption in adult , alcohol-positive traffic casualties . METHODS Patients were recruited at the emergency room of a trauma hospital and screened for alcohol by a qualitative saliva test ( positive from a blood alcohol concentration of 0.02 g/l ) . Positive patients ( 13.3 % ) who accepted entering the study were r and omly allocated into BI and MI . Baseline assessment was the same for all patients . Blind telephone follow-ups were performed at months 3 , 6 , and 12 , and results were analysed by protocol and by intention-to-treat analysis . RESULTS After 1 year of follow-up , 67 % of the patients had reduced their consumption , the percentage of heavy drinkers had dropped by 47 % , and 62 % of baseline AUDIT-C positive patients ( hazardous drinkers ) had become negative . Binge drinking dropped significantly ( P < 0.05 ) . Results at month 12 were in line with the previous ones . CONCLUSIONS The effectiveness of BI compared with MI has not been verified , but a significant reduction in consumption has been observed in the whole sample , without significant differences by type of intervention . The persistence and dimension of changes suggest a real effect of both interventions , although the lack of a pure control group does not allow definitive conclusions . Traffic casualties are in a teachable moments to benefit from easy and cheap interventions This study tested the efficacy of behavioral treatments for alcohol use disorders ( AUD ) among men who have sex with men ( MSM ) and who are at risk for HIV transmission . HIV-negative MSM with current AUD ( N = 198 ) were recruited , offered treatment focused on reducing drinking and HIV risk , and followed during treatment and 12 months posttreatment . Participants ( n = 89 ) accepted treatment and were r and omized to either 4 sessions of motivational interviewing ( MI ) or 12 sessions of combined MI and coping skills training ( MI + CBT ) . Other participants ( n = 109 ) declined treatment but were followed , forming a non-help-seeking group ( NHS ) . MI yielded significantly better drinking outcomes during the 12-week treatment period than MI + CBT , but posttreatment outcomes were equivalent . NHS participants significantly reduced their drinking as well . Service delivery and treatment research implication s are discussed Group motivational interviewing ( MI ) interventions that target youth at-risk for alcohol and other drug ( AOD ) use may prevent future negative consequences . Youth in a teen court setting [ n=193 ; 67 % male , 45 % Hispanic ; mean age 16.6 ( SD=1.05 ) ] were r and omized to receive either a group MI intervention , Free Talk , or usual care ( UC ) . We examined client acceptance , and intervention feasibility and conducted a preliminary outcome evaluation . Free Talk teens reported higher quality and satisfaction ratings , and MI integrity scores were higher for Free Talk groups . AOD use and delinquency decreased for both groups at 3 months , and 12-month recidivism rates were lower but not significantly different for the Free Talk group compared to UC . Results contribute to emerging literature on MI in a group setting . A longer term follow-up is warranted BACKGROUND Brief motivational intervention ( BMI ) has shown promising results to reduce alcohol use in young adults . Knowledge on mechanisms that predict BMI efficacy could potentially improve treatment effect sizes through data that optimize clinical training and implementation . Particularly , little attention has been given to counselor influence on treatment mechanisms . METHODS We investigated the influence of counselors on BMI efficacy in reducing alcohol use among non-treatment-seeking young men ( age 20 ) screened as hazardous drinkers . Participants were r and omly allocated to ( i ) a group receiving a single BMI from 1 of 18 counselors selected to maximize differences in several of their characteristics ( gender , professional status , clinical experience , and motivational interviewing [ MI ] experience ) or ( ii ) a control group receiving assessment only . Drinking at 3-month follow-up was first compared between the BMI and control groups to assess efficacy . Then , the influence of counselors ' characteristics ( i.e. , gender , professional status , clinical experience , MI experience , BMI attitudes , and expectancies ) and within-session behaviors ( i.e. , measured by the Motivational Interviewing Skill Code ) on outcome was tested in regression analyses . RESULTS There was a significant ( p = 0.02 ) decrease in alcohol use among the BMI group compared to the control group . Counselors that were male , more experienced , that had more favorable BMI attitudes and expectancies , higher MI skills , but surprisingly less MI-consistent behaviors , had significantly better outcomes than the control group while their counterparts did not . CONCLUSIONS The current study demonstrated BMI efficacy on alcohol use reduction within a sample of non-treatment-seeking young adult males . Moreover , BMI effect was related to interindividual differences among counselors , and results therefore provide recommendations for BMI training and implementation with similar population OBJECTIVES Adolescents in their late teens and early 20s have the highest alcohol consumption in the United States ; binge drinking peaks at age 21 - 25 years . Underage drinking is associated with many negative consequences , including academic problems and risk of intentional and unintentional injuries . This study tested the effectiveness of pediatric emergency department ( PED ) screening and brief intervention to reduce alcohol consumption and associated risks . METHODS A three-group r and omized assignment trial was structured to test differences between intervention ( I ) and st and ard assessed control ( AC ) groups in alcohol consumption and alcohol-related behaviors from baseline to 12 months and to compare the AC group with a minimally assessed control ( MAC ) group to adjust for the effect of assessment reactivity on control group behavior . Patients aged 14 - 21 years were eligible if they screened positive on the Alcohol Use Disorders Identification Test ( AUDIT ) or for binge drinking or high-risk behaviors . The MAC group received a re source h and out , written advice about alcohol-related risks , and a 12-month follow-up appointment . Patients in the AC group were assessed using st and ardized instruments in addition to the MAC protocol . The I group received a peer-conducted motivational intervention , referral to community re sources and treatment if indicated , and a 10-day booster in addition to assessment . Measurements included 30-day self-report of alcohol consumption and alcohol-related behaviors , screens for depression and posttraumatic stress disorder , and self-report of attempts to quit , cut back , or change conditions of use , all repeated at follow-up . Motor vehicle records and medical records were also analyzed for changes from baseline to 1-year follow-up . RESULTS Among 7,807 PED patients screened , 1,202 were eligible ; 853 enrolled ( I , n = 283 ; AC , n = 284 ; MAC , n = 286 ) , with a 12-month follow-up rate of 72 % . At 12 months , more than half of enrollees in Reaching Adolescents for Prevention ( RAP ) attempted to cut back on drinking , and over a third tried to quit . A significantly larger proportion of the I group made efforts to quit drinking and to be careful about situations when drinking compared to AC enrollees , and there was a numerically but not significantly greater likelihood ( p = 0.065 ) among the I group for efforts to cut back on drinking . At 3 months , the likelihood of the I group making attempts to cut back was almost triple that of ACs . For efforts to quit , it was double , and for trying to be careful about situations when drinking , there was a 72 % increase in the odds ratio ( OR ) for the I group . Three-month results for attempts were sustained at 12 months for quit attempts and efforts to be careful . Consumption declined in both groups from baseline to 3 months to 12 months , but there were no significant between-group differences in alcohol-related consequences at 12 months or in alcohol-related risk behaviors . We found a pattern suggestive of assessment reactivity in only one variable at 12 months : the attempt to cut back ( 73.3 % for the I group vs. 64.9 % among the AC group and 54.8 % among the MAC group ) . CONCLUSIONS Brief motivational intervention result ed in significant efforts to change behavior ( quit drinking and be careful about situations while drinking ) but did not alter between-group consumption or consequences By the age of 18 , between 16 and 27 % of adolescents in the U.S. have been arrested for an offense and by the age of 23 this increases to a staggering 25 - 41 % . Most youth that get into legal trouble have a substance abuse problem and many youth report high risk driving behaviors . Adjudication of adolescents for an offense may provide an opportunity to provide a secondary prevention program for such high risk behaviors . In this regard the primary aim of the present study was to test two hypotheses : ( 1 ) that interventions involving group motivational interviewing would decrease future legal charges beyond those achieved by the combination of sanctions and remedial actions otherwise m and ated by the court ; and ( 2 ) that the addition of a trauma room exposure to the group MI intervention would increase the effectiveness of MI in decreasing these future legal charges . Court m and ated youth who have had a high risk driving police charge and /or alcohol related police charge and who are drivers ( n=992 ) were r and omly assigned to one of the three 20h interventions ; enhanced prototypic community service ( CS ) , Motivational Intervention with typical community service ( MI ) , and Motivational Intervention with exposure to a hospital trauma center ( MI-H ) . As hypothesized , the probability of being charged with an offense within the 6 months post-treatment was significantly less for participants in the combined MI groups than those in the CS group . The combined MI groups also had significantly fewer overall number of police charge events than the CS group at 6 months . Mediation analyses revealed that the relationship between MI vs. CS interventions and subsequent police charges was partially accounted for by the youth 's experience of the MI component of the intervention . Despite fewer police charges at 6 months the combined MI group reported ( 1 ) significantly more hazardous drinking and ( 2 ) a greater amount of speeding and distracted driving than the control group over this same 6-month period . Hypothesis 2 , that MI-H would be more effective than MI in reducing police charges , was not supported . This was so despite evidence supporting the hypotheses that ( 1 ) trauma room exposure would increase participants ' emotional arousal during the intervention and ( 2 ) increased arousal would be predictive of fewer police charges . Despite support for the theorized causal pathway , the combination of trauma room exposure and MI did not result in better outcomes than MI combined with traditional community service . Given this discrepancy between empirical supports for the theory Output:	MAIN RESULTS We included a total of 84 trials ( 22,872 participants ) , with 70/84 studies reporting interventions in higher risk individuals or setting s. Studies with follow-up periods of at least four months were of more interest in assessing the sustainability of intervention effects and were also less susceptible to short-term reporting or publication bias . Subgroup analyses revealed no clear subgroup effects for longer-term outcomes ( four or more months ) for assessment only versus alternative intervention controls ; for university/college vs other setting s ; or for higher risk vs all/low risk participants .None of the studies reported harms related to MI . AUTHORS ' CONCLUSIONS The results of this review indicate that there are no substantive , meaningful benefits of MI interventions for preventing alcohol use , misuse or alcohol-related problems .
MS22279	*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 in vitro was to evaluate the effects of tricalcium phosphate ( TCP ) and amorphous calcium phosphate ( ACP ) containing varnish material s and Er : YAG laser irradiation on enamel demineralization around orthodontic brackets . Forty extracted human premolar teeth were r and omly divided into four treatment groups ( i.e. , 10 in each group ) : ( 1 ) 5 % NaF-ACP varnish , ( 2 ) 5 % NaF-TCP varnish , ( 3 ) Er : YAG laser , and ( 4 ) control ( no treatment ) . Er : YAG laser was operated at a wavelength of 2.94 μm and the energy output was 80 mJ per pulse ; a pulse duration of 200 μsec and and a frequency of 2 Hz were used with water cooling . All sample s were then put into pH cycles . Surface microhardness values and representative SEM images were assessed . Surface microhardness values were evaluated using Kruskal-Wallis and Mann-Whitney U tests . The results revealed that demineralization was significantly lower in the TCP and ACP varnish groups , whereas mean surface microhardness values of the TCP varnish were found higher than the ACP ( P < 0.05 ) . TCP and ACP varnish material s were found effective for reducing enamel demineralization around orthodontic brackets . Use of Er : YAG laser irradiation as described in this study for inhibition of demineralization was found not satisfactory OBJECTIVE This clinical pilot study was conducted to investigate the effectiveness of argon laser irradiation to reduce demineralization or loss of tooth structure in vivo . SUMMARY BACKGROUND DATA In vitro research previously demonstrated the ability of argon laser irradiation to reduce demineralization or loss of tooth structure . METHODS Using the Ogaard model of producing demineralization , the experimental teeth were irradiated with argon laser of 250 mW ( producing approximately 12 J/cm2 ) prior to b and ing . Polarized light evaluation of the sectioned , extracted teeth was used to determine the amount of demineralization . RESULTS Results showed a 29.1 % reduction in demineralization in the experimental teeth as compared to the bilateral control teeth . CONCLUSION Low-power argon laser irradiation significantly reduced demineralization clinical ly 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 A prospect i ve clinical trial was carried out to compare argon laser-curing of a traditional light-activated composite resin with conventional visible light-curing in terms of bond failure rate and incidence of enamel decalcification . Forty-five patients with a total of 742 metal brackets bonded to the upper and /or lower teeth in a modified split-mouth design participated in the study . The adhesive ( Transbond XT ) on the control teeth was cured by conventional visible light for 40 seconds , and the experimental teeth were exposed to 10 seconds of 250 mW argon laser irradiation . The patients were monitored for a period of 14 months . Intraoral photographic slides of the maxillary anterior teeth ( 212 in total ) were taken at the beginning of treatment , after 12 months of treatment , following application of a plaque disclosing agent , and at the end of the observation period , following temporary debonding . Seven dentists used st and ardized rating systems to evaluate decalcification and plaque accumulation . The results of this study indicated that there were no significant differences between curing methods for the incidence of decalcification and plaque accumulation . However , the 10 second argon laser-curing method showed a statistically lower bond failure rate ( 2.4 per cent , P < 0.05 ) than the 40 second conventional visible light-curing method ( 5.7 per cent ) . It is concluded that the use of argon laser curing is superior to that of conventional light-curing with respect to bond failure and chairside time . However , the incidence of decalcification seems to be similar Objective This study was design ed to evaluate the effect of argon laser irradiation on development and progress of enamel demineralization around orthodontic brackets . Material s and Methods : Fifty caries-free , intact human premolars were r and omly assigned to one of the following five equal groups : Groups 1 ( control ) and 2 : The brackets were bonded using conventional halogen light for 40s and argon laser for 10s , respectively . Teeth in group 3 were lased with argon laser for 10s before bracket bonding with halogen light . Group 4 was the same as group 3 except that brackets were also bonded with argon laser . In group 5 sample s were bonded conventionally , immersed in an artificial caries solution for two days and then irradiated for 10s with argon laser . All sample s were subjected to demineralization by artificial caries solution for 10 days . After bracket removal , sample s were buccolingually sectioned and evaluated by polarized light microscopy . Decalcified lesion depth in each section was measured by a trained examiner in a blind fashion . Data were analyzed in SPSS 14 using one-way ANOVA and Tukey ’s HSD post hoc test . Results : The control group showed the greatest mean lesion depth while group 5 revealed the lowest . The laser-treated groups had significantly lower mean lesion depth compared with the control group ( P<0.05 ) except for group 4 ( P=0.192 ) . Conclusion : Argon laser irradiation for 10s before or during bracket bonding can increase caries resistance of intact and demineralized enamel Plaque control during the course of orthodontic treatment is not an easy task , and dental caries are not an unlikely complication . We examined the possibility of controlling dental caries with Nd-YAG laser irradiation in orthodontic patients . As a preliminary experiment , we used the Nd-YAG laser to irradiate an extracted tooth and then left it to soak in lactic acid . The decay of the tooth was evaluated with a scanning electron microscope ( SEM ) ; tooth decay was inhibited by the action of the laser . Twenty patients undergoing orthodontic treatment for early decalcification of the teeth ( white spot lesions ) were selected , and photographs were taken of their oral cavities . White spot lesions on the four incisors and two canines of the maxilla were traced on tracing paper , and their areas were calculated by computer . Ten of the patients received laser treatment and acidulated phosphate fluoride solution ( APF ) ; the other ten acted as the control group . Between 11 and 12 months later , we photographed the oral cavity as we had previously ; the white spot lesions were again traced and their areas calculated . The changes in the areas of the white spots of the laser-irradiated and control groups showed the following increases : laser-irradiated group , 1.41 times ; controls , 2.87 times . The difference was statistically significant . These results demonstrate that Nd-YAG laser irradiation with application of APF acts as an effective method of caries control during orthodontic treatment Enamel decalcification is a significant problem in orthodontic patients . The argon laser has been shown to reduce decalcification during an acidic challenge in vitro . The purpose of this study was to investigate the in vivo effects of argon laser irradiation on enamel decalcification during orthodontic treatment . Nine volunteers whose treatment plans included 4 first premolar extraction s were enrolled in the study . The 36 extracted premolars were assigned to 1 of the following 4 groups : group 1 , control group with no treatment ; group 2 ( pumice-laser ) , teeth were pumiced for 3 seconds and treated with a 325 mW , 5-mm diameter laser beam for 60 seconds ; group 3 ( pumice-etch-laser ) , teeth were pumiced for 3 seconds , acid-etched with 30 % phosphoric acid for 30 seconds , and treated for 60 seconds with laser ; and group 4 ( laser only ) , teeth were treated for 60 seconds with laser . A specially design ed ( oversized ) orthodontic b and was fitted on each of the premolars to create a pocket for decalcification . The b and s were cemented in place for 5 weeks . After extraction , the teeth were sectioned and examined under polarized light microscopy . Images of lesions were digitally analyzed and measured . Average lesion depths were calculated from 3 depth measurements recorded 10 microm apart . Average lesion area was calculated with the aid of imaging analysis software . Data were analyzed with analysis of variance ( P < .05 ) and Student t tests . Significant differences were found in lesion depth ( P < .001 ) and lesion area ( P < .01 ) among the 4 test groups . The average lesion depths were 15.93 + /- 9.31 microm ( control ) , 6.45 + /- 8.70 microm ( pumice-laser ) , 1.71 + /- 4.82 microm ( pumice-etch-laser ) , and 1.34 + /- 3.80 microm ( laser only ) . The average lesion areas were 1028.67 + /- 725.68 microm ( 2 ) ( control ) , 555.49 + /- 948.20 microm ( 2 ) ( pumice-laser ) , 79.91 + /- 226.03 microm ( 2 ) ( pumice-etch-laser ) , and 55.71 + /- 157.59 microm ( 2 ) ( laser only ) . The average lesion depth in the laser-only group was reduced by 94.1 % and the average lesion area was reduced by 94.4 % when compared with the control group . In the pumice-etch-laser group , the average lesion depth was reduced by 89.1 % and the average lesion area was reduced by 92.2 % when compared with the control group . There were no significant differences in lesion depth and lesion area between maxillary and m and ibular teeth ( P < .06 and P < .08 , respectively ) and between the teeth on the right and left sides ( P < .68 and P < .55 , respectively ) . These results show that argon laser irradiation is effective in reducing enamel decalcification during orthodontic treatment . Pumicing and etching do not appear to reduce the effect of laser on enamel solubility Argon lasers , because of their significant timesavings over conventional curing lights , have been investigated for use in bonding orthodontic brackets . They are also being investigated for their ability to confer demineralization resistance on enamel , which is of great interest in orthodontics . A two-part in vitro study on 86 human posterior teeth was conducted to determine the effects of a five-second argon laser exposure on shear bond strength and to evaluate the effects of a five- and 10-second argon laser exposure ( 250 mW ) on demineralization of enamel surrounding orthodontic brackets after exposure to an artificial caries bath . Brackets cured with the argon laser for five seconds yielded mean bond strengths similar to those attained with a 40-second conventional light-cured control ( n = 13 per group , 20.4 vs 17.8 MPa ) . Brackets cured with the argon laser for 10 seconds result ed in significantly lower mean lesion depth when compared with a visible light control ( n = 20 per group , 107.8 vs 137.2 microm , P = .038 ) . There were no statistically significant differences in lesion depth between the five-second argon laser and the visible light control groups . Overall , there was a 15 % and 22 % reduction in lesion depths for the five- and 10-second group , respectively . Poor correlations were found between the clinical appearance of decalcifications and their lesion depth . Argon lasers used for bonding orthodontic brackets would save a significant amount of chair time while possibly conferring demineralization resistance upon the enamel Introduction : The aim of this study was to assess the caries-preventive potential of carbon dioxide ( CO2 ) laser application in conjunction with the use of titanium tetra fluoride solution on the enamel adjacent to bracket . Methods : Seventy-five freshly extracted bovine incisors were used . In order to attach the brackets , the area of examination was covered with adhesive tape to limit acid etching of the entire enamel surface . Metal orthodontic brackets for upper central were bonded to all the teeth following the manufacturer 's instruction . Then all the teeth were painted with 2 layers of acid-resistant nail varnish on all surfaces except the boxes area cervical to the brackets . The teeth were then r and omly divided into five groups ( n = 15 ) : control group ( C ) ; laser group ( L ) ; titanium group ( T ) ; laser-titanium group ( LT ) and titanium-laser group ( TL ) . The laser-titanium group was first irradiated with CO2 laser ( same as the L group ) then TiF4 solution was applied on the enamel ( same as the T group ) . Sample s in the TL group were first treated with TiF4 solution ( same as the T group ) and then irradiated with CO2 laser on the surface ( same as the L group ) . Then , the teeth were immersed in pH-cycling solutions . After that , the amount of calcium released into the two solutions ( de- and re-mineralization ) was measured with an atomic absorption spectroscopy . The data were analyzed by one-way Analysis of var-iance ( ANOVA ) and Tukey test . Results : Calcium loss in LT , TL and T groups were significantly lower than those in the L and C groups ( P < 0.0 Output:	Significant differences were observed in enamel demineralization between laser-irradiated and control groups for all laser types : argon laser , CO2 laser , neodymium-doped yttrium aluminum garnet ( Nd : YAG ) laser , and Optodan ® laser , except for argon laser application for curing bracket adhesives , where no statistically significant differences were noted .
MS22280	*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 effectiveness of anterior cruciate ligament reconstruction for restoring normal knee kinematics is largely unknown , particularly during sports movements generating large , rapidly applied forces . Hypothesis Under dynamic in vivo loading , significant differences in 3-dimensional kinematics exist between anterior cruciate ligament-reconstructed knees and the contralateral , uninjured knees . Study Design Prospect i ve , in vivo laboratory study . Methods Kinematics of anterior cruciate ligament-reconstructed and contralateral ( uninjured ) knees were evaluated for 6 subjects during downhill running 4 to 12 months after anterior cruciate ligament reconstruction , using a 250 frame/s stereoradiographic system . Anatomical reference axes were determined from computed tomography scans . Kinematic differences between the uninjured and reconstructed limbs were evaluated with a repeated- measures analysis of variance . Results Anterior tibial translation was similar for the reconstructed and uninjured limbs . However , reconstructed knees were more externally rotated on average by 3.8 ± 2.3 ° across all subjects and time points ( P = .0011 ) . Reconstructed knees were also more adducted , by an average of 2.8 ± 1.6 ° ( P = .0091 ) . Although differences were small , they were consistent in all subjects . Conclusions Anterior cruciate ligament reconstruction failed to restore normal rotational knee kinematics during dynamic loading . Clinical Relevance Although further study is required , these abnormal motions may contribute to long-term joint degeneration associated with anterior cruciate ligament injury/reconstruction Background : Limited knee flexion and increased muscle co-contraction during jump l and ing are believed to diminish outcomes after anterior cruciate ligament ( ACL ) reconstruction . The efficacy of jump training to improve patients ’ mechanical and neuromuscular deficits is understudied . Hypothesis : Jump training will improve functional , mechanical , and neuromuscular outcomes and higher repetition training augmented by body weight support will result in better retention of gains . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Thirty athletes ( 18 months after surgery ) were screened , and 19 with mechanical deficits and limited clinical outcomes were enrolled in the trial . Testing included the International Knee Documentation Committee ( IKDC ) question naire , leg l and ing mechanics via motion analysis , knee joint effusion using a stroke test , and a surface electromyography – generated co-contraction index during a single-legged l and ing . Participants were r and omly assigned to 1 of 2 groups : jump training with normal body weight ( JTBW ) and high-repetition jump training with body weight support ( JTBWS ) . Knee effusion grading throughout training was used to assess joint tolerance . Changes in outcomes over time were analyzed with mixed-effects modeling . Immediate outcomes were compared with retention testing at 8 weeks after training by use of 2-way analyses of variance with effects of time and group . Results : Significant effects of time were found during the training phase for all outcome measures , but no effects of group or sex were found . IKDC score ( pooled ; mean ± SD ) increased from 76 ± 12 to 87 ± 8 ( P < .001 ) . Knee flexion during single-legged l and ing increased from 57 ° ± 11 ° to 73 ° ± 9 ° ( P < .001 ) . Average co-contraction index decreased from 37 ± 15 to 19 ± 6 ( P < .001 ) . All measures were retained over the retention period in both groups . The relative risk of knee effusion of the JTBW group versus the JTBWS group was 4.2 ( 95 % CI , 2.25 - 7.71 ; P < .001 ) . Conclusion : Jump training mitigated some risk factors for second injury and osteoarthritis in patients after ACL reconstruction . Training made lasting improvements in physical function measures as well as mechanical and neuromuscular coordination deficits . Higher repetitions used with body weight support did not improve retention but substantially reduced risk for effusion . Clinical Relevance : Jump training is an efficacious intervention for athletes with poor outcomes after ACL reconstruction , and training with body weight support lessens the risk for excessive joint stress during practice . Registration : NCT02148172 ( Clinical Trials.gov identifier Background Knee reinjury after ACL reconstruction is common and increases the risk of osteoarthritis . There is sparse evidence to guide return to sport ( RTS ) decisions in this population . Objectives To assess the relationship between knee reinjury after ACL reconstruction and ( 1 ) return to level I sports , ( 2 ) timing of RTS and ( 3 ) knee function prior to return . Methods 106 patients who participated in pivoting sports participated in this prospect i ve 2-year cohort study . Sports participation and knee reinjury were recorded monthly . Knee function was assessed with the Knee Outcome Survey — Activities of Daily Living Scale , global rating scale of function , and quadriceps strength and hop test symmetry . Pass RTS criteria were defined as scores > 90 on all tests , failure as failing any . Results Patients who returned to level I sports had a 4.32 ( p=0.048 ) times higher reinjury rate than those who did not . The reinjury rate was significantly reduced by 51 % for each month RTS was delayed until 9 months after surgery , after which no further risk reduction was observed . 38.2 % of those who failed RTS criteria suffered reinjuries versus 5.6 % of those who passed ( HR 0.16 , p=0.075 ) . More symmetrical quadriceps strength prior to return significantly reduced the knee reinjury rate . Conclusions Returning to level I sports after ACL reconstruction leads to a more than 4-fold increase in reinjury rates over 2 years . RTS 9 months or later after surgery and more symmetrical quadriceps strength prior to return substantially reduce the reinjury rate Background : It has been hypothesized that quadriceps muscle weakness is directly associated with the onset and progression of posttraumatic osteoarthritis after anterior cruciate ligament ( ACL ) injury and reconstruction ( ACLR ) . This relationship , however , has not been studied with a prospect i ve approach that includes the use of tibiofemoral joint space width difference ( JSW-D ) measurements to characterize the onset of posttraumatic osteoarthritis before the clinical manifestation of the disease . Purpose : To assess the relationship between thigh muscle strength and JSW-D at presurgery baseline and at 1- and 4-year follow-up after ACLR compared with healthy , noninjured participants of similar sex , age , body mass index , and activity level . Study Design : Cohort study ; Level of evidence , 3 . Methods : A total of 39 unilateral ACL-injured patients and 32 healthy controls were followed prospect ively . During each follow-up , JSW , isokinetic knee strength , single-legged hop , and clinical - and patient-oriented outcomes were assessed . At final follow-up , ACL-injured participants who had JSW-D values ( considered as the injured minus normal knee ) that were less than the 95 % confidence interval of controls were considered to be in the ACLR-narrow group , while those with JSW-D values that fell within the confidence intervals were in the ACLR-normal group . Relationships were evaluated between ACLR groups and controls via multilevel regression , as well as Kruskal-Wallis tests for between-group comparisons at 4-year follow-up . Results : At 4-year follow-up , 30 participants ( 79 % ) were in the ACLR-normal group and 8 ( 21 % ) were in the ACLR-narrow group . At baseline , the extension , flexion , and extension/flexion ratio strength values for both ACLR groups were significantly lower than those of controls ( P ≤ .05 ) , while the ACLR-narrow group had significantly lower extension strength at 60 and 180 deg/s ( P = .04 and .03 , respectively ) , as well as extension/flexion ratio at 60 deg/s ( P = .04 ) in comparison with the ACL-normal group . At 4-year follow-up , 60 deg/s extension strength deficits persisted in the ACLR-narrow group compared with controls and ACLR-normal participants ( P = .01 and .04 , respectively ) . Flexion strength at 180 and 300 deg/s was also significantly lower in the ACLR-narrow group compared with ACLR-normal ( P = .02 and .04 , respectively ) , as was single-legged hop distance ( P = .04 ) . Conclusion : Strength deficits present within months after ACL injury and persist through 4 years after ACLR in participants with significantly narrowed JSW-D , compared with ACLR participants with normal JSW-D and controls . This study revealed a significant relationship between quadriceps strength loss that occurred soon after injury and JSW narrowing Purpose Unrealistic patient expectations have been shown to negatively influence patient-reported outcomes in orthopaedic surgery . Knowledge about patient expectations is important to associate preoperative expectations with the reasonable outcome of a specific procedure . The purpose of this study was to prospect ively analyse and to compare patient expectations of primary and revision anterior cruciate ligament reconstruction ( ACLR ) and to assess the factors associated with patient expectations . Methods Preoperative expectations of 181 consecutive patients undergoing ACLR were assessed prospect ively using a 5-item question naire . Primary ACLR ( P-ACLR ) was performed in 133 patients ( 73 % ) , whereas 48 patients ( 27 % ) underwent revision ACLR ( R-ACLR ) . The question naire assessed the expectation of the overall condition of the knee joint , return to sports , instability , pain , and risk of osteoarthritis . Results All patients expected a normal ( 38 % ) or nearly normal ( 62 % ) condition of the knee joint . Return to sports at the same level was expected by 91 % . With regard to instability ( pain ) , no instability ( pain ) independent of the activity level was expected by 77 % ( 58 % ) . No or only a slightly increased risk of the development of osteoarthritis was expected by 98 % . The R-ACLR group showed a significantly lower expectation of the overall condition ( p = 0.001 ) , return to sports ( p < 0.001 ) , and pain ( p = 0.002 ) . No statistically significant difference was found between female and male patients ( n.s . ) . In the P-ACLR group , patients with a history of previous knee surgery showed inferior expectations of return to sports ( p = 0.015 ) and risk of osteoarthritis ( p = 0.011 ) . Age , number of previous knee surgeries , and pre-injury sports level significantly influenced patient expectations . Conclusions Overall , patient expectations of ACL reconstruction are high . Patients undergoing revision ACL reconstruction have lower but still dem and ing expectations . Younger patients , patients without a history of knee surgery , and highly active patients have higher expectations . Explicit patient information about realistic goals of ACL reconstruction seems to be necessary in order to prevent postoperative dissatisfaction despite a successful operation in the surgeons ’ point of view . Level of evidence Prospect i ve case series , Level IV Abstract Purpose To compare the ability of three different anterior cruciate ligament ( ACL ) reconstruction techniques to normalize rotational knee stability 1 year after ACL reconstruction . Two of these techniques are so-called anatomic techniques . Methods Three different ACL reconstruction techniques were tested for their ability to normalize rotational knee stability in a prospect i ve r and omized study . Forty-seven ACL-deficient ( ACLD ) patients were r and omized to transtibial single-bundle ( SB ) , anatomic SB , and double-bundle ACL reconstruction . Three-dimensional motion analysis was performed preoperatively and at 1-year follow-up to evaluate tibial rotation and rotational stiffness . Motion data were captured using an eight-camera motion analysis system . Tibial rotation was determined during walking , running , and a pivoting task . Other outcome parameters were KT-1000 knee laxity measurements and the subjective outcome scores KOOS and IKDC . Results Three-dimensional motion analysis demonstrated that the tibial internal rotation and the rotational stiffness did not differ between the ACL reconstruction techniques during walking , running , and pivoting at 1-year follow-up . Objective knee stability and subjective outcome scores did not differ between the reconstruction groups . Conclusion No significant difference in rotational stability walking , running , and pivoting was seen between anatomic and nonanatomic ACL reconstruction techniques at 1-year follow-up . Level of evidence Therapeutic study , Level OBJECTIVES To examine the effects of 2 gait retraining protocol s on the gait patterns of patients with bone-patellar tendon-bone anterior cruciate ligament ( ACL ) reconstruction . DESIGN R and omized control , repeated- measures design . SETTING Private orthopedic center and research facility . PARTICIPANTS Sixteen patients with bone-patellar tendon-bone ACL reconstruction , r and omly subdivided into 2 groups ( group 1 , n=8 ; group 2 , n=8 ) , and a healthy control group of 8 subjects . INTERVENTION The 16 subjects with ACL reconstruction were r and omly assigned to 2 different gait retraining protocol s over a 6-week training interval : ( 1 ) . a protocol using a predicted stride frequency calculated from the resonant frequency of a force-driven harmonic oscillator ( FDHO ) model or ( 2 ) . a protocol using the preferred stride frequency ( PSF ) . MAIN OUTCOME MEASURES Gait analyses examining the lower-extremity kinematic , kinetic , and energetic gait patterns of each group . RESULTS Gait retraining with the FDHO model showed improvements in lower-extremity positions , hip and knee extensor angular impulse , and work parameters . Gait re Output:	Inconsistent results were found for both peak vertical ground reaction force and impact forces after ACL-R. Patellofemoral and tibiofemoral joint contact forces differed from both contralateral or control limbs up until at least 2.5 years after ACL-R and moderate evidence indicated no difference for muscle activations during moderate speed running . Quadriceps and hamstring strength asymmetries , and knee function , but not surgical techniques , were likely to be associated with both knee kinematics and kinetics during running after ACL-R. Conclusion After ACL-R , knee flexion motion and internal knee extension moment are the most affected variables and are consistently smaller in the injured limb during running when pooling evidence . Clinicians should be aware that these deficits do not appear to resolve with time and , thus , specific clinical interventions may be needed to reduce long-term disability .
MS22281	*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 Histamine‐releasing activity ( HRA ) is detectable in up to 50 % of patients with chronic ordinary urticaria . Objectives To determine the effect of cyclosporin on clinical features and HRA in patients with chronic urticaria . Methods Thirty patients with severe unremitting disease , responding poorly to antihistamines and showing a positive autologous serum skin test ( ASST ) as a marker of HRA , were r and omized to 4 mg kg−1 daily of cyclosporin ( S and immun ® , n = 20 ) or placebo ( n = 10 ) for 4 weeks . Non‐responders were offered open‐label cyclosporin for 4 weeks . All were followed for up to 20 weeks or until clinical relapse ; all took cetirizine 20 mg daily throughout the study . The primary measure of efficacy was a daily urticaria activity score ( UAS ) of weal numbers and itch ( maximum score 42 per week ) . A positive response was defined as a reduction to < 25 % of baseline weekly UAS and relapse as a return to > 75 % . The effect of cyclosporin on serum HRA was assessed by in vitro basophil histamine release assays and ASSTs before and after treatment . Results Twenty‐nine patients ( 19 active , 10 controls ) completed the r and omized trial medication . Eight of 19 on active treatment but none on placebo had responded at 4 weeks ( P < 0·05 ) . Three others on active drug met the criterion for response at 2 weeks but not at 4 weeks . Mean reduction in UAS between weeks 0 and 4 was 12·7 ( 95 % confidence interval , CI 6·6–18·8 ) for active and 2·3 ( 95 % CI − 3·3–7·9 ) for placebo ( P = 0·005 ) . Seventeen non‐responders ( seven r and omized to active and 10 to placebo ) chose open‐label cyclosporin and 11 responded after 4 weeks . Six of the eight r and omized active drug responders relapsed within 6 weeks . Of the 19 responders to r and omized and open‐label cyclosporin , five ( 26 % ) had not relapsed by the study end‐point . Mean in vitro serum HRA fell from 36 % ( 95 % CI 22–49 % ) to 5 % ( 95 % CI 1–8 % ) after cyclosporin treatment ( n = 11 , P < 0·0001 ) . The ASST response to post‐treatment serum was also reduced ( P < 0·05 ) . Conclusions This study shows that cyclosporin is effective for chronic urticaria and provides further evidence for a role of histamine‐releasing autoantibodies in the pathogenesis of this chronic ‘ idiopathic ’ disease This study evaluates the effectiveness and safety of cyclosporine ( CsA ) in the treatment of patients with chronic idiopathic urticaria with a positive autologous serum skin test ( ASST ) , who fail to respond to conventional therapy , and requiring long-term oral steroid treatment . In a double-blind study , 40 adults were assigned r and omly to receive CsA ( 5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks ) or cetirizine ( 10 mg/day ) and then they were followed up for 9 months . After 2 weeks , the study was opened because 16 patients ( 40 % ) had daily severe relapses requiring systemic steroids treatment . All of these patients had been receiving antihistamines and , therefore , all patients also were assigned to the CsA treatment regimen ( 5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks ) . The ASST and clinical severity score were evaluated before and after treatment . All of the 40 patients completed the 16-week CsA course without dropping out because of relevant side effects . In three patients , CsA was reduced by 0.5 mg/kg per day after the 1st month of treatment for a mild and reversible increase in serum creatinine . During CsA treatment , 20 patients had relapses resolving spontaneously ( 8 patients ) or with antihistamines ( 12 patients ) . During the 9-month follow-up period , 22 patients had relapses resolving spontaneously ( 10 patients ) or with antihistamines ( 12 patients ) . Only two patients failed to complete the study because of severe symptoms occurring after 4 and 7 days of follow-up and requiring long-term steroid treatment . After 9 months of follow-up , 16 patients were still in full remission . The clinical severity score of chronic idiopathic urticaria dropped significantly by the end of the 4th month of treatment ( p = 0.002 ) as well as by the completion of follow-up ( p = 0.007 ) . The ASST was negative in 13 patients and positive in 3 of 16 patients , with total remission of symptoms . Significant score reduction also was observed in patients experiencing relapses that resolved spontaneously ( p = 0.005 ) or with antihistamines ( p = 0.03 ) . These results show the long-term efficacy and tolerability of CsA in patients with severe chronic idiopathic urticaria , unresponsive to conventional treatments The present study aim ed to evaluate the effectiveness of 2.5 mg/kg/day cyclosporin ( CsA ) treatment in patients with severe chronic idiopathic urticaria ( CIU ) and the impact of CsA treatment on several cytokines involved in the etiopathogenesis of CIU . Twenty-seven CIU patients and 24 healthy control subjects were included in the study . The autologous serum skin test ( ASST ) for autoantibodies and urticaria activity scoring ( UAS ) were measured for the evaluation of the clinical severity and the response to therapy , and the serum levels of interleukin (IL)-6 , IL-8 , IL-2 receptor , IL-1beta , tumor necrosis factor (TNF)-alpha and IL-5 were measured . The mean UAS score was 32.07 + /- 7.05 and 6.22 + /- 3.84 before and after CsA treatment , respectively . The serum IL-2 receptor , TNF-alpha and IL-5 levels of patients before CsA treatment were statistically higher than those of the control group ( P = 0.001 ) , and after 4 weeks of CsA therapy the mean IL-2R , TNF-alpha and IL-5 levels were significantly decreased . The data from this study demonstrate that CsA therapy is efficient and safe for CIU patients . Increase in clinical efficacy and marked decreases in serum cytokine levels suggest that inhibition of cytokine generation is involved in the action of the drug in this clinical setting BACKGROUND Chronic idiopathic urticaria is sometimes difficult to treat , with little response to antihistamine therapy . OBJECTIVE In a limited number of severe chronic idiopathic urticaria patients , cyclosporine A ( CsA ) therapy was found to be effective . In this study , we compared the clinical efficacy and safety of short- and long-term CsA applications . METHODS Twenty patients with severe disease , unresponsive to antihistamines and showing a positive autologous serum skin test ( ASST ) were r and omized to 4 mg/kg per day of CsA for 4 or 12 weeks . The clinical efficacy was measured with a daily activity score of weal numbers and itch ( UAS ) . The two groups were compared in terms of mean reduction in UAS and ASST response to pre- and post-treatment sera . RESULTS The clinical improvement was dramatic in the first month of treatment in both groups . There was no significant difference in the frequency of responses , side effects and the reduction of UAS in either group . CONCLUSION The preliminary results of our study suggest that CsA is clinical ly effective for chronic urticaria . The prolonged use of this therapy for more than 1 month provides little benefit in the clinical improvement Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument Chronic Idiopathic Urticaria ( CIU ) is a cutaneous disorder for which there is no identifiable specific etiologic agent . Some recent evidence s suggest that CIU might be an autoimmune disease . We analyzed immunological features occurring in CIU and evaluated effectiveness and tolerance of Cyclosporin A ( CsA ) treatment in patients unresponsive to antihistaminic treatment . Twenty patients with CIU were recruited after a selective diagnostic protocol and were divided into two groups . CsA was prescribed for group 1 and Prednisone for group 2 as control , for 8 weeks . Before and after the therapy we performed on all patients immunological studies . For all patients symptoms disappeared after a few days of therapy . Before therapy all patients showed activated B cells ( CD19+CD23 + cells ) and among B CD19 + cells , about 20 % were CD5 + ( cells that synthesize natural autoantibodies ) . After treatment with Prednisone in group 2 , a significant reduction of CD4 + lymphocytes ( p + 0,01 ) was observed . Our findings might support the CIU autoimmune pathogenetic hypothesis . The clinical remission in the CsA-treated group confirmed the therapeutic effectiveness of this therapy in antihistaminic unresponsive CIU and , at dosage used , side effects were rare , mild and reversible . Thus , CsA might be a good therapeutic alternative in CIU patients unresponsive to conventional treatments Patients with autoimmune urticaria ( AIU ) and positive autologous serum skin test ( ASST ) represent a more serious type of chronic urticaria that does not respond to treatment with antihistamines , but responds completely to systemic corticosteroids . Because of the chronic course of the disease , there is a risk of side-effects . Cyclosporin A ( CsA ) is an alternative treatment for patients with AIU . In order to determine the efficacy of CsA at the lowest possible dose in patients with chronic idiopathic urticaria and positive ASST , 30 patients were included in a 5-month study with a follow-up one year after the end of treatment . All patients had positive ASST before treatment and autoantibodies were present in 73 % . Twenty- three patients completed the study and responded to low-dose CsA treatment . Three patients did not respond to a dose of 2.5 mg/kg CsA , and 4 patients dropped-out due to side-effects . After the first month of treatment , an improvement of 31 % was noted , reaching 88 % after the fifth month of treatment . The mean dose of CsA was 2.16 mg/kg for the first month and 0.55 mg/kg for the fifth month . Three to 6 months after the end of the study , the ASST was repeated and was negative in 78.3 % of patients . At the one-year follow-up , 20 patients were symptom-free ( 87 % ) and 3 had relapsed ( 13 % ) . CsA , even in low-doses , can be an effective and short-term treat- ment with minimum side-effects in patients with AIU Output:	Our systematic review showed that positive autologous serum skin test results , positive baseline basophil histamine release assays , positive baseline basophil activation test responses , elevated baseline plasma D-dimer levels , elevated baseline serum interleukin (IL)-2 , IL-5 , and tumor necrosis factor-alpha ( TNF-α ) levels , and low baseline serum IgE levels might assist in predicting favorable CsA responses in CSU patients . Decreased plasma D-dimer levels ; and decreased serum IL-2 , IL-5 , and TNF-α levels were reported to be correlated with clinical improvement after CsA treatment . Since most positive results were from non- RCT articles and some data were still inconsistent , this systematic review identified no reliable practical biomarker for predicting CsA treatment response in patients with CSU . There were no positive predictors with good consistency and mechanical plausibility
MS22282	*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 Trastuzumab for Gastric Cancer ( ToGA ) study is the first international trial to include Japanese patients with human epidermal growth factor 2 ( HER2 ) positive advanced/metastatic gastric or gastroesophageal junction cancer . ToGA showed that trastuzumab plus chemotherapy ( capecitabine/cisplatin or 5-fluorouracil/cisplatin ) improved overall survival in the overall population ( hazard ratio 0.74 ) . Regional differences in outcome in favor of Japanese population s were observed in other studies ; therefore , subgroup analyses of ToGA may contribute to the evaluation of the potential benefits of this regimen in Japanese patients . Methods We performed subgroup analyses on 101 Japanese patients enrolled into ToGA ( trastuzumab plus chemotherapy , n = 51 ; chemotherapy , n = 50 ) . Results Median overall survival in the Japanese subgroup was 15.9 months ( 95 % confidence interval 12–25 ) for trastuzumab plus chemotherapy and 17.7 months ( 95 % confidence interval 12–24 ) for chemotherapy ( hazard ratio 1.00 ; 95 % confidence interval 0.59–1.69 ) . After adjusting for prespecified covariates , the estimated hazard ratio for overall survival was 0.68 ( 95 % confidence interval 0.36–1.27 ) . Further post hoc and exploratory examinations supported the robustness of the adjusted hazard ratios . Conclusions After adjusting for imbalanced patient background s between arms , overall survival of Japanese patients with human epidermal growth factor 2 positive advanced/metastatic gastric or gastroesophageal junction cancer who received trastuzumab plus chemotherapy was improved compared with patients who received chemotherapy alone Objective : To better underst and the clinical implication s of insulin-like growth factor type 1 receptor ( IGF-1R ) , epidermal growth factor receptor ( EGFR ) and HER2 expressions in gastric cancer ( GC ) . Methods : The study group comprised 86 patients who received first-line chemotherapy for advanced GC at the National Cancer Center Hospital . Using laser-captured microdissection and a real-time RT-PCR assay , we quantitatively evaluated mRNA levels of IGF-1R , EGFR and HER2 in paraffin-embedded cancer specimens of surgically removed primary tumors . Results : In univariate analysis of the study group as a whole , patients with low expression of both IGF-1R and EGFR ( n = 13 ) had a significantly longer overall survival than the other patients ( n = 51 ; median , 24.6 vs. 12.8 months ; log-rank p = 0.013 ) . Multivariate survival analysis demonstrated that high EGFR expression [ hazard ratio , HR : 2.94 ( 95 % confidence interval , CI : 1.40–6.17 ) , p = 0.004 ] and poor performance status [ HR : 1.96 ( 95 % CI : 1.12–3.42 ) , p = 0.018 ] were significant predictors of poor survival . In patients given first-line S-1 monotherapy ( n = 29 ) , low IGF-1R ( p = 0.002 ) and low EGFR ( p = 0.035 ) gene expression correlated with a better response , without a significant prolongation of survival . Conclusion : Our data warrant further investigations on the strategy of co-targeting IGF-1R and EGFR in GC BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche Purpose : EGF receptor ( EGFR ) and HER2 positivity are considered to be negative prognostic factors in gastric cancer . Biomarker analysis was conducted to evaluate the impact of EGFR and HER2 expression on the outcome of patients enrolled in the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer ( ACTS-GC ) , a r and omized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer . Experimental Design : Formalin-fixed , paraffin-embedded surgical specimens were retrospectively examined in 829 patients ( 78.3 % ) . The effects of EGFR and HER2 positivity on survival were analyzed on the basis of the 5-year survival data from the study . EGFR positivity was defined as an immunohistochemistry ( IHC ) score of 3 + , and HER2 positivity as an IHC score of 3 + or an IHC score of 2 + with a positive dual-color in situ hybridization status . Results : EGFR and HER2 were positive in 75 ( 9.0 % ) and 113 ( 13.6 % ) patients , respectively . The overall and relapse-free survival rates were significantly lower in EGFR-positive patients than in EGFR-negative patients , whereas they were similar in HER2-positive and HER2-negative patients . Multivariate analysis showed that EGFR positivity correlated with poor outcomes [ HR = 1.504 ; 95 % confidence interval ( CI ) = 1.020–2.149 ; P = 0.040 ] . Treatment with S-1 improved survival compared with surgery alone , irrespective of EGFR and HER2 status . Conclusions : EGFR positivity , but not HER2 positivity , was associated with poor patient outcomes after curative resection of stage II/III gastric cancer . There was no interaction between S-1 and EGFR or HER2 status with respect to survival outcome . Clin Cancer Res ; 18(21 ) ; 5992–6000 . © 2012 AACR The optimal adjuvant treatment for gastric cancer remains controversial . We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen , in patients with high-risk gastric cancer , with that of the same chemotherapy plus radiation therapy ( RT ) . In addition , we evaluated the prognostic and /or predictive value of a panel of molecular markers . Patients with histologically proven , radically resected gastric cancer , stage ≥T3 and /or N+ were r and omized to 6 cycles of docetaxel with cisplatin , both at 75 mg/m2 every 3 weeks ( arm A ) or the same treatment with RT ( arm B ; 45 Gy ) . Due to excessive nausea and vomiting , cisplatin was substituted by carboplatin at AUC ( area under the curve ) of 5 after the first 45 patients ( 22 group A , 23 group B ) . The prognostic value of EGFR , ERCC1 , HER2 , MET/HGFR , MAP-Tau , and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays ( TMAs ) . A total of 147 patients were r and omized . After a median follow-up of 53.7 months , no differences in overall ( OS ) and disease-free survival ( DFS ) were found between the two arms . The most common grade 3/4 toxicities for arms A and B ( excluding alopecia ) were non-febrile neutropenia ( 11 and 17 % , respectively ) , febrile neutropenia ( 9 and 7 % ) and diarrhea ( 7 and 4 % , respectively ) . Patients with ERCC1 positive tumors had significantly longer median DFS ( 33.1 vs. 11.8 months , Wald P = 0.016 ) and OS ( 63.2 vs. 18.8 months , Wald P = 0.046 ) . Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk , radically resected gastric cancer . However , the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded BACKGROUND Cetuximab plus irinotecan/folinic acid/5-fluorouracil ( 5-FU ) ( IF ) was evaluated as first-line treatment of patients with advanced gastric cancer and gastroesophageal junction tumors . Preplanned analyses of the influence of tumor biomarkers on treatment outcome were carried out . PATIENTS AND METHODS Patients received weekly cetuximab ( 400 mg/m(2 ) on day 1 , subsequently 250 mg/m(2 ) ) plus irinotecan ( 80 mg/m(2 ) ) and a 24-hour continuous infusion of folinic acid ( 200 mg/m(2 ) ) and 5-FU ( 1500 mg/m(2 ) ) on days 1 , 8 , 15 , 22 , 29 and 36 of a 50-day cycle , until progressive disease ( PD ) . RESULTS The most common grade 3/4 toxic effects in 49 patients were diarrhea ( 15 % ) and skin toxic effects ( 14 % ) . In 48 assessable patients , the overall response rate was 46 % and disease control rate was 79 % . Median progression-free survival ( PFS ) and overall survival ( OS ) was 9.0 months [ 95 % confidence interval ( CI ) 7.1 - 15.6 ] and 16.5 months ( 95 % CI 11.7 - 30.1 ) , respectively . Tumor response was more common than nonresponse in epidermal growth factor receptor-expressing tumors ( P = 0.041 ) . Tumor PTEN expression was associated with longer PFS ( P = 0.035 ) and OS ( P = 0.0127 ) than no PTEN expression . CONCLUSION Cetuximab plus IF was well tolerated and efficacy data were encouraging . This treatment combination and the role of selected biomarkers are under investigation in the ongoing phase III EXP AND trial Output:	This meta- analysis result suggested that EGFR or HER2 should have significant predictive ability for estimating overall survival in GC patients and may be useful for defining prognosis of GC patients
MS22283	*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 compare overall survival ( OS ) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer . Patients and Methods The Fulvestrant First-Line Study Comparing Endocrine Treatments ( FIRST ) was a phase II , r and omized , open-label , multicenter trial . Postmenopausal women with estrogen receptor – positive , locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg ( days 0 , 14 , 28 , and every 28 days thereafter ) or anastrozole 1 mg ( daily ) . The primary end point ( clinical benefit rate [ 72.5 % and 67.0 % ] ) and a follow-up analysis ( median time to progression [ 23.4 months and 13.1 months ] ) have been reported previously for fulvestrant 500 mg and anastrozole , respectively . Subsequently , the protocol was amended to assess OS by unadjusted log-rank test after approximately 65 % of patients had died . Treatment effect on OS across several subgroups was examined . Tolerability was evaluated by adverse event monitoring . Results In total , 205 patients were r and omly assigned ( fulvestrant 500 mg , n = 102 ; anastrozole , n = 103 ) . At data cutoff , 61.8 % ( fulvestrant 500 mg , n = 63 ) and 71.8 % ( anastrozole , n = 74 ) had died . The hazard ratio ( 95 % CI ) for OS with fulvestrant 500 mg versus anastrozole was 0.70 ( 0.50 to 0.98 ; P = .04 ; median OS , 54.1 months v 48.4 months ) . Treatment effects seemed generally consistent across the subgroups analyzed . No new safety issues were observed . Conclusion There are several limitations of this OS analysis , including that it was not planned in the original protocol but instead was added after time-to-progression results were analyzed , and that not all patients participated in additional OS follow-up . However , the present results suggest fulvestrant 500 mg extends OS versus anastrozole . This finding now awaits prospect i ve confirmation in the larger phase III FALCON ( Fulvestrant and Anastrozole Compared in Hormonal Therapy Naïve Advanced Breast Cancer ) trial ( Clinical Trials.gov identifier : NCT01602380 ) PURPOSE To test whether combining bevacizumab , an anti-vascular endothelial growth factor treatment , with endocrine therapy ( ET ) could potentially delay the emergence of resistance to ET . PATIENTS AND METHODS A multicenter , r and omized , open-label , phase III , binational ( Spain and Germany ) study added bevacizumab ( 15 mg/kg every 3 weeks ) to ET ( ET-B ; letrozole or fulvestrant ) as first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 ( HER2 ) -negative and hormone receptor-positive advanced breast cancer . We compared progression-free survival ( PFS ) , overall survival ( OS ) , overall response rate ( ORR ) , response duration ( RD ) , time to treatment failure ( TTF ) , clinical benefit rate ( CBR ) , and safety . RESULTS From 380 patients recruited ( 2007 to 2011 ) , 374 were analyzed by intent to-treat ( 184 patients on ET and 190 patients on ET-B ) . Median age was 65 years , 270 patients ( 72 % ) had Eastern Cooperative Oncology Group performance status of 0 , 178 patients ( 48 % ) had visceral metastases , and 171 patients ( 46 % ) and 195 patients ( 52 % ) had received prior chemotherapy or ET , respectively . Median PFS was 14.4 months in the ET arm and 19.3 months in the ET-B arm ( hazard ratio , 0.83 ; 95 % CI , 0.65 to 1.06 ; P = .126 ) . ORR , CBR , and RD with ET versus ET-B were 22 % versus 41 % ( P < .001 ) , 67 % versus 77 % ( P = .041 ) , and 13.3 months versus 17.6 months ( P = .434 ) , respectively . TTF and OS were comparable in both arms . Grade 3 to 4 hypertension , aminotransferase elevation , and proteinuria were significantly higher in the ET-B arm . Eight patients ( 4.2 % ) receiving ET-B died during study or within 30 days of end of treatment . CONCLUSION The addition of bevacizumab to ET in first-line treatment failed to produce a statistically significant increase in PFS or OS in women with HER2-negative/hormone receptor-positive advanced breast cancer BACKGROUND The BOLERO-2 study previously demonstrated that adding everolimus ( EVE ) to exemestane ( EXE ) significantly improved progression-free survival ( PFS ) by more than twofold in patients with hormone-receptor-positive ( HR(+ ) ) , HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors ( NSAIs ) . The overall survival ( OS ) analysis is presented here . PATIENTS AND METHODS BOLERO-2 is a phase III , double-blind , r and omized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo ( PBO ) + EXE 25 mg/day in postmenopausal women with HR(+ ) advanced breast cancer with prior exposure to NSAIs . The primary end point was PFS by local investigator assessment ; OS was a key secondary end point . RESULTS At the time of data cutoff ( 3 October 2013 ) , 410 deaths had occurred and 13 patients remained on treatment . Median OS in patients receiving EVE + EXE was 31.0 months [ 95 % confidence interval ( CI ) 28.0 - 34.6 months ] compared with 26.6 months ( 95 % CI 22.6 - 33.1 months ) in patients receiving PBO + EXE ( hazard ratio = 0.89 ; 95 % CI 0.73 - 1.10 ; log-rank P = 0.14 ) . Post study treatments were received by 84 % of patients in the EVE + EXE arm versus 90 % of patients in the PBO + EXE arm . Types of post study therapies were balanced across arms , except for chemotherapy ( 53 % EVE + EXE versus 63 % PBO + EXE ) . No new safety concerns were identified . CONCLUSIONS In BOLERO-2 , adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinical ly meaningful and statistically significant improvement in the primary end point , PFS ( 4.6-months prolongation in median PFS ; P < 0.0001 ) . Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting . TRIAL REGISTRATION NUMBER NCT00863655 Fulvestrant fIRst-line Study comparing endocrine Treatments is a phase II , r and omized , open-label study comparing fulvestrant 500 mg with anastrozole 1 mg as first-line endocrine therapy for postmenopausal women with hormone receptor-positive ( HR+ ) advanced breast cancer . At data cut-off , only 36 % of patients had progressed and the median time to progression ( TTP ) had not been reached for fulvestrant . Here , we report follow-up data for TTP for fulvestrant 500 mg versus anastrozole 1 mg . Key inclusion criteria were postmenopausal women with estrogen receptor-positive and /or progesterone receptor-positive locally advanced or metastatic breast cancer and no prior endocrine therapy . Key exclusion criteria were presence of life-threatening metastases and prior treatment with a non-approved drug . Fulvestrant was administered 500 mg/month plus 500 mg on day 14 of month 1 ; anastrozole was administered 1 mg/day . TTP was defined by modified Response Evaluation Criteria in Solid Tumors v1.0 before data cut-off for the primary analysis , and investigator opinion after data cut-off . Best overall response to subsequent therapy and serious adverse events are also reported . In total , 205 patients received fulvestrant 500 mg ( n = 102 ) or anastrozole ( n = 103 ) . Follow-up analysis was performed when 79.5 % of patients had discontinued study treatment . Median TTP was 23.4 months for fulvestrant versus 13.1 months for anastrozole ; a 34 % reduction in risk of progression ( hazard ratio 0.66 ; 95 % confidence interval : 0.47 , 0.92 ; P = 0.01 ) . Best overall response to subsequent therapy and clinical benefit rate for subsequent endocrine therapy was similar between the treatment groups . No new safety concerns for fulvestrant 500 mg were documented . These longer-term , follow-up results confirm efficacy benefit for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for HR+ advanced breast cancer in terms of TTP , and , importantly , show similar best overall response rates to subsequent endocrine therapy Introduction Effective treatments for hormone-receptor-positive ( HR+ ) breast cancer ( BC ) following relapse/progression on nonsteroidal aromatase inhibitor ( NSAI ) therapy are needed . Initial Breast Cancer Trials of OraL EveROlimus-2 ( BOLERO-2 ) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival ( PFS ) versus placebo plus exemestane alone in this patient population . Methods BOLERO-2 is a phase 3 , double-blind , r and omized , international trial comparing everolimus ( 10 mg/day ) plus exemestane ( 25 mg/day ) versus placebo plus exemestane in postmenopausal women with HR+ advanced BC with recurrence/progression during or after NSAIs . The primary endpoint was PFS by local investigator review , and was confirmed by independent central radiology review . Overall survival , response rate , and clinical benefit rate were secondary endpoints . Results Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [ investigator review : 7.8 versus 3.2 months , respectively ; hazard ratio = 0.45 ( 95 % confidence interval 0.38–0.54 ) ; log-rank P < 0.0001 ; central review : 11.0 versus 4.1 months , respectively ; hazard ratio = 0.38 ( 95 % confidence interval 0.31–0.48 ) ; log-rank P < 0.0001 ] in the overall population and in all prospect ively defined subgroups , including patients with visceral metastases , patients with recurrence during or within 12 months of completion of adjuvant therapy , and irrespective of age . The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials . Conclusion The addition of everolimus to exemestane markedly prolonged PFS in patients with HR+ advanced BC with disease recurrence/progression following prior NSAIs . These results further support the use of everolimus plus exemestane in this patient population . Clinical Trials.gov # NCT00863655 Background At the time of the initial analysis of overall survival ( OS ) for the Comparison of Faslodex in Recurrent or Metastatic Breast Cancer ( CONFIRM ) r and omized , double-blind , phase III trial , approximately 50 % of patients had died . A final analysis of OS was subsequently planned for when 75 % of patients had died . Methods Patients were r and omly assigned 1:1 to fulvestrant 500 mg administered as two 5-mL intramuscular injections on days 0 , 14 , and 28 and every 28 ( ±3 ) days thereafter or fulvestrant 250 mg administered as two 5-mL intramuscular injections ( one fulvestrant and one placebo [ identical in appearance to study drug ] ) on days 0 , 14 ( two placebo injections only ) , and 28 and every 28 ( ±3 ) days thereafter . OS was analyzed using an unadjusted log-rank test . No adjustments were made for multiplicity . Serious adverse events ( SAEs ) and best response to subsequent therapy were also reported . All statistical tests were two-sided . Results In total , 736 women ( median age = 61.0 years ) were r and omly assigned to fulvestrant 500 mg ( n = 362 ) or 250 mg ( n = 374 ) . At the final survival analysis , 554 of 736 ( 75.3 % ) patients had died . Median OS was 26.4 months for fulvestrant 500 mg and 22.3 months for 250 mg ( hazard ratio = 0.81 ; 95 % confidence interval = 0.69–0.96 ; nominal P = .02 ) . There were no clinical ly important differences in SAE profiles between the treatment groups ; no clustering of SAEs could be detected in either treatment group . Type of first subsequent therapy and objective Output:	Overall survival ( OS ) improved with the use of mTOR inhibitors and a SERD ; however , studies were not powered for an OS endpoint . Study discontinuation rates and toxicity-related deaths were highest with VEGF inhibitors in combination with endocrine therapy , limiting their use in hormone receptor positive breast cancer . CDK4/6 inhibitors and mTOR inhibitors appeared to have activity in both first and second line setting s , but required additional monitoring for common toxicities . The activity of epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors was limited to the first-line setting and treatment discontinuation rates were higher than with mTOR inhibitors and SERDs . Overall , PFS benefit appears to be greatest when agents acting on CDK4/6 , mTOR and Pi3 K pathways , and SERDs are added to st and ard endocrine therapy .
MS22284	*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 the study was to establish the specific use of advice and exercise by physiotherapists , for the management of chronic low back pain ( LBP ) . A question naire was mailed to a r and om sample of 600 members of the Irish Society of Chartered Physiotherapists . Open and closed questions were used to obtain information on treatments provided to chronic LBP patients . Respondents ' treatment goals were also investigated , along with the typical methods used to assess treatment outcome . Four hundred and nineteen of the sample returned the question naire ; 280/419 ( 67 % ) indicated that they currently treated LBP of which 76 % ( n=214 ) were senior grade therapists . Advice and exercise , respectively , were the treatments most frequently used for chronic LBP : advice was most commonly delivered as part of an exercise programme , with strengthening ( including core stability ) the most frequently used exercise type . Supervision of exercise and follow-up advice were underutilised with respect to the recommendations of relevant clinical guidelines . Pain relief was an important treatment goal . Emphasis on exercise programme supervision , incorporating reassurance that its safe to stay active and ' hurt does not mean harm ' , must be more effectively disseminated and promoted in practice . The influence of follow-up advice on exercise adherence warrants further investigation Background Traction is commonly used for the treatment of low back pain ( LBP ) , predominately with nerve root involvement ; however its benefits remain to be established . The aim of this study was to test the feasibility of a pragmatic r and omized controlled trial to compare the difference between two treatment protocol s ( manual therapy , exercise and advice , with or without traction ) in the management of acute/sub acute LBP with ' nerve root ' involvement . Methods 30 LBP patients with nerve root pain were recruited and r and omly assigned to one of two treatment groups . Primary outcome measures were the : McGill pain question naire , Rol and Morris disability question naire , and the SF36 Question naire ; recorded at baseline , discharge , 3 and 6 months post-discharge . Results 27 patients completed treatment with a loss of another four patients at follow up . Intention to treat analysis demonstrated an improvement in all outcomes at follow up points but there appeared to be little difference between the groups . Conclusion This study has shown that a trial recruiting patients with ' nerve root ' problems is feasible . Further research based upon a fully powered trial is required to ascertain if the addition of traction has any benefit in the management of these patients .Trial Registration Registration number : IS RCT BACKGROUND AND PURPOSE Since the release of acute low back pain management guidelines in 1994 , little was known about the effect of these guidelines on clinical practice . The purpose of this study was to examine physical therapists ' reported management of acute and subacute lumbar impairment . SUBJECTS One in 10 registered physical therapists who were r and omly selected from southern Ontario , Canada , ( n=454 ) and all registered physical therapists from northern Ontario ( n=331 ) were surveyed . METHODS In the question naire , case scenarios covered 3 areas related to the management of lumbar impairment : ( 1 ) physical examination , ( 2 ) treatment and recommendations , and ( 3 ) therapists ' beliefs regarding its management . RESULTS Five hundred sixty-nine question naires were returned ( response rate=72.5 % ) . Only data obtained for therapists ( n=274 ) whose weekly workload included more than 10 % of people with lumbar impairment were used in the analysis . Overall , patient education , exercise , and electrotherapeutic and thermal modalities were the preferred interventions for acute lumbar impairment ( symptom onset of less than 5 weeks ) with or without sciatica , whereas exercise and work modification were preferred for subacute lumbar impairment ( symptom onset of 5 weeks or longer ) . There was a trend of using electrotherapeutic and thermal modalities with uncertain effectiveness . Only 46.3 % of the therapists agreed or strongly agreed that practice guidelines were useful for managing lumbar impairment . DISCUSSION AND CONCLUSION Although the physical therapists surveyed , in general , followed the guidelines in managing acute lumbar impairment , they felt uncertain regarding the value of practice guidelines . Future research should focus on identifying effective treatment approaches and exploring the effectiveness of practice guidelines Background Patients with signs of nerve root irritation represent a sub-group of those with low back pain who are at increased risk of persistent symptoms and progression to costly and invasive management strategies including surgery . A period of non-surgical management is recommended for most patients , but there is little evidence to guide non-surgical decision-making . We conducted a preliminary study examining the effectiveness of a treatment protocol of mechanical traction with extension-oriented activities for patients with low back pain and signs of nerve root irritation . The results suggested this approach may be effective , particularly in a more specific sub-group of patients . The aim of this study will be to examine the effectiveness of treatment that includes traction for patients with low back pain and signs of nerve root irritation , and within the pre-defined sub-group . Methods / Design The study will recruit 120 patients with low back pain and signs of nerve root irritation . Patients will be r and omized to receive an extension-oriented treatment approach , with or without the addition of mechanical traction . R and omization will be stratified based on the presence of the pre-defined sub-grouping criteria . All patients will receive 12 physical therapy treatment sessions over 6 weeks . Follow-up assessment s will occur after 6 weeks , 6 months , and 1 year . The primary outcome will be disability measured with a modified Oswestry question naire . Secondary outcomes will include self-reports of low back and leg pain intensity , quality of life , global rating of improvement , additional healthcare utilization , and work absence . Statistical analysis will be based on intention to treat principles and will use linear mixed model analysis to compare treatment groups , and examine the interaction between treatment and sub-grouping status . Discussion This trial will provide a method ologically rigorous evaluation of the effectiveness of using traction for patients with low back pain and signs of nerve root irritation , and will examine the validity of a pre-defined sub-grouping hypothesis . The results will provide evidence to inform non-surgical decision-making for these patients .Trial Registration This trial has been registered with http:// Clinical Trials.gov : Four treatment regimens for patients with specified combinations of low back pain and sciatica were evaluated . The largest group studied had low back pain with limited straight-leg raising ( SLR ) and in them the beneficial effect of manipulation in hastening pain relief was highly significant . In similar patients without limitation of SLR , the effect was of borderline significance . In all the other groups , treated patients also recovered more quickly than their controls . Traction , for patients with low back pain and sciatica , and epidural injections when a root palsy was present also produced some significant pain relief . The effect of sclerosants for back pain was less clear BACKGROUND CONTEXT Low back pain ( LBP ) is a prevalent disorder in society that has been associated with increased loss of work time and medical expenses . A common intervention for LBP is spinal manipulation , a technique that is not specific to one scope of practice or profession . PURPOSE The purpose of this systematic review was to examine the effectiveness of physical therapy spinal manipulations for the treatment of patients with low back pain . METHODS A search of the current literature was conducted using PubMed , CINAHL , SPORTD iscus , Pro Quest Nursing and Allied Health Source , Scopus , and Cochrane Controlled Trials Register . Studies were included if each involved : 1 ) individuals with LBP ; 2 ) spinal manipulations performed by physical therapists compared to any control group that did not receive manipulations ; 3 ) measurable clinical outcomes or efficiency of treatment measures , and 4 ) r and omized control trials . The quality of included articles was determined by two independent authors using the criteria developed and used by the Physiotherapy Evidence Data base ( PEDro ) . RESULTS Six r and omized control trials met the inclusion criteria of this systematic review . The most commonly used outcomes in these studies were some variation of pain rating scales and disability indexes . Notable results included varying degrees of effect sizes favoring physical therapy spinal manipulations and minimal adverse events result ing from this intervention . Additionally , the manipulation group in one study reported statistically significantly less medication use , health care utilization , and lost work time . CONCLUSION Based on the findings of this systematic review there is evidence to support the use of spinal manipulation by physical therapists in clinical practice . Physical therapy spinal manipulation appears to be a safe intervention that improves clinical outcomes for patients with low back pain PURPOSE S to compare the efficacy of mechanical lumbar traction with low ( 10 % of body weight ) and high traction force ( 50 % of body weight ) on the separation of the vertebrae in vivo using stature variations as criterion . Additionally , we aim ed to determine the time that the effects of traction last . MATERIAL AND METHODS Thirty apparently healthy subjects ( age : 20.9 ± 1.7 years old ) , 14 male and 16 female , were su bmi tted to two protocol s of 15 minutes of continuous traction ( with intensity of 10 % and 50 % of body weight ) , in two sessions one week apart . The protocol order was determined r and omly . Stature was assessed before and immediately after the traction and every five minutes for 30 minutes after traction ceased . RESULTS Immediately after the traction both protocol s induced a significant increase in stature , however the magnitude of the increase was significantly superior in the traction with 50 % of body weight ( 0.567 ± 0.049 vs. 0.298 ± 0.041 cm , p>0.001 ) . After the traction with 50 % of body weight the increase in the stature was maintained until ten minutes after the end of the traction , while after the traction with 10 % of body weight the effects on stature disappeared after five minutes . CONCLUSIONS The mechanical vertebral traction of the lumbar region performed continuously with 50 % of body weight during 15 minutes induced an increase in stature superior and longer in time than that observed with a traction force of 10 % of body weight STUDY DESIGN Single group test-retest repeated measures . OBJECTIVES To determine the effects of lumbar traction with 3 different amounts of force ( 10 % , 30 % and 60 % body weight ) on pain-free mobility of the lower extremity as measured by the straight leg raise ( SLR ) test . BACKGROUND There are several recommendations on how lumbar traction should be performed , but the duration , frequency , force , and type of technique to be applied differ among the sources . METHODS AND MEASURES Ten subjects with subjective complaints of low back pain or radicular symptoms with a positive unilateral SLR test below 45 degrees participated in this study . The pain-free mobility of the lower extremity in the SLR test position was measured prior to and immediately following 5 minutes of static traction in the supine position . R and om assignment in the order of the amount of applied traction was implemented . RESULTS The straight leg raise measurements were found to be significantly greater immediately following 30 % and 60 % of body weight traction as compared to pretraction and 10 % of body weight traction . The mean ( SD ) SLR measurements were pretraction ( 24.1 degrees + /- 13.0 ) , 10 % of body weight traction ( 27.4 degrees + /- 14.5 ) , 30 % of body weight traction ( 34.0 degrees + /- 14.3 ) , 60 % of body weight traction ( 36.5 degrees + /- 15.8 ) . CONCLUSIONS The results of this study indicate that traction in this group of patients improved the mobility of the lower extremity during the SLR test . Both 30 % and 60 % of body weight tractions were shown to be effective for increasing motion beyond pretraction levels Study Design . A prospect i ve , consecutive , cohort study of patients with acute low back pain classified into subgroups based on examination data and treated with a specific treatment approach . Objective . To calculate the interrater reliability of a classification system , and to compare initial patient characteristics and outcomes of physical therapy treatment when a classification approach is used . Summary of Background Data . Classification of patients with low back pain into homogeneous subgroups has been identified as a research priority . Identifying relevant subgroups of patients could improve clinical outcomes and research efficiency . Methods . Consecutive patients referred to physical therapy for treatment of acute low back pain were evaluated and classified into one of four subgroups ( immobilization , mobilization , specific exercise , or traction ) before treatment . Physical therapy treatment was based on the patient ’s classification . The classifications were compared for initial patient characteristics , frequency and duration of physical therapy , and improvement in Oswestry scores . Results . In this study , 120 patients were evaluated and classified . Analysis of interrater reliability showed a kappa value of 0.56 . Differences were found among the classifications for age , initial Oswestry score , history of low back pain , symptom distribution , and average change in Oswestry score with treatment . Conclusions . Reaching a consensus regarding relevant patient subgroups requires data on the reliability and validity of existing classification systems . Further work is required to vali date improvement in treatment outcomes using a classification approach Study Design . A r and omized clinical trial . Objectives . To assess the efficacy of motorized continuous traction for low back pain . Summary of Background Data . The available studies on the efficacy of lumbar traction do not allow clear conclusions because of severe method ologic flaws . The current trial aim ed to overcome these shortcomings . Methods . Patients with at least 6 weeks of nonspecific low back pain were selected . High‐dose traction was compared with sham ( or low‐dose ) traction . Sham traction was given with a specially developed brace that becomes tighter in the back during traction . This was experienced as if real traction were exerted . The patients and the outcome assessor were unaware of treatment allocation . Outcome measures were : patient 's global perceived effect , severity of main complaints , functional status , pain , range of motion , work absence , and medical treatment . Results for the outcome measures at 12 weeks Output:	Most of the orthopaedic physical therapists in the United States who responded to our survey reported that they used lumbar traction , though not necessarily consistent with proposed criteria that identify patients most likely to benefit from traction . They used various traction delivery modes/parameters and used traction within comprehensive plans of care incorporating multiple interventions . Professional characteristics ( education levels and clinical specialist credentialing ) were associated with traction usage
MS22285	*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 Purpose To compare tachycardia and cardiac strain between 24-hour shifts ( 24hS ) and 14-hour night shifts ( 14hS ) in emergency physicians ( EPs ) , and to investigate key factors influencing tachycardia and cardiac strain . Methods We monitored heart rate ( HR ) with Holter-ECG in a shift-r and omized trial comparing a 24hS , a 14hS , and a control day , within a potential for 19 EPs . We also measured 24-h HR the third day ( D3 ) after both shifts . We measured perceived stress by visual analog scale and the number of life- and -death emergencies . Results The 17 EPs completing the whole protocol reached maximal HR ( 180.9 ± 6.9 bpm ) during both shifts . Minutes of tachycardia > 100 bpm were higher in 24hS ( 208.3 ± 63.8 ) than in any other days ( 14hS : 142.3 ± 36.9 ; D3/14hS : 64.8 ± 31.4 ; D3/24hS : 57.6 ± 19.1 ; control day : 39.2 ± 11.6 min , p < .05 ) . Shifts induced a cardiac strain twice higher than in days not involving patients contact . Each life- and -death emergency enhanced 26 min of tachycardia ≥100 bpm ( p < .001 ) , 7 min ≥ 110 bpm ( p < .001 ) , 2 min ≥ 120 bpm ( p < .001 ) and 19 min of cardiac strain ≥30 % ( p = .014 ) . Stress was associated with greater duration of tachycardia ≥100 , 110 and 120 bpm , and of cardiac strain ≥30 % ( p < .001 ) . Conclusion We demonstrated several incidences of maximal HR during shifts combined with a high cardiac strain . Duration of tachycardia were the highest in 24hS and lasted several hours . Such values are comparable to those of workers exposed to high physical dem and ing tasks or heat . Therefore , we suggest that EPs limit their exposure to 24hS. We , furthermore , demonstrated benefits of HR monitoring for identifying stressful events . Clinical Trials.gov identifier : NCT01874704 Background The study investigated the extent to which approaches to work , workplace climate , stress , burnout and satisfaction with medicine as a career in doctors aged about thirty are predicted by measures of learning style and personality measured five to twelve years earlier when the doctors were applicants to medical school or were medical students . Methods Prospect i ve study of a large cohort of doctors . The participants were first studied when they applied to any of five UK medical schools in 1990 . Postal question naires were sent to all doctors with a traceable address on the current or a previous Medical Register . The current question naire included measures of Approaches to Work , Workplace Climate , stress ( General Health Question naire ) , burnout ( Maslach Burnout Inventory ) , and satisfaction with medicine as a career and personality ( Big Five ) . Previous question naires had included measures of learning style ( Study Process Question naire ) and personality . Results Doctors ' approaches to work were predicted by study habits and learning styles , both at application to medical school and in the final year . How doctors perceive their workplace climate and workload is predicted both by approaches to work and by measures of stress , burnout and satisfaction with medicine . These characteristics are partially predicted by trait measures of personality taken five years earlier . Stress , burnout and satisfaction also correlate with trait measures of personality taken five years earlier . Conclusions Differences in approach to work and perceived workplace climate seem mainly to reflect stable , long-term individual differences in doctors themselves , reflected in measures of personality and learning style BACKGROUND To examine the mortality pattern of Danish doctors for the period 1973 - 1992 . METHODS A historical prospect i ve cohort study based on the membership register of the Danish Medical Association . The study population consisted of 21,943 medical doctors , 6012 of whom were women . The doctors ' cause-specific mortality was compared with that of the general population . RESULTS The study covered about 277,000 person-years . A total of 2387 deaths occurred from 1 January 1973 to 31 December 1992 . The doctors ' mortality was lower than that of the general population . Both sexes showed a st and ardized mortality ratio ( SMR ) below one for cancer , circulatory diseases and other natural causes . Mortality due to lung cancer was particularly low . The SMR for suicide was significantly increased , 1.6 for males ( 95 % CI : 1.4 - 1.9 ) and 1.7 for females ( 95 % CI : 1.1 - 2.5 ) . The suicide rate was increased , in particular because of an increased number of suicides by poisoning . In addition female doctors displayed a relatively high mortality due to accidents and other types of violent death . CONCLUSIONS Compared with the general population the doctors ' mortality was low , but the mortality from external causes was increased , mainly due to an excess number of suicides Abstract OBJECTIVE : To assess the association between HMO practice , time pressure , and physician job satisfaction . DESIGN : National r and om stratified sample of 5,704 primary care and specialty physicians in the United States . Surveys contained 150 items reflecting 10 facets ( components ) of satisfaction in addition to global satisfaction with current job , one ’s career and one ’s specialty . Linear regression-modeled satisfaction ( on 1–5 scale ) as a function of specialty , practice setting ( solo , small group , large group , academic , or HMO ) , gender , ethnicity , full-time versus part-time status , and time pressure during office visits . “ HMO physicians ” ( 9 % of total ) were those in group or staff model HMOs with > 50 % of patients capitated or in managed care . RESULTS : Of the 2,326 respondents , 735 ( 32 % ) were female , 607 ( 26 % ) were minority ( adjusted response rate 52 % ) . HMO physicians reported significantly higher satisfaction with autonomy and administrative issues when compared with other practice types ( moderate to large effect sizes ) . However , physicians in many other practice setting s averaged higher satisfaction than HMO physicians with re sources and relationships with staff and community ( small to moderate effect sizes ) . Small and large group practice and academic physicians had higher global job satisfaction scores than HMO physicians ( P<.05 ) , and private practice physicians had quarter to half the odds of HMO physicians of intending to leave their current practice within 2 years ( P<.05 ) . Time pressure detracted from satisfaction in 7 of 10 satisfaction facets ( P<.05 ) and from job , career , and specialty satisfaction ( P<.01 ) . Time allotted for new patients in HMOs ( 31 min ) was less than that allotted in solo ( 39 min ) and academic practice s ( 44 min ) , while 83 % of family physicians in HMOs felt they needed more time than allotted for new patients versus 54 % of family physicians in small group practice s ( P<.05 after Bonferroni ’s correction ) . CONCLUSIONS : HMO physicians are generally less satisfied with their jobs and more likely to intend to leave their practice s than physicians in many other practice setting s. Our data suggest that HMO physicians ’ satisfaction with staff , community , re sources , and the duration of new patients visits should be assessed and optimized . Whether providing more time for patient encounters would improve job satisfaction in HMOs or other practice setting s remains to be determined Background Emergency physicians are exposed to greater stress during a 24-hour shift ( 24 hS ) than a 14-hour night shift ( 14 hS ) , with an impact lasting several days . Interleukin-8 ( IL-8 ) is postulated to be a chronic stress biomarker . However , no studies have tracked IL-8 over several shifts or used it for monitoring short-term residual stress . The IL-8 response to the shifts may also increase with age . Conveniently , IL-8 can be measured non-intrusively from urine . Methods We conducted a shifts-r and omized trial comparing 17 emergency physicians ’ urinary IL-8 levels during a 24 hS , a 14 hS , and a control day ( clerical work on return from leave ) . Mean levels of IL-8 were compared using a Wilcoxon matched-pairs test . Independent associations of key factors including shifts , stress , and age with IL-8 levels were further assessed in a multivariable generalized estimating equations model . Results Mean urinary IL-8 levels almost doubled during and after a 24 hS compared with a 14 hS or a control day . Furthermore , IL-8 levels failed to return to control values at the end of the third day after the shift despite a rest day following the 24 hS. In the multivariable model , engaging in a 24 hS , self-reported stress , and age were independently associated with higher IL-8 levels . A 24 hS significantly increased IL-8 levels by 1.9 ng ( p = .007 ) . Similarly , for every unit increase in self-reported stress , there was a 0.11 ng increase in IL-8 levels ( p = .003 ) ; and for every one year advance in age of physicians , IL-8 levels also increased by 0.11 ng ( p = .018 ) . Conclusion The 24 hS generated a prolonged response of the immune system . Urinary IL-8 was a strong biomarker of stress under intensive and prolonged dem and s , both acutely and over time . Because elevated IL-8 levels are associated with cardiovascular disease and negative psychological consequences , we suggest that emergency physicians limit their exposure to 24 hS , especially with advancing age Objectives Appropriate reporting is central to the application of findings from research to clinical practice . The Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) recommendations consist of a checklist of 22 items that provide guidance on the reporting of cohort , case – control and cross-sectional studies , in order to facilitate critical appraisal and interpretation of results . STROBE was published in October 2007 in several journals including The Lancet , BMJ , Annals of Internal Medicine and PLoS Medicine . Within the framework of the revision of the STROBE recommendations , the authors examined the context and circumstances in which the STROBE statement was used in the past . Design The authors search ed the Web of Science data base in August 2010 for articles which cited STROBE and examined a r and om sample of 100 articles using a st and ardised , piloted data extraction form . The use of STROBE in observational studies and systematic review s ( including meta-analyses ) was classified as appropriate or inappropriate . The use of STROBE to guide the reporting of observational studies was considered appropriate . Inappropriate uses included the use of STROBE as a tool to assess the method ological quality of studies or as a guideline on how to design and conduct studies . Results The authors identified 640 articles that cited STROBE . In the r and om sample of 100 articles , about half were observational studies ( 32 % ) or systematic review s ( 19 % ) . Comments , editorials and letters accounted for 15 % , method ological articles for 8 % , and recommendations and narrative review s for 26 % of articles . Of the 32 observational studies , 26 ( 81 % ) made appropriate use of STROBE , and three uses ( 10 % ) were considered inappropriate . Among 19 systematic review s , 10 ( 53 % ) used STROBE inappropriately as a tool to assess study quality . Conclusions The STROBE reporting recommendations are frequently used inappropriately in systematic review s and meta-analyses as an instrument to assess the method ological quality of observational studies OBJECTIVE Physician job satisfaction has been the subject of much research . However , no studies have been conducted comparing academic and private practice physician satisfaction in obstetrics and gynecology . This study was undertaken to measure satisfaction levels for academic and private practice obstetrician-gynecologists and compare different aspects of their practice that contributed to their satisfaction . STUDY DESIGN A survey was mailed to r and omly selected obstetrician-gynecologists in Memphis , TN ; Birmingham , AL ; Little Rock , AR ; and Jackson , MS . Physicians were asked to respond to questions concerning demographics and career satisfaction . They were also asked to assess the contribution of 13 different aspects of their practice in contributing to their job selection and satisfaction using a Likert scale . A score of 1 meant the physician completely disagreed with a statement regarding a factor 's contribution or was completely dissatisfied ; a score of 5 meant the physician completely agreed with a factor 's contribution or was completely satisfied . Simple descriptive statistics , as well as the 2- sample t test , were used . Likert scale values were assumed to be interval measurements . RESULTS Of the 297 question naires mailed , 129 ( 43 % ) physicians responded . Ninety-five ( 74 % ) respondents rated their overall satisfaction as 4 or 5 . No significant difference was found between academic and private physicians when comparing overall job satisfaction ( P = .25 ) . When compared to private practice physicians , the aspects most likely contributing to overall job satisfaction for academic physicians were the ability to teach , conduct research , and practice variety ( P = .0001 , P = .0001 , and P = .007 , respectively ) . When compared with academic physicians , the aspects most likely contributing to job satisfaction for private practice physicians were autonomy , physician-patient relationship , and insurance reimbursement ( P = .0058 , P = .0001 , and P = .0098 , respectively ) . When choosing a practice setting , academic physicians found variety , teaching , and research to be more important ( P = .0027 , P = .0001 , and Output:	Some specialties might be at higher risk such as anesthesiologists , psychiatrists , general practitioners and general surgeons . Physicians are an at-risk profession of suicide , with women particularly at risk . The rate of suicide in physicians decreased over time , especially in Europe .
MS22286	*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 examine the effects of aerobic interval training on the decline in short-passing ability caused by a short bout of high-intensity intermittent activities . For this r and omized controlled trial , 26 junior soccer players ( mean age , 17.8 + /- 0.6 years ; mean height , 178 + /- 5 cm ; mean body mass , 74.5 + /- 6.9 kg ) were recruited . After baseline measurements , subjects were r and omly allocated to 1 of 2 groups : the control group ( CG ) or the aerobic interval training group ( ITG ) . The ITG completed 4 weeks of high-intensity aerobic training , consisting of 4 bouts of running for 4 min at 90%-95 % of maximal heart rate , with 3 min of active recovery between sets , in addition to normal training . Maximum oxygen uptake , Yo-Yo Intermittent Recovery Test level 1 ( YYIRT ) , and short-passing ability ( measured using the Loughborough Soccer Passing Test ( LSPT ) ) were measured before and after a 5 min high-intensity simulation ( HIS ) , reproducing the most intense phase of a match . The ITG ( n = 11 ) , but not the CG ( n = 10 ) , showed a significant 12 % and 4 % increase in YYIRT and maximal oxygen consumption after training , respectively , and reduced the worsening in LSPT penalty time after the HIS ( p < 0.05 ) . The relative exercise intensity during HIS decreased in the ITG only ( p < 0.01 ) . Our results demonstrated that junior soccer players may benefit from aerobic training to attenuate the decline in short-passing ability caused by a short bout of intermittent activities completed at the same pretraining workload The effects of high-intensity , short- duration , re-warm-ups on team-sport-related performance were investigated . In a r and omised , cross-over study , participants performed 2 × 26-min periods of an intermittent activity protocol ( IAP ) on a non-motorized treadmill , interspersed by 15-min of passive recovery ( CON ) ; 3-min small-sided game ( SSG ) ; or a 5RM leg-press . Measures included counter-movement jump , repeated-sprint , the Loughborough soccer passing test ( LSPT ) , blood lactate concentration , heart-rate , and perceptual measures . Data were analyzed using effect size ( 90 % confidence intervals ) , and percentage change ; determining magnitudes of effects . A 5RM re-warm-up improved flight-time to contraction-time ratio when compared to SSG ( 9.8 % , ES ; 0.5±0.3 ) and CON ( ES : 9.4 % , 0.7±0.5 ) re-warm-ups , remaining higher following the second IAP ( 8.8 % , ES ; 0.5±0.3 and 10.2 % , ES ; 0.6±0.6 , respectively ) . Relative-maximum rate-of-force development was greater in the 5RM condition following the second IAP compared to SSG ( 29.3 % , ES ; 0.7±0.5 ) and CON ( 16.2 % , ES ; 0.6±0.6 ) . Repeated-sprint ability during the second IAP improved in the 5RM re-warm-up ; peak velocity , mean velocity , and acceleration were 4 , 3 , and 18 % greater , respectively . Within groups , the SSG re-warm-up improved LSPT performance post-intervention ; 6.4 % ( ES : 0.6±0.8 ) and following the second IAP 6.2 % ( ES : 0.6±0.6 ) , compared to pre-intervention . A 5RM leg-press re-warm-up improved physical performance , while a SSG re-warm-up enhanced skill execution following st and ardized intermittent exercise The aim of this experiment was to evaluate bilateral motor performance effects from training the non-dominant leg of competitive soccer players . The subjects were 39 soccer players , 15 - 20 years of age , performance-matched and r and omly divided into a training group ( n = 18 ) and a control group ( n = 21 ) both belonging to the same team . Both groups were tested by using two st and ardised foot-tapping tests and three soccer-specific tests . The training intervention consisted of the experimental group participating in all parts of their soccer training except full play , using the non-dominant leg for 8 weeks . Statistical analyses for the soccer-specific tests revealed that the experimental group improved significantly as compared to the control group from the pre-test to the post-test period in their use of the trained non-dominant leg . Somewhat unexpectedly , the experimental group also improved significantly in the tests , which made use of the dominant side . The st and ardised foot-tapping tests revealed similar results . The results might be explained by improved generalised motor programmes , or from a Dynamic Systems Approach , indicating that the actual training relates to the h and ling of all the information available to the subject in the situation , and that the body self-organises the motor performance Abstract Reliability refers to the reproducibility of values of a test , assay or other measurement in repeated trials on the same individuals . Better reliability implies better precision of single measurements and better tracking of changes in measurements in research or practical setting s. The main measures of reliability are within-subject r and om variation , systematic change in the mean , and retest correlation . A simple , adaptable form of within-subject variation is the typical ( st and ard ) error of measurement : the st and ard deviation of an individual ’s repeated measurements . For many measurements in sports medicine and science , the typical error is best expressed as a coefficient of variation ( percentage of the mean ) . A biased , more limited form of within-subject variation is the limits of agreement : the 95 % likely range of change of an individual ’s measurements between 2 trials . Systematic changes in the mean of a measure between consecutive trials represent such effects as learning , motivation or fatigue ; these changes need to be eliminated from estimates of within-subject variation . Retest correlation is difficult to interpret , mainly because its value is sensitive to the heterogeneity of the sample of participants . Uses of reliability include decision-making when monitoring individuals , comparison of tests or equipment , estimation of sample size in experiments and estimation of the magnitude of individual differences in the response to a treatment . Reasonable precision for estimates of reliability requires approximately 50 study participants and at least 3 trials . Studies aim ed at assessing variation in reliability between tests or equipment require complex design s and analyses that research ers seldom perform correctly . A wider underst and ing of reliability and adoption of the typical error as the st and ard measure of reliability would improve the assessment of tests and equipment in our disciplines UNLABELLED There is little evidence regarding the benefits of caffeine ingestion on cognitive function and skillful actions during sporting performance , especially in sports that are multifaceted in their physiological , skill , and cognitive dem and s. PURPOSE To examine the influence of caffeine on performance during simulated soccer activity . METHODS Twelve male soccer players completed two 90-min soccer-specific intermittent running trials interspersed with tests of soccer skill ( LSPT ) . The trials were separated by 7 days and adhered to a r and omized crossover design . On each occasion participants ingested 6 mg/kg body mass ( BM ) of caffeine ( CAF ) or a placebo ( PLA ) in a double-blind fashion 60 min before exercise . Movement time , penalties accrued , and total time were recorded for the LSPT . Physiological and performance markers were measured throughout the protocol . Water ( 3 ml/kg BM ) was ingested every 15 min . RESULTS Participants accrued significantly less penalty time in the CAF trial ( 9.7 + /- 6.6 s vs. PLA 11.6 + /- 7.4 s ; p = .02 ) , leading to a significantly lower total time in this trial ( CAF 51.6 + /- 7.7 s vs. PLA 53.9 + /- 8.5 s ; p = .02 ) . This decrease in penalty time was probably attributable to an increased passing accuracy in the CAF trial ( p = .06 ) . Jump height was 2.7 % ( + /- 1.1 % ) higher in the CAF trial ( 57.1 + /- 5.1 cm vs. PLA 55.6 + /- 5.1 cm ; p = .01 ) . CONCLUSIONS Caffeine ingestion before simulated soccer activity improved players ' passing accuracy and jump performance without any detrimental effects on other performance parameters PURPOSE To investigate the effects of mental fatigue on soccer-specific physical and technical performance . METHODS This investigation consisted of two separate studies . Study 1 assessed the soccer-specific physical performance of 12 moderately trained soccer players using the Yo-Yo Intermittent Recovery Test , Level 1 ( Yo-Yo IR1 ) . Study 2 assessed the soccer-specific technical performance of 14 experienced soccer players using the Loughborough Soccer Passing and Shooting Tests ( LSPT , LSST ) . Each test was performed on two occasions and preceded , in a r and omized , counterbalanced order , by 30 min of the Stroop task ( mentally fatiguing treatment ) or 30 min of reading magazines ( control treatment ) . Subjective ratings of mental fatigue were measured before and after treatment , and mental effort and motivation were measured after treatment . Distance run , heart rate , and ratings of perceived exertion were recorded during the Yo-Yo IR1 . LSPT performance time was calculated as original time plus penalty time . LSST performance was assessed using shot speed , shot accuracy , and shot sequence time . RESULTS Subjective ratings of mental fatigue and effort were higher after the Stroop task in both studies ( P < 0.001 ) , whereas motivation was similar between conditions . This mental fatigue significantly reduced running distance in the Yo-Yo IR1 ( P < 0.001 ) . No difference in heart rate existed between conditions , whereas ratings of perceived exertion were significantly higher at iso-time in the mental fatigue condition ( P < 0.01 ) . LSPT original time and performance time were not different between conditions ; however , penalty time significantly increased in the mental fatigue condition ( P = 0.015 ) . Mental fatigue also impaired shot speed ( P = 0.024 ) and accuracy ( P < 0.01 ) , whereas shot sequence time was similar between conditions . CONCLUSIONS Mental fatigue impairs soccer-specific running , passing , and shooting performance This study aim ed to investigate whether isolated or combined carbohydrate ( CHO ) and caffeine ( CAF ) supplementation have beneficial effects on performance during soccer-related tests performed after a previous training session . Eleven male , amateur soccer players completed 4 trials in a r and omized , double-blind , and crossover design . In the morning , participants performed the Loughborough Intermittent Shuttle Test ( LIST ) . Then , participants ingested ( i ) 1.2 g·kg(-1 ) body mass·h(-1 ) CHO in a 20 % CHO solution immediately after and 1 , 2 , and 3 h after the LIST ; ( ii ) CAF ( 6 mg·kg(-1 ) body mass ) 3 h after the LIST ; ( iii ) CHO combined with CAF ( CHO+CAF ) ; and ( iv ) placebo . All drinks were taste-matched and flavourless . After this 4-h recovery , participants performed a countermovement jump ( CMJ ) test , a Loughborough Soccer Passing Test ( LSPT ) , and a repeated-sprint test . There were no main effects of supplementation for CMJ , LSPT total time , or best sprint and total sprint time from the repeated-sprint test ( p>0.05 ) . There were also no main effects of supplementation for heart rate , plasma lactate concentration , rating of perceived exertion ( RPE ) , pleasure-displeasure , and perceived activation ( p>0.05 ) . However , there were significant time effects ( p<0.05 ) , with heart rate , plasma lactate concentration , RPE , and perceived activation increasing with time , and pleasure-displeasure decreasing with time . In conclusion , isolated and /or combined CHO and CAF supplementation is not able to improve soccer-related performance tests when performed after a previous training session Abstract The purpose of this study was to determine the recovery rate of football skill performance following resistance exercise of moderate or high intensity . Ten elite football players participated in three different trials : control , low-intensity resistance exercise ( 4 sets , 8–10 repetitions/set , 65–70 % 1 repetition maximum [ 1RM ] ) and high-intensity resistance exercise ( 4 sets , 4–6 repetitions/set , 85–90 % 1RM ) in a counterbalanced manner . In each experimental condition , participants were evaluated pre , post , and at 24 , 48 , 72 h post exercise time points . Football skill performance was assessed through the Loughborough Soccer Passing Test , long passing , dribbling , shooting and heading . Delayed onset muscle soreness , knee joint range of motion , and muscle strength ( 1RM ) in squat were considered as muscle damage markers . Blood sample s analysed for creatine kinase activity , C-reactive protein , and leukocyte count . Passing and shooting performance declined ( P < 0.05 ) post-exercise following resistance exercise . Strength declined post-exercise following high-intensity resistance exercise . Both trials induced only a mild muscle damage and inflammatory response in an intensity-dependent manner . These results indicate that football skill performance is minimally affected by acute resistance exercise independent of intensity suggesting that elite players may be able to participate in a football practice or match after only 24 h following a strength training session Abstract In this study , we examined the reliability and construct validity of new soccer skills tests . Twenty soccer players ( 10 professional and 10 recreational ) repeated trials of passing , shooting , and dribbling skills on different days . Passing and shooting skills required players to kick a moving ball , delivered at constant speed , towards one of Output:	Good discriminative validity was found between playing levels and ages . The LSPT was positively correlated with sprint , dribbling , and agility test ; however , a weak correlation was established with in-game performance . The findings indicate that the LSPT has acceptable test-retest reliability and discriminative validity . However , it may not be a feasible and effective way to interpret the intra-individual change of skill performance in practice .
MS22287	*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 first planned interim analysis ( median follow-up , 3 years ) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival , the primary end point . The results were therefore opened at the recommendation of an independent data and safety monitoring committee . We report 5-year follow-up data on patients enrolled onto the ACTS-GC study . PATIENTS AND METHODS Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were r and omly assigned to receive S-1 after surgery or surgery only . S-1 ( 80 to 120 mg per day ) was given for 4 weeks , followed by 2 weeks of rest . This 6-week cycle was repeated for 1 year . The primary end point was overall survival , and the secondary end points were relapse-free survival and safety . RESULTS The overall survival rate at 5 years was 71.7 % in the S-1 group and 61.1 % in the surgery-only group ( hazard ratio [ HR ] , 0.669 ; 95 % CI , 0.540 to 0.828 ) . The relapse-free survival rate at 5 years was 65.4 % in the S-1 group and 53.1 % in the surgery-only group ( HR , 0.653 ; 95 % CI , 0.537 to 0.793 ) . Subgroup analyses according to principal demographic factors such as sex , age , disease stage , and histologic type showed no interaction between treatment and any characteristic . CONCLUSION On the basis of 5-year follow-up data , postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy Background Radical surgery is the cornerstone in the treatment of resectable gastric cancer . The Intergroup 0116 and MAGIC trials have shown benefit of postoperative chemoradiation and perioperative chemotherapy , respectively . Since these trials can not be compared directly , both regimens are evaluated prospect ively in the CRITICS trial . This study aims to obtain an improved overall survival for patients treated with preoperative chemotherapy and surgery by incorporating radiotherapy concurrently with chemotherapy postoperatively . Methods / design In this phase III multicentre study , patients with resectable gastric cancer are treated with three cycles of preoperative ECC ( epirubicin , cisplatin and capecitabine ) , followed by surgery with adequate lymph node dissection , and then either another three cycles of ECC or concurrent chemoradiation ( 45 Gy , cisplatin and capecitabine ) . Surgical , pathological , and radiotherapeutic quality control is performed . The primary endpoint is overall survival , secondary endpoints are disease-free survival ( DFS ) , toxicity , health-related quality of life ( HRQL ) , prediction of response , and recurrence risk assessed by genomic and expression profiling . Accrual for the CRITICS trial is from the Netherl and s , Sweden , and Denmark , and more countries are invited to participate . Conclusion Results of this study will demonstrate whether the combination of preoperative chemotherapy and postoperative chemoradiotherapy will improve the clinical outcome of the current European st and ard of perioperative chemotherapy , and will therefore play a key role in the future management of patients with resectable gastric cancer . Trial registration clinical trials.gov PURPOSE The Intergroup 0116 trial has demonstrated that postoperative chemoradiotherapy ( CRT ) improves survival in gastric cancer . We retrospectively compared survival and recurrence patterns in two phase I/II studies evaluating more intensified postoperative CRT with those from the Dutch Gastric Cancer Group Trial ( DGCT ) that r and omly assigned patients between D1 and D2 lymphadenectomy . PATIENTS AND METHODS Survival and recurrence patterns of 91 patients with adenocarcinoma of the stomach who had received surgery followed by radiotherapy combined with fluorouracil and leucovorin ( n = 5 ) , capecitabine ( n = 39 ) , or capecitabine and cisplatin ( n = 47 ) were analyzed and compared with survival and recurrence patterns of 694 patients from the DGCT ( D1 , n = 369 ; D2 , n = 325 ) . For both groups , the Maruyama Index of Unresected Disease ( MI ) was calculated and correlated with survival and recurrence patterns . RESULTS With a median follow-up of 19 months in the CRT group , local recurrence rate after 2 years was significantly higher in the surgery only ( DGCT ) group ( 17 % v 5 % ; P = .0015 ) . Separate analysis of CRT patients who underwent a D1 dissection ( n = 39 ) versus DGCT-D1 ( n = 369 ) showed fewer local recurrences after chemoradiotherapy ( 2 % v 8 % ; P = .001 ) , whereas comparison of CRT-D2 ( n = 25 ) versus DGCT-D2 ( n = 325 ) demonstrated no significant difference . CRT significantly improved survival after a microscopically irradical ( R1 ) resection . The MI was found to be a strong independent predictor of survival . CONCLUSION After D1 surgery , the addition of postoperative CRT had a major impact on local recurrence in resectable gastric cancer INTRODUCTION Worldwide , gastric cancer remains one of the most common malignancies . Discouraging survival rates after surgical treatment promote the study of adjuvant therapy . A prospect ively , r and omized , controlled clinical trial was performed in order to determine whether pre-operative and intraoperative radiotherapy improves treatment results of gastrectomy for stomach carcinoma . METHODS From 1993 to 1998 , 112 patients were r and omized and underwent exploratory laparotomy ; among them 78 satisfied protocol requirements and entered in the trial . Patients in the experimental group were treated with pre-operative radiotherapy ( 20 Gy/5 days ) , gastrectomy and intraoperative radiotherapy ( 20 Gy using 8 - 12 electrons ) . Patients in the control group underwent surgery alone . RESULTS Incidence and distribution of post-operative complications were similar in both groups except significantly higher incidence of pancreatitis after surgical treatment . No late radiation-related morbidity was registered . There was no significant difference in survival between the two treatment groups ( Chi(2)=1.026 , df=1 , P=0 . 311 ) as well as in N0 ( Chi(2)=0.0029 , df=1 , P=0.956 ) and T1 - 2 subgroups ( Chi(2)=0.1928 , df=1 , P=0.660 ) . In contrast , combined treatment had marked survival advantage in more advanced stages : in the case of lymph-node involvement ( Chi(2)=4.19 , df=1 , P=0.04 ) and extragastric tumour extension ( Chi(2)=4.118 , df=1 , P=0.042 ) . CONCLUSION The proposed intensive treatment programme is feasible , shows good acute and late tolerance and has the potential to improve survival in patients with locally advanced gastric cancer PURPOSE Preoperative chemotherapy is an accepted st and ard in the treatment of localized esophagogastric adenocarcinoma . Adding radiation therapy to preoperative chemotherapy appears promising , but its definitive value remains unknown . PATIENTS AND METHODS Patients with locally advanced ( uT3 - 4NXM0 ) adenocarcinoma of the lower esophagus or gastric cardia were r and omly allocated to one of two treatment groups : induction chemotherapy ( 15 weeks ) followed by surgery ( arm A ) ; or chemotherapy ( 12 weeks ) followed by chemoradiotherapy ( 3 weeks ) followed by surgery ( arm B ) . Primary outcome was overall survival time . A total of 354 patients were needed to detect a 10 % increase in 3-year survival from 25 % to 35 % by addition of radiation therapy . The study was prematurely closed due to low accrual . RESULTS The median observation time was 46 months . A total of 126 patients were r and omly assigned and 119 eligible patients were evaluated . The number of patients undergoing complete tumor resection was not different between treatment groups ( 69.5 % v 71.5 % ) . Patients in arm B had a significant higher probability of showing pathologic complete response ( 15.6 % v 2.0 % ) or tumor-free lymph nodes ( 64.4 % v 37.7 % ) at resection . Preoperative radiation therapy improved 3-year survival rate from 27.7 % to 47.4 % ( log-rank P = .07 , hazard ratio adjusted for r and omization strata variables 0.67 , 95 % CI , 0.41 to 1.07 ) . Postoperative mortality was nonsignificantly increased in the chemoradiotherapy group ( 10.2 % v 3.8 % ; P = .26 ) . CONCLUSION Although the study was closed early and statistical significance was not achieved , results point to a survival advantage for preoperative chemoradiotherapy compared with preoperative chemotherapy in adenocarcinomas of the esophagogastric junction BACKGROUND AND PURPOSE The role of postoperative chemoradiotherapy in the treatment of patients with gastric cancer with D2 lymph node curative dissection is not well established . In this study , we compared postoperative intensity-modulated radiotherapy plus chemotherapy ( IMRT-C ) with chemotherapy-only in this patient population . MATERIAL S AND METHODS We r and omly assigned patients with D2 lymph node dissection in gastric cancer to IMRT-C or chemotherapy-only groups . The adjuvant IMRT-C consisted of 400 mg of fluorouracil per square meter of body-surface area per day plus 20 mg of leucovorin per square meter of body-surface area per day for 5 days , followed by 45 Gy of IMRT for 5 weeks , with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy . Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of IMRT . Chemotherapy-only group was given the same chemotherapy regimens as IMRT-C group . RESULTS The median overall survival ( OS ) in the chemotherapy-only group was 48 months , as compared with 58 months in the IMRT-C group ; the hazard ratio for death was 1.24 ( 95 % confidence interval , 0.94 - 1.65 ; P=0.122 ) . IMRT-C was associated with increases in the median duration of recurrence-free survival ( RFS ) ( 36 months vs. 50 months ) , the hazard ratio for recurrence was 1.35 ( 95 % confidence interval , 1.03 - 1.78 ; P=0.029 ) . COX multivariate regression analysis showed that lymph node metastasis and TNM stage were both the independent prognostic factors . Rates of all grade adverse events were similar in the two treatment groups . CONCLUSIONS IMRT-C improved RFS , but did not significantly improve OS among patients with D2 lymph node dissection in gastric cancer . Using IMRT plus chemotherapy was feasible and well tolerated in patients with gastric cancer after D2 resection Sixty-two patients with resectable but poor-prognosis gastric carcinoma were r and omized to either no surgical adjuvant therapy or treatment with 5-fluorouracil ( 15 mg/kg by rapid intravenous injection X 3 ) plus radiation ( 3,750 rad in 24 fractions ) initiated 3 1/2 to six weeks postoperatively . Informed consent was obtained after r and omization and only from the 39 r and omized to treatment . Ten patients refused their treatment assignment . The five-year survival rate for patients r and omized to treatment was 23 % , and for those r and omized to no treatment , 4 % ( P less than .05 ) . Both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups ( P = .024 ) and favored treatment assignment . When the treatment assignment group was broken down to those patients actually receiving treatment and those refusing , five-year survival rates were : treated , 20 % ; treatment refusal , 30 % ; controls , 4 % ; the three survival distributions were not significantly different . Thirty-nine percent of patients actually treated had a local-regional component of first clinical recurrence compared with 54 % of those who received no treatment . This study does not establish 5-fluorouracil plus radiation as effective surgical adjuvant therapy for gastric cancer but suggests this approach as a possible fruitful area for continued research . This study also illustrates the potential problems that may be encountered in interpreting results when patients are r and omized to a study before consent is obtained BACKGROUND Adjuvant chemoradiotherapy does not represent the st and ard of care in patients with resected high-risk gastric cancer ; however , results from phase 2 and r and omized trials suggest improvement in overall survival . We assessed the feasibility and toxic effects of chemoradiotherapy as adjuvant treatment in locally advanced gastric cancer . DESIGN Pilot study . SETTING University hospital . PATIENTS Twenty-nine patients with T4N+ or any TN23 gastric cancer previously treated with potentially curative surgery were enrolled . All Output:	We provide a critical , non- systematic review of gastric cancer and discuss the role of perioperative radiation therapy in its treatment
MS22288	*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 project is to develop and evaluate a psycho-educational program that assists nurses to develop stress management plans . Discussion of nursing-specific risk factors , practice with relaxation techniques , and exploration via art are used as interventions . Quantitative and qualitative measures of stress and burnout are conducted pre- and postcourse using the Maslach Burnout Inventory , Draw-a-Person-in-the-Rain Art Assessment , and wellness plans . Descriptive statistics are used , and preliminary analysis indicates that the course is useful in impacting levels of emotional exhaustion . There are opportunities for evolving the program so that more enduring change in self-care is generated Highly stressed employees are subject to greater health risks , increased cost , and productivity losses than those with normal stress levels . To address this issue in an evidence -based manner , worksite stress management programs must be able to engage individuals as well as capture data on stress , health indices , work productivity , and health care costs . In this r and omized controlled pilot , our primary objective was to evaluate the viability and proof of concept for two mind-body workplace stress reduction programs ( one therapeutic yoga-based and the other mindfulness-based ) , in order to set the stage for larger cost-effectiveness trials . A second objective was to evaluate 2 delivery venues of the mindfulness-based intervention ( online vs. in-person ) . Intention-to-treat principles and 2 ( pre and post ) × 3 ( group ) repeated- measures analysis of covariance procedures examined group differences over time on perceived stress and secondary measures to clarify which variables to include in future studies : sleep quality , mood , pain levels , work productivity , mindfulness , blood pressure , breathing rate , and heart rate variability ( a measure of autonomic balance ) . Two hundred and thirty-nine employee volunteers were r and omized into a therapeutic yoga worksite stress reduction program , 1 of 2 mindfulness-based programs , or a control group that participated only in assessment . Compared with the control group , the mind-body interventions showed significantly greater improvements on perceived stress , sleep quality , and the heart rhythm coherence ratio of heart rate variability . The two delivery venues for the mindfulness program produced basically equivalent results . Both the mindfulness-based and therapeutic yoga programs may provide viable and effective interventions to target high stress levels , sleep quality , and autonomic balance in employees 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 Part III of the study on mindfulness-based stress reduction ( MBSR ) describes qualitative data and discusses the implication s of the findings . Study analysis revealed that nurses found MBSR helpful . Greater relaxation and self-care and improvement in work and family relationships were among reported benefits . Challenges included restlessness , physical pain , and dealing with difficult emotions Mindfulness-based stress reduction ( MBSR ) has produced behavioral , psychological , and physiological benefits , but these programs typically require a substantial time commitment from the participants . This study assessed the effects of a shortened ( low-dose [ ld ] ) work-site MBSR intervention ( MBSR-ld ) on indicators of stress in healthy working adults to determine if results similar to those obtained in traditional MBSR could be demonstrated . Participants were r and omized into MBSR-ld and wait-list control groups . Self-reported perceived stress , sleep quality , and mindfulness were measured at the beginning and end of the 6-week intervention . Salivary cortisol was assessed weekly . Significant reductions in perceived stress ( p = .0025 ) and increases in mindfulness ( p = .0149 ) were obtained for only the MBSR-ld group ( n = 22 ) . Scores on the global measure of sleep improved for the MBSR-ld group ( p = .0018 ) as well as for the control group ( p = .0072 ; n = 20 ) . Implication s and future research are discussed This article is the second in a series reporting on research exploring the effects of Mindfulness-based Stress Reduction on nurses and describes the quantitative data . The third article describes qualitative data . Treatment group participants reduced scores on 2 of 3 subscales of the Maslach Burnout Inventory significantly more than wait-list controls ; within-group comparisons for both groups pretreatment and posttreatment revealed similar findings . Changes were maintained as long as 3-month posttreatment . Implication s of these findings are discussed OBJECTIVE To assess the effect of a meditation training program , Mindfulness-Based Stress Reduction ( MBSR ) , on depressive symptoms , psychological status , and disease activity in patients with rheumatoid arthritis ( RA ) through a r and omized , waitlist-controlled pilot study . METHODS Participants were r and omized to either an MBSR group , where they attended an 8-week course and 4-month maintenance program , or to a waitlist control group , where they attended all assessment visits and received MBSR free of charge after study end . Participants received usual care from their rheumatologists throughout the trial . Self-report question naires were used to evaluate depressive symptoms , psychological distress , well-being , and mindfulness . Evaluation of RA disease activity ( by Disease Activity Score in 28 joints ) included examination by a physician masked to treatment status . Adjusted means and mean changes in outcomes were estimated in mixed model repeated measures analyses . RESULTS Sixty-three participants were r and omized : 31 to MBSR and 32 to control . At 2 months , there were no statistically significant differences between groups in any outcomes . At 6 months , there was significant improvement in psychological distress and well-being ( P = 0.04 and P = 0.03 , respectively ) , and marginally significant improvement in depressive symptoms and mindfulness ( P = 0.08 and P = 0.09 , respectively ) . There was a 35 % reduction in psychological distress among those treated . The intervention had no impact on RA disease activity . CONCLUSION An 8-week MBSR class was not associated with change in depressive symptoms or other outcomes at 2-month followup . Significant improvements in psychological distress and well-being were observed following MBSR plus a 4-month program of continued reinforcement . Mindfulness meditation may complement medical disease management by improving psychological distress and strengthening well-being in patients with RA This study sought to develop a stress management program based on the arousal-attribution stress model and to evaluate the effectiveness of the program in reducing anxiety and depression experienced by nursing students . Forty-two sophomore and 34 senior nursing students in a private , sectarian , liberal arts college were r and omly assigned to experimental and control groups . All subjects were given pre- and posttests consisting of the State form of the State-Trait Anxiety Inventory and the Institute for Personality and Ability Testing Depression Scale . Posttest analysis indicated that the experimental group had significantly lower anxiety and depression than the control group ( p less than .05 ) . These results support the use of the arousal-attribution stress model as a theoretical framework for stress management training This study examined the effectiveness of a stress coping program based on mindfulness meditation on the stress , anxiety , and depression experienced by nursing students in Korea . A nonequivalent , control group , pre-posttest design was used . A convenience sample of 41 nursing students were r and omly assigned to experimental ( n=21 ) and control groups ( n=20 ) . Stress was measured with the PWI-SF ( 5-point ) developed by Chang . Anxiety was measured with Spieberger 's state anxiety inventory . Depression was measured with the Beck depression inventory . The experimental group attended 90-min sessions for eight weeks . No intervention was administered to the control group . Nine participants were excluded from the analysis because they did not complete the study due to personal circumstances , result ing in 16 participants in each group for the final analysis . Results for the two groups showed ( 1 ) a significant difference in stress scores ( F=6.145 , p=0.020 ) , ( 2 ) a significant difference in anxiety scores ( F=6.985 , p=0.013 ) , and ( 3 ) no significant difference in depression scores ( t=1.986 , p=0.056 ) . A stress coping program based on mindfulness meditation was an effective intervention for nursing students to decrease their stress and anxiety , and could be used to manage stress in student nurses . In the future , long-term studies should be pursued to st and ardize and detail the program , with particular emphasis on studies to confirm the effects of the program in patients with diseases , such as cancer Mindfulness describes a state of consciousness in which individuals attend to ongoing events and experiences in a receptive and non-judgmental way . The present research investigated the idea that mindfulness reduces emotional exhaustion and improves job satisfaction . The authors further suggest that these associations are mediated by the emotion regulation strategy of surface acting . Study 1 was a 5-day diary study with 219 employees and revealed that mindfulness negatively related to emotional exhaustion and positively related to job satisfaction at both the within- and the between-person levels . Both relationships were mediated by surface acting at both levels of analysis . Study 2 was an experimental field study , in which participants ( N = 64 ) were r and omly assigned to a self-training mindfulness intervention group or a control group . Results revealed that participants in the mindfulness intervention group experienced significantly less emotional exhaustion and more job satisfaction than participants in the control group . The causal effect of mindfulness self-training on emotional exhaustion was mediated by surface acting . Implication s for using mindfulness and mindfulness training interventions in organizational research and practice are discussed in conclusion This study implemented an innovative new model of delivering a Mindfulness-Based Stress Reduction ( MBSR ) program that replaces six of the eight traditional in-person sessions with group telephonic sessions ( tMBSR ) and measured the program 's impact on the health and well-being of nurses employed within a large health care organization . As part of a nonr and omized pre – post intervention study , 36 nurses completed measures of health , stress , burnout , self-compassion , serenity , and empathy at three points in time . Between baseline ( Time 1 ) and the end of the 8-week tMBSR intervention ( Time 2 ) , participants showed improvement in general health , t(37 ) = 2.8 , p < .01 , decreased stress , t(37 ) = 6.8 , p < .001 , decreased work burnout , t(37 ) = 4.0 , p < .001 , and improvement in several other areas . Improvements were sustained 4 months later ( Time 3 ) , and individuals who continued their MBSR practice after the program demonstrated better outcomes than those that did not . Findings suggest that the tMBSR program can be a low cost , feasible , and scalable intervention that shows positive impact on health and well-being , and could allow MBSR to be delivered to employees who are otherwise unable to access traditional , on-site programs This qualitative study assesses the experience of an intervention that provided spiritually based self-management tools to hospital-based nurses . Drawing on wisdom traditions of the major world religions , the eight point program can be practice d by adherents to any religious faith , or those outside of all traditions . Five of eight program points were perceived as directly useful in improving the nurses ’ workplace interactions and enhancing fulfillment of compassionate caregiving missions . The findings suggest that this program can be an effective intervention among nurses in dealing with the dem and s of the healthcare environment and may be a re source for continuing education curricula Background . Nursing students experiencing debilitating test anxiety may be unable to demonstrate their knowledge and have potential for poor academic performance . Method . A biofeedback‐assisted relaxation training program was created to reduce test anxiety . Anxiety was measured using Spielberger 's Test Anxiety Inventory and monitoring peripheral skin temperature , pulse , and respiration rates during the training . Participants were introduced to diaphragmatic breathing , progressive muscle relaxation , and autogenic training . Results . Statistically significant changes occurred in respiratory rates and skin temperatures during the diaphragmatic breathing session ; respiratory rates and peripheral skin temperatures during progressive muscle relaxation session ; respiratory and pulse rates , and peripheral skin temperatures during the autogenic sessions . No statistically significant difference was noted between the first and second TAI . Subjective test anxiety scores of the students did not decrease by the end of training . Conclusion . Autogenic training session was most effective in showing a statistically significant change in decreased respiratory and pulse rates and increased peripheral skin temperature AIM This paper reports a study to determine the effectiveness of autogenic training in reducing anxiety in nursing students . BACKGROUND Nursing is stressful , and nursing students also have the additional pressures and uncertainties shared with all academic students . Autogenic training is a relaxation technique consisting of six mental exercises and is aim ed at relieving tension , anger and stress . Meta- analysis has found large effect sizes for autogenic trainings intervention comparisons , medium effect sizes against control groups , and no effects when compared with other psychological therapies . A controlled trial with 50 nursing students found that the number of certified days off sick was reduced by autogenic training compared with no treatment , and a second trial with only 18 students reported greater improvement in Trait Anxiety , but not State Anxiety , compared with untreated controls . METHODS A r and omized controlled trial with three parallel arms was completed in 1998 with 93 nursing students aged 19 - 49 years . The setting was a university college in the United Kingdom . The treatment group received eight weekly sessions of autogenic training , the attention control group received eight weekly sessions of laughter therapy , and the time control group received no intervention . The outcome measures were the State-Trait Anxiety Inventory , the Maslach Burnout Inventory , blood pressure and pulse rate completed at baseline , 2 months ( end of treatment ) Output:	Meta- analysis suggests that mindfulness-based interventions may be effective in significantly reducing state anxiety and depression at posttreatment and state anxiety and trait anxiety at follow-up . Qualitative studies and uncontrolled studies shed light on benefits overlooked in RCTs , including improvements in the well-being of individuals ( e.g. inner state of calmness , awareness and enthusiasm ) and improved performance at work ( better communication with colleagues and patients , higher sensitivity to patients ' experiences , clearer analysis of complex situations and emotional regulation in stressful context s ) . Mindfulness appeared to improve nurses ' mental health significantly . It could be used in worksite health promotion programmes . Only a few studies have explored the impact of mindfulness on nurses ' professional behaviours and their relationships with patients and colleagues .
MS22289	*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 Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces mortality among survivors of acute myocardial infa rct ion , but whether to use ACE inhibitors in all patients or only in selected patients is uncertain . METHODS We screened 6676 consecutive patients with 7001 myocardial infa rct ions confirmed by enzyme studies . A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction ( ejection fraction , < or = 35 percent ) . On days 3 to 7 after infa rct ion , 1749 patients were r and omly assigned to receive oral tr and olapril ( 876 patients ) or placebo ( 873 patients ) . The duration of follow-up was 24 to 50 months . RESULTS During the study period , 304 patients ( 34.7 percent ) in the tr and olapril group died , as compared with 369 ( 42.3 percent ) in the placebo group ( P = 0.001 ) . The relative risk of death in the tr and olapril group , as compared with the placebo group , was 0.78 ( 95 percent confidence interval , 0.67 to 0.91 ) . Tr and olapril also reduced the risk of death from cardiovascular causes ( relative risk , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ; P = 0.001 ) and sudden death ( relative risk , 0.76 ; 95 percent confidence interval , 0.59 to 0.98 ; P = 0.03 ) . Progression to severe heart failure was less frequent in the tr and olapril group ( relative risk , 0.71 ; 95 percent confidence interval , 0.56 to 0.89 ; P = 0.003 ) . In contrast , the risk of recurrent myocardial infa rct ion ( fatal or nonfatal ) was not significantly reduced ( relative risk , 0.86 ; 95 percent confidence interval , 0.66 to 1.13 ; P = 0.29 ) . CONCLUSIONS Long-term treatment with tr and olapril in patients with reduced left ventricular function soon after myocardial infa rct ion significantly reduced the risk of overall mortality , mortality from cardiovascular causes , sudden death , and the development of severe heart failure . That mortality was reduced in a r and omized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infa rct ion Background The aim of the present study was to investigate whether a previously shown survival benefit result ing from routine early invasive management of unselected patients with acute non-ST-segment elevation myocardial infa rct ion ( NSTEMI ) may differ according to smoking status and age . Methods Post-hoc analysis of a prospect i ve observational cohort study of consecutive patients admitted for NSTEMI in 2003 ( conservative strategy cohort [ CS ] ; n = 185 ) and 2006 ( invasive strategy cohort [ IS ] ; n = 200 ) . A strategy for transfer to a high-volume invasive center and routine early invasive management was implemented in 2005 . Patients were subdivided into current smokers and non-smokers ( including ex-smokers ) on admission . Results The one-year mortality rate of smokers was reduced from 37 % in the CS to 6 % in the IS ( p < 0.001 ) , and from 30 % to 23 % for non-smokers ( p = 0.18 ) . Non-smokers were considerably older than smokers ( median age 80 vs. 63 years , p < 0.001 ) . The percentage of smokers who underwent revascularization ( angioplasty or coronary artery bypass grafting ) within 7 days increased from 9 % in the CS to 53 % in the IS ( p < 0.001 ) . The corresponding numbers for non-smokers were 5 % and 27 % ( p < 0.001 ) . There was no interaction between strategy and age ( p = 0.25 ) , as opposed to a significant interaction between strategy and smoking status ( p = 0.024 ) . Current smoking was an independent predictor of one-year mortality ( hazard ratio 2.61 , 95 % confidence interval 1.43 - 4.79 , p = 0.002 ) . Conclusions The treatment effect of an early invasive strategy in unselected patients with NSTEMI was more pronounced among smokers than non-smokers . The benefit for smokers was not entirely explained by differences in baseline confounders , such as their younger age OBJECTIVES This study sought to compare the relation between smoking and the 30-day and 6-month outcome after acute myocardial infa rct ion in an Israeli nationwide survey . BACKGROUND Studies before and during the thrombolytic era reported similar or lower early mortality after acute myocardial infa rct ion in smokers than in nonsmokers . This finding is intriguing and may be misleading because numerous epidemiologic studies have clearly shown that smoking is an independent risk factor for atherosclerosis , myocardial infa rct ion and death . METHODS The study cohort comprised 999 consecutive patients with an acute myocardial infa rct ion from a prospect i ve nationwide survey conducted during January and February 1994 in all coronary care units operating in Israel . The prognosis of 367 patients ( 37 % ) who were smokers ( current smokers and those who smoked up to 1 month before admission ) was compared with that of 632 nonsmokers ( past smokers or those who never smoked ) . RESULTS Smokers were on average 10 years younger and were more frequently men and patients with a family history of coronary heart disease and inferior infa rct ion and less frequently patients with a previous infa rct ion or a history of angina , hypertension and diabetes than nonsmokers . Smokers also had a lower incidence of congestive heart failure on admission or during the hospital period . Thrombolytic therapy ( 49 % vs. 40 % , p < 0.01 ) and aspirin ( 89 % vs. 80 % , p < 0.001 ) were administered more frequently in smokers than nonsmokers . The crude 30-day ( 6.0 % vs. 15.7 % ) and cumulative 6-month ( 7.9 % vs. 21.5 % ) mortality rates were significantly lower ( p < 0.0001 for both ) in smokers than nonsmokers , respectively . However , after adjustment for age , baseline characteristics , thrombolytic therapy and invasive coronary procedures , the lower 30-day ( odds ratio [ OR ] 0.75 , 95 % confidence interval [ CI ] 0.43 to 1.29 , p = 0.30 ) and 6-month ( hazard ratio 0.84 , 95 % CI 0.54 to 1.30 , p = 0.42 ) mortality rates in smokers and nonsmokers were not significantly different . The model had a power of 0.80 for OR 0.50 , with alpha 0.1 . CONCLUSIONS In our nationwide survey , the seemingly better prognosis of smokers early after acute myocardial infa rct ion was no longer evident after adjustment for baseline and clinical variables and may be explained by their younger age and a more favorable risk profile . Smokers develop acute myocardial infa rct ion a decade earlier than nonsmokers . Efforts to lower the prevalence of smoking should continue OBJECTIVES Our purpose was to evaluate the relation between smoking and the outcomes of patients receiving thrombolysis for acute myocardial infa rct ion . BACKGROUND A paradoxic beneficial effect has been observed in smokers with a myocardial infa rct ion . We analyzed outcomes and baseline characteristics of 11,975 nonsmokers , 11,117 ex-smokers and 17,507 current smokers in a multinational trial of thrombolysis for acute myocardial infa rct ion . METHODS Patients were r and omized to one of four thrombolytic protocol s. An angiographic sub study in 2,431 patients evaluated reperfusion , reocclusion and ventricular function . Effects of smoking were evaluated by logistic regression analysis after adjustment for age and gender . A mortality model evaluated the simultaneous effect of baseline characteristics on the prognostic importance of smoking . These processes were performed with data from both the main trial and the angiographic sub study ; then angiographic factors ( coronary anatomy , patency and ejection fraction ) were added to the model . RESULTS Smokers were significantly younger by a mean of 11 years ) and had less comorbidity or severe coronary artery disease than nonsmokers . Nonsmokers had significantly higher hospital and 30-day mortality rates ( 9.9 % and 10.3 % , respectively ) than smokers ( 3.7 % vs. 4 % , respectively , both p < 0.001 ) and more in-hospital complications . The unadjusted odds ratio for 30-day mortality in nonsmokers was 3.36 ( 95 % confidence interval [ CI ] 2.08 to 5.41 ) , 1.21 ( 95 % CI 0.71 to 2.08 ) after adjustment for age and gender and 1.08 ( 95 % CI 0.59 to 1.96 ) after adjustment for all clinical baseline characteristics . CONCLUSIONS Smokers receiving thrombolysis for acute myocardial infa rct ion presented 11 years earlier than nonsmokers , which generally accounted for their better outcome . When other differences in clinical and angiographic baseline factors and therapeutic responses were evaluated , no significant difference in mortality was seen between smokers and nonsmokers BACKGROUND Despite advances in pharmacologic therapy and invasive management strategies for patients with non-ST-segment elevation acute coronary syndromes ( NSTE ACS ) , these patients still suffer substantial morbidity and mortality . OBJECTIVE The objective of this study was to analyze independent predictors of 1-year mortality in patients with high-risk NSTE ACS . DESIGN AND PARTICIPANTS A total of 9,978 patients were assigned to receive enoxaparin or unfractionated heparin ( UFH ) in this prospect i ve , r and omized , open-label , international trial . MEASUREMENTS Vital status at 1 year was collected . Univariable and multivariable predictors of 1-year mortality were identified . Three different multivariable regression models were constructed to identify : ( 1 ) predictors of 30-day mortality ; ( 2 ) predictors of 1-year mortality ; ( 3 ) predictors of 1-year mortality in 30-day survivors . The last model is the focus of this paper . RESULTS Overall , 9,922 ( 99.4 % ) of patients had 1-year follow-up . Of the 56 patients ( 37 UFH-assigned and 19 enoxaparin-assigned ) without 1-year data , 11 patients were excluded because of withdrawal of consent , and 45 could not be located . One-year mortality was 7.5 % ( 7.7 % enoxaparin-assigned patients ; 7.3 % UFH-assigned patients ; P = 0.4 ) . In patients surviving 30 days after enrollment , independent predictors of 1-year mortality included factors known at baseline such as increased age , male sex , decreased weight , having ever smoked , decreased creatinine clearance , ST-segment depression , history of diabetes , history of angina , congestive heart failure , coronary artery bypass grafting , increased heart rate , rales , increased hematocrit , lowered hemoglobin , and higher platelet count . Factors predictive of mortality during the hospitalization and 30-day follow-up period were decreased weight at 30 days from baseline , atrial fibrillation , decreased nadir platelet , no use of beta-blockers and statins up to 30 days , and not receiving an intervention ( c-index = 0.82 ) . CONCLUSIONS Easily determined baseline clinical characteristics can be used to predict 1-year mortality with reasonable discriminative power . These models corroborate prior work in a contemporary aggressively managed population . A model to predict 1-year mortality in patients surviving at least 30 days may be quite helpful to healthcare providers in setting expectations and goals with patients after ACS BACKGROUND Smoking is known to be a strong risk factor for premature atherosclerosis , myocardial infa rct ion , and sudden cardiac death . Unexpectedly , in the reperfusion era , investigators have reported that patients who smoke have a more favorable prognosis after thrombolysis compared with non-smokers . Since smoking is associated with a relatively hyper-coagulable state , we hypothesized that the coronary occlusion responsible for infa rct ion may be primarily thrombotic , with improved outcome relating to enhanced patency or the absence of a residual stenosis after thrombolytic therapy . METHODS AND RESULTS To examine this issue , we evaluated 1619 patients treated with TPA , urokinase , or both in six consecutive myocardial infa rct ion trials , of whom 878 ( 54 % ) were currently smoking . Patients underwent 90-minute and predischarge catheterizations , which were quantified blinded to the patients ' Output:	Conclusion The " smoker 's paradox " was observed in some studies of AMI patients in the pre-thrombolytic and thrombolytic era , whereas no studies of a contemporary population with acute coronary syndrome have found evidence for such a paradox
MS22290	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A double-blind study was design ed to investigate the effects of antenatal glucocorticoids on the incidence of respiratory distress syndrome ( RDS ) in 128 premature human infants . There was a significant reduction ( P<0.05 ) in the incidence of RDS in the betamethasone-treated infants to 8.7 % compared to an incidence of 22.6 % in the saline-treated controls and 25.0 % in infants whose mothers received methylprednisolone . The effectiveness of betamethasone in reducing RDS was limited to premature infants delivered to mothers with intact fetal membranes and with an initial L/S ratio less than 2.0 . The time between administration of the glucocorticoid and delivery did not significantly affect the incidence of RDS in this study . The failure of methylprednisolone to reduce the development of RDS in premature infants suggests its potential use in maternal therapy during pregnancy with minimal effects on fetal maturation A prospect i ve double-blind r and omized clinical trial was carried out to determine whether glucocorticoid treatment reduces the risk of respiratory distress syndrome ( RDS ) in prematurely born infants . There were 127 infants born to 122 mothers who received either steroid ( dexamethasone phosphate ) or placebo . No differences between groups occurred in risk factors for RDS ( eg , prepartum asphyxia , male sex , cesarean section ) . When those who received a full course of dexamethasone therapy were compared with those who received placebo , a significant reduction was found in risk , severity , and deaths due to RDS . An increased incidence of infection in mothers treated with steroid was evident , particularly after premature rupture of membranes . We conclude that steroids are effective in reducing risk of RDS , but safer and more efficacious approaches for the prevention of RDS should be sought One hundred forty-six pregnant women were enrolled in a prospect i ve double-blind study to assess the effectiveness and side-effects of antenatal administration of betamethasone in the prevention of respiratory distress syndrome ( RDS ) in potentially premature infants . On admission to the study , the women were given , at r and om , either 12 mg of betamethasone or placebo . The same dose was repeated 24 hours later and then weekly up to 34 weeks of gestation . Gestational age of the infants ranged from 25 to 34 weeks , and birth weights ranged between 730 and 2,650 gm . Statistically significant differences in favor of the infants in the betamethasone group were found in the incidence of RDS , 20.7 % in the betamethasone group compared with 59.5 % in the control group ( P less than .005 ) ; in the severity of RDS ( P less than .05 ) ; and in the death rate ( P less than .05 ) . A higher incidence of hypoglycemia was found among infants in the betamethasone group ( P less than .05 ) . Prolonged rupture of the membranes played no protective role against RDS , and the incidence of infection was similar in both groups A r and omized study was conducted to investigate the effects of antenatal corticosteroids and ampicillin in the management of preterm pregnancies under 34 weeks complicated by premature rupture of membranes . Patients with documented lecithin/sphingomyelin ( L/S ) ratios of less than 2.0 and a singleton gestation were eligible to participate in the study . One hundred sixty-five patients qualified and were r and omized , using sealed envelopes , to four study groups . All patients were followed expectantly . Group I ( 41 patients ) received neither ampicillin nor corticosteroids . Group II ( 43 patients ) received 24 mg of antenatal betamethasone . Group III ( 37 patients ) received 2 g of intravenous ampicillin every 6 hours , with discontinuation of antibiotic therapy if cultures were negative for pathogenic bacteria . Group IV ( 44 patients ) received both corticosteroids and ampicillin as described for groups II and III , respectively . Compared with patients not receiving corticosteroids , those administered antenatal corticosteroids experienced a reduction in the incidences of respiratory distress syndrome ( 53 versus 26 % ) , bronchopulmonary dysplasia ( 23 versus 9 % ) , severe grade s of intracranial hemorrhage ( 15 versus 3 % ) , and patent ductus arteriosus ( 18 versus 6 % ) , with no difference in the incidence of maternal or neonatal infection . Compared with patients not receiving antenatal antibiotics , the group of patients treated with ampicillin on admission had a lower incidence of clinical chorioamnionitis ( 4 versus 26 % ) and neonatal sepsis ( 5 versus 10 % ) . This reduction in infectious morbidity by antenatal ampicillin was restricted to those patients ( 28.4 % of the study population ) colonized with group B streptococci . This r and omized study suggests that the outcome of preterm pregnancies with premature rupture of membranes and an L/S ratio less than 2.0 can be improved by the concurrent use of corticosteroids and ampicillin A prospect i ve , r and omized study was conducted comparing the use of betamethasone and early delivery , early delivery alone , and expectant management in patients in the 28th to 34th week of pregnancy with premature rupture of the membranes ( PROM ) . Tocolytic drugs were used to delay delivery until 24 hours had elapsed after the first dose of steroid or 24 to 48 hours of latent period had elapsed in the second group . There were ho significant differences in maternal age , gestation at PROM , maximum maternal temperature , birth weights , maternal hospital days , respiratory distress , maternal sepsis , or delivery routes in the three groups . Comparisons with one other similar prospect i ve , r and omized study support the concept that expectant management offers less risk from tocolytic side effects A prospect i ve r and omized study involving patients with premature rupture of the membranes between the twenty-eighth week and the thirty-fourth week of pregnancy was conducted . Patients with chorioamnionitis , advanced labor , and fetal distress , as well as those with mature lecithin/sphingomyelin ratios and /or Gram stains positive for bacteria , were delivered immediately . The remaining patients were r and omized . One group received betamethasone . Tocolytic agents were used in this group when necessary . After 48 hours all patients given corticosteroids ( CS group ) were delivered ) . The second group was managed expectantly ( EM group ) and were delivered only when spontaneous labor or infection occurred . A total of 160 patients were r and omized , 80 in each group . Maternal outcome , including chorioamnionitis and cesarean section rates , was not different ; however , the endometritis rate was significantly higher in the CS group ( p less than 0.05 ) . Neonatal outcome did not differ in mean birth weights , perinatal death rates , neonatal infections , or incidences of respiratory distress . The frequency of prolonged hospital stay ( greater than 4 weeks ) was higher in the neonates in the CS group ( p less than 0.01 ) . The conclusion is that corticosteroids and active management in patients with premature rupture of the membranes and premature gestations do not decrease the incidence of respiratory distress syndrome or perinatal mortality and may aggravate certain infectious complications OBJECTIVE To assess whether administration of dexamethasone in women with preterm premature rupture of membranes ( PPROM ) has an effect on the prevalence of maternal sepsis , neonatal respiratory distress syndrome ( RDS ) , perinatal mortality and neonatal sepsis in a developing country . SETTING Six public hospitals in South Africa that deal mainly with indigent women . METHOD A multicentre , double-blind , placebo-controlled , r and omised trial was performed on women with PPROM and fetuses of 28 - 34 weeks ' gestation or clinical ly estimated fetal weight between 1,000 and 2,000 g if the gestational age was unknown . Women were r and omised to receive either dexamethasone 24 mg intramuscularly or placebo in two divided doses 24 hours apart . All women received amoxycillin and metronidazole and were managed expectantly . Hexoprenaline was administered if contractions occurred within the first 24 hours after admission to the trial . OUTCOME MEASURES The maternal outcome measures were clinical chorio-amnionitis and postpartum sepsis . The outcome measures for infants were perinatal death , RDS , mechanical ventilation , necrotising enterocolitis , and neonatal infection within 72 hours . RESULTS One hundred and two women who delivered 105 babies were r and omised to the dexamethasone group and 102 women who delivered 103 babies , to the placebo group . The groups were well balanced with regard to clinical features . There was a trend towards fewer perinatal deaths in the dexamethasone group : 4 compared with 10 ( P = 0.16 , odds ratio 0.37 , 95 % confidence intervals 0.09 - 1.34 ) . A sub analysis of mothers who delivered more than 24 hours after admission to the study and their infants revealed a significant reduction in perinatal deaths ; 1 death in the dexamethasone group and 7 in the placebo group , P = 0.047 ( Fisher 's exact test ) . No woman in either group developed severe sepsis , and the incidence of sepsis in the women did not differ significantly . Eleven infants in each group developed sepsis . CONCLUSION This is the first r and omised trial in women with PPROM to compare the effects of the use of corticosteroids with placebo , where all women received prophylactic antibiotics concomitantly with the corticosteroids . A trend towards an improved perinatal outcome was demonstrated in the women who received dexamethasone . There was no increased risk of infection in the women or their infants where dexamethasone was administered . Administration of corticosteroids to women with PPROM has more advantages than disadvantages in developing countries The use of hydrocortisone and timed delivery was compared to expectant management of pregnancies complicated by preterm prematurely ruptured membranes in a prospect i ve r and omized trial of 73 patients . The incidence of maternal and neonatal complications was compared . There was no significant difference in the incidence of respiratory distress syndrome . Steroid-treated mothers had an increased incidence of postpartum febrile morbidity . We conclude that treatment of women with preterm prematurely ruptured membranes with hydrocortisone and timed delivery offers no advantage over expectant management Output:	the benefit of corticosteroids clearly outweighs their potential harmful effects .
MS22291	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aim The aim of this study was to determine whether an educational intervention delivered by a computer aided learning package improved the sensitivity and specificity of dentists ' restorative treatment decisions Method The study was a r and omised controlled study using a Solomon three-group design . Ninety-five dentists were r and omly allocated to the three study groups . One group of dentists read the radiographs pre and post an educational intervention , a second group read the radiographs once , after the intervention , and a third group read the radiographs twice , but received no intervention . On each occasion the dentists read 24 surfaces on each of 15 radiographs and made 360 decisions on how certain they were about restoring the tooth surface . Comparisons of mean sensitivity , specificity and areas under ROC curves were made within and between the study groups . Kappa values were used to assess changes in the level of agreement between dentists . Results There were no significant changes in sensitivity , specificity or area under ROC curves caused by the intervention . There was no evidence that the level of agreement between the dentists improved after the intervention . Conclusion A computer aided learning package had no effect on dentists ' treatment decision-making behaviour Objective To investigate the effectiveness and cost-effectiveness of different guideline implementation strategies , using the Scottish Intercollegiate Guidelines Network ( SIGN ) Guideline 42 ' Management of unerupted and impacted third molar teeth ' ( published 2000 ) as a model . Design A pragmatic , cluster RCT ( 2 × 2 factorial design ) .Subjects Sixty-three dental practice s across Scotl and . Clinical records of all 16—24-year-old patients over two , four-month periods in 1999 ( pre-intervention ) and 2000 ( post-intervention ) were search ed by a clinical research er blind to the intervention group . Data were also gathered on the costs of the interventions . Interventions Group 1 received a copy of SIGN 42 Guideline and had an opportunity to attend a postgraduate education course ( PGEC ) . In addition to this , group 2 received audit and feedback ( A and F ) . Group 3 received a computer aided learning ( CAL ) package . Group 4 received A and F and CAL.Principal outcome measurement The proportion of patients whose treatment complied with the guideline . Results The weighted t-test for A and F versus no A and F ( P=0.62 ) and CAL versus no CAL ( P=0.76 ) were not statistically significant . Given the effectiveness results ( no difference ) the cost effectiveness calculation became a cost-minimisation calculation . The minimum cost intervention in the trial consisted of providing general dental practitioners ( GDPs ) with guidelines and the option of attending PGEC courses . Routine data which subsequently became available showed a Scotl and -wide fall in extraction s prior to data collection . Conclusion In an environment in which pre-intervention compliance was unexpectedly high , neither CAL nor A and F increased the dentists ' compliance with the SIGN guideline compared with mailing of the guideline and the opportunity to attend a postgraduate course . The cost of the CAL arm of the trial was greater than the A and F arm . Further work is required to underst and dental professionals ' behaviour in response to guideline implementation strategies Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Objective To assess the effect of educational outreach visits on antibiotic prescribing for acute dental pain in primary care . Study design R and omised controlled trial ( RCT ) . Setting General dental practice s in four health authority areas in Wales . Subjects and methods General dental practitioners were recruited to the study and r and omly allocated to one of the three study groups ( control group , guideline group or intervention group ) . Following the intervention , practitioners completed a st and ardised question naire for each patient that presented with acute dental pain . Interventions The control group received no intervention . The guideline group received educational material by post . The intervention group received educational material by post and an academic detailing visit by a trained pharmacist . The educational material included evidence -based guidelines on prescribing for acute dental pain and patient information leaflets . Main outcome measures The number of antibiotic prescriptions issued to patients presenting with dental pain and the number of ' inappropriate ' antibiotic prescriptions . Antibiotics were considered to be inappropriate if the patient did not have symptoms indicative of spreading infection . Results A total of 1,497 completed question naires were received from 23 , 20 and 27 general dental practitioners in the control , guideline and intervention group respectively . Patients in the intervention group received significantly fewer antibiotic prescriptions than patients in the control group ( OR ( 95 % CI ) 0.63 ( 0.41 , 0.95 ) ) and significantly fewer inappropriate antibiotic prescriptions ( OR ( 95 % CI ) 0.33 ( 0.21 , 0.54 ) ) . However , antibiotic and inappropriate antibiotic prescribing were not significantly different in the guideline group compared to the control group ( OR ( 95 % CI ) 0.83 ( 0.55 , 1.21 ) and OR ( 95 % CI ) 0.82 ( 0.53 , 1.29 ) respectively ) . Conclusions Strategies based upon educational outreach visits may be successfully employed to rationalise antibiotic prescribing by dental practitioners Background Routine oral examination ( ROE ) refers to periodic monitoring of the general and oral health status of patients . In most developed Western countries a decreasing prevalence of oral diseases underpins the need for a more individualised approach in assigning individualised recall intervals for regular attendees instead of systematic fixed intervals . From a quality -of-care perspective , the effectiveness of the widespread prophylactic removal of m and ibular impacted asymptomatic third molars ( MIM ) in adolescents and adults is also question able . Data on the effectiveness of appropriate interventions to tackle such problems , and for promoting continuing professional development in oral health care are rare . Methods / design This study is a cluster r and omised controlled trial with groups of GDPs as the unit of r and omisation . The aim is to determine the effectiveness and efficiency of small group quality improvement on professional decision-making of general dental practitioners ( GDPs ) in daily practice . Six peer groups ( ' IQual-groups ' ) shall be r and omised either to the intervention arm I or arm II . Groups of GDPs allocated to either of these arms act as each other 's control group . An IQual peer group consists of eight to ten GDPs who meet in monthly structured sessions scheduled for discussion on practice -related topics . GDPs in both trial arms receive recently developed evidence -based clinical practice guidelines ( CPG ) on ROE or MIM . The implementation strategy consists of one interactive IQual group meeting of two to three hours . In addition , both groups of GDPs receive feedback on personal and group characteristics , and are invited to make use of web-based patient risk vignettes for further individual training on risk assessment policy . Reminders ( flow charts ) will be sent by mail several weeks after the meeting . The main outcome measure for the ROE intervention arm is the use and appropriateness of individualised risk assessment in assigning recall intervals , and for the MIM-intervention group the use and appropriateness of individualised m and ibular impacted third molar risk management . Both groups act as each other 's control . Pre-intervention data will be collected in study months one through three . Post-intervention data collection will be performed after nine months AIM To test the hypothesis that an increased utilization of nickel-titanium rotary instrumentation ( NTRI ) by general dental practitioners will lead to an increased frequency of good quality root fillings . A second aim was to determine whether the educational format would exert influence on the quality . METHODOLOGY Dentists were assigned at r and om to three intervention groups : a 4-h lecture ( L-group , n = 40 ) ; a 4-h lecture plus a full day h and s-on course ( LH-group , n = 40 ) ; or a control group receiving no instruction ( n = 68 ) . The control group received education later on in the study . Radiographs of two root filled molar teeth per dentist were selected at r and om before the start of the education program and after a 6-month clinical learning period . Using length , seal and shape of root-fillings a 5-level variable was created . RESULTS The rate of good quality root fillings increased after the introduction of NTRI . Calculated over all types of roots the frequency of excellent ( score 1 ) root fillings increased from 31 % to 51 % ( P = 0.006 ) in the L-group and from 27 % to 47 % ( P = 0.016 ) in the LH-group . The frequency of low quality root-fillings ( score 5 ) dropped in the L-group from 22 % to 16 % ( P = 0.29 ) and in the LH-group from 13 % to 9 % ( P = 0.48 ) . No statistically significant difference was seen among the controls . CONCLUSIONS When NTRI technology replaced manual stainless steel techniques the rate of good quality root fillings increased . A significant drop in the rate of low quality root fillings was not found The objective of this study was twofold , namely to evaluate the effectiveness of a dental clinical practice guideline on the management of asymptomatic impacted lower third molars ( i ) on referral rates and ( ii ) on dentists ' change in knowledge . A two-arm cluster r and omized controlled trial , with pre- and post-test assessment s , was conducted . A guideline was implemented by multifaceted interventions ( i.e. feedback , reminders , and an interactive meeting ) . The effect was evaluated after 1 yr by repeating the baseline question naire and by monitoring the number of patients who were referred for removal of their asymptomatic impacted m and ibular third molars . Instruments were question naires for detecting changes in knowledge , patient records , and panoramic radiographs . The knowledge of dentists regarding asymptomatic m and ibular third molar management was found to increase significantly in the intervention group as compared to the control group . There was no statistically significant difference between the groups in guideline -consistent patient referral rates at the post-test assessment . It was concluded that the methodology employed for dissemination and implementation of a clinical practice guideline on asymptomatic m and ibular third molar management improves dentists ' knowledge on this topic and is effective in improving decision-making in simulated cases ; however , no clinical effect was demonstrated BACKGROUND Continuing education is incumbent upon dentists as health professionals , but its promotion may be required , particularly in order to ensure regular professional updating . Continuing professional development may be delivered in a variety of ways , and new strategies and techniques must be evaluated for effectiveness . AIM To evaluate the effectiveness of two interventions utilizing the philosophies and techniques of the discipline of Quality Improvement . METHOD A self- assessment instrument ( a manual ) for quality dental practice was developed using the Delphi technique . A r and omized , controlled trial of the interventions was conducted under field conditions for dental practice in Victoria , Australia . Dentists in Test Groups 1 and 2 completed the self- assessment manual , and received relevant references and their own scores for the manual in comparison with empirical st and ards . Dentists in Test Group 1 also attended a continuing education course on Quality Improvement . Dentists in Control Group 1 completed the manual only and received feedback of their scores . Dentists in Test Groups 1 and 2 , and in Control Group 1 completed the manual again after 1 year as a post-intervention follow-up . Dentists in Control Group 2 completed the manual only at 1 year . RESULTS The intervention involving self- assessment , receipt of scores and references for the manual result ed in modest improvements in total scores for dentists after 1 year , although a response bias was apparent . CONCLUSION An effective method of facilitating change in quality dental practice was identified . Assessment of strategies and techniques for professional development of dentists should include observation of patterns of participation This study evaluated the effects of three modes of education on dentists ' knowledge , attitudes , and use of pit and fissure sealants . A r and omly Output:	A black box combination of interventions was rigorously evaluated and showed moderate impact on patient care . This finding suggests that multi method and multiphased CPD has potential for the greatest impact .
MS22292	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIM To evaluate , in young adults , the effect of different preventive programmes on oral hygiene and to determine whether the variables investigated are predictors of gingival health . MATERIAL AND METHODS This r and omized , blinded , parallel , controlled clinical study examined the effectiveness of three dental health programmes . Four hundred subjects aged 20 - 27 years , 211 males and 189 females , participated in the study . They were recruited from a Public Dental Service clinic and from a private dental practice in Jönköping , Sweden . The effect of the programmes on plaque and gingivitis was evaluated over a 3-year period . The programmes included activities that were adapted for individuals as well as for groups . The plaque indices ( PLI ) and gingival indices ( GI ) were used to evaluate the programmes . RESULTS All programmes result ed in a decrease in PLI and GI . The greatest decrease was found in the group that was followed-up every 2 months . Professional tooth cleaning was non-significant for the clinical result . Gingival health at baseline , participation in any of the test programmes , and knowledge of the dental diseases caries , gingivitis or periodontitis were significant predictors of good gingival health . CONCLUSIONS The study confirms the efficacy of three different preventive programmes in reducing supragingival plaque and gingival inflammation . Professional tooth cleaning provided no clinical benefit beyond that derived from individual and group-based health education The present report describes the result of a clinical trial in which a group of adults have been maintained on a proper oral hygiene st and ard over a 6-year period . In 1971 - -72 , 375 individuals were recruited to a test group and 180 to a control group . During the 6 years of trial , 65 persons from the test group and 34 controls were lost . The patients were divided into three age groups ; I less than 35 years , II 36 - -50 years , III greater than 50 years . The members of the test and control groups were first subjected to a Baseline examination which included assessment s of oral hygiene , gingivitis , periodontal disease and caries . Following this examination all caries lesions were treated and ill-fitting dental restorations adjusted . Each patient was also given a detailed case presentation and a dental prophylaxis . The control group patients were not involved in any further dental health programs during the subsequent 6-year period . Once a year , however , they were recalled to a public dental health clinic for examination and received symptomatic dental treatment . The test group participants , on the other h and , were given a preventive treatment , repeated once every 2 - 3 months which included ( 1 ) instruction and practice in oral hygiene techniques and ( 2 ) meticulous prophylaxis . The patients were re-examined 3 and 6 years after the baseline examination . At the Follow-up examinations the parameters studied at the Baseline examination were recorded again . The findings demonstrated that a preventive program which stimulates individuals to adopt proper oral hygiene habits may resolve gingivitis and prevent progression of periodontal disease and caries . Traditional dental care , on the other h and , did not prevent the progression of caries and periodontitis in adults 69 adults ranging in age from 20 to 73 ( mean age : 37 ) were r and omly assigned to a control ( C ) and a test ( T ) group . Of these , 61 completed the 3-year longitudinal study . All subjects had varying degrees of gingivitis at the start , but no overt periodontitis . Following a base line examination for P1I , GI , probing depth ( PD ) and recession , a differential darkfield microscopic ( DDFM ) count of subgingival bacterial morphotypes was carried out on a pooled sample originating from one tooth surface in each sextant with the greatest probing depth . Examinations were repeated every 6 months for 3 years . The C group received regular prophylaxes every 6 months . The T subjects received prophylaxes according to a previously described schedule , and on the basis of the DDFM test outcome . Recall intervals at the end of the study for the T group ranged from 1 to 24 months ( mean : 15.7 months ) . Of 30 subjects in the T group at the end of the study , one half had not had their teeth cleaned for periods of 18 to 36 months without any detectable deterioration in their periodontal status by comparison with the other T subjects or the patients in the C group . Both C and T subjects exhibited increased mean P1I and GI scores as compared to base line during the first half of the study . However , mean PD measurements remained unchanged . Increases in PD from base line of 3 mm or more were observed only in approximately 1 out of a 1000 individual tooth surface comparisons , a frequency comparable to that expected to occur by chance alone . This observation indicates that in this population , little if any pocket formation occurred during the study period . GI score increases of 2 units or more occurred in relatively few subjects . 2 of 31 C patients accounted for 42 % of the affected dental units , while 5 out of 30 T subjects accounted for 40.8 % of the affected dental units in that group . These observations suggest that despite the relatively high prevalence and incidence of gingivitis , the subjects were relatively resistant to periodontitis . Neither preventive schedule was effective in eliminating gingivitis . The lack of significant destructive disease in this population prevented any meaningful comparison of the relative effectiveness of the two preventive maintenance regimens in preventing recurrences of periodontitis The beneficial effects of comprehensive dental prophylaxis programs are well recognized . In order to study the factors determining the effectiveness of these programs , 28 periodontal recall patients were subjected to monthly professional mechanical tooth cleanings . Experimental and control teeth were r and omly selected according to a splitmouth cross-over method . The Plaque and Gingival indices were recorded 1 month prior to the study , at the start , and at 4 , 8 , and 12 months . One month prior to the study calculus and bacterial plaque were thoroughly removed from all teeth . During the study period only the experimental teeth were cleaned . Efforts were made not to influence the oral hygiene of the participants by any other means . Following the initial tooth cleaning and during the preexperimental period the Plaque and Gingival indices decreased to a low level on both the experimental and control teeth ( mean P1I = 0.4 , mean GI = 0.3 ) . This high st and ard of oral hygiene and gingival health was maintained throughout the study period , and no differences could be observed between experimental and control teeth . This indicates that factors other than the mechanical professional cleaning were responsible for the maintenance of gingival health . It is suggested that participation in the program in itself may have motivated the patients to improve their oral home care The twice yearly application to children 's teeth of acidulated phosphate fluoride ( APF ) gel in dental trays preceded by a professionally rendered ' dental prophylaxis ' has become the st and ard and most commonly used dental chairside procedure for prevention of dental caries . This study was a r and omized , 3-year , community-based clinical trial of professionally applied APF gel involving the use and non-use of a prior dental prophylaxis and annual and biannual APF applications for children in age groups 6 - 7 ( n = 176 ) and 10 - 11 ( n = 153 ) years initially , who are likely at high risk of future dental caries . The 3-year results of this study show no significant effect on dental caries reduction of either a prior prophylaxis or annual versus biannual APF gel applications . A significant reduction in the frequency of provision of these dental services , limited to high caries risk patients only , is recommended Output:	A generalisation on dental prophylaxis before PATF can not be applied to adolescents and adults . Available evidence ( two other studies ) fails to demonstrate any benefit in the prevention of gingivitis from further dental prophylaxis at interval used for recall examinations . Dental prophylaxis at intervals of four months or more is not justified for the prevention of gingivitis in the general population
MS22293	*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: Oxytocin was administered in a r and omized fashion via either the umbilical or maternal intravenous route . Women who received intraumbilical oxytocin had significantly greater calculated blood loss compared with those who received peripheral administration ( P = .01 ) . This greater blood loss was confirmed by a decrease in hematocrit and hemoglobin concentrations after delivery . There was no difference between the groups in the length of the third stage of labor . The incidence of fetomaternal transfusion was higher in the intraumbilical group ( P = .07 ) . We conclude that intraumbilical oxytocin is no more beneficial than peripheral administration Objective To compare intravenous oxytocin administration ( Partocon ® 10 IU ) with saline solution in the management of postpartum haemorrhage in the third stage of labour OBJECTIVE --To compare the effects on fetal and maternal morbidity of routine active management of third stage of labour and expectant ( physiological ) management , in particular to determine whether active management reduced incidence of postpartum haemorrhage . DESIGN --R and omised trial of active versus physiological management . Women entered trial on admission to labour ward with allocation revealed just before vaginal delivery . Five months into trial high rate of postpartum haemorrhage in physiological group ( 16.5 % v 3.8 % ) prompted modification of protocol to exclude more women and allow those allocated to physiological group who needed some active management to be switched to fully active management . Sample size of 3900 was planned , but even after protocol modification a planned interim analysis after first 1500 deliveries showed continuing high postpartum haemorrhage rate in physiological group and study was stopped . SETTING --Maternity hospital . PARTICIPANTS --Of 4709 women delivered from 1 January 1986 to 31 January 1987 , 1695 were admitted to trial and allocated r and omly to physiological ( 849 ) or active ( 846 ) management . Reasons for exclusion were : refusal , antepartum haemorrhage , cardiac disease , breech presentation , multiple pregnancy , intrauterine death , and , after May 1986 , ritodrine given two hours before delivery , anticoagulant treatment , and any condition needing a particular management of third stage . INTERVENTIONS --All but six women allocated to active management actually received it , having prophylactic oxytocic , cord clamping before placental delivery , and cord traction ; whereas just under half those allocated to physiological management achieved it . A fifth of physiological group received prophylactic oxytocic , two fifths underwent cord traction and just over half clamping of the cord before placental delivery . ENDPOINT -- Reduction in incidence of postpartum haemorrhage from 7.5 % under physiological management to 5.0 % under active management . MEASUREMENTS AND MAIN RESULTS --Incidence of postpartum haemorrhage was 5.9 % in active management group and 17.9 % in physiological group ( odds ratio 3.13 ; 95 % confidence interval 2.3 to 4.2 ) , a contrast reflected in other indices of blood loss . In physiological group third stage was longer ( median 15 min v 5 min ) and more women needed therapeutic oxytocics ( 29.7 % v 6.4 % ) . Apgar scores at one and five minutes and incidence of neonatal respiratory problems were not significantly different between groups . Babies in physiological group weighed mean of 85 g more than those in active group . When women allocated to and receiving active management ( 840 ) were compared with those who actually received physiological management ( 403 ) active management still produced lower rate of postpartum haemorrhage ( odds ratio 2.4;95 % CI1.6 to 3.7 ) . CONCLUSIONS --Policy of active management practised in this trial reduces incidence of postpartum haemorrhage , shortens third stage , and results in reduced neonatal packed cell volume The authors analysed the effect of the i.v . oxytocin induced third stage of labour in a controlled trial concerning 1000 patients . The appliance of such an policy in a unit that already had a fairly active management of delivery was very encouraging . The incidence of post-partum haemorrhage ( greater than 500 ml ) is significantly ( P less than 0.001 ) less than in the control group ; and the same for severe haemorrhage . The third stage is significantly ( P less than 0.001 ) shorter in the oxytocin-injected group than in the control group . Moreover , there is no significant difference between the two groups for retained placenta . The economy of blood transfusion , which is a major concern nowadays , could be the real interest of this active management of the third stage of labour Cynthia Stanton and colleagues conducted a cluster-r and omized controlled trial in rural Ghana to assess whether oxytocin given by injection by community health officers at home births was a feasible and safe option in preventing postpartum hemorrhage . Please see later in the article for the Editors ' Background Hemorrhage is the leading direct cause of maternal death globally . While oxytocin is the drug of choice for postpartum hemorrhage prevention , its use has generally been limited to health facilities . This trial assesses the effectiveness , safety , and feasibility of exp and ing the use of prophylactic intramuscular oxytocin to peripheral health care providers at home births in four predominantly rural districts in central Ghana . Methods This study is design ed as a community-based cluster-r and omized trial in which Community Health Officers are r and omized to provide ( or not provide ) an injection of oxytocin 10 IU via the UnijectTM injection system within one minute of delivery of the baby to women who request their presence at home at the onset of labor . The primary aim is to determine if administration of prophylactic oxytocin via Uniject ™ by this cadre will reduce the risk of postpartum hemorrhage by 50 % relative to deliveries which do not receive the prophylactic intervention . Postpartum hemorrhage is examined under three sequential definitions : 1 ) blood loss ≥500 ml ( BL ) ; 2 ) treatment for bleeding ( TX ) and /or BL ; 3 ) hospital referral for bleeding and /or TX and /or BL . Secondary outcomes address safety and feasibility of the intervention and include adverse maternal and fetal outcomes and logistical concerns regarding assistance at home births and the storage and h and ling of oxytocin , respectively . Discussion Results from this trial will build evidence for the effectiveness of exp and ing the delivery of this established prophylactic intervention to peripheral setting s. Complementary data on safety and logistical issues related to this intervention will assist policymakers in low-income countries in selecting both the best uterotonic and service delivery strategy for postpartum hemorrhage prevention . Results of this trial are expected in mid-2013 . The trial is registered at Clinical Trials.gov : NCT01108289 Background There are two approaches to care during the third stage of labour : Active management includes three components : administration of a prophylactic uterotonic drug , cord clamping and controlled cord traction . For physiological care , intervention occurs only if there is clinical need . Evidence to guide care during the third stage is limited and there is variation in recommendations which may contribute to differences in practice . This paper describes current UK practice during the third stage of labour . Methods A postal survey of 2230 fellows and members of the Royal College of Obstetricians and Gynaecologists ( RCOG ) and 2400 members of the Royal College of Midwives was undertaken . Respondents were asked about care during the third stage of labour , for vaginal and caesarean births and their views on the need for more evidence to guide care in the third stage . The data were analysed in Excel and presented as descriptive statistics . Results 1189 ( 53 % ) fellows and members of the RCOG and 1702 ( 71 % ) midwives responded , of whom 926 ( 78 % ) and 1297 ( 76 % ) respectively had conducted or supervised births in the last year . 93 % ( 863/926 ) of obstetricians and 73 % ( 942/1297 ) of midwives report ' always or usually ' using active management . 66 % ( 611/926 ) of obstetricians and 33 % ( 430/1297 ) of midwives give the uterotonic drug with delivery of the anterior shoulder ; this was intramuscular Syntometrine ® for 79 % ( 728/926 ) and 86 % ( 1118/1293 ) respectively . For term births , 74 % ( 682/926 ) of obstetricians and 41 % ( 526/1297 ) of midwives clamp the cord within 20 seconds , as do 57 % ( 523/926 ) and 55 % ( 707/1297 ) for preterm births . Controlled cord traction was used by 94 % of both obstetricians and midwives . For caesarean births , intravenous oxytocin was the uterotonic used by 90 % ( 837/926 ) of obstetricians ; 79 % ( 726/926 ) clamp the cord within 20 seconds for term births as do 63 % ( 576/926 ) for preterm births . Physiological management was used ' always or usually ' by 2 % ( 21/926 ) of obstetricians and 9 % ( 121/1297 ) of midwives . 81 % ( 747/926 ) of obstetricians and 89 % ( 1151/1297 ) of midwives thought more evidence from r and omised trials was needed ; the most popular question was when is best to clamp the cord . Conclusions Active management of the third stage of labour is widely used by both obstetricians and midwives in the UK . Syntometrine ® is usually used for vaginal births and oxytocin for caesarean births ; when this is given and when the cord is clamped varies OBJECTIVE Comparison of 3 regimens for third-stage management after second-trimester intravaginal misoprostol termination . STUDY DESIGN Prospect i ve r and omized trial . Three third-stage management strategies were compared : 10 units of intramuscular oxytocin ( group 1 ) , 600 microg oral misoprostol ( group 2 ) , or no additional medication ( group 3 ) after fetal expulsion . Primary study outcome was the incidence of placental retention . RESULTS Two hundred fifty-one women were r and omly assigned to the groups . There was a significant difference in placental retention rates : group 1 , 8 of 83 ( 10 % ) vs group 2 , 24 of 83 ( 29 % ) vs group 3 , 26 of 85 ( 31 % ) ; P = .002 . Blood loss was significantly lower in group 1 , 100 mL ( interquartile ranges , 50 - 200 ) vs group 2 , 200 mL ( interquartile ranges , 100 - 370 ) vs group 3 , 200 mL ( interquartile ranges , 100 - 375 ) ; P < .001 . Requirement for blood transfusion : group 1 , 1 of 83 ( 1 % ) vs group 2 , 1 of 83 ( 1 % ) vs group 3 , 5 of 85 ( 6 % ) ; P = .103 . CONCLUSION Intramuscular oxytocin administered after fetal delivery after second-trimester medical termination significantly increases placental expulsion rates and decreases short-term postpartum blood loss Background . The single most common direct obstetric disorder accounting for 25 % of all maternal deaths globally is severe hemorrhage , generally occurring postpartum . Nearly all these deaths occur in the developing world . The role of oxytocic drugs in the management of the third stage of labor as a strategy to reduce maternal mortality has been emphasized . However , the adverse effects of these oxytocic agents , in particular ergometrine , have not been properly evaluated in our environment . Objectives . To evaluate the effect of ergometrine and oxytocin on the cardiovascular system when used for active management of the third stage of labor . Study design . A double-blind , r and omized controlled study was carried out at the Federal Medical Centre , Makurdi over 24 months . Five hundred and ten patients were r and omized to treatment with either 0.5 mg of intramuscular ergometrine or 10 IU of intravenous oxytocin , respectively , as single injections . Their effects on the cardiovascular system were observed using blood pressure as a marker . Results . Ergometrine unlike oxytocin was observed to cause a significant rise in blood pressure , and this effect was most marked in the first 24 hours of the puerperium . Conclusions . These results suggest that ergometrine may be safe in normotensive parturients but hazardous in hypertensive parturients in whom oxytocin would be a safer option The incidences of postpartum haemorrhage and retained placenta have decreased with the use of synthetic oxytocin and controlled cord traction . Whether such treatment is valuable is open to question because of the lack of clinical and physiological studies . The physiological effects of synthetic oxytocin on plasma concentrations of oxytocin and events during delivery were assessed . Plasma oxytocin concentration was determined in serial sample s during the late second stage and throughout the third stage of labour in 25 women . Ten women received combined ergotamine and synthetic oxytocin intramuscularly and 15 were not treated . The geometric mean plasma oxytocin concentration Output:	AUTHORS ' CONCLUSIONS Prophylactic oxytocin at any dose decreases both PPH greater than 500 mL and the need for therapeutic uterotonics compared to placebo alone . If IV delivery is not possible , IM delivery may be used as this route of delivery did show a benefit to prevent PPH greater than 500 mL and there was a trend to decrease the need for therapeutic uterotonics , albeit not statistically significant . Prophylactic oxytocin was superior to ergot alkaloids in preventing PPH greater than 500 mL ; however , in subgroup analysis this benefit did not persist when only r and omised trials with low risk of method ologic bias were analysed . Based on this , there is limited high- quality evidence supporting a benefit of prophylactic oxytocin over ergot alkaloids . Importantly , there is no evidence to suggest that prophylactic oxytocin increases the risk of retained placenta when compared to placebo or ergot alkaloids .
MS22294	*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 assess differences in magnetic resonance imaging (MRI)-based compositional ( T2 ) and morphometric ( volume and thickness ) parameters of the tibio-femoral joint cartilage in subjects with and without osteoarthritis ( OA ) and compare these with clinical assessment tools during a 1-year follow-up . METHOD Three Tesla MRI of the knee joint was performed in eight female patients ( body mass index [ BMI ] > 30 ) with early OA and 10 age-matched female controls ( BMI < 30 ) at baseline ( BL ) and after 3 , 6 and 12 months . Cartilage T2 maps , volume and average thickness were calculated in five compartments ( medial/lateral femoral condyle , medial/lateral tibia and trochlea ) . These data were correlated with changes in clinical parameters and joint space width determined in st and ardized knee radiographs using a mixed r and om effects model . RESULTS At BL , T2 was significantly higher ( P<0.05 ) across the cartilage in patients ( 45.68+/-5.17ms ) compared to controls ( 41.75+/-4.33ms ) . Patients had significantly ( P<0.05 ) less cartilage volume and less average cartilage thickness in the tibia than controls ( 2.10+/-0.53cm(3 ) vs 2.91+/-0.49cm(3 ) and 1.59+/-0.24 mm vs 1.90+/-0.29 mm , respectively ) . A significant change in clinical parameters of OA , cartilage T2 values or a decrease of volume and average thickness could not be demonstrated within both groups . CONCLUSION Significant differences between the groups indicate that both T2 and morphometric parameters may be useful in quantifying early OA related changes . In a 12-month follow-up , however , no significant alterations of the studied parameters were found , which may be due to the length of the observation interval Purpose To prospect ively evaluate changes in T1rho and T2 relaxation time in the meniscus using 3.0 T MRI in asymptomatic knees of marathon runners and to compare these findings with those of age-matched healthy subjects . Material and methods Thirteen marathon runners underwent 3.0 T MRI including T1rho and T2 mapping sequences before , 48–72 h after , and 3 months after competition . Ten controls were examined at baseline and after 3 months . All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage , meniscal , ligamentous . and other knee abnormalities with WORMS scores . Meniscal segmentation was performed to generate T1rho and T2 maps in six compartments . Results No differences in morphological knee abnormalities were found before and after the marathon . However , all marathon runners showed a significant increase in T1rho and T2 values after competition in all meniscus compartments ( p < 0.0001 ) , which may indicate changes in the biochemical composition of meniscal tissue . While T2 values decreased after 3 months T1rho values remained at a high level , indicating persisting changes in the meniscal matrix composition after a marathon . Conclusion T2 values in menisci have the potential to be used as biomarkers for identifying reversible meniscus matrix changes indicating potential tissue damage . T1rho values need further study , but may be a valuable marker for diagnosing early , degenerative changes in the menisci following exercise OBJECTIVE To longitudinally estimate the change in glycosaminoglycan content of knee cartilage in asymptomatic untrained female novice runners participating in a Start To Run program ( STR ) compared to sedentary controls . METHOD Nine females enrolling in a 10-week STR and 10 sedentary controls participated voluntarily . Prior to and after the 10-week period , both groups were subjected to dGEMRIC imaging . dGEMRIC indices of knee cartilage were determined at baseline and for the change after the 10-week period in both groups . Based on a self-reported weekly log , physical activity change during the study was depicted as decreased , unchanged or increased . The Mann-Whitney U and Kruskal-Wallis tests were applied to test the hypotheses that dGEMRIC changes occurred between groups and according to physical activity changes respectively . RESULTS No significant differences were established between groups for dGEMRIC indices at baseline ( P=0.541 ) . A significant positive change of the median dGEMRIC index in the runners group was demonstrated when compared to the controls [ + 11.66ms ( 95 % CI : -25.29 , 44.43 ) vs -9.56ms ( 95 % CI : -29.55 , 5.83 ) , P=0.006 ] . The change in dGEMRIC index differed significantly according to physical activity change ( P=0.014 ) , showing an increase in dGEMRIC index with increasing physical activity . CONCLUSION Since cartilage appears to positively respond to moderate running when compared to a sedentary lifestyle , this running scheme might be considered a valuable tool in osteoarthritis prevention strategies . Caution is warranted when applying these results to a wider population and to longer training periods OBJECTIVE To detect by magnetic resonance imaging ( MRI ) the presence and type of knee injuries in non-professional runners after running an ultra-marathon , and to determine whether ultra-marathon running exacerbates pre-existing knee injuries or results in new permanent injuries . DESIGN A prospect i ve MRI study of one knee of 10 r and omly selected participants who completed the Comrades Marathon between 1997 and 2002 . Their knees were scanned 48 hours before the race , and 48 hours and 1 month after the race . SETTING All scans were performed at the Radiology Department , Wentworth Hospital , Durban , and the University of KwaZulu-Natal . MAIN OUTCOME MEASURES Scores of all knee injuries detected on MRI scans immediately before the race , compared with the scores after the race . RESULTS All scanned knees demonstrated an abnormal amount of joint fluid before the race ; this increased immediately after the race in 5 runners and remained unchanged in another 5 . At 1 month , 5 knees showed decreased joint fluid and 5 remained unchanged , but these were not the same runners as in the post-race groups . There was increased signal intensity in the distal patellar and quadriceps tendons in 4 runners before the race , which increased or remained the same on post-race scans in 6 knees . There was a decrease in signal intensity on scans taken 1 month later in 3 runners , with complete resolution in 2 and no change in 1 . Old injuries to ligaments , tendons or other knee structures were unaffected by the race . No bone bruising , cartilage defects or meniscal abnormalities were observed . There was no significant difference in the pre- and post-race or 1-month scan scores . CONCLUSIONS The race appears to have had a detrimental effect on runners who started the ultra-marathon with tendinopathy , which worsened post-race by MRI criteria . One month after the race , the scan appearance of the overuse injury had either improved or resolved completely . Bone bruising or meniscal damage did not appear to occur , and the presence of increased joint fluid probably relates to stress or injury RATIONALE AND OBJECTIVES The authors performed this study to ( a ) measure changes in T2 relaxation rates , signal-to-noise ratio ( SNR ) , and contrast with sequential depletion of proteoglycan in cartilage ; ( b ) determine whether there is a relationship between the T2 relaxation rate and proteoglycan in cartilage ; and ( c ) compare the T2 mapping method with the spin-lattice relaxation time in the rotating frame ( T1rho ) mapping method in the quantification of proteoglycan-induced changes . MATERIAL S AND METHODS T2- and T1rho-weighted magnetic resonance ( MR ) images were obtained in five bovine patellae . All images were obtained with a 4-T whole-body MR unit and a 10-cm-diameter transmit-receive quadrature birdcage coil tuned to 170 MHz . T2 and T1rho maps were computed . RESULTS The SNR and contrast on the T2-weighted images were , on average , about 43 % lower than those on the corresponding T1rho-weighted images . The T2 relaxation rates varied r and omly without any particular trend , which yielded a poor correlation with sequential depletion of proteoglycan ( R2 = 0.008 , P < .70 ) . There was excellent linear correlation between the percentage of proteoglycan in the tissue and the T1rho relaxation rate ( R2 = 0.85 , P < .0001 ) . CONCLUSION T2-weighted imaging neither yields quantitative information about the changes in proteoglycan distribution in cartilage nor can be used for longitudinal studies to quantify proteoglycan-induced changes . T1rho-weighted imaging , however , is sensitive to sequential depletion of proteoglycan in bovine cartilage and can be used to quantify proteoglycan-induced changes Background Articular cartilage contributes to transferring enormous loads as uniformly as possible from one skeletal segment to the next . Whether it manages this task when subjected to the high repetitive loading cycles occurring during long-distance running and can remain intact is still the topic of controversy . Purpose To investigate the changes in cartilaginous volumes of the tibia , patella , and medial and lateral menisci after extreme dynamic loading as occurs in long-distance runners . Study Design Controlled laboratory study . Methods Forty-eight knees of male athletes were studied ( 38 ± 14 years ) . The subjects ran around a predetermined and precisely measured course ( 5 , 10 , 20 km ) , the beginning and end of the run being in the magnetic resonance imaging investigation room . The scan protocol was 60-minute rest period , first measurement , run , 3-minute delay , and second measurement . Results Overall , there were significant reductions in volume ( P < .05 ) for the patella , tibia , and menisci . There was evidence of significant change after a running distance of 5 km . A further statistical reduction of the volume could only be demonstrated for the medial meniscus after 10 and 20 km . Conclusion Tibial , patellar , and meniscal cartilaginous volumes show not only load-dependent volume changes but also an asymptotic curve . This is the first time that meniscal volume changes due to loading have been used as an indicator of the important mechanical contribution that the menisci make to sustaining the knee during repetitive loading . Clinical Relevance On the basis of the results of this study , the authors assume that the cartilage is able to adapt well to the loads caused by running Long distance running has become a fashionable recreational activity . This study investigated the effects of external impact loading on bone and cartilage introduced by performing a marathon race . Seven beginners were compared to six experienced recreational long distance runners and two professional athletes . All participants underwent magnetic resonance imaging of the hip and knee before and after a marathon run . Coronal T1 weighted and STIR sequences were used . The pre MRI served as a baseline investigation and monitored the training effect . All athletes demonstrated normal findings in the pre run scan . All but one athlete in the beginner group demonstrated joint effusions after the race . The experienced and professional runners failed to demonstrate pathology in the post run scans . Recreational and professional long distance runners tolerate high impact forces well . Beginners demonstrate significant changes on the post run scans . Whether those findings are a result of inadequate training ( miles and duration ) warrant further studies . We conclude that adequate endurance training results in adaptation mechanisms that allow the athlete to compensate for the stresses introduced by long distance running and do not predispose to the onset of osteoarthritis . Significant malalignment of the lower extremity may cause increased focal loading of joint and cartilage This prospect i ve study evaluated regular physical activity and self-reported physician-diagnosed osteoarthritis of the knee and /or hip joints among 16,961 people , ages 20 - 87 , examined at the Cooper Clinic between 1970 and 1995 . Among those aged 50 years and older , osteoarthritis incidence was higher among women ( 7.0 per 1000 person-years ) than among men ( 4.9 per 1000 person-years , P = 0.001 ) , while among those under 50 years of age , osteoarthritis incidence was similar between men ( 2.6 ) and women ( 2.7 ) . High levels of physical activity ( running 20 or more miles per week ) were associated with osteoarthritis among men under age 50 after controlling for body mass index , smoking , and use of alcohol or caffeine ( hazard ratio = 2.4 , 95 % CI : 1.5 , 3.9 ) , while no relationship was suggested among women or older men . These findings support the conclusion that high levels of physical activity may be a risk factor for symptomatic osteoarthritis among men under age 50 Output:	Conclusion : These data suggest that healthy athletes who have no risk factors for degenerative joint disease may present fleeting quantitative alterations after running . No irreversible , qualitative harmful effects seemed to occur , with the exception of persistent T1ρ elevation representing a proteoglycan depletion .
MS22295	*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: Patients with primary insomnia overestimate their sleep onset latency ( SOL ) and underestimate their total sleep time ( TST ) . The present study aim ed to test the utility of a novel behavioural experiment design ed to correct distorted perception of sleep among patients diagnosed with primary insomnia . Individuals with primary insomnia were asked to wear an actigraph and keep a sleep diary for three nights . On the following day , half were shown the discrepancy between the data recorded on the actigraph and their sleep diary ( Shown-Discrepancy Group ) , the other half were not shown the discrepancy ( No-Demonstration Group ) . Participants were then asked to wear the actigraph and keep a sleep diary for three further nights . Following the behavioural experiment , the Shown-Discrepancy Group estimated their SOL more accurately and reported less anxiety and preoccupation about sleep compared to the No-Demonstration Group . The theoretical and clinical implication s of these findings are discussed Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract Recent research in the treatment of insomnia by paradoxical intention has utilized two different methods of instruction . Studies utilizing the r and om assignment of subjects to treatment groups employ a procedure in which clients are provided with a straight-forward explanation based on the present authors ' underst and ing of the use of paradoxical intention with insomnia ( type A administration ) . In contrast , controlled case studies have employed reframing , a procedure which explains the need for the paradoxical intention in a manner which best suits the specific underst and ing of the individual client ( type B administration ) . The present study employed the type B method in a design employing the r and om assignment of clients to groups . Three additional groups ( type A administration , placebo control , no-treatment control ) completed the design . The results indicated that the type A method was superior to the type B procedure when the same method for administering paradoxical intention was applied to a r and omized group of individuals This investigation assessed the efficacy of a technique specifically design ed to change the style and content of presleep thoughts in order to reduce nighttime cognitive arousal and decrease insomnia severity . This investigation , termed " cognitive refocusing treatment for insomnia " ( CRT-I ) , previously improved sleep in a small sample of veterans with primary insomnia . In this investigation , university students with poor sleep were r and omly assigned to attend either one session of CRT-I and sleep hygiene education ( SH : n=27 ) or one session of only SH ( n=24 ) . Insomnia severity ( assessed by the Insomnia Severity Index ) and nighttime arousal ( assessed by the Pre-Sleep Arousal Scale ) were measured at baseline and 1month posttreatment . A significant Group × Time interaction for insomnia severity suggested more improved sleep over time for those receiving CRT-I+SH . A trend for a Group × Time interaction showed decreased cognitive arousal over time among those receiving CRT-I. These findings provide preliminary support for the efficacy of CRT-I for insomnia treatment among college students . Continued study of CRT-I in a community-based sample appears warranted It seems sensible to tailor treatments of insomnia in relation to the presenting characteristics of the sleeper and of the complaint . This report describes the first study formally to examine the comparative effectiveness of tailored and untailored ( r and omly allocated ) treatments . We developed a question naire to facilitate the design ing of individualized programmes . Results indicated that statistical analysis may underestimate the benefits of tailoring . Measures of clinical ly significant change , however , suggested that tailored treatment though it may be highly effective , is no more so than stimulus control therapy We describe the development of a cognitive therapy intervention for chronic insomnia . The therapy is based on a cognitive model which suggests that the processes that maintain insomnia include : ( 1 ) worry and rumination , ( 2 ) attentional bias and monitoring for sleep-related threat , ( 3 ) unhelpful beliefs about sleep , ( 4 ) misperception of sleep and daytime deficits and ( 5 ) the use of safety behaviors that maintain unhelpful beliefs . The aim of cognitive therapy for insomnia is to reverse all five maintaining processes during both the night and the day . In an open trial 19 patients meeting diagnostic criteria for primary insomnia were treated with cognitive therapy for insomnia . Assessment s were completed pretreatment , posttreatment and at 3- , 6- and 12-month followup . The significant improvement in both nighttime and daytime impairment evident at the posttreatment assessment was retained up to the 12 month followup Objective : To examine the mediators and the potential of treatment matching to improve outcome for cognitive behavior therapy ( CBT ) for insomnia . Method : Participants were 188 adults ( 117 women ; Mage = 47.4 years , SD = 12.6 ) meeting the Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; text rev . ; DSM – IV – TR ; American Psychiatric Association [ APA ] , 2000 ) diagnostic criteria for chronic insomnia ( M duration : 14.5 years , SD : 12.8 ) . Participants were r and omized to behavior therapy ( BT ; n = 63 ) , cognitive therapy ( CT ; n = 65 ) , or CBT ( n = 60 ) . The outcome measure was the Insomnia Severity Index ( ISI ) . Hypothesized BT mediators were sleep-incompatible behaviors , bedtime variability ( BTv ) , risetime variability ( RTv ) and time in bed ( TIB ) . Hypothesized CT mediators were worry , unhelpful beliefs , and monitoring for sleep-related threat . Results : The behavioral processes mediated outcome for BT but not CT . The cognitive processes mediated outcome in both BT and CT . The subgroup scoring high on both behavioral and cognitive processes had a marginally significant better outcome if they received CBT relative to BT or CT . The subgroup scoring relatively high on behavioral but low on cognitive processes and received BT or CBT did not differ from those who received CT . The subgroup scoring relatively high on cognitive but low on behavioral processes and received CT or CBT did not differ from those who received BT . Conclusion : The behavioral mediators were specific to BT relative to CT . The cognitive mediators were significant for both BT and CT outcomes . Patients exhibiting high levels of both behavioral and cognitive processes achieve better outcome if they receive CBT relative to BT or CT alone Insomniacs commonly complain that they are unable to get to sleep at night due to unwanted thoughts , worries and concerns . The present study investigated whether brief training in identifying and elaborating an interesting and engaging imagery task for use during the pre-sleep period can reduce unwanted pre-sleep cognitive activity and sleep onset latency . Forty one people with insomnia were given one of three instructional sets to follow on the experimental night ; instructions to distract using imagery , general instructions to distract , or no instructions . Based on previous findings reported by Salkovskis & Campbell ( 1994 ) ' Behaviour Research and Therapy 32 ( 1994 ) 1 ' and ironic control theory ( Wegner , 1994 ) ' Psychological Review 101 ( 1994 ) 34 ' , it was predicted that ( 1 ) " imagery distraction " would be associated with shorter sleep onset latency and less frequent and distressing pre-sleep cognitive activity compared to the " no instruction " group and that ( 2 ) " general distraction " would be associated with longer sleep onset latency and more frequent and distressing pre-sleep cognitive activity compared to the " no instruction " group . Support was found for the first but not the second prediction . The success of the " imagery distraction " task is attributed to it occupying sufficient " cognitive space " to keep the individual from re-engaging with thoughts , worries , and concerns during the pre-sleep period . In addition , " imagery distraction " involved a very specific alternative cognitive task hence the operating process was given a feature positive search , conditions where mental control is likely to be achieved This study considers the role of pre-sleep cognitive arousal , worry , and inhibition in sleep onset difficulties . The Pennebaker writing task , which promotes emotional processing by asking people to write about their thoughts , worries , and emotions , has proven effective in several areas of health . Here , the paradigm 's ability to reduce pre-sleep cognitive arousal ( PSCA ) and sleep onset latency ( SOL ) in people with insomnia was tested . Twenty-eight people with insomnia were r and omized to three nights of Pennebaker writing or a control condition , following a one-night baseline . The outcomes of change over baseline at Day 4 in pre-sleep cognitive arousal and SOL were compared . Writing significantly reduced pre-sleep cognitive arousal on one out of two measures , but did not significantly reduce SOL A new cognitive therapy ( CT ) program was compared with an established behavioral treatment . Sixty-two patients meeting Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; American Psychiatric Association , 1994 ) criteria for social phobia were r and omly assigned to CT , exposure plus applied relaxation ( EXP = AR ) , or wait-list ( WAIT ) . CT and EXP = AR were superior to WAIT on all measures . On measures of social phobia , CT led to greater improvement than did EXP = AR . Percentages of patients who no longer met diagnostic criteria for social phobia at posttreatment-wait were as follows : 84 % in CT , 42 % in EXP = AR , and 0 % in WAIT . At the 1-year follow-up , differences in outcome persisted . In addition , patients in EXP = AR were more likely to have sought additional treatment . Therapist effects were small and nonsignificant . CT appears to be superior to EXP = AR in the treatment of social phobia STUDY OBJECTIVES To compare the efficacy of problem-solving therapy ( PST ) combined with behavioral sleep strategies to st and ard cognitive therapy ( CT ) combined with behavioral sleep strategies in the treatment of insomnia . DESIGN A six-week r and omized controlled trial with one month follow-up . SETTING The Australian National University Psychology Clinic , Canberra , Australia . PARTICIPANTS Forty-seven adults aged 18 - 60 years recruited from the community meeting the Research Diagnostic Criteria for insomnia . INTERVENTIONS Participants received 6 weeks of treatment including one group session ( sleep education and hygiene , stimulus control instructions and progressive muscle relaxation ) followed by 5 weeks of individual treatment of PST or CT . MEASUREMENTS AND RESULTS Primary outcomes included sleep efficiency ( SE ) from sleep diaries , the Insomnia Severity Index ( ISI ) , and the Pittsburgh Sleep Quality Index ( PSQI ) . Secondary measures assessed dysfunctional sleep beliefs , problem-solving skills and orientations , and worry . Both treatments produced significant post therapy improvements in sleep which were maintained at 1 month follow-up ( on SE Cohen d = 1.42 , 95 % CI 1.02 - 1.87 for PST ; d = 1.26 , 95 % CI 0.81 - 1.65 for CT ; on ISI d = 1.46 , 95 % CI 1.03 - 1.88 for PST ; d = 1.95 , 95 % CI 0.52 - 2.38 for CT ; for PSQI d = 0.97 , 95 % CI 0.55 - 1.40 for PST and d = 1.34 , 95 % CI 0.90 - 1.79 for the CT ) . There were no differences in PST and CT in the size or rate of improvement in sleep although CT produced a significant faster rate of decline in negative beliefs about sleep than PST and there was a trend ( P = 0.08 ) for PST to produce a faster rate of improvement in negative problem orientation than CT . CONCLUSIONS The results provide preliminary support for problem solving treatment as an equally efficacious alternative component to cognitive therapy in psychological interventions for insomnia This study compared the effectiveness of paradoxical intention , stimulus control , information and a control group on severe sleep onset insomnia . Results showed that paradoxical intention and stimulus control were equally effective but significantly better than the information and control groups . It is suggested that treatment be adapted for each individual according to data collected from the intensive behavioral analysis of each case Patients with insomnia commonly complain that they are unable to get to sleep because of unwanted thoughts and worries . One account given of this excess cognitive activity is that it results from the incomplete processing of daytime stressors and hassles . Previous research has demonstrated the benefits of writing about emotional experiences as a method to facilitate emotional processing . This pilot study tested the hypothesis that writing about worries and concerns , with an emphasis on the expression and processing of emotion , will reduce sleep onset latency among an analogue sample of poor sleepers . Forty-two poor sleepers were r and omly allocated to 1 of 3 groups for 3 nights ; the instructions for the " problems " writing group emphasized the expression and processing of worries and concerns , the instructions for the " hobbies " writing group emphasized distraction from worries and concerns by writing about hobbies and interests , the " no writing " group were not given a writing task . The " problems " writing group reported shorter sleep onset latency compared to the " no writing " group . The results of this pilot study highlight the potential of research exploring the utility of a Pennebaker-style writing intervention for improving sleep Abstract A study by Turner and Ascher ( 1978 ) compared the efficacy of progressive relaxation , stimulus control , and paradoxical intention in ameliorating sleep onset insomnia . Results indicated that the three were equally effective . The present study is a partial replication of Turner and Ascher ( 1978 ) and focuses on the use of paradoxical intention in reducing sleep difficulties . Twenty-five individuals complaining of sleep discomfort were r and omly assigned to three groups : paradoxical intention , Output:	It is concluded that there is support for paradoxical intention and cognitive therapy . There are also other cognitive interventions that appears promising , such as cognitive refocusing and behavioral experiments . We conclude that several cognitive treatment components and therapies can be viewed as efficacious or promising interventions for patients with insomnia disorder .
MS22296	*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 Although health literacy and quality of life are important concepts in health care , the link between them is unclear , especially for a population of frequent users of health care services with chronic diseases . Low health literacy is a common problem that has been linked to several negative health outcomes . Quality of life is an important health outcome in patient-centered care . Frequent users of health care services are a vulnerable population that deserves attention due to high costs and negative outcomes such as lower quality of life and higher mortality . The objective of this study was to examine the relationship between health literacy and the physical and mental components of quality of life among frequent users of health care services with chronic diseases . Methods This study presents the cross-sectional analysis of data collected through the V1SAGES project , a r and omized controlled trial on the effectiveness of a case management intervention in primary care in Quebec , Canada . Participants ( n = 247 ) were frequent users of health care services presenting at least one chronic condition . Health literacy was measured by the Newest Vital Sign ( NVS ) , and the physical and mental components of quality of life were evaluated by the Short Form Health Survey Version 2 ( SF-12v2 ) . The association between health literacy ( independent variable ) and the physical and mental components of quality of life was examined using biserial correlation . Results No association was found between health literacy and quality of life ( physical component : r = 0.108 , ρ = 0.11 ; mental component : r = 0.147 , ρ = 0.15 ) . Conclusion This study suggests that there is no relationship between health literacy and the physical and mental components of quality of life among frequent users of health care services . Trial registration NCT01719991 . Registered October 25 , 2012 Purpose The levels of health literacy in patients with long-term conditions ( LTCs ) are critical for better disease management and quality of life ( QoL ) . However , the impact of health literacy on QoL in older adults with LTCs is unclear . This study examined the association between health literacy and domains of QoL in older people with LTCs , investigating key socio-demographic and clinical variables , as confounders . Methods A prospect i ve cohort study was conducted on older adults ( n = 4278 ; aged 65 years and over ) with at least one LTC , registered in general practice s in Salford , UK . Participants completed measures of health literacy , QoL , multi-morbidity , depression , social support , and socio-demographic characteristics . Multivariate linear regressions were performed to examine the effects of health literacy on four QoL domains at baseline , and then changes in QoL over 12 months . Results At baseline , poor health literacy was associated with lower scores in all four QoL domains ( physical , psychological , social relationships and environment ) , after adjusting for the effects of multi-morbidity , depression , social support and socio-demographic factors . At 12-month follow-up , low health literacy significantly predicted declines in the physical , psychological and environment domains of QoL , but not in social relationships QoL. Conclusions This is the largest , most complete assessment of the effects of health literacy on QoL in older adults with LTCs . Low health literacy is an independent indicator of poor QoL older patients with LTCs . Interventions to improve health literacy in older people with LTCs are encouraged by these findings Background Limited evidence exists regarding the relationship between health literacy and health-related quality of life ( HRQoL ) in Australian patients from primary care . The objective of this study was to investigate the impact of health literacy on HRQoL in a large sample of patients without known vascular disease or diabetes and to examine whether the difference in HRQoL between low and high health literacy groups was clinical ly significant . Methods This was a cross-sectional study of baseline data from a cluster r and omised trial . The study included 739 patients from 30 general practice s across four Australian states conducted in 2012 and 2013 using the st and ard Short Form Health Survey ( SF-12 ) version 2 . SF-12 physical component score ( PCS-12 ) and mental component score ( MCS-12 ) are derived using the st and ard US algorithm . Health literacy was measured using the Health Literacy Management Scale ( HeLMS ) . Multilevel regression analysis ( patients at level 1 and general practice s at level 2 ) was applied to relate PCS-12 and MCS-12 to patient reported life style risk behaviours including health literacy and demographic factors . Results Low health literacy patients were more likely to be smokers ( 12 % vs 6 % , P = 0.005 ) , do insufficient physical activity ( 63 % vs 47 % , P < 0.001 ) , be overweight ( 68 % vs 52 % , P < 0.001 ) , and have lower physical health and lower mental health with large clinical ly significant effect sizes of 0.56 ( B ( regression coefficient ) = −5.4 , P < 0.001 ) and 0.78(B = -6.4 , P < 0.001 ) respectively after adjustment for confounding factors . Patients with insufficient physical activity were likely to have a lower physical health score ( effect size = 0.42 , B = −3.1 , P < 0.001 ) and lower mental health ( effect size = 0.37 , B = −2.6 , P < 0.001 ) . Being overweight tended to be related to a lower PCS-12 ( effect size = 0.41 , B = −1.8 , P < 0.05 ) . Less well-educated , unemployed and smoking patients with low health literacy reported worse physical health . Health literacy accounted for 45 and 70 % of the total between patient variance explained in PCS-12 and MCS-12 respectively . Conclusions Addressing health literacy related barriers to preventive care may help reduce some of the disparities in HRQoL. Recognising and tailoring health related communication to those with low health literacy may improve health outcomes including HRQoL in general practice OBJECTIVE To measure the level of functional health literacy ( FHL ) in an Australian population , and to explore the level of risk associated with level of FHL . DESIGN , SETTING AND PARTICIPANTS Cross-sectional , r and om population survey administered to 2824 South Australians aged > or=15 years , September-October 2008 . MAIN OUTCOME MEASURES Newest Vital Sign as a measure of FHL , self-reported general health status , and use of health services . RESULTS 24 % of respondents were at risk of limited FHL , and 21 % had a high likelihood of inadequate FHL ; this increased with age ( > or=65 years , 50 % v 25 - 44 years , 11 % ) . In multiple logistic regression models , a high likelihood of inadequate FHL was significantly more common among those with lower education ( left school < or=15 years of age , odds ratio [ OR ] , 8.1 ; 95 % CI , 4.8 - 13.6 ) ; with lower annual income ( < $ 20 000 , OR , 4.1 ; 95 % CI , 2.3 - 7.4 ) ; who were born in countries other than Australia , New Zeal and , the United Kingdom and Irel and ; and with poorer health status ( OR , 1.6 ; 95 % CI , 1.2 - 2.2 ) . Inadequate FHL was significantly less common among females ( OR , 0.6 ; 95 % CI , 0.5 - 0.8 ) . People with inadequate or at-risk FHL were significantly more likely to report having diabetes , cardiac disease or stroke , and significantly less likely to have recently attended a doctor . Respondents aged > or=65 years with inadequate FHL were more likely to have been admitted to hospital ( OR , 2.2 ; 95 % CI , 1.1 - 4.5 ) . CONCLUSION Many Australians are likely to have limited health literacy , and this is a risk to effective health care delivery and health improvement across the community Background Hypertension is a common and frequently occurring chronic disease of the cardiovascular system . Besides the pathological factors , the occurrence and exacerbation of hypertension are also associated with many factors of lifestyle and behaviors . Thus hypertensive patients ’ Health-related quality of life ( HRQL ) is not only influenced by the disease itself but also by many subjective factors such as health literacy and self-management efficacy , especially in the deeper part of southwestern China and thus is less developed compared to the other places . The purpose of this study was to examine the association between the HRQL of hypertensive patients and health literacy and self-management efficacy as well as how they affect the HRQL , so as to provide a theoretical reference for improving the HRQL of patients with hypertension in less developed areas . Methods This was a cross-sectional study of baseline data from a clustered r and omized controlled trial . The study design had passed a cross-national peer review and accepted grants by the China Medical Board . It was also registered in the Chinese Clinical Trial Registry (ChiCTR-OOR-14005563).A st and ardized question naire adapted from a previous vali date d WHO question naire was used for the survey which included detailed questions about patient ’s socio-demographic characteristics and self-reported information . Patients ’ HRQL was measured by the M and arin version of the 36-item Short Form . We used the vali date d M and arin version of the Self-Efficacy for Managing Chronic Disease 6-Item Scale to assess patients ’ self-management efficacy . The vali date d three-item Brief Health Literacy Screening ( BHLS ) was used to measure the patients ’ health literacy . A structural equation model was constructed , and p ≤ 0.05 was taken as significant . Results Demographic characteristics , health literacy and self-management efficacy have all significant effects on HRQL . Age , education level , self-management efficacy and health literacy were significantly related to the HRQL . The constructed model had a good fit for the data according to the model fit indices . Based on the model , health literacy ( r = 0.604 , p = 0.029 ) and Self-management efficacy ( r = 0.714 , p = 0.018 ) have a significant impact on HRQL . Demographic characteristics were inversely related to HRQL ( r = −0.419 , p = 0.007 ) , but have a significant impact on health literacy ( r = 0.675 , p = 0.029 ) and self-management efficacy ( r = 0.379 , p = 0.029 ) . At the same time , self-management efficacy was positively correlated to health literacy ( r = 0.413 , p < 0.01 ) . Conclusions Age , education level , self-management efficacy and health literacy were all related to the HRQL of patient with hypertension , which means that patients who are more elderly and have lower education level , low self-management efficacy and poor health literacy get worse HRQL . This may imply the necessary to introduce routine assessment of health literacy and self-management efficacy into assessment procedures for hypertensive patients ’ health management . Such assessment can help professionals to identify the population at greatest risk for poor health outcomes and low well-being in the future . In clinical practice , effective interventions such as direct guidance and education to raise the self-management efficacy and enhance health literacy might improve the HRQL of patients with hypertension . Trial registration Retrospectively registered Chinese Clinical Trial Registry (ChiCTR-OOR-14005563).Name of registry : Effects of the integrated delivery system and payment system of community-based intervention on rural patients of chronic diseases in Qianjiang District , China Date of registration : Retrospectively registered 23 November 2014 . Date of enrolment of the first participant to the trial : 5 July Output:	Meta-regression showed that cohort study design , studies conducted in China , and publication before 2012 may be important influencing factors .
MS22297	*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 bacterial endophthalmitis has been 3 - 6 % after cataract extraction in the eye camps of South India from 1961 - 75 . During this time 50 791 cases were operated using systemic and topical chloramphenicol prophylaxis . This study evaluated the prophylactic intracameral injection of 50 microng of gentamicin in eye camp cataract extraction s. Only 6 of 1626 patients treated with intracameral gentamicin at operation developed bacterial endophthalmitis , an incidence of 0 - 37 % PURPOSE : To report results in the European Society of Cataract & Refractive Surgeons ( ESCRS ) multicenter study of the prophylaxis of endophthalmitis after cataract surgery . SETTING : Twenty‐four ophthalmology units and eye clinics in Austria , Belgium , Germany , Italy , Pol and , Portugal , Spain , Turkey , and the United Kingdom , with an administrative office in Irel and , coordinating center in Engl and , and data management and statistical unit in Scotl and . METHODS : This partially masked r and omized placebo‐controlled multinational clinical study to evaluate prospect ively the prophylactic effect of intracameral cefuroxime injection and /or perioperative levofloxacin eyedrops on the incidence of endophthalmitis after phacoemulsification cataract surgery began in September 2003 and was terminated early in January 2006 . The study used r and om allocation of patients in a 2 × 2 factorial design . RESULTS : By the end of 2005 , complete follow‐up records had been received for 13 698 study patients . Such a clear beneficial effect from the use of intracameral cefuroxime had been observed that it was agreed it would be unethical to continue the study and to wait for the completion of all follow‐up procedures before reporting this important result . If total reported cases of endophthalmitis are considered , the incidence rate observed in those treatment groups not receiving cefuroxime prophylaxis ( 23 cases in 6862 patients ) was almost 5 times as high ( odds ratio [ OR ] , 4.59 ; 95 % confidence interval [ CI ] , 1.74‐12.08 ; P = .002 ) as that in the groups receiving this treatment ( 5 cases in 6836 patients ) . If only cases proved to be due to infection are considered , the rate was more than 5 times as high ( OR , 5.32 ; 95 % CI , 1.55‐18.26 ; P = .008 ) in the treatment groups not receiving cefuroxime . Although the use of perioperative levofloxacin eyedrops as prophylaxis was also associated with a reduction in the observed incidence rate of postoperative endophthalmitis , this effect was smaller and was not statistically significant , whether total reported cases or only cases proven to be due to infection are used in calculating the rates . As not all follow‐up procedures are complete , it is possible that further cases of endophthalmitis may be reported ; however , it is not expected that this will alter the main conclusion . Nevertheless , it is anticipated that successful completion of follow‐up procedures in all patients will increase the total number in the study to approximately 16 000 . CONCLUSION : Intracameral cefuroxime administered at the time of surgery significantly reduced the risk for developing endophthalmitis after cataract surgery OBJECTIVE : To compare the efficacy and tolerability of a fixed combination of 0.3 % gatifloxacin and 1 % prednisolone ( Zypred ® ) versus the individual components used separately ( Zymar ® and Predfort ® ) for infection prophylaxis and inflammation control after cataract surgery with intraocular lens implantation . METHODS : A prospect i ve , r and omized , double-blind , parallel-group study of 108 patients who underwent phacoemulsification and intraocular lens implantation was conducted . After r and om assignment , 47 eyes received the fixed combination of topical 0.3 % gatifloxacin/1 % prednisolone drops , and 61 eyes received the same doses of the individual components as separate solutions four times a day for 15 days . Baseline and postoperative assessment s were made on postoperative days 1 , 7 , 15 , and 20 . RESULTS : All objective ( best corrected visual acuity , sign of active ocular inflammation , central and incisional corneal edema , the number of cells per high-power field in the anterior chamber , and intraocular pressure ) and subjective ( eye pain , photophobia , burning sensation , itching , and foreign body sensation ) criteria of efficacy were similar in both groups , with no significant differences . Group I included 47 eyes that received the fixed combination of gatifloxacin/prednisolone acetate eye drops and a placebo eye drop solution . Group II included 61 eyes that were treated with 0.3 % gatifloxacin and 1 % prednisolone acetate eye drops separately . The intraocular pressure was slightly higher in Group II ( p<0.05 ) . CONCLUSION : Treatment with the fixed-dose combination of gatifloxacin/prednisolone eye drops was as effective as the non-fixed combination in preventing infection and controlling inflammation after phacoemulsification and intraocular lens implantation IMPORTANCE Postoperative endophthalmitis ( POE ) often results in severe visual impairment . In clinical studies , an intracameral cefuroxime injection at the end of surgery was found to be effective at reducing the incidence of POE . Two important issues are the retinal safety of cefuroxime and its use for patients with perioperative capsular rupture where the risk of POE is dramatically increased . OBJECTIVE To assess the effectiveness and retinal safety of an intracameral injection of cefuroxime sodium for the prevention of POE and its possible use in cases of a perioperative capsular rupture of the lens . DESIGN , SETTING , AND PARTICIPANTS Population -based cohort study of patients 40 years of age or older who underwent cataract surgery at 1 of 1546 French health care facilities , public or private , and whose medical records were obtained from the national administrative data base . Data analyses were performed between March and November 2015 . MAIN OUTCOMES AND MEASURES The effectiveness and safety of the prophylactic injection of cefuroxime as measured by the incidence of POE and cystoid macular edema . RESULTS From January 2010 to October 2014 , a total of 3 351 401 eyes of 2 434 008 patients 40 years of age or older ( 58.9 % were women , and the mean [ SD ] age was 73.9 [ 9.5 ] years ) underwent cataract surgery ; 1941 patients ( 0.08 % ) developed POE during the 6 weeks after cataract surgery . The incidence of POE after cataract surgery decreased over the course of the study ( 0.11 % , 0.09 % , 0.08 % , 0.06 % , and 0.05 % in 2010 , 2011 , 2012 , 2013 , and 2014 , respectively [ P = .001 for trend ] ) as the use of cefuroxime prophylactic injections increased ( 11.1 % , 14.4 % , 32.8 % , 64.8 % , and 79.1 % in 2010 , 2011 , 2012 , 2013 , and 2014 , respectively [ P = .001 for trend ] ) . After multivariate adjustment , the risk of POE was reduced with the use of cefuroxime ( odds ratio , 0.61 [ 95 % CI , 0.56 - 0.68 ] ) . The retinal safety of an injection of cefuroxime , which was assessed by multiadjusted odds of retinal cystoid macular edema , was not increased for patients receiving cefuroxime injections ( odds ratio , 0.86 [ 95 % CI , 0.71 - 1.05 ] ) . For patients with a perioperative capsular rupture of the lens ( the major risk factor for POE ) , the incidence of POE was lower for those who received an injection of cefuroxime than for those who did not ( 0.37 % vs 0.51 % , respectively [ P = .001 ] ) , whereas an increased risk of cystoid macular edema was not identified for those who received or did not receive an injection of cefuroxime ( 5.6 % vs 7.3 % , respectively [ P = .12 ] ) . CONCLUSIONS AND RELEVANCE These data suggest that , in routine practice , the intracameral injection of cefuroxime at the conclusion of cataract surgery is associated with a lower risk of POE and is safe for patients with or without a perioperative capsular rupture . While these data might be used to support the consideration of its routine use to prevent POE , in the absence of a r and omized clinical trial , they can not prove a direct cause- and -effect relationship between the injection of cefuroxime and POE PURPOSE To compare intraoperative injection of triamcinolone and ciprofloxacin in a controlled-release system ( DuoCat ) with prednisolone and ciprofloxacin eye drops after cataract surgery . METHODS In this r and omized , double-masked , controlled trial , a total of 135 patients undergoing cataract surgery were r and omly allocated to two groups : 67 patients treated after surgery with prednisolone 1 % and ciprofloxacin 3 % eye drops four times daily ( week 1 ) , three times daily ( week 2 ) , twice daily ( week 3 ) , and once daily ( week 4 ) and 0.3 % ciprofloxacin drops four times daily ( weeks 1 and 2 ) , and 68 patients treated at the end of surgery with a sub-Tenon 's injection of 25 mg triamcinolone and 2 mg ciprofloxacin in biodegradable microspheres . The patients were examined on postoperative days 1 , 3 , 7 , 14 , and 28 . The main outcome measures were postoperative anterior chamber cell and flare , intraocular pressure ( IOP ) , lack of anti-inflammatory response , and presence of infection . RESULTS No significant differences were observed between the groups in anterior chamber cell ( P > 0.14 ) and flare ( P > 0.02 ) at any postoperative visits . The mean ( 99 % confidence interval ) differences in IOP between the prednisolone and triamcinolone groups on days 1 , 3 , 7 , 14 , and 28 were -0.4 mm Hg ( -2.1 to 1.3 ) , 0.0 mm Hg ( -1.4 to 1.3 ) , 0.0 mm Hg ( -1.1 to 1.1 ) , -0.2 mm Hg ( -1.1 to 0.8 ) , and -0.1 mm Hg ( -1.1 to 0.9 ) , respectively . No patient had a postoperative infection . CONCLUSIONS One injection of DuoCat had a therapeutic response and ocular tolerance that were equivalent to conventional eye drops in controlling inflammation after cataract surgery . ( Clinical Trials.gov number , NCT00431028 . ) Purpose To report the nationwide incidence and risk factors for endophthalmitis after cataract surgery in Sweden . Setting Swedish National Cataract Register containing reports on cataract operations from all Swedish ophthalmic surgical units . Design Prospect i ve epidemiologic study . Methods Endophthalmitis case reports were collected from 2005 through 2010 . Case and control parameters pertaining to patient characteristics and surgical technique were generated from the data base . In addition , information from annual surveys regarding the topical prophylactic protocol was analyzed . Results The reports showed 135 endophthalmitis cases in 464 996 operations , equaling an incidence of 0.029 % . Patient age over 85 years , perioperative communication with the vitreous and , above all , nonuse of intracameral cefuroxime showed a statistically significant association with endophthalmitis in the logistic regression . Short‐term topical antibiotics given as add‐on prophylaxis to the intracameral regimen before , after , or before and after the operation did not confer a clear‐cut benefit . Groups with topical treatment were small , comprising 14 % of the sample . Conclusions The incidence of endophthalmitis after cataract surgery in Sweden is declining , which appears to be explained by a fall in the frequency of major risk factors . Operating earlier in the cataract course , avoiding capsule breakage , and giving intracameral antibiotics universally should further reduce the endophthalmitis rate . Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned Purpose To compare two different postcataract surgery antibiotic/steroid therapeutic combinations , for clinical results as well as patient satisfaction . Methods Prospect i ve r and omized clinical trial of patients with bilateral operative cataract . Postoperatively , for 15 days one eye was r and omly assigned to therapy with the combination chloramphenicol 0.25%-betamethasone 0.13 % gel three times a day ( Group 1 ) and the other to the combination tobramycin 0.3%-dexamethasone 0.1 % eyedro Output:	High-certainty evidence shows that injection with cefuroxime with or without topical levofloxacin lowers the chance of endophthalmitis after surgery , and there is moderate-certainty evidence to suggest that using antibiotic eye drops in addition to antibiotic injection probably lowers the chance of endophthalmitis compared with using injections or eye drops alone .
MS22298	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND There is great heterogeneity of clinical presentation and outcome in paediatric depression . AIMS To identify which clinical and environmental risk factors at baseline and during treatment predicted major depression at 28-week follow-up in a sample of adolescents with depression . METHOD One hundred and ninety-two British adolescents with unipolar major depression were enrolled in a r and omised controlled trial ( the Adolescent Depression Antidepressants and Psychotherapy Trial , ADAPT ) . Participants were treated for 28 weeks with routine psychosocial care and selective serotonin reuptake inhibitors ( SSRIs ) , with half also receiving cognitive-behavioural therapy ( CBT ) . Full clinical and demographic assessment was carried out at baseline and 28 weeks . RESULTS Depression at 28 weeks was predicted by the additive effects of severity , obsessive-compulsive disorder and suicidal ideation at entry together with presence of at least one disappointing life event over the follow-up period . CONCLUSIONS Clinicians should assess for severity , suicidality and comorbid obsessive-compulsive disorder at presentation and should monitor closely for subsequent life events during treatment OBJECTIVE Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and adolescents . The current study investigated the efficacy and safety of citalopram compared with placebo in the treatment of pediatric patients with major depression . METHOD An 8-week , r and omized , double-blind , placebo-controlled study compared the safety and efficacy of citalopram with placebo in the treatment of children ( ages 7 - 11 ) and adolescents ( ages 12 - 17 ) with major depressive disorder . Diagnosis was established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version . Patients ( N=174 ) were treated initially with placebo or 20 mg/day of citalopram , with an option to increase the dose to 40 mg/day at week 4 if clinical ly indicated . The primary outcome measure was score on the Children 's Depression Rating Scale-Revised ; the response criterion was defined as a score of < or = 28 . RESULTS The overall mean citalopram dose was approximately 24 mg/day . Mean Children 's Depression Rating Scale-Revised scores decreased significantly more from baseline in the citalopram treatment group than in the placebo treatment group , beginning at week 1 and continuing at every observation point to the end of the study ( effect size=2.9 ) . The difference in response rate at week 8 between placebo ( 24 % ) and citalopram ( 36 % ) also was statistically significant . Citalopram treatment was well tolerated . Rates of discontinuation due to adverse events were comparable in the placebo and citalopram groups ( 5.9 % versus 5.6 % , respectively ) . Rhinitis , nausea , and abdominal pain were the only adverse events to occur with a frequency exceeding 10 % in either treatment group . CONCLUSIONS In this population of children and adolescents , treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated OBJECTIVE To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression . METHOD After a 7- to 14-day screening period , 275 adolescents with major depression began 8 weeks of double-blind paroxetine ( 20 - 40 mg ) , imipramine ( gradual upward titration to 200 - 300 mg ) , or placebo . The two primary outcome measures were endpoint response ( Hamilton Rating Scale for Depression [ HAM-D ] score < or = 8 or > or = 50 % reduction in baseline HAM-D ) and change from baseline HAM-D score . Other depression-related variables were ( 1 ) HAM-D depressed mood item ; ( 2 ) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version ( K-SADS-L ) ; ( 3 ) Clinical Global Impression ( CGI ) improvement scores of 1 or 2 ; ( 4 ) nine-item depression subscale of K-SADS-L ; and ( 5 ) mean CGI improvement scores . RESULTS Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8 , HAM-D depressed mood item , K-SADS-L depressed mood item , and CGI score of 1 or 2 . The response to imipramine was not significantly different from placebo for any measure . Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures . Withdrawal rates for adverse effects were 9.7 % and 6.9 % for paroxetine and placebo , respectively . Of 31.5 % of subjects stopping imipramine therapy because of adverse effects , nearly one third did so because of adverse cardiovascular effects . CONCLUSIONS Paroxetine is generally well tolerated and effective for major depression in adolescents OBJECTIVE To examine the course of depression during the treatment of adolescents with depression who had recently attempted suicide . METHOD Adolescents ( N = 124 ) , ages 12 to 18 years , with a 90-day history of suicide attempt , a current diagnosis of depressive disorder ( 96.0 % had major depressive disorder ) , and a Children 's Depression Rating Scale-Revised ( CDRS-R ) score of 36 or higher , entered a 6-month treatment with antidepressant medication , cognitive-behavioral therapy focused on suicide prevention , or their combination ( Comb ) , at five academic sites . Treatment assignment could be either r and om or chosen by study participants . Intent-to-treat , mixed effects regression models of depression and other relevant ratings were estimated . Improvement and remission rates were computed with the last observation carried forward . RESULTS Most patients ( n = 104 or 84 % ) chose treatment assignment , and overall , three fourths ( n = 93 ) received Comb . In Comb , CDRS-R declined from a baseline adjusted mean of 49.6 ( SD 12.3 ) to 38.3 ( 8.0 ) at week 12 and to 27.0 ( 10.1 ) at week 24 ( p < .0001 ) , with a Clinical Global Impression -defined improvement rate of 58.0 % at week 12 and 72.2 % at week 24 and a remission ( CDRS-R ≤ 28 ) rate of 32.5 % at week 12 and 50.0 % at week 24 . The CDRS-R and the Scale for Suicidal Ideation scores were correlated at baseline ( r = 0.43 , p < .0001 ) and declined in parallel . CONCLUSIONS When vigorously treated with a combination of medication and psychotherapy , adolescents with depression who have recently attempted suicide show rates of improvement and remission of depression that seem comparable to those observed in nonsuicidal adolescents with depression BACKGROUND Psychiatric clinics have high non-attendance rates and failure to attend may be a sign of deteriorating mental health . AIMS To investigate why psychiatric out- patients fail to attend , and the outcome of attenders and non-attenders . METHOD Prospect i ve cohort study of r and omly selected attenders and non-attenders at general adult psychiatric out-patient clinics . Subjects were interviewed at recruitment and severity of mental disorder and degree of social adjustment were measured . Six and 12 months later their engagement with the clinic and any psychiatric admissions were ascertained . RESULTS Of the 365 patients included in the study , 30 were untraceable and 224 consented to participate . Follow-up patients were more psychiatrically unwell than new patients . For follow-up patients , non-attenders had lower social functioning and more severe mental disorder than those who attended . At 12-month follow-up patients who missed their appointment were more likely to have been admitted than those who attended . CONCLUSIONS Those who miss psychiatric follow-up out-patient appointments are more unwell and more poorly socially functioning than those who attend . They have a greater chance of drop-out from clinic contact and subsequent admission Our recent 8-week , r and omized , placebo-controlled trial of fluoxetine in adolescents ( ages 12 - 17 years ) with comorbid depression and substance use disorder ( SUD ) did not detect a significant antidepressant treatment effect . The purpose of this secondary analysis was to explore moderators of the effect of fluoxetine in this sample . Static moderators measured at baseline were depression chronicity and hopelessness severity ; time-varying moderators measured at baseline and weekly during the 8-week trial period were alcohol and marijuana use severity . Treatment effects on depression outcomes were examined among moderating subgroups in r and om effects regression models . Subjects assigned to fluoxetine treatment with chronic depression at baseline ( p = .04 ) or no more than moderate alcohol use during the trial ( p = .04 ) showed significantly greater decline in depression symptoms in comparison to placebo-assigned subgroups . The current analysis suggests that youth with chronic depression and no more than moderate alcohol consumption are likely to respond better to treatment with fluoxetine compared with placebo than youth with transient depression and heavy alcohol use OBJECTIVE A r and omized , double-blind , placebo-controlled flexible-dose , parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system ( STS ) ( EMSAM ® ) in adolescents ( ages 12 - 17 years ) meeting American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . ( DSM-IV ) criteria for moderate to severe major depressive disorder ( MDD ) without psychotic features . METHODS Adolescents ( n=308 ) with moderate to severe MDD were r and omized to either STS ( n=152 ) or placebo ( n=156 ) . Two hundred and fifteen ( 69.8 % ) subjects completed the study and 17 ( 5.5 % ) reported discontinuation because of adverse events ( AEs ) . The primary efficacy outcome measure was the mean change from baseline to end of study ( week 12 last observation carried forward [ LOCF ] ) in the Children 's Depression Rating Scale-Revised ( CDRS-R ) total score . Secondary outcome measures included end-point Clinical Global Impressions - Severity ( CGI-S ) and Clinical Global Impressions - Improvement ( CGI-I ) . RESULTS Patients on STS or placebo had a significant decline from baseline ( p<0.001 ) on their CDRS-R total score with mean reductions±SD as follows : STS 21.4±16.6 ; placebo 21.5±16.5 . Both groups had similar response rates ( 58.6 % vs. 59.3 % ) defined as CGI-I of 1 or 2 at study end . However , these between-group efficacy findings were without statistical significance . The overall incidence of reported AEs was 62.5 % for STS-treated patients and 57.7 % for placebo-treated patients . Most commonly reported AEs in STS or placebo groups were application site reactions ( STS=24.3 % ; placebo=21.8 % ) , headache ( STS=17.1 % ; placebo=16.7 % ) , and nausea ( STS=7.2 % ; placebo=7.7 % ) . Treatment groups did not differ on any laboratory parameters , vital signs , or electrocardiogram ( ECG ) findings . No suspected hypertensive crises were reported in the trial . CONCLUSIONS These data demonstrated that the STS was safe and well tolerated in this adolescent sample . However , both STS-treated and placebo-treated subjects demonstrated a decline from baseline in depressive symptoms ( CDRS-R total score ) over the length of the study , without statistical superiority by either group OBJECTIVE To determine amitriptyline 's ( AMI ) efficacy in the acute treatment of adolescent major depressive disorder ( MDD ) . METHOD Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD , diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children ( K-SADS ) , participated in a 2-week placebo-washout followed by an 8-week , r and omized , double-blind , parallel- design , placebo-controlled trial of AMI , 5 mg/kg per day . The K-SADS nine-item scale , the Hamilton Depression Rating Scale , and the Clinical Global Impressions rating scale were used as outcome measures . RESULTS Thirty-one subjects were r and omized ( 18 AMI , 13 placebo ) . Twenty-two subjects were study completers ( 12 AMI , 10 placebo ) . AMI 's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data . Perhaps the primary limitation of the current study is its small sample size . CONCLUSION No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD OBJECTIVE The safety , efficacy , and tolerability of venlafaxine extended release ( ER ) in subjects ages 7 to 17 years with major depressive disorder were evaluated in two multicenter , r and omized , double-blind , placebo- Output:	The adverse effects most associated with dropout were attempted suicide followed by mania , skin rash , and headache . Problems relating to clinical trials and family arbitration were also related with dropout . Selective serotonin reuptake inhibitors were linked to the lowest prevalence , probably due to fewer perceived problems with related adverse effects and higher efficacy in adolescents . Cognitive-behavioral therapy combined with pharmacotherapy produced a lower nonadherence prevalence ; this approach can be an alternative to avoid dropouts and relapse .
MS22299	*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 Diabetes mellitus is a strong risk factor for cardiovascular and renal disease . We investigated whether the angiotensin-converting-enzyme ( ACE ) inhibitor ramipril can lower these risks in patients with diabetes . METHODS 3577 people with diabetes included in the Heart Outcomes Prevention Evaluation study , aged 55 years or older , who had a previous cardiovascular event or at least one other cardiovascular risk factor , no clinical proteinuria , heart failure , or low ejection fraction , and who were not taking ACE inhibitors , were r and omly assigned ramipril ( 10 mg/day ) or placebo , and vitamin E or placebo , according to a two-by-two factorial design . The combined primary outcome was myocardial infa rct ion , stroke , or cardiovascular death . Overt nephropathy was a main outcome in a sub study . FINDINGS The study was stopped 6 months early ( after 4.5 years ) by the independent data safety and monitoring board because of a consistent benefit of ramipril compared with placebo . Ramipril lowered the risk of the combined primary outcome by 25 % ( 95 % CI 12 - 36 , p=0.0004 ) , myocardial infa rct ion by 22 % ( 6 - 36 ) , stroke by 33 % ( 10 - 50 ) , cardiovascular death by 37 % ( 21 - 51 ) , total mortality by 24 % ( 8 - 37 ) , revascularisation by 17 % ( 2 - 30 ) , and overt nephropathy by 24 % ( 3 - 40 , p=0.027 ) . After adjustment for the changes in systolic ( 2.4 mm Hg ) and diastolic ( 1.0 mm Hg ) blood pressures , ramipril still lowered the risk of the combined primary outcome by 25 % ( 12 - 36 , p=0.0004 ) . INTERPRETATION Ramipril was beneficial for cardiovascular events and overt nephropathy in people with diabetes . The cardiovascular benefit was greater than that attributable to the decrease in blood pressure . This treatment represents a vasculoprotective and renoprotective effect for people with diabetes The primary results of a three-year prospect i ve , double-blind , placebo-controlled trial in non-insulin-dependent diabetic ( NIDDM ) patients show that an anti-hypertensive regimen , which includes the ACE inhibitor enalapril , preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors ( J Am Soc Nephrol 3:335 , 1992 ) . The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis . Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [ baseline glomerular filtration rate ( GFR ) 30 to 100 ml/min/1.73 m2 ] . Twenty-four hour urinary excretion of albumin ( UAE ) , protein , urea nitrogen , creatinine and isotopically determined GFR were measured at baseline and six month intervals . Glycemic control and blood pressure regulation were assessed every three months . The rate of loss of GFR was significantly greater in patients with overt proteinuria at baseline ( UAE > 300 mg/24 hr ) as compared to patients with baseline sub- clinical proteinuria ( UAE < or = 300 mg/24 hr ) . Antihypertensive treatment with enalapril preserved GFR significantly better ( P < 0.01 ) in the patients with sub- clinical proteinuria at baseline ( UAE < or = 300 mg/24 hr ) than other antihypertensive treatments which excluded the ACE inhibitor . Furthermore , only 7 % of the enalapril-treated group progressed to clinical albuminuria compared to 21 % of control treated patients . Although the enalapril-treated group had a lower mean blood pressure during the maintenance period , no correlation between blood pressure ( systolic , diastolic or mean arterial ) and rate of change of GFR was observed . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Determine the prevalence of microalbuminuria in patients with type 2 diabetes mellitus ( DM ) in general practice , as an independent risk factor for cardiovascular diseases . DESIGN Prospect i ve , descriptive . METHOD Data were collected on patients with type 2 DM in the Zwolle region of the Netherl and s , all of whom were being treated by their general practitioner . The inclusion period was 1 February 2000 - 31 January 2001 . The study formed part of a larger investigation , in which the albumin concentration in a urine sample and the albumin-creatinin ratio were determined once per year . A total of 32 general practitioners took part in the study . RESULTS In the general practice s studied , 2094 patients were known with type 2 DM and 1653 ( 79 % ) were treated exclusively by the general practitioner . Of these 1653 patients , 67 ( 4 % ) were excluded and of the 1586 invited patients remaining , 1441 ( 91 % ) participated . Microalbuminuria was present in 33 % of the patients and macroalbuminuria in 7 % of the patients , and the prevalences increased with age : < 50 , 50 - 70 and > 70 years . 18 % ( 6/33 ) of the patients aged < 50 years with microalbuminuria were treated with an ACE inhibitor or angiotensin II antagonist compared to 33 % ( 183/548 ) of patients > or = 50 years . 91 % ( 488/539 ) of the patients > or = 50 years with microalbuminuria had hypertension and /or lipid profile abnormalities and 82 % ( 402/488 ) of them were not treated or did not receive adequate treatment for this condition . CONCLUSION Microalbuminuria and macroalbuminuria were present in respectively 33 % and 7 % of the patients with type 2 DM in primary care . The treatment of hypertension and lipid profile abnormalities was often inadequate . Therefore , screening patients aged 50 years and older with type 2 DM for albuminuria is justified Background —The aim of this study was to assess the level of urinary albumin excretion ( microalbuminuria ) , which is associated with increased risk of coronary heart disease and death , in the population . Microalbuminuria has been suggested as an atherosclerotic risk factor . However , the lower cutoff level of urinary albumin excretion is unknown . It is also unknown whether impaired renal function confounds the association . Methods and Results —In the Third Copenhagen City Heart Study in 1992 to 1994 , 2762 men and women 30 to 70 years of age underwent a detailed cardiovascular investigation program , including a timed overnight urine sample . The participants were then followed up prospect ively by registers until 1999 with respect to coronary heart disease and until 2001 with respect to death . During follow-up , 109 incident cases of coronary heart disease and 276 deaths were traced . A urinary albumin excretion above the upper quartile , ie , 4.8 μg/min , was associated with increased risk of coronary heart disease ( RR , 2.0 ; 95 % CI , 1.4 to 3.0 ; P < 0.001 ) and death ( RR , 1.9 ; 95 % CI , 1.5 to 2.4 ; P < 0.001 ) independently of age , sex , renal creatinine clearance , diabetes mellitus , hypertension , and plasma lipids . Lower levels of urinary albumin excretion were not associated with increased risk . Conclusions —Microalbuminuria , defined as urinary albumin excretion > 4.8 μg/min ( corresponding to ≈6.4 μg/min during daytime ) , is a strong and independent determinant of coronary heart disease and death . Our suggestion is to redefine microalbuminuria accordingly and perform intervention studies Objective The aim of this open-labelled , r and omised , parallel-group study was to evaluate the effect of long-term monotherapy with manidipine or lisinopril on albumin excretion rate ( AER ) and left ventricular mass index ( LVMI ) in hypertensive patients with type-2 diabetes and microalbuminuria . Methods After a 4-week wash-out period , 174 patients with essential hypertension [ diastolic blood pressure ( DBP ) > 80 mmHg and < 100 mmHg ] , type-2 diabetes and microalbuminuria were r and omised to manidipine 10 mg o.d . or lisinopril 10 mg o.d . ; after 8 weeks , the dose was doubled in non-responders ( DBP > 80 mmHg ) ; after 3 months , treatment was discontinued in the non-responder patients and in those complaining of side effects ; the remaining 121 patients continued their therapy with manidipine or lisinopril , and 99 completed the 2-year study . At the end of the wash-out period , of the titration period and after 6 , 12 , 18 and 24 months of treatment , BP was measured , AER , creatinine clearance , glycosylated haemoglobin ( HbA1c ) and body mass index ( BMI ) were evaluated and an echocardiographic evaluation was performed . Results The 99 patients who completed the study were statistically analysed according to a per- protocol evaluation . Manidipine and lisinopril significantly reduced systolic blood pressure ( SBP ) and DBP levels ( at 24 months , −22.3/15.5 mmHg , P<0.001 versus baseline and −21.4/15.7 mmHg , P<0.01 versus baseline , respectively ) . Both drugs provided a significant decrease in AER , but it was significantly more pronounced with lisinopril ( at 24 weeks , −37.2 mg/24 h , P<0.001 versus baseline ) than with manidipine ( –29.9 mg/24 h , P<0.05 versus baseline ) and became evident earlier in the lisinopril group ( after 3 months versus 6 months of treatment ) . Manidipine produced a greater reduction of LVMI than lisinopril ( −14.9 g/m2 versus –10.8 g/m2 at 24 months ) . The effect was more pronounced in patients with left ventricular hypertrophy at baseline ( −19.8 g/m2 versus –12.8 g/m2 , P<0.05 ) . Conclusion These data suggest that , despite similar BP lowering , non-haemodynamic factors play an important role in the pharmacological reduction of AER and LVMI in diabetic hypertensive patients The aim of this study was to compare the effects of ramipril and nitrendipine chronic treatment on urinary albumin excretion ( UAE ) in hypertensive patients with type II non-insulin-dependent diabetes mellitus ( NIDDM ) and impaired renal function . A 2-year , prospect i ve , r and omised study was conducted on 51 men with a diastolic blood pressure ( DBP ) ⩾95 and ⩽105 mm Hg , stable NIDDM , serum creatinine between 1.6 and 3.0 mg/dl and persistent UAE > 300 and < 2000 mg/24 h. after a 3-month preliminary observation period , during which patients began a low-protein , low-sodium diet , and a subsequent 4-week run-in period on placebo , patients were r and omly treated with ramipril 5 mg or nitrendipine 20 mg for 2 years . both drugs similarly reduced bp without affecting glucose homeostasis . in the ramipril group uae significantly decreased after only 3 months of treatment , whereas in the nitrendipine group a significant although lesser reduction in uae was observed only after 1 year . during the second year the uae% change was not statistically different between the two treatments . serum creatinine and creatinine clearance showed no significant change with both drugs . the progression of renal insufficiency as assessed by the rate of reduction of creatinine clearance over the 2 years of the study was similar in the ramipril and the nitrendipine groups . in conclusion both ramipril and nitrendipine were associated with a decrease in uae although such a reduction was earlier and more marked with ramipril . the decline of renal function did not differ significantly between the two treatments 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 Output:	The ACEI/ARB benefit over placebo was significant for all outcomes except microalbuminuria . A network meta- analysis detected significant treatment effects across all outcomes for both active drugs and placebo comparisons . Conclusions /interpretationOur review suggests a consistent reno-protective effect of ACEI/ARB over other antihypertensive drugs , mainly CCBs , and placebo in type 2 diabetes . The lack of any differences in BP decrease between ACEI/ARB and active comparators suggest this benefit is not due simply to the antihypertensive effect

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